Hoth Therapeutics Reports FDA Orphan Drug Designation and Strong Preclinical Data for HT-KIT in Rare c-KIT-Driven Cancers
Hoth Therapeutics (NASDAQ: HOTH) announced FDA Orphan Drug Designation for HT-KIT and presented preclinical results showing >80% KIT mRNA/protein suppression and statistically significant tumor-volume reduction by Day 8 in systemic mastocytosis and GIST models. GLP-validated bioanalytical methods are complete to support IND-enabling studies, and Japan Patent No. 7677628 protects the platform through 2039. Reported tolerability showed no dose-limiting toxicities in the described preclinical work. Near-term plans include completing GLP toxicology and CMC packages, submitting an IND, and initiating a Phase 1/2 dose-escalation/expansion study with translational biomarkers and early efficacy readouts.
Hoth Therapeutics (NASDAQ: HOTH) ha annunciato la Designazione come Farmaco Orfano FDA per HT-KIT e ha presentato risultati preclinici che mostrano >80% soppressione di KIT mRNA/proteina e una riduzione della dimensione del tumore statisticamente significativa entro il Day 8 nei modelli di mastocitosi sistemica e GIST. Metodi bioanalitici con validazione GLP sono completi per supportare studi abilitanti l'IND, e la patente giapponese n. 7677628 protegge la piattaforma fino al 2039. La tollerabilità riportata non ha mostrato tossicità dose-limitante nel lavoro preclinico descritto. I piani a breve termine includono completare i pacchetti GLP di tossicologia e CMC, presentare l'IND e avviare uno studio di fase 1/2 di escursione/dosaggio con biomarcatori di traslazione e letture precoci di efficacia.
Hoth Therapeutics (NASDAQ: HOTH) anunció la Designación de Fármaco Huérfano de la FDA para HT-KIT y presentó resultados preclínicos que muestran >80% de supresión de KIT mRNA/proteína y una reducción del volumen tumoral estadísticamente significativa para el Día 8 en modelos de mastocitosis sistémica y GIST. Los métodos bioanalíticos validados por GLP están completos para apoyar estudios que habilitarán el IND, y la patente japonesa No. 7677628 protege la plataforma hasta 2039. La tolerabilidad reportada no mostró toxicidad límite de dosis en el trabajo preclínico descrito. Los planes a corto plazo incluyen completar los paquetes GLP de toxicología y CMC, presentar un IND e iniciar un estudio de Fase 1/2 de escalamiento de dosis/expansión con biomarcadores de translación y lecturas tempranas de eficacia.
Hoth Therapeutics (NASDAQ: HOTH)은 HT-KIT에 대한 FDA의 고아약 지정을 발표했고, >80% KIT mRNA/단백질 억제 및 8일 차에 시스템성 비만세포증 및 GIST 모델에서 통계적으로 유의한 종양 부피 감소를 보인 전임상 결과를 제시했습니다. GLP로 검증된 생물분석 방법은 IND 가능 연구를 지원하기 위해 완료되었고, 일본 특허 No. 7677628은 2039년까지 플랫폼을 보호합니다. 보고된 내약성은 설명된 전임상 연구에서 용량 제한 독성을 보이지 않았습니다. 단기 계획으로는 GLP 독성학 및 CMC 패키지 완료, IND 제출, 전달 가능한 바이오마커 및 초기 효능 지표를 포함하는 용량 증가/확장 1상/2상 연구를 시작하는 것이 포함됩니다.
Hoth Therapeutics (NASDAQ: HOTH) a annoncé une designation de médicament orphelin par la FDA pour HT-KIT et a présenté des résultats précliniques montrant une suppressions >80% de l'ARNm/protéine KIT et une réduction statistiquement significative du volume tumoral dès le Jour 8 dans des modèles de mastocytose systémique et de GIST. Des méthodes bioanalytiques validées GLP sont complètes pour soutenir les études en vue de l'IND, et le brevet japonais n° 7677628 protège la plateforme jusqu'en 2039. La tolérance rapportée n'a montré aucune toxicité limitante de dose dans les travaux précliniques décrits. Les plans à court terme incluent la finalisation des paquets GLP de toxicologie et de CMC, le dépôt d'un IND et le démarrage d'une étude de phase 1/2 à dose-échelons/expansion avec des biomarqueurs translationnels et des premiers retours d'efficacité.
Hoth Therapeutics (NASDAQ: HOTH) gab die FDA Orphan Drug Designation für HT-KIT bekannt und präsentierte präklinische Ergebnisse, die eine >80% KIT mRNA/Proteinsuppression sowie eine statistisch signifikante Reduktion des Tumorvolumens bis Tag 8 in Modellen der systemischen Mastzellenerkrankung und GIST zeigen. GLP-validierte bioanalytische Methoden sind abgeschlossen, um IND-fähige Studien zu unterstützen, und Japan Patent Nr. 7677628 schützt die Plattform bis 2039. Die berichtete Verträglichkeit zeigte in der beschriebenen präklinischen Arbeit keine dosislimitierenden Toxizitäten. Kurzfristige Pläne umfassen den Abschluss von GLP-toxikologie- und CMC-Paketen, die Einreichung eines IND und die Einleitung einer Phase-1/2-Dosis-Skalierungs-/Expansionsstudie mit translationalen Biomarkern und frühen Wirksamkeitskennzahlen.
Hoth Therapeutics (NASDAQ: HOTH) أعلنت عن تصنيف دواء يتيم من FDA لـ HT-KIT وقدمت نتائج ما قبل سريرية تُظهر أكثر من 80% قمع لـ KIT mRNA/البروتين وتخفيضاً ذا دلالة إحصائية في حجم الورم بحلول اليوم 8 في نماذج المتعددة النظامية للوشاح وGIST. الطرق البيواناليتيكية المعتمدة من GLP جاهزة لدعم دراسات IND، وتحمي البراءة اليابانية رقم 7677628 المنصة حتى 2039. التحمل المبلغ عنه لم يظهر سمية محدودة للجرعة في العمل ما قبل السريري الموصوف. تشمل الخطط القريبة الأجل إكمال حزم GLP في علم السموم وCMC، وتقديم IND، والبدء في دراسة من المرحلة 1/2 بزيادة جرعة/توسيع مع علامات ترجمة ومؤشرات فاعلية مبكرة.
Hoth Therapeutics (NASDAQ: HOTH) 宣布 FDA 的 孤儿药指令 授予 HT-KIT，并展示了前临床结果，显示在系统性肥大细胞增多症和GIST模型中在第8天之前实现了 >80% KIT mRNA/蛋白抑制 以及肿瘤体积的统计学显著降低。GLP 验证的生物分析方法已完成，可支持 IND 启用研究，且日本专利 № 7677628 通过 2039 保护该平台。所报告的耐受性在所述前临床工作中未显示剂量限制性毒性。近期计划包括完成 GLP 毒理学与 CMC 包、提交 IND，并启动带有转化性生物标志物与早期有效性读数的阶段 1/2 剂量爬坡/扩展研究。
- Orphan Drug Designation granted by FDA (U.S.)
- >80% KIT mRNA/protein suppression in preclinical models
- Statistically significant tumor-volume reduction by Day 8
- GLP-validated bioanalytical methods completed for IND support
- Japan Patent No. 7677628 protecting platform through 2039
- Program remains preclinical; no human clinical data yet
- IND submission still pending pending completion of GLP toxicology and CMC
- Clinical efficacy and safety in humans are unproven despite preclinical signals
Insights
Orphan designation, GLP analytics, strong preclinical KIT suppression (>80%) and IND work mark a cautiously positive preclinical milestone for HT-KIT.
Hoth Therapeutics shows clear preclinical advancement as of
The business mechanism is transcript-level silencing of KIT, which directly reduces KIT mRNA/protein rather than inhibiting kinase activity. Reported tolerability in the disclosed preclinical work showed no dose-limiting toxicities to date. Dependencies and risks are explicit: IND-enabling GLP toxicology and CMC packages must be completed, and human safety/efficacy remain untested. The data are preclinical only, so human outcomes and regulatory review are unresolved.
Concrete near-term items to watch are completion of GLP toxicology and CMC packages, IND submission, and initiation of the planned Phase 1/2 dose-escalation/expansion study with translational biomarkers and early efficacy endpoints (ORR, DCR, PFS signals) as stated. These steps define the next actionable milestones for the program and the timeline for first-in-human evaluation.
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Planned Next Steps (Near-Term):
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Complete GLP toxicology and CMC packages; submit IND.
- Initiate Phase 1/2 dose-escalation/expansion study in advanced systemic mastocytosis and other KIT-driven tumors with translational biomarkers of target engagement (KIT knock-down, tryptase/MRK signaling) and early efficacy readouts (ORR, DCR, PFS signals).
Preclinical Summary (2025):
- Potent gene-level target suppression: HT-KIT achieved >
80% reduction of KIT mRNA/protein across in-vitro systems and in vivo models of systemic mastocytosis and GIST. - Rapid anti-tumor activity: In xenograft models, statistically significant tumor-volume reduction by Day 8 was observed, accompanied by apoptotic signaling consistent with KIT pathway knock-down.
- Favorable tolerability in early studies: No dose-limiting toxicities observed in the reported preclinical work to date.
- Bioanalytical readiness: GLP-validated bioanalytical methods completed to support pharmacokinetic, biodistribution, and exposure-response analyses for IND.
Mechanistic Rationale:
Unlike small-molecule TKIs that inhibit kinase activity, HT-KIT operates upstream at the transcript level, silencing both mutant and wild-type KIT. This mechanism is designed to bypass resistance pathways (secondary mutations, compensatory signaling) and reduce off-target liabilities, potentially improving durability and tolerability in KIT-driven diseases such as aggressive systemic mastocytosis (ASM), SM-AHN, mast cell leukemia (MCL), GIST, and select leukemias.
- Orphan Drug Designation (
U.S. ) supports development in a rare disease with incentives including potential exclusivity upon approval, tax credits, and fee waivers.
Planned Next Steps (Near-Term):
- Complete GLP toxicology and CMC packages; submit IND.
- Initiate Phase 1/2 dose-escalation/expansion study in advanced systemic mastocytosis and other KIT-driven tumors with translational biomarkers of target engagement (KIT knock-down, tryptase/MRK signaling) and early efficacy readouts (ORR, DCR, PFS signals).
- Continue regional IP expansion and evaluate strategic partnerships for development and commercialization.
"HT-KIT's transcript-level suppression of KIT has now produced consistent anti-tumor performance across models, with a clean preclinical tolerability profile and GLP-ready analytics," said Robb Knie, Chief Executive Officer. "With Orphan Drug Designation secured and an IND-enabling package progressing, we are preparing for a disciplined entry into first-in-human evaluation."
About HT-KIT:
HT-KIT is a precision ASO designed to silence KIT at the mRNA level, aiming to overcome resistance and off-target toxicity seen with kinase inhibitors in systemic mastocytosis, GIST, and select leukemias.
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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