kt-3283 / Rakovina Therap - LARVOL DELTA

Development of a lipid nanoparticle formulation of the bifunctional PARP and HDAC inhibitor kt-3283 (AACR 2026) - "Physicochemical parameters of kt-3283 (solubility, pKa, thermal behavior, and metabolic stability) are being integrated for optimal pLNP/kt-3283 fabrication supporting enhanced encapsulation efficiency, and superior in vitro cell uptake, stability and bioavailability. Development of pLNP/kt-3283 uniquely combines design, formulation, and evaluation of a DDR-targeting compound, overcoming metabolic instability, and off-target limitations, and improving the therapeutic index."

Breast Cancer • Oncology • Solid Tumor

Novel AI-Designed Lipid Nanoparticle Formulation of kt-3283 Successfully Characterized (The Manila Times) - "kt-3283 integrates PARP inhibition and HDAC-mediated chromatin remodeling into a single compound, thereby improving the PARP efficacy, and eliminating the need for combination drug regimens and their associated toxicity risks...Data presented confirm the successful assembly of the EnsaliX-designed patterned lipid nanoparticles. Physicochemical characterization confirmed uniform particle size, stable colloidal behavior, and a structured surface texture predicted to enhance cellular uptake. The pLNP/kt-3283 formulation demonstrated structure and particle size consistency supporting further biological evaluation...Next steps include in vitro and in vivo characterization to confirm activity against PARP and HDAC enzymes...Rakovina intends to use these findings to advance best-in-class lead candidates toward IND-enabling studies in collaboration with pharmaceutical partners."

Preclinical • Solid Tumor

A bi-functional PARP-HDAC inhibitor with activity in Ewing sarcoma. (PubMed, Clin Cancer Res) - "Our data demonstrates the preclinical justification for studying the benefit of dual PARP and HDAC inhibition in the treatment of Ewing sarcoma in a clinical trial and provides proof-of-concept for a bi-functional single-molecule therapeutic strategy."

Journal • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor

A bifunctional inhibitor of PARP and HDAC enzymes with activity in Ewing sarcoma 3D spheroid and metastasis models (AACR 2023) - "PARP inhibition combined with HDAC inhibition has demonstrated enhanced efficacy in pre-clinical studies in various tumor indications, and a clinical trial of olaparib and vorinostat combination therapy against metastatic breast cancer is currently ongoing. Kt-3283 shows potent inhibition of PARP1/2 and HDAC activities. It induces S and G2/M cell cycle arrest and DNA damage, and inhibits 3D spheroid growth and metastatic potential of ES cells. Further investigation of this bifunctional single-molecule inhibitor may offer a novel treatment opportunity for ES and other solid tumors with limited responses to PARPi."

Breast Cancer • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • PARP2

Rakovina Therapeutics Announces Publication Highlighting Activity of Novel Bi-functional PARP-HDAC Inhibitor in Preclinical Models of Ewing Sarcoma (GlobeNewswire) - "Rakovina Therapeutics...announced publication of a scientific article on the anti-cancer activity of the Company’s novel dual PARP-HDAC inhibitor in models of Ewing sarcoma....Rakovina Therapeutics researchers characterized and tested kt-3283, a novel dual-function single molecule of PARP and HDAC in Ewing sarcoma model systems. In these studies, kt-3283 demonstrated higher efficacy than treatment with single-agent PARP or HDAC inhibitors....Publication to be available on pre-print server, bioRxiv, and will be submitted for scientific journal peer-review."

Preclinical • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor

Rakovina Therapeutics Presents Preclinical Data on its Novel kt-3000 Series at the 2022 AACR Special Conference on Sarcomas (GlobeNewswire) - "New kt-3000 data presented by Rakovina Therapeutics’ researchers at the AACR Special Conference on Sarcomas demonstrate that:...Rakovina Therapeutics’ kt-3283 prototype lead drug candidate exhibits potent bi-functional activity as evidenced by inhibition of PARP and PARylation at a low nanomolar potency plus potent inhibition of HDAC enzyme activity; kt-3283 treatment reduced viability of Ewing sarcoma cells >25 fold more potently than an FDA-approved PARP inhibitor or FDA-approved HDAC inhibitor"

Preclinical • Ewing Sarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor