HST-1021 / HotSpot Therap - LARVOL DELTA

HotSpot Therapeutics Presents Preclinical Data from Small Molecule CBM Signalosome Inhibitor Program at ESMO Gastrointestinal Cancers Congress 2025 (PRNewswire) - "HotSpot Therapeutics...announced the presentation of preclinical data from the Company's CARD11-BCL10-MALT1 (CBM) signalosome program at the European Society for Medical Oncology (ESMO) Gastrointestinal Cancers Congress 2025....HotSpot's CBM signalosome inhibitors demonstrated selectively induced potent apoptosis in KRASG12 CRC cell lines, outperforming KRAS, BCL2 and Bcl-xL inhibitors. In combination with a KRAS inhibitor, HotSpot's CBM signalosome inhibitor achieved complete suppression of downstream signaling in KRASG12X cell lines. HotSpot's CBM signalosome inhibitor demonstrated dose-dependent tumor inhibition or regression both alone and in combination with a KRAS inhibitor in multiple in vivo models."

Preclinical • Colorectal Cancer

Targeting the CBM signalosome with a MALT1 scaffolding inhibitor for treatment of NFkB driven solid tumors (EORTC-NCI-AACR 2024) - "Our potent, selective MALT1 scaffolding inhibitor, HST-1021, was tested on NPC models in vitro and in vivo. Unsupervised consensus clustering of 9125 patient samples from 33 cancer types in the TCGA pan-cancer atlas was performed using 11 known oncogenic pathways and the NFκB pathway... The bioinformatics analysis provided the first evidence that NFκB is a potential driver in SCC. As a proof of principle, the MALT1 scaffolding inhibitor demonstrated pre-clinical activity against NFκB driven NPC, highlighting its potential as a precision oncology approach for NFκB driven solid tumors."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Nasopharyngeal Carcinoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • IKBKE • MALT1

HotSpot Therapeutics Presents Preclinical Data from MALT1 CBM Signalosome Glue Program at 36th EORTC-NCI-AACR Symposium (PRNewswire) - "HotSpot Therapeutics, Inc...announced it will present preclinical data from the Company's mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) CARD11-BCL10-MALT1 (CBM) signalosome glue program highlighting its potential in NF-kB-driven solid tumors in a poster presentation at the 36th EORTC-NCI-AACR Symposium....The presentation describes preclinical data for HST-1021, HotSpot's MALT1 CBM signalosome glue development candidate: In contrast to MALT1 protease inhibitors, HST-1021 demonstrated robust inhibition of CBM signalosome activity. In an NF-kB-driven nasopharyngeal carcinoma patient-derived xenograft model, HST-1021 demonstrated dose-dependent anti-tumor activity, supporting HST-1021's potential for the treatment of NF-kB-driven solid tumors."

Preclinical • Nasopharyngeal Carcinoma

HotSpot Therapeutics to Present Preclinical Data from MALT1 CBM Signalosome Glue Program at 36th EORTC-NCI-AACR Symposium (PRNewswire) - "HotSpot Therapeutics, Inc...announced it will present preclinical data from the Company's mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) CARD11-BCL10-MALT1 (CBM) signalosome glue program highlighting its potential NF-kB-driven solid tumors in a poster presentation at the 36th EORTC-NCI-AACR Symposium, taking place October 23-25, 2024, in Barcelona, Spain."

Preclinical • Oncology • Solid Tumor

HotSpot Therapeutics Presents Preclinical Data for Potential First-in-Class MALT1 Scaffolding Inhibitor at the 4th AACR International Meeting: Advances in Malignant Lymphoma (PRNewswire) - "HotSpot Therapeutics...announced the presentation of preclinical data from the Company's highly differentiated mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) program at the 4th American Association for Cancer Research (AACR) International Meeting: Advances in Malignant Lymphoma....HST-1021 demonstrated potent inhibition of NF-kB and AP1 activity in vitro, two key markers of MALT1 scaffolding activity....HST-1021 demonstrated more significant and broader anti-tumor activity as compared to a MALT1 protease inhibitor."

Preclinical • Lymphoma

HotSpot Therapeutics to Present Additional Preclinical Data on Potential First-in-Class MALT1 Scaffolding Inhibitor at the 4th AACR International Meeting: Advances in Malignant Lymphoma (PRNewswire) - "HotSpot Therapeutics, Inc...announced it will present additional preclinical data from the Company's highly differentiated mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) program at the 4th American Association for Cancer Research (AACR) International Meeting: Advances in Malignant Lymphoma, taking place June 19-22, 2024, in Philadelphia, PA."

Preclinical • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

HotSpot Therapeutics Presents Preclinical Data for Potential First-in-Class MALT1 Scaffolding Inhibitor at 65th ASH Annual Meeting (PRNewswire) - "HotSpot Therapeutics...today announced the presentation of preclinical data from the Company's highly differentiated mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) program in an oral presentation at the 2023 American Society of Hematology (ASH) Annual Meeting...The presentation describes preclinical data for HST-1021, HotSpot's MALT1 inhibitor development candidate....In several B-cell lymphoma xenograft models, HST-1021 demonstrated robust, dose-dependent tumor growth inhibition (TGI), including in both MALT1 protease-inhibitor sensitive ABC-DLBCL and MALT1 protease-resistant NFkB-driven DLBCL models."

Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

HotSpot Therapeutics to Introduce First-in-Class MALT1 Scaffolding Inhibitor at 65th ASH Annual Meeting (PRNewswire) - "HotSpot Therapeutics...today announced it will present preclinical data from the Company's highly differentiated mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) program in an oral presentation at the 2023 American Society of Hemotology (ASH) Annual Meeting, taking place December 9-12, 2023, in San Diego, CA....This oral presentation will describe the differentiated preclinical profile for HotSpot's scaffolding inhibitor, including the potential for an improved efficacy and safety profile versus traditional MALT1 inhibitors that target protease function. HotSpot plans to file an IND for HST-1021, its Development Candidate, in 2024."

IND • Preclinical • Hematological Malignancies • Oncology