SKY-1214 / Skyhawk Therap - LARVOL DELTA

Sky-1214, a Small Molecule Splicing Modulator Targeting FANCL and Fanci, Provides a New Mechanism of Action Targeting Multiple Myeloma and Non-Hodgkin's Lymphoma (ASH 2024) - "Cell lines resistant to dexamethasone and bortezomib (MM.1R and KMS-11/BTZ) remained as responsive to SKY-1214 as the parental non-resistant cell lines. Tumor regressions were observed in CDX models of high-risk MM and NHL treated with SKY-1214, both as monotherapy and in combination with selinexor or vincristine, respectively. These data, together with the favorable oral bioavailability and pharmacologic characteristics of SKY-1214 with a distinctive mechanism of action, were the basis for an IND submission and a planned FIH study to address the unmet medical need of the growing multi-refractory MM and NHL patient populations."

Anemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Disorders • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • FANCI • FANCL

SKY-1214, a small molecule splicing modulator of members of the Fanconi anemia pathway, exerts anti-cancer activity both as single agent and in combination in multiple myeloma and non-Hodgkin's lymphoma (AACR 2025) - "The combination of SKY-1214 with small molecule agents used for the treatment of MM and NHL, including vincristine, dexamethasone and selinexor, results in improved inhibition of cell growth and viability in multiple cell lines...Combination of SKY-1214 with the BCMA-targeting ADC belantamab mafodotin shows additive and synergistic effect in specific concentration ranges resulting in enhanced cell killing in a panel of MM cell lines...SKY-1214 treatment shows single agent anti-cancer activity in vitro and in vivo in MM and NHL models and combines well with small molecule agents, ADCs and monoclonal antibodies used for the treatment of these disorders. These data, together with the favorable oral bioavailability and pharmacologic characteristics of SKY-1214 with a distinctive mechanism of action, warrants future development in the clinic."

Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • FANCI • FANCL

Breakthroughs in treatment for hematological malignancies: latest updates on molecular glue, PROTACs and RNA degraders from ASH 2024. (PubMed, J Hematol Oncol) - "Currently, the main categories developed based on degraders include molecular glue (such as Cemsidomide, NX-5948), PROTACs (such as BGB-16673, AC-676, KT-333 ), and RNA degraders (such as SKY-1214). This correspondence summarizes the preclinical and clinical updates on degrader therapies presented at the ASH 2024 annual meeting."

Journal • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation

Skyhawk Therapeutics to Present Preclinical Data of SKY-1214 Combination Treatment in Hematologic Cancers at the 66th American Society of Hematology Annual Meeting (PRNewswire) - "Skyhawk Therapeutics...announced that the Company will deliver a poster presentation highlighting preclinical data that support SKY-1214 as a potential treatment for relapsed/refractory (R/R) multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL) at the upcoming 66th American Society of Hematology (ASH) Annual Meeting....Treatment with SKY-1214 in combination with dexamethasone, vincristine, and selinexor showed additive and/or synergistic effect, resulting in improved inhibition of cell growth and viability in multiple cell lines compared to the effect of SKY-1214 alone. In vivo, in MM and NHL cell line derived xenograft (CDX) models, the combinations showed superior activity as compared with monotherapy treatments, demonstrated tumor regressions, and showed enhanced durability of effect upon treatment cessation."

Preclinical • Multiple Myeloma • Non-Hodgkin’s Lymphoma

Preclinical characterization of SKY-1214, a small molecule splicing modulator of Fanconi Anemia pathway members for the treatment of multiple myeloma and non-Hodgkin's lymphoma (EORTC-NCI-AACR 2024) - "SKY-1214 is a splicing modulator of FANCL and FANCI that shows anti-cancer activity in vitro and in vivo in MM and NHL models. The new mechanism of action of this oral small molecule, together with its excellent bioavailability and pharmacologic properties, warrants future development in the clinic."

Preclinical • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • FANCI • FANCL

Skyhawk Therapeutics Presents Compelling Preclinical Data on SKY-1214 at the EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium (PRNewswire) - "Skyhawk Therapeutics...announced that the Company presented compelling preclinical data highlighting the therapeutic potential of its first-in-class compound, SKY-1214, at the European Organization for Research and Treatment of Cancer (EORTC)-National Cancer Institute (NCI)-American Association for Cancer Research (AACR) Molecular Targets and Cancer Therapeutics Symposium....Study authors concluded that SKY-1214 shows potent and efficacious anti-cancer activity in MM and NHL models in vitro, including in models with high-risk cytogenetic and/or genetic alterations (e.g., t(14;16), t(4;14), 1q+, and double-hit lymphoma). Additionally, in vivo treatment with SKY-1214 as a monotherapy resulted in tumor growth inhibition and regression to undetectable levels at tolerated doses in NHL and difficult-to-treat MM xenograft mouse models, including KMS-28BM."

Preclinical • Multiple Myeloma • Non-Hodgkin’s Lymphoma