#USA #New York #FDA #Hoth Therapeutics #HT-KIT

Hoth Therapeutics Makes Strides with HT-KIT

Hoth Therapeutics, Inc., a clinical-stage biopharmaceutical company, has recently reported significant advancements regarding its investigational drug HT-KIT, which is designed to treat rare c-KIT-driven cancers. Notably, the company has secured the FDA Orphan Drug Designation for HT-KIT, a milestone that brings various incentives, including potential market exclusivity upon approval, tax credits, and fee waivers. The combination of regulatory recognition and strong preclinical data positions HT-KIT as a potential game-changer for patients with limited treatment options.

What Sets HT-KIT Apart?

HT-KIT is a precision antisense oligonucleotide (ASO) specifically targeting KIT mRNA, aiming to silence both mutant and wild-type forms of the KIT gene. Unlike conventional small-molecule kinase inhibitors, HT-KIT operates at the genetic level, which may help circumvent typical resistance pathways that can complicate treatment for diseases such as aggressive systemic mastocytosis (ASM), gastrointestinal stromal tumors (GIST), and select leukemias.

In preclinical studies, HT-KIT demonstrated over 80% suppression of KIT expression and significant reduction in tumor volume. By Day 8 in xenograft models, substantial anti-tumor activity was observed, correlated with apoptotic signaling aligned with effective KIT pathway knock-down. These promising results come alongside successful completion of Good Laboratory Practice (GLP)-validated bioanalytical methods, crucial for the upcoming Investigational New Drug (IND) application.

Details of the Preclinical Results

1. Gene-Level Target Suppression: HT-KIT achieved impressive reductions in both KIT mRNA and protein across various in vitro and in vivo systems, providing a robust foundation for its expected efficacy.
2. Rapid Anti-Tumor Activity: The efficacy of HT-KIT manifested rapidly in xenograft models, demonstrating statistically significant decreases in tumor volume by Day 8, indicating the therapy's potential speed of action.
3. Favorable Tolerability: Early studies reported no dose-limiting toxicities, underscoring its potential safety profile which could enhance patient adherence and outcomes.
4. Bioanalytical Readiness: The completion of the GLP bioanalytical methods paves the way for vital pharmacokinetic and biodistribution analyses essential for IND submission.

Strategic Next Steps

Hoth is now focusing on completing the GLP toxicology and Chemistry, Manufacturing, and Controls (CMC) requirements needed for submitting the IND. Once submitted, the company plans to initiate Phase 1/2 dose-escalation and expansion studies targeting advanced systemic mastocytosis and other KIT-driven tumors. Furthermore, these studies will include translational biomarkers to track treatment response and effectiveness early in the evaluation phases.

As Robb Knie, the Chief Executive Officer of Hoth Therapeutics, expressed, "HT-KIT's consistent anti-tumor performance across models, coupled with a clean preclinical tolerability profile and GLP-ready analytics, prepares us for a disciplined first-in-human evaluation."

Conclusion

With the Orphan Drug Designation and substantial preclinical progress, Hoth Therapeutics is strategically positioned to advance HT-KIT into clinical trials. The company continues to expand its intellectual property and seeks strategic partnerships to further develop and commercialize HT-KIT, with a vision to revolutionize treatment options for patients fighting rare cancers. These advancements emphasize Hoth Therapeutics' commitment to improving patient quality of life through innovative therapies.