President and CEO of Totus Medicines, betting a covalent-chemistry library and a machine-learning engine can hit the targets the industry gave up on.
There is a specific kind of stubbornness required to spend a career on the parts of biology that don't cooperate. Some proteins fold in ways that leave nothing for a drug to grab. The industry calls them undruggable and moves on. Nassim Usman moved toward them. As President and CEO of Totus Medicines, a clinical-stage company in Emeryville, California, he runs an operation whose entire premise is that "undruggable" was always just shorthand for "we haven't done the chemistry yet."
His lead molecule, TOS-358, binds covalently to a single cysteine residue on PI3K-alpha - a cancer target that has frustrated drug hunters for years - and holds on more than 95% of the time. That is not a marketing number. It is a chemist's number, the kind you can only appreciate if you once spent nights coaxing a reaction to completion. Usman spent those nights. He has the PhD to prove it, and the scar tissue.
*Early Phase 1b, TOS-358 + fulvestrant, HR+/HER2- breast cancer, ESMO Breast 2026. Early-stage data.
Usman took the top job at Totus in December 2023, the same day the company announced its $66 million Series B led by DCVC Bio. He did not arrive for the title. By his own account he arrived for the machine that co-founder Neil Dhawan and the team had built.
That machine is OmniDEL - a DNA-encoded covalent library platform married to machine learning. In plain terms: instead of testing drug candidates a few at a time, Totus can screen billions of covalent molecules against thousands of protein targets at once, then let the models sort the signal from the noise. The output is a shortlist of molecules that permanently latch onto their target instead of drifting off. For hard targets, permanence is the whole game.
Within roughly a year of Usman taking the chair, that platform's lead output was in human trials. By 2026 the company was standing on stage at oncology congresses in Europe presenting data.
Company
Totus Medicines
Role
President & CEO (since Dec 2023)
HQ
Emeryville, California
Lead drug
TOS-358, covalent PI3K-alpha inhibitor
Platform
OmniDEL - DNA-encoded covalent library + ML
Neil and the entire team at Totus have built an extraordinary platform that has the potential to transform small molecule discovery.
Most drugs bind their target the way a hand rests on a doorknob - temporarily. Covalent drugs weld themselves on. That permanence lets you use lower doses and avoid flooding the body with drug, which is where a lot of side effects come from. The trick is aiming the weld precisely. Totus does it by targeting a cysteine on PI3K-alpha that stays reachable across the mutations that cancers throw at it.
DNA-encoded libraries let Totus test enormous chemical space in a single experiment instead of one plate at a time.
TOS-358 latches onto a single residue that stays accessible across helical and kinase-domain PI3K-alpha mutants.
Sustained target coverage at clinically relevant doses - without the high plasma peaks that drive off-target trouble.
Read his resume and a pattern appears: Usman keeps joining companies right when the science gets hard, and he keeps building ones that either break through or get bought. Sirna went to Merck. Principia went to Sanofi. Catalyst became Gyre, where he still holds a board seat. The bench chemist became an operator, then a venture capitalist, then an operator again.
The companies attached to Usman's name have a habit of getting acquired. It is not luck so much as taste - a preference for hard science that larger players eventually want to own. Below, a rough map of where his career has intersected with the industry's dealmaking.
Illustrative. Bar lengths are editorial, not financial figures.
McGill University
B.Sc., Organic Chemistry
McGill University
Ph.D., Organic Chemistry
MIT
Post-doctoral fellowship
Two degrees in the same demanding discipline, at the same institution, followed by a postdoc at one of the toughest chemistry environments on the planet. He did not shortcut the foundation. It shows in how he talks about molecules - as things you earn, not things you order.
Our life's work is to save lives.
From drawing molecules at a bench to running the company that wants to drug the undruggable.
One chemist. Three CEO chairs. A platform that screens billions of molecules at once.
TOS-358: the first and only covalent PI3K-alpha inhibitor in the clinic.
Sirna to Merck. Principia to Sanofi. He keeps building biotechs that break through.
He joined Totus for the platform, not the title. Then he took it into the clinic.
His whole career is one long argument for working on the hard targets.