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Archive for the ‘Gene Therapy Research’ Category

Vertex invests in gene therapy manufacturing –

Across 2019, Vertex has struck deals intended to yield a new generation of breakthrough medicines.

In June, Vertex agreed to pay $245m (220m) upfront to acquire Exonics Therapeutics for its gene editing technology and pipeline of programs targeting diseases including Duchenne muscular dystrophy (DMD). Months later, Vertex put up another $950m to buy Semma Therapeutics and its cell therapy treatment for type I diabetes.

The acquisitions moved Vertex, which started out in small molecules, into new areas, and building out capabilities in those areas will cost money.

In recent years, Vertex has grown its annual operating expenses by 10% to 14%. Talking on a recent quarterly results conference call, Vertex CFO Charles Wagner warned investors to expect costs to rise faster in 2020.

Wagner said, Our current expectation is that the rate of growth will be somewhat higher in 2020 as we invest in research and preclinical manufacturing for selling genetic therapies in support of our programs in type I diabetes, DMD and other diseases.

The move into type I diabetes also takes Vertex into territory that, to some observers, looks different than the areas the company has targeted historically.

Asked by an analyst about the shift in focus, Vertex CEO Jeff Leiden downplayed the differences, noting that type I diabetes is treated in the US in a relatively small number ofcenters that can be targeted by a speciality sales force.

Researchers have achieved positive, long-term outcomes by transplanting cadaveric islets into patients but two barriers have stopped companies from industrialising that approach.

Firstly, there are too few cadaveric islets to treat all type I diabetics. Secondly, immunosuppression is needed to stop patients from rejecting the transplanted cells.

Semma is trying to tackle the problems by differentiating stem cells and using a device to protect them from the immune system. Vertex thinks these technologies are the breakthroughs the field needs to industrialize the concept.

Leiden said, We were watching companies who are addressing those two problems for the last two, three years. And over the last six to eight months, we were convinced that Semma has actually solved both of those problems.

Vertex reached that conclusion on the strength of preclinical data. Now, Vertex is set to invest to find out whether the idea works in the clinic.

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Vertex invests in gene therapy manufacturing -

Year in Review: Ophthalmology – MedPage Today

Events backed up a prominent neurologist's declaration in May that "2019 is the year of NMO" -- neuromyelitis optica -- but that was not the year's only major news, as advances against age-related macular degeneration (AMD), diabetic retinopathy, and even eye hazards from radiation were also reported.


Neuromyelitis optica, of course, is the vision disorder once seen as a form of multiple sclerosis. It's now known to result from autoantibodies to the aquaporin-4 water channel that degrade the optic nerve. That etiology makes it a neurological as well as ophthalmological condition, which is why neurologist Natalia Rost, MD, of Massachusetts General Hospital, was speaking about it at the American Academy of Neurology's (AAN) annual meeting. There, three important trials of three different drugs for NMO spectrum disorder were being presented.

Among them were findings from the so-called PREVENT trial of eculizumab (Soliris), a complement C5 inhibitor, versus placebo, showing that the active drug cut NMO relapses by a whopping 94% relative to placebo over 48 weeks of treatment. Eculizumab also reduced hospital admissions and use of rescue therapies for acute attacks. Preventing attacks is especially important in NMO because they are responsible for permanent vision loss (unlike multiple sclerosis, in which disability progression occurs between acute relapses).

And just a month after those findings were reported at the AAN meeting, the FDA approved eculizumab for NMO spectrum disorder, making it the first drug indicated specifically for the condition.

Also making a splash was a drug taking another approach to NMO. That was the investigational interleukin-6 inhibitor satralizumab, for which results of two phase III trials were presented, respectively, at AAN and later in the year at the European Committee for Treatment and Research in Multiple Sclerosis meeting. SAkuraSky, reported at the former, tested satralizumab as add-on to conventional treatment (immunosuppressants and/or corticosteroids), while the other, SAkuraStar, focused on the drug as monotherapy. At least superficially, results were not quite as impressive as with eculizumab in PREVENT -- attack frequency was reduced 55%-74% in one of the satralizumab trials and 62%-79% in the other, relative to placebo and depending on whether patients tested positive for anti-aquaporin antibodies -- but the differences could easily stem from the differing trial designs.

Still another drug in development with positive phase III findings in hand (also reported at AAN) was inebilizumab, a B-cell depleting agent not unlike rituximab (Rituxan), which showed reductions in attack frequency similar to those seen with satralizumab.


One of the most common forms of vision loss and the least treatable is now looking as though it may soon be conquered. Researchers reported at the American Academy of Ophthalmology (AAO) meeting last month that an investigational antioxidant agent helped restore vision in patients with "non-exudative" (dry) AMD.

Called risuteganib, the agent is delivered by intravitreal injection and acts to inhibit oxidative stress in the macula. In a 28-week phase II trial, half of the active-drug group showed improvement of at least eight letters on a standard eye chart, compared with 7% of patients getting sham injections. Mean changes in the two groups were +6.1 vs +2.1 letters, respectively, after 28 weeks.

After hearing these results, one academic ophthalmologist commented, "I think having 50% of intermediate AMD patients who have eight letters of improvement is pretty stunning."

Meanwhile, the "wet" form of AMD may also soon have a new treatment option. Though, like existing medications, its mechanism is to inhibit angiogenesis in the retina, this one could be more durable and even permanent. That's because it's a gene therapy.

At AAO last month, researchers presented findings from a pilot study with RGX-314, an adeno-associated virus engineered to express an antibody fragment that inactivates vascular endothelial growth factor (VEGF), the target of other existing drugs. However, those agents require intravitreal injections every few weeks. The RGX-314 study involved just a single injection, with patients followed for up to 18 months.

Three of six patients with that much follow-up required no rescue treatment with conventional anti-VEGF agents; nine of 12 patients with 6 months of follow-up needed no rescue treatment. The gene therapy was also reported to be well tolerated.

And early results reported at AAO with a similar gene therapy, using aflibercept (Eylea) as the anti-VEGF payload, also were promising.

Diabetic Retinopathy

One potentially practice-changing study was reported back in January, when a Taiwanese cohort study found that patients with type 2 diabetes were less likely to develop diabetic retinopathy if they were taking statins.

In a propensity-matching analysis involving about 40,000 patients with type 2 diabetes, rates of retinopathy were lower in those on statin therapy (10.6% vs 12.0%; HR 0.86, 95% CI 0.81-0.91). Other ocular diabetic complications were also significantly reduced -- and more markedly -- in the statin group, including vitreous hemorrhage, tractional retinal detachment, and macular edema, rates of which were all lower by about 40% with statin therapy.

Naturally, the study came with a number of limitations, but the authors nevertheless concluded that the findings could inform management of diabetic patients.

Closer to home, another study suggested that primary care is a relatively untapped resource in identifying patients with diabetic retinopathy. Patients with type 2 diabetes may skimp on eye-doctor visits, but they tend to be diligent at seeing their regular physicians.

That was confirmed in a survey of some 3,200 diabetic patients, among whom 88% had a primary care visit in the past year -- and the figure was 82% for those without a dilated eye exam within the previous 12 months. The study's lead author told MedPage Today, "This report adds further evidence that screening for diabetic retinopathy in primary care settings could provide timely screening to a large portion of U.S. adults with diabetes, including those at high-risk of missing recommended eye examinations." That, in turn, could improve early detection and treatment before vision loss becomes severe.

Leaded Glasses for Radiation Protection

Certain procedures in healthcare, such as imaging-guided cardiovascular interventions, expose operators to radiation that can damage the eye. Leaded glasses are commonly worn to block the radiation, but how well, really, do they work?

Canadian researchers put it to the test in a study reported at the Society for Interventional Radiology meeting in March. The verdict: the glasses don't work very well.

During real-world fluoroscopic-guided procedures, in which radiation penetration to operators' eyes was measured, use of leaded glasses cut exposure by just 9.5%-142%, the researchers reported.

"Lead glasses may be providing a false sense of security," said the study's lead investigator. A more effective approach to minimizing the hazard was to place the monitor across or above the table, rather than to one side.

Other Notable Ophthalmology News:

Novel LHON Therapy Effective -- Maybe -- in Phase III Trial

Do Those Yellow 'Night-Driving' Glasses Really Work?

Durable IOP Control With Ocular Implant

No Verdict on Glasses for Farsighted Kids

Faulty Amino Acid Metabolism Linked to Rare Eye Disease


last updated 11.11.2019

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Year in Review: Ophthalmology - MedPage Today

Hemophilia Patients, Caregivers Identify Factors in Switching Treatments – Hemophilia News Today

Ease of use, fear of the unknown, and healthcare providers advice are all major factors that play a role in whether people with hemophilia want to switch to new treatment options, a small study suggests.

The study, Patient Perspectives on Novel Treatments in Haemophilia: A Qualitative Study, was published in the journal The Patient.

The current standard-of-care for people with hemophilia is replacement of the missing coagulation factors, given via injection. But there are numerous imperfections with these therapies, from the need for frequent injections to the possibility of developing resistance.

In recent years, new hemophilia treatments, including products with longer half-lives and gene therapies, are being developed or entering the market. Although these therapies may be improvements over standard care in some regards, they have drawbacks of their own and since they are newer, some of these issues may not even be known yet.

Still, there exists the possibility that people with hemophilia may want to switch treatment regimens as new options become available. In this study, researchers set out to better understand the factors that influence such a choice.

To do this, they conducted interviews with 12 people with moderate or severe hemophilia, as well as two parents of children with hemophilia. All participants were Dutch, and they represented a range of backgrounds, including different ages, hemophilia types, infection statuses (such as HIV and hepatitis C), and even fear of needles.

The participants generally reported satisfaction with their current treatment methods (all but one were treated at home; one went to the hospital for bleeds), though they acknowledged some challenges, such as the hassle of self-injecting.

Cost was a particular concern; six participants reported avoiding injections when possible to save money even against the advice of their healthcare providers.

When asked how they felt about switching to a new therapy, eight participants said they were open to the idea, but did not feel they urgently needed something different, while three participants all of whom were younger and had few bleeding problems said they didnt feel the need to switch. The two parents said they were adopting a wait-and-see approach.

The researchers summarized factors that participants said would make them more or less likely to switch therapies. Factors in favor of switching included the possibility of the new medication being more effective and being easier or more convenient to use.

If I had to switch to a different medication, I would switch to one with a longer half-life. That would be a bit better for me so I have to inject less often, one participant said.

However, participants expressed a general fear of the unknown and a reluctance to take therapies that have relatively less research to back them up, saying they didnt want to be a guinea pig or research subject.

There is also the possibility that a new therapy even one that works well in general might not work for a given individual, posing a risk for switching from a treatment that is known to work.

I know two guys that participated in a gene therapy trial. One was out of luck, he didnt achieve higher factor levels. The other one did. Yes, fantastic if it works, said one participant. On the other hand, if you have good treatment, why would you change it?

More broadly, participants expressed confidence that their healthcare providers would inform them if new therapies that would benefit them became available.

The doctors are specialists, one participant said, and at some point theyll say: hey, we have this new treatment for you, so Ill say: sure, bring it on!'

Overall, the study highlights the factors that are important to people with hemophilia who are considering their treatment options.

It is important for hemophilia treatment teams to be aware of these factors in providing information to facilitate shared decision making, the researchers concluded.

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.

Total Posts: 121

Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Tcnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.

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Hemophilia Patients, Caregivers Identify Factors in Switching Treatments - Hemophilia News Today

A New Treatment Method May Cure Patients of Genetic Hearing Loss –

Why choose gene therapy to do research?

Hearing loss is the most common sensory impairment in humans, which, according to statistics, currently disables 466 million people in the world. And the incidence of genetic hearing loss in newborns reaches up to 1. Many cases show that hearing loss is actually related to genetic DNA mutations, and there are nearly 100 genes known to be related, such as GJB2, SLC26A4, 12SrRNA, etc. Mutations in hereditary hearing loss include single nucleotide substitution, base deletion and insertion. These mutations lead to missense and nonsense mutations in the deafness gene.

Thus, selective correction at gene level may serve as an innovative and effective treatment for genetic hearing loss.

How does gene therapy work to heal deafness of mice?

Most cases of genetic hearing loss are result from mutations in DNA. DFNB9 is one of them, which is caused by a mutation in the otoferlin (OTOF) gene. The OTOF gene produces a protein called otoferlin, a component of the sound-sensing hair cells, without which the brain cant receive any sound information.

Before doing clinical research on humans, the researchers of the team used mice as a model of human DFNB9 deafness. Their method restores the normal function of the ear by using viruses and protein that can infect cells and integrate DNA into that of cells. In this study, the researches edited healthy copies of the OTOF gene into an adeno-associated virus (AAV), which is stable and efficient without causing a significant immune response. However, it is quite small and not able to match with huge human genes, so the researchers engineered two different AAV vectors, each containing half of the gene.

The inner ear has a unique advantage in structure for its being relatively easy to touch, but close and filled with liquid, which allows the drug injected into the cochlea to maintain a high concentration in the target organ. The researchers injected these engineered viruses into the cochlea of the DFNB9 model mice and the result showed that this restored communication between the ear and the brain.

What are the advantages and disadvantages of gene therapy?

Gene therapy can restore the normal hearing better because its essentially a method to repair the ear, not artificially simulating the ear. However, gene therapy for hearing loss still faces some challenges, for example, the exogenous genes may not be stably expressed in vivo for a long time, the product of exogenous genes may cause a serious immune response, etc.

At present, most of the research on genetic hearing loss remains in genetic screening, diagnosis and guidance. Further research is needed on the correction of gene mutations, which proves a promising future for gene therapy for genetic hearing loss. As a CRO specializing in gene therapy, Creative Biolabs has a team of experienced scientists and well-treated staff and has established dozens of world-leading platforms. Concentrating on providing a wide range of early development services, such as the gene therapy strategy design, hair cell regeneration, validation & function assessment in vitro and in vivo and other customized services, Creative Biolabs works with worldwide clients to find the best way to conquer genetic hearing loss.

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A New Treatment Method May Cure Patients of Genetic Hearing Loss -

Global Bleeding Disorders Therapeutics Market 2020-2024 | Evolving Opportunities with Baxter International Inc. & Bayer AG | Technavio – Business…

LONDON--(BUSINESS WIRE)--The global bleeding disorders therapeutics market size is poised to grow by USD 4.32 billion during 2020-2024, according to a new report by Technavio, progressing at a CAGR of close to 7% during the forecast period. Request Free Sample Pages

Read the 170-page research report with TOC on "Bleeding disorders therapeutics Market Analysis Report by Type (Hemophilia A, Hemophilia B, Von Willebrand disease, and Other disorders) and geography (North America, Europe, Asia, and ROW) 2020-2024".

The market is driven by rising initiatives to increase awareness about bleeding disorders. Also, the emergence of gene therapy is anticipated to further boost the growth of the bleeding disorders therapeutics market.

The market is witnessing rising initiatives by public and private organizations and governments, to increase awareness about bleeding disorders. These actions and campaigns have created awareness about the advances and discoveries in medicine for bleeding disorders in recent years. Organizations such as the National Hemophilia Foundation, von Willebrand Education Network, and World Federation of Hemophilia support are engaged in creating awareness about bleeding disorders. Such awareness campaigns will have a significant impact on the growth of the market during the forecast period.

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Major Five Bleeding Disorders Therapeutics Companies:

Baxter International Inc.

Baxter International Inc. has business operations in various segments, including renal care, medication delivery, pharmaceuticals, clinical nutrition, advanced surgery, acute therapies, and other. The companys key product offerings include FEIBA, HEMOFIL M, RIXUBIS, and Prothromplex TOTAL.

Bayer AG

Bayer AG operates the business under various segments, namely pharmaceuticals, crop science, consumer health, and animal health. Some of the companys key offerings include Jivi, KOVALTRY, and Kogenate FS.

CSL Ltd.

CSL Ltd. manufactures, markets, and develops plasma therapies and conducts early-stage research on plasma and non-plasma therapies. The companys key offerings in the bleeding disorders therapeutics market include Corifact, RiaSTAP, Stimate, Humate-P, AFSTYLA, IDELVION, and MONONINE.

F. Hoffmann-La Roche Ltd.

F. Hoffmann-La Roche Ltd. focuses on the development of drugs in the oncology, immunology, neuroscience, ophthalmology, and infectious diseases areas, as well as other therapeutic areas. The company offers HEMLIBRA, which is a prophylactic treatment for patients with hemophilia A with or without factor VIII inhibitors.

Grifols SA

Grifols SA has business operations under various segments, which include bioscience, hospital, diagnostic, bio supplies, and others. The companys key offerings include ALPHANATE, Profilnine SD, and AlphaNine SD.

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Bleeding Disorders Therapeutics Type Outlook (Revenue, USD Million, 2020-2024)

Bleeding Disorders Therapeutics Regional Outlook (Revenue, USD Million, 2020-2024)

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Related Reports on Health Care are:

Hemophilia A Therapeutics Market Hemophilia A Therapeutics Market by product (recombinant therapies, plasma-derived therapies, hormonal therapies, and others), type (on-demand treatment, prophylactic treatment, and inhibitor treatment) and geography (Americas, APAC, and EMEA).

Hematology Analyzers and Reagents Market Hematology Analyzers and Reagents Market by end-users (hospitals and diagnostic centers, blood bank centers, and others) and geography (North America, Europe, Asia, and ROW).

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GOVX: Third Quarter 2019 Results and Update – Zacks Small Cap Research


GeoVax Labs, Inc. (OTC:GOVX) filed its third quarter 2019 10-Q and issued the accompanying press release on November 7, 2019 providing an operational and financial update on the companys performance. During the third quarter and to date GeoVax gave several presentations related to the Lassa fever, HIV and Marburg programs, issued additional shares to satisfy convertible preferred liquidation, further oriented the company towards an oncology focus and announced a partners Investigational new Drug (IND) application for an HIV cure. Looking forward to the rest of 2019, we expect GeoVax will continue to seek additional capital to support its initiatives in immuno-oncology and apply for further grant funding to support the many vaccine programs in development.

Grant and collaboration revenues for 3Q:19 were $215,000, representing a 5% decrease compared to 3Q:18 levels. Revenues were recognized for Lassa fever related to the SBIR and US Army grants, while the Zika SBIR grant has been exhausted. Total expenditures for the first quarter were $759,000, down 25% from prior year levels. R&D expenditures of $0.5 million compared to $0.6 million in the prior year. G&A was $0.3 million, falling 36% from 3Q:18 levels with the decrease primarily attributable to lower levels of stock based compensation.

As of September 30, cash on the balance sheet was $569,000 and notes outstanding were carried at $42,000. Cash burn for the three month period was ($0.3) million, which compares to ($0.3) million in the comparable period. GeoVax received $700,000 in proceeds from sale of preferred stock. Following the end of the quarter, additional convertible preferred instruments were exercised increasing the shares outstanding to 426 million as of November 6, 2019.

Shift to Immuno-Oncology

GeoVax expects to continue to develop its HIV and infectious disease programs with grants and other available funding; but will shift its primary development focus towards immuno-oncology (IO). The company plans to leverage its validated Modified Vaccinia Ankara (MVA) Virus-Like Particle (VLP) platform technology to deliver tumor-associated antigens (TAAs) to the immune system so that it may mark cancer cells for destruction. The primary target for the IO program is Mucin 1 (MUC1), which is an oncogenic transmembrane glycoprotein overexpressed in many hematologic malignancies and solid tumors. Some of the cancers that have been shown to overexpress MUC1 include breast cancer, lung cancer and multiple myeloma. GeoVax is seeking support to pursue a triple-combination approach with its MUC1 vaccine, checkpoint inhibitors and standard of care. Preclinical work with GeoVaxs candidate demonstrated a 57% reduction in tumor growth compared to controls when MVA-VLP-MUC1 was combined with anti-PD-1 antibodies. GeoVax will also pursue a second TAA, Cyclin B1, in collaboration with Vaxeal Holding SA. Other partners participating in the oncology collaboration include Emory University and Leidos, Inc., with the latter contributing a PD-1 checkpoint inhibitor to the effort.

Exhibit I MVA-MUC1 Preclinical Model Data1

GeoVax is seeking collaborations with larger pharmaceutical or biotechnology companies or from government or non-profit organizations to support IO development. Due to the greater level of demand for new cancer therapies, GeoVax anticipates that after preclinical validation, funds could be raised to advance IO candidates through the clinic.

GeoVax has formed a separate subsidiary to house the oncology assets, which will allow targeted funding for these programs. All oncology work is expected to be performed in the new subsidiary, with joint development and licensing opportunities available. We expect further details on this structure in future quarters.

Partner IND Submission

Partner American Gene Technologies (AGT) submitted an IND application in mid-October for its lentiviral vector-based gene therapy candidate designated AGT103-T. If the FDA has no questions regarding the filing and does not place a clinical hold, AGT plans to enroll its first patients in January 2020. GeoVax will contribute its MVA-VLP HIV vaccine (MVA62B) to be used as a boost prior to removing T cells from the patient for reprogramming ex vivo. The trial will evaluate the use of AGT103-T alone and in combination with MVA62B. GeoVaxs Dr. Guirakhoo noted that in a Phase I trial the vaccine has stimulated CD8+ and CD4+ T cells in HIV-positive individuals, which suggests added efficacy from the boost.

Infectious Disease Programs

On July 16, GeoVax announced a presentation entitled A Single Dose of MVA-Based Lassa Virus Vaccine Provides Complete Protection in a Mouse Lethal Challenge Model at the Annual Meeting of the American Society of Virology in late July 2019. The topic of the presentation addresses the preclinical efficacy of a novel vaccine candidate for Lassa fever based on an MVA vector expressing two immunogens derived from the Lassa virus. After vaccination, the immunogens stimulate the formation of virus like particles (VLPs) that will develop immunity in the host against subsequent infections of Lassa. The study was funded by a Fast Track Phase I/II Small Business Innovative Research (SBIR) grant to GeoVax from the National Institute of Allergy and Infectious Diseases (NIAID).

In the fourth week of July, GeoVaxs Chief Scientific Officer, Dr. Harriet Robinson, delivered a presentation entitled Protein-Supplemented DNA/MVA Vaccines: Preclinical Immunogenicity and Protection for Transmitted/Founder and CD4-induced gp120 Proteins at the 10th International AIDS Society Conference in late July.

July was a busy month, and before it was over GeoVax reported 100% protection from preclinical challenge studies of its Marburg virus vaccine. GeoVaxs candidate, GEO-EM05, was administered to guinea pigs and compared against a control group. Eight weeks after inoculation, the animals were challenged with Marburg virus. In the active group, all animals survived with no negative health issues while all animals in the control group developed conditions that required them to be euthanized.

GeoVax has offered the infectious disease vaccines to public health agencies worldwide in return for development funding to advance the candidates towards approval. This approach could have benefits as it would further validate the MVA-VLP based vaccine platform and allow the company to potentially attract funds for development of other candidates in the portfolio as well as more quickly making life-saving vaccines available for populations that need them.

Year to Date Highlights

Collaboration with Enesi Pharma to develop vaccines using ImplaVax January 2019

Ebola vaccine study published in Atlas of Science March 2019

Expansion of Leidos collaboration in malaria March 2019

Execution of 500:1 reverse stock split May 2019

Marburg Virus Vaccine Study Results July 2019

Publication of Lassa Fever Study Results for GEO-LM01 September 2019

Presentation at World Immunotherapy Congress October 2019

Presentation at International Society of Virology October 2019

Presentation at World Vaccine Congress October 2019

Exhibit II GeoVax Vaccine Pipeline2


GeoVax continues to develop programs with a variety of grants while it seeks a partner and funding for later phase development of HIV projects. The company has reoriented its focus towards IO and has identified two targets that are appropriate for further research and combination therapies. GeoVax faces substantial dilution from conversions of its preferred stock and will be focused on identifying sources of investment that may potentially eliminate the additional $2.5 million in preferred stock outstanding. GeoVaxs portfolio has substantial value and company management is focused on identifying funding in order to advance the portfolio candidates. Participation in AGTs HIV trial and an offer from non-profits to develop infectious disease candidates may bring additional attention and validation to the MVA-VLP platform and potentially attract investment funds.

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1. Source: GeoVax Press Release. Leveraging GeoVax's Vaccine Expertise To Take On Cancer, Atlanta, GA, September 9, 2019.

2. Source: GeoVax Website Accessed November 2019.

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GOVX: Third Quarter 2019 Results and Update - Zacks Small Cap Research

Gene Therapy Market Trends, Technology and Forecast | by Top Companies Novartis AG, MeiraGTx Limited, Rocket Pharmaceuticals, Lonza, Biogen, Gilead…

Gene Therapy Market report has been structured after a thorough study of various key market segments like market size, latest trends, market threats and key drivers which drives the market. This market study report has been prepared with the use of in-depth qualitative analysis of the global market. The report displays a fresh market research study that explores several significant facets related to Gene Therapy Market covering industry environment, segmentation analysis, and competitive landscape. This global market research report is a proven source to gain valuable market insights and take better decisions about the important business strategies.

Industry Analysis:

Global gene therapy market is rising gradually with a healthy CAGR of 36.1% in the forecast period of 2019-2026. Increasing incidence of cancer and rare life threatening diseases and strong clinical pipeline drugs for gene therapy are major drivers for market growth.

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Top Dominating Competitors are: Pfizer Inc., Thermo Fisher Scientific Inc., F. Hoffmann-La Roche Ltd, Spark Therapeutics, Inc., bluebird bio, Inc., ALLERGAN, Krystal Biotech, Inc., Amicus Therapeutics, Inc., Sarepta Therapeutics, Novartis AG, MeiraGTx Limited, Rocket Pharmaceuticals, Lonza, Biogen, Gilead Sciences, Inc., REGENXBIO Inc., uniQure N.V., Solid Biosciences Inc., Audentes Therapeutics among others.

Gene Therapy Market Report incorporates the precisely contemplated and surveyed information related to the Gene Therapy Market by utilizing various explanatory tools and techniques. The explanatory devices, for example, PEST analysis, Porters five Forces examination, SWOT investigation, speculation return examination and feasibility analysis have been utilized to break down complex Gene Therapy Market data

Market Drivers and Restraint:

Table of Contents:

Chapter 1 Industry Overview:

Chapter 2 Premium Insights

Chapter 3 Production Market Analysis:

Chapter 4 Major Market Classification:

Chapter 5 Major Application Analysis:

Chapter 6 Industry Chain Analysis:

Chapter 7 Major Manufacturers Analysis:

Chapter 8 New Project Investment Feasibility Analysis:

Chapter 9 Market Driving Factors:

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Gene Therapy Market Trends, Technology and Forecast | by Top Companies Novartis AG, MeiraGTx Limited, Rocket Pharmaceuticals, Lonza, Biogen, Gilead...

Modified Protein Enhances the Accuracy of CRISPR Gene Therapy – DocWire News

A new protein that can enhance the accuracy of CRISPR gene therapy was recently developed by researchers from City University of Hong Kong (CityU) and Karolinska Institutet. This work, published in the Proceedings of the National Academy of Sciences, could potentially have a strong impact on how gene therapies are administered in the future.

CRISPR-Cas9, often referred to as just CRISPR, is a powerful gene-editing technology that has the potential to treat a myriad of genetic diseases such as beta-thalassemia and sickle cell anemia. As opposed to traditional gene therapies, which involve the introduction of healthy copies of a gene to a patient, CRISPR repairs the genetic mutation underlying a disease to restore function.

CRISPR-Cas9 was discovered in the bacterial immune system, where it is used to defend against and deactivate invading viral DNA. Cas9 is an endonuclease, or an enzyme that can selectively cut DNA. The Cas9 enzyme is complexed with a guide RNA molecule to form what is known as CRISPR-Cas9. Cas9 is often referred to as the molecular scissors, being that they cut and remove defective portions of DNA. Being that it is not perfectly precise, the enzyme will sometimes make unintended cuts in the DNA that can cause serious consequences. For this reason, enhancing the precision of the CRISPR-Cas9 system is of paramount importance.

Two versions of Cas9 are currently being used in CRISPR therapies: SpCas9 (derived from the bacteriaStreptococcus pyogenes) and SaCas9 (derived fromStaphylococcus aureus). Researchers have engineered variants of the SpCas9 enzyme to improve its precision, but these variants are too large to fit into the adeno-associated viral (AAV) vector that is often used to administer CRISPR to living organisms. SaCas9, however, is a much smaller protein that can easily fit into AAV vectors to deliver gene therapy in vivo. Being that no SaCas9 variants with enhanced precision are currently available, these CityU researchers aimed to identify a viable variant.

This recent research led to the successful engineering of SaCas9-HF, a Cas9 variant with high accuracy in genome-wide targeting in human cells and preserved efficiency. This work was led by Dr. Zheng Zongli, Assistant Professor of Department of Biomedical Sciences at CityU and the Ming Wai Lau Centre for Reparative Medicine of Karolinska Institutet in Hong Kong, and Dr. Shi Jiahai, Assistant Professor of Department of Biomedical Sciences at CityU.

Their work was based on a rigorous evaluation of 24 targeted human genetic locations which compared the wild-type SaCas9 to the SaCas9-HF. The new Cas9 variant was found to reduce the off-target activity by about 90% for targets with very similar sequences that are prone to errors by the wild-type enzyme. For targets that pose less of a challenge to the wild-type enzyme, SaCas9-HF made almost no detectable errors.

Our development of this new SaCas9 provides an alternative to the wild-type Cas9 toolbox, where highly precise genome editing is needed, explained Zheng. It will be particularly useful for future gene therapy using AAV vectors to deliver genome editing drug in vivo and would be compatible with the latest prime editing CRISPR platform, which can search-and-replace the targeted genes.

Dr. Shi and Dr. Zheng are the corresponding authors of this publication. The first authors are PhD student Tan Yuanyan from CityUs Department of Biomedical Sciences and Senior Research Assistant Dr. Athena H. Y. Chu from Ming Wai Lau Centre for Reparative Medicine (MWLC) at Karolinska Institutet in Hong Kong. Other members of the research team were CityUs Dr. Xiong Wenjun, Assistant Professor of Department of Biomedical Sciences, research assistant Bao Siyu (now at MWLC), PhD students Hoang Anh Duc and Firaol Tamiru Kebede, and Professor Ji Mingfang from the Zhongshan Peoples Hospital.

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Modified Protein Enhances the Accuracy of CRISPR Gene Therapy - DocWire News

Scientists are using gene therapy to treat a heart disease in dogs. Could humans be next? – 10News

Scientists are working to eliminate a type of heart disease in dogs using gene therapy.

They're zoning in on a heart condition called mitral valve disease thats common in 6% of dogs.

Scientists are using Cavalier King Charles spaniels for the research.

They tend to develop it at a younger age.

Scientists at Tufts University have already tested gene therapy in mice.

A virus is injected into them to deliver DNA to cells which causes them to create a protein.

What it essentially does is stops the heart valve from getting thicker, stopping the valve from leaking.

Researchers are now moving on to testing this in dogs.

But they think the treatment could go beyond just canines.

Many of the dog diseases are naturally occurring and really great models for human disease, says Dr. Vicky Yang, a veterinary cardiologist and research assistant professor at Cummings School of Veterinary Medicine at Tufts University. And I can see this, if it becomes successful in dogs, potentially going into thinking about treatment for humans for mitral valve disease.

The biotech company behind the treatment agrees. It says it could also expand beyond heart problems.

I think a larger question, though, is if we are able to prove this thesis of treating aging, making the animal generally healthier, could also treat heart failure, what other diseases could we treat in dogs? says Daniel Oliver, the CEO of Rejuvenate Bio. And could we progress this treatment onto past dogs and other animals and possibly humans?

The gene therapy would only be used for dogs just starting to experience heart problems.

Researchers still need to make sure the gene therapy is safe for all breeds before they make it available to the public.

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Scientists are using gene therapy to treat a heart disease in dogs. Could humans be next? - 10News

Triple-Gene Announces Completion of Enrollment and Dosing in Phase 1 Trial of INXN4001, First Multigenic Investigational Therapeutic Candidate for…

"We are excited to have reached this important milestone in the clinical evaluation of INXN-4001 for treatment of end-stage heart failure," stated Amit Patel, MD, MS, Co-Founder and Medical Director of TripleGene. "Heart failure rarely results from a single genetic defect, and while single gene therapy approaches have been studied, these treatments may not fully address the causes of the disease. Our unique multigenic approach is designed to stimulate biological activity targeting multiple points in the disease progression pathway."

Triple-Gene's investigational therapy uses non-viral delivery of a constitutively expressed multigenic plasmid designed to express human S100A1, SDF-1, and VEGF165 gene products, which affect progenitor cell recruitment, angiogenesis, and calcium handling, respectively, and target the underlying molecular mechanisms of pathological myocardial remodeling. The plasmid therapy is delivered via RCSI which allows for cardiac-specific delivery to the ventricle.

"Heart failure is the leading cause of death worldwide and represents a significant and growing global health problem. Aside from heart transplant and LVAD, current treatment options for those patients with end-stage disease are limited," commented Timothy Henry, MD, FACC, MSCAI, Medical Director of the Carl and Edyth Lindner Center for Research and Education at The Christ Hospital and a member of the Triple-Gene Medical Advisory Board. "The INXN4001 investigational therapy represents a biologically-based method focused on repairing the multiple malfunctions of cardiomyocytes, and I look forward to seeing the results of this initial safety study and further exploring the promise of this innovative treatment approach."

Triple-Gene will present preliminary data from the Phase 1 study at theAmerican Heart Association Scientific Sessionsat the Pennsylvania Convention Center in Philadelphia. A poster titled "Safety of First in Human Triple-Gene Therapy Candidate for Heart Failure Patients" will be presented on Sunday, November 17thfrom 3:00 pm - 3:30 pm ETin Zone 4 of the Science and Technology Hall.

About the Phase 1 Trial of INXN-4001INXN-4001 is being evaluated in a Phase I open label study in adult patients with implanted Left Ventricular Assist Device (LVAD). The study is designed to investigate the safety and feasibility of supplemental cardiac expression of S100A1, SDF-1 and VEGF-165 from a single, multigenic plasmid delivered via Retrograde Coronary Sinus Infusion (RCSI) in stable patients implanted with a LVAD for mechanical support of end-stage heart failure. Twelve stable patients with an implanted LVAD were allocated into 2 cohorts (6 subjects each) to evaluate the safety and feasibility of infusing 80mg of INXN4001 in either a 40mL (Cohort 1) or 80mL (Cohort 2) volume. The primary endpoint of safety and feasibility is assessed at the 6-month endpoint. Daily activity data are also collected throughout the study using a wearable biosensor. Dosing on both Cohorts 1 and 2 has been completed, and patients continue follow-up per protocol.

About Triple-GeneTriple-Gene LLC is a clinical stage gene therapy company focused on advancing targeted, controllable, and multigenic gene therapies for the treatment of complex cardiovascular diseases. The Company's lead product is a non-viral investigational gene therapy candidate that drives expression of three candidate effector genes involved in heart failure. Triple-Gene is a majority owned subsidiary ofIntrexon Corporation(NASDAQ: XON) co-founded by Amit Patel, MD, MS, and Thomas D. Reed, PhD, Founder and Chief Science Officer of Intrexon. Learn more about Triple-Gene

About Intrexon CorporationIntrexon Corporation (NASDAQ: XON) is Powering the Bioindustrial Revolution with Better DNAto create biologically-based products that improve the quality of life and the health of the planet through two operating units Intrexon Health and Intrexon Bioengineering. Intrexon Health is focused on addressing unmet medical needs through a diverse spectrum of therapeutic modalities, including gene and cell therapies, microbial bioproduction, and regenerative medicine. Intrexon Bioengineering seeks to address global challenges across food, agriculture, environmental, energy, and industrial fields by advancing biologically engineered solutions to improve sustainability and efficiency. Our integrated technology suite provides industrial-scale design and development of complex biological systems delivering unprecedented control, quality, function, and performance of living cells. We call our synthetic biology approach Better DNA, and we invite you to discover more atwww.dna.comor follow us on Twitter at@Intrexon, onFacebook, andLinkedIn.

TrademarksIntrexon, Powering the Bioindustrial Revolution with Better DNA,and Better DNA are trademarks of Intrexon and/or its affiliates. Other names may be trademarks of their respective owners.

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Triple-Gene Announces Completion of Enrollment and Dosing in Phase 1 Trial of INXN4001, First Multigenic Investigational Therapeutic Candidate for...

Here Are the Early Results From the First US CRISPR Trial for Cancer – Philadelphia magazine


This year, researchers from the University of Pennsylvania launched the first-ever clinical trial to genetically edit the immune cells of cancer patients using the technology.

Penn Perelman Center for Advanced Medicine | Courtesy photo

Researchers from the Abramson Cancer Center at the University of Pennsylvania are the first in the United States to attempt to genetically edit a cancer patients immune cells in the lab using CRISPR-Cas9 technology. Penn launched the first-ever U.S. clinical trial for this research earlier this year with support from the Parker Institute for Cancer Immunotherapy(PICI) andTmunity Therapeutics. On Wednesday, researchers confirmed they have successfully infused three participants in the trial thus far two with multiple myeloma and one with sarcoma and have observed the edited cells expand and bind to their tumor target with no serious side effects.

This trial is primarily concerned with three questions: Can we edit T cells in this specific way? Are the resulting T cells functional? And, are these cells safe to infuse into a patient? This early data suggests that the answer to all three questions may be yes, said Edward Stadtmauer, the studys principal investigator and the section chief of hematologic malignancies at Penn.

Its still too early, however, to answer the more pressing question the trial has posed: Can these genetically modified cells destroy cancer cells? But researchers believe the feasibility and safety theyve demonstrated so far provides optimism that the approach may be applicable across multiple areas of gene therapy research.

These early findings are the first step as we determine if this new breakthrough technology can help rewrite how we treat patients with cancer and perhaps other deadly diseases, said Sean Parker, the billionaire entrepreneur and founder and chairman of PICI. CRISPR editing could be the next generation of T-cell therapy, and we are proud to be a part of the first human trial in the United States.

It has taken Penn more than two years to get the appropriate institutional and federal regulatory approvals, and to recruit optimal participants for the trial. Patients had to be screened ahead of time to make sure their tumors were a match for the approach. Participants who met the requirements received other therapy as needed while they waited for their cells to be manufactured. Once that process was complete, all three received the gene-edited cells in a single infusion after a short course of chemotherapy.

Analysis of blood samples revealed that the CRISPR-edited T cells expanded and survived in all three participants. While none of the patients cancer cells have yet responded to the therapy, researchers say there were no treatment-related serious adverse events.

CRISPR has been more popularly known for its ethically questionable potential to alter human DNA, but the studys senior author and immunotherapy pioneer Carl June says his team is squarely focused on moving the field of gene therapy forward.

Our use of CRISPR editing is geared toward improving the effectiveness of gene therapies, not editing a patients DNA, June said. We leaned heavily on our experience as pioneers of the earliest trials for modified T-cell therapies and gene therapies, as well as the strength of Penns research infrastructure, to make this study a reality.

Previous human trials using CRISPR technology have predominantly been conducted in China until several trials launched in the U.S. this year. The technology is currently being tested by researchers in Massachusetts to potentially treat genetic blood disorders like sickle cell disease and certain forms of inherited blindness. Penns team aims to test the approach on a total of 18 patients by the end of the trial.

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Here Are the Early Results From the First US CRISPR Trial for Cancer - Philadelphia magazine

Gene Tech Company Claims to Have Found a Cure for HIV/AIDS – NewNowNext

by Sam Manzella 11/8/2019

A group of medical researchers in Maryland believe the answer for curing HIV/AIDS may be gene therapy.

American Gene Technologies (AGT), a Rockville-based medical research company, has submitted a Investigational New Drug (IND) application with the FDA to begin gene therapy trials that researchers believe could eliminate HIV in people already living with the virus.

The drugan HIV treatment program called AGT103-Tis a single-dose, lentiviral vector-based gene therapy that AGT says could remove infected cells from the body and decrease or eliminate the need for lifelong antiretroviral treatment in HIV-positive patients.

If approved, the company hopes to begin a Phase 1 clinical trial that will examine the safety of AGT103-T in humans.

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In a press statement, AGT chief science officer C. David Pauza, PhD, said the companys objective is to treat HIV disease with an innovative cell and gene therapy that reconstitutes immunity to HIV and will control virus growth in the absence of antiretroviral drugs.

AGTs approach differs from other medical researchers attempts to cure HIV. As NewNowNext reported earlier this year, researchers in Europe made headlines when two separate HIV-positive patients no longer had the virus after obtaining bone marrow transplants from donors with an HIV-resistant mutation to treat unrelated cancers.

Those patients marked the second and third time doctors were able to effectively cure patients living with HIV via bone marrow transplant in the history of modern medicine. However, HIV/AIDS activists and medical professionals were quick to raise concerns about the feasibility of curing HIV with bone marrow transplants on a more widespread basis.

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Kenneth Freedberg, MD, a professor of medicine at Harvard Medical School and Massachusetts General Hospital, told NewNowNext in March that the method is not a remotely plausible strategy for HIV treatment for the vast majority of patients.

A bone marrow transplant is an extraordinarily toxic and life-threatening intervention, which you do if someone has an illness thats clearly going to be fatal, Freedberg explained. There must be no other treatment options available. It puts people at massive risk for infections and toxicity complications.

As the fight against HIV/AIDS wages on, communities at risk of contracting the virus continue to take preventative measures against new infectionsincluding daily use of Pre-exposure prophylaxis (PrEP), a potentially life-saving HIV prevention drug that is massively popular among gay, bisexual, and queer men.

In the United States, PrEP is pretty much exclusively available as Truvada, its brand-name version manufactured by Gilead Sciences with a very high retail markup. That may change soon, though: Earlier this week, the government filed a lawsuit against Gilead alleging patent infringement on PrEP, which was patented by public health researchers at the Department of Health and Human Services years ago.

Brooklyn-based writer and editor. Probably drinking iced coffee or getting tattooed.

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Gene Tech Company Claims to Have Found a Cure for HIV/AIDS - NewNowNext

3 Cancer Treatment Stocks to Buy Right Now – The Motley Fool

Now is a great time to have biotech stocks in your portfolio. While biotech investing can be scary, because the small-cap companies are often unprofitable research-and-development labs, this is also where a lot of the cutting-edge science is happening.

Let's see how Mirati Therapeutics (NASDAQ:MRTX), Iovance Biotherapeutics (NASDAQ:IOVA), and Personalis (NASDAQ:PSNL) are all using gene therapy in the fight against cancer.

Image source: Getty Images.

Mirati Therapeutics is in a race with Amgen (NASDAQ:AMGN) to find a drug that successfully inhibits KRAS mutations. KRAS is a gene in our bodies that has been identified as a cause of multiple cancers. Right now one of Mirati's drugs is targeting a specific sub-mutation identified as KRAS G12C. This genetic malfunction is seen in 14% of non-small cell lung cancers, 5% of colon cancers, and 2% of pancreatic cancers. The company's drug is an attempt to shut down this mutated gene so it will stop producing cancer cells.

Investors who want to play it safe might want to invest in Amgen, not Mirati; Amgen is also pursuing drugs to inhibit the KRAS mutations. However, Amgen is a highly profitable, $130 billion megacap biotech with multiple drugs in clinical trials. If its KRAS program fails, Amgen's stock will take a minor hit and the company will continue onwards and upwards. On the other hand, if Amgen and Mirati are both right about the importance of KRAS genes, then Mirati shareholders are likely to see far bigger returns on their investments. With the smaller biotech, the risk is higher but the rewards are greater.

Mirati is a $4 billion small cap with extensive knowledge of KRAS. Failure here would be brutal to the stock. On the other hand, any success would boost the stock into the stratosphere. So far, investors in Mirati have been winning big. Amgen has returned 56% to investors over the last five years, slightly underperforming the S&P 500, but tiny Mirati has returned 523%.

Iovance Biotherapeutics is introducing a novel way to fight against cancer. The company relies upon medicine that is specialized for each patient. When a cancer starts attacking your body, your system starts producing lymphocytes that are designed to infiltrate and attack the tumor. Cancer cells adopt and mutate to avoid destruction.

What Iovance does is remove some of these cancer-fighting agents, referred to as tumor-infiltrating lymphocytes (TILs), from your body. The company's technology amplifies and multiplies these cells in the lab, creating billions of them. Then your own cancer-fighting agents are injected back into your body.

Iovance is running a phase 3 trial trial for Lifileucel, its treatment for skin cancer. But what's causing the most excitement is LN-145, which is being tested on multiple cancers. The company is running a phase 3 trial for cervical cancer, and a phase 2 trial for head and neck cancers. Also, MD Anderson Cancer Network is running a phase 2 test on LN-145 for ovarian cancer and sarcoma.

The stock took off after it was reported that LN-145 had a 44% overall response rate against cervical cancer, and Lifileucel had a 38% overall response rate against melanoma. Iovance is a $2.72 billion small cap. It has $400 million in cash, $12 million in debt, and no revenue. So far in 2019 it's returned 132% to investors.

Personalis is developing the NeXT platform, a hugely ambitious undertaking that is mapping approximately 20,000 genes in the human body. Spun out of Stanford University, the company has a contract with the U.S. Department of Veterans Affairs. The federal agency is providing it the DNA information of over 775,000 veterans, so with this data, Personalis is mapping over 15 billion human genes. With all these volunteers, it's developing a massive library of genetic data. Biotechs that subscribe to its service can access this information as they design cancer-fighting drugs in the lab.

The company's immediate market is all the biotech companies doing cancer research. Using its library, subscribers can find cancer targets and design specific drugs to suppress the mutating genes that spread cancer in human beings. Right now Personalis has over 45 biopharma subscribers to its service. The company estimates this is a $5 billion market opportunity.

Next year Personalis hopes to compete in the $14 billion market of cancer diagnostics. It will offer its own liquid biopsy designed to detect cancer, and compete with Guardant Health (NASDAQ:GH), as well as NantHealth, Grail (a start-up funded in part by Jeff Bezos and Bill Gates), Thrive (a start-up spun out of Johns Hopkins), and others. We don't yet know how much Personalis will charge for its biopsy, or how successful it will be.

But what we do know is that right now the company is a lot cheaper than its market-leading peer:

Data source: Bloomberg and Yahoo Finance. P/S = price to sales; IPO = initial public offering.

The market appears to be taking a wait-and-see attitude toward Personalis; certainly there's no excitement right now about its shares. That might change when its liquid biopsy is introduced next year.

In the meantime, Personalis is developing a very impressive library of knowledge of the human genome. Maybe one day the company will be competing with 23andme to provide personalized medicine to individuals (a market estimated to be worth $40 billion). It's definitely a stock to keep an eye on, as the future looks bright.

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3 Cancer Treatment Stocks to Buy Right Now - The Motley Fool

How Gene Therapy Is Evolving to Tackle Complex… –

Gene therapy has traditionally been applied to well-understood diseases where a single genetic mutation was to blame. A new generation of technology is expanding the potential of gene therapy to treat conditions that were previously unreachable.

Since the first gene therapy clinical trials in the 1990s, the technology has made its way into the market for conditions ranging from blindness to cancer.

Gene therapy has the potential to fix any genetic mutation causing disease by inserting a new copy of the faulty gene. However, its reach has historically been limited.

Weve been constrained with the things we can do with gene therapy, said Dmitry Kuzmin, Managing Partner at 4BIO Capital, a London-based VC that specifically invests in advanced therapies. If you look across the successes in gene therapy in the last five years, most of these were in diseases that are pretty straightforward from the engineering perspective.

Technical limitations have meant that gene therapy has been restricted to rare diseases caused by a single genetic mutation, as well as to certain areas of the body, such as the eye and the liver.

According to Kuzmin, there have been so far three generations of gene therapy technology. Generation one would be classic single-gene replacement, such as Luxturna, a gene therapy to fix a specific genetic mutation causing blindness. Generation two would consist of using gene therapy to introduce new functions. An example is Kymriah, where immune cells are equipped with a molecule that helps them hunt down cancer cells.

The third generation is the one that could hold the key to unlocking the full potential of gene therapy. It englobes several technologies that can be used to introduce a new drug target into the patient, making it possible to turn the therapy on and off as well as to tune its intensity.

As the first two generations get optimized and the third generation enters the clinic, we are now expanding our reach into areas that have been previously rather inaccessible, Kuzmin told me. One of them is the brain.

Treating the brain has long been a huge challenge for medicine. Take epilepsy, for example.

Epilepsy affects 1% of the whole population and about 30% of people with seizures of epilepsy continue to have seizures despite medication, said Dimitry Kullmann, Professor at University College London. Theres a paradox. We have a good understanding of the mechanisms behind epilepsy, but were unable to suppress seizures in a significant proportion of people with epilepsy.

The reason is that the molecules that we use for drugs dont target the epileptic zone of the brain; they bathe the entire body with medication, Kullmann told me. These drugs dont differentiate between neurons and synapses that derive the seizures, and those parts of the brain that are responsible for memory, sensory functions, motor functions and balance.

Gene therapy could provide a solution for this problem. Kullmanns group has been researching this approach for years and is now getting ready to start the first clinical trial in humans within a year.

A gene therapy can be directly injected in the area of the brain causing seizures. Furthermore, using DNA sequences called promoters, it is possible to restrict the effect of gene therapy to specific neurons within that area. In the case of epilepsy, gene therapy can be used to decrease the activity of only excitatory neurons, which cause epileptic seizures when they are overactive.

Another approach that Kullmans group is testing is chemogenetics. The idea here is to use gene therapy to put a specific receptor into the neurons, explained Kullmann. This receptor is designed to respond to a drug that, when given to the patient, decreases the activity of the neuron to suppress seizures.

The advantage is that you can switch on and off the therapeutic effect on demand by just giving, or not giving the drug, Kullmann said. This approach can thus make gene therapy more precise, being able to tune it to the specific needs of each patient. In addition, it reduces the big challenge of getting the dose right in a one-off treatment.

Ultimately, this technology could allow scientists to target a wide range of conditions that come under the umbrella of epilepsy, rather than just a specific form of the condition caused by a genetic mutation.

The approach could be extended to other conditions involving the brain, such as Parkinsons, ALS and pain. However, this kind of research is still at an early stage and it will take a while until its potential is proven in humans.

Blindness has been a major target of gene therapy because of the fact that the eye is an ideal target for this technology. The activity of the immune system is suppressed in the eye, minimizing the chances of rejection. In addition, unlike other cells in the body, those involved in vision are not renewed over time, being able to retain the injected DNA for years.

However, there are hundreds of genetic mutations that can cause blindness. With the classical gene therapy approach, a different therapy would have to be developed from scratch for each mutation. While some companies are doing just this for the most common mutations causing blindness, many other less frequent mutations are being left behind.

Others are turning to new generations of gene therapy technology. We figured out that it would be very, very difficult to use the classical gene therapy approach in each individual mutation, said Bernard Gilly, CEO of GenSight, a Parisian biotech developing gene therapies for blindness.

While the companys leading programs follow this classical approach, the company has also started clinical trials using a technology called optogenetics. Following a similar principle to gene therapy, optogenetics consists of introducing a protein that reacts to light into a cell.

GenSight is using optogenetics to develop a single therapy for the treatment of retinitis pigmentosa. This genetic condition can be caused by mutations in any of over 200 genes and results in progressive vision loss in children due to the degeneration of photoreceptor cells that perceive light and send signals to the brain.

With optogenetics, it would be possible to transfer the lost photoreceptor function to the cells in the retina that are responsible for relaying visual information to the brain. Using specialized goggles, the images captured by a camera are transformed into light patterns that stimulate these cells in the precise way needed for the brain to form images.

The company is currently testing this approach in clinical trials. We believe that this approach will allow us to restore vision in those patients who became blind because of retinitis pigmentosa, Gilly told me.

Optogenetics would not work a miracle, but it might be able to give people back the ability to navigate an unknown environment with a certain level of autonomy. Recognizing faces is a more challenging goal; although reading is not yet on the horizon, according to Gilly.

Still, the potential of optogenetics to address multiple genetic mutations with a single treatment might be revolutionary. As long as the neurons responsible for sending light signals to the brain are intact, this approach could be extended to other forms of blindness. In addition, conditions affecting the brain such as epilepsy, Parkinsons or ALS could be treated with this approach by introducing an implant to shine light on the target neurons.

However, approaches applying optogenetics to the brain are still further down the line. While optogenetics technology has been around for over 20 years, its application in humans is still very limited and in the early stages of research.

Chemogenetics and optogenetics are just two out of a wave of new technologies addressing the historical limitations of gene therapy. Other approaches are in development, such as using thermogenetics, which consists of introducing proteins that are activated by the heat created by infrared light.

With a growing range of tools available, it is becoming easier than ever for scientists to develop gene therapies that can address the specific challenges of different conditions affecting areas of the body. Traditionally, locations such as the heart, the lungs or the pancreas have been particularly difficult to target with gene therapy. That might soon stop being the case.

As we go forward, were interested in taking gene therapy out of this little box and trying to use all the knowledge we have to benefit patients in larger indications, said Kuzmin.

As gene therapy expands into more mainstream conditions, it could take precision medicine to a whole new level and help address the big variability that is often seen across patients with the same diagnosis.

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How Gene Therapy Is Evolving to Tackle Complex... -

Sangamo Announces Gene Therapy and Ex Vivo Gene-Edited Cell Therapy Data Presentations at the American Society of Hematology Annual Meeting – Business…

BRISBANE, Calif.--(BUSINESS WIRE)--Sangamo Therapeutics, Inc. (NASDAQ: SGMO), a genomic medicine company, today announced that hemophilia A gene therapy clinical data and hemoglobinopathies ex vivo gene-edited cell therapy data will be featured in poster presentations at the 61st Annual Meeting of the American Society of Hematology (ASH). The ASH abstracts, which were submitted on August 3, 2019, were released online this morning. The conference will take place in Orlando, FL, from December 7-10, 2019.

Gene Therapy

The SB-525 poster will show updated Alta study data including durability of Factor VIII (FVIII) levels, bleeding rate, factor usage, and safety, for all five patients in the high dose cohort of 3e13 vg/kg, with approximately 4 months to 11 months of follow-up after treatment with SB-525.

As of the abstract submission date, four patients in the 3e13 vg/kg cohort achieved FVIII levels within the normal range with no bleeding events reported up to 24 weeks post-administration. These patients did not require FVIII replacement therapy following the initial prophylactic period of up to approximately 3 weeks post-SB-525 administration. The fifth patient in the 3e13 vg/kg cohort had only recently undergone treatment with SB-525 at the time of the abstract submission. As previously reported, one patient had treatment-related serious adverse events (SAEs) of hypotension and fever, which occurred approximately 6 hours after completion of the vector infusion and resolved with treatment within 24 hours, with no loss of FVIII expression. SB-525 is being developed as part of a global collaboration between Sangamo and Pfizer.

The rapid kinetics of Factor VIII expression, durability of response, and the relatively low intra-cohort variability in the context of a complete cessation of bleeding events and elimination of exogenous Factor VIII usage continues to suggest SB-525 is a differentiated hemophilia A gene therapy, said Bettina Cockroft, M.D., M.B.A., Chief Medical Officer of Sangamo, commenting on the published abstract. We are pleased with the progress of the program toward a registrational Phase 3 study led by Pfizer, who announced it has enrolled its first patient in the 6-month Phase 3 lead-in study. We have recently completed the manufacturing technology transfer to Pfizer and initiated the transfer of the IND.

Ex Vivo Gene-Edited Cell Therapy

The ST-400 beta thalassemia poster will show preliminary results from the first three patients enrolled in the Phase 1/2 THALES study. In this study, hematopoietic stem progenitor cells (HSPCs) are apheresed from the patient, edited to knock out the erythroid specific enhancer of the BCL11A gene, and cryopreserved prior to infusion back into the patient following myeloablative conditioning with busulfan. The first three patients all have severe beta thalassemia genotypes: 0/0, homozygous for the severe + IVS-I-5 (G>C) mutation, and 0/+ genotype including the severe IVS-II-654 (C>T) mutation, respectively.

As of the abstract submission date, Patient 1 and Patient 2 had experienced prompt hematopoietic reconstitution. Patient 1 had increasing fetal hemoglobin (HbF) fraction that contributed to a stable total hemoglobin. After being free from packed red blood cell (PRBC) transfusions for 6 weeks, the patient subsequently required intermittent transfusions. Patient 2 had rising HbF levels observed through 90 days post-infusion. For both patients, as of the most recent follow-up reported in the abstract, on-target insertions and deletions (indels) were present in circulating white blood cells. Patient 3 had just completed ST-400 manufacturing at the time of abstract submission. As previously disclosed, Patient 1 experienced an SAE of hypersensitivity during ST-400 infusion considered by the investigator to be related to the product cryoprotectant, DSMO, and which resolved by the end of the infusion. No other SAEs related to ST-400 have been reported and all other AEs have been consistent with myeloablation. No clonal hematopoiesis has been observed. Longer follow-up will be required to assess the clinical significance of these early results. ST-400 is being developed as part of a global collaboration between Sangamo and Sanofi, along with support through a grant from the California Institute for Regenerative Medicine (CIRM).

The first three patients enrolled in the THALES study all have severe beta thalassemia genotypes that result in almost no endogenous beta globin production. The increases in fetal hemoglobin and presence of on-target indels in circulating blood cells suggests successful editing using zinc finger nucleases. The results are preliminary and will require additional patients and longer-term follow-up to assess their clinical significance, said Adrian Woolfson, BM., B.Ch., Ph.D., Head of Research and Development. It is important to note that myeloablative hematopoietic stem cell transplantation reboots the hematopoietic system, and that sufficient time is required for the stem cells to fully repopulate the marrow and for new blood cells to form. In other myeloablative conditioning studies in a similar patient population, full manifestation of the effects of gene modification in the red blood cell compartment has taken as long as 12 months or more to become evident.

Sanofis in vitro sickle cell disease poster details a similar approach to ST-400, using mobilized HSPCs from normal donors and SCD patients and utilizing the same zinc finger nuclease for gene editing, delivered as transient non-viral RNA, and designed to disrupt the erythroid specific enhancer of the BCL11A gene, which represses the expression of the gamma globin genes, thereby switching off HbF synthesis. Results from ex vivo studies demonstrated enriched biallelic editing, increased HbF, and reduced sickling in erythroid cells derived from non-treated sickle cell disease patients. Sanofi has initiated a Phase 1/2 trial evaluating BIVV003, an ex vivo gene-edited cell therapy using ZFN gene editing technology to modify autologous hematopoietic stem cells using fetal hemoglobin to produce functional red blood cells with higher BhF content that are resistant to sickling in patients with severe sickle cell disease. Recruitment is ongoing.

About the Alta study

The Phase 1/2 Alta study is an open-label, dose-ranging clinical trial designed to assess the safety and tolerability of SB-525 gene therapy in patients with severe hemophilia A. SB-525 was administered to 11 patients in 4 cohorts of 2 patients each across 4 ascending doses (9e11 vg/kg, 2e12 vg/kg, 1e13vg/kg and 3e13vg/kg) with expansion of the highest dose cohort by 3 additional patients. The U.S. Food and Drug Administration (FDA) has granted Orphan Drug, Fast Track, and regenerative medicine advanced therapy (RMAT) designations to SB-525, which also received Orphan Medicinal Product designation from the European Medicines Agency.

About the THALES study

The Phase 1/2 THALES study is a single-arm, multi-site study to assess the safety, tolerability, and efficacy of ST-400 autologous hematopoietic stem cell transplant in 6 patients with transfusion-dependent beta thalassemia (TDT). ST-400 is manufactured by ex vivo gene editing of a patient's own (autologous) hematopoietic stem cells using non-viral delivery of zinc finger nuclease technology. The THALES study inclusion criteria include all patients with TDT (0/0 or non- 0/0) who have received at least 8 packed red blood cell transfusions per year for the two years before enrollment in the study. The FDA has granted Orphan Drug status to ST-400.

About Sangamo Therapeutics

Sangamo Therapeutics, Inc. is focused on translating ground-breaking science into genomic medicines with the potential to transform patients' lives using gene therapy, ex vivo gene-edited cell therapy, in vivo genome editing, and gene regulation. For more information about Sangamo, visit

Forward-Looking Statements

This press release contains forward-looking statements regarding Sangamo's current expectations. These forward-looking statements include, without limitation, statements regarding the Company's ability to develop and commercialize product candidates to address genetic diseases with the Company's proprietary technologies, as well as the timing of commencement of clinical programs and the anticipated benefits therefrom. These statements are not guarantees of future performance and are subject to certain risks, uncertainties and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, the outcomes of clinical trials, the uncertain regulatory approval process, uncertainties related to the execution of clinical trials, Sangamo's reliance on partners and other third-parties to meet their clinical and manufacturing obligations, and the ability to maintain strategic partnerships. Further, there can be no assurance that the necessary regulatory approvals will be obtained or that Sangamo and its partners will be able to develop commercially viable product candidates. Actual results may differ from those projected in forward-looking statements due to risks and uncertainties that exist in Sangamo's operations and business environments. These risks and uncertainties are described more fully in Sangamo's Annual Report on Form 10-K for the year ended December 31, 2018 as filed with the Securities and Exchange Commission and Sangamo's most recent Quarterly Report on Form 10-Q. Forward-looking statements contained in this announcement are made as of this date, and Sangamo undertakes no duty to update such information except as required under applicable law.

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Sangamo Announces Gene Therapy and Ex Vivo Gene-Edited Cell Therapy Data Presentations at the American Society of Hematology Annual Meeting - Business...

Edited Transcript of VYGR earnings conference call or presentation 6-Nov-19 1:00pm GMT – Yahoo Finance

CAMBRIDGE Nov 11, 2019 (Thomson StreetEvents) -- Edited Transcript of Voyager Therapeutics Inc earnings conference call or presentation Wednesday, November 6, 2019 at 1:00:00pm GMT

* G. Andre Turenne

Voyager Therapeutics, Inc. - CEO, President & Director

* Matthew P. Ottmer

Voyager Therapeutics, Inc. - COO

Voyager Therapeutics, Inc. - Chief Medical Officer and Head of Research & Development

H.C. Wainwright & Co, LLC, Research Division - Analyst

Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst

* Philip M. Nadeau

Good morning, and welcome to the Voyager Therapeutics Third Quarter 2019 Financial Results and Corporate Highlights Conference Call. (Operator Instructions) Please be advised that this call is being recorded. At this time, I'd like to turn the call over to Vasilis Kariolis, Voyager's Assistant Controller. Please proceed.

Thank you. Good morning, and thank you for joining us. With me on the call today are Andre Turenne, our President and Chief Executive Officer; Omar Khwaja, Chief Medical Officer and Head of R&D; and Matt Ottmer, Chief Operating Officer.

Earlier today, we issued a press release, which outlines the financial results and corporate highlights for the third quarter of 2019. The release is available at

Before we begin, just a reminder that the forward-looking statements included in this call represent the company's view as of today, November 6, 2019. Voyager disclaims any obligation to update these statements to reflect future events or circumstances, except as required by law. Please refer to today's press release as well as Voyager's filings with the SEC for information concerning risk factors that could cause actual results to differ materially from those expressed or implied by such statements.

With that, I'll pass the call over to Andre.

G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [3]

Thank you, Vasilis, and good morning, everyone. Welcome to our Q3 earnings and corporate highlights call. Our CFO, Allison Dorval, is unable to participate in the call this morning due to a death in her immediate family, which sadly occurred on Sunday. Our heartfelt thoughts are with Allison and her family. I thank Vasilis, our Assistant Controller, for stepping in and covering our financial highlights.

I'll begin today by walking you through some of our recent corporate developments. Omar will then provide a pipeline update, and Vasilis will wrap up with the financial results. Once we've concluded our remarks, we'll have some time to take your questions.

We've had another productive quarter in Q3 at Voyager, building on a transformative first half of the year during which we entered into 2 important collaborations and a restructured one. It's an exciting time at Voyager as we gain momentum and expand on our foundation. Voyager sits squarely at the intersection of gene therapy and neuroscience. This dual focus on AAV gene therapy and neurological diseases provides us with several advantages. For one, as we've continued to hire key talent, we've been able to add colleagues with specialized expertise precisely in our chosen area. Their experience is already proving to add significant value to our efforts.

Another benefit of our focus as we keep advancing our pipeline is that we're finding invaluable learnings translating from program to program. We're seeing this, for example, as we've begun planning for the rapid transition from IND to first patient treated in our Huntington's disease program. Given the similar nature of the neurosurgical procedure involved for the onetime HD treatment and the onetime PD treatment, we expect to more rapidly enable sites to enroll study participants than what have otherwise been possible without our prior experience.

The benefits of our focused experience also apply to our earlier-stage programs. Our work on a vectorized antibody against pathological species of alpha-synuclein with our partner, AbbVie, is progressing faster than expected in light of the early learnings from our anti-tau vectorized antibody efforts. These learnings in turn are now being applied to our own additional efforts in vectorized antibodies. Moving forward, we'll continue to rigorously apply our learnings and those from others working in the space as we further advance our pipeline and platform.

Regarding our lead program, VY-AADC for Parkinson's disease, which is partnered with Neurocrine, we expect to present final 3-year data from all 3 cohorts of the 1101 Phase I trial at a medical conference in 2020.

2020 is also expected to be an important year for our Huntington's program as we anticipate filing an IND application and beginning screening and enrollment into the clinical trial. As we announced in a press release this morning, we presented some positive data on VY-HTT01 at ESGCT last month. Omar will share more details on this shortly.

Finally, we're pleased to announce today that Allen Nunnally has been promoted to the position of Chief Business Officer, from his previous role as VP of Corporate and Business Development. Allen has been a key collaborator in my first year at Voyager, and I look forward to his continued success in his new role.

I'll now turn the call over to Omar to provide more detail on our pipeline programs.


Omar Khwaja, Voyager Therapeutics, Inc. - Chief Medical Officer and Head of Research & Development [4]


Thank you, Andre. First, I'll go through recent updates on our Parkinson's disease program. As Andre mentioned, the collaboration with Neurocrine, which we entered earlier this year, is off to a good start. We've agreed to the proposed statistical analysis plan for RESTORE-1 and are requesting feedback from the FDA before year-end. Steady progress continues to be made towards enrollment of the RESTORE-1 trial. We'll provide a more detailed update on RESTORE-1 after we receive feedback from the agency.

As a reminder, our approach to Parkinson's disease with the VY-AADC program is highly differentiated. It consists of the targeted delivery of a small volume of gene therapy to the region of the brain where it is needed for motor function. The result is a regulatable system, controllable by the standard-of-care oral medication. This ability to regulate the transient activity is highly desirable and a rather unique feature for AAV gene therapy. By creating a reservoir of AADC, the enzyme needed to convert levodopa to dopamine in the putamen, we're bypassing dying presynaptic neurons and introducing AADC into healthy postsynaptic neurons, where it can then be used to produce dopamine. AADC delivered into the putamen will do nothing on its own. But AADC in combination with levodopa will produce dopamine. Our approach gives the patient the exogenous control as to the amount of dose they needed to manage their motor function and the ability to avoid the negative impacts of too much dopamine in brain regions where it is not needed.

The Phase Ib trial was initiated in 2014. So we're now starting to see longer-term results that may speak to both the durability of effect and in the context of a progressive degenerative disease, contrast against the predicted course of disease progression. We expect to present 36 months data from all 3 cohorts in PD 1101 as well as 2-year data from PD 1102 at scientific meetings in 2020. The patients completing the 3-year protocol on PD 1101 and PD 1102 are now enrolling in our longer-term extension study. This will eventually provide us with over 5 years of data in addition to the placebo-controlled data at the time of the BLA filing and payer discussions.

Our Huntington's disease program is also progressing well. We've held advisory meetings with both neurologists and neurosurgeons and have received positive feedback on our delivery approach as well as our proposed clinical trial design and biomarker assessment. Our delivery approach leverages our learnings from the Parkinson's program, with local delivery of VY-HTT01 into the putamen. For Huntington's disease, we're also delivering directly into the thalamus. We chose this delivery approach based on our understanding of the disease pathology and the importance of delivering vector to the striatum as well as to the cortex. Pathological changes of Huntington's disease are evident earliest in the striatum, with changes in the cortex becoming noticeable as the disease progresses.

In fact, certain areas of the brain of a patient with Huntington's disease are deteriorating well before symptoms appear. The thalamus, in contrast, is a largely preserved structure in the early stages of Huntington's disease. Delivery of our gene therapy to the thalamus as well as to the putamen should allow us to deliver enough vector to impact the striatum as well as leverage the rich connections between the thalamus and the cortex to reach the outer brain.

Last month, at the European Society of Gene and Cell Therapy Meeting in Barcelona, we presented an update on our VY-HTT01 program during an oral platform presentation. We've previously presented data on dose-dependent vector biodistribution as well as HTT mRNA knockdown in the brains of nonhuman primates. In our recent presentation, we provided new evidence that VY-HTT01 also efficiently lowers huntingtin protein, and that huntingtin protein reduction is commensurate with the mRNA lowering and vector genome distribution in the NHP brain regions analyzed. These findings provide further evidence that our gene therapy, delivered to the thalamus and putamen, results in significant reductions in HTT, mRNA and in huntingtin protein to levels that are predicted to be clinically efficacious.

We now expect filing an IND for VY-HTT01 for Huntington's disease during the first half of 2020. As the kinetics of Huntington knockdown appear to be different in nonhuman primates than in rodents, we plan on submitting an IND application with final 1-year data from our preclinical studies instead of the previously planned interim 6 months data. Our goal is to minimize the amount of time between IND acceptance and first patient dose. We will be leveraging our related clinical experience in Parkinson's disease to achieve this.

Activities towards site selection engagement have already begun and will continue to take place in the fourth quarter and the beginning of 2020. We continue to expect screening and dosing of the first patient planned clinical study during 2020.

Our other pipeline programs, including the Friedreich's ataxia program with Neurocrine, and our 2 vectorized antibody programs with AbbVie, continue to progress. We are working on studies to support lead candidate selection for Friedreich's ataxia and continue to deliver on or ahead of schedule against our work plans on the AbbVie collaborations. Additionally, we've agreed on the 2 discovery sets with Neurocrine and are working on our own discovery efforts against new targets.

With our focus and expertise in neurological disease, we're pursuing several opportunities that are compelling targets for AAV gene therapy. We expect to provide more information on new programs during 2020.

I'll now pass the call on to Vasilis with the financial update.


Vasilis Kariolis, [5]


Thank you, Omar. Voyager reported net loss of $15 million or $0.41 per share for the third quarter ended September 30, 2019 compared to net loss of $20.3 million or $0.63 per share for the third quarter of 2018. Collaboration revenues of $20.4 million for the third quarter ended September 30, 2019, compared to collaboration revenues of $2.1 million for the third quarter of 2018. These 2019 revenues reflect the recognition of noncash amounts for research services that were performed for various programs under the Abbvie and Neurocrine collaboration agreements, in addition to amounts expected to be reimbursed by Neurocrine as per that collaboration agreement. Amounts can vary based on quarterly assessments of our efforts under each of these collaborations.

The increase in collaboration revenue during the third quarter of 2019 compared to the same period in 2018 primarily relates to the recognition of amounts from the Neurocrine and AbbVie alpha-synuclein collaborations, both of which were entered into in Q1 2019. Additionally, revenue related to the Abbvie tau collaboration increased year-over-year as our efforts continue to increase. These increases were offset by a reduction in collaboration revenue from our collaboration with Sanofi Genzyme, which was restructured in June 2019.

R&D expenses of $29.8 million for the third quarter ended September 30, 2019, compared to $16.6 million for the third quarter of 2018. These expenses include costs incurred under the Neurocrine collaboration, which are expected to be reimbursed. The increase in R&D expenses in the third quarter of 2019 related primarily to external research and development costs and increased employee-related and facility costs to support the advancement of our pipeline programs, including our RESTORE-1 Phase II clinical trial for VY-AADC.

General and administrative expenses of $8.5 million for the third quarter ended September 30, 2019, compared to $6.6 million for the third quarter of 2018. The increase in G&A expenses in the third quarter of 2019 is primarily due to an increase in employee-related and facility costs to support the advancement of our pipeline programs and growing operations.

As of September 30, 2019, we had $307.4 million in cash, cash equivalents and marketable debt securities compared to $155.8 million at December 31, 2018. Operating expenses are anticipated to be $150 million to $155 million, exceeding our previously forecasted range of $140 million to $150 million, largely as a result of higher-than-planned noncash expenses. Nevertheless, we continue to project year-end cash, cash equivalents and marketable debt securities to be in the previously forecasted range of $280 million to $290 million. Based on our current operating plans, we expect these amounts to be sufficient to meet our operating needs and capital expenditure requirements into mid-2022.

With that, we would like to now open the call up for questions. Operator?


Questions and Answers


Operator [1]


(Operator Instructions) And our first question comes from Phil Nadeau with Cowen and Company.


Philip M. Nadeau, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [2]


My question's on the Huntington's program. You mentioned in your prepared remarks that, I think, 1-year data is necessary for the IND, given the difference in kinetics in the knockdown between rodents and nonhuman primates. Can you talk a little bit more about the difference? What exactly are you seeing? And why is 1-year data more informative than 6 months in?


G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [3]


Yes. Thanks, Phil, for the question. I'll ask Omar to address it.


Omar Khwaja, Voyager Therapeutics, Inc. - Chief Medical Officer and Head of Research & Development [4]


Yes. So in -- back in 2017, Voyager had a pre-IND meeting with the FDA. And in the discussions around the definitive toxicology and biodistribution study that was planned, the feedback from the FDA was that the selected time points for assessment of toxicology should match the kinetics of transient expression and the specific request was that the time points would co-onset with the onset peak and plateaued expression of the transgene. At 26 weeks, the -- in terms of the bioanalytics we have, we don't yet -- aren't yet confident that we can say that the transgene expression has plateaued, and that their knockdown impact is also at its plateau as well. So that's why -- that's the reason that we've decided to not submit with interim 26-week data, but to continue the study to 53 weeks and submit with a full data set.


Philip M. Nadeau, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [5]


That's helpful. And I guess, when you say hasn't plateaued, is the level of knockdown continuing to increase? Or is it decreasing towards a plateau? And what are the implications for the human data? When -- at what time point do you think human proof-of-concept data, therefore would be available? Is it going to take 52 weeks to follow-up for that as well?


Omar Khwaja, Voyager Therapeutics, Inc. - Chief Medical Officer and Head of Research & Development [6]


Yes. That's a great question. I mean, I think it's not so much that the knockdown in protein levels haven't plateaued, but we really need another data time point to ensure that, that is a true plateau rather than, that's just 2 time points that we're saying that we've got knocked down and it's stable. I think we need to have a third one to be certain for that.

I think we'll probably have to directly extrapolate that to the human situation until we actually conduct the human study. It's going to be difficult to know how that extrapolates, but it certainly implies, based on what we've observed so far, that on the profile that we see so far, it means that it's likely that it's going to be at least 3 months in the human that we would see the maximum expression of the transgene.


G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [7]


To -- just to add to the clarification, Phil, what we're seeing is a continued reduction in the -- or increase in the knockdown over time. So that's the direction. So if that could be a positive clinically, that you have the peak lowering that is higher than what we've observed at the 5 weeks in the earlier studies, what -- as Omar said, what we're looking to have is just the comfort that we have an understanding of how low it goes and at what point that is achieved.


Operator [8]


And our next question comes from Charles Duncan with Cantor Fitzgerald.


Charles Cliff Duncan, Cantor Fitzgerald & Co., Research Division - Senior Analyst [9]


Condolences to Allison. Had a question on the PD program and then a follow-up on the HD program. Regarding the PD program, I'm wondering, you said that you have agreed to the staff plan with Neurocrine for RESTORE. And I'm just kind of wondering if you can provide additional color now that you're thinking about what to do there. In terms of the patient population, sizing and timing for RESTORE-1, can you provide any additional color on that?


G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [10]


Yes. Thanks, Chaz, for the question. So at this stage, we're not ready yet to give the further guidance as to the exact size of the study. We anticipate, as we've said previously, that it will be in the range that we've guided, 75 to 100 patients. And the work that we've done is just to determine with our new partner what the precise target is going to be within that range and then to get that same alignment with the agency. So when we have that in alignment with the agency, we're going to be able to provide that update, along with an update on -- given the number of patients and where we're at in the enrollment, some new targets for when we expect to be able to complete the enrollment to the full enrollment of the study.


Charles Cliff Duncan, Cantor Fitzgerald & Co., Research Division - Senior Analyst [11]


Okay. It sounds consistent with your previous thinking. And then, if I can ask a follow-up on that. There are other AADC gene therapy programs for neuro indications, and Omar did a great job in terms of talking about your differentiation with regard to where the drug is really administered. But I guess, if you look across AADC programs, how do you see you being differentiated from others in terms of, say, vector use or basic construct?


G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [12]


Yes. No, thanks for that question, and Omar can add to it. But I think in his prepared remarks, he touched on a key differentiation, which is this activity to modulate the response with the control of the exogenous levodopa. So that, I think, is in contrast with the alternative approach that's in development, which provides a more direct production of dopamine.

Our approach is, one, again, as highlighted, that allows for the dialing of the amount of dopamine to be produced, like in our delivery in the putamen is in common. And that's a good target, to have a stable reservoir of that enzyme, as it's a structure that is not too impacted in Parkinson's disease. And we've been able to observe in our experience to date, in our preclinical experience that a very durable expression of the enzyme production in the -- after administration in the putamen. I don't know if Omar, you want to highlight any additional points?


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Edited Transcript of VYGR earnings conference call or presentation 6-Nov-19 1:00pm GMT - Yahoo Finance

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The woman who should have got Alzheimers by 50, but didnt – The Irish Times

The womans genetic profile showed she would develop Alzheimers by the time she turned 50.

She, like thousands of her relatives, going back generations, was born with a gene mutation that causes people to begin having memory and thinking problems in their 40s and deteriorate rapidly towards death around age 60.

But remarkably, she experienced no cognitive decline at all until her 70s, nearly three decades later than expected.

How did that happen?

New research provides an answer, one that experts say could change the scientific understanding of Alzheimers disease and inspire new ideas about how to prevent and treat it.

In a study published in the journal Nature Medicine, researchers say the woman, whose name they withheld to protect her privacy, has another mutation that has protected her from dementia, even though her brain has developed a major neurological feature of Alzheimers disease. This ultra-rare mutation appears to help stave off the disease by minimising the binding of a particular sugar compound to an important gene. That finding suggests that treatments could be developed to give other people that same protective mechanism.

A drug or gene therapy would not be available any time soon because scientists first need to replicate the protective mechanism found in this one patient by testing it in laboratory animals and human brain cells. Still, this case comes at a time when the Alzheimers field is craving new approaches after billions of dollars have been spent on developing and testing treatments and some 200 drug trials have failed. It has been more than 15 years since the last treatment for dementia was approved, and the few drugs available do not work very well for very long.

The woman is entering her late 70s now and lives in Medelln, the epicentre for the worlds largest family to experience Alzheimers. It is an extended Colombian family of about 6,000 people whose members have been plagued with dementia for centuries, a condition they called La Bobera the foolishness and attributed to superstitious causes.

Decades ago Colombian neurologist Dr Francisco Lopera began painstakingly collecting the familys birth and death records in Medelln and remote Andes mountain villages. He documented the sprawling family tree and took dangerous risks in guerrilla and drug-trafficking territory to cajole relatives of people who died with dementia into giving him their brains for analysis.

Through this work, Dr Lopera, whose brain bank at the University of Antioquia now contains 300 brains, helped discover that their Alzheimers was caused by a mutation on a gene called Presenilin 1. Although this type of hereditary early-onset dementia accounts for only a small proportion of the roughly 30 million people worldwide with Alzheimers, it is important because, unlike most forms of the disease, the Colombian version has been traced to a specific cause and a consistent pattern. So Dr Lopera and a team of American scientists have spent years studying the family, searching for answers both to help the Colombians and to address the mounting epidemic of the more typical old-age Alzheimers disease.

When they found that the woman had the Presenilin 1 mutation, but had not yet even developed a pre-Alzheimers condition called mild cognitive impairment, the scientists were mystified. We have a single person who is resilient to Alzheimers disease when she should be at high risk, said Dr Eric Reiman, executive director of the Banner Alzheimers Institute in Phoenix and a leader of the research team.

The woman was flown to Boston, where some of the researchers are based, for brain scans and other tests. Those results were puzzling, said Yakeel Quiroz, a Colombian neuropsychologist who directs the familial dementia neuroimaging lab at Massachusetts General Hospital.

The womans brain was laden with the foremost hallmark of Alzheimers: plaques of amyloid protein. She had the highest levels of amyloid that we have seen so far, said Quiroz, adding that the excessive amyloid probably accumulated because the woman had lived much longer than other family members with the Alzheimers-causing mutation.

But the woman had few other neurological signs of the disease not much of a protein called tau, which forms tangles in Alzheimers brains, and little neurodegeneration or brain atrophy. Her brain was functioning really well, said Quiroz, who, like Dr Reiman, is a senior author of the study. Compared to people who are 45 or 50, shes actually better.

She said the woman, who raised four children, had only one year of formal education and could barely read or write, so it was unlikely her cognitive protection came from educational stimulation. She has a secret in her biology, Dr Lopera said. This case is a big window to discover new approaches.

Quiroz consulted Dr Joseph Arboleda-Velasquez, who, like her, is an assistant professor at Harvard Medical School (he is also Quirozs husband). Dr Arboleda-Velasquez, a cell biologist at Massachusetts eye and ear, conducted extensive genetic testing and sequencing, determining that the woman had an extremely rare mutation on a gene called APOE.

APOE is important in general-population Alzheimers. It has three variants. One, APOE4, greatly increases risk and is present in 40 per cent of people with Alzheimers. The Colombian woman has two copies of APOE3, the variant that most people are born with but both copies have a mutation called Christchurch (for the New Zealand city where it was discovered). The Christchurch mutation is extremely rare, but several years ago, Reimans daughter Rebecca, a technologist, helped determine that a handful of Colombian family members have that mutation on one of their APOE genes. They developed Alzheimers as early as their family members typically did. The fact that she had two copies, not just one, really kind of sealed the deal, Dr Arboleda-Velasquez said.

Dr Guojun Bu, chairman of the neuroscience department at the Mayo Clinic in Jacksonville, Florida, who studies APOE, said that while the findings involved a single case and more research was needed, the implications could be profound.

When you have delayed onset of Alzheimers by three decades, you say wow. New York Times

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The woman who should have got Alzheimers by 50, but didnt - The Irish Times

Edited Transcript of SRPT earnings conference call or presentation 7-Nov-19 9:30pm GMT – Yahoo Finance

BOTHELL Nov 8, 2019 (Thomson StreetEvents) -- Edited Transcript of Sarepta Therapeutics Inc earnings conference call or presentation Thursday, November 7, 2019 at 9:30:00pm GMT

* Alexander G. Cumbo

Sarepta Therapeutics, Inc. - Executive VP & Chief Commercial Officer

* Douglas S. Ingram

Sarepta Therapeutics, Inc. - President, CEO & Director

Sarepta Therapeutics, Inc. - Executive VP of R&D and Chief Medical Officer

* Ian M. Estepan

Sarepta Therapeutics, Inc. - Senior VP of Corporate Affairs & Chief of Staff

Sarepta Therapeutics, Inc. - SVP of Gene Therapy

Sarepta Therapeutics, Inc. - Executive VP, CFO & Chief Business Officer

Robert W. Baird & Co. Incorporated, Research Division - Senior Research Analyst

* Christopher N. Marai

Nomura Securities Co. Ltd., Research Division - MD & Senior Analyst of Biotechnology

* Debjit D. Chattopadhyay

H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst

BTIG, LLC, Research Division - MD and Specialty Pharmaceutical & Biotechnology Research Analyst

Janney Montgomery Scott LLC, Research Division - Equity Research Analyst & Director of Biotechnology Research

Good day, ladies and gentlemen, and welcome to the Sarepta Therapeutics Third Quarter 2019 Earnings Call. (Operator Instructions) As a reminder, today's call is being recorded.

And now I'd like to introduce your host for today's program, Ian Estepan, Senior Vice President, Chief of Staff and Corporate Affairs.

Ian M. Estepan, Sarepta Therapeutics, Inc. - Senior VP of Corporate Affairs & Chief of Staff [2]

Thank you, Michelle, and thank you all for joining today's call. Earlier today, we released our financial results for the third quarter of 2019. The press release is available on our website at, and our 10-Q was filed with the SEC earlier this afternoon. Joining us on the call today are Doug Ingram, Sandy Mahatme; Bo Cumbo, Dr. Gilmore O'Neill; and Dr. Rodino-Klapac. After our formal remarks, we'll open up the call for questions.

I'd like to note that during this call, we'll be making a number of forward-looking statements. Please take a moment to review our slide on the webcast which contains our forward-looking statements. These forward-looking statements involve risks and uncertainties, many of which are beyond Sarepta's control. Actual results could materially differ from these forward-looking statements, and any such risks can materially and adversely affect the business, the results of operations and the trading prices of Sarepta's common stock.

For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent quarterly report on Form 10-Q filed with the Securities and Exchange Commission as well as the company's other SEC filings. The company does not undertake any obligation to publicly update its forward-looking statements, including any financial projections provided today, based on subsequent events or circumstances.

And with that, let me turn the call over to our CEO, Doug Ingram, who will provide an overview on our recent progress. Doug?


Douglas S. Ingram, Sarepta Therapeutics, Inc. - President, CEO & Director [3]


Thank you, Ian. Good afternoon and evening, and thank you all for joining us for Sarepta Therapeutics Third Quarter 2019 Conference Call.

Our ambitious strategy involving one of the deepest multi-platform genetic medicine pipelines in biotech has required focused execution over the course of 2019. To remind you, we have more than 25 active programs across our RNA and gene therapy platforms, and we're either actively in or in late-stage planning for some 9 human clinical trials to advance our plans. I am pleased to say that over the course of 2019 and in the third quarter specifically, we have made very significant strides in advancing our programs and our strategic vision, and I'm excited to discuss those advancements. However, while doing so, I must also acknowledge what we all know that we had a setback in the third quarter. And rather than burying it among or after a discussion of our successes, I will begin by commenting on a CRL disappointment that occurred in August.

Having worked diligently on our submission for VYONDYS 53, the generic name of that is golodirsen, for well over a year and based on all of our interactions with the Division of Neurology Products, we were very confident that we would obtain an approval on our PDUFA date, which was August 19. Instead, as you know, we were surprised to have received a complete response letter, also known as a CRL, signed by the Office of Drug Evaluation I. Our disappointment extends beyond Sarepta to the 8% of exon 53 amenable DMD patients in the United States who degenerate every day while they await access to this therapy.

When I joined Sarepta, I made some commitments externally and to the Division of Neurology, that we intended to build a positive relationship with the Division of Neurology, one founded on transparency and on solid evidence-based science. And consistent with that commitment, we will work with the agency to address the reasons for the CRL and determine a pathway for a potential approval if one is possible.

I've heard from those who would prefer that I speak more often and more publicly on this issue and/or that I would attempt to engage the patient community or others to assist, for instance, in applying external pressure to bring this therapy along faster. I have no intention of doing either of those things. If we can win the day with this therapy and with this issue, we will have done so on the science and on the regulations and in collaborative evidence-based discussions with our reviewers at the FDA.

Now I've also heard some speculation about the implications of the CRL. So let me take a moment to address these as well. First, the VYONDYS CRL does have implications for our submission for our next PMO, casimersen. As they are closely related, we will await clarity on the VYONDYS matter before we submit for casimersen in the United States. But let me [just dissuade] anyone who might have concerns for our other programs. The CRL does not have any read-through to our micro-dystrophin gene therapy program. The CRL involves 2 safety signals in connection with an application for an accelerated approval. Our micro-dystrophin program is overseen by a different part of the FDA, CBER, and we are not seeking accelerated approval there. There is simply no overlap in either substance or personnel.

Secondly, to those who may believe that the CRL suggests some sort of bias on behalf of the Division of Neurology towards Sarepta, I would unequivocally and emphatically disagree. Let me reiterate that I remain convinced that we were treated very fairly and professionally by the Division of Neurology. Also, I'm very proud of the Sarepta team and how they comported themselves during this review. From my perspective, we have gone a long way in the last 2.5 years in forging a positive evidence-based working relationship with the division. We will work diligently to address the VYONDYS CRL. But with that, I do not intend to provide a prediction on outcome or on timing or to provide interviews during the process. However, I will provide an update to the patient, physician and investment communities once we have definitive clarity on the outcome of those discussions.

Now moving to our positive achievements in the quarter. We have made some enormous amount of progress in this third quarter. EXONDYS continues to perform well with third quarter sales above consensus at $99 million. That is a 26% increase over the same quarter last year. Commenting for a moment on a confirmatory trial for EXONDYS, to remind you, this trial comprises 3 arms: one with EXONDYS at 100 mg per kg and another at 200 mg per kg versus our current dose at 30 mg per kg. The trial design, which was an FDA requirement, will answer whether higher doses of EXONDYS provide even more benefit than the currently approved dose. Now since the comparator arms involve higher doses than the currently approved dose, we were required to begin our confirmatory trial with a healthy human volunteer study. We have completed this trial, and based on the results, we have initiated the main confirmatory trial. We will begin dosing this quarter.

Staying on our RNA franchise. We have moved to our multi-ascending dose trial for our next-generation RNA platform, the PPMO, and we are dosing trial participants now. We will have safety and dosing insight in 2020. If our PPMO shows encouraging results, in addition to SRP-5051, that's the construct that we're currently in a multi-ascending dose regarding, we have 5 additional constructs that have already been built, which in total have the potential to treat as much as 43% of the DMD community. We are also conducting research now on new therapeutic targets that could be served by our PPMO platform.

Moving next to our gene therapy platform. As you know, we are spending enormous resource and energy to build out our vision of an enduring gene therapy engine. Between our research and clinical-stage programs, we have more than 14 therapeutic candidates advancing through research and development. We have made great progress thus far this year and quarter, led by our most advanced program, SRP-9001, for DMD, which, at least to my knowledge, is the highest-potential late-stage gene therapy program currently in biotech. As you should be aware, our double-blind, placebo-controlled SRP-9001 micro-dystrophin trial, the trial that we call Study 2, was fully dosed by midyear, but we took advantage of the availability of additional study material and previously announced that we had increased the study n from 24 patients to 40 patients, significantly increasing the study power and confidence in this study. In addition to our initial site with Dr. Jerry Mendell at Nationwide Children's Hospital, we have added a second site at UCLA with Dr. Perry Shieh. And I'm very proud to be associated with that clinician and investigator. Both sites are actively dosing patients, and we remain on target to complete our dosing by year-end.

Micro-dystrophin manufacturing is progressing well. From a capacity perspective, Brammer has now completed the buildout of our single-use micro-dystrophin manufacturing facility in Lexington, Massachusetts. We also have dedicated suites with Paragon in Maryland with actually substantially greater capacity than our dedicated Lexington facility, which means we have robustly secured capacity well in advance of launch.

Our analytical development work proceeds well, and we continue to make progress on process development and yield optimization. Given our recent capacity, analytical development and process development progress, we remain on track to commence our next trial, Study 301, with commercial development supply by mid-2020. Now Study 2 is being conducted with clinical material from Nationwide Children's Hospital. Study 301 will be a multicenter, multi-country, placebo-controlled trial using commercial process material from our hybrid manufacturing model with Brammer and Paragon. The main study will include DMD patients ages 4 to 7, but we are also planning a separate study for older and non-ambulatory patients as well.

Commenting on a few of our other gene therapy programs. Following exceptional expression and biomarker results in our first 3-patient cohort dosed with our construct for limb-girdle 2E, in October, we announced positive 9-month functional results in that same cohort. Consistent with robust expression of the native beta-sarcoglycan protein, that is the cause of the disease, all patients improved on every functional endpoint by the 9-month time point. Consistent with the protocol, we will treat an additional 3-patient cohort with a higher dose, and then in early 2020, we will decide on the dose for what we hope to be the pivotal trial. These results will help inform dosing not only of our 2E program but also on the other limb-girdle programs in our pipeline. We will also meet with the FDA in the near term to discuss the development pathway for our limb-girdle programs. And informed by this and further work on manufacturing, we will provide an update on the clinical pathway and the timing for our limb-girdle portfolio in 2020.

Next, led by our partner Lysogene, the AAVance gene therapy study for MPS IIIA, also known as Sanfilippo Syndrome Type A, is proceeding well with 13 patients having been dosed to date. MPS IIIA is a rare autosomal recessive lysosomal storage disease that primarily affects the brain and the spinal cord, causing severe cognitive decline, motor disease, behavioral decline and unfortunately death at a young age. AAVance is a single-arm trial evaluating the safety and efficacy of an rh10-mediated gene therapy to deliver the missing SGSH gene with the goal of robustly expressing the missing enzyme in the brain that is the cause of MPS IIIA.

Moving to Charcot-Marie-Tooth, or CMT. Dr. Zarife Sahenk of Nationwide Children's Hospital intends to commence dosing of the proof-of-concept study for CMT 1A subject only to obtaining final release of trial material for that study. CMT is the largest inherited neuromuscular disease in the world. And CMT 1A, a devastating peripheral nerve disease, is also the most prevalent form of CMT. Dr. Sahenk's gene therapy is an AAV 1-mediated construct to deliver the neurotrophic factor-3, NT-3. In animal models, NT-3 has been shown to promote nerve regeneration, improved motor function, histopathology and electrophysiology of peripheral nerves. And in early proof-of-principle studies, NT-3 has shown markers of clinical benefits in patients with CMT 1A when administered subcutaneously.

In summary, we have made great progress in the third quarter and over the course of 2019 toward our ambitions, advancing our RNA and gene therapy platforms, advancing our many development programs, building out our gene therapy manufacturing capacity and building out our tower. As with any ambitious strategy, our progress this quarter was met with an obstacle in the form of VYONDYS CRL. The breadth of our ambition inevitably comes with challenges and obstacles to address and to overcome. But to those who might at times feel discouraged or disheartened by the need to overcome the occasional barrier, we should keep top of mind what we are doing with all of this. If we are successful in our mission, we will not merely be among the most significant gene therapy and genetic medicine biotechnology companies in existence, but we will have, more importantly, extended, improved and saved the lives of countless patients who would otherwise have been left hopeless.

And with that, I will turn the call over to Sandy to provide an update on the financials. Sandy?


Sandesh Mahatme, Sarepta Therapeutics, Inc. - Executive VP, CFO & Chief Business Officer [4]


Thanks, Doug. Good afternoon, everyone. Let me start by saying that we had another strong quarter both in terms of financial performance and in progress towards the pipeline and manufacturing capabilities. With a current top line run rate of approximately $400 million and a cash balance over $1 billion, we are in a strong position to continue to accelerate our strategic imperatives and invest in the growth of Sarepta. Net product revenue for the third quarter of 2019 was $99 million compared to $78.5 million for the same period of 2018. The increase primarily reflects higher demand for EXONDYS 51.

On a GAAP basis, the company reported a net loss of $126.3 million and $76.4 million or approximately $1.70 and $1.15 per share for the third quarter of 2019 and 2018, respectively. We reported a non-GAAP net loss of $84.4 million or $1.14 per share compared to non-GAAP net loss of $37.1 million or $0.56 per share in the third quarter of 2018.

In the third quarter of 2019, we recorded approximately $13 million in cost of sales compared to $8.7 million in the same period of 2018. The increase was primarily driven by inventory costs related to higher demand for EXONDYS 51 during the third quarter of 2019 as well as accrued royalty payments to BioMarin and the University of Western Australia.

On a GAAP basis, we recorded $133.9 million and $86.6 million of R&D expenses for the third quarters of 2019 and 2018, respectively, which is a year-over-year increase of $47.3 million. R&D expenses were $110.5 million for the third quarter of 2019 compared to $64.2 million for the same period of 2018, an increase of $46.3 million. The year-over-year growth in non-GAAP R&D expense was driven primarily due to continuing ramp-up of our micro-dystrophin program, our ESSENCE program and initiation of certain post-marketing studies for EXONDYS 51.

Turning to SG&A. On a GAAP basis, we recorded $75.4 million and $53 million of expenses for the third quarters of 2019 and '18, respectively, a year-over-year increase of $22.4 million. On a non-GAAP basis, the SG&A expenses were $59.6 million for the third quarter of 2019 compared to $42.5 million for the same period of 2018, an increase of $17.1 million. The year-over-year increase was primarily driven by significant organizational growth and continued expansion to support a commercial launch -- to support our commercial launch plans globally and almost 30 therapies in various stages of development across several therapeutic modalities.

On a GAAP basis, we recorded $2.5 million in other expenses for the third quarter of 2019 compared to $7 million for the same period of 2018. The favorable change is primarily driven by the payoff of certain debt instruments during the third quarter of 2018 as well as a higher return on investments over the third quarter of 2019.

We had approximately $1.1 billion in cash, cash equivalents and investments as of September 30, 2019.

With that, I'd like to turn the call over to Bo for a commercial update. Bo?


Alexander G. Cumbo, Sarepta Therapeutics, Inc. - Executive VP & Chief Commercial Officer [5]


Thank you, Sandy. Good afternoon, everyone. To begin, we are pleased with the continued strong performance of EXONDYS 51 in the third quarter. Total revenues reached $99 million. We were also pleased to be in a position to increase our 2019 revenue guidance range from $365 million to $375 million to a range of $370 million to $380 million for EXONDYS 51. Sales have increased quarter-over-quarter for over 3 years now, and we continue to see consistent demand for EXONDYS 51 as we speak today.

Compliance and adherence have remained high and stable since launch and to date continue to remain steady. It should be noted that in the past 2 years, we've experienced ordering volatility at the end of the year and suspect that we could see a change in ordering patterns with both Christmas and New Year's falling in the middle of the week. Internally, we are assuming the pattern from previous years could be more extreme this year due to both holidays falling midweek. With that said, we feel comfortable with the guidance provided.

The success we achieved this year reflects the impact EXONDYS 51 continues to have on patient lives. We remain the leading voice with KOLs and payers across the world in support of Duchenne patients and are recognized as the leader in RNA and gene therapies within the Duchenne field. Our strategy to advance the very best science, build awareness and appreciation for Duchenne and pave new pathways so Duchenne patients gain access to therapy have resulted in the successful trajectory of EXONDYS 51 since its approval just over 3 years ago and will play a role for future therapies.

As for golodirsen, if approved, we will be ready to launch, leveraging our knowledge and experience to facilitate rapid access to individuals amenable to exon 53. Our work is focused on delivering, and grounding us in all we do is the patient. That journey begins with identifying patients in our core therapeutic areas: Duchenne, the limb-girdle muscular dystrophy and MPS IIIA. Patient identification will be central to the commercial organization for the balance of 2019 and leading into 2020 and beyond. The genetic testing program, Decode Duchenne, which we started with PPMD many years ago, consistently identifies patients. We are also in the process of building genetic testing programs for our other disease states we are working on as well. We believe patient identification will always be one of our primary commercial goals, and we will continue to place resources on these programs.

Another important goal will be gene therapy site readiness. We are already working on global site readiness for our DMD micro-dystrophin program and working with many of the Zolgensma and Spinraza sites treating SMA. Based on the very strong results Novartis demonstrated with their recent launch of Zolgensma and understanding the label and the differences in patient population sizes between the 2 disease states, we believe having a strong network of sites ready and trained to handle gene therapies will be critical. We will continue to focus on this as we move through worldwide development and, if successful, commercialization.

We also believe it is critical to focus on access and reimbursement as early as possible. We're already speaking to and educating large to midsized insurance plans as well as CMS and Medicaid providers on the differences between chronic therapies and onetime gene therapies and the importance of quickly gaining access to these therapies for diseases like Duchenne. We have built constructive relationships with payers over time and look forward to continuing to work with them to support broad access.

In the limb-girdle muscular dystrophy, we are focused on disease education and identifying patients. The limb-girdle muscular dystrophies are a family of diseases, over 30 subtypes in all. Therefore, patient identification is of critical importance. Our plan is to leverage our knowledge and experience to ensure that we're able to serve these communities as we have in Duchenne. We've already attended limb-girdle muscular dystrophy conferences, held educational symposiums at major neuromuscular conferences, held advisory boards to understand how physicians identify and treat patients and already have a digital presence within the community. All of this will help us prepare for the potential to support multiple launches in the years to come.

Sarepta's prospects to transform the lives of patients with rare diseases is unparalleled in the industry. We have the largest neuromuscular RNA and gene therapy pipeline in the industry, and we understand the responsibility that comes with such an important mission.

With that, I will turn the call back to Doug for closing remarks.


Douglas S. Ingram, Sarepta Therapeutics, Inc. - President, CEO & Director [6]


Thank you, Bo. So looking forward, we have a number of significant milestones to achieve over the rest of 2019 and through 2020. First, we intend to complete dosing of our SRP-9001 Study 2, that's our micro-dystrophin study, by year-end with functional readout 48 weeks thereafter. We soon intend to launch process development for SRP-9001, not manufacturing for purposes of conducting our next clinical trial, gain insight from the agency on CMC and on our trial itself and then to commence Study 301 by mid-2020. We intend to dose an additional high-dose cohort for limb-girdle 2E and then make a dose selection. We intend to gain regulatory and manufacturing insight and to present an update on the development pathway and time line for our entire limb-girdle program in 2020. Dr. Sahenk intends to commence a proof-of-concept study for CMT gene therapy, NT-3. And we intend to obtain safety and dosing insight for our PPMO program in the first half of 2020. So we obviously have a lot to do but a lot of milestones as well over the coming months and quarters.

Thank you all for joining us tonight, and I'll open up the line for questions now.


Questions and Answers


Operator [1]


(Operator Instructions) Our first question comes from Alethia Young of Cantor Fitzgerald.


Alethia Rene Young, Cantor Fitzgerald & Co., Research Division - Head of Healthcare Research [2]


Congrats on all the progress over the quarter. This may be a simple one, but I was just curious to get your perspective around Zolgensma partial hold. And like should we -- is there any -- are there any reads to potentially make thinking about other gene therapy programs?


Douglas S. Ingram, Sarepta Therapeutics, Inc. - President, CEO & Director [3]


Thank you for that question, Alethia. Okay. So well, first, let me say this. Let's make sure we're all on the same page. For those of you maybe unaware, I expect everyone is aware, Novartis recently announced that their clinical trial for their AAV9-mediated SMA gene therapy for intrathecal administration was placed on a partial clinical hold due to neurotoxicity that was seen in animal models. So first, understand this, we do not have a unique insight into the Zolgensma clinical hold itself or the Zolgensma program. Certainly, one should look at Novartis to gain accurate insight on that program and those issues.

So with that said, I should tell you, we see no read-through to our program, and there's a host of reasons for that. First, understand that we are dosing peripherally with IV administration. We're not dosing intrathecally as was the issue, as announced by Novartis, regarding that partial clinical hold. And second of all, understand that we're not using AAV9. Dr. Louise Rodino-Klapac who is with us tonight and Dr. Jerry Mendell chose rh74 for a number of specific attributes. One of the significant ones was that rh74, unlike AAV9 as an example, does not promiscuously cross the blood-brain barrier. And unlike SMA where that would be of value, there is absolutely no value to these micro-dystrophin constructs in the CNS at all. They have promoters that wouldn't turn on in the CNS, so there would be no value there. So this seems to have been a very wise choice.

And also note this, that we have an enormous amount of preclinical and animal model evidence with respect to rh74. And even at doses that are multiples higher than we're using in our clinical trial, we have never seen evidence of neurotoxicity as relates to AAVrh74.


Operator [4]


Our next question comes from Whitney Ijem of Guggenheim.


Whitney Glad Ijem, Guggenheim Securities, LLC, Research Division - Senior Analyst of Biotechnology [5]


Congrats on all the progress. I'll ask a question on the original 4 micro-dystrophin patients. Curious if we'll get an update on them in 2020 either in an update from you or possibly a publication from Dr. Mendell.


Douglas S. Ingram, Sarepta Therapeutics, Inc. - President, CEO & Director [6]


Yes. Thanks for that question. Thank you for your comments. So yes, Dr. Mendell has always had a keen interest in publishing the 1-year data on the 4 patients, and he is working on the manuscript even as we speak. So I feel very confident that we'll have a publication in 2020 on the first 4 patients.

Original post:
Edited Transcript of SRPT earnings conference call or presentation 7-Nov-19 9:30pm GMT - Yahoo Finance

Orchard Therapeutics to Present New Registrational Data of Investigational Gene Therapies at the 61st American Society of Hematology Annual Meeting -…

Registrational Trial for Wiskott-Aldrich Syndrome Met Key Primary and Secondary Endpoints at Three Years; Data from Integrated Analysis Reinforce Treatment Benefits of Gene Therapy and Durability of Effect in Additional Patients

Similar Profiles Reported Between Cryopreserved and Fresh Formulations of OTL-101, Further Supporting Upcoming Regulatory Filing and Broad Patient Availability

BOSTON and LONDON, Nov. 06, 2019 (GLOBE NEWSWIRE) -- Orchard Therapeutics (ORTX), a leading commercial-stage biopharmaceutical company dedicated to transforming the lives of patients with serious and life-threatening rare diseases through innovative gene therapies, today announced the upcoming presentation of registrational data from multiple programs at the 61st American Society of Hematology (ASH) Annual Meeting in Orlando, FL.

Investigators will describe ongoing clinical progress for two lead development programs in the companys primary immune deficiencies portfolio: OTL-103, an investigational gene therapy in development for the treatment of Wiskott-Aldrich syndrome (WAS) at theSan Raffaele-Telethon Institute for Gene Therapy(SR-Tiget) inMilan, Italy; and OTL-101, an investigational gene therapy in development for the treatment of adenosine deaminase severe combined immunodeficiency (ADA-SCID).

In addition, investigators will deliver an oral presentation featuring updated data from the ongoing proof-of-concept study of OTL-203, an investigational gene therapy in development for the treatment of mucopolysaccharidosis type I (MPS-I) atSR-Tiget.

This growing body of positive data, from dozens of patients across multiple diseases, provides a solid foundation as we advance each program toward its next phase of development, including upcoming regulatory submissions for ADA-SCID and WAS, saidMark Rothera, president and chief executive officer ofOrchard Therapeutics. We now have two supportive data sets one from our OTL-101 program in ADA-SCID and one from our OTL-200 program in metachromatic leukodystrophy that demonstrate cryopreserved formulations are engrafting as expected, similar to the fresh formulation. This supports our strategy for making these therapies, if approved, broadly available to patients in need throughout the world.

We are extremely pleased with our continued clinical progress, including the duration of benefits seen in our WAS trial, which is the longest published follow-up of hematopoietic stem cell gene therapy durability to date using lentiviral vector transduction, said Bobby Gaspar, M.D., Ph.D., chief scientific officer of OrchardTherapeutics. The totality of these data underscores the broad applicability of our gene therapy platform approach and the opportunity we have to deliver potentially curative treatments for a variety of devastating and rare genetic disorders.

Full presentation details are below:

Poster Presentation Details

Lentiviral Hematopoietic Stem and Progenitor Cell Gene Therapy for Wiskott-Aldrich Syndrome (WAS): Up to 8 Years of Follow up in 17 Subjects Treated Since 2010Publication Number: 3346Session: 801. Gene Therapy and Transfer: Poster IIDate and time:Sunday, December 8, 6:00-8:00pm ET

This presentation includes results from an integrated analysis of 17 patients treated with OTL-103 for the treatment of WAS, including the complete data set for the eight patients from the registrational study and nine who received OTL-103 as part of an expanded access program (EAP). Participants have been followed for a median of three years.

In the eight-patient registrational trial, investigators reported that the study achieved its key primary and secondary endpoints at three years, including the elimination of severe bleeding episodes and a significant reduction in the frequency of moderate bleeding episodes. Successful engraftment was observed within three months, leading to an increase in WAS protein expression and a vector copy number that has been maintained for up to eight years. Nine months post-administration, all patients stopped receiving platelet transfusions, and no severe bleeding events were reported. A significant reduction in the rate of severe infections was also observed and all patients were able to stop immunoglobin replacement therapy (IgRT), suggesting a complete reconstitution of immune function with durability of effect of up to eight years of follow-up post-gene therapy.

Story continues

Similar clinical results were seen in the integrated analysis of 17 patients and overall survival was 94% (16/17). One death occurred among the EAP cohort that was considered by the investigator to be unrelated to OTL-103.

Across the original and integrated data sets, there were no adverse events considered to be related to OTL-103, including no evidence of oncogenesis, replication competent lentivirus or abnormal clonal proliferation. Clinical benefit was also attained in patients older than five years of age, a group considered at higher risk when treated with allogeneic hematopoietic stem cell transplantation (HSCT).

Lentiviral Gene Therapy with Autologous Hematopoietic Stem and Progenitor Cells (HSPCs) for the Treatment of Severe Combined Immune Deficiency Due to Adenosine Deaminase Deficiency (ADA-SCID): Results in an Expanded CohortPublication Number: 3345Session: 801. Gene Therapy and Transfer: Poster IIDate and time: Sunday, December 8, 6:00-8:00pm ET

This presentation details the safety and efficacy of OTL-101 in 30 individuals with ADA-SCID, treated with either fresh (n=20) or cryopreserved (n=10) formulations. Patients were followed for a median of 24 months (range 12-24 months overall and 12-18 months for patients treated with the cryopreserved formulation), and results were compared with a historical cohort of 26 ADA-SCID patients treated with allogeneic hematopoietic stem cell transplantation (HSCT), including HSCT both with, and without, a matched related donor.

Results showed engraftment of genetically modified hematopoietic stem cells in 29 of 30 OTL-101 patients by six to eight months, which persisted through follow-up in both studies. Analysis of both the vector copy number in granulocytes (a measure of engraftment) and T-cell reconstitution (a relevant measure of immune recovery) showed consistent performance across the fresh and cryopreserved-treated patients.

In the OTL-101 treated patients, overall survival was 30/30 (100%) and event-free survival was 29/30 (97%). One of the 30 patients restarted treatment with enzyme replacement therapy (ERT) and subsequently withdrew from the study and received a rescue HSCT. In the historical control population, 42% of HSCT patients required re-initiation of ERT, rescue HSCT or other intervention, or died. As expected, there was no incidence of graft versus host disease in the OTL-101 group, compared with eight patients who received HSCT.

Eighteen of 20 patients (90%) in the fresh formulation study stopped immunoglobin replacement therapy (IgRT) after two years, compared to 52% of HSCT patients. Of the seven patients treated with the cryopreserved formulation with 18 months of follow-up, five had discontinued IgRT (71%), which is comparable to the 18-month data for patients treated with the fresh formulation.

Oral Presentation Details

Extensive Metabolic Correction of Hurler Disease by Hematopoietic Stem Cell-Based Gene Therapy: Preliminary Results from a Phase I/II TrialPublication Number: 607Session: 801. Gene Therapy and Transfer: Gene Therapies for Non-Malignant DisordersDate and time:Monday, December 9, 7:00am ET

Investigators will present updated analyses from the ongoing proof-of-concept trial of OTL-203 for mucopolysaccharidosis type I (MPS-I).

About ADA-SCID and OTL-101Severe combined immune deficiency due to adenosine deaminase deficiency (ADA-SCID) is a rare, life-threatening, inherited disease of the immune system caused by mutations in the ADA gene resulting in a lack of, or minimal, immune system development.1-4The first symptoms of ADA-SCID typically manifest during infancy with recurrent severe bacterial, viral and fungal infections and overall failure to thrive, and without treatment the condition can be fatal within the first two years of life. The incidence of ADA-SCID is currently estimated to be one in 500,000 live births inthe United Statesand between one in 200,000 and one in 1 million inEurope.3OTL-101 is an autologous,ex vivo,hematopoietic stem cell-based gene therapy for the treatment of patients diagnosed with ADA-SCID being investigated in multiple clinical trials inthe United StatesandEurope, including a registrational trial at theUniversity of California, Los Angeles(UCLA). OTL-101 has received orphan drug designation from theU.S. Food and Drug Administration(FDA) and the European Medicines Agency (EMA) for the treatment of ADA-SCID, and Breakthrough Therapy Designation from theFDA.

About WAS and OTL-103Wiskott-Aldrich Syndrome (WAS) is a life-threatening inherited immune disorder characterized by autoimmunity and abnormal platelet function and manifests with recurrent, severe infections and severe bleeding episodes, which are the leading causes of death in this disease. Without treatment, the median survival for WAS patients is 14 years of age. Treatment with stem cell transplant carries significant risk of mortality and morbidities. OTL-103 is anex vivo,autologous, hematopoietic stem cell-based gene therapy developed for the treatment of WAS that Orchard acquired from GSK in April 2018 and has been developed at theSan Raffaele-Telethon Institute for Gene Therapy(SR-Tiget) inMilan, Italy. The global incidence of WAS is estimated to be about 100-260 births per year, with a global prevalence of 2,900-4,700 patients.

About MPS-I and OTL-203Mucopolysaccharidosis type I (MPS-I) is a rare inherited neurometabolic disease caused by a deficiency of the IDUA (alpha-L-iduronidase) lysosomal enzyme required to break down glycosaminoglycans (also known as GAGs or mucopolysaccharides). The accumulation of GAGs across multiple organ systems results in the symptoms of MPS-I including neurocognitive impairment, skeletal deformity, loss of vision and hearing, hydrocephalus, and cardiovascular and pulmonary complications. MPS-I occurs at an overall estimated frequency of one in every 100,000 live births.5There are three subtypes of MPS-I; approximately 60 percent of MPS-I patients have the severe Hurler subtype and, when untreated, these patients rarely live past the age of 10.IdTreatment options for MPS-I include hematopoietic stem cell transplant and chronic enzyme replacement therapy, both of which have significant limitations. Though early intervention with enzyme replacement therapy has been shown to delay or prevent some clinical features of the condition, it has only limited efficacy on neurological symptoms. OTL-203 is anex vivo, autologous, hematopoietic stem cell-based gene therapy being studied for the treatment of MPS-I. Orchard was granted an exclusive worldwide license to intellectual property rights to research, develop, manufacture and commercialize the gene therapy program for the treatment of MPS-I developed by theSan Raffaele-Telethon Institute for Gene TherapyinMilan, Italy.

About Orchard Orchard Therapeuticsis a fully integrated commercial-stage biopharmaceutical company dedicated to transforming the lives of patients with serious and life-threatening rare diseases through innovative gene therapies.

Orchards portfolio ofex vivo, autologous, hematopoietic stem cell (HSC) based gene therapies includes Strimvelis, a gammaretroviral vector-based gene therapy and the first such treatment approved by theEuropean Medicines Agencyfor severe combined immune deficiency due to adenosine deaminase deficiency (ADA-SCID). Additional programs for neurometabolic disorders, primary immune deficiencies and hemoglobinopathies are all based on lentiviral vector-based gene modification of autologous HSCs and include three advanced registrational studies for metachromatic leukodystrophy (MLD), ADA-SCID and Wiskott-Aldrich syndrome (WAS), clinical programs for X-linked chronic granulomatous disease (X-CGD), transfusion-dependent beta-thalassemia (TDT) and mucopolysaccharidosis type I (MPS-I), as well as an extensive preclinical pipeline. Strimvelis, as well as the programs in MLD, WAS and TDT were acquired by Orchard from GSK inApril 2018and originated from a pioneering collaboration between GSK and theSan Raffaele Telethon Institute for Gene TherapyinMilan, Italyinitiated in 2010.

Orchard currently has offices in the UK and the U.S., including London, San Francisco and Boston.

Forward-Looking StatementsThis press release contains certain forward-looking statements about Orchards strategy, future plans and prospects, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements may be identified by words such as anticipates, believes, expects, intends, projects, and future or similar expressions that are intended to identify forward-looking statements.Forward-looking statements include express or implied statements relating to, among other things, the therapeutic potential of Orchards product candidates, including the product candidate or candidates referred to in this release, Orchards expectations regarding the timing of regulatory submissions for approval of its product candidates, including the product candidate or candidates referred to in this release, the timing of announcement of clinical data for its product candidates and the likelihood that such data will be positive and support further clinical development and regulatory approval of these product candidates, including any cryopreserved formulations of such product candidates, and the likelihood of approval of such product candidates by the applicable regulatory authorities. These statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond Orchards control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, the risks and uncertainties include, without limitation: the risk that any one or more of Orchards product candidates, including the product candidate or candidates referred to in this release, will not be successfully developed or commercialized, the risk of cessation or delay of any of Orchards ongoing or planned clinical trials, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies or clinical trials will not be replicated or will not continue in ongoing or future studies or trials involving Orchards product candidates, the delay of any of Orchards regulatory submissions, the failure to obtain marketing approval from the applicable regulatory authorities for any of Orchards product candidates, the receipt of restricted marketing approvals, and the risk of delays in Orchards ability to commercialize its product candidates, if approved.Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements.

Other risks and uncertainties faced by Orchard include those identified under the heading "Risk Factors" in Orchards annual report on Form 20-F for the year endedDecember 31, 2018as filed with theU.S. Securities and Exchange Commission(SEC) onMarch 22, 2019, as well as subsequent filings and reports filed with theSEC. The forward-looking statements contained in this press release reflect Orchards views as of the date hereof, and Orchard does not assume and specifically disclaims any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

1Orphanet. SCID due to ADA deficiency.2Whitmore KV, Gaspar HB. Front Immunol. 2016;7:314.3Kwan A, et al. JAMA. 2014;312:729-738.4Sauer AV, et al. Front Immunol. 2012;3:265. 5Beck et al. The Natural History of MPS I: Global Perspectives from the MPS I Registry. Genetics in Medicine 2014, 16(10), 759.


InvestorsRenee LeckDirector, Investor Relations+1

MediaMolly CameronManager, Corporate Communications+1

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Orchard Therapeutics to Present New Registrational Data of Investigational Gene Therapies at the 61st American Society of Hematology Annual Meeting -...

Insightful Growth of Cancer Gene Therapy Market 2019- 2025| Research Methodologies Offers High Business Outlook growth – Daily Watch Reports

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Insightful Growth of Cancer Gene Therapy Market 2019- 2025| Research Methodologies Offers High Business Outlook growth - Daily Watch Reports

Her daughter may die by age 10, but this mom keeps fighting to cure her rare disease – GMA

Her daughter may die by age 10, but this mom keeps fighting to cure her rare disease  GMA

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Her daughter may die by age 10, but this mom keeps fighting to cure her rare disease - GMA

Edited Transcript of OTIC earnings conference call or presentation 5-Nov-19 9:30pm GMT – Yahoo Finance

SAN DIEGO Nov 10, 2019 (Thomson StreetEvents) -- Edited Transcript of Otonomy Inc earnings conference call or presentation Tuesday, November 5, 2019 at 9:30:00pm GMT

Otonomy, Inc. - President, CEO & Director

* Paul E. Cayer

Otonomy, Inc. - Chief Financial & Business Officer

H.C. Wainwright & Co, LLC, Research Division - MD & Senior Healthcare Analyst

* Tara A. Bancroft

Good afternoon, ladies and gentlemen, and welcome to the Q3 2019 Otonomy, Inc. Earnings Conference Call.

I would now like to turn the conference over to your host, Mr. Stephen Jasper from Westwicke Partners, please go ahead.

Good afternoon and welcome to Otonomy's Third Quarter 2019 Financial Results and Business Update Conference Call. Joining me on the call from Otonomy are Dr. David Weber, President and Chief Executive Officer; and Paul Cayer, Chief Financial and Business Officer.

Before I turn the call over to Dr. Weber, I would like to remind you that today's call will include forward-looking statements based on current expectations. Such statements represent management's judgment as of today and may involve risks and uncertainties that could cause actual results to differ materially from expected results. Such statements include but are not limited to timing of results, patient's recruitment and enrollment plans for and designing conduct of the Phase III clinical trial for OTIVIDEX, the Phase I/II clinical trial for OTO-313 and the Phase I/II clinical trial for OTO-413. Expectations regarding preclinical development, including but not limited to the potential benefits of activities under the collaboration agreement between AGTC and Otonomy, expectations regarding the benefits and value potential of Otonomy's programs, expectations regarding funding of clinical development program advancement and company operations into 2021 and expectations regarding financial guidance, including operating expenses for 2019 and 2020.

Please refer to Otonomy's filings with the SEC, which are available from the SEC or on the Otonomy website for information concerning the risk factors that could affect the company.

I will now turn the call over to Dave Weber, President and CEO of Otonomy.

David Allen Weber, Otonomy, Inc. - President, CEO & Director [3]

Thank you, Stephen. Good afternoon, everyone and thank you for joining us on this call to discuss Otonomy's business updates and third quarter 2019 financial results.

We made significant progress in the third quarter toward our goal of reporting results from 3 clinical trials in 2020. Most importantly, we advanced enrollment in the Phase III trial of OTIVIDEX in Mnire's disease with all participating countries actively enrolling patients. For OTO-313, we successfully completed the initial safety cohort and initiated enrollment in the exploratory efficacy cohort of the Phase I/II trial in tinnitus patients.

And finally, we received FDA clearance to initiate the Phase I/II trial of OTO-413 in patients with hearing loss, which was an important milestone for this innovative program. The successful completion of these trials is our highest priority and greatest focus. In parallel, we continue to advance multiple preclinical programs addressing important unmet needs in neurotology, including a recently announced gene therapy collaboration targeting the most common cause of congenital hearing loss. I'll provide an update on our clinical programs and an overview of this collaboration in my brief comments.

I will also highlight the financial results from the quarter and lower spending guidance for the year. It is important to note that our existing capital will fund the company through the 3 clinical catalysts next year and into 2021. I plan to keep my remarks brief, and we can then open up the call for any questions.

Beginning with the OTIVIDEX Phase III trial in Mnire's disease, we updated the timing in our earnings release today. We expect results in the third quarter of 2020, which is a slight adjustment from our original timing of data late in the first half of 2020. We are pleased with the progress we have made on enrollment of the trial and the timing reflects the care and methodical approach we've taken in site selection and patient recruitment. We have 60 sites enrolling patients across all participating countries. As a reminder, the conduct and design of this study is based on the successful AVERTS-2 trial, and we plan to enroll approximately 160 patients in the United States and Europe.

The next product candidate in our clinical development pipeline is OTO-313, a sustained exposure formulation of the NMDA receptor antagonist gacyclidine in development for the treatment of tinnitus. We have successfully completed the initial safety cohort of the Phase I/II trial and are now enrolling patients in the second cohort, which is the exploratory efficacy part of the study.

Cohort 2 will enroll approximately 50 patients with persistent tinnitus who will be assessed across a number of endpoints, including the Tinnitus Functional Index or TFI, which is a validated clinical instrument that measures tinnitus severity and its impact on patients. Importantly for entry into cohort 2, patients must have a TFI score that exceeds a specified level to ensure adequate disease severity at baseline.

Patients in cohort 2 receive a single intratympanic injection of OTO-313 or placebo, randomized 1:1 and are followed for 2 months. We expect results in the second quarter of 2020.

Our third clinical stage program is OTO-413, a sustained exposure formulation of brain-derived neurotrophic factor or BDNF that we are developing for the repair of cochlear synaptopathy. Recent research has identified damage to synaptic connections as the underlying pathology in noise and age-related hearing loss that manifests as speech-in-noise hearing difficulty. Neurotrophic factors, including BDNF have potential therapeutic effects in the cochlea by promoting the survival of spiral ganglion neurons, increasing neurite outgrowth and reconnecting neurons with cochlea hair cells after damage.

As I mentioned in my opening comments, we have recently initiated a Phase I/II clinical trial and expect to have results in the second half of 2020. This is an ascending dose safety and exploratory efficacy study that will enroll up to 40 patients with speech-in-noise hearing difficulty. Patients will receive a single intratympanic injection of OTO-413 or placebo and be followed for 3 months. A number of efficacy endpoints will be evaluated, including electrophysiological measurements of hearing function and speech-in-noise hearing test.

We are excited to be the first company conducting a clinical trial of a therapeutic for synaptopathy, which has been an active area of neurotology research during the past decade. We believe that OTO-413 will not only provide clinical benefits for the many patients with impaired hearing in a noisy environment but more generally for the large population of patients with loss of hearing function due to aging or noise exposure.

In addition to OTO-413 for synaptopathy, we have -- I have also have ongoing preclinical development for OTO-6XX, which is our hair cell regeneration program to treat patients with severe hearing loss. Cochlea hair cells play a central role in hearing by converting sound waves into electrical signals that are then transmitted to the brain via auditory nerves. It is well-established that damage to hair cells through aging, excessive noise or exposure to ototoxic chemicals leads to hearing loss. Unfortunately for humans, we cannot naturally regenerate hair cells like non-mammalian species, such as birds and chickens. However, it is possible to activate regenerative path waves via drug intervention, thereby providing an approach to treat this pathology.

We have demonstrated hair cell regeneration in a nonclinical proof-of-concept model using a class of small molecules and have identified a candidate for further development. Between our OTO-413 and OTO-6XX programs, we addressed 2 of the critical pathologies believed to underlie acquired forms of hearing loss, and with our recently announced strategic collaboration with AGTC, we extend the reach of our pipeline to now also include genetic hearing loss.

The goal of this program is to develop an AAV based gene therapy to restore hearing in patients with sensorineural hearing loss caused by mutation in the gap junction protein beta 2 gene, otherwise known as GJB2. Mutations in this gene are the most common cause of congenital hearing loss, accounting for approximately 30% of all genetic hearing loss cases. Patients born with this mutation can have severe to profound deafness in both ears as identified in screening test now performed routinely in newborns.

The collaboration leverages the expertise, technology and capabilities of each partner, allowing each of us to do what we do best. In addition, the structure is highly cost efficient by utilizing each partner's existing resources, sharing the workload and splitting the cost. We look forward to sharing more information about this program in the future.

Taken together, our clinical and preclinical programs comprise the broadest and most advanced product pipeline in the emerging field of neurotology, and we have the cash on hand to support the rich advancement. As you all know from our financial statements in the earnings release and 10-Q, we finished the third quarter with $68 million in cash and short-term investments. We continue to manage our spending levels carefully and are in fact lowering our non-GAAP operating expense guidance by $5 million for full year 2019.

We also expect as we previously stated that 2020 operating expenses will be lower than 2019 and that our current capital will fund the company's operation through the 3 clinical trial readouts and into 2021.

In summary, we have positioned Otonomy for a breakout year in 2020. The OTIVIDEX Phase III trial, OTO-313 Phase I/II trial and OTO-413 Phase I/II trial provide multiple value creation catalysts for the company, and we are laser focused on their successful completion. We look forward to bringing this message to investors through an expanded set of outreach activities beginning this quarter and continuing into 2020.

To this point, we will be attending the Piper Jaffray Health Care Conference on December 3 in New York and participating in a hearing loss panel at investor meetings at the Evercore ISI Conference in Boston on December 4.

Operator, we are now ready for questions.


Questions and Answers


Operator [1]


(Operator Instructions) Your first question comes from line of Tyler Van Buren from Piper Jaffray.


Tara A. Bancroft, Piper Jaffray Companies, Research Division - Research Analyst [2]


This is Tara on for Tyler. So in thinking ahead to the OTIVIDEX Phase III readout, can you kind of set the bar for us as far as expectations and what are meaningful changes in these patients? Should we expect a similar vertigo day benefit like we saw on AVERTS-2? And what about percent of vertigo decrease?


David Allen Weber, Otonomy, Inc. - President, CEO & Director [3]


Thank you, Tara. Yes, what you can expect is similar to what we reported for AVERTS-2 and the Phase IIb trial that's in our corporate deck. We continue to focus in the primary outcome, is on definitive vertigo days, and change in definitive vertigo days. And importantly, achieving the p value that we've discussed with the agency. We have, as you know, one successful trial with AVERTS-2. So it really is duplicating that trial to provide two separate successful Phase III trials for submission of the NDA. So the data would be consistent with what we've shown previously, the trail design is the same, the endpoints are the same, and the data that we would expect to present both to investors and to the FDA are the same as AVERTS-2.


Tara A. Bancroft, Piper Jaffray Companies, Research Division - Research Analyst [4]


Okay. Can I ask then similarly for the Phase II and 313. Can you explain more about how the TFI questionnaire will maybe inform future registration endpoints and approval? Like what specifics are you looking for regarding changes in hearing quality there?


David Allen Weber, Otonomy, Inc. - President, CEO & Director [5]


Yes, thank you. So the TFI is a validated -- considered a validated instrument. It was actually developed by a consortium of researchers and it plays out in that testing, which is represented by 25 questions that cover things like intrusiveness of the tinnitus, a sense of control that the patients have, their cognition, their ability to sleep, their auditory function and more quality of life like their emotional state is in that TFI through those 25 questions. It's established through the validation of that work of what represents generally a meaningful change is 13 points and based on the work that has been done there, and we also understand the classification of patients. So patients that typically are less than 25 on the TFI score are considered mild, whereas 25 to 50 are moderate, and higher than that are 50 and severe. Generally, physicians consider any patient that has 25 and higher to be patients in need of treatment. That will be our primary outcome because we do believe that, as I've said, a very measurable and validated instrument, we are also assessing separately other types of rating scales, such as tentative loudness and annoyance and then also a patient global impression of change, basically where we are asking the patients of how they perceive their tinnitus since the beginning of the study to understand their overall perception of change.


Tara A. Bancroft, Piper Jaffray Companies, Research Division - Research Analyst [6]


Yes, that's super helpful. If I can ask one more question about the gene therapy pipeline?


David Allen Weber, Otonomy, Inc. - President, CEO & Director [7]




Tara A. Bancroft, Piper Jaffray Companies, Research Division - Research Analyst [8]


Okay. So you mentioned in the press release regarding the AGTC collaboration that you are targeting the patients with GJB2 mutation that has been identified from the routine hearing screens in newborns. So I'm assuming your target population will include like newborns and infants with hearing loss due to that mutation, but we also know that the same genes that are responsible for homogenic deafness may also contribute to environmental hearing loss due to like drug exposure, noise and aging. So will those patient also be included in your target population for this gene therapy?


David Allen Weber, Otonomy, Inc. - President, CEO & Director [9]


No, not initially at least. This will be focused more on the pediatric population because they are the most severely threatened with hearing loss and progressive hearing loss. So typically, this can be picked up on newborn screening and patients will continue to progress from there. So it's very important to catch them at an early stage and so that will be our initial focus for the gene therapy.


Operator [10]


Your next question comes from the line of Oren Livnat from H.C. Wainwright.


Oren Gabriel Livnat, H.C. Wainwright & Co, LLC, Research Division - MD & Senior Healthcare Analyst [11]


I have a few. With the OTIVIDEX Phase III that's enrolling little bit slower than we had modeled, can you just remind us what you're doing differently in this trial maybe from AVERTS-1 such that a more deliberate enrollment speed is potentially an indicator of improved likelihood of success? And I have a couple of others.


David Allen Weber, Otonomy, Inc. - President, CEO & Director [12]


Yes, thanks Oren. I'm taking one at a time, that's fine. So great question, and that actually is the key, as we are very focused on being very careful here, and very deliberate in our enrollment. We think that its very key to the success of the trial based on our learnings from AVERTS-1. As we've discussed previously, the real learnings was around AVERTS-1 so as to control the placebo response and manage the patient expectation bias. And that was really kind of focused on 3 major areas and one of those was careful site selection. So we have gone through, obviously, now we have 60 centers enrolling across all participating countries, that took time. We needed to make sure we got it right, the right clinical centers, and right investigators, and we feel very confident in the group that we've assembled that are now all participating and enrolling. So that was the first.

From there it's really careful selection of the patients. In this case, there are no -- there is no advertising going on direct to patients, unlike with the AVERTS-1, where there were investigators who were reaching out in the general population. This is all very controlled and targeted patient enrollment and so it's very -- in that regard, it does take time and it is important that investigators are identifying these patients and carefully selecting them.

So we're not putting pressure on the investigators in terms of trying to advertise or increase the enrollment, we want to be very deliberate in that patient population. So we think that the few weeks to few months that we're talking about here in extending is just a safeguard to make sure we get -- ultimately are able to deliver a successful trial as well step.


Oren Gabriel Livnat, H.C. Wainwright & Co, LLC, Research Division - MD & Senior Healthcare Analyst [13]


All right. And just a follow-up on the tinnitus question. You mentioned that the TFI improvement of more than 13 is believed to be clinically meaningful. Is that what you're targeting? Are you expecting any statistical significance in this small study? Or are you just looking for any signal? And if so, if you do see a signal, what do you think the next steps are? Should we expect another Phase II before jumping into the more advanced?


David Allen Weber, Otonomy, Inc. - President, CEO & Director [14]


Well, let's take that one at a time there. In terms of Phase II to Phase III, but I think first of all, this is not size for power. It is the exploratory efficacy trial because it is the first of its kind. We have no prior clinical data to base sizing and powering on, it is what we consider exploratory and so we are looking for signals through these different endpoints, including the TFI. The TFI, as I mentioned, when the instrument was developed and validated by the consortium, they identified 13 point difference as being clinically meaningful, but I should point out that's in the absence of a therapeutic that really is through other types of both behavioral treatment of tinnitus and even some devices that have been tried in tinnitus. So I think it'll be up to -- as we look at the data to understand what do we see with the TFI but clearly that gives us the benchmark at least based on some prior work, even if it was in a pharmaceutical treatment. I think clearly the patient global impression of change and the other endpoints that I mentioned of loudness perception and annoyance perception are also very key to these patients given that it is the loudness and that annoyance that is the most debilitating for them in this disorder. So that's how we look at the study, and we would look to utilize the Phase I/II trial for then powering the future study. With regards to Phase II, additional Phase II, Phase III, I think that is something that we will consider based on that data.

One of the things -- so clearly with very strong signals, the opportunity is to do what I will call a larger Phase II type Phase III trial or obviously based on the data if we had confidence to go into a Phase III from there, I think one of the things that we also will want to look at, however, in addition to this patient population we are currently studying is to look at bilateral patients as well. So it's something that we're interested in because there are many patients that have bilateral tinnitus and that potentially be eligible, but that is something we want to look at probably in a separate study before including those patients.

Currently, we're focused on unilateral patients and that is because there has been concern clinically and working with our KOLs of whether patients can really tell the difference if they have bilateral, can they really talk and understand the difference in their tinnitus between one ear and the other or is there a confusion there because of both ears. And so that's why we're being very careful here using unilateral patients, but I think one of the things you can probably expect from us in future work is to also include some bilateral patients to look at the ability to detect changes in those patients as well. I'd say detect because I think that's the key. We and our KOLs all believe that showing an effect in a single ear will equate to treatment of both ears, ultimately that you'd be able to treat both ears mechanistically. It's more ability to differentiate the signaling for their patient reported outcome here. Can they report the outcome very carefully between one ear versus the other is something I think we have to look at clinically if that makes sense.


Oren Gabriel Livnat, H.C. Wainwright & Co, LLC, Research Division - MD & Senior Healthcare Analyst [15]


All right. And at the risk of abusing my time, it was lost to me that there was a recent IPO of Frequency Therapeutics and other therapeutic company working I think on hair cell regeneration, and I'm just curious, obviously you can't speak too much to what they're doing but maybe you can just highlight how similar or different your approaches are? And if you think that there will be any key learnings from what they are doing?


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Edited Transcript of OTIC earnings conference call or presentation 5-Nov-19 9:30pm GMT - Yahoo Finance

Harvard study advances gene therapy in fighting age-related diseases – The Boston Globe

If you hit enough specific diseases, youre getting at the core aging components that are common to all of them, Church, a Wyss core faculty member, said in an interview Monday. Gene therapy gives you a testable therapy at scale in mice. And we can move from mice to dogs and then to humans. Were focusing on the reversal of age-related diseases so well be more healthy and youthful later in life.

The research is part of a broader emerging field, sometimes called geroscience. Its advocates believe that the best way to treat a variety of illnesses from cancers and heart disease to Alzheimers and macular degeneration is to attack the aging process itself.

Were taking a holistic approach, said Noah Davidsohn, a former research scientist in Churchs lab who is first author of the study. Rather than attack specific diseases, were trying to make patients generally healthier and, in the process, getting rid of as many age-related diseases as possible. Nobody wants to be old and in a wheelchair and not doing anything.

Bostons biomedical hub has become a hotbed of geroscience research.

Last winter, 16 of the worlds top longevity scientists, including Harvard scientist David Sinclair, professor of genetics and director of the Paul F. Glenn Center for the Biology of Aging, formed a Boston-based academy that will seek to spotlight medical research on extending human life and developing drugs to slow the aging process. The nonprofit Academy for Health and Lifespan Research will share research and lobby governments in the United States, Europe, and elsewhere to increase funding and create new paths to approve age-slowing therapies.

Previous studies in the field have also sought to slow aging and extend healthy life spans through small molecules that increase blood flow and endurance, or weed out zombie cells that send out toxins causing age-related maladies. But the Wyss Institute is the first to use therapy that combines genes to boost protein levels that diminish with aging. The genes were selected from a database developed over the past decade at Churchs lab.

We looked at the ones that had the biggest impact individually and then wanted to see if they would work more effectively in pairs and triples, Church said. Such an approach, he said, had the greatest potential to target multiple diseases through a one-and-done injection into the blood or muscle, a simple procedure akin to getting an influenza vaccine shot.

When deployed against obesity, type II diabetes, heart failure, and renal failure, a single formulation ... was able to treat all four diseases, according to the study published in PNAS. These results emphasize the promise of gene therapy for treating diverse age-related ailments, and demonstrate a new approach of combination gene therapy that may improve healthspan and longevity by addressing multiple diseases at once.

San Diego-based biotech startup Rejuvenate Bio, founded by Church and a pair of coauthors of the PNAS study, Davidsohn and Daniel Oliver, is pursuing a gene therapy to fight age-related diseases. The company has already begun working with the Cummings School of Veterinary Medicine at Tufts University in North Grafton to test the gene therapy combination in dogs.

Davidsohn, chief technology officer at Rejuvenate, said the company is focused for now on developing and marketing a treatment that can extend the health span of dogs, which can suffer from a range of age-related illnesses including heart and kidney problems, obesity, dementia, and hearing and vision loss similar to those afflicting humans.

His own 5-year-old dog, Bear, whom Davidsohn adopted while working in the Wyss Institute lab, was an inspiration and now holds the honorary title of chief inspiration officer at Rejuvenate. The company was launched in stealth mode about a year ago and now has eight employees.

While dogs will be an important market in their own right for the combination gene therapy, Davidsohn said, We would be happy if this ended up in humans.

Church said testing the experimental therapy in dogs is likely to take about two years. Then, if regulators approve it, clinical trials could begin in humans. But even if all goes well, he said, the gene therapy probably wont be available as a marketed product for more than a decade.

By then, he said, the cost of a gene therapy which now can top $1 million per patient for rare diseases could drop to thousands of dollars per patient in what would be a much larger market to treat multiple age-related diseases.

Some supporters of age-slowing research, such as Jay Olshansky, public health professor at the University of Illinois at Chicago, have cautioned against expectations that scientists can radically lengthen life spans. Instead, they believe, the goal should be, as Olshansky puts it, pushing out the red zone, the time of frailty and disability at the end of life.

Church, however, has a more ambitious vision.

The important thing is getting good at age reversal, he said. If age reversal truly works, there is no upper limit on how long healthy lives can be extended.

Robert Weisman can be reached at robert.weisman Follow him on Twitter @GlobeRobW.

Correction: An earlier version of this story incorrectly characterized the status of the collaboration between Rejuvenate Bio and George Churchs Wyss Institute Lab.

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Harvard study advances gene therapy in fighting age-related diseases - The Boston Globe

Combination Gene Therapy Could Treat Multiple Age-related Diseases – Technology Networks

As people age, they tend to develop diseases such as heart failure, kidney failure, diabetes, and obesity, and the presence of any one disease increases the risk of developing others. Traditional drug treatments, however, each target one condition. That means patients often have to take multiple medications, increasing both the risk of negative side effects and the likelihood of forgetting one.

New research from the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard Medical School (HMS) suggests that it may be possible someday to tend to multiple ailments with one treatment.

In the Wyss study, a single administration of an adeno-associated virus (AAV)-based gene therapy, which delivered combinations of three longevity-associated genes to mice, dramatically improved or completely reversed multiple age-related diseases, suggesting that a systems-level approach to treating such diseases could improve overall health and lifespan. The research is reported in PNAS.

The results we saw were stunning and suggest that holistically addressing aging via gene therapy could be more effective than the piecemeal approach that currently exists, said first author Noah Davidsohn, a former research scientist at the Wyss Institute and HMS who is now chief technology officer of Rejuvenate Bio. Everyone wants to stay as healthy as possible for as long as possible, and this study is a first step toward reducing the suffering caused by debilitating diseases.

The study was conducted in the lab of Wyss core faculty member George Church as part of Davidsohns postdoctoral research into the genetics of aging. Davidsohn, Church, and their co-authors homed in on three genes that had been shown to confer increased health and lifespan benefits in mice that were genetically engineered to overexpress them: FGF21, sTGFR2, and Klotho. They hypothesized that providing extra copies of those genes to nonengineered mice via gene therapy would similarly combat age-related diseases and bring health benefits.

The team created separate gene therapy constructs for each gene using the AAV8 serotype as a delivery vehicle, and injected them into mouse models of obesity, Type 2 diabetes, heart failure, and renal failure both individually and in combination with the other genes to see whether there was a positive synergistic effect.

FGF21 caused complete reversal of weight gain and Type 2 diabetes in obese, diabetic mice following a single gene therapy administration, and its combination with sTGFR2 reduced kidney atrophy by 75 percent in mice with renal fibrosis. Heart function in mice with heart failure improved by 58 percent when they were given sTGFR2 alone or in combination with either of the other two genes, showing that a combined therapeutic treatment of FGF21 and sTGFR2 could successfully treat all four age-related conditions, therefore improving health and survival. Administering all three genes together resulted in slightly worse outcomes, likely from an adverse interaction between FGF21 and Klotho, which remains to be studied.

Importantly, the injected genes remained separate from the animals native genomes, did not modify their DNA, and could not be passed to future generations or between living animals.

Achieving these results in nontransgenic mice is a major step toward being able to develop this treatment into a therapy, and co-administering multiple disease-addressing genes could help alleviate the immune issues that could arise from the alternative of delivering multiple, separate gene therapies for each disease, said Church, who is also a professor of genetics at HMS and professor of health sciences and technology at Harvard and MIT. This research marks a milestone in being able to effectively treat the many diseases associated with aging, and perhaps could lead to a means of addressing aging itself.

Church, Davidsohn, and co-author Daniel Oliver are co-founders of Rejuvenate Bio, a biotechnology company that is pursuing gene-therapy treatments for dogs. Each holds equity in Rejuvenate Bio.

The finding that targeting one or two key genes has therapeutic effects in multiple diseases makes enormous sense from the perspective of pathophysiology, but this is not how drugs are normally developed. This ability to tackle several age-related diseases at once using gene therapy offers a potential path to make aging a more manageable and less debilitating process, said Wyss Founding Director Donald Ingber, who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Childrens Hospital, as well as professor of bioengineering at Harvards John A. Paulson School of Engineering and Applied Sciences.

Reference: Davidsohn et al. 2019.A single combination gene therapy treats multiple age-related diseases. PNAS.

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Combination Gene Therapy Could Treat Multiple Age-related Diseases - Technology Networks