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University of Michigan Innovation Partnerships
University of Michigan Innovation Partnerships

Venture Accelerator: Mekanistic Therapeutics


Mekanistic Therapeutics, a startup company focused on the development of cancer therapeutics, will soon move into the U-M Innovation Partnerships Venture Accelerator, where company founders Drs. Judith Sebolt-Leopold and Christopher Whitehead will progress with their clinical trial development and fundraising efforts.

In their University of Michigan lab, Sebolt-Leopold and Whitehead, discovered and designed small molecules that can selectively hit two cancer targets simultaneously with reduced risk of drug-drug interactions. Sebolt-Leopold has 20+ years in the pharmaceutical industry and a strong track record of advancing oncology drug candidates into the clinic. Specifically, her experience includes pioneering the discovery and development of MEK inhibitors, now in clinical use for the treatment of melanoma. Whitehead, whose computational chemistry expertise complements the cancer biology expertise of his co-founder, has almost 20 years of research and development experience in biotechnology and pharmaceutical companies. The pair first worked together at Pfizer on the MEK inhibitor research team.

Working together again at University of Michigan, they share a common vision for the need to design more effective drugs to circumvent resistance mechanisms commonly encountered with currently available kinase-targeted agents. “The mission of Mekanistic Therapeutics is precision polypharmacology,” Whitehead explained.

The team discovered and developed a molecule to selectively and concurrently impair EGFR and PI3K signaling in cancer cells. EGFR and PI3K are frequently found to be concurrently dysfunctional in a variety of tumor types, leading to poor prognosis. Their lead compound, MTX-211, represents a first-in-class molecule that selectively and potently inhibits both of these critical oncogenic kinases, which are known to drive progression in a number of tumor types, including colorectal cancer. Currently, there are no approved treatments for patients diagnosed with metastatic KRAS mutant colorectal cancer. MTX-211 is innovative because it attacks KRAS oncogenic signaling using two independent mechanisms, serving effectively as a combination approach in a single molecule.

Mekanistic recently received a STTR grant that supports its move into the U-M Innovation Partnerships Venture Accelerator. Sebolt-Leopold and Whitehead previously received translational funding from MEDC’s MTRAC program, which is co-managed by FFMI and U-M Innovation Partnerships, as well as funding from the U-M Cancer Center to identify a lead compound. They are currently working with Innovation Partnerships mentors-in-residence with expertise in drug development and regulatory strategy to develop a commercialization plan to take their lead compound into human clinical trials and broaden their pipeline.