Special report: Twenty extraordinary women blazing trails in biopharma R&D Covid-19 and beyond – Endpoints News

Posted: December 11, 2020 at 9:56 am

In the second year of Endpoints Newsbudding tradition of highlighting women blazing trails in biopharma R&D, weve seen a number of firsts.

For the first time, the biggest story in R&D is also top of mind for a world anxious to end the most devastating health crisis in decades. With its sweeping effects, the Covid-19 pandemic is turning the daily routines for many working women upside down, taking a toll on not just their physical and mental health, but also their career prospects. At the same time, the biotech industry is doing some serious soul searching with a new scorecard and plan for diversity and inclusion.

It is more important than ever to shine light on the growing number of women who have scaled the heights of drug discovery and development even though the odds are stacked against them, breaking open paths in labs and C-suites that can be followed by future generations, some of whom they are also actively nurturing and mentoring.

We set out this year with a dual goal: to celebrate women at the forefront of subduing Covid-19 either with diagnostics, vaccines or treatments and to honor those working day in and day out to address other equally pressing medical needs.

Profiles are, by definition, snapshots. Some of the women recognized in our 2019 special report have since become household names: Jennifer Doudna became a Nobel laureate for her pioneering work in CRISPR gene editing and zlem Treci helped create the worlds first vaccine proven effective against Covid-19. Even in the short period since we interviewed this years honorees, weve seen them mark new milestones, from taking a biotech public to scoring historic clinical data and regulatory authorizations.

We hope our profiles capture a unique moment in history as these highly accomplished figures take us with them down memory lane to illustrate what brought them to this moment and how they are helping other women do the same if not even more.

We hosted an online live event to introduce this years top women in biopharma R&D, followed by a panel discussion on what it will take to truly achieve gender diversity in the industry. You can watch the full event here.

Carolyn Bertozzi wasnt exactly looking to start a company when she tweeted about a preprint her group posted on ChemRxiv last November. The paper described LYTACs molecules that can tag extracellular proteins for degradation.

She was heading out to the American Chemical Society Conference in Orlando to talk about the project, led by a postdoc in her Stanford lab named Steve Banik.

(Steve) was about to go on the academic job market, so its a good time for me to go and sort of talk about his work publicly and drop his name and get him some name recognition, she recalled.

Within 24 hours, though, she got a dozen phone calls from venture capital groups who picked up on the preprint. There was a proliferation of startups utilizing and improving on PROTACs a targeted degradation technology born out of Craig Crews academic work at Yale but that magic was limited to intracellular proteins. Bertozzi was a self-described jealous fan of Crews work because glycoproteins, the subject of her own research, reside exclusively on cell surfaces; it turned out VCs had also been wishing there were ways to target secreted and membrane proteins.

In the end, she found Versant Ventures to be the best fit for the science. Now, Lycia Therapeutics, which unveiled a $50 million Series A just a few months ago, has been taking off like a rocket ship, she said.

The enthusiasm from investors might be expected for a scientist and entrepreneur whose last biotech creation, Palleon Pharmaceuticals, recently reeled in $100 million in fresh financing. Redwood, the one that came before, recently reported Phase I data as a subsidiary of the CRO giant Catalent. Then there are the handful of diagnostics players that she created with researchers under her wing.

But for Bertozzi, its all about timing.

Her first experience with entrepreneurship a biotech startup she co-founded in the late 1990s after completing a postdoc with Steve Rosen at UCSF actually ended in failure. Thios Pharmaceuticals, as it was known, had zeroed in on a target for sickle cell acute vaso-occlusive crisis and in-licensed a molecule that worked in a similar way as two therapies approved by the FDA late last year.

They raised $10 million for it, a respectable amount for a Series A at that time, but it wasnt enough to sustain the 30-person company when investors decided not to continue funding it. The drug was shelved as Thios closed up shop.

It was always very heartbreaking to us that we couldnt have brought that to those patients 15 years earlier, Bertozzi said. But thats how it goes in this business, and every company has a story like that.

In her day job as an academic, Bertozzi is known for spearheading a glycorevolution: developing chemical tools and technologies to elucidate the roles that complex sugar structures play in biological systems. Glycans, as she learned during her doctorate, are an order of magnitude more technically complex than polypeptides and oligonucleotides because of their structural diversity. But papers dating as far back as the 1950s have suggested they do play a role in diseases such as cancer, and spectacular breakthroughs in chemical synthesis the challenge that drew her to the space initially have helped scientists make inroads in their study.

Her biggest breakthrough which won her a MacArthur genius grant at age 33 came in what she coined bioorthogonal chemistry, a way for chemical reactions to take place within biological systems.

Both the tools and her deep knowledge of glycobiology provided the foundation for the subsequent technologies her group would later develop. Site-specific chemical modification of recombinant proteins promised to make better antibody-drug conjugates (ADC) than the very sloppy molecules that characterized the first generation of ADCs; digging deeper into new findings on how cancer cells sprouts sugars on their surfaces to evade the immune system led them to bispecific antibody-enzyme constructs that target the siglec-sialic acid pathway, billed as the next big I/O checkpoint; and utilization of lysosomal trafficking shuttles one of the first things you learn when you study glycobiology gave birth to chimeras that send unwanted extracellular proteins to the lysosome for targeted degradation.

More so than any particular technology, though, she considers the young scientists who trained with her and are now standing on their own feet her most important achievement.

Carolyns genius is not only in the research she leads, but also in those she recruits, Mireille Kamariza, a former PhD student, said. Now a junior fellow at Harvard University, she co-founded with Bertozzi a public benefit corporation to advance a point-of-care diagnostic device for tuberculosis.

She has an uncanny ability to bring out the best in people, Kamariza added. She leads by example and gives unyielding support to her students interests and pursuits.

Now 54, Bertozzi recently found herself reflecting on her career after the death of late Supreme Court Justice Ruth Bader Ginsburg. Harvard, after all, had only integrated with Radcliffe a few years before shed start undergraduate studies there.

I consider myself to be in sort of the first generation where you see a critical mass of women who made it through the academic pipeline and into industry, she said. There arent many of us, but you can count us. Were visible.

Having seen every shade of gender discrimination and bias (show me a woman who hasnt), Bertozzi is leveraging her influence as the co-director of Stanford ChEM-H to bring in more voices from outside the usual suspects reaching out and forging relationships with public universities and institutions serving underrepresented communities to find talent that is hiding in plain sight.

In previous interviews, shes noted that part of what got her hooked in those first organic chemistry classes was how molecules have personalities like people. So I couldnt help but ask: What molecule would she be?

The answer was surprisingly simple. She aspires to be a monoclonal antibody.

They multitask all over the place, she said. In fact, all of the next-generation biologics out of her lab have had antibodies as their backbones.

I have gotten so much mileage out of antibodies, she said. And so I would like to think maybe my students could get the mileage out of me that same way. That would be my aspiration.

Thats not all: Oh, and they are glycosylated. Amber Tong

Kathy Bowdish was sitting down at a San Diego restaurant after her first pitch meeting in 1997 when one of the potential investors turned and asked her a question: Does your husband know youre doing this?

Taken aback, Bowdish, 39 at the time, said yes, and that part of this was his idea. Of the 12 angel investors at the table that day, the concerned citizen was the only one who didnt decide to back her first startup. And he was the only one who didnt get a cut of the profits three years later, when Bowdish sold the startup to Alexion for 10 times their investment.

When the press release for the buyout hit the wire, her phone rang. It was the lone investor.

If you do this again, I want to be on speed dial, the investor told her. Bowdish looks back on that moment with victory-tinged humor: Clearly, his question had been troubling him.

The seed investor had made two mistakes. One shouldve been obvious at the time: plain misogyny. But the other would only become fully apparent over the ensuing 23 years as the young scientist-executive enmeshed herself in a series of top biotechs and eventually was handpicked by Elias Zerhouni to lead a unique and under her direction fruitful venture in Sanofis upper ranks.

He had underestimated Kathy Bowdish.

Bowdish would prove over the years a rare triple-threat in biotech: a brilliant scientist who could handle the business side but also had the poise and emotional IQ to massage needed personal relationships and wheedle folks who could get things done. After nearly two decades in biotech, she used those skills to build powerful new companies at Sanofi. And when the winds changed there, she pivoted mid-career to what she first learned to do in San Diego: build a company with cutting-edge science from the ground up.

Kathy impressed me because she had been CSO, she was a very good scientist, Zerhouni told me. But she had this very special natural calm A very thoughtful calm, a resilience. She had this analytical mind.

Bowdish is now working from her home in Cambridge, trying to get a three-person,RNA-based startup off the ground with $5 million in seed cash. Its a significant departure from her Sanofi perch, but its a position she knows and a place shes thrived before.

The daughter of an engineer and an artist, Bowdish was seduced by the cerebral yet creative challenge that scientific problems posed. After studying biology at William & Mary, she moved to the West Coast, where she was quickly recruited for a position at Scripps Research and worked with Richard Lerner on the then-pioneering field of catalytic antibodies.

She was clever and ambitious, devising new ways of sequencing antibodies in an era before you could simply plug them into RNA-Seq. She left to get a PhD at Columbia University, and picked a yeast lab because yeast multiplies like microbial rabbits, which meant you could do a lot of genetics work in a single program.

A postdoc followed, but she soon grew impatient. These were still early days for antibodies. She pitched Lerner on the idea of building a company around the work they did on combinatorial antibody libraries basically discovery engines in a test tube.

His immediate question to me was can you live without a salary for 6 months? Cause thats what its going to take in order to raise the money. And I said yes, she said. I was pretty naive maybe the naivet was a good thing.

The investors (but one) came on board, Bowdish finagled her way into some cheap equipment, hired another scientist a woman and for a year the pair worked at the bench to discover antibodies that would activate, rather than inactivate, receptors. She shifted over to a full CEO role after year one, and after year three Alexion bought the company for $41 million, betting that it could serve as their discovery engine.

She stayed at Alexion until 2007, by which time she was a sought-after name for biotechs with big ideas. Investors recruited her to relaunch Anaphore, a Danish biotech trying to develop antibody-like alternatives that were more selective or more potent. They struggled for years, which worried Bowdish until she realized every company in the space was struggling. It taught her a valuable lesson about what makes for good translational science.

You just cant beat evolution, she said.

Then ARCH and Flagship came calling. They had funded a bold Bob Langer idea for delivering proteins inside cells. Quickly, she realized they had to start testing this in animals to have any idea if it worked. And quickly they learned that it didnt everything went to the liver. So she leveraged their tech into antibody-drug conjugates.

It looked really good in vitro, she said. In vivo, not so much.

By then it was 2013. and Bowdish had been in the league for 16 years, helping run five biotechs on both coasts. She knew the game, but she was curious: about pharma, that behemoth in the background, and about investment, a general-esque perch from which she could ponder and evaluate. At the same time, Zerhouni was conceiving a new initiative at Sanofi: Sunrise, a way of giving biotechs the resources and expertise of pharma while allowing them to flourish on their own. It married the two.

Bowdish got the job, beating out such biotech titans as Michael Gilman. Inside, she learned how pharma worked and she built new companies. She was, Zerhouni said, singlehandedly responsible for MyoKardia, the cardiovascular upstart that Bristol Myers Squibb recently purchased for $13 billion. She found them, he said, designed a deal to get them the best resources and convinced Sanofi leadership to get on board.

Shes able to move the needle from a pretty established sort of approach to an innovative one, Zerhouni said. Shes a change agent.

Then Paul Hudson came in, reshuffled Sanofi, and Bowdish found herself on the outs (Sanofi also pulled out of her MyoKardia deal, a blunder that cost them a cool $1 billion). She went home, relaxed and did what she always does dove back into the literature: papers on immunology, diabetes, biomolecular condensates, whatever fascinated her.

Eventually, a recruiter called. She realized it was time to get moving. She mentioned to Gilman they had stayed in touch after a conference that she was on a hunt, and Gilman put her in touch with Genzyme Ventures vet Alan Waltz, who was looking for a CEO for a company that would develop small molecules that target structures on mRNA in an effort to block multiple oncogenes. She liked the science and the potential impact.

It was back to some of my earlier learnings, in terms of the right constellation of people around the table and the science that was ready for this very directed effort, she said.

So now she works from home, poring over the literature, directing CROs and her team of three, preparing for a fundraising round and building a whole team. Its a smaller company than she had led since she was just out of grad school, ignoring the pretensions of a sexist investor, and she couldnt be happier.

Its actually a lot of fun, she said. Jason Mast

Diana Brainard was studying abroad in France when she realized something just didnt quite feel right.

Intending to become a comparative literature professor while attending Brown, Brainard enrolled at a French university as part of her major and fully immersed herself for the first time in literature and lit theory classes. Brainard had mainly taken a balanced diet of courses stateside everything from math and science to English and the Study Abroad program was a necessary part of her program. She went into it head-on as her literature seminars were her favorite undergrad classes, with passionate professors seemingly putting on a production every class.

But after diving in, Brainard felt her studies had lost their attachments to the real world.

All of a sudden there was this realization of Wow, what Im really being assessed on in these classes, and how my career will be assessed in this field, is coming up with a theory and making that theory sexy, Brainard said. But that theory doesnt have to be true. It just has to be sexy and interesting and I can do all of that, but there is no truth here.

Since then, Brainard has moved past the days of Thomas Manns The Magic Mountain, though she hasnt lost her love of literature. Now, shes a senior executive at Gilead and has been a major part of the team that developed remdesivir, recently approved by the FDA as the first Covid-19 treatment for hospitalized patients.

The path from France to Gilead wasnt a straight line, however. Brainard notes that after Brown, she eventually went to med school expecting to become a physician. But that didnt end up being the right fit either, especially after Brainard fell in love with infectious diseases. She ended up as a researcher at Harvard focused on HIV, content to work off NIH-backed grants for the rest of her career.

Then biopharma came calling.

Leaving academics was really hard because I was happy doing what I was doing, and I hadnt envisioned in the future that I would be going to industry, Brainard said. There werent a lot of people at Harvard who had done that before, and so I felt like I was taking a big risk, I was leaving behind NIH funding, we were leaving Boston where wed been for a long time, and I didnt know if I would wind up regretting all of the things that I was letting go of.

Brainard jumped aboard first at Merck, then joined Gilead in 2010. Shes spent her entire career, in academia and otherwise, working in infectious diseases and immunology, and much of her time at Gilead has centered on hepatitis C treatments. When she was first alerted to remdesivirs potential benefits for a new coronavirus strain out of China almost a year ago, Brainard moved to get it into the lab as quickly and efficiently as possible.

Remdesivir was a team effort, Brainard said, and shes reluctant to take credit for spearheading the drugs pivot to Covid-19. Originally tested in hepatitis C and then Ebola, remdesivir showed early signs of in vitro activity in SARS and MERS. Brainard pushed for Gilead to begin a compassionate use program for the drug, and it received partial emergency authorization in May for severe Covid-19 cases.

That EUA was expanded in August to include moderate cases, and the FDA handed down a full approval in October for patients who have been hospitalized with the disease.

Its been exhilarating to do [this] for Covid because of the acute, unprecedented medical need, and because scientifically its fascinating to have a disease, as an infectious disease expert, to learn about a disease at the same time youre trying to figure out if a therapy for a disease works, Brainard said a few weeks before the approval. Its a really difficult problem, and one that doesnt come around very often.

The drug has received some pushback, as a study backed by the WHO found in mid-October that remdesivir had little to no effect in reducing mortality rates or the need for ventilators.

Though Brainard was originally hesitant to move from academia, shes happy to have found a home at Gilead and not have to deal with what she says are liabilities in that arena. She never really enjoyed the structure of how academic careers are traditionally judged, where the main goal is to work your way up the authorship ranks and get a couple of papers under your belt.

Brainard much prefers the collaborative environment in industry. And at Gilead, she thinks that collaboration helps her be a better role model for younger women rising through the field.

The impact that I have, a lot of it is the drugs, Brainard said, but a lot of it is the people. The people who I work with, a lot of the people who come to Gilead, for example, come right out of training and they make that transition in the same way that I did. Helping them learn how to think in this new environment and thrive, and flourish in a new environment, thats really meaningful to me. Max Gelman

Janice Chen is all about democratizing diagnostics.

The Mammoth Biosciences co-founder has made that her mission over the last three and a half years, working alongside newly-minted Nobel laureate Jennifer Doudna to develop diagnostic tools centered around CRISPRs gene editing techniques. But what might that look like in practice? Chen theorized some potential uses in a TEDx CERN Talk two years ago.

What if you could directly and accurately test for the flu at home? Chen said. What if you receive the prescription and treatment plan without having to step foot into a clinic? And what if the same principle could be applied to other dangerous diseases such as Ebola?

Chen kicked off her scientific career as an undergrad at Johns Hopkins, where she took a course in which students built the yeast genome from scratch. She credits that class with getting her the technical skills needed to apply to research and lab assistant positions, as well as explore how synthetic biology could lead to a swath of applications.

It also served as a jumping-off point for Chens ambitions, where she said she was able to get her hands wet in something with real-world applications rather than reading lines from a textbook. After a yearlong stint as a research technician at Harvard, where her work focused on Ralstonia eutropha bacteria, Chen moved on to her doctorate at UC Berkeley and joined Doudnas lab.

Its there where she first hooked on to CRISPR research.

Myself and colleagues in the lab, including co-founder Lucas Harrington, came across this unexpected finding that some of these Cas proteins were able to detect DNA, Chen told Endpoints News. A lot of it was serendipitous in terms discovering this activity, and being able to demonstrate it on real patient samples I think was really an exciting moment for me in thinking about OK, can we actually take this outside the academic lab and try to do something with it?

Though CRISPR has largely settled in the mainstream consciousness as a way to potentially cure a range of severe diseases along with the occasional headline that scientists are out to create gene-edited embryos in a lab Chen and the Mammoth team are looking at ways these tools can be used for disease detection. Instead of using the scissors normally associated with CRISPR to edit genes, Chen programs the tech to find a defined gene sequence and sends out a signal once its been located.

With the Covid-19 pandemic in full swing, Mammoth has also steered its research toward creating accessible and easy-to-use tests for the detection of SARS-CoV-2. In that instance, the platform is programmed with a guide RNA, and Chen hopes by working on tests that can function outside of the typical lab setting, this can be one of the ways to democratize the technology.

Its been successful because its programmable, Chen said. Theres a whole world of testing thats just starting to be closer to reality that has never quite been able to be done because of the limitations of infrastructure needs, the accuracy to actually be a viable solution. With CRISPR now on the scene, were really excited about the potential to address these point-of-need environments that dont rely on your traditional clinical laboratory.

Chen credits her doctoral advisors from Berkeley, Doudna included, with keeping her focused and transitioning from academia to becoming an entrepreneur at Mammoth. Ultimately, that led Chen to her north star of not just engineering new uses for CRISPR, but being able to create impactful technology in general.

(Doudna) herself is a serial entrepreneur, and so its been really important to have her mentorship, and seeing her as a role model being very successful in both the academic world as well as the startup world, Chen said, a few weeks before Doudna won the Nobel Prize.

As someone whos still in the early stages of her career, Chen recognizes the opportunity she has to make an impact on the women who follow in her footsteps. Shes already been named to Forbes 30 under 30 healthcare list from 2018 for being among the most influential millennials in the sector. By coincidence, all of her major research experiences from Johns Hopkins through Berkeley were led by women principal investigators.

And while Chen says theres not going to be one magic bullet that fixes everything in the industry, the best place to get started is by recruiting talent from all sorts of different backgrounds.

Once you have that talent and have them in the company its really important to ensure that they have the support systems and mentorship internally to help them grow, Chen said. Its important to recognize that there are really great leaders in companies that might not fit the traditional mold, and I think that there are a lot of companies that are starting to figure that out. Max Gelman

In a cramped, windowless lab basement beside Cambridges Blue Room bar, Ann Cheung stuck her head in the freezer and, with a vial of cells in one hand, used the other to phone a world-famous professor across town and a tech entrepreneur in San Francisco.

Cheung was 34. She had the academic pedigree: Brown, MIT, a postdoc at CalTech where she built nanoparticles and studied immunotherapy with a Nobel laureate. But it had been over four years since she worked with flasks and centrifuges. Her last job was at MIT but as an administrator and communicator. It involved a lot of tweeting.

Then a call came from Tyler Jacks, the renowned head of the MIT Center for Cancer Research (now called the Koch Institute) and her old doctoral advisor. Along with an old college friend, the Silicon Valley inventor Bill Haney, they wanted to bootstrap this new idea out of Jacks lab, a jackknife way of getting the immune system to turn on cancer. And Jacks knew Cheung was itching to get back to the bench.

Soon she found herself in the basement of a Kendall Square bar, in a lab no bigger than a university office, growing antibodies and natural killer cells with a single other employee and hearing the sounds of eating and loud talking whenever they went in the hall. She was the gritty and brilliant, if unlikely, CSO of Dragonfly Therapeutics, and her work there and in the shiny offices theyve since moved to would prove and develop ideas that eventually landed collaborations with Celgene, AbbVie and Bristol Myers Squibb. Last year, it entered patients for the first time.

Her growth has never stopped and this has been true for her entire career, Jacks told me. Theres no challenge that discourages her. Shes kind of fearless.

Cheung didnt arrive as a graduate student at Jacks MIT lab wanting to study immuno-oncology. This was 2002. Checkpoint inhibitors were still a fringe idea in the head of a wild-haired Berkeley professor. No one studied immuno-oncology in Jacks lab.

One evening, though, Bob Schreiber came in for a lecture. Schreibers mice work was just beginning to resurrect the idea of using T cells to attack tumors, and Cheung was captivated. On the walk back that night, she turned to Jacks with an epiphany. Of course the immune system can fight cancer, Cheung said. Cancer is something that is foreign to the body even though it comes from the body, so it absolutely makes sense.

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Special report: Twenty extraordinary women blazing trails in biopharma R&D Covid-19 and beyond - Endpoints News

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