Hoth Therapeutics Announces Positive Preclinical Results for HT-KIT in Aggressive Cancer Gastrointestinal Stromal Tumors (GIST). HT-KIT Triggered Significant Tumor Cell Death as Early as 24 Hours Post-treatment

Rhea-AI Summary

Hoth Therapeutics (NASDAQ: HOTH) has announced breakthrough preclinical results for HT-KIT, their novel targeted therapy for gastrointestinal stromal tumors (GIST). The study demonstrated significant efficacy in several key areas:

• Tumor cell death occurred within 24 hours of treatment
• Reduced KIT receptor expression was sustained for 72 hours
• Decreased tumor cell proliferation in GIST-T1 cells
• Significant tumor growth reduction in humanized xenograft models by day 8
• Smaller and lighter tumors in HT-KIT-treated mice compared to control group

HT-KIT targets KIT mutations, which drive GIST progression, potentially offering a new treatment option for patients who develop resistance to current therapies. The company plans to conduct additional preclinical studies before initiating regulatory discussions for first-in-human trials.

Positive

• Significant tumor cell death achieved within 24 hours of treatment
• Sustained reduction in KIT receptor expression for 72 hours
• Statistically significant tumor growth reduction by day 8 in mouse models
• Demonstrated efficacy at both high and low doses
• Potential to overcome current treatment resistance in GIST patients

Negative

• Still in preclinical phase, requiring extensive additional studies
• Timeline for human trials not yet established
• Regulatory approval process not initiated

Insights

Oncology Research Scientist

Hoth Therapeutics' preclinical data for HT-KIT demonstrates compelling efficacy against gastrointestinal stromal tumors (GIST) through a mechanism targeting KIT mutations, which drive approximately 80% of GIST cases. The data reveals multi-modal anti-tumor activity through three critical mechanisms: reduced KIT receptor expression, direct tumor cell death induction, and inhibition of cancer cell proliferation.

The xenograft model results are particularly promising, showing statistically significant tumor volume reduction by day 8 of treatment, with sustained and increasing effects over time. This early response timing suggests potential for rapid clinical benefit if translated to humans. The 12.5 mg/kg intravenous dosing every three days showed manageable administration requirements while maintaining efficacy.

In the context of GIST treatment landscape, this approach is scientifically sound. Current tyrosine kinase inhibitors (TKIs) like imatinib temporarily control GIST but face resistance mechanisms. HT-KIT's approach of directly reducing KIT receptor expression represents a fundamentally different mechanism that could potentially overcome resistance pathways seen with conventional TKIs.

However, investors should note this remains early-stage research with the critical caveat that approximately 90% of preclinical cancer candidates fail to reach market approval. The next key milestone will be IND-enabling toxicology studies to determine safety profile before potential human trials.

Biotechnology Financial Analyst

Hoth Therapeutics' preclinical HT-KIT data represents meaningful progress for this micro-cap biotech with a $14.9 million market capitalization. The company appears to be executing effectively on advancing this oncology asset targeting an established molecular pathway (KIT mutations) in GIST – a specialized cancer indication with treatment options after resistance develops.

The most compelling aspect from an investment perspective is HT-KIT's differentiated mechanism versus current standard-of-care TKIs. By directly reducing KIT receptor expression rather than just inhibiting its activity, Hoth potentially addresses fundamental resistance mechanisms. If successfully translated to humans, this could position HT-KIT for significant market opportunity in relapsed/refractory GIST.

The current market for GIST therapies exceeds $1 billion annually, providing substantial revenue potential relative to Hoth's current valuation. However, investors must weigh this against substantial development hurdles ahead – IND-enabling studies, phase 1 safety trials, and registration-directed efficacy studies – each requiring significant capital. With no mention of development partners, the company likely faces future dilutive financing rounds to advance HT-KIT.

Timeline to potential commercialization remains lengthy, with at minimum 5-7 years before potential approval assuming successful development. Near-term catalysts will focus on regulatory interactions for clinical trial planning and potential partnership discussions to fund development.

New Data Demonstrates Significant Reduction in Tumor Growth and KIT Expression in Preclinical GIST Models

• Induction of Tumor Cell Death – HT-KIT triggered significant tumor cell death as early as 24 hours post-treatment, while the lower dose led to delayed but substantial cell death at 72 hours.
• Decreased Tumor Cell Proliferation – HT-KIT treatment inhibited cell growth and proliferation in GIST-T1 cells, as confirmed by cell count reductions and decreased fluorescence intensity in proliferation assays.
• Marked Tumor Volume Reduction in GIST Mouse Models – In a humanized xenograft model, HT-KIT treatment (12.5 mg/kg IV every three days) led to a significant reduction in tumor growth, with differences becoming statistically significant by day 8 and increasing over time.
• Consistent Tumor Size Reduction – Excised tumors from HT-KIT-treated mice were smaller and lighter than those in the control group, reinforcing tumor volume measurements.

NEW YORK, March 18, 2025 /PRNewswire/ -- Hoth Therapeutics, Inc. (NASDAQ: HOTH), a clinical-stage biopharmaceutical company, today announced breakthrough preclinical findings demonstrating the efficacy of HT-KIT, a novel targeted therapy for gastrointestinal stromal tumors (GIST). The results highlight HT-KIT's ability to significantly reduce tumor burden in humanized mouse models, disrupt KIT signaling pathways, and induce tumor cell death.

"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."

Key Findings from the Preclinical Study:

• Significant Reduction in KIT Expression – HT-KIT effectively reduced KIT receptor expression within 24 hours, with effects sustained for 72 hours.
• Induction of Tumor Cell Death – HT-KIT triggered significant tumor cell death as early as 24 hours post-treatment, while the lower dose led to delayed but substantial cell death at 72 hours.
• Decreased Tumor Cell Proliferation – HT-KIT treatment inhibited cell growth and proliferation in GIST-T1 cells, as confirmed by cell count reductions and decreased fluorescence intensity in proliferation assays.
• Marked Tumor Volume Reduction in GIST Mouse Models – In a humanized xenograft model, HT-KIT treatment led to a significant reduction in tumor growth, with differences becoming statistically significant by day 8 and increasing over time.
• Consistent Tumor Size Reduction – Excised tumors from HT-KIT-treated mice were smaller and lighter than those in the control group, reinforcing tumor volume measurements.

HT-KIT: A Potential New Treatment for GIST

GIST is a rare but aggressive cancer often driven by activating mutations in the KIT receptor. Current treatment options, including tyrosine kinase inhibitors (TKIs), can face resistance over time, leading to disease progression. Hoth Therapeutics' HT-KIT offers a novel approach by effectively reducing KIT receptor expression, disrupting tumor survival pathways, and inhibiting tumor growth in vivo.

"These results provide compelling preclinical proof-of-concept for HT-KIT in GIST treatment," said Robb Knie. "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."

Next Steps in Development

Hoth Therapeutics is committed to advancing HT-KIT toward clinical evaluation. The company is currently conducting additional preclinical studies to further validate HT-KIT's efficacy and safety profile, with plans to initiate regulatory discussions for first-in-human trials.

For more information on Hoth Therapeutics and its innovative pipeline, please visit www.hoththerapeutics.com.

About Hoth Therapeutics, Inc.

Hoth Therapeutics is a clinical-stage biopharmaceutical company dedicated to developing innovative, impactful, and ground-breaking treatments with a goal to improve patient quality of life. We are a catalyst in early-stage pharmaceutical research and development, elevating drugs from the bench to pre-clinical and clinical testing. Utilizing a patient-centric approach, we collaborate and partner with a team of scientists, clinicians, and key opinion leaders to seek out and investigate therapeutics that hold immense potential to create breakthroughs and diversify treatment options. To learn more, please visit https://ir.hoththerapeutics.com/.

Forward-Looking Statement

This press release includes forward-looking statements based upon Hoth's current expectations, which may constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 and other federal securities laws, and are subject to substantial risks, uncertainties, and assumptions. These statements concern Hoth's business strategies; the timing of regulatory submissions; the ability to obtain and maintain regulatory approval of existing product candidates and any other product candidates we may develop, and the labeling under any approval we may obtain; the timing and costs of clinical trials, and the timing and costs of other expenses; market acceptance of our products; the ultimate impact of the current coronavirus pandemic, or any other health epidemic, on our business, our clinical trials, our research programs, healthcare systems, or the global economy as a whole; our intellectual property; our reliance on third-party organizations; our competitive position; our industry environment; our anticipated financial and operating results, including anticipated sources of revenues; our assumptions regarding the size of the available market, benefits of our products, product pricing, and timing of product launches; management's expectation with respect to future acquisitions; statements regarding our goals, intentions, plans, and expectations, including the introduction of new products and markets; and our cash needs and financing plans. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. You should not place reliance on these forward-looking statements, which include words such as "could," "believe," "anticipate," "intend," "estimate," "expect," "may," "continue," "predict," "potential," "project" or similar terms, variations of such terms, or the negative of those terms. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, the Company cannot guarantee such outcomes. Hoth may not realize its expectations, and its beliefs may not prove correct. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, market conditions and the factors described in the section titled "Risk Factors" in Hoth's most recent Annual Report on Form 10-K and Hoth's other filings made with the U. S. Securities and Exchange Commission. All such statements speak only as of the date made. Consequently, forward-looking statements should be regarded solely as Hoth's current plans, estimates, and beliefs. Investors should not place undue reliance on forward-looking statements. Hoth cannot guarantee future results, events, levels of activity, performance, or achievements. Hoth does not undertake and specifically declines any obligation to update, republish, or revise any forward-looking statements to reflect new information, future events, or circumstances or to reflect the occurrences of unanticipated events, except as may be required by applicable law.

Investor Contact:
LR Advisors LLC 
Email: investorrelations@hoththerapeutics.com
www.hoththerapeutics.com
Phone: (678) 570-6791

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SOURCE Hoth Therapeutics, Inc.

FAQ

What are the key preclinical results of Hoth Therapeutics' HT-KIT treatment for GIST?

HT-KIT showed significant tumor cell death within 24 hours, reduced KIT receptor expression for 72 hours, decreased tumor cell proliferation, and achieved significant tumor growth reduction in mouse models by day 8.

How does HT-KIT's mechanism of action differ from current GIST treatments?

HT-KIT directly reduces KIT receptor expression and disrupts tumor survival pathways, potentially overcoming resistance to current tyrosine kinase inhibitors (TKIs) used in GIST treatment.

What dosage of HT-KIT showed efficacy in the GIST mouse models?

The study used 12.5 mg/kg IV administered every three days, which led to significant reduction in tumor growth.

What are the next development steps for Hoth Therapeutics' HT-KIT?

Hoth is conducting additional preclinical studies to validate efficacy and safety, followed by regulatory discussions for first-in-human trials.