UH and CWRU Biotech Startup Rodeo Therapeutics Corp. Sold to Amgen Inc.

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Drug at heart of deal, developed in Cleveland, could make recovery from bone marrow transplant quicker and safer, among other applications

Innovations in Cancer | Summer 2021

Research that began 10 years ago at University Hospitals Seidman Cancer Center and Case Western Reserve University School of Medicine, supported along the way by the Harrington Discovery Institute at University Hospitals, has resulted in a major pharmaceutical company investing in an important discovery in regenerative medicine, bringing the possibility of a breakthrough drug one step closer.

Sanford Markowitz, MDSanford Markowitz, MD

In 2015, UH Seidman oncologist Sanford Markowitz, MD, PhD, and oncologist Stan Gerson, MD, now Interim Dean of the School of Medicine and Director of the Case Comprehensive Cancer Center, reported in Science that their team had identified a small molecule that inhibits 15-PGDH, an enzyme implicated in tissue damage.

“We identified a pathway that inhibits the ability of stem cells to respond when tissues are damaged,” Dr. Markowitz says. “That included how the bone marrow responds in the setting of having to recover after a bone marrow transplantation. We set out to try to find ways to reverse the effects of that pathway.”

Working with collaborators at the University of Texas Southwestern, Dr. Markowitz, Dr. Gerson and team evaluated 250,000 candidate chemicals, finally identifying SW033291 as an agent that could inhibit 15-PGDH in an animal model. As their research demonstrated, SW033291 accelerated hematopoietic stem cell reconstitution in mice following bone marrow transplant, while also promoting tissue regeneration in mouse models of colon and liver injury. In fact, SW033291 was able to cut liver regeneration time in half for mice undergoing liver surgery, heal the ulcers of ulcerative colitis and reverse idiopathic pulmonary fibrosis in an animal model.

“This really opened up the door to what we think is a platform technology for regenerative medicine,” Dr. Markowitz says. “It has clear applications to oncology, but also clear applications to diseases in addition to cancer.”

Recognizing the potential, the Harrington Discovery Institute at University Hospitals named Dr. Markowitz a Harrington Scholar and supported this research with grant money and valuable drug development mentoring from its Therapeutics Development Center Advisors.

“Harrington Discovery Institute provided the initial grant funding for the project,” says Jonathan Stamler, MD, the organization’s president, holder of the Robert S. & Sylvia K. Reitman Family Foundation Distinguished Chair in Cardiovascular Innovation and Professor of Medicine and Biochemistry at the School of Medicine. “The scholar award also included engagement with pharmaceutical veterans, who provided insight about how to de-risk the technology and attract additional investment. Our funding allowed Dr. Markowitz to attract additional support from the venture community and an NIH program aimed at accelerating innovation.”

Two years later, Dr. Markowitz had the opportunity to present to the School of Medicine’s Council to Advance Human Health, a group of industry experts who volunteered their time to assess the commercial promise of faculty research and provide advice regarding potential investments. The advisers said Dr. Markowitz’s efforts “were on a good track,” which led to additional financial support, as well as engagement from the School of Medicine’s chief translation officer and Technology Management Office.

“With this help, we were able to take that first chemical that we had identified and make it more drug-like – more soluble, easier to absorb, something that would last in the body,” adds Dr. Markowitz. “We worked with the Harrington Discovery Institute group for two years improving the drug. In 2017, that work enabled us to form a startup company called Rodeo Therapeutics."

It is this startup company that has now been sold to Amgen Inc.

“Rodeo's lead 15-prostaglandin dehydrogenase (15-PGDH) modulators have generated compelling data in extensive preclinical studies and have clinical potential in multiple indications,” says Raymond Deshaies, PhD, senior vice president of global research at Amgen. "The enzyme 15-PGDH plays a key role in many disease-relevant processes such as stem cell self-renewal and epithelial barrier repair. Given the encouraging preclinical data to date, we are excited about the opportunity to develop a novel therapy with potential in a range of important inflammatory disease indications,"

Dr. Markowitz says he’s excited at what comes next for this promising therapy.

“With Amgen’s technical acumen, their scientific resources, their clinical resources and their financial ability to support the further development of this drug, we're really excited and enthusiastic,” he says. “We now think this idea has an excellent chance of moving forward into human trials.”

Dr. Markowitz says he expects the latest generation of the 15-PGDH modulator to be tested first in patients with ulcerative colitis, since they are the most numerous among those the agent could help treat. However, he says he’s hopeful that because the drug is already being developed, it will also be available eventually for people with less common conditions, such as cancer patients undergoing a bone marrow transplant, or patients with pulmonary fibrosis.

“For individuals who are having a bone marrow transplant, we'd like to make the recovery quicker and safer,” he says. “It will take us first developing the use of the drug for a large number of patients with more common diseases so that we can then additionally bring it to other individuals with less common conditions, but who can also benefit from the treatment.”

As he looks ahead, Dr. Markowitz is grateful for the support from the Harrington Discovery Institute in helping get the project to this point, dating back from that groundbreaking paper in Science six years ago.

“Harrington Discovery Institute has the experts, and they provided us the roadmap,” he says. “You publish a paper in a top tier journal like Science, and you expect that the world's going to come running to your door. But it doesn’t work that way. The folks that really do this realize how big the gap is between that first discovery and creating an actual drug. So it was Harrington Discovery Institute who enabled us to bridge that gap, bridge that chasm. Now we’ll see what happens next.”

Contributing expert:

Sanford Markowitz, MD, PhD
Hematologist/Oncologist
UH Seidman Cancer Center
Markowitz-Ingalls Professorship of Cancer Genetics
Case Western Reserve University School of Medicine
Case Comprehensive Cancer Center

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