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One of the challenges of treating cancer is the ability of cancer cells to mutate, which leads to resistance to currently available therapies. Theseus Pharmaceuticals has spent the past two years quietly developing a way to overcome this drug resistance and it picked one of the biggest cancer conferences of the year to unveil its technology, along with $100 million funding, as it looks ahead to clinical trials.
Theseus is taking a new approach to tyrosine kinase inhibitors, a type of drug that is well established in cancer care. Mutations lead to variants that render these treatments ineffective. Boston-based Theseus takes what it describes as a pan-variant approach. The company has developed technology that predicts how a cancer will mutate, enabling the company to target known mutations and stay ahead of future variants.
Theseus’s first cancer target is gastrointestinal stromal tumor (GIST), a type of cancer affecting the gut that can be driven by mutations to the KIT gene. Patients diagnosed with GIST have imatinib as their first treatment option and sunitinib as a second-line treatment. Theseus aims to provide another tyrosine kinase inhibitor option for cases that have advanced beyond second-line therapy.
Theseus has results from preclinical tests of its lead program, THE-630. During last week’s annual meeting of the American Association of Cancer Research, the company presented data showing that its drug had potent activity against all classes of mutations observed in KIT-mutated GIST. The preclinical studies needed for an investigational new drug application are underway; Theseus plans to begin a Phase 1 study in the second half of this year.
Beyond GIST, Theseus is also developing a drug designed to selectively block a protein called EGFR to overcome resistance to the AstraZeneca tyrosine kinase inhibitor osimertinib in patients with non-small cell lung cancer. Theseus has a third drug candidate in development for an undisclosed indication.
Theseus was incubated by OrbiMed, which funded the company’s 2018 Series A round. The biotech is led by a management team with experience at Ariad Pharmaceuticals, a Cambridge, Massachusetts-based cancer drug developer that Takeda Pharmaceutical acquired in 2017 for $5.2 billion. That biotech had commercialized two tyrosine kinase inhibitors, ponatinib and brigatinib. A third one, mobocertinib, is in late-stage clinical development.
The latest Theseus financing, a Series B round, was led by led by Foresite Capital. Other investors in Theseus’s latest round include Adage Capital Management, Boxer Capital, Farallon Capital Management, Longitude Capital, Nextech Ventures, Omega Healthcare Investors, Pontifax Venture Capital, Rock Springs Capital, T. Rowe Price, and OrbiMed. In conjunction with the financing, Michael Rome, Foresite’s managing director, has joined the Theseus board of directors.
Photo by Flickr user Hey Paul Studios via a Creative Commons license

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