Hoth Therapeutics' Cancer Therapeutic HT-KIT Surpasses Preclinical Milestones With Potent Anti-Tumor Activity and GLP-Validated Bioanalytical Results, Exceeding Regulatory Standards

Rhea-AI Summary

Hoth Therapeutics (NASDAQ: HOTH) reported significant preclinical milestones for its cancer therapeutic HT-KIT. The drug demonstrated potent anti-tumor activity in gastrointestinal stromal tumors (GIST) and systemic mastocytosis models, achieving over 80% knockdown of KIT expression and significant tumor shrinkage within 8 days.

The GLP-validated bioanalytical results, conducted by Altasciences, exceeded regulatory standards with 90.5% of ISR values within ±30% (above 66.7% requirement). The drug showed clean safety profiles across multiple organs and demonstrated extended stability in serum for 37 days at -80°C. The company is now advancing toward IND submission and first-in-human trials.

Positive

• Significant tumor cell death achieved within 24 hours of treatment
• Over 80% knockdown of KIT expression in vitro
• Clean safety profile with no off-target toxicity across critical organs
• Bioanalytical results exceeded regulatory standards with 90.5% ISR values compliance
• Extended stability period of 37 days, surpassing the 28-day requirement

Negative

• Still in preclinical stage, requiring full IND submission and human trials
• Increased liver engagement noted with higher doses (1.11g to 1.32g at 3.0 mg/kg)

Insights

Oncology & Drug Development Expert

Hoth's HT-KIT cancer drug shows impressive preclinical results with rapid tumor killing and clean safety profile, advancing toward clinical trials.

Hoth Therapeutics has achieved significant preclinical milestones with its HT-KIT antisense therapeutic, targeting cancers driven by KIT mutations. The data reveals rapid anti-tumor activity with tumor cell death observed within just 24 hours post-treatment and statistically significant tumor shrinkage by day 8 in models of gastrointestinal stromal tumors (GIST) and systemic mastocytosis.

The mechanism appears robust, with over 80% knockdown of KIT expression in vitro. KIT is a well-established oncogenic driver in several aggressive cancers, making this level of suppression particularly promising. The dose-dependent biological signal, evidenced by proportional liver engagement, suggests a predictable pharmacological response without triggering toxicity concerns.

What's particularly impressive is the clean safety profile across multiple vital organs with no observed pathology. This favorable toxicity profile is often a major hurdle in cancer drug development, where efficacy must be balanced against systemic toxicity.

The GLP-validated bioanalytical results exceed regulatory standards, with 90.5% of Incurred Sample Reanalysis values falling within ±30% (well above the 66.7% regulatory minimum). This demonstrates exceptional reproducibility and data integrity – critical factors for regulatory approval. The extended stability profile (37 days at -80°C) provides practical advantages for clinical implementation.

The combination of rapid tumor kill, clean safety profile, and strong analytical validation positions HT-KIT favorably as it progresses toward IND submission. While still in preclinical stages, these results significantly de-risk the program's next development phases for KIT-driven cancers.

NEW YORK, Sept. 2, 2025 /PRNewswire/ -- Hoth Therapeutics, Inc. (NASDAQ: HOTH), a clinical-stage biopharmaceutical innovator, today announced combined positive findings from multiple preclinical programs evaluating its precision antisense candidate HT-KIT, including compelling anti-tumor efficacy, a clean safety profile, and new GLP-validated bioanalytical results that exceeded internationally recognized regulatory thresholds.

Preclinical Efficacy & Safety Highlights

• Rapid Tumor Kill: HT-KIT triggered significant tumor cell death in preclinical models of gastrointestinal stromal tumors (GIST) and systemic mastocytosis as early as 24 hours post-treatment, with statistically significant tumor shrinkage observed by day 8.
• Strong KIT Suppression: In vitro, HT-KIT achieved over 80% knockdown of KIT expression, the oncogenic driver in multiple aggressive cancers.
• Clean Safety Profile: Multi-dose in vivo studies confirmed no off-target toxicity across critical organs including liver, kidneys, spleen, bone marrow, and thymus.
• Dose-Dependent Biological Signal: A preclinical safety study demonstrated proportional liver engagement (increase from 1.11g to 1.32g at 3.0 mg/kg) with zero gross pathology at any organ site.

GLP-Validated Bioanalytical Results

The study, conducted by Altasciences Company, Inc. under OECD, FDA, and EMA GLP standards, demonstrated that HT-KIT meets or exceeds strict bioanalytical benchmarks:

• Regulatory-Grade Validation: All calibration curve, quality control, and dilution integrity requirements passed with high reproducibility.
• Superior Data Integrity: 90.5% of Incurred Sample Reanalysis (ISR) values fell within ±30%, well above the 66.7% regulatory minimum.
• Extended Stability: HT-KIT remained stable in serum for 37 days at -80°C, surpassing the validated 28-day stability period, with further studies ongoing.
• Flawless Compliance: No protocol or SOP deviations impacted study reliability.

"These results combine a rare and powerful story — tumor kill within 24 hours, clean safety across all systems, and GLP-validated reproducibility beyond regulatory standards," said Robb Knie, CEO of Hoth Therapeutics. "We believe HT-KIT has the potential to transform outcomes in KIT-driven cancers, and these milestones accelerate our path toward IND submission and first-in-human trials."

Next Steps

Hoth expects to integrate this bioanalytical data into its formal GLP toxicology package and is preparing for an IND.

About HT-KIT

HT-KIT is a precision antisense oligonucleotide designed to silence mutant KIT mRNA, an oncogenic driver in gastrointestinal stromal tumors (GIST), systemic mastocytosis, and certain leukemias. By targeting KIT expression at the genetic level, HT-KIT seeks to overcome resistance to tyrosine kinase inhibitors while minimizing systemic side effects.

About Hoth Therapeutics, Inc.

Hoth Therapeutics, Inc. (NASDAQ: HOTH) is a clinical-stage biopharmaceutical company developing targeted, first-in-class therapies for oncology, dermatology, and rare diseases.

For more information, visit http://www.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 for Hoth Therapeutics' (NASDAQ: HOTH) HT-KIT cancer drug?

HT-KIT demonstrated significant tumor cell death within 24 hours, achieved over 80% KIT expression knockdown, and showed clean safety profiles across multiple organs.

How effective was HOTH's HT-KIT in tumor reduction during preclinical trials?

HT-KIT triggered tumor cell death as early as 24 hours post-treatment with statistically significant tumor shrinkage by day 8 in GIST and systemic mastocytosis models.

What were the safety results of Hoth Therapeutics' HT-KIT drug?

HT-KIT showed no off-target toxicity across critical organs including liver, kidneys, spleen, bone marrow, and thymus, with zero gross pathology at any organ site.

How did HOTH's HT-KIT perform in regulatory validation tests?

HT-KIT exceeded regulatory standards with 90.5% of ISR values within ±30% (above 66.7% requirement) and demonstrated stability in serum for 37 days at -80°C.

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

Hoth is preparing to integrate the bioanalytical data into its GLP toxicology package and moving forward with IND submission for first-in-human trials.