Hoth Therapeutics, Inc. has announced breakthrough preclinical findings for its novel targeted therapy HT-KIT in the treatment of gastrointestinal stromal tumors (GIST). The results demonstrate significant efficacy in reducing tumor burden, disrupting KIT signaling pathways, and inducing tumor cell death in humanized mouse models.
The preclinical study revealed multiple promising outcomes that highlight HT-KIT's potential as a new therapeutic approach for GIST, a rare but aggressive cancer often driven by activating mutations in the KIT receptor.
Significant Anti-Tumor Activity in Preclinical Models
HT-KIT demonstrated rapid and sustained effects on KIT expression, effectively reducing KIT receptor levels within 24 hours of administration, with these effects persisting for at least 72 hours. This reduction in KIT expression is particularly significant as KIT mutations are a major driver of GIST progression.
The treatment also triggered substantial tumor cell death as early as 24 hours post-treatment at higher doses, while lower doses led to delayed but still significant cell death at the 72-hour mark. Additionally, HT-KIT inhibited cell growth and proliferation in GIST-T1 cells, confirmed through reduced cell counts and decreased fluorescence intensity in proliferation assays.
"These exciting findings mark a significant milestone in the development of HT-KIT as a potential new therapeutic for patients with GIST," said Robb Knie, CEO of Hoth Therapeutics. "By targeting KIT mutations, which are a major driver of GIST progression, HT-KIT has shown remarkable efficacy in preclinical models, demonstrating its potential as a transformative treatment option for this difficult-to-treat cancer."
Compelling In Vivo Results
In humanized xenograft models, HT-KIT treatment led to a significant reduction in tumor growth compared to control groups. The differences in tumor volume became statistically significant by day 8 of treatment and continued to increase over time, suggesting durable anti-tumor activity.
Further supporting these findings, tumors excised from HT-KIT-treated mice were consistently smaller and lighter than those from the control group, reinforcing the tumor volume measurements observed during the study.
Addressing an Unmet Medical Need
GIST represents a challenging therapeutic area where current treatment options, including tyrosine kinase inhibitors (TKIs), often face resistance over time, leading to disease progression and limited options for patients.
HT-KIT's novel approach directly targets the underlying genetic drivers of GIST, potentially overcoming the limitations of existing therapies. By effectively reducing KIT receptor expression and disrupting tumor survival pathways, HT-KIT offers a promising new strategy for patients with KIT-driven malignancies.
"These results provide compelling preclinical proof-of-concept for HT-KIT in GIST treatment," Knie added. "By directly targeting the underlying genetic drivers of GIST, HT-KIT has the potential to overcome limitations of existing therapies and provide a new therapeutic strategy for patients with KIT-driven malignancies."
Path Forward
Hoth Therapeutics is currently conducting additional preclinical studies to further validate HT-KIT's efficacy and safety profile. The company has indicated plans to initiate regulatory discussions for first-in-human trials, moving this promising therapy closer to clinical evaluation.
The development of HT-KIT aligns with Hoth Therapeutics' broader mission as a clinical-stage biopharmaceutical company dedicated to developing innovative treatments that improve patient quality of life. If successful in clinical trials, HT-KIT could represent an important advancement in the treatment landscape for GIST patients, particularly those who have developed resistance to current standard-of-care therapies.
