Ep207: Jason Coloma on Genetic Medicines for Kidney Diseases

Episode Summary

Executive Summary: Jason Coloma traces Maze Therapeutics from its genetics-first origins to a public company focused on kidney disease. He describes how immigrant upbringing, Jesuit training, and years in biotech shaped his leadership, and how Maze weathered financing challenges and an FTC-blocked Sanofi deal to build resilience. The company’s lead programs now target APOL1 and SLC6A19, with a near-term clinical readout ahead.

Main Topics: Coloma’s personal and educational path (Priority: 5/5): He grew up in an immigrant, military family, gravitated toward science, rejected a military academy path, and was shaped by Jesuit values, Berkeley training, and an MBA at Dartmouth that helped bridge science and business. Early biotech exposure at Cytokinetics (Priority: 4/5): His first industry role showed him how biotech combines science, medicine, and business, and introduced him to the value of partnerships, business development, and company-building. Roche/Genentech and the importance of culture (Priority: 4/5): Working in biotech business development and later in Basel gave him a close view of the Roche-Genentech integration, international drug development, and how large companies preserve innovative culture. Third Rock and company creation (Priority: 5/5): At Third Rock, he helped build multiple data- and genetics-driven ventures, learning venture-style company formation and gaining exposure to the convergence of data, diagnostics, and therapeutics. Maze’s genetics-driven kidney strategy (Priority: 5/5): Maze was built around using human genetics, large datasets, and protective variants to identify drug targets for complex kidney diseases, especially APOL1 and SLC6A19. FTC intervention and resilience around Pompe disease (Priority: 5/5): Maze’s Sanofi Pompe partnership was blocked on antitrust grounds, forcing a strategic reset; the company recovered by securing another partner and strengthening its culture and contingency planning. Clinical and regulatory outlook for APOL1 kidney disease (Priority: 5/5): Coloma explains why kidney disease is attractive despite historical trial challenges, citing more flexible biomarkers, growing industry interest, and an emerging regulatory pathway that could enable Maze’s late-stage progress.

Key Arguments: Human genetics is the best foundation for discovering therapies that can meaningfully alter disease biology, especially in heterogeneous conditions like kidney disease. Companies should reduce risk by pairing novel biology with proven modalities; Maze therefore focused on small molecules rather than layering in modality uncertainty. Complex diseases can be subdivided using large biobank-scale datasets, enabling target discovery from both disease-causing and protective human variants. The FDA and kidney-disease community are becoming more open to biomarker-driven development, making the field more investable and more tractable than it was a decade ago. Setbacks like the Sanofi/FTC event can strengthen a company if it develops contingency plans, leadership cohesion, and strategic flexibility. Maze’s long-term aspiration is not just a pipeline, but an enduring company that can discover, develop, and ultimately commercialize medicines. Industry momentum around kidney disease is rising, which helps validate Maze’s thesis and improves the odds of both regulatory clarity and capital inflow.

Data Points: Immigration background: Immigrated from the Philippines in the 1960s - Coloma described his parents’ move to the U.S. and the resilience of an immigrant family Military academy admission: Accepted to the Air Force Academy but declined - He said he chose not to follow his father’s path into the military MBA location: Dartmouth - He pursued an MBA to build business skills alongside science Cytokinetics public offering: $75 million - He recalled Cytokinetics going public during his early industry career Roche acquisition timeline: 2009 - He noted Roche had completed its acquisition of the rest of Genentech around that time Basel stint duration: A little over 5 years - He worked at Roche headquarters in Basel for more than five years Maze founding capital: $190 million - He said the company was launched with significant Series A financing Maze size at his CEO transition: Below 20 people / about 20–25 people - He took over as CEO when Maze was still a very small organization Kidney disease prevalence: 37 million people in the U.S. - He cited the size of the chronic kidney disease population APOL1 clinical timing: Phase 2 data expected later this year and early 2027 - He discussed the expected readouts and regulatory relevance Dialysis burden: A couple of days a week - He used this to describe the treatment burden for patients on dialysis Kidney innovation drought: A whole decade without a new approval - He referenced the historical stagnation in kidney drug development ASN industry growth: From a handful of posters to ~8–10x more publications - He described the expansion of industry and academic attention at nephrology meetings Partner replacement timeline: About six months - He said Maze found a new Pompe partner relatively quickly after the Sanofi deal collapsed

Pivotal Quotes: "How do you think about more complex diseases? And are there ways to actually use genetics plus... tools like single-cell genomics ... to better understand, can we start to segment or better understand subpopulations of more complex diseases so that we can develop more medicines?" — Jason Coloma: Explaining the founding idea behind Maze Therapeutics "You don't want to compound risk, novel biology with novel modality, probably not a good recipe for value creation." — Jason Coloma: Why Maze chose to focus on small molecules for genetically validated targets "If we can phenocopy that with a small molecule, well, we might be able to help some people." — Jason Coloma: Describing the APOL1 protective-variant strategy

Implications: Maze’s story suggests kidney drug development is becoming more scientifically and regulatorily viable. If APOL1 and SLC6A19 succeed, genetics-led, small-molecule discovery could become a repeatable model for complex diseases and an important validation of biotech resilience.