TTX-810 / Anji Pharma, Broad Institute - LARVOL DELTA

Inhibition of MCL-1-mediated anti-apoptotic signalling as a potential therapeutic strategy for paediatric high-grade gliomas (ISPNO 2026) - P1/2 | "Selective MCL-1 inhibitors (S63845, MIK665, BRD-810) and the BCL-2 inhibitor venetoclax were screened in cytotoxicity assays, with MIK665 showing the greatest efficacy against both HGG and DMG cells. The discovery that MCL-1 inhibition restores H3K27me3 reveals a novel mechanistic link between apoptotic evasion and epigenetic dysregulation. The robust synergy with epigenetic inhibitor CBL-0137 provides a compelling rationale for further preclinical development in DMG and HGG tumours."

IO biomarker • Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Glioma • High Grade Glioma • Mantle Cell Lymphoma • Pediatrics • Solid Tumor • ANXA5 • PDGFRA

Rapidly cleared MCL1 inhibitor TTX-810 showing robust efficacy in preclinical tumor models with no effects on cardiomyocytes in vitro and in vivo (AACR-NCI-EORTC 2023) - No abstract available

Late-breaking abstract • Preclinical • Oncology

Trueline Therapeutics Announces Completion of IND-Enabling Studies for MCL1 Inhibitor TTX-810 (Businesswire) - "Trueline Therapeutics Inc...announced the successful completion of IND-enabling studies with MCL1 inhibitor TTX-810, a highly potent and selective macrocyclic compound to treat patients with solid tumor or hematological cancers. A distinguishing feature of TTX-810 is a rapid clearance profile to minimize the potential risks of sustained MCL1 inhibition in non-cancerous tissues....The exquisite potency of TTX-810 was achieved by structure-guided design and comprehensive profiling versus over 500 cancer cell lines to define the optimal cellular context for rapid and selective induction of cell death. Following candidate selection, Trueline Therapeutics scientists designed and executed the IND-enabling program in preparation for first-in-human testing."

Preclinical • Hematological Malignancies • Oncology • Solid Tumor

ANJ810 is a highly selective novel MCL1 inhibitor with optimized in vivo clearance showing robust efficacy in preclinical solid and hematological tumor models (AACR 2023) - "ANJ810 induces efficient cancer cell killing within 4 hours in vitro but has no impact on cell viability or troponin I release in hiPSC-derived cardiomyocytes at supra-pharmacologic concentrations.In vivo, i.v. bolus injections of ANJ810 lead to short plasma residence time, yet are efficacious in xenograft models of multiple myeloma, DLBCL, NSCLC and HCC. ANJ810 will test the hypothesis in human clinical trials that short-term inhibition of MCL1 can overcome tumor resistance with an acceptable safety profile to improve current standard of care."

IO biomarker • Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lung Cancer • Lymphoma • Melanoma • Multiple Myeloma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • BAK1 • BCL2 • BCL2L1 • CASP3 • PMAIP1