P1, N=40, Active, not recruiting, Tolremo Therapeutics AG | Recruiting --> Active, not recruiting

P1, N=40, Not yet recruiting, TOLREMO therapeutics AG | N=90 --> 40

To investigate multimodal therapeutic approaches that combine epigenetic modulation with immunogenic and cytotoxic effects of oncolytic viruses (OVs), we evaluated two recombinant OVs, including the herpes simplex virus talimogene laherparepvec (T-VEC) and a measles vaccine virus (MeV-GFP), in combination with NEO2734 in four distinct NC cell lines. Evaluation of immunogenic cell death (ICD) markers displayed elevated ATP and HMGB1 levels and increased surface calreticulin with T-VEC and NEO2734 combinations. Overall, these findings indicate that combining OVs with BET/p300 inhibitors elicits potent antitumor responses, supports synergistic interactions and immunogenicity, and warrants further investigation in multimodal therapeutic strategies for NC.

The lead compound, 10k (ZX079), induces potent, dose- and time-dependent degradation of BRD4 and CBP and demonstrates superior suppression of oncogenic transcription and inhibition of AML cell proliferation compared with the dual BET/CBP inhibitor NEO2734. In vivo, 10k significantly reduces tumor growth in an AML xenograft model with TGI over 90%. Collectively, these findings highlight dual degradation of BRD4 and CBP as a promising strategy for AML.

P2, N=100, Recruiting, CellCentric Ltd. | Not yet recruiting --> Recruiting

Both compounds displayed potent antiproliferative activity across multiple cancer cell lines, with higher potency than NEO2734, paclitaxel (PTX), and ARV-771. In a PC-3 xenograft mouse model, compound 29c achieved dose-dependent tumor growth inhibition (TGI) of up to 81.5% at a low dose of 0.2 mg/kg, administered every other day, significantly surpassing the efficacy of NEO2734 and PTX at higher doses. Together, 29c, a highly efficient CBP/p300 and BRD4 dual-target degrader, demonstrates significant therapeutic potential in prostate cancer and warrants further development.

Compared to CCS1477, it shows comparable in vivo efficacy in the OPM-2 xenograft model and demonstrates more potent antitumor activity in the 22RV1 xenograft model, with tumor growth inhibition values of 56.2% and 72.8%, respectively. Overall, CZL-077 is a promising candidate for the treatment of human cancer as a p300/CBP BRD inhibitor.

By selectively targeting EP300, CCS1477 orchestrates a dual pro-death mechanism involving both intrinsic apoptosis execution and PINK1-driven mitochondrial clearance, resulting in significant inhibition of diffuse large B-cell lymphoma pathogenesis.

P1/2, N=220, Completed, CellCentric Ltd. | Active, not recruiting --> Completed

P2, N=100, Not yet recruiting, CellCentric Ltd.

P1, N=50, Recruiting, TOLREMO therapeutics AG | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Jul 2025 --> Aug 2026

P1/2, N=350, Active, not recruiting, CellCentric Ltd. | Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> Aug 2025 | Trial primary completion date: Dec 2024 --> Aug 2025