Teon Therapeutics Announces Clinical Trial Collaboration With Merck to Evaluate Novel Oral Immune Response Modifier in Combination with KEYTRUDA

Teon Therapeutics (Teon) recently announced it has entered into the clinical trial collaboration agreement with Merck for the combination arm of Teon’s ongoing, two-armed, open-label, dose escalation and expansion clinical study and will evaluate Teon’s oral, immune response modifier, TT-816, in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), for patients with advanced solid tumors. The study will include patients with many difficult-to-treat cancers with high unmet medical need who have not responded to the standard-of-care and may have limited treatment options.

“We are fortunate to have the opportunity to collaborate with Merck for this Phase 1/2 trial. The collaboration of the combination arm of our TT-816 clinical trial represents an important advancement in our comprehensive development program and further supports our mission to invent new hope for patients by potentially providing meaningful treatments to those with few remaining alternatives,” said Serge Messerlian, Chief Executive Officer of Teon Therapeutics. “In addition to its great potential as a monotherapy, by blocking both the PD-1 and CB2 pathways, we believe that TT-816 in combination with KEYTRUDA may have an additive benefit in ‘hot’ tumors and synergistic effect in ‘cold’ tumors that may result in improved outcomes for more patients. Results of our preclinical studies indicate that TT-816 has unique mechanisms of action that enhance both T cell and NK cell antitumor immunity, prevent broad-based T cell exhaustion, synergize antitumor effects with current immune checkpoint inhibitor therapies, and directly promote T cell infiltration into solid tumors.”

“New treatment options are desperately needed in oncology care as today, most patients see their cancer return on current immunotherapy treatment. TT-816 in combination with KEYTRUDA could potentially offer a clinically meaningful new option that can overcome tumor resistance mechanisms in many patients with difficult-to-treat cancers,” said Anthony W. Tolcher, MD, FRCPC, FACP, principal investigator and CEO, founder of NEXT Oncology.

This clinical trial is an open-label, Phase 1/2, first-in-human (FIH), multiple ascending dose and dose-expansion study of TT-816 orally administered as monotherapy and in combination with KEYTRUDA, Merck’s anti-PD-1 therapy. An estimated 200 patients will be enrolled. Phase 1 will evaluate safety, tolerability, pharmacokinetics, preliminary clinical activity and establish a recommended dose of TT-816 to be used as a monotherapy and in a combination therapy for Phase 2. Phase 2 will continue to evaluate safety and define the preliminary efficacy of these regimens in the setting of advanced solid tumors with high unmet medical needs including Non-Small Cell Lung Cancer (NSCLC), Ovarian Cancer and Renal Cell Carcinoma (RCC).

Additional information about the trial can be found on clinicaltrials.gov using the study identifier (NCT05525455).

TT-816 is a first-in-class, oral cannabinoid CB2 receptor antagonist acting as a novel immune response modifier for the treatment of a broad range of solid tumors and is highly selective for the CB2 receptor versus the CB1 receptor. By inhibiting the actions of the CB2 receptors on immune cells in many difficult-to-treat cancers, including lung, renal, and ovarian, TT-816 has the potential to enhance T cell and NK cell activity and directly promote T cell infiltration into solid tumors.

Preclinical results indicate that TT-816 enhances both the effect of NK cell tumor killing and T cell activation in vitro, increases both tumor infiltrating T cells and NK cells in vivo and prevents broad-based T cell exhaustion. TT-816 dose-dependently inhibits tumor growth in animal models, has an additive effect with anti-PD-1 in the ‘hot’ tumor model and acts synergistically with anti-PD-1 in the ‘cold’ tumor model where the anti-PD-1 alone had no effect.

The cannabinoid CB2 receptor belongs to the G protein-coupled receptor (GPCR) family. The cannabinoid CB2 receptor, selectively inhibited by TT-816, is a peripheral receptor found predominantly in the immune system and regulates inflammation and the immune response. Elevated CB2 receptor expression is associated with worse overall survival and aggressiveness of cancer. Research has shown that CB2 receptor activation does not have any psychoactive properties unlike CB1 receptors which are located primarily in the brain.

Teon Therapeutics is a clinical-stage biopharmaceutical company dedicated to improving the lives of cancer patients by developing a focused portfolio of oral, GPCR-targeted small molecules that inhibit immunosuppressive and cancer-promoting signaling pathways in difficult-to-treat cancers. Teon’s rich pipeline includes a small molecule, cannabinoid CB2 receptor antagonist acting as a novel immune response modifier and adenosine pathway inhibitors. Teon has an ongoing Phase 1/2 trial evaluating TT-816, a cannabinoid CB2 antagonist and a Phase1/2 trial evaluating TT-702, an A2B receptor-specific antagonist. The Company is also advancing additional first- or best-in-class GPCR pipeline programs to treat cancer. The highly accomplished scientific leadership team are experts in tumor metabolism, cell signaling and GPCR therapeutic design. Teon completed its $30M Series A financing round in February 2021. For more information, visit www.teontherapeutics.com.