Interview With Dr. Alex Federation, CEO and Co-Founder of Talus Bio
In this edition of Founder Spotlight, we introduce a prominent figure in the biotechnology sector, Alex Federation, the co-founder and CEO of Talus Bio, a company focused on developing innovative cancer therapeutics. Under Alex’s leadership, Talus Bio employs advanced methods such as functional proteomics and machine learning to explore and target transcription factors, aiming to create first-in-class drugs with high potency and selectivity while minimizing toxicity. The company has gained recognition for its innovative approach to drug discovery, particularly in addressing challenges associated with targeting transcription factors that were once deemed undruggable.
Let’s explore Alex’s story about Talus Bio and its unique approach to drug discovery.
What inspired the creation of Talus Bio, and how did the idea for targeting previously “undruggable” transcription factors evolve?
The ideas that spawned Talus Bio go back to my early training with Jay Bradner at Harvard Medical School, where I had the privilege of training in a dynamic, multidisciplinary, entrepreneurial and rigorous environment that believed that “nothing is undruggable”. After contributing to several innovative therapeutic programs and to work that led to half a dozen new startup biotechnology companies, I continued my training in the Genome Sciences Department at the University of Washington, where I met my co-founder, Lindsay Pino.
Lindsay was innovating new methods that allowed, for the first time, truly scalable proteomics with the precision required for drug development. That technology, combined with my historical interest in this the significant gap in our ability to target “undruggable” transcription factors was a perfect match. This intersection inspired the creation of the technology that eventually became MARMOT platform, leveraging advances in AI, proteomics, and automated biology to overcome the barriers traditionally associated with these transcription factors. When we had the opportunity to spin out this technology and commercialize the MARMOT platform, we knew that this was a once-in-a-lifetime opportunity to build something that wouldn’t have existed otherwise and we took the leap.
Can you explain how the MARMOT platform works and why it represents a breakthrough in transcription factor drug discovery?
The MARMOT platform integrates functional proteomics, automated biology, and machine learning to report, for any molecule tested, how it modulates any one of the 1000s of proteins interacting with DNA in a live, unmodified human cell. This provides, for the first time, a global view of transcription factor activity in human cells. Traditional methods for assessing transcription factor activity require artificial systems that destroy the native environment where transcription factors fold and function normally.
Using this technology, we have amassed a dataset that is currently the largest in the world (to our knowledge) for transcription factor activity. MARMOT’s AI models, trained on these tens of millions of data points, allow scientists to rapidly discover and optimize modulators for transcription factors. This platform represents a breakthrough because it bypasses the inefficiencies of traditional high-throughput screening, which is limited to few targets in artificial environments. The result is a dramatic acceleration in identifying potential drug candidates for these historically “undruggable” targets.
Recently, Talus Bio raised $11.2 million in funding. How do you plan to use this investment to scale your platform and accelerate drug development?
The $11.2M Seed+ financing led by Two Bear Capital will be used to expand the MARMOT platform and accelerate drug development in Talus Bio’s therapeutic programs. This includes progressing their programs targeting Brachyury-driven cancers and additional transcription factor programs including in prostate cancer. The investment will also help scale the company’s AI-driven discovery process, with a focus on growing the team of data scientists and building partnerships to advance the transcription factor modulators already identified by the platform.
How did Talus Bio’s cap table evolve post-funding, and how do you plan to manage it effectively?
With the participation of new investors such as Two Bear Capital, WRF Capital, and others, Talus Bio’s cap table now includes a broader mix of institutional investors. In assembling this syndicate, we prioritized (and will continue to prioritize) partnering with investors that are strongly aligned with our vision of the company and the massive opportunity that our platform technology represents.
Your Brachyury program targets a transcription factor involved in chordoma. Could you discuss what its potential impact is on cancer treatment?
Talus Bio’s Brachyury program focuses on targeting a transcription factor involved in chordoma, a rare type of cancer. Brachyury is a developmental transcription factor that is normally only active in the developing embryo, but it is reactivated to drive chordoma progression and metastasis. Chordoma has no other approved and effective drugs today, so Talus Bio’s efforts to develop modulators against this target could provide a breakthrough treatment for chordoma patients. Beyond chordoma, brachyury is overexpressed across many cancer types, most notably non-small cell lung cancer and triple negative breast cancer, two additional indications that we are also exploring.
What advantages does Talus Bio’s integration of functional proteomics, automated biology, and machine learning bring to drug discovery compared to traditional methods?
Simply put, this unique combination of functional proteomics, automated biology, and machine learning gives Talus Bio a unique glimpse into how transcription factors fold and function within the native living human cell, a perspective that has been missing in drug discovery historically. This allows us to tackle transcription factors in ways traditional drug discovery cannot. The MARMOT platform accelerates drug discovery by using AI to predict the best compounds for modulation, while functional proteomics enables a deeper understanding of protein:compound interactions in their native cellular environment. This integrated approach is more efficient and scalable than traditional methods, allowing for faster identification of potential drug candidates and faster optimization for potency and selectivity
Given the scalability of your drug discovery engine, what therapeutic areas are you most excited about exploring beyond cancer?
Our MARMOT platform has the potential to expand beyond cancer into a variety of disease areas where transcription factors play a pivotal role. These include metabolic disorders like diabetes and obesity, inflammatory diseases, fibrosis, and neurological conditions – all of which have characteristic transcription factors known to play a central role in pathogenesis.
Looking forward, what is your vision for Talus Bio over the next five years?
In the next five years, the sentiment will shift in drug discovery from scientists and physicians looking at transcription factors as “undruggable” to a new frontier for targeted therapeutics, much like kinases took center stage in the early 2000’s. At Talus, we will continue unlocking new transcription factors, expanding our pipeline, moving more drug candidates into clinical trials, and forming strategic partnerships with pharmaceutical companies for targets outside of our area of expertise. Their ultimate goal is to redefine how transcription factors are targeted, paving the way for a new wave of therapies to treat complex diseases with high unmet medical needs.
How do you plan to stay ahead of the competition as more companies enter the space?
Talus Bio’s competitive edge lies in the unique blend of skills required to build a technology like the MARMOT platform that integrates AI, proteomics, and automation to build a flywheel that enables transcription factor drug discovery at scale. New data drives better models, which predict new TF drugs that are tested in the lab and fed back into the model. By continuing to amass and leverage this unique data and improve our AI, Talus Bio will continue to maintain its leadership in the field.
What advice would you give to entrepreneurs looking to start companies that aim to solve both financial and environmental challenges?
One of our earliest investors developed something they call the “Mr Burns test” when thinking about companies solving important problems for humanity. The idea is that for a product to succeed at scale, it must be something that even a character like Mr. Burns from The Simpsons—the epitome of self-absorbed, greedy capitalism—would buy, not because it’s sustainable, but because it’s the best, cheapest, or most convenient for him. While it might be a sobering reality of human nature, we believe that passing the “Mr Burns test” is key to achieving large-scale impact. In other words, focus on building something that excels on its own merits, which will naturally drive both financial and environmental success.
