Towards a pipeline of differentiated medicines, bolstered by genomics, data science, and synthetic biology breakthroughs
Twenty years ago, Maureen was working at a lab at the University of Notre Dame, just as The Human Genome Project was being completed. This landmark global scientific effort aimed at deciphering the chemical makeup of the entire human genetic code (i.e., the genome), showed Maureen the early innings of what might be possible when biology meets computer science.
As a biologist who knew how to code, and someone whose family was personally impacted by cancer, Maureen was determined to contribute to this quickly evolving, highly impactful field. She believed it simply wasn’t moving fast enough because there weren’t enough people working on it, and threw herself into the mix, pursuing a PhD in Biomedical Informatics at Stanford University. There, she started building the foundational technology that would soon become Hexagon Bio, working with peers and co-founders Brian Naughton and Colin Harvey.
Fast forward to today, and Hexagon Bio is innovating at the intersection of computation and drug discovery, applying advancements in DNA sequencing to help accelerate and overcome many of the challenges of natural product drug discovery.
Maureen shares how historically, half of cancer drugs and three-quarters of all antibiotics were found from natural sources. Drugs discovered from microbes and plants include penicillin (antibiotic), statins (cholesterol-lowering) and taxanes (cancer therapy). These potent drugs evolved in the wild in what she describes as “chemical warfare,” to compete with their neighbors in nature.
Many blockbuster drugs were discovered in nature before DNA sequencing. Their discovery involved laborious processes to culture strains and isolate metabolites, and Maureen speaks to how these perpetuated a lack of understanding of the protein targets of the metabolites. In creating Hexagon Bio, Maureen recognized how genomes could enable a more efficient and effective approach to the discovery of evolved medicines, though it wouldn’t be an easy feat.
Hexagon Bio’s platform and workflow begins with what the team calls “sequencing the earth”–starting with fungi, with plans to later expand into bacteria and plants.
One team at Hexagon Bio is sequencing samples around the U.S. to start (and around the world one day), building a vast proprietary database of genomes, while another team of data and software engineers analyzes that database to find new compounds, using machine learning. They train algorithms on earlier known true positive examples, and also train the algorithms to look ahead at new genomic data and form predictions on what solutions might exist.
As with all deep learning systems that improve over time, more high quality data means more relevant and accurate predictions. This helps for the next step, harnessing innovations in synthetic biology to produce and identify potent metabolites, leveraging biomolecular machines that can reproduce complex chemicals.
The next step involves confirming hit molecules in the laboratory, which involves transplanting the DNA from these wild species into baker’s yeast commonly used in beer and bread. “You can see flasks shaking in the lab,” says Maureen, laughing, “but instead of fermenting ethanol, we’re fermenting new chemicals that we’ll go and test for cancer and infectious disease activity.”
What a sight to behold–the Hexagon Bio brewery where Maureen and team are serving up a pipeline of molecules that may become differentiated medicines, with an initial focus on oncology and fungal disease, and an intention to later expand into other therapeutic areas.
The next quantum leap forward for drug discovery?
Speaking with Maureen, we might be at the precipice of another big breakthrough for biotech.
Maureen references how there have already been some advancements in the generative AI space for molecular biology, such as AlphaFold demonstrating how protein amino acid sequences can be converted into images of their 3D structures.
“Hexagon Bio is nicely placed there, because a lot of what the algorithms will predict are complex molecules that chemists can’t make easily through traditional synthetic chemistry. Some years from now, if AI is better at predicting molecules, but chemistry fails to make them, our platform could easily step in,” Maureen shares.
Amidst so much opportunity, Maureen encourages other scientists and biotech founders 1) to surround themselves with good mentors and peers, and 2) to retain a healthy dose of skepticism. That’s because at times, the demands of scientific rigor, and the path to clinic and real world impact may seem to be at odds. On one hand, if a scientist misses a lead on a good drug, that can be devastating for the company; on the other hand, spending time chasing false positives brings a huge opportunity cost, versus getting started on the next lead in the pipeline.
On the heels of their recent $77.3M Series B financing, Hexagon Bio announced key appointments to their leadership team, including the promotion of Tara Arvedson, PhD to Chief Scientific Officer and Victor Cee, PhD, joining as SVP, Drug Discovery. Maureen is excited to bring on board more highly experienced scientists across all disciplines, who will continue to challenge each other to see in new ways as they unearth opportunities encoded in nature’s DNA.
Reflecting on Hexagon Bio’s growth and future opportunities, Dusan Perovic, Partner at Two Sigma Ventures who led our investment in Hexagon Bio, says, “We have been strong supporters of Maureen and Hexagon Bio since investing in their seed extension note, and have enjoyed the privilege of seeing Maureen build an incredible team and an impressive drug discovery platform, with a number of programs making their way to the clinic. One of the most important drivers of the company’s successes are Maureen’s personal traits as a ‘selfless leader.’ This is the quality which has enabled Maureen to build such a strong multidisciplinary organization, where technical talent is equally motivated, engaged and exceptional as the life sciences team.”
This conversation forms part of our Two Steps Forward series, where we profile founders who are pioneering the future.