Cure
Overview
Mathai Mammen, MD, Chairman, CEO, and President of Parabilis Medicines, shares how great biotech founders decide which diseases are worth pursuing, and why problem selection shapes everything that follows.
Long before a drug enters a clinic, most biotech companies have already made their biggest bet: which disease is worth a decade of work.
Mathai Mammen, MD, learned that lesson early. Looking back on his career, from founding a startup out of his PhD work to leading global R&D at Johnson & Johnson, he knows a thing or two about where things tend to go wrong. Founders tend to fixate on platforms, hires, and fundraising. Far fewer spend real time pressure-testing the one choice that determines everything that follows.
In drug discovery, that decision isn’t easily reversed. Once a problem is chosen, the science, the timeline, and the company’s future tend to fall in line behind it. The question stops being how ambitious the idea sounds and starts being whether it’s the right one to commit to at all.
View the entire lesson of our Concept to Cure course: Product Development with Mathai Mammen. All lessons available exclusively to Cure members.
Starting Without a Playbook
Mammen founded Theravance Biopharma straight out of his doctoral work at Harvard University. He didn’t have a roadmap. He had ideas, some conviction, and a loose plan shaped by conversations with mentors. When he took those ideas to investors, the response was a nearly unanimous “no.”
Friends and family questioned why he’d walk away from a stable path to pursue something so uncertain. In retrospect, Mammen admits he didn’t fully know what he was doing. But persistence mattered. One investor eventually said yes. A $5 million Series A was enough to get the company moving and turn uncertainty into momentum.
That early struggle crystallized a belief he still holds, choosing the right problem is everything.
What Makes a Problem Worth Solving
In Mammen’s view, good problem selection comes down to three hard questions.
First, will this medicine actually matter by the time it reaches patients? Drug development lives in the future. Founders have to anticipate what treatments will exist years from now and whether their approach will still fill a real gap.
Second, can you realistically get there? Every program faces technical hurdles, often dozens of them. Biology is unforgiving. A strong problem choice includes a credible reason to believe those barriers can be overcome, not just optimism.
Third, will investors understand the value along the way? Capital has its own timelines. If investors can’t see how progress translates into value over the next few years, the science alone won’t carry the company.
Too often, he says, founders don’t spend enough time immersed in patient reality, understanding not just the disease, but the options patients have today and the ones they may have tomorrow.
Fewer Bets, Bigger Swings
Mammen says success rarely comes from running dozens of programs. It comes from choosing a small number of problems that truly matter and committing to them fully. Life is short. Incremental advances add up, but they don’t always justify the personal and professional cost of building a company from scratch.
At Parabilis Medicines, that philosophy shaped the company’s strategy from the beginning. Rather than chase crowded targets, the team focused on protein interactions long considered unreachable, including beta-catenin signaling in cancer. Their technology created a real barrier to entry, something others couldn’t easily replicate.
Equally important, they invested early in defining the right patients. By shaping the clinical path before trials began, they aligned the science with the people most likely to benefit. The result, Mammen notes, is something rare in medicine, consistent patient responses driven by disciplined problem choice.
Concept to Cure Video Series
We are proud to introduce Concept to Cure, our 12-part video series built for healthcare founders and operators turning breakthrough ideas into real-world impact.
Across these expert-led lessons, biotech CEOs, venture investors, and policy leaders share the frameworks and hard-won lessons that move innovations from early concept to clinic and beyond.
From validating your market and building investor-ready business models to navigating FDA approvals, scaling commercialization, and leading high-performing teams, each episode distills the practical insights entrepreneurs need most.
Concept to Cure lessons are available exclusively to Cure members.
