On November 1, 2022 Teon Therapeutics (Teon), a clinical-stage biopharmaceutical company targeting metabolic signaling pathways and pioneering the development of G-Protein Coupled Receptor (GPCR) immuno-oncology therapies in difficult-to-treat cancers, reported that 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 (Press release, Teon Therapeutics, NOV 1, 2022, View Source [SID1234622734]).
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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," said Anthony W. Tolcher, M.D., 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).
About Teon’s Multicenter TT-816 Phase 1/2 Clinical Trial
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).
About TT-816
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.
About the CB2 receptor
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.