IND submitted for CTIM-76 in testicular and gynecologic cancers

An investigational new drug (IND) application has been submitted to the FDA for a study of CTIM-76 in claudin 6 (CLDN6)-positive testicular and gynecologic tumors, according to a news release from Context Therapeutics, the developer of the therapy.¹

Preclinical data demonstrated the specificity and potential cell-killing effects of CTIM-76, suggesting potential as a treatment option against CLDN6-positive solid tumors.

“Our IND submission for CTIM-76 is a significant milestone for Context. In 2021, we set an aggressive timeline to advance CTIM-76 into the clinic, and we prioritized this program as we believe it is a potentially best-in-class CLDN6-targeting therapy that is highly selective for CLDN6,” said Martin Lehr, CEO of Context, in the news release.¹ “The IND application includes extensive manufacturing, preclinical, and toxicology data to support a first-in-human trial. I am incredibly proud of the entire Context team who worked tirelessly to complete this IND submission.”

According to Context Therapeutics, CTIM-76 is a CLDN6 x CD3 T cell engaging bispecific antibody.Acceptance of the IND application would initiate a first-in-human phase 1 dose expansion and escalation trial of CTIM-76 in patients with testicular and gynecologic cancers.

Lehr added in the news release,¹ “We are excited to continue advancing the development of CTIM-76 and remain focused on preparing for the initiation of the phase 1 clinical trial so that we can make CTIM-76 available to physicians and their patients as soon as possible.”

Preclinical data on CTIM-76

Preclinical data on CTIM-76 were presented in November 2023 at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) in San Diego, California.²

Overall, the data demonstrated the specificity and potential cell-killing effects of CTIM-76, suggesting potential as a treatment option against CLDN6-positive solid tumors.

Specifically, CTIM-76 was shown to have high potency and target selectivity in binding and cytotoxicity assays.

In the toxicology studies that enabled the IND application submission, CTIM-76 was well-tolerated, and the investigators identified a potential first-in-human dose level. Further, the therapy induced dose-proportional tumor regressions during in vivo xenograft toxicology studies.

Additional data showed that the activity of CTIM-76 was maintained across cell lines that had a range of low to high CLDN6 expression, whereas the activity of TORL-1-23, a benchmarking clone of a clinical-stage molecule, was dependent on high levels of CLDN6 expression. Further, when compared with AMG-794 for benchmarking, CTIM-76 demonstrated a 10-fold higher potency in in vitro cytotoxicity and cytokine activation.

“It is estimated that there are 70,000 patients with CLDN6-positive metastatic solid tumors in the United States, and no approved targeted treatment options exist,” said Lehr in a news release on the SITC presentation.³ “We’re encouraged by the promise CTIM-76 has shown with these first in vivo data, which reinforce the selectivity and potency seen in earlier in vitro data and demonstrate CTIM-76’s ability to induce complete tumor regressions across multiple dose levels. Moreover, our comparison to clones of clinical-stage molecules demonstrates CTIM-76’s ability to address potential target density and toxicity challenges associated with first-generation approaches, as well as highlights CTIM-76’s pharmacologically distinct profile and broad therapeutic potential.”

References

1. Context Therapeutics submits IND application to evaluate CTIM-76 in claudin 6-positive cancers. News release. Context Therapeutics Inc. Published online and accessed April 1, 2024. https://ir.contexttherapeutics.com/news-releases/news-release-details/context-therapeutics-submits-ind-application-evaluate-ctim-76

2. Rucker J, Sanchez I, Doolan K, et al. Development of CTIM-76, a highly specific Claudin 6 bispecific antibody. Presented at the 38th Annual Meeting of the Society for Immunotherapy of Cancer. November 3, 2023. San Diego, California. Abstract 1183

3. Context Therapeutics announces preclinical data demonstrating differentiated and active profile of its claudin 6-targeted bispecific antibody CTIM-76. News release. Context Therapeutics, Inc. October 31, 2023. Accessed April 1, 2024. https://ir.contexttherapeutics.com/news-releases/news-release-details/context-therapeutics-announces-preclinical-data-demonstrating