Companies team up to ID biomarkers for cancer treatment in RDEB
Onconova and Pangea seek new ways to predict response to rigosertib
Onconova Therapeutics and Pangea Biomed are teaming up to identify biomarkers that can help predict a response to the experimental cancer therapy rigosertib in people with recessive dystrophic epidermolysis bullosa (RDEB).
Multiple clinical trials are underway to test rigosertib — developed by Onconova — as a potential treatment for squamous cell carcinoma (SCC) in individuals with RDEB, a rare disorder in which the skin tears and blisters easily when touched. RDEB patients are known to be at increased risk of SCC, which is an aggressive and potentially life-threatening form of skin cancer.
Pangea brings to the partnership its proprietary algorithmic platform, ENLIGHT, which uses artificial intelligence (AI) to help identify predictive biomarkers.
“Precision medicine is the future of oncology, but gaps in the industry’s current biomarker approaches overly narrow patient populations for promising drugs,” Tuvik Beker, PhD, CEO of Pangea, said in an Onconova press release.
“ENLIGHT goes beyond standard biomarkers to expand patient populations for targeted therapies, in addition to surfacing new biomarkers for existing drugs,” Beker said.
Seeking biomarkers for rigosertib treatment
An early Phase 1 clinical trial (NCT04177498) in the U.S. is evaluating both oral and intravenous (into-the-bloodstream) formulations of rigosertib in people with RDEB and SSC. The study began in 2021 at Thomas Jefferson University, in Philadelphia.
Another early clinical trial (NCT03786237), this one in Europe, is testing rigosertib in RDEB-associated SSC, with two centers planned — one in London and the other in Salzburg, Austria.
Rigosertib is thought to work by blocking the activity of polo-like kinase 1 (PLK1), a protein that’s involved in cell division. Increased PLK1 levels is a feature of SSC associated with RDEB, and is thought to promote the uncontrolled cell division that drives tumor growth.
The therapy candidate also is believed to modulate another molecular signaling pathway involved in regulating cell growth. Called the PI3K pathway, it is hyperactivated in most cancers.
“Rigosertib’s ability to potently inhibit PLK1 and modulate the tumor immune microenvironment confers broad potential to treat a range of solid cancers,” said Steven M. Fruchtman, MD, president and CEO of Onconova.
We’re hopeful our platform can help Onconova accelerate rigosertib’s successful development in a variety of difficult-to-treat cancers.
Under the new agreement, the companies will be leveraging Pangea’s ENLIGHT analysis platform to identify biomarkers of response to rigosertib. The platform uses AI to assess the molecular context in which therapies operate and build functional genetic models of how different genes interact with each other.
Specifically, the companies specifically plan to use the ENLIGHT platform to analyze relationships with PLK1, allowing them to identify biomarkers that can be used to detect whether rigosertib is blocking the protein as expected.
“By leveraging Pangea’s AI platform to identify predictive biomarkers of response to rigosertib, we aim to inform a precision medicine approach to selecting additional PLK1-dependent tumors and other indications for its potential evaluation,” Fruchtman said. “We believe this approach will increase the probability of success for rigosertib’s future development programs.”
Under the terms of the agreement, Onconova will retain all rights to rigosertib and also will own any intellectual property that results from the partnership.
“We’re hopeful our platform can help Onconova accelerate rigosertib’s successful development in a variety of difficult-to-treat cancers,” Beker said.
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