From Lab Bench to Wall Street: UCSF Innovation Behind FDA-Approved Autoimmune Drug

The remarkable story of Rilzabrutinib, a UCSF discovery that defied the odds to fuel Principia Therapeutics’ IPO and deliver a breakthrough therapy.

When Principia Therapeutics launched its IPO in 2018, ringing the NASDAQ bell in celebration of its arrival on Wall Street, it marked a defining moment for the biotech company. Principia had captured the attention of investors with its promise of innovative therapies targeting autoimmune diseases, and its lead drug, Rilzabrutinib (later branded as Wayrilz) was poised to revolutionize treatment for patients with chronic autoimmune conditions.

But behind the glitz of the IPO lay a story of extraordinary perseverance, scientific discovery, and collaboration—a story that began in the academic labs of UCSF more than a decade earlier. For Rilzabrutinib to reach FDA approval in 2025, it had to overcome one of the most challenging paths in medicine: transforming a university invention into a marketable drug. The odds were stacked against it, with only a fraction of one percent of academic discoveries ever making it to patients.

This is the story of a long, complex journey, a rare success that underscores the immense difficulty and incredible rewards of drug discovery.

The Origin Story

The roots of Rilzabrutinib (RILL-zuh-BROO-tih-nib) trace back to the lab of UCSF chemical biologist Jack Taunton, who founded his research group in 2000 to explore innovative approaches to drug discovery. By 2005, a graduate student in Taunton’s lab, Mike Cohen, developed a novel chemical compound, a cyanoacrylate inhibitor, against Taunton’s initial advice. Despite skepticism, Cohen pursued the idea, creating a compound that targeted a kinase called RSK.

“I actually thought maybe this wasn’t such a great idea,” Taunton admitted in an interview. “I advised Mike to maybe not go down this road of making cyanoacrylates, but luckily Mike stuck to his guns and ignored me.”

In science, some of the greatest discoveries came either by accident, like penicillin, which was simply a mold that contaminated a Staphylococcus bacteria culture dish, inhibiting bacterial growth, or because a novice researcher can look at a thing with fresh eyes and see what the experienced eye has taken for granted.

Cohen, saw a new possibility, but the real breakthrough came when another graduate student, Iana Serafimova, discovered that these compounds formed a surprising reversible covalent bond with their target protein, a finding that challenged conventional wisdom about highly reactive chemistries. Published in Nature Chemical Biology in 2012, this discovery became the foundation for a new class of covalent inhibitors.

Postdoctoral researcher Jesse McFarland then applied this chemistry to Bruton’s tyrosine kinase (BTK), a key therapeutic target for autoimmune diseases. BTK inhibitors had previously been developed for cancer treatments, but McFarland’s work demonstrated their potential in chronic autoimmune conditions requiring higher selectivity and safety.

These discoveries laid the groundwork for Rilzabrutinib, and Professor Taunton reflected on how rare it is for academic research to reach this level of impact: “I would say that it’s pretty rare for an academic lab to generate chemical matter and have a patent application on a compound that covers a compound approved by the FDA.”

From Lab to Startup

In 2009, UCSF licensed the intellectual property surrounding Taunton Lab’s discoveries to Principia Therapeutics, a biotech startup founded by Jack Taunton and serial entrepreneur Richard Miller. Ellen Kats, a Technology Management Officer at UCSF at the time, negotiated the exclusive license agreement—the first she handled independently.

“God, it’s crazy,” Kats recalled. “You have to understand, it wasn't the first exclusive license that I worked on, but it was the first one that I negotiated as an independent portfolio manager, on my own.”

However, the early days of Principia, like any new company, were fraught with challenges. Kats recounted debates between the scientific and entrepreneurial founders, describing their initial collaboration as a “difficult marriage.” Despite these setbacks, Principia pivoted strategically in 2012, shifting its focus from JAK inhibitors to BTK inhibitors, a decision that proved pivotal to the company’s success.

“This is why we’re here,” Kats emphasizes the importance of UCSF’s role in enabling the transition from academic research to industry product. ”For situations like this, when the best-case scenario is you actually get a drug on the market that helps out a very specific patient population that has a high need.”

Scientific Innovation and Development

Rilzabrutinib’s mechanism of action, a reversible covalent bond targeting BTK, represented a groundbreaking approach to drug design. Unlike traditional covalent inhibitors, which form irreversible bonds, the reversibility of Rilzabrutinib’s chemistry allowed for greater precision and fewer off-target effects, making it ideal for treating autoimmune diseases without the severe side effects seen in cancer therapies.

Ken Jenkins, UCSF’s external patent counsel, played a key role in protecting the intellectual property behind this innovation. In 2011, UCSF filed a broad “genus” patent covering a class of chemical compounds, which Principia later optimized to create the specific drug compound.

“They knew what this compound was and were very jazzed,” Jenkins explained. “We were able to then construct a chemical genus in a patent claim form that covers the drug.”

This is common. Jenkins described academic research like a Venn diagram, with many segments included and overlapping. Once the company acquires the license, it then optimizes the science, revealing the precise compound it will work with.

Jenkins pointed out the rarity of an academic discovery making it all the way to FDA approval.

“It’s really hard to get a drug approved,” Jenkins said. “As patent counsel, when you see something you worked on, a patent where the drug is approved, it’s very exciting.”

Principia’s growth trajectory showcased the immense financial and logistical scale required to bring a drug to market. Over the course of several funding rounds, the company raised tens of millions of dollars before launching its IPO in 2018.

"It took 16 years,” Kats recalled the bell-ringing ceremony as a testament to years of hard work and perseverance. “No big deal... I mean, it really puts things in perspective. It's not an easy process."

In 2020, French pharmaceutical giant Sanofi acquired Principia for $3.7 billion, marking a major milestone in this scientific discovery’s journey to becoming a drug.

Impact and Validation

In 2025, two decades after Mike Cohen recognized the original cyanoacrylate inhibitor, Rilzabrutinib finally received FDA approval, bringing much-needed relief to patients suffering from chronic autoimmune diseases such as immune thrombocytopenia—a condition that causes dangerously low platelet counts. For Kats, the drug’s approval carried personal significance, as a close friend had suffered from the same condition.

“It actually feels really good,” Kats said. “This is a very validating moment. As a tech transfer officer, this is a best-case scenario; something you license actually turns into a technology that contributes to the greater public good.”

“The success rate is a fraction of 1%, Jenkins said. “It’s extremely rare for a chemical compound discovered in an academic lab to become an FDA-approved drug.”

Principia, the startup originally founded on a broader platform technology interested in many targets, took an extraordinary journey that ultimately focused on the BTK inhibitor.

“It turned out that BTK was the thing that was most exciting to the investors and to the scientists at Principia,” Taunton said. “They ran with BTK and developed not just Rilzabrutinib, but other compounds that target BTK.”

The Consequence of Persistence

The story of Rilzabrutinib is a testament to the power of collaboration between academia and industry. From the serendipitous discoveries in Jack Taunton’s UCSF lab to the entrepreneurial vision of Principia Therapeutics, and the global reach enabled by Sanofi, the journey illustrates the immense challenges and rewards of translating scientific innovation into life-saving therapies.

UCSF Innovation Venture has collaborated actively with Principia and Sanofi to manage the patent portfolio and license agreement. While the initial license agreement establishes the foundation, maintaining this partnership requires significant ongoing effort. Innovation officers, like Ellen Kats, worked closely with the licensee to ensure the intellectual property is strategically protected and compliant with the evolving requirements throughout the commercialization process of Rilzabrutinib, or Wayrilz, as it is currently labeled.

This is not just the story of a drug—it is the story of perseverance, creativity, and the people behind the science. As UCSF continues to push the boundaries of research and technology transfer, the success of Rilzabrutinib serves as an inspiration for what’s possible when science, business, and persistence align.