He spent 28 years at Bristol Myers Squibb turning molecular intuition into drugs that saved lives. Now he's chasing the proteins everyone else wrote off as unreachable.
JOEL BARRISH — PRESIDENT & CEO, AVILAR THERAPEUTICS
Somewhere in the late 1990s, Joel Barrish helped make a molecule that would eventually save hundreds of thousands of lives. SPRYCEL - dasatinib - became one of the most important drugs in CML treatment, a kinase inhibitor that hit the target BCR-ABL even in patients where the original generation of therapy had stopped working. It had Barrish's fingerprints on it. So did forty-some patents and a stack of papers that would take most people a decade to produce.
That's the kind of career that earns you a comfortable VP title and a long runway to retirement. Barrish chose a different exit. After almost three decades at Bristol Myers Squibb - rising to VP and Global Head of Discovery Chemistry - he walked toward the frontier rather than away from it.
First came Achillion Pharmaceuticals, where he took the EVP and Chief Scientific Officer role and dove into Factor D inhibitor research. Then Jnana Therapeutics, which he co-founded and built into a platform company around RAPID, a chemoproteomic system for locking onto the proteins that had always been considered too structurally featureless to drug. He was eventually promoted to President and Chief Scientific Officer there.
"With limited portfolios, smaller biotech firms must take more risks - which paradoxically fosters greater innovation."- Joel Barrish, in conversation with Forbes, 2017
And then, almost in parallel, he started building the thing that would become his defining bet: Avilar Therapeutics.
The insight at Avilar is specific and deceptively simple. Most of the excitement in protein degradation - PROTACs, molecular glues, the whole targeted degrader revolution - works on proteins inside the cell. But the human body is full of disease-causing proteins that live outside it: circulating in blood, anchored in membranes, floating where no PROTAC can reach them. Barrish built Avilar around the question of what happens if you route those proteins through the cell's own endolysosomal trash system and destroy them there.
The answer is two platforms. ATAC - ASGPR-Targeting Chimeras - recruits the asialoglycoprotein receptor, a natural scavenger that liver cells use to sweep glycoproteins out of circulation. Couple your disease target to an ATAC molecule, and the receptor internalizes it, the endosome swallows it, the lysosome digests it. Gone. MTAC - the M6PR-Targeting Chimera version - extends the same logic to mannose-6-phosphate receptors, widening the net to a new set of targets.
It's an elegant piece of biology turned into a drug discovery engine. And it took the kind of scientist who had spent three decades watching which molecules actually get swallowed, which ones survive the gut, which ones make it to clinic, and which ones quietly disappear - to see how it could work.
After 28 years at BMS, Barrish's fingerprints are on some of pharma's most consequential recent approvals. These aren't legacy compounds gathering dust - they're actively being prescribed right now.
Co-invented at BMS for Chronic Myeloid Leukemia. A second-generation kinase inhibitor effective against patients who had become resistant to imatinib. Became a multi-billion dollar oncology franchise and a textbook example of rational drug design.
Oncology • CML • ALLAn oral TYK2 (tyrosine kinase 2) inhibitor for plaque psoriasis and other autoimmune conditions. Its regulatory allosteric mechanism of action - targeting the pseudokinase domain rather than the active site - represented a novel approach to kinase selectivity that Barrish's teams helped pioneer.
Autoimmune • DermatologyDeveloped through the DARA (Dual-Acting Endothelin Angiotensin Receptor Antagonist) concept that Barrish's team advanced. Approved for IgA Nephropathy - a rare kidney disease with limited treatment options. A rare example of a single molecule successfully hitting two therapeutic targets simultaneously.
Nephrology • IgA NephropathyThe central claim at Avilar is not incremental. It's this: the universe of disease-relevant proteins just got dramatically larger, because you no longer need the target to be inside a cell.
Recruits the asialoglycoprotein receptor (ASGPR), a high-capacity scavenger expressed on hepatocytes. ASGPR naturally cycles continuously between the cell surface and endosomes - Avilar's ATACs exploit this trafficking loop to pull extracellular and circulating disease proteins into the lysosomal degradation pathway. Particularly powerful for autoimmune, neurological, and cardiovascular targets.
A complementary platform built around the mannose-6-phosphate receptor (M6PR). Avilar's proprietary M6PR ligands open access to a wider and distinct set of protein targets compared to ATAC, extending the degradation concept to diseases where ASGPR-mediated approaches have limitations. Together, ATAC and MTAC represent a modular toolkit for extracellular proteome control.
Barrish's career reads like a guided tour through three eras of drug discovery. He started at Hoffmann-La Roche when combinatorial chemistry was the future. He rose through BMS when structure-based drug design matured into a reliable machine. And he built companies in the era when platforms - not individual drugs - became the unit of value.
The throughline is chemistry. His Ph.D. at Columbia, under Professor W. Clark Still (the same Clark Still who gave chemistry Still-Gennari olefination and the MacroModel molecular mechanics software), was a training in the kind of synthetic rigor that turns abstract structures into real molecules. That discipline never left him, even as the surrounding technology evolved around it.
When he left BMS in the mid-2010s, it wasn't escape velocity. It was gravitational pull - smaller companies move faster, carry less ballast, and have no choice but to bet on bold science or cease to exist. In a 2017 Forbes interview, he put it directly: at a small biotech, every employee is essential. That accountability creates something that scale struggles to manufacture.
Avilar's seed round is one of the largest in extracellular protein degradation. The investor syndicate reads like a who's-who of strategic biotech money, including pharma-affiliated funds with direct interest in the biology.
There's a particular advantage that comes from spending 28 years inside one of the world's largest pharmaceutical R&D engines. You see exactly which parts of the drug discovery machine work because of scale - and which parts get worse because of it. When Barrish describes small biotech culture, he's not romanticizing the scrappiness. He's identifying a specific mechanism: constraint forces prioritization, and prioritization forces bets.
At BMS, he managed more than 100 projects simultaneously across multiple therapeutic areas. At Avilar, with 25 people, every project is visible, every decision is immediate, and there's no organizational layer between the scientist and the strategy. The ATAC and MTAC programs aren't hedged portfolios. They're concentrated conviction bets from someone with enough pattern-matching experience to know exactly what he's betting on.
"Doors are always open for employees to approach leadership in small companies."- Joel Barrish
His simultaneous roles - CEO at Avilar, Venture Partner at RA Capital, scientific advisory board member at Adcendo, Nimble Therapeutics, and Kojin Therapeutics - are not scattered attention. They're the operating model of the new biotech scientist: someone who builds companies, funds companies, and advises companies all at once, cross-pollinating ideas across the portfolio.
The protein degradation field made its name on intracellular targets - the proteins inside cells that drive cancer, neurodegeneration, and inflammation. PROTACs, molecular glues, targeted degraders of every variety took aim at the roughly 20,000 proteins the cell manufactures for its own internal use. It was a genuine revolution. It also left out an enormous portion of the biology that drives disease.
Proteins that circulate in blood. Proteins embedded in cell membranes. Proteins that the body secretes into extracellular space. These are targets for some of the most consequential diseases in medicine - autoimmune conditions, cardiovascular disease, neurodegenerative disorders - and the existing degrader toolbox largely couldn't reach them.
Barrish looked at that gap and built a company specifically to close it. ATAC and MTAC don't just extend an existing concept - they create an entirely new category of therapeutic modality. The bifunctional molecule that physically links a disease target to a recycling receptor, sends it into the cell, and lets the lysosome do the rest.
It's the kind of idea that only makes sense once you've spent three decades thinking about how drugs actually behave in biological systems. About what gets internalized and what doesn't. About receptor trafficking and endosomal pH and the thousand small physical facts that determine whether a molecule ever becomes a drug. Joel Barrish has been accumulating those facts since his days in Clark Still's lab at Columbia. Avilar is what you build when you've finally collected enough of them.