Kyn Therapeutics Announces Initiation of Phase 1b/2 Clinical Studies of ARY-007 in Collaboration with Merck
Boston, Mass. – December 19, 2018 – Kyn Therapeutics, a biotechnology company advancing new immunometabolism therapies for treating cancer, today announced the initiation of two clinical trials of ARY-007 (also known as Grapiprant), an EP4 receptor antagonist, in collaboration with Merck (known as MSD outside the United States and Canada). ARY-007 will be assessed in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in checkpoint-refractory and -resistant solid tumors, an area of high unmet medical need.
Prostaglandin E2 (PGE2) has been shown to contribute to an immunosuppressive environment in cancer by enhancing the activity of regulatory immune cells and suppressing the activity of effector immune cells. EP4 is a high-affinity receptor of PGE2 and is known to facilitate these immunosuppressive activities. ARY-007 is an oral, potent and highly selective antagonist of EP4. In preclinical models, EP4 inhibition leads to antitumor activity and also significantly enhances the antitumor activity of checkpoint inhibitors. While in development for a non-oncology indication, ARY-007 was found to be well-tolerated in multiple studies which enrolled approximately 1000 human subjects.
The Phase 1b/2 multicenter, open-label, single arm clinical trials are designed to assess the safety and efficacy of ARY-007 in combination with pembrolizumab in patients with advanced or progressive Microsatellite Stable (MSS) Colorectal Cancer (CRC), and with advanced or metastatic PD-1/L1 refractory Non-Small Cell Lung Cancer (NSCLC) adenocarcinoma. MSS CRC is inherently resistant to anti-PD-1 therapies – these agents have only shown activity in the microsatellite instability-high (MSI-H) subset of CRC. The NSCLC study is enrolling patients who have progressed while on PD-1 or PD-L1 therapy. Both studies incorporate a robust translational biomarker strategy.
“The Kyn team believes immunometabolism pathways hold great promise as therapeutics that could deliver breakthrough improvements for patients non-responsive to immunotherapy regimens. We believe EP4 is the right target and ARY-007 is the right molecule for overcoming the immunosuppressive effects of PGE2 in these cancers where increased pathway expression is associated with poor outcome,” said Mark Manfredi, Ph.D., president and chief executive officer of Kyn Therapeutics. “We welcome the opportunity to collaborate with Merck as we initiate clinical studies.”
ARY-007 is an orally available, potent and highly selective antagonist of the EP4 receptor, a component of the prostaglandin E2 (PGE2) pathway which significantly influences the composition of the tumor microenvironment. In preclinical studies, inhibition of EP4 has been shown to boost the immune response through modulation of multiple immune cell types, and in combination with checkpoint inhibitors has yielded significant reduction in tumor growth relative to either agent alone.
About Kyn Therapeutics
Kyn Therapeutics is a biotechnology company advancing new immuno-metabolic therapies for cancer. A growing body of research indicates that key metabolites can exert broad suppressive or enhancing effects on the immune system through a complex network of cellular interactions, providing targets for new therapies that could significantly enhance patient response rates to checkpoint inhibitors. Kyn Therapeutics is advancing three development programs with targets strongly implicated in immunosuppression across a range of tumor types and via multiple immune cell effects. Kyn Therapeutics is based in Boston, Massachusetts. For more information, visit www.kyntherapeutics.com. Follow us on Twitter and LinkedIn.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., USA.