Five Questions with…Jason Pontin

Jason Pontin was decades into a career as a science and technology editor and publisher, when he entered the biotech world as a co-founder of Totus Medicines. Science became less theoretical and more personal for him after the death of his brother-in-law from a form of brain cancer in 2018. Today, he is driven by a desire to help scientist-entrepreneurs create life-saving medicines.

We talked with Jason about his transition from science and tech media to biotech, the potential for broad genome screening, and the impact Totus’ work will have in the future.

Tell me about how you moved from your career in publishing into the biotech/healthcare world.?

I was an editor at Red Herring magazine, and I then founded Acumen, a life sciences publication. In 2004, I moved to the MIT Technology Review, where I was the editor-in-chief and publisher for 14 years. While I was at MIT, I also led the MIT Enterprise Forum, their global entrepreneurial network, and I co-founded Solve, one of MIT’s venture capital platforms. I began talking to venture capital firms during this work, and eventually ended up as a senior partner at Flagship Pioneering. I’ve been at DCVC as a partner since 2021.?

How did you find out about Totus?

I took a meeting with the founder, Neil Dhawan, because I was interested in the chemistry. In one sense, Neil had come to the wrong guy. Flagship was doing no outside investment at all: their science was all internally generated. But at the same time, he’d come to the right guy. There was serendipity to Neil approaching me. He had come to someone whose journalistic background made him curious about new ideas. I had served on the board of the Children’s Tumor Foundation (CTF) for ten years, where we had worked on KRAS, the drug target Neil described in his paper in Nature. I also understood the chemistry he proposed, because CTF had pondered covalency, too. I helped Neil raise his seed round of $2 million, and then a $40 million Series A.?

You wrote a beautiful story in Wired about your brother-in-law’s brain cancer. How much does your personal connection to this work motivate your efforts at the day-to-day level?

It motivates me every day. Totus has a target called IDH1, which is responsible for a very large number of glioblastomas and astrocytomas, which is what killed my brother-in-law, the artist Joe Heaps Nelson. Flagship had founded a company named Agios that developed IDH1 inhibitors — but they couldn’t cross the blood-brain barrier and so weren’t appropriate for brain cancer.?I was powerfully motivated by the idea of using covalency to inhibit tumors for patients like my late brother-in-law.??

It’s too late for Joe, but I remember Scott Plotkin, head of neuro-oncology at Massachusetts General Hospital, telling me this: We are in a liminal stage of cancer medicine where we know almost everything about why someone gets cancer, but there’s no standard of care for many cancers. There are a large number of cancers with very well-validated targets, but we’ve got no good medicines to treat them. I was interested in working with Neil to use breakthrough medicinal chemistry to rapidly advance treatments for those cancers, rather than spending a decade or more generating biological insights that might find new targets.??

Tell me why you’re optimistic about the Totus platform.

We can screen the entire genome across hundreds of thousands, if not millions, of different compounds to find the precise chemistry that will target the gene we want to perturb. That is a distinctly useful and powerful breakthrough, and it’s the product not just of advances like machine learning and AI, but of accompanying innovations in high-throughput screening and medicinal and quantum chemistry. It’s not that we predict the winning lottery ticket for the right medicine for the right disease. It’s more like we already know the winning ticket.?

Totus’ breakthrough drug, TOS-358, was brought to trial within just two years. What does it say that the company was able to do that in that timeframe?

That’s nearly unprecedented. That tells me that TOS-358 can meet an urgent medical human need, which is to not just slow the growth of cancers caused by the PI3Kα oncogene, the most mutated oncogene, but to do so in multiple cancers, like lung cancer, colorectal cancer, breast cancer, and many more. It suggests that if we can do this in two years, we can do the same for a whole variety of other cancers and perhaps for a variety of currently intractable diseases, including neurodegenerative diseases. We have a genuine breakthrough and a once-in-a-generation CEO.