Journey to multi-million dollar Amgen acquisition required curiosity, collaboration and commercial expertise
Twenty years after starting a cancer fellowship at the National Institutes of Health (NIH), Sanford “Sandy” Markowitz published a groundbreaking study regarding the role of a gene called 15-PGDH in suppressing colon cancer.
Seventeen years later, a start-up based on his work with that very same gene—but having nothing to do with cancer—sold for $55 million.
The story of how a 2004 discovery involving one disease led to a valuable venture aimed at others underscores three factors essential to successful clinical innovation: curiosity, collaboration and commercial expertise.
“You just can’t do this without people who are smart and skillful,” Markowitz said. “Without them, it would have died.”
Without his own inquisitiveness, though, it wouldn’t have even begun.
What if?
While identifying the significance of 15-PGDH in beating back colon cancer was impressive enough on its own, Markowitz found himself thinking about other implications of the finding. If this gene could inhibit malignant cells from spreading, could it somehow be tackled in such a way that it supported the growth of good ones?
“We just rolled the dice with the idea that maybe not having a lot of [15-PGDH] would help tissue grow back,” Markowitz said. “We ran out and tested it in a mouse and… right away we knew we had something.”
Recognizing the promise of the idea was an important first step, but paled compared to the challenge of assessing thousands of options for the next one—an approach that could actually deliver on the perceived potential.
After a few years of initial efforts in his own lab, Markowitz’s team was far enough along to turn to one with more specific expertise; with assistance from a former Case Western Reserve colleague now at the University of Texas Southwestern Medical School he found it. Representatives from both institutions came together to test 250,000 different molecular candidates until finding one that acted on 15-PGDH as hoped.
Next came five more years of work in Cleveland—including collaboration with the lab of Interim Dean Stan Gerson, director of the Case Comprehensive Cancer Center—to tweak and refine the selected molecule (known as SW033291) so that it would catalyze repair of damaged tissues, or even support entirely new growth.
“It was just one fun scientific breakthrough after another,” Markowitz recalled. “The question was, how to make it a drug.”
The next step
In 2012 University Hospitals announced a $50 million gift from the Harrington family to assist physician scientists in bringing their research out of the lab and into settings where their discoveries could benefit people in need. The funding supported creation of the Harrington Discovery Institute (HDI), which that same year announced an annual grant competition to support ‘scholar innovators’ in turning their scientific breakthroughs into solutions for patients. Markowitz applied, and found himself among the program’s 10 inaugural recipients.
“Our mission at University Hospitals is ‘To Heal. To Teach. To Discover’ and we strongly support our own community,” said Daniel I. Simon, UH’s chief clinical and scientific officer.
Added Jonathan S. Stamler, HDI’s president: “… we saw the potential for impact.”
The Harrington investment ($150,000 over two years) allowed Markowitz to attract additional funding from an NIH award program that aimed to ‘accelerate innovation. But the Harrington grant also included engagement with pharmaceutical veterans, who provided advice and insight about how to attract additional investment. “[They] laid out a roadmap of the milestones we would need to meet.”
Two years later, Markowitz had the opportunity to present to the medical school’s Council to Advance Human Health, a group of industry experts who volunteered their time to assess the commercial promise of faculty research and advise Vice Dean for Research Mark Chance regarding potential investments. The advisers said Markowitz’s efforts “were on a good track,” which led to additional financial support, as well as engagement from Bill Harte, the school’s chief translation officer and Michael Haag, executive director of the university’s Technology Management Office, which supports efforts to commercialize research.
Sharing signs of success
In 2015 Markowitz, Gerson and UT Southwestern collaborators Joseph Ready and James Willson published findings in Science that showed their SW033291 molecule had helped repair and regenerate damaged tissue in the bone marrow, colons and livers of mice.
The article drew global attention and helped kickstart months of meetings—or, as Markowitz put it, “auditions” with venture capital companies and incubators.
“This is very much a stepping-stone work in progress,” Gerson, also a UH physician. It is “an example of the long haul of drug discovery and development…It’s a huge sequence of effort and events.”
Two years later, Markowitz, Gerson and Ready announced the launch of Rodeo Therapeutics, along with $5.9 million of Series A financing coordinated by venture capital firm Accelerator Life Science Partners. Investors included AbbVie, Alexandria Venture Investments, Arch Venture Partners, Eli Lilly & Co., Johnson & Johnson Innovation – JJDC Inc., Watson Fund, L.P., WRF Capital and WuXi AppTec.
The funding provided the resources necessary to advance the research to a point where it would appeal to a major pharmaceutical company like Amgen. In addition to the initial $55 million paid to acquire Rodeo, and rights to the patents of Markowitz, Gerson and Ready, plus rights to related technology from medical school faculty members Andrew Pieper, Amar Desai and Derek Taylor, the deal includes development milestones whose success could add $666 million additional to the total for stakeholders.
“It was truly a team effort,” said Markowitz, who will continue to be involved in the work as a consultant to Amgen. “Every link in the chain was vital.”