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

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