Why We Invested in Gilgamesh (Again)

One of the most exciting things about being a conviction investor is that we have the optionality to double down on our winners. This is not something that we consider lightly, as it clearly represents increasing our ownership, exposure, and …well… conviction in an investment. At Prime Movers Lab, when we do this, we bring in an additional partner who didn’t lead the original investment for fresh eyes and a fresh perspective to make sure that we still keep our wits about us when making these important allocations. As we considered doubling down on our original Series A investment, I was joined by my partner Gaetano Crupi Jr., a seasoned operator and experienced Series B investor to take a fresh look at Gilgamesh Pharmaceuticals. Together, what we saw more than convinced us that Gilgamesh was ready to be accelerated with further investment.

Since we first invested, CEO Jonathan Sporn and Co-founder/Head of Chemistry Andrew Kruegel have assembled an incredible team of seasoned biotech operators. With the addition of Yoni Falkson as COO, Laszlo Kiss as CBO & Head of Research, Gerard Marek as CMO, Zoe Hughes as VP Head of Biology, and William Leong as Head of CMC (just to name a few of the new personnel), we knew that Gilgamesh leadership had recruited a strong execution-oriented team to bring their programs forward. In addition to the core team members, they added Phil Skolnick to the board this year. Phil has substantial drug development experience, is the current CSO at Opiant, and was the former division director at NIH. Gilgamesh also recently announced that John Macor joined as a Senior Adviser. Macor most recently served as the Global Head of Integrated Drug Discovery at Sanofi and will be focused on serotonin and NMDA receptor targeting.

We always emphasize team and team development at Prime Movers Lab, as we believe top-functioning leadership is essential to any company’s success. But in the drug development world, great teams need great programs to work on and bring forward into the clinic. Again, Gilgamesh has used the last 18 months wisely, creating not just strong clinic-ready programs but a flywheel of novel drug development.

As described in their Nature Biopharma Dealmakers paper, Gilgamesh uses a platform approach leveraging a mix of in-vitro and in-vivo approaches to guide the selection of the most promising candidate compounds. Those approaches include machine-learning analysis of animal behavior and electrophysiology in collaboration with their academic partners. This engine of development is yielding results and has delivered massive opportunities for the company with the creation of intellectual property and novel compounds for either internal development or partnering. These new molecules are currently being evaluated and the most promising will be advanced to lead selection this coming year.

Most importantly, Series B funding fuels the rapid advancement of Gilgamesh’s two lead programs, GM-1020 and GM-2505 through Phase 1/1b safety and efficacy studies.

GM-1020 is a novel, patented, orally active small molecule antagonist of the N-methyl-D-aspartate (NMDA) receptor with potential rapid-acting antidepressant activity without adverse behavioral effects at therapeutic doses. Unlike IV ketamine and intranasal esketamine, GM-1020 is orally bioavailable. In preclinical models of depression, it demonstrates rapid and marked effects, while avoiding the typical side effects of ketamine/esketamine. These properties may make GM-1020 suitable for a new at-home use paradigm, which would be revolutionary in this molecule family for the treatment of depression.

GM-2505 is a novel, patented, small molecule, short-acting 5-HT2A receptor agonist/5-HT releaser with an expected rapid and durable antidepressant effect. Early preclinical work indicates that GM-2505 is likely to produce dramatic changes in the central nervous system. In humans, this may impact consciousness, perception, emotion, and cognition. GM-2505 was designed to have a much more rapid onset/offset than traditional 5-HT2A agonists, which may provide a reduced in-clinic time with the same “reset experience” efficacy demonstrated by traditional longer-acting molecules.

Both of these compounds will be in clinic by Q1 of 2023.

Given all of that progress, we are pleased to announce the closing of Gilgamesh Pharmaceuticals’ $39 million Series B financing, led by Prime Movers Lab. We are joined in this investment by Alumni Ventures, Palo Santo, Negev Capital, Route 66, JLS Fund, Satori Capital and Gron Ventures. Together, with Gilgamesh, we look forward to the arrival of these compounds into clinical trials and the continued work of their entire team to reshape the treatment of mental illness. There is much to do, but we are confident that Gilgamesh is leading the way.

Prime Movers Lab invests in breakthrough scientific startups founded by Prime Movers, the inventors who transform billions of lives. We invest in companies reinventing energy, transportation, infrastructure, manufacturing, human augmentation and agriculture.

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