F-Prime: Stacie Weninger, PhD

“I'm not looking for the slightly better or marginal effect—we are looking for ideas that will fundamentally change human health.”

Reading is hard. Ask any grad student—whilst running experiments, revising manuscripts, meeting with collaborators, and preparing for an impending thesis defense, one must also find the time to sit and read the literature. In the lab, the “fight or flight” (experiment, publish) too often trumps the “rest and digest” (read, plan).

To gain an intuition for high-impact science, reading broadly is paramount. Yet going through a technical scientific journal “cover to cover” is easier said than done. When she was a neuroscience grad student at Harvard, Stacie Weninger always found reading to be…well, fun: “I found that I would rather sit at my desk and read Neuron cover to cover—articles often having nothing to do with my project,” says Dr. Weninger, now president of FBRI and an investor at F-Prime Capital.

For Weninger, reading broadly offered a way to think about many exciting advances within neuroscience, all at once. After finishing her Ph.D. in Joseph Mazjoub’s lab, and a post-doc with Bruce Yankner, Weninger decided she might as well join the journal she loved so much. From 2001-2005, Weninger was a Senior Scientist at Neuron, a role that prepared her well for her future career as an investor: “I felt like the training that I had at Neuron has helped me identify high-impact science.”

Though she loved working in scientific publishing, Weninger was approached with an offer she couldn’t refuse: to head the Task Force on Women in Science at Harvard University and identify barriers preventing women from reaching senior positions: “I learned a lot about project management: running big programs and getting a lot of stakeholders aligned was a totally new experience…but I did miss the science.” Following her report, Weninger took a role at the Fidelity Foundation, investing in early-stage and promising science.

In 2008, days after the collapse of Bear Stearns and Lehmann Brothers, Weninger transitioned to the “for-profit” side at FBRI and officially became a VC: “it definitely was a crazy time to make the move into venture,” she now reflects.  Despite a financial crisis and initially “not knowing what venture capital was,” Weninger soon demonstrated a knack for identifying high impact companies. She has led investments in ventures such as Denali (DNLI), Annexon (ANNX), Atalanta, Aratome, Sironax, Neumora, Inscopix and Enspectra. She currently chairs the Collaboration for Alzheimer’s Prevention; is President of Alzforum; serves as CEO and Chair of the Board of Directors for Rugen Therapeutics; serves as a member of the Board of Directors for many companies and organizations including Atalanta, Neumora, Sironax and Target ALS.

In her grad student days of flipping through journals at her lab bench, Weninger may never have imagined that she would one day impact so many different areas of neuroscience: “I get to use the skills and science that I was trained with, in a way that has been really exciting and satisfying.” Now an established investor, Weninger shares how she thinks about high-impact science, identifies transformative companies, guides entrepreneurs to pursue critical experiments and, in doing so, “has an incredible amount of fun.”

Happy reading.

Below is an interview with Dr. Stacie Weninger from December 2022:

Stacie Weninger, PhD. President of FBRI and investor at F-Prime Capital

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1.     What first got you interested in medicine and science?

I’ve always been interested in science. But it wasn’t until late high school that I really started thinking about doing science. The turning point was honestly a biology class and learning about genetics, which I thought was very cool. This was a long time ago (the 1980s to date myself), and frankly, we didn’t know all that much. Genetic engineering (e.g., recombinant DNA/cloning) was a totally new thing back in the 80s and was really intriguing to me. In college, I was a chemistry major because I really thought that that was a good broad base for whatever I wanted to do. As I started thinking more about the kind of science I like, I took a biopsychology class, which was much more neuroscience-based. I just became fascinated with the brain. Neuroscience was a good mix between metaphysical questions like, “what is consciousness?” and trying to understand the underlying neurobiology. These types of questions intrigued me, so I decided to go to graduate school in neuroscience at Harvard. In thinking about what I wanted to study, I always wanted to impact human health and do disease-based research

In part, this interest in neuroscience and human health may come from my father—he was a psychiatrist. I grew up talking about the brain and psychiatric illness, which is devastating for so many people. But psychiatric disease also raises many of these fundamental questions about how the brain establishes personality or causes certain behaviors—not all of which are bad. For example, you hear these stories of people with bipolar depression who will lament a loss of creativity that comes with proper treatment of their illness.   . A lot of great art—throughout history has come from people who suffer from psychiatric illness, but the human suffering caused by these illness is far too heavy a price to pay in my mind.  The therapeutics we currently have for many psychiatric illnesses are also inadequate for far too many people.    So, I think these diseases raise many interesting questions about the brain, humanity and human illness.  Furthermore, so much of what makes a person who they are, is their memories. So understanding memory has fed my interests in metaphysical philosophy as well as the biology of the brain.   Seeing the devastation of losing one’s memories, and in some ways oneself, in diseases such as Alzheimer’s disease, has pulled me into the study of the neurobiology of disease.   I realized this is where I wanted to have a positive impact.

2. What was neuroscience graduate school like?

I loved grad school. It was probably one of my favorite times—I had so much fun. I loved the Program in Neuroscience at Harvard. It was an incredibly supportive and stimulating environment, and meeting other students and faculty members with the same sorts of passions as I had was inspiring—I remain close friends with many of my classmates and colleagues from my time in grad school today.   I also loved being able to just focus on the brain—the fact that all of my classes had to do with the nervous system was really exciting.

I did my Ph.D. in Joe Majzoub’s lab, which focused on neuroendocrine physiology. I was interested in studying the HPA axis as a way to try to understand the biological basis of depression.   Joe was a fantastic mentor and the lab offered a great environment to learn how to be a scientist.   The lab had generated a knockout model that many thought would help us address some of the biological basis of depression.   This was when mouse knockouts were new and frankly merely characterizing a knockout was the bulk of my thesis [this was 25 years ago).  While I learned a tremendous amount during my Ph.D.,  I felt that studying psychiatric disease was unsatisfactory with the tools and knowledge we had at the time—so I shifted my postdoc to Alzheimer’s disease. I felt like at the time [ late 90’s/early 2000’s] that Alzheimer’s Disease was more tractable than psychiatric illness from a neurobiology point of view.   It was in the 90s when most of the autosomal dominant genes were discovered for familial AD (presenilin and APP), so I felt like as a trainee there was a lot more that I could in the lab. Yet here we are 30 years later, and we still can't do very much for these neurodegenerative diseases—so I'm not sure how much more tractable they really were. But we definitely understood more of the fundamental biology and genetics than in neuropsych.

It wasn't until I was a postdoc that I started looking around and thinking that the lab is not what I enjoy. While I could certainly ask some more fundamental questions within the field of Alzheimer’s disease at the bench, what I was realizing was that all the questions I could ask were relatively narrow: if you are running a lab, you have to be somewhat focused on one topic. I loved thinking about the brain more broadly, and I found myself feeling way too limited by what I could ask in one project or frankly even if I were to eventually run one lab. I was also frustrated doing benchwork, which I found pretty boring. As a grad student, it was like: “this is what you do to get a Ph.D.” But as a postdoc, it felt like a waste of time—you often have to dedicate hours to running tedious experiments that anyone could do with a little bit of hands-on training. I realized that I liked thinking about science more than doing it. I found that I would rather sit at my desk and read Neuron cover to cover—articles having nothing to do with my postdoctoral project—than get up and run another Western Blot. Around this time, I saw an ad in Neuron for a senior scientific editor, and I thought: “well, this is what I like doing. Maybe I should go for it.”

[On how folks in academia viewed her career change]

Many people were very disappointed. A close  mentor was devastated and said to me: “Aren't you disappointed? You're never going to create new knowledge.” And that stung at the time. But I will say with 100% certainty I have contributed to the creation of more new knowledge in the career path I've taken than I ever would have by running my own lab and studying a narrower area of neuroscience.

3. What was making the transition to an editor at Neuron like?

To add color to this, I was also pregnant as a postdoc. At the time, daycare was going to cost more than my postdoc salary—not to mention that having a baby would take away the time I could contribute to experiments. That is not why I left, but it certainly spurred me to think about alternate career paths, and the opportunity at Neuron came along at just the right time. I loved being an editor, I had so much fun. To harken back to my mentor’s stinging comment, at Neuron, I felt like I was contributing to the creation of new knowledge because we were giving people feedback on their papers and ideas for alternative hypotheses and ways to test these new ideas. And we're helping to set the bar and standards for high-impact science in the field of neuroscience.  I definitely thought: “I wish I could have gone back and done grad school after being an editor.”  It really does help you identify what high-impact science looks like. Not that my labs were in any way bad, but I would have made better choices on rotation projects or perhaps done different experiments. Being an editor is great training and is a stepping stone to being able to do other things.

So, I really enjoyed my time at Neuron.

[What specific skills did you learn as an editor]

I think the quick recognition of: “what are the key experiments that would take something from uninteresting to high-impact science?” has been an invaluable skill for me.  Being able to quickly hone in on the fundamental questions of significance and how to design experiments from the which the results could change the way we view an aspect of science are key skills I acquired.  Science that can fundamentally change our understanding or definitively answer a question is what high-impact science really means. Being an editor trains you to think: how do we quickly get definitive? What are the feasible experiments that speak to relevance and give clear answers? This skill set is incredibly relevant to the biotech field and investing, where it is crucial to ask those questions.

4. What was your time on the Harvard Task Force for Women in Science like?

You may recall some comments that created quite a stir in early 2005 with regards to hypotheses around the lack of senior women in science.   Harvard responded to these comments by creating a Task Force on Women in Science that was charged with identifying barriers to women’s advancements to the highest levels of academic science.   I was recruited to run this task force.  

There was a very intense and short effort: I started in February, and we reported our findings in May. Running the task force was really about identifying some of the barriers and coming up with potential solutions for women in science. While I do believe that some of the ideas we suggested have been helpful, one of the challenges with implementing real change is that a considerable amount of the fallout happens at the postdoc level. Some of that is just life circumstances—if daycare is going to cost more than your salary, how are you supposed to have a child and be successful if you don’t have other means? Also, postdocs are getting longer and longer. Another issue is that universities recruit their grad students and choose their junior faculty, but they don't have a say in the postdocs, which are recruited by individual labs. It is thus hard for a university to invest in larger programs to help postdocs because they don't help select them in a meaningful way. I think there's a lot that can be done at the junior faculty level and earlier in the pipeline. But I still think the postdoc period is a challenge, and there are many barriers for women during this time period that still need to be addressed.

Running the task force was a great learning experience for me. I learned a lot about project management: running big programs and getting a lot of stakeholders aligned was a totally new experience. But I did miss the science and wanted to get back to thinking about the brain. So although the plan or me was to stay in the Provost's Office and implement policy after the task force was finished, I wanted to get back to being more focused on science as opposed to policy. 

5. How did you first get involved with the Fidelity Foundation? What was hardest about making this transition?

Being at the Foundation was everything I loved about being a journal editor, only better. Part of what I loved at Neuron was that you could sit down and read a paper that represented five years of work and get to see it before anyone else. You then got to help guide some of the experiments and revisions, before the paper gets published. At the Foundation, we were involved in the science at the start of those five years of work. We were proactive in trying to identify the needs in the field and how we could have a real impact. It was incredibly rewarding to be able to contribute to the field in a myriad of different ways. 

[On transitioning to VC]

After a few years, it was suggested that I move into the “for-profit” side. At the time, I didn't even know what that meant—I truly did not know what venture capital was. To be honest, I had the “evil venture capitalist” in mind. I thought a VC would invest and then just sit back and see if it works out. To me, investing also seemed very stressful—if you invest in something that doesn't work you could lose a lot of money. I thought I would hate it. After much soul searching I finally I promised myself I would give it a try for a year. That was in 2008, and I’m still at it. I actually had my first conversations about moving to investing in August [‘08]—within days of the Bear Stearns and Lehman Brothers collapse. It definitely was a crazy time to make the move into venture.

6. What advice would you give about being a good investor? Lessons from early/memorable deals?

It all comes back to really trying to identify what is going to be transformative. From the standpoint of therapeutics, I felt like my training at Neuron has helped me identify high-impact science. I also learned how to think about the key experiments that will give you definitive answers. I think that successful companies will bring transformational ideas or technology.  These could be novel approaches to hit well-validated targets or novel ways to identify targets.   Furthermore, as an investor, you have to gain conviction that if you hit your target you will affect disease, that the modality at hand will allow you to hit your target, that there will be a way to measure that you have hit the target in people, and that you can identify the right people at the right to carry it off.   Alternatively, novel platform technologies are hugely interesting if they make the formerly undruggable [proteins/molecules] druggable.   So, you kind of put all of these points together in an investment thesis.

When you can see a company has addressed these different aspects, it may make for a good investment—something that will be transformational. I'm not looking for a slightly better or marginal effect—we are looking for ideas that will fundamentally change human health. Another  aspect of being in VC that I initially did not understand, but is really refreshing, is the idea that we are going to roll our sleeves up and make sure this venture has the best chance of working. So, we're going to get involved, and we're going to do everything we can to guide the entrepreneurs. I also get to use my scientific training in a way that has been exciting and really satisfying.

In my day-to-day job, I wear two hats, one at FBRI and the other as a member of the F-Prime team. FBRI is our mission-driven fund, which very much seeds early-stage companies. The first deal I did, which became an F-Prime investment, was Denali (DNLI). It was a company that FBRI started and seeded before F-Prime came in. We at FBRI have also done a lot of other smaller companies that were never expected to be the right fit for a follow-on F-Prime investment. Early on we had a lot of these projects helping academics spin out with some early-stage seed funding. For example, we did one such early-stage deal in the psychiatric space, which is still playing out today. We'll see where that goes. Another FBRI-seeded program that is now in the clinic is Ben Barres’ company Annexon.  With some FBRI seed funding, we also helped spin-out some interesting technology for neuroscience research, including one   with Mark Schnitzer at Stanford, called Inscopix [develops miniature microscopes for imaging in models—currently used by over 500 labs]. Inscopix was just recently acquired.

7. Which broad areas of science and medicine are you most excited about seeing develop in the next 5-10yrs?

Within neuroscience, it is understanding the role of the immune system in neurological disease. Just as understanding some of the role of the immune system in cancer has revolutionized oncology therapeutics, I think understanding the role of the immune system in neurological diseases will lead to equally revolutionary therapeutics.  It is absolutely clear that dysfunction or over-activation of the immune system is contributing to both psychiatric illnesses as well as neurodegenerative diseases, whether that be resident immune cells, like microglia, or how the peripheral immune system affects the brain. I think that in both neurodegenerative and psychiatric disease, understanding the immune system’s role is going to fundamentally change how we think about and treat these diseases.

8. In today’s climate what is one short piece of advice you would give to prospective and early-stage biotech entrepreneurs?

The answer may depend on the kind and stage of the company it is, but a general piece of advice may be regarding choosing potential investors. It's really not about who's going to give you the best valuation or the most money, it comes down to who truly wants to help you build a successful company. I think that can be very different from issues of valuation. As an entrepreneur, you must recognize the value different investors can bring to what you're trying to develop.

9. If you were in med school/grad school/business school today, and could sign up for a class, which topic/area would you choose? why?  

I think there's an explosion in technology around genome engineering—so much has changed since I became interested in science in the 80s. It seems almost like sci-fi, what we can now do, using tools like CRISPR, prime and base editing, or ex vivo and in vivo gene therapies. I would want to better understand all I could about the fundamental biology of these technologies, which will help inform the next generation of these tools. I think these technologies are opening up the therapeutics space in ways that we have never seen before—so I would take a collection of courses in molecular biology, bioengineering and genetics focused on these emerging technologies.

10. What are you reading in your free time? 

I just finished The Perfect Predator, which is about the potential of bacteriophage for treating antibiotic-resistant bacterial infections. It's non-fiction but is written as a really engaging story of how a Steffanie Strathdee, an infectious disease epidemiologist at UCSD,  helped save the life of her husband, Tom Patterson—an evolutionary socioibologist. They were on a trip in Egypt together, and he got an antibiotic-resistant infection. Because of their scientific knowledge and her contacts, she was able to actually come up with a treatment using bacteriophage and cure her husband. It's a true story with enough science to be very interesting, but it also is quite a page turner.