In the second year of Endpoints News’ budding tradition of highlighting women blazing trails in biopharma R&D, we’ve 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 Özlem Türeci helped create the world’s first vaccine proven effective against Covid-19. Even in the short period since we interviewed this year’s honorees, we’ve 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.
Meet the honorees today at our live event
As you dive into these deeply reported profiles, we invite you to join us in another first. This afternoon at 2 pm ET, we are hosting an online live event to introduce this year’s top women in biopharma R&D, followed by a panel discussion on what it will take to truly achieve gender diversity in the industry. We hope to see you there.
Twenty one years after her ‘genius’ breakthrough, Carolyn Bertozzi keeps pushing the limits of glycobiology
Carolyn Bertozzi wasn’t 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 it’s 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, it’s 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 wasn’t 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 couldn’t have brought that to those patients 15 years earlier,” Bertozzi said. “But that’s 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.
“Carolyn’s 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 she’d 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 aren’t many of us, but you can count us. We’re visible.”
Having seen every shade of gender discrimination and bias (“show me a woman who hasn’t”), 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, she’s noted that part of what got her hooked in those first organic chemistry classes was how molecules have personalities like people. So I couldn’t 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.”
That’s not all: “Oh, and they are glycosylated.” — Amber Tong
Kathy Bowdish flouts a misogynist investor acquaintance with big profits and a bigger career
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 you’re 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 didn’t decide to back her first startup. And he was the only one who didn’t 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 should’ve 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 Sanofi’s 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. It’s a significant departure from her Sanofi perch, but it’s a position she knows and a place she’s 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 that’s what it’s going to take in order to raise the money.’ And I said yes,” she said. “I was pretty naive — maybe the naiveté 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 can’t 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 didn’t — 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.
“She’s able to move the needle from a pretty established sort of approach to an innovative one,” Zerhouni said. “She’s 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. It’s a smaller company than she had led since she was just out of grad school, ignoring the pretensions of a sexist investor, and she couldn’t be happier.
“It’s actually a lot of fun,” she said. — Jason Mast
Once an aspiring professor, Diana Brainard is instead leading Gilead’s Covid-19 charge
Diana Brainard was studying abroad in France when she realized something just didn’t 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 I’m 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 doesn’t 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 Mann’s The Magic Mountain, though she hasn’t lost her love of literature. Now, she’s 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 wasn’t a straight line, however. Brainard notes that after Brown, she eventually went to med school expecting to become a physician. But that didn’t 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 hadn’t envisioned in the future that I would be going to industry,” Brainard said. “There weren’t 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 we’d been for a long time, and I didn’t 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. She’s 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 remdesivir’s 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 she’s reluctant to take credit for spearheading the drug’s 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.
“It’s been exhilarating to do [this] for Covid because of the acute, unprecedented medical need, and because scientifically it’s fascinating to have a disease, as an infectious disease expert, to learn about a disease at the same time you’re trying to figure out if a therapy for a disease works,” Brainard said a few weeks before the approval. “It’s a really difficult problem, and one that doesn’t 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, she’s 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, that’s really meaningful to me.” — Max Gelman
Mammoth’s Janice Chen, a Jennifer Doudna acolyte, wants to bring diagnostics to your doorstep
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 CRISPR’s 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 Chen’s 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 Doudna’s lab.
It’s 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 it’s 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.
“It’s been successful because it’s programmable,” Chen said. “There’s a whole world of testing that’s 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, we’re really excited about the potential to address these point-of-need environments that don’t 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 it’s 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 who’s 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. She’s 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 there’s 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 it’s really important to ensure that they have the support systems and mentorship internally to help them grow,” Chen said. “It’s 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
Ann Cheung builds next-gen I/O beneath a Cambridge bar
In a cramped, windowless lab basement beside Cambridge’s 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 they’ve 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. “There’s no challenge that discourages her. She’s kind of fearless.”
Cheung didn’t 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. Schreiber’s 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.”
Jacks was famous for making mouse models to study cancer genetics, paving the way for precision drugs that target tumor proteins, but he had had his eye on immunology for a while. He was just waiting for a grad student willing to take on a field that was still only mainstream-adjacent. Cheung became that student, working alone in a prestigious lab on an idea that the rest of the grad students and postdocs thought would likely fail.
“I remember a lot of conversations and talks I gave where essentially there was a lot of skepticism,” Cheung told me. “Many people thought that immune responses that fought cancer and occasionally even caused spontaneous remissions were just anecdotal things and not something that could be harnessed.”
In time, of course, immuno-oncology would take over the cancer field, and Cheung would move from an outsider to a minor pioneer; half of Jacks’ lab is now focused on immunotherapy. Many members are conducting similar work to Cheung, developing mouse models for immuno-oncology, a notoriously difficult task because the immune system is more difficult to simulate than any individual cancer protein or tumor type.
Cheung had a background in engineering, too, and after MIT, she worked at a nanotech lab at CalTech. She helped develop microfluidic devices that could analyze individual cells and used them to analyze the T cells of cancer patients who received a new cell receptor therapy from Nobel laureate David Baltimore.
From there, she took a job at Cell press — an amazing one, she said, that allowed her to read and think widely across cancer and biology, but one that eventually grew wearisome. She was a critic there, but she wanted to be a builder. She went back to MIT, this time as an administrator for collaborations between the Koch Institute and other centers. She knew early on it’d be a way station to biotech. She was about to accept a different offer when Jacks called, talking about this idea of developing “TriNKets” that can grab tumors and link them with the body’s own natural killer cells.
Cheung became Employee No. 1. The three met in the Cambridge basement. Jacks drew a big blue dot in the center of the whiteboard — the NK cell — and the three charted out all they could imagine, sketching diagrams that underlay a drug now in the clinic, diagrams they would never build, diagrams that still represent some of their biggest dreams.
Haney eschewed VC money, relying instead on family investors and early collaborations. So in year 1, it was just Cheung and her personal Employee No. 1, Gregory Chang, in the basement, trying to kill cancer cells in test tubes and calling back with the results. It was a lot of responsibility and a lot of work for someone in their first biotech job, but Cheung said she never thought of it that way. In fact, she never really thought of it.
“I come from an immigrant family. My parents, they had a Chinese takeout, so in a way they were entrepreneurs,” she said. “And for a takeout or even a Chinese restaurant, you don’t have a lot of people but there are a lot of positions that need to be filled. So this kind of mentality of just stepping in and doing what’s needed, I’ve pretty much carried with me through life. And that’s what startup’s all about.”
The results came, and so did a lab with windows and breathing space. Jacks said Cheung not only proved the early science but also proved shrewd, confident and invaluable at the table with Big Pharmas as they presented and negotiated collaborations.
She now directs a sizeable team as head of biology and she no longer has her head in the freezer on a daily basis. The thrills are bigger, too: not crude proof-of-concepts, but emails from the FDA confirming they can start a trial. She remembers when the first two OKs came, and she drew up a plan for when, hopefully, the big call comes — confirmation that the thing they first drew up beneath a Cambridge bar actually works.
“When that day comes, I’ve decided I’m going to tattoo myself with the dragonfly,” she said. “I’ve said it many times, this is going to happen.” — Jason Mast
Chase for Covid-19 antibodies brings Lynn Connolly back full circle
When Lynn Connolly, inspired by her undergraduate experience working with both basic scientists and clinicians, was interviewing for MD/PhD programs at the turn of 1990, she had two different program directors tell her point-blank: Her aspirational dual-career would not be possible for a woman.
It was long before Connolly would come to Adagio Therapeutics, where she is now working with a team of senior women leaders to develop antibodies against SARS-CoV-2. Although she had never met a woman MD/PhD in person, it had always struck her as a possibility. She was immediately taken aback.
“My response was like, ‘I respectfully disagree.’ And amazingly I got into one of those programs,” she said. “I didn’t go there, clearly.”
She ended up at the University of California, San Francisco, where she began considering a pivot in her research focus from human genetics to infectious diseases. The HIV epidemic was in full force while drugmakers still had little to offer, and she found herself engrossed in medical microbiology and epidemiology classes as well as Laurie Garrett’s book on the coming plague.
Virology was a natural path to go down after working on vaccines for herpes and HIV during short stints at Chiron. But her supervisor’s departure led Connolly to Carol Gross’ lab in the middle of her PhD program, where she would switch her focus to bacteriology — specifically to establish a chain of proteins involved in a transduction pathway for E coli.
“She just conceptualized the problem so clearly that as soon as she said it I said, “You know, of course, it should’ve been this way,’” recalled Gross, whom Connolly credits as a key mentor. They grew so close, in fact, that Connolly said she’s also the one who inspired a then-unusual decision to have a child while in graduate school.
That background served her well when she eventually moved to her first industry job as medical director at the antibiotics shop Achaogen. During the decade-plus in between as Connolly completed her residency, fellowship and later became junior faculty at UCSF, the whole infectious disease field had a “huge technological revolution that has allowed us to study some of these pathogens that have been historically very challenging to study,” she noted. Intransigent bacteria like Mycobacterium tuberculosis can now be easily manipulated; there were now protease inhibitors for HIV patients.
At the same time, she’d learn at Achaogen, the traditions hadn’t changed much for the development of a new antibiotic. Large non-inferiority trials were required even for agents targeting multidrug-resistant gram-negative pathogens, recruiting patient populations that don’t exactly reflect who they’re trying to address.
Connolly says playing a part in changing that standard process is one of her proudest accomplishments, as she came up with proposals for streamlined clinical trials that not just worked with regulators to nail down that new path, but worked in the trenches with physicians to enroll these specific, often very weak, patients. Then there was all the advocacy work with payers to devise new reimbursement models.
“I think as a society, as not just in the US, but on the whole, I think folks have come to think of antibiotics as things that should be readily available, low cost — where in fact these are very precious commodities,” she said. “These drugs are not designed to be blockbusters. They’re really designed to be reserved for the patients who need them most.”
Ultimately it was all too little, too late for Achaogen, which struggled financially despite getting a drug approved. By the time it declared bankruptcy, Connolly had landed a new clinical research role at Vir, the big-money infectious disease startup helmed by George Scangos.
The many facets of infectious disease drug development on display at Vir, from monoclonal antibodies to siRNA to live attenuated vaccines targeting a wide range of pathogens, was a “candy shop” for someone interested in tackling some of those global health challenges.
Just a few months after she was promoted to senior vice president, though, Tillman Gerngross of Adimab called.
Together with Laura Walker, the director of antibody sciences as Adimab, he’d spun out a startup named Adagio dedicated to tackling not just the coronavirus causing this pandemic but the others to come. For Connolly, the move would mean returning to a group of illustrious women whom she had gotten to know from working in the antibacterial space.
There’s René Russo, the former CEO of Arsanis who’s coming in as co-founder and chair; Cubist vet Ellie Hershberger is the chief development officer; and the rest of the C-suite features CSO Walker, chief technology & manufacturing officer Becky Dabora and chief operating & business officer Halley Gilbert.
“Here’s a company where 80% of the C-level leadership is female. You don’t find that often, and you certainly don’t find it in this pandemic,” Gerngross said. “We were not trying at all to make this a predominantly female leadership team, but that’s where we ended up, in a very organic process.”
These are also people who likely share Connolly’s experience of getting called out for questioning deeply around scientific data — even as men around her were asking the same questions.
“That was really the first time where I really understood, aha! This is what everyone is talking about, where certain behavior in the context of a woman is seen as aggressive and negative, whereas male colleagues participating in this behavior is rewarded,” she said. “That double standard became just incredibly clear to me at that point.”
Addressing these double standards head-on is something biopharma companies can do to support women, according to her, in addition to having programs to support childcare.
“It requires open dialogue,” she said. “You have to acknowledge that it’s happening.” — Amber Tong
Six years into her job at the NIH, Kizzmekia Corbett lends an important hand in Covid-19 vaccine development
NIH research fellow Kizzmekia Corbett has been preparing for this moment for six years.
On a Friday in October 2014, Corbett defended her PhD thesis at the University of North Carolina at Chapel Hill, then packed her bags for a road trip. The following Monday, she was off to Maryland, where she was starting a job at the NIH’s Vaccine Research Center studying coronaviruses.
Before the pandemic, Corbett was focused on MERS vaccine development. Her team takes a “prototype pathogen approach,” she explained, in which they pick a prototypic virus from a huge viral family, then design and evaluate vaccines that could be used as a starting point in case of a pandemic.
“There has always been this idea that coronaviruses would have pandemic potential,” she said. “I think at this point, we can say ‘I told you so.’”
When the Covid-19 crisis struck, Corbett sprang into action. A lot of what she does is “organizing small pieces of the bigger thing”: analyzing and interpreting data, planning, designing experiments, speaking and writing.
When scientists first realized that Covid-19 is related to SARS, it was “exciting and scary,” Corbett said.
“Exciting because at that time in January … we weren’t in a pandemic, but it was really exciting to be able to utilize the knowledge that we have for a proof of principle around this entire pandemic preparedness plan. And then it became scary when it got closer to home in the US and then people started to die.”
The last few months have been surreal, she said. And exhausting. Since her team largely focuses on non-clinical development, they’ve had a chance to breathe and get back to other work. Corbett will still be working on coronaviruses, “just whatever the next one is,” she said.
When asked about her greatest accomplishment in the field, the 34-year-old paused. “I don’t think I’ve had it yet,” she said after some thought. “I still haven’t fulfilled my dreams yet.”
One of those dreams, she said, is a vaccine. But she’d also like to be a principal investigator and have her own lab, or maybe tap into entrepreneurship.
If she had to choose, though, she’d choose her PhD, which she earned in microbiology and immunology. “PhDs are a dime a dozen in the boardrooms that I sit in now, but where I’m from they’re not. So I think maybe that is my greatest accomplishment,” she said.
Growing up in Hillsborough, NC, Corbett was always gifted in school. But it was a high school internship through the American Chemical Society’s Project SEED that cemented her love of science. The program provides disadvantaged students with paid laboratory internships for 8 to 10 weeks over the summer. Corbett worked in an organic chemistry lab at UNC when she was just 16, under the mentorship of professor James Morken.
“Kizzy was passionate about science, enthusiastic about learning and really strove for excellence,” Morken said in a statement. “What she did not have were many opportunities to do research, and Project SEED offered that.”
For Corbett, that was the moment “it sort of clicked that it was possible.”
After graduating from Orange High School, she got her bachelor’s in biology from the University of Maryland, Baltimore County, then returned to her home state for her PhD.
To attract women to the field and not lose them in the pipeline, Corbett urges companies to promote diversity and inclusion, and “put your money where your mouth is.”
“Every time someone hears about a diversity and inclusion problem, they form a committee, but then nothing comes from it … A lot of times places focus on diversity so much that they forget the inclusion part. So … if you’re going to hire women, then shouldn’t you have a lactation room?”
There are identity intersections, Corbett said, adding that she identifies more so with the struggle of being Black than the struggle of being a woman. The pandemic has been the longest period of time in the last 6 years that she’s worn her hair straight. Normally, she feels comfortable wearing it in braids, or however she wants at work.
“But now that I am visible outside of that workplace, knowing how that will be accepted everywhere is not necessarily sure,” she said.
Being held to standards — such as looking or speaking a certain way — can be draining. “The way that we tend to think about professionalism and work, that just doesn’t fit into everyone’s cultural perception,” she said.
Then there’s the societal pressure to do “all of the things that women should be doing,” like getting married and having children, she added. “It’s okay to shake up that narrative,” she said.
Her advice to young female scientists? “Find your voice really early and speak very loud.” — Nicole DeFeudis
An I/O pioneer returns from pharma to find the next big breakthrough
If you or someone you know has benefited from the checkpoint inhibitors that have remade cancer treatment over the last decade, there are a few people you might consider thanking: Jim Allison, of course, the Nobel Prize winner. Or maybe Merck, the pharma that developed the most successful inhibitor, which now annually earns them the GDP of a small Eastern European nation. But somewhere on the list, you might also consider a lesser known name, a thoracic oncologist named Leena Gandhi.
Gandhi has done much over the past few years — she’s got a gaudy project up going right now — but to understand the magnitude of her contribution, it’s probably worth going back nearly a decade, to a time when the first checkpoint had been approved but the question of just how big an impact they would have, and for whom, was still unclear. Specifically, to ASCO 2014, and a small conference room inside Chicago’s glassy McCormick Place hotel.
Gandhi, then the young director of Dana-Farber’s thoracic oncology trials, stood up and presented data suggesting that an experimental checkpoint inhibitor known as MK-3475 worked far better in lung cancer patients whose tumors expressed the protein PD-L1 than in those whose didn’t.
It was a deceptively obscure finding. Checkpoint inhibitors were supposed to take the “brakes” off the immune system, unleashing T cells to attack tumors. But early trials produced mixed and wildly varying results: Some patients’ tumors vanished and others didn’t and there was little way of predicting which would do which. That was trouble; without a good predictor for who would benefit, the drug would look mediocre in the aggregate, and doctors wouldn’t prescribe it or would prescribe it less.
Oncologists weren’t convinced PD-L1 was the predictor. For one, it was difficult to measure; the technology used at the time to examine tumors was relatively rudimentary and often missed the protein when it was there. “We thought we’d never be able to use PD-L1,” Gandhi told me.
There were also varying results depending on the cancer; on the same day Gandhi presented her results, UCSF’s Adil Daud presented data showing that in melanoma, many patients responded regardless of whether they expressed PD-L1.
Yale’s Mario Sznol, a melanoma specialist who was moderating the session, discussed both and threw up his hands. “Well I’m not sure,” Gandhi recalled him saying. “It’s not clear cut.”
MK-3475, of course, would become Keytruda. And Gandhi, firm in her belief that PD-L1 could be that predictor, would lead Keynote-024, the landmark study that proved that, for PD-L1 positive lung cancer patients, the checkpoint inhibitor was better than chemotherapy.
That’s when the questions stopped. Now virtually every trial for PD-1 inhibitor contains a biomarker breakdown and most non-small cell lung cancer patients are screened.
“Why throw the baby out with the bathwater?” she said. “It’s an imperfect biomarker. But it works.”
Gandhi was well-positioned to spot PD-L1’s potential. She had studied to be a thoracic oncologist in the early 2000s, a time when the field was beginning to undergo a radical transformation. When Gandhi finished med school, lung cancer specialists were still experts in palliative care; a diagnosis was a death sentence, one that chemo could only delay.
Beginning in 2004, though, with the first EGFR inhibitor, the story changed. Researchers learned to screen for tumor proteins and develop drugs to target them, often extending lives by years.
Gandhi, who as a resident picked the field because she wanted to help patients navigate the turmoil of a terminal diagnosis, spent her first year after fellowship helping run a Phase I trial on crizotinib. The results on patients with ALK+ tumors were so profound the FDA gave the drug accelerated approval on two Phase Is alone.
“I remember having a patient who had such a great response, he was a young man, and he ended up having two children after being diagnosed,” she said. “It was very gratifying to be a part of that.”
That led her to the early immunotherapy trials, a place that gave her not only time with patients but a unique impact on the science. You can’t model the immune system well in animals; the Phase I trials tell you everything.
Over the next decade, Gandhi would help lead dozens of trials, helping define and excavate the limits of PD-1, showing more data on biomarkers, exploring the tumor environment, and posing key questions about combinations with chemotherapy: Would the old and new interventions be synergistic, or could the chemo kill the immune response PD-1s were supposed to boost? (Synergistic, it seems.)
Then in 2018, a call came from Levi Garraway, the Broad Institute researcher recently tapped to run Eli Lilly’s oncology department. It would net the slow-footed pharma one of their biggest hires, and soon after, one of their louder exits.
Gandhi took the job running their immuno-oncology program to work with Garraway, someone she saw as having a proven track record and with whom she could make an impact. But then Garraway left for Roche and Lilly handed their cancer work to the Loxo team, who was known for pushing low-risk targeted drugs that could move quickly through the clinic.
Gandhi left in June. “I went there to do science,” she told Endpoints at the time. “It was not tenable to stay.”
She had also landed a formidable new opportunity. She’s working to build a Phase I translational center at Dana-Farber. The goal is to create a place that can test new I/O ideas, putting them in humans because, as she learned early in her career, you can’t test them in mice. She’ll work with other institutions and pharma, using knowledge she learned from two years in the industry.
Immuno-oncology has become foundational in the last decade, in a way chemo once was, she said. That success depended on figuring out on which patients the drugs work best; the next successes just might depend on the same thing.
“We haven’t seen a lot of change the field, in terms of immunotherapeutics, since PD-1 inhibitors,” she said. “And I think part of that is the model of drug development that’s being used for a lot of that is the old model of drug development.” — Jason Mast
From pharma enclaves to China to biotech startup, Pearl Huang follows her curiosity into new adventures
Curiosity keeps Pearl Huang going.
It was what drove her to study molecular genetics almost 35 years ago; make the unfashionable jump into pharma right after finishing her PhD at Princeton (learning firsthand as a mother of two what it took to get to tenure and seeing few successful women on that tract there, to be sure, was also a big push factor); move from the frontlines of cancer drug discovery deeper into positions where she was more involved in strategy and decision making, through a series of fruitful jobs at Merck, DuPont, GlaxoSmithKline and then Roche; and take up an invitation from Flagship to now lead Cygnal, a startup focused on exoneural biology.
Growing up in the Midwest, there was also a specific place Huang yearned to know more about: China, her parents’ homeland.
They met in the US, and until Richard Nixon and Deng Xiaoping opened up relations around 1977, they had never visited each other’s families in China. “There were letters,” she said. “I remember the letters, but they were few and far between.”
Huang visited the country for the first time in 1999, together with her five siblings and all their families — a three-week tour that she considered transformative.
She knew she would go back. The opportunity came in the early 2000s, when GSK wanted to explore expanding clinical trials to China for the pipeline she helped build. Together with Peter Ho, a Chinese American colleague on the clinical pharmacology team, they made trips to various national hospitals in different provinces.
“And we were both overwhelmed by the number of people who needed access to cancer medicines,” she said. “You go to a place like Guangzhou, and you go to the cancer hospital, you can see the patients lining up every morning to get in line to see the doctors. And so the need was so powerful, but also we were trying to develop our molecules that had already been proven to work in the US and in Europe, and it would be years before — at that time — patients in China would have access.”
As they talked about ways to bring medicines to Chinese patients faster, John Oyler — whom they knew as the chief of a CRO that did a lot of business with Big Pharma — called with the idea of what would become BeiGene. At that time, it was a pioneering idea: a biotech company in China, for China, by China.
The year was 2010, and the stars were aligned. Overseas scientists were increasingly returning, the contract business was booming and China offered the most capital-efficient way to do drug discovery — pick targets, make molecules — for someone who knows what they’re doing.
With Oyler and another co-founder, Xiaodong Wang, traveling back and forth, Huang and Ho opened the first office at the Ben Franklin Center in Philadelphia, recruiting and drafting business plans in a tiny room for two months before getting on a plane to Beijing. There, she filed the first two patents for BeiGene, one for a BRAF inhibitor and the other for a PARP inhibitor, and negotiated with pharma on licensing deals over 15 months. After going through several places she ended up subletting from the Washington Post an apartment in an area by the Second Ring, where diplomats and foreign service officers lived, riding the subway everywhere to explore the Chinese capital.
“I always thought that that reflected a very adventurous spirit in Pearl to do that” instead of staying at the hotel arranged for expats like them, Ho recalled. “I always thought that that was something that — I don’t think many people would have chosen to do. I certainly didn’t.”
But it was clear from the beginning that a company whose central platform is geography wasn’t going to be a long-term fit for Huang, who made the hard decision to go back to GSK once BeiGene’s crew grew to a decent 110.
Building teams that could stand on their own feet and break through barriers, after all, amount to Huang’s greatest accomplishments in her own mind.
“I would say for all the teams that I’ve worked on for drug discovery, the ones that succeeded you hear about, the ones that got closed and didn’t make it you don’t hear about, but those teams worked just as hard and made great decisions because they had the expertise and the ability to do that,” she said.
Her first time at GSK, for instance, she led a collaboration with Cytokinetics around kinesin spindle protein inhibitors. It was some of the best science she’d ever participated in. Yet, the “beautiful therapeutic index” in mice didn’t translate into the patient population they tested the drug in. In the end, they killed it.
She credits the scientists on her team who “defined the problem in great precision” and generated the data to answer it. To this day, she’d take the Cygnal team out to celebrate a decision to drop a program.
So how do you encourage a culture like that on your team? Huang draws lessons from her first stint in the industry, as a senior research biochemist at Merck Research Labs. Between 1990 and 1992, cancer research was a growing area of science and she was brought in alongside over half a dozen new young PhDs, all angling each other to figure out the right target, experiment and molecule.
“It was a very lively, lively place, but I was pretty quiet,” she said. “And I remember this person who became my mentor, sitting in a room where everybody was arguing about this, that and the other, and this person said, ‘I want to know what Pearl thinks.’”
That person was Allen Oliff, who now heads GSK’s Center of Excellence for Drug Discovery. The seasoned drug hunter calls Huang one of the best scientists he’s worked with in academia, government or pharma industry positions, impressed by the creative solutions she brings to preclinical evaluation of drugs.
“It was clear that she was a very bright and careful thinker, understood the biology and the molecular genetics of the programs she was at,” he said, noting that he remembered the exact meeting because he recalled trying to pull ideas out of Huang multiple times. “Many people, not just me, many of the other people in the lab go to Pearl and ask her for advice.”
It is a practice that she now employs as a leader. Engaging people like herself — a double minority as an Asian woman — and getting rid of rules on how someone should behave, she believes, will be the key to combating all shades of gender bias.
“The closer you get to parity, the closer you get to these problems going away,” she said. — Amber Tong
Always looking for the problems, Kathrin Jansen found a historic Covid-19 solution
Before Kathrin Jansen celebrated the historical moment when her team at Pfizer, together with partners at BioNTech, delivered the good news that their Covid-19 vaccine may indeed help put an end to the pandemic, she remembered the sirens.
“I’m located in New York, being in the hot zone so to speak, when the virus cut loose in the United States,” she recalled around a month before the groundbreaking readout. “We’re close to several hospitals where we live. Hearing the sirens all day, all night, and you know exactly what that meant, right? It was people, you know, fighting for their lives, getting into the hospital to be treated for Covid-19. Seeing the refrigeration trucks, where individuals that succumbed to Covid-19 pile up, in the streets in front of the hospitals.”
It all put the seasoned scientist right in the midst of a completely different dimension than what she’s weathered through close to three decades in the industry. All bets are off; how do you approach it differently than normal circumstances, yet still maintain the standards required to develop a safe and effective inoculation?
How to do things right under normal circumstances, to be sure, is something Jansen knows well. With three marketed vaccines under her belt — Gardasil for prevention of cancers and other diseases caused by HPV; Trumenba for meningitis B; and the pneumococcal conjugate vaccine Prevnar 13 — and 11 years of experience as Pfizer’s head of vaccine R&D, she was overseeing a pipeline of eight experimental immunizations against both bacterial and viral pathogens before switching all her attention to the mysterious coronavirus that devastated first China, then Italy, then eventually the US.
But her career almost didn’t turn out that way.
Jansen arrived at her first vaccine job, in Merck’s vaccine group, at a time the pharma giant was thinking about getting out of vaccines. The unit was looking to reinvent itself, and Jansen was hired to work on a non-vaccine related topic.
After completing a postdoc at Cornell on a Humboldt Fellowship focused on yeast genetics, she had spent several years expressing in a recombinant system a receptor believed to be a drug target to prevent allergies and asthma with colleagues at Glaxo Institute for Molecular Biology in Geneva. The program didn’t end up leading to a drug — a lesson she had by then learned about the industry she’d always dreamed of joining. But it equipped her for the new task.
Soon enough, though, Jansen and her Merck colleagues realized that the data they’d been handed were what she called “artifacts.” They couldn’t reproduce a single one of the results.
At around the same time, Merck was bringing in a new technology discovered at the University of Queensland out in Australia, suggesting that the capsid proteins derived from the outer coat of the human papillomavirus would induce antibodies to the virus.
“I told my boss, ‘This is not working, this makes no sense,’” Jansen said and, because she had an idea of how to make a vaccine using the infrastructure Merck already had, added: “I want to work on the human papillomavirus.”
It was an instrumental vaccine for humanity as well as for her who, as a first-time program lead, experienced everything and learned what it means to create a construct, develop processes, interact with regulators, and think from a commercial standpoint.
Two habits formed that would stick even after she left Merck, through short stints at the ill-fated biotech VaxGen and then pre-merger Wyeth: Never make assumptions, and focus on where problems could lurk.
“I always say, I’m always looking for the problems,” she said. “The solutions will come — I’m sure about this. I’m worried about the problems, and where do we run into problems.”
Some of those problems they were able to avoid in developing the BNT162 program, because Jansen’s team was told by Pfizer CEO Albert Bourla, whom she’d meet twice a week, that they could get whatever they needed. Others were addressed quickly once they were raised. There were no competing programs, no need to scramble for resources, nothing standing in the way.
“The only constraint is time,” she said, “and time you don’t have. So you become very creative.”
They made no assumptions preclinically, taking not one but four slightly different mRNA constructs into the clinic — which turned out to be a good decision because “we would’ve been so wrong” — collapsing a sequential workflow into a parallel one, and making decisions on the fly. The last data from the Phase II study came in on July 24; the team had a meeting the next day to debate on the two frontrunners that had the best data; and they locked in the b2 candidate. The Phase III portion of the study started on July 27.
Jansen, who was born in East Germany and educated in West Germany before settling in the US with her American husband, credits company culture as a big driver in all this — both at Pfizer and BioNTech.
As a woman in biopharma, supportive environments matter. She likes to tell the story from her PhD days when her microbiology class visited a company in Germany. The man showing them around saw that half of the group were women and asked: “So you want your PhD, why do you bother? You know you’re not going to work anyway.”
Despite that jaw-dropping experience and the dearth of senior women leaders in pharma at the time, she noted that the US felt different from the get-go. And even if you can’t change a discriminatory environment, Jansen is of the belief that you can change your own.
“I think one always has to make decisions of where — where do you want to be,” she said.
Right now, right here at the crossways of history is exactly where she wants to be. — Amber Tong
The co-inventor of modified mRNA, Katalin Karikó is finally getting her moment
Katalin Karikó remembers sitting in her father’s butcher shop as a little girl, unafraid of the blood and entrails.
She’d sit in the small store in Hungary, watching animal after animal get chopped up and sold to customers. Her father would have to kill the animals as well, and she’d sit and watch while her mother and sister couldn’t bear to even listen to the noises. Just sitting, just curious about the inner workings of living beings.
It’s that innate curiosity that’s driven Karikó her scientific entire career, a career that’s led to helping solve the riddle of one of the technologies at the forefront of the Covid-19 pandemic fight: modified messenger RNA.
“I wrote a little preview called ‘Out of the Shadow, Into the Spotlight,’ this was about the messenger RNA because it was always in the shadow and it’s finally in the spotlight,” Karikó said. “Not many scientists can say that I was thinking of something, proved it, published it, had a patent on it, everything and then it ended up finally in the highly-seen product.”
The road to the discovery that’s come to define her research was not always smooth. Karikó first came to the United States in 1985, taking a job at the University of Pennsylvania. She had been focusing on mRNA technology even then, but ran into headwinds as early synthetic RNA proved highly susceptible to violent immune responses.
Despite submitting her first mRNA therapy application in 1989, she couldn’t get any grant funding to develop it. After a few years, Karikó’s bosses at UPenn demoted her.
But Karikó kept plugging away at the research, convinced of the technology’s potential. Eventually, she teamed up with one of her colleagues at Penn, Drew Weissman, and came up with a solution to the immune response problem — by modifying one of the nucleosides that make up the RNA and using that version of the therapy instead, Karikó and Weissman created a way to evade the body’s natural defenses.
In 2006, she and Weissman used the basis of that discovery to found a company called RNARx, where Karikó served as CEO. By the time their patent for the technology was accepted in 2012, however, Penn sublicensed it out to another company. A few months later, Moderna — which at the time was still a nascent Flagship biotech — signed a $240 million deal with AstraZeneca to develop a VEGF mRNA.
Those blows essentially forced Karikó’s outfit to close up shop, and Kariko herself decided she’d had enough of academia. She took a role at BioNTech soon after as senior vice president.
Now that mRNA vaccines are two of the leading candidates in the race for a Covid-19 cure at BioNTech/Pfizer and Moderna, whose technology is based on her old patent, Karikó is happy that her research is a part of the answer. But she also feels validated after so many professional setbacks.
“I wish to tell some of those people who put me down and ridiculed me and whatnot to see that, ‘You see?’” Karikó said. “But that’s OK. I am happy that the two leading mRNA vaccines, Moderna and BioNTech with Pfizer products, both of them are including something that I contributed. Even other people who will not know because Moderna usually says that they discovered everything, but they did pay for that patent and sublicensed it from Penn.”
The technology that Karikó co-invented could end up saving thousands of lives and has significant ramifications in areas outside Covid-19. Karikó said she originally began looking into the research aiming to develop an HIV vaccine, but mRNA-based therapies have been popping up in other rare diseases and certain cancers.
Karikó predicts that in the near future, it’s very likely mRNA will successfully be applied to other infectious diseases. It’s a bit farther off in cancer, as the science needs to be improved and understood better, she says.
One possible mRNA-based treatment that could come far in the future is a therapeutic spray or cream, similar to Neosporin, that people can keep in their freezers at home and apply to open wounds. Individuals would use the spray as needed, and it would accelerate collagen repair and lessen their pain.
“Many times before, the mRNA has been rejected because it is temporary, because it degrades. But it is a very good thing that it degrades,” Karikó said. “It can be applied like medicine. If you need more, then you take more. But it degrades, and it will not have a continuous effect.”
Regardless of what comes next for mRNA, it’s already had a huge impact on the biotech and pharmaceutical world, particularly in 2020. Notably, Moderna’s own co-founder Derrick Rossi has called for Karikó and Weissman to win the Nobel Prize in Chemistry for their mRNA research.
And for the next generation of women in biotech, Karikó wants them to know that you don’t have to choose between a career and your family. Karikó remembers several instances where she’d be asked who her boss was, as many simply assumed that the “woman with the accent” had to report to somebody else. But the times are changing.
“In Germany, I gave several lectures for students, and some of them approached me that they were told that if they want to have a career then forget about family. I also say, ‘You don’t have to do that,’” Karikó said. “My daughter … she always said that our work ethic was helping her, so my message was for the younger generation that they don’t have to give up family life, especially when things are hard you need support, moral support from your family, after another grant rejection.” — Max Gelman
Inspired by her grandfather, Sara Kenkare-Mitra finds her higher calling in medicine
Sara Kenkare-Mitra grew up loving the stories her grandfather would tell her of his time as a physician in India.
Working in a very rural part of the country, he would often end up as the only physician patients could turn to in a crisis. Kenkare-Mitra recalled a time where he spoke of being awakened in the middle of the night to help people on a ship who had nowhere else to turn, given that he was the only doctor around for miles.
That passion for medicine was ultimately passed down to Kenkare-Mitra, now a 22-year veteran at Genentech where she serves as senior vice president of development sciences.
“He became the physician of the common people,” Kenkare-Mitra told Endpoints News. “The stories of him impacting people’s lives through the skillsets he had gotten was just amazing and thrilling to me. We used to talk about medicines, I grew a deep interest in medicine, sort of asking just what medicines you take and when, even as a young girl, I remember that that was something I had a lot of questions around.”
Being exposed to her grandfather’s tales set Kenkare-Mitra on the path where she finds herself today. She always knew she wanted a career in a science-related field, but veered toward drug R&D rather than work directly with patients in order to get involved in the research. When she was first looking to go to grad school, pharmaceuticals was still a nascent field in India with most programs focusing on pharma tech and manufacturing.
Kenkare-Mitra soon found herself at the University of Texas at Austin, but didn’t feel like that was a great match. Coming to the US was no small task either in the era before cell phones and the internet, Kenkare-Mitra says, so adjusting on the fly proved to be another challenge. Eventually, she settled into a PhD program at UCSF where Leslie Benet, the “Father of Pharmacokinetics,” was one of her professors.
Realizing that most of that work was equivalent to preclinical development and that she likely wouldn’t see the effect on patients for years, Kenkare-Mitra still felt something was missing. Until the HER2-positive breast cancer therapy Herceptin made headlines in the late 1990s.
“[Herceptin] told a story that, for me, as a pharmaceutical scientist, someone that’s always been interested in medicine, I thought, ‘Wow, that’s innovative,’” Kenkare-Mitra said. “We were all used to drugs that aren’t really targeted, they aren’t really personalized, but now here’s a drug that’s to be given to women that have a specific type of tumor that shows the HER2 positivity, and it actually works. To me, it was a big leap in medicine.”
It was around that time when someone from Genentech reached out to her with a job offer. Kenkare-Mitra accepted and started as a scientist, but worked in several different roles, including leadership positions. She’s worked in the same organization within Genentech for most of her time there, and said her teams have brought 15 drugs to market over her two-plus decades.
The theme that’s strung her career together has been translation, or ensuring that during the R&D process, the experimental drugs will continue to produce meaningful results as they advance through the clinic. Kenkare-Mitra says she’s always been able to recruit the right talent from many disciplines for her projects, crediting her postdoc experience where she was one of only a few PhDs in a program normally reserved for clinicians.
Kenkare-Mitra said one of the biggest challenges in her job is when, after realizing that a certain program may not translate as well as originally hoped, she has to make a decision on whether or not to punt.
“That translation is not trivial. It’s really understanding the science and data enough to say, ‘Ah, I think this has got legs and should move forward,’” she said. “And then also learning from the forward and bringing it back, reverse-translating that. Saying, ‘These are the lessons we’ve learned, and this is how it applies to the world.’
“The best thing that you can do is if a particular medicine is not going to move forward, you need to make that decision and stop it, without wasting more money and research, and then finding out it doesn’t work,” she added.
Now, though, Kenkare-Mitra says she’s found her higher purpose in life helping patients, though in a different way than her grandfather. It took her a while to get to this stage, as earlier in her career she felt somewhat overwhelmed and wasn’t thinking too much about the future.
And if there’s one piece of advice she could give to up-and-coming women in the industry, it’s to make sure one keeps the big picture in mind.
“Science, as well as work in this industry, really requires long-term thinking and requires a level of resilience,” Kenkare-Mitra said. “You have to be in it for the long run, but the rewards in terms of satisfaction, you’ll get in life, are so very high. But you have to realize that you won’t have rewards tomorrow.” — Max Gelman
After climbing the ranks at Genentech, Lynne Krummen digs into immunology at Vir
Lynne Krummen didn’t know a whole lot about drug development when she started at Genentech in 1990 — but she remembers the moment she was hooked.
It was in a sidebar meeting, after a guest scientist spoke about work related to the cloning of the LH receptor. Ideas were flying around the room: “We could start PK studies,” some coworkers said, while others brainstormed possible indications.
“Wow, this is where this happens,” Krummen thought to herself. “I just got exposed to this whole world of: How do you take an idea in research and turn it into a medicine that helps people?”
When Krummen graduated with her PhD in endocrinology from the University of Cincinnati College of Medicine in 1987, the biotech field was still warming up. But she knew of one company that was a “maverick,” and that was Genentech. They were working on a growth hormone at the time, which is an endocrine molecule, and Krummen was set on joining them.
“I sort of tried every avenue I could to get a job at that company,” she said.
She landed a postdoc spot in 1990, then transitioned into scientist and management roles, working her way up to VP of technical development before leaving for her current position: senior VP of regulatory and development program leadership and management at Vir Biotechnology.
Krummen’s career with Genentech spanned 27 years. She was there for the Roche merger, and to work on blockbuster Avastin, which was first approved in 2004 for colon cancer, and has since snagged OKs in advanced lung, kidney and brain cancers. While developing the drug, Krummen and her coworkers lost several family members to cancer.
“It was just very important that we could be doing work that was useful in something that was … affecting us so personally,” she said.
She also got the chance to learn from mentors, some of whom “probably never knew they were,” like oncology expert Sue Desmond-Hellmann. The former Bill & Melinda Gates Foundation CEO worked at Genentech for 14 years, ending as president of product development.
“I always felt smarter after having been in a meeting that she was chairing,” Krummen said of Desmond-Hellmann. “She made you feel like you were telling her something that was important when in fact she knew the answer all along.”
Krummen was fortunate. As she climbed the ladder at Genentech, she says there were always women in leadership roles at senior levels, though they were in the minority. And she recognizes that is a unique experience.
“Even though I think there have been purposeful efforts to try to balance recruiting pools and other kinds of things … It still comes down to people making choices at the end of the day. And you can interview a lot of women, but the choice to hire that woman is one that I think we have to hold leadership accountable for,” she said.
Krummen picked up various titles at Genentech: senior director of process development, VP and global head of biologics regulatory CMC, and VP of technical development. But one of the greatest challenges was figuring out how to add mom to the list, she says.
Genentech was one of the few companies at the time with its own daycare just a couple blocks from the office, which Krummen said was helpful before her two kids, now 23 and 26 years old, were school age. Because the daycare was so close, she could swing by for lunch, or the Halloween parade. Once her kids started school, the routine got more complicated. Krummen and her husband split up the after-school games and ballet, and they leaned on other parents and a nanny when possible.
“There’s only so much you can do,” she said, adding that there’s no shame in outsourcing. “Figure out where you need the help and don’t be afraid to ask for the help so that you can focus on the things that are most important.”
About three years ago, Krummen jumped to Vir. There’s a much deeper understanding of the immune system now than there was when she studied immunology in school, and she wanted to dig in.
“The tools now are just astounding and I think they’re going to continue to become more and more sophisticated over the next several years, and there will be new types of modalities that we don’t even have available to us today,” she said.
Vir currently has several candidates in the clinic, including two Phase II Alnylam-partnered drugs for hepatitis B, and a GSK-partnered early Covid-19 treatment in Phase III.
“I would like Vir to realize its mission statement of … a world without infectious disease,” Krummen said. “It’s so important … we couldn’t have lived in a time when that is not clearer how important the mission of the company is.” — Nicole DeFeudis
Regeneron’s master planner finds power in listening and being the most influential voice in the room
One of the biggest challenges Leah Lipsich has faced in her career dates back to her lengthy tenure at Boehringer Ingelheim. She had just become the director of pharmaceutics, a department tasked with formulating drugs. But the heads of R&D and commercial came to her with a completely different problem: The German pharma had just gotten an asthma inhaler approved by the FDA, yet they were having trouble manufacturing it to specifications required for commercial launch.
The men, Stephen Carter and Hans Leuchs, wanted Lipsich to handle it. Fast.
“This was so far out of my area of expertise, I knew nothing about it,” she said. “I pretty much said to them, ‘Are you kidding me? I know nothing about this. How can I possibly do this?’ And they said, ‘You’ll surround yourself with the people who do know things technically and you’ll use your leadership skills to solve the problem.’”
The daunting task, in a way, would serve as a test run for many of the projects Lipsich has since spearheaded. It was a turning point where she realized that bringing the best out of subject matter experts, rather than knowing everything, is the key to getting the job done.
That same lesson was true through stints at Purdue, UCB and Elan — and especially so now. As the VP of strategic program direction responsible for infectious diseases, she is managing the same team of scientists, ops and manufacturing experts that helped develop an effective Ebola drug in pursuit of an antibody cocktail that works against Covid-19.
Before she embarked on a career in drug development, Lipsich said, a biology teacher in high school had sparked her interest in science, so much so that she had actually wanted to teach. But her father — an academic himself — encouraged her to first get a degree.
A love of laboratory science soon turned into a passion for clinical science. Her first job as a freshly minted PhD, at a Seattle-based biotech named Genetic Systems, technically lasted one day before Bristol Myers Squibb acquired it. So Lipsich was immediately plugged into Big Pharma, working on none other than monoclonal antibodies for infectious diseases. For bacteria, no less.
Having studied antibodies on and off through the years, it was easy to appreciate Regeneron’s investment into technologies that could reliably identify and manufacture fully human antibodies, eliminating all the roadblocks that marked the beginning of her career.
Lipsich took pride in the company’s decision to apply that platform on Ebola, which paid off last year when the three-drug cocktail was shown to work in a trial across West Africa. Yet she and the team had just a few months to savor and celebrate the moment before she found herself talking to Christos Kyratsous, Regeneron’s chief scientist in infectious diseases, frightened by reports about nursing homes in Seattle being overrun with the mysterious new virus.
They were able to best their own record and go a little bit faster this time around — an improvement Lipsich chalks up to better knowledge of the technology and an ability to interpret the data faster. Collaborations with researchers as physically far as Singapore also helped, as did the government stepping in to remove obstacles.
Kyratsous might add a third factor: Lipsich’s ability to pull all the strings together, prioritize them properly for presentation to senior management, government officials or regulators, while highlighting the individual components as needed.
“It’s not just that she’s looking at a task on hand, but she’s — it’s the task on hand that is being done by a person,” he told Endpoints News just after responding to an email from Lipsich. “So she understands how this person operates, she understands the specific. Everybody’s different, everybody’s working different times of day, they have completely different schedules, they have different styles of working, and she is able basically to personalize the program, basically, for each individual team.”
Having enjoyed lifelong relationships with mentors, she finds it equally satisfying to advise and coach young people working under her, many of whom are women.
“I still think women struggle being heard,” she said. “We’re not comfortable being the loudest voice in the room. And I don’t know that that will ever change. But I do think that there are ways to be the most powerful voice, or the most influential voice, in the room.”
Women, in her observation, generally feel uncomfortable talking about their salary. She would know: Early in her career at Bristol Myers, she hadn’t realized that she wasn’t compensated as well as her male counterparts until her boss, a man named Philip Sauer, pointed it out to her and took steps to change it. The sense of recognition eventually emboldened her to ask for a promotion in a later role, even though she has still never negotiated her salary in any of her roles — something she now presses her mentees to always do.
As the Covid-19 schedule pushes her into 10, 12 or even 16-hour days, the self-described avid vegetable gardener makes sure to carve out 10 to 15 minutes a day just for herself, going out to see what she can harvest in her garden out on Shelter Island, NY — and just breathe.
“I’m sure that women take care of others before they take care of themselves,” she said. “But it’s really important, even if it’s just 5 minutes, take 5 minutes, walk around the block, breathe. And take care of yourself.” — Amber Tong
Stacey Ma follows great-grandfather’s footsteps to a top seat at startup Sana
Stacey Ma’s entire career traces back to Shanghai in the 1980s, her great-grandfather and a wooden China cabinet.
While living with her great-grandparents, 10-year-old Ma was captivated by Yi-Fan Jiang’s cabinet of medicines. The former medical school dean was around 90 years old at the time and in a wheelchair — but that didn’t stop him from tinkering with his ointments and other concoctions.
Decades earlier, around 1915, Jiang was on his way to study medicine in Germany when he got sidetracked in the US. He stayed for 17 years, studying at the University of Minnesota and the University of Chicago before returning to China to teach. He was the dean of two medical schools. He spoke nine languages. And even in his 90s, he was curious, his head often buried in a newspaper or magazine.
He taught Ma to dream big. And she dreamed of being like him.
So in 1987, she, too, packed her bags for the University of Minnesota. “The original intent was to actually practice medicine, but somehow I ended up being an engineer … making medicine,” Ma said.
The trajectory change was practical: Going to medical school as an international student was expensive, and Minnesota had a good chemical engineering program.
Ma graduated in 1991, then continued on to Yale and eventually Genentech, where she stayed for 23 years. She arrived just as the company was preparing its filing for Rituxan, the monoclonal antibody first approved in 1997 for Hodgkin’s lymphoma. Last year, the drug raked in $6.75 billion in net sales.
“I kind of rode the wave of monoclonal antibodies,” Ma said.
She served various roles in tech development, quality and supply chain, and was named global head of pharmaceutical technical innovation and manufacturing sciences and technology in 2018.
“It’s been a career that I definitely did not imagine, and I have been really enjoying it,” she said.
Toward the end of her time at Genentech, Ma was intrigued by the prospects of cell and gene therapy. “It kind of … reminded me of the early days of monoclonal antibodies,” she said.
That curiosity brought her to Sana Biotechnology, a biotech founded in 2018 on a mission to manipulate or control genes to replace or repair any cell in the body. She was tapped last year as executive VP and head of technical operations, and has since watched the startup expand to more than 250 employees. By June, a syndicate had raised more than $700 million to support the fledgling biotech that CEO Steve Harr said is still several years away from the clinic.
“One of the key reasons for me joining Sana is because I truly believe cell and gene therapy is the next kind of excitement in terms of really being able to bring some more innovative solutions to these patients,” Ma said.
One thing Ma has noticed on her climb to the top? The higher she got, the fewer women there were.
It’s like a pyramid, she said. At the entry level, right out of school, Ma saw a strong base of women entering the field. But as she moved up, she witnessed a “very clear, oh-so-obvious shift”: Most of her managers were men. Few women in the industry were making it to the executive level.
“I see that sort of glass ceiling for females … we still have a long ways to go,” Ma said.
The VP encourages women to pull each other up. “How do we also network more and … create that strong support system for each other?” she asked. “We don’t have to be like men and lead like men … leading the way we are can be just as effective.”
When faced with a challenge, Ma said she thinks back to that old, wooden China cabinet in her great-grandfather’s house. “It’s the yin and yang right?” She reminds herself of another one of Jiang’s lessons: With every challenge, there is opportunity.
“I do see the industry has evolved,” Ma said. “The fact that I’m here talking to you I think is one (example). So I think there’s definitely hope that we will get there.” — Nicole DeFeudis
‘Never had a grand plan’: A winding career path led Jennifer Petter to launch her own company
Jennifer Petter didn’t realize it at the time, but not getting tenure was actually a good thing — a great thing, even.
It spurred her jump from academics to drug making, sending her on a decades-long path that led to the launch of her own company, Arrakis Therapeutics.
As with any setback, “you have to spend at least one weekend just watching TV and eating ice cream,” she said. “Whenever you’ve dried your tears, you can kind of stand up and look around (and say), ‘Ok, well, what are we going to do now?’”
With her days teaching chemistry at the University of Pittsburgh behind her, Petter landed a lab job at Sandoz in 1991. Transitioning from academics to lab work was easy, she said. “You put some music on and you get to work.” Today, her playlist ranges from Monteverdi’s Vespers to Paul Simon.
Petter stayed at Sandoz for 5 years, leaving just as it was becoming Novartis. Then she spent 9 years at Biogen, where she was director of small molecule drug discovery until losing her spot in a 650-person layoff in 2006. After that, she served as VP of research, drug discovery and chemistry at Mersana, Avila and Celgene, respectively.
When asked if launching a company was always part of her plan, Petter chuckled.
“I never had a grand plan for my life, or even my career,” she said. “I’ve just completely thrown myself into the things that I’ve done and pursued them until I had to stop. And then I threw myself into something new.”
Arrakis — named after the desert planet from the novel Dune — is on a mission to develop small molecules that target disease-causing RNA. It emerged back in 2017 with a $38 million Series A round, and recently pulled in $190 million upfront in a Roche deal.
Petter, now CSO, said:
When I first heard about RNA being addressed by small molecules, I was immediately galvanized — I want to do that. And it wasn’t because I knew what the answer was, but because I loved the problem.
In 2018, over sushi and munchies at a company happy hour, Petter came out to her coworkers as transgender. Arrakis CEO Michael Gilman applauded her bravery in a blog post, and the biotech got right to work on a document outlining the obligations of employees, leadership and the company as a whole.
While nearly everything in the document was already guaranteed by law, Petter saw value in the simple act of drawing it up.
“Sometimes the fact that something is already mandated by law, at least here in Massachusetts, doesn’t mean there isn’t some value in affirming it,” she said. “I think in some cases it’s just a matter of going, you know, not even that extra mile — the extra couple hundred feet just to make sure that people understand … what your views are in this matter.”
Petter doesn’t doubt that coming out earlier in her career would have made the journey more difficult. Many legal protections weren’t in place years ago, even in Massachusetts. And “there’s no question” that making progress in the biopharma field is more challenging as a woman, she said.
“Just from a purely statistical perspective, it is undeniable that women are underrepresented in senior leadership positions across our industry and others,” Petter said.
The timing of her decision to come out had to do with “internal drivers,” and not the career challenges she would have faced. Nevertheless, it’s on companies to promote diversity and inclusion, she said.
“Diversity is about getting people in the door,” she said. “Inclusion is about actually getting them involved and … moving along in their careers while they’re in your company or in your institution.”
Getting women through the door can be challenging when there are simply more men waiting on the stoop. For top positions, there are often far fewer women in the running, Petter said.
It’s our responsibility to use networking as a way to bring people along, and make them more ready for these opportunities. And to go out and cultivate scientists that you know are not ready for the job you have now, but might be good for a job like that in five years.
As for her own future, Petter said she wants to see Arrakis bloom. “If there’s an opportunity to start another company somewhere in there, that might be fun too,” she added. — Nicole DeFeudis
Genentech taps an ambitious pioneer to guide them through biology’s future
To understand Genentech’s new head of research, begin on a cold, Tel Aviv winter, when Aviv Regev is not yet 30, not yet a world-famous researcher, just a promising graduate student whose friend is on the verge of quitting.
Dana Pe’er studied computer science at Hebrew University in Jerusalem. The two had struck up a friendship at a conference, each of them interested in similar questions about genetics and computational biology. But in the months since, Pe’er’s data had come in and provided, rather than an answer, a bewildering mess that the computer scientist, new to biology, couldn’t make heads or tails of. She called Regev.
“I said my data failed, my project failed, I’m a failure and I’m going to quit,” Pe’er recalled. “And she said, let me look at the data.”
Regev would make her name as a computationalist, but her grasp of biology was almost philosophical — the kind of intuitive thinking that allows quantum physicists to discern deep, abstract principles of reality by looking at particles breaking in a collider. She looked over the results and then sat down with Pe’er at a conference: “What do you mean it failed?”
Pe’er didn’t get the answer she was looking for, but, Regev told her, she had managed to recapitulate much of the genetic circuitry for cell metabolism. The two would co-write a study for Oxford’s Bioinformatics, one of the first papers either of them ever published.
“She gets excited, it’s very infectious — her tone,” Pe’er, who now runs a computational biology lab at Memorial Sloan Kettering, said. “The pace of her words just quickened and it’s amazing.”
Pe’er said Regev hasn’t changed much over the two decades since, a remarkable thing given how far those years have taken her: through a PhD at Tel Aviv University, a professorship at MIT and the Broad Institute, one of the most audacious biology projects of the last decade and, now, one of the most-coveted and watched perches in biopharma.
It was a notable selection, reflective of how much the industry has moved over Regev’s career (driven, in no small part, by Regev). Michael Varney, her predecessor, was a traditional organic chemist who had come up through Agouron and Pfizer and started at Genentech as a small molecule discoverer. Regev’s hiring reflected a bet on where the best computational tools and minds are already pulling biotech and where Genentech will have to move to stay atop the industry they birthed.
Arguably more than that, though, it was a bet on the person. Over Zoom, Regev is effervescent yet sharp, laying out the future of AI in biology while directing her very patient daughter on where to find colored pencils and laughing about the struggles of coming onto a job that’s still fully remote. Colleagues and former mentors describe a figure they’ve rarely encountered: a computer scientist who thinks about and is fascinated first and foremost by biology, an academic supremely confident of her own convictions and yet clear-headed about what she can do — and also what you can do, which often turns out to be a lot, with a little help. She is, they say, curious and fiercely kind.
“I had many students — believe me I had some very brilliant people, no less good in terms of intellect than she is,” Eva Jablonka, her thesis advisor and a well-known geneticist at Tel Aviv University, told me. “But I never had somebody like her.”
Computational biology is big these days — big enough that some forms, such as artificial intelligence, get knocked as overhyped. But that wasn’t yet the case when Regev started out. She hadn’t set out to be a biologist. After her military service, she was accepted into Tel Aviv University’s Interdisciplinary Program for Outstanding Students, a select program that took 15 students and accelerated them to a four-year master’s, allowing them to study whatever they wanted in the process. She loved computer science, math, philosophy, law. “I didn’t want to choose,” she told me.
Jablonka’s genetics course changed that. It was abstract, its puzzles cracked by inference. “I said, ‘Oh that’s fantastic.’ Biology is exactly the way I like to think about the world,” she recalled.
Jablonka, too, was a compelling figure. She had almost single-handedly revived the Lamarckian idea that acquired traits could be passed on, showing amid extreme skepticism that epigenetics made it not only feasible but pivotal in evolution. It taught Regev that science was not a popularity contest; you could be derided and still be right.
In time, of course, would come microbiology with its pipettes and PCR machines, its messy results mucking those abstract principles. And yet Regev saw a symmetry between the history of microbiology and the future of computational biology. Microbiology gave biologists new tools, but it also demanded a new way of thinking and forced results to be explained in new terms. Computation could do the same.
She tried that with her PhD proposal: a project to use natural language processing — the same AI technique that allows computers to “understand” the contents of a document or chatbox — to model the circuits that govern how cells differentiate and function. Jablonka thought it was brilliant, allowing biologists to look beyond the messy details and see the overall logic of the system, but Regev soon ran into trouble. Biologists didn’t yet know enough to design such a model. “In reality, we only knew a smidge,” she said. “There was just so much we didn’t know. ”
With inspiration from Pe’er, she took a different approach: not trying to model the system directly, but devising machine learning techniques that would let the data tell you what the system is. It’s also how she eventually ended up with her own wet lab at the Broad Institute. Needing to perturb the system to prove the system was correct, she became the rare computationalist standing over a petri dish.
“You do computational biology, you come up with methods and then you search for ways to apply those methods,” Ramnik Xavier, an immunologist and colleague at the Broad, told me. “Whereas Aviv went the other way, she started with the human biology question and she wanted to find the solution to that question and develop methods that would allow one to answer (it).”
In many ways, Regev’s goals haven’t changed since. She’s still trying to uncover those systems in search of better drugs.
“If we know how the system works, then we can predict it, and if we can predict it then we should be able to develop better drugs, more safely, fast,” Regev said. “I don’t think it was a new insight but I also don’t think it was that executable a decade ago.”
A decade ago, Regev said, three things changed: On the floor above her, Feng Zhang helped pioneer CRISPR, making genetic knockout experiments vastly easier. Machine learning advanced to an inflection point. And Regev herself pioneered RNA sequencing, allowing researchers for the first time to closely probe the genetic networks inside cells.
In a groundbreaking 2013 Nature study, Regev and a team sequenced 18 individual immune cells. Then, in 2014, she was invited as one of several speakers to propose a hypothetical yet realistic project for the NIH to spend $50 million on. She proposed profiling every cell in the human body — a Google Maps for the cellular body.
“It was a completely crazy, crazy idea,” Sarah Teichmann, who was then director of Trinity College, Cambridge, told me. Five years prior, scientists broke ground sequencing 5 cells. The human body has 37.2 trillion cells. “It was completely crazy at that time to think about like this or anything at this scale.”
Teichmann, though, had toyed with a similar idea. So had a couple of others, and when Teichmann two years later was appointed head of cellular genetics at the Wellcome Sanger Institute, she emailed Regev. With a couple of dozen other scientists they founded the Human Cell Atlas, which has already had therapeutic implications.
Regev helped figure out that, contrary to years of published work, the gene behind cystic fibrosis, CFTR, is actually only expressed in a small subset of specialized cells, potentially affecting how you would build a gene therapy. With Xavier, she mapped GI cells, studying rare neurons instrumental in diseases like IBS. We’ve long viewed multiple sclerosis or Crohn’s as a single disease, but single-cell sequencing is showing how diverse they are and how diverse the treatments have to be. “Textbooks will be re-written,” Xavier said.
The atlas also put her at the head of an international coalition that spanned disciplines, requiring finesse, organization and interdisciplinary knowledge that few academics have to deal with — but which big biotech execs need. “I can’t imagine a better person to transition,” Jayaraj Rajagopal, a Harvard stem cell biologist who collaborated with Regev on the CFTR work, told me.
But why leave? Regev puts it bluntly: “Because I actually believe the things I say.”
For two decades, she had argued that if biologists could understand molecular systems, you could turn them into better drugs. Now, researchers had amassed ways of looking at cells in unparalleled resolution, collected unheard-of human genetic data and human biopsies, and devised incredibly powerful machine learning algorithms. There were few other places where she would be able to stitch it all together.
Now, she plots building an engine grander than the small molecule AI machines that dominate headlines. The idea is that you can build drugs differently at every step, designing preclinical and clinical trials to get the data machine learning can then turn into answers. And with enough experiments, you could be predictive in a way few biologists are, collecting enough data and feeding it through enough algorithms to turn the confounding messiness of biology into your friend and allow you to see, for example, what happens if you disturb 3 genes.
Sometimes, she says, she ponders moving away from the single molecular “target” altogether, to use these tools to try to understand the bird’s-eye system of cells, as she tried to do as a graduate student, and drug accordingly. But that’s still speculative, a far-off possibility. She’s certain the rest will happen.
“I wholeheartedly think the inflection point is upon us,” Regev said. “We are not exactly inflected yet, though, and I want to make that inflection happen.” — Jason Mast
An early CAR researcher and Yescarta leader, Margo Roberts is back in the game at Lyell
Margo Roberts never thought she’d end up at Lyell after leaving her previous job.
The longtime biotech vet spent decades working on CAR therapies and had just wrapped up a successful run at Kite Pharma in 2018, where she was CSO and put together the team that developed the groundbreaking cancer drug Yescarta. One of two CAR-T treatments approved in late 2017, along with Novartis’ Kymriah, the drug appeared to be the capstone for Roberts’ decades-long career as a leader in CAR research.
But when she heard that the Rick Klausner-backed Lyell wanted to take the cell therapy technology and use it to treat solid tumors, Roberts came down with a case of curiosity, and perhaps a little bit of FOMO. And there are no FDA-approved drugs for that — not yet, anyway.
“I just felt like I really needed a break,” Roberts said. “And I wasn’t expecting to come back to a position like this, but I did, because … when I heard the vision of the company, I thought to myself, ‘I can’t let this happen without me.’ I’d be so upset if I had to read about this company in the news and I’m not part of it, I’d be pissed at myself.”
So Roberts joined the squad at Lyell a little over a year ago, where she’s again serving as CSO and leading another CAR charge. Klausner brought her on with the goal of assembling one of the most impressive teams of scientists to tackle cell therapy 2.0, while raising an impressive $600 million to get the research off the ground. Included in that heap of cash is a contribution from GSK well within the nine-figure range.
Roberts has worked with several smart individuals throughout her career, but there’s more to R&D than simple expertise, she says. There are a lot of strong opinions out there but what’s most important is finding an environment where people are willing to question the scientific dogma.
That’s ultimately what led Roberts to what she considers one of the greatest accomplishments in her career pre-Yescarta: applying the concept of CAR-Ts and T cell manufacturing to HIV treatment.
“I remember the reviews coming back from the NIAID, and they were saying, ‘Wow this is really interesting, this is a really cool thing that you’re proposing.’ But one reviewer said, ‘But this is Star Wars, and it will never work,’” Roberts said. “I wish I’d kept that because I’d love to have framed it and have lights flashing all around it. We were in the clinic 16 to 18 months later.”
Since then, the technology has proven itself to be one of the most promising areas in the pharma industry. As evidenced by Lyell’s own funding, there’s a lot riding on the type of research where Roberts has spent most of her career. It’s been a long and rocky road fighting against that dogma of what’s believed to be possible.
She remembers working on an early project involving cosymmetry signals in the context of a CAR, another of her major contributions to the field. At the time, her patent for the idea drew some controversy and the program was eventually shut down. But continuing to fight for the idea and the rationale behind it, Roberts ultimately felt vindicated with the Yescarta approval, she said.
Keeping up the fight for what you believe in takes a lot of courage, and Roberts said she aims to surround herself with people who share that mindset. It was one of the driving motivators behind building her team at Kite.
“Courage is hugely important, it takes guts to make a lot of the decisions that we do,” Roberts said. “Most of the time, you’re not necessarily knowing — you don’t have a crystal ball — which scientific direction you’re going, which direction is the necessary one to take. And you’re going to make mistakes, you’re going to make bad calls. It’s really critical that you select the people who aren’t afraid of making the rapid decision based on the available information.”
Roberts’ biggest hope for the next generation of women in biopharma is to continue that courage. She says she didn’t have many women role models coming up through the ranks and recalls attending the early days of the JP Morgan conference in San Francisco where she’d walk into a room and find “a sea of men.”
One of the biggest signs things are changing is how the phrase “I was able to communicate this to my mother” has fallen out of vogue in less than a generation, Roberts says. She used to hear this saying rather frequently intended as a joke when scientists would present their findings, but when her son heard this at an IT conference a few years ago he didn’t understand what it meant.
And as more women come up the ranks in biotech, Roberts wants them to see that holding leadership positions is a goal that’s well within reach.
“One of the things I’ve grown up with is this concept, or where I’ve been exposed to it, where you can be — especially if you’re a man — a real bastard, frankly, and it’s OK, you can get away with it because ‘Oh he’s brilliant,’” Roberts said. “There’s still a lot that can be done there in terms of allowing girls to realize that if that’s a natural interest that they have, this is really doable, it doesn’t require a superpower.” — Max Gelman
‘Just say yes’: Laura Shawver leads her fifth biotech with an all-female C-suite
Laura Shawver was walking down a hallway at Davenport Central High School in Iowa when she was stopped by her AP chemistry teacher, who asked about her plans for college.
Maybe study nursing, or major in music, Shawver replied. She was “always kind of a nerd” — the type of grade school kid who loved making science fair projects.
The teacher looked at Shawver. “Well, why would you be a nurse, when you could be a doctor?” she pressed.
It was the ’70s, and until that moment, it hadn’t dawned on Shawver: “I could be a doctor,” she thought.
So she did it. Shawver earned her bachelor’s degree in microbiology from the University of Iowa, fell in love with research, then got her PhD in pharmacology. And that AP chem teacher? She followed Shawver’s long career in drug development, which landed her as CEO of Silverback Therapeutics, where she’s now leading efforts to reconceptualize antibody-drug conjugates for treating cancer.
“I think it’s important … that as we enter into a field, as we grow in our confidence, as we think about expanding our horizons, that we always have somebody that is in some way saying, ‘Yeah you can do it, you can do it,’” Shawver said.
After finishing graduate school, Shawver let curiosity guide her to a postdoc fellowship at the University of Virginia Cancer Center in the microbiology department. It was the mid-80s, and the scientific community was buzzing over the prospects of cloning.
“Of course now any high school student can clone, but back then it took years and it was very difficult, and I wanted that opportunity to learn molecular and cell biology,” she said.
Shawver recalled her first seminar at UVA. Someone was presenting on some oncogene, but it was like they were speaking a new language. Shawver knew pharmacology, but molecular biology was a different beast.
“I remember leaving work that day, thinking to myself: ‘Oh my God, what have I gotten myself into? I’m never going to understand this.’” (Spoiler alert: With time and effort, she did.)
In 1989, Shawver started a job at cancer-focused Triton Biosciences, which inked a deal in 1990 to sell off its pharmaceuticals business to Berlin-based Schering. Two years later, she hopped over to Sugen.
“I grew up with that company,” she said.
As director of preclinical development, Shawver helped put five drugs into the clinic, and saw two pop out the other side: Sutent, which is approved for kidney cancer and other gastrointestinal stromal tumors, and Palladia, which is approved to treat mast cell tumors in dogs. She jumped from director to senior director to vice president to senior vice president to president, as the company went public, was acquired and merged.
“Almost everything that happens in a biotechnology company happened in one company at Sugen in that 10 years,” Shawver said.
She served as CEO of Phenomix from 2002 to 2010, then CEO of Cleave Biosciences from 2011 to 2017, then president and CEO of Synthorx — a biotech built around the invention of a new DNA base pair — from 2017 to this year.
“There’s been so many, I’ve lost track now,” she said with a laugh.
In 2006, while working at Phenomix, Shawver was diagnosed with ovarian cancer. She had already been making oncology drugs for 15 years, but suddenly, her perspective changed.
As a drug developer, she had looked for improvements that were statistically significant enough to get a product to market. “We look at an overall improvement in survival of 6 months or a 50% response rate as being phenomenal,” she said. “What I realized when I … was diagnosed myself with ovarian cancer: That’s not phenomenal at all.”
“I mean, you’re missing half the population, you’re only buying a little bit more time, you’re not actually doing anything to fundamentally change the outcome of the cancer. The cancer typically wins,” she added.
Shawver recovered with surgery and chemotherapy treatment, and she did two things: First, she launched the Clearity Foundation in 2008 to help ovarian cancer patients get access to molecular profiling to inform their treatment decisions. Then, she got thinking about cures.
That’s what drew her to Silverback, which is focused on using ADCs to drive an immune response to give “more and more people with solid tumors their cures,” she said. And her C-suite is all-female, including CSO and president Valerie Odegard and CMO Naomi Hunder.
“It’s really important for women when they are presented with an opportunity to just say yes,” Shawver said. “Whether you have the experience or not, whether you have the confidence or not, just say, ‘Yes I can do that…’ When you see that there’s a gap, raise your hand…”
“Go for it. Do it. You’ll never have such an exciting career,” she said. — Nicole DeFeudis
Kimberly Smith goes inside the industry to build a new kind of HIV biotech executive
Before ViiV R&D chief Kimberly Smith was a biotech executive, she was a doctor for 22 years at the HIV ward of Philadelphia’s Rush University Hospital. And before that, she was a 24-year-old student protesting the president of the University of Michigan, demanding they recognize MLK Day and the racism students were facing on campus.
The path from clinic to corporate is well-trodden, less so the path there from protest. It’s one of a few things that make Smith different than the average head of R&D.
HIV biotechs have always existed in uneasy tension with activists, perhaps more so than drug developers for any other disease: In 1987, Burroughs Wellcome set the cost of the first HIV drug, AZT, so high it led to TV-grabbing protests that turned public opinion. Activists employ some of the same tactics today to protest Gilead and the long-rising, now $23,000-per-year cost of Truvada.
Smith was at Michigan when the protests over AZT began, and she watched with support as activists fought to change how drug research was done. Although a naturally curious thinker who dissected frogs from the creek near her house at age 12 and pursued infectious disease in part because infectious disease physicians are medicine’s detectives, she would spend as much of her career excavating the biology of HIV as she would fighting for research that was fair, diverse and inclusive. In numerous articles and one book, she documented the treatment needs of women and people of color and how often they were left out of trials.
And had it not been for a surprise call from a former mentor, she likely would have stayed in Philadelphia, working to change the system from the outside. Instead, she’s cut the mold of a new kind of HIV biotech executive, one that, within the constraints of a Big Pharma-owned company, is more attuned to pricing, to activist demands and more committed to diversity in their research.
“Power concedes nothing without demand,” she told me when I asked about activist critiques of industry, quoting Frederick Douglass. “Of course there should be a challenge to pharmaceutical companies.”
ViiV spun out of GSK in 2009 and Smith joined in 2013. She takes pride in the fact that the Fair Pricing Coalition gave ViiV, as she puts it, “a soft thumbs up” on pricing. A 2019 FPC statement says the price the company put on their Dovato daily pill “bucks the trend of runaway HIV drug pricing”: “FPC asked and ViiV listened,” chair Tim Horn added.
In 2013, the year Smith joined, ViiV became the only major company to put some of its HIV drugs in a medicine patents pool set up by the UN, prompting Public Citizen to send letters to six other major drug companies asking why they didn’t do the same.
She also takes pride in her company’s diversity, both of her employees and of the research they conduct. It’s been an issue for Smith since her med school days, when she watched HIV afflict the worst of society and much of the medical world turn their back on the people they were supposed to help. “HIV was fascinating to me, scientifically and medically … But there was also the social-political aspect of it, because back in those days, people with HIV — the stigma still exists, but the stigma then was horrific,” Smith said. “I was a political person, I wanted to be part of that.”
At the time, 1993, the first antiretrovirals were reaching the market, offering hope of changing the course of the disease. Still, they weren’t yet a cure and Smith pronounced one or two patients dead per night. “It was heartbreaking,” she said. “And these were young people, young men who have sex with men and in many cases young women, it was all of America.”
Smith pulled through, buoyed in part by the families who relied on her. She began studying how the new drugs affected the immune system. She tracked the newest advances with excitement but also growing frustration. The public face of HIV at the time was white, male and gay and those were often the faces of drug trial participants. But that image didn’t reflect the faces Smith tended to at Rush, nor the actual national statistics.
Smith read paper after paper and then looked with dismay at the demographics. She started writing about it and, as her profile grew, lobbying the NIH to do something. Eventually, they formed the under-represented population’s committee of the AIDS clinical trial network and named Smith co-chair.
“It was like, ‘OK, Kim, we’re going to shut you up and give you your own committee, where you can fight this out,” Smith said.
Then in 2013, her phone rang. It was John Pottage. Pottage had been an attending at Rush when Smith was a resident, before he left to join Vertex, which was then focused on antivirals. Pottage had kept up with Smith’s work, as a clinician and a clinical trialist, and wanted to know if she might want to help run ViiV’s clinical research.
“She has this ability, this talent but she’s also able to communicate it,” Pottage told me. “To get people to understand where she’s coming from and take people with her.”
Smith had never considered industry but ViiV was different. It was all HIV, and it meant an opportunity to make a larger impact on the field that had become her life’s work. After working under Pottage for 6 years and helping develop four different HIV drugs, she was named to his old position of head of R&D last year.
Now she tries to mold HIV research in a vision she’s built over 3 decades. That means long-injecting that helps patients avoid daily pills and the stigma that, for some, can come with them. It also means trials that draw from patients who are most affected.
The contrast was clear over the summer. In a significant achievement for Smith and the company, a trial they were running comparing once-every-8-week experimental injection vs daily PrEP was cut short in July for overwhelming efficacy. The study included 4,600 people across 40 continents, half of the participants were black and 12% were transgender women.
At the same time, they awaited results for a study that was entirely composed of women. On November 9, that trial read out, showing their injectable was 89% more effective at preventing HIV than daily pills.
Gilead, meanwhile, won approval for Descovy, a Truvada follow-up, after a trial that generated widespread criticism for including zero women.
“Obviously, I can’t complain to their faces anymore like I used to when I was their advisor and I was not in industry,” Smith said of companies that don’t include diverse participants. “But what I do is make sure that we set an example of trying to do it better.” — Jason Mast