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What excites you most about the biotech industry at the moment?
The convergence of advanced biology, technology, and data analytics is opening up possibilities we couldn't have imagined a decade ago. The work we're doing today could pave the way for new treatments across a range of diseases. I'm incredibly optimistic about the future. I believe we're entering a golden era of innovation.
And what’s your part in that? Can you explain the science behind chromatin regulation and what makes the approach of Foghorn Therapeutics unique?
At its core, the chromatin regulatory system acts like the architect of the cell—it determines which blueprints, or genes, are used at any given time. If this system malfunctions, it's like an architect making mistakes in a building plan— it causes chaos. In cancer, this leads to uncontrolled cell growth and proliferation.
Our DNA is incredibly long—about two meters if you stretched it out—but it has to fit into the nucleus of a cell. This is achieved by packaging the DNA into chromatin, winding it around proteins called histones to form nucleosomes. For genes to be expressed, the chromatin must be unwound or opened up, and that's where chromatin remodeling complexes come into play.
One such complex is the mammalian SWI/SNF complex, also known as the BAF complex. Mutations or malfunctions in components of this complex are implicated in about 20% of all cancers. If you include transcription factors involved in chromatin regulation, that number rises to about 50%. That doesn't mean all these cases are directly druggable, but it highlights how critical this system is.
At Foghorn, we've built a platform that allows us to systematically interrogate this biology. We can produce and purify these complex protein machines in a highly specific way, enabling us to run precise assays and identify novel chemical matter. Essentially, we're a small molecule company focused on discovering and developing therapeutics that target these difficult proteins within the chromatin regulatory system.
You've recently announced dosing of the first patient in your Phase 1 trial of FHD-909 in collaboration with Eli Lilly. Can you tell us more about that milestone and the significance of the partnership?
Absolutely. FHD-909 is a selective inhibitor targeting SMARCA2, also known as BRM. This protein creates a critical dependency in certain cancers, like non-small cell lung cancer. The challenge has been to develop a drug that selectively inhibits SMARCA2 without affecting its closely related counterpart, SMARCA4—they're about 90% similar. Achieving this specificity is key to avoiding unintended effects.
We've managed to develop a selective enzymatic inhibitor for SMARCA2—the only one of its kind, as far as I know. Partnering with Lilly has been a huge validation of our approach. It's a 50/50 economic share, with Lilly leading the clinical development. We dosed the first patient recently, and while it's an exciting milestone, it's also a sobering reminder that we're dealing with life-and-death situations.
On a personal note, I lost my father to a rare cancer almost five years ago. He was diagnosed in April and passed away in November of the same year. So, while we're excited about the potential of our drug, we remain grounded in the reality that each patient represents a life we're striving to impact positively.
How is your pipeline progressing beyond FHD-909?
Beyond FHD-909, we have several programs in our pipeline. FHD-286 is a dual inhibitor of both SMARCA2 and SMARCA4, currently in a dose-escalation study for acute myelogenous leukemia (AML). We expect to have data on that in the fourth quarter and will make decisions on how to proceed based on those results.
We have other programs in collaboration with Lilly that we hope will reach the clinic in the next 12 to 15 months. Additionally, we're advancing targets like CBP and EP300. CBP is on track to start IND-enabling studies towards the end of this year, setting us up for an IND filing in 2025. EP300 is progressing behind that.
We're also exploring applications beyond cancer, potentially in areas like autoimmunity and metabolic disorders. Our platform's ability to modulate gene expression opens doors to a variety of therapeutic areas.
With such a broad pipeline, what are your main goals for the next year or so?
Execution is our watchword. Over the next 6 to 15 months, we're focused on progressing our pipeline efficiently. That means advancing our clinical trials, generating meaningful data, and making informed decisions based on those results.
We're also looking at business development opportunities, including potential partnerships that can leverage our platform and assets not currently partnered with Lilly. The aim is to create value while staying true to our mission of developing transformative therapies.
How do you see developments like artificial intelligence impacting biotech?
AI can help in predicting protein structures, optimizing clinical trial designs, and identifying patient populations more effectively. While we're not at the point where AI can replace wet lab work entirely, it's a valuable tool that can enhance and accelerate drug discovery and development. We've integrated AI tools across various functions—from computational chemistry in drug design to operational efficiencies in HR.
On the flip side, are there any industry challenges or headwinds you're concerned about?
Overregulation and government intervention in drug pricing and reimbursement are significant concerns. While regulations are necessary to ensure safety and efficacy, excessive intervention can stifle innovation.
The development of new medicines is a costly and risky endeavor. If the financial incentives diminish due to stringent pricing controls, it could lead to reduced investment in research and development, ultimately affecting patients who need new therapies.
What are some of your guiding principles on leadership and culture?
My leadership philosophy centers on servant-based leadership—the idea that leaders are here to serve and support their teams. It's about fostering an environment where everyone feels valued and empowered to contribute.
At Foghorn, our core values reflect this philosophy. We put "people first," which means caring for our employees so they, in turn, can focus on helping others through their work. Developing medicines is inherently a team effort. No one person can do it alone; it's the collective expertise and dedication that drive success.
We believe in "data over dogma." Decisions should be based on evidence and facts, not hierarchies or preconceived notions. Good ideas can come from anywhere in the organization, regardless of title or tenure.
And what about your personal career journey, did you always know this was the field you wanted to work in?
Well I grew up around Medicine—my father was an orthopedic surgeon who trained in South Africa, Germany, and Switzerland, and was a fellow of the Royal College of Surgeons in Edinburgh. We moved from Johannesburg to the U.S. when I was about eight or nine years old.
I got accepted into medical school but then reconsidered. Long story short, I decided to pursue an undergraduate degree in biochemistry but ended up in IT consulting for upstream oil and gas—a bit of a detour. The desire to return to the medical field never left me. I found an MBA program at MIT Sloan School, and while there, I joined a joint program between Harvard and MIT called the Biomedical Enterprise Program. It was a mix of science, medical courses, and business—perfect for someone with my interests.
During that time, I did a summer MBA internship at Biogen in 2002. Between my time there and my graduate work, it became clear that biotech was where I wanted to be. I realized that by developing medicines, I could potentially help hundreds of thousands, if not millions, of people.
I spent almost 14 years at Biogen, starting as a summer intern and eventually becoming a senior vice president. I held various roles, from corporate strategy to running the Japanese affiliate and overseeing regions like Japan, Australia, emerging markets, Latin America, and South America. Toward the end, I was leading the Alzheimer's programs.
When Biogen underwent a CEO transition, I felt it was the right time to pursue something more entrepreneurial. I wanted to join a smaller company where I could make a significant impact on the culture and trajectory. I met my now chairman, a partner at Flagship Pioneering, and our principal scientific founder, Cigall Kadoch. The science of chromatin regulation at Foghorn was absolutely fascinating—an underappreciated and underexplored area with immense potential.
