Teon Therapeutics Announces First Patient Treated in Phase 1/2 Clinical Trial of a Novel Oral Immune Checkpoint Inhibitor

Teon Therapeutics recently announced the first patient has been treated in its Phase 1/2 clinical trial evaluating the safety and efficacy of TT-816, an oral CB₂ receptor antagonist acting as an immune checkpoint inhibitor while promoting T cell infiltration of cold tumors and stimulating NK cell tumor killing.

The study (NCT05525455) is an open-label, first-in-human multiple ascending dose and dose-expansion study evaluating TT-816 administered orally as a monotherapy in Phase 1 and, in Phase 2, as a monotherapy and in combination with a PD-1 inhibitor. The study will include patients with advanced solid tumors with high unmet medical need who have not responded to the standard-of-care and may have no more treatment options.

“The initiation of our Phase 1/2 trial of TT-816 is an important step in our mission to invent new hope for patients by providing meaningful treatments to those with few remaining alternatives. It’s our hope that TT-816 represents a new option for these patients who haven’t been served by current immunotherapies,” said Serge Messerlian, Chief Executive Officer of Teon. “Supported by strong preclinical data, we believe TT-816 has unique mechanisms of action that go beyond current checkpoint inhibitors by enhancing both T cell and NK cell antitumor immunity, preventing broad-based T cell exhaustion, synergizing antitumor effects with current immune checkpoint inhibitor therapies, and directly promoting T cell infiltration into solid tumors.”

“Today, most patients fail on current immunotherapy treatment options and a therapy that is able to overcome tumor resistance mechanisms in many difficult-to-treat cancers is desperately needed in oncology care,” added Anthony W. Tolcher, MD, FRCPC, FACP, principal investigator and CEO, founder of NEXT Oncology. “As a novel checkpoint inhibitor with unique mechanisms of action, I am hopeful about the role of TT-816 in the treatment landscape. TT-816 could potentially offer a clinically meaningful, new option for the treatment of patients with many types of difficult-to-treat cancers.”

The Phase 1/2 clinical trial is actively recruiting patients with advanced solid tumors in several sites. More information on the clinical trial including eligibility, enrollment information and trial sites can be found on clinicaltrials.gov using the study identifier (NCT05525455).

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 a PD-1 inhibitor. 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 an immune checkpoint inhibitor 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 an immune checkpoint inhibitor 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.