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Hoth Therapeutics' mRNA 'Frameshifting' Therapy HT-KIT for Mast Cell Cancers Reduces Size, Spread - Research Published in Molecular Therapy

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Targeting KIT by frameshifting mRNA transcripts as a therapeutic strategy for aggressive mast cell neoplasm

NEW YORK, Aug. 11, 2021 /PRNewswire/ -- Hoth Therapeutics, Inc. (NASDAQ: HOTH), a patient-focused biopharmaceutical company, today highlights recent findings from North Carolina State University, that its new treatment for mast cell cancers, known as HT-KIT, reduces the number of mast cells by "mutating" the messenger RNA (mRNA) before it can deliver instructions for manufacturing the gene responsible for cell proliferation.

(PRNewsfoto/Hoth Therapeutics Inc.)
(PRNewsfoto/Hoth Therapeutics Inc.)

"Current treatments for mast cell cancers target signaling from the receptor encoded by the c-KIT gene, and the efficacy of current therapies can be negatively affected by c-KIT mutations associated with disease development," says Glenn Cruse, assistant professor of immunology at North Carolina State University and a Scientific Advisor to Hoth and corresponding author of the research. "We are targeting the gene itself, regardless of mutation. If we target the gene that drives progression, then we can target the disease."

"We are altering the message that makes the protein – flipping an 'on' switch to 'off,'" Cruse says. "If you get mRNA to produce a protein that is mutated and severely truncated, your cell will recognize that and degrade the message so that the protein isn't produced."

The researchers used their frameshifted c-KIT mRNA approach on mast cell leukemia cells in vitro and found that KIT protein expression, signaling and function were reduced. The cancer cells stopped proliferating and began dying within hours. In a mouse model, tumor growth and infiltration of other organs were reduced, and tumor cell death increased when the frameshifted c-KIT mRNA was induced.

"The other advantage to our technique is that it solves the problem of degradation evasion," Cruse says. "Occasionally faulty messages will evade degradation and their mutated proteins get produced anyway. But proteins produced by the frameshifted c-KIT mRNA are inert, or non-functional. So even if they get produced, they cannot cause more harm."

The research appears in Molecular Therapy and is supported by the National Institutes of Health. NC State postdoctoral researcher Douglas Snider is first author. The technology described in the paper has been exclusively licensed by Hoth Therapeutics and being developed as HT-KIT.

In an article written by NC State, it states that the novel process of frameshifting changes the pre-mRNA so that the mature mRNA is degraded, and any protein produced from its instructions is altered and inert. In a mouse model, frameshifting directed at the c-KIT gene reduced mast cell tumor size and prevented infiltration into other organs.

Earlier this year, Hoth announced that its novel HT-KIT exhibited highly positive results in humanized mast cell neoplasm models, representative in vitro and in vivo models for aggressive, mast cell-derived cancers such as mast cell leukemia and mast cell sarcoma. The anti-cancer therapeutic, which is currently in development, uses mRNA frame shifting that induces apoptosis of neoplastic mast cells.

About Hoth Therapeutics, Inc.
Hoth Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing new generation therapies for unmet medical needs. Hoth's pipeline development is focused to improve the quality of life for patients suffering from indications including atopic dermatitis, skin toxicities associated with cancer therapy, chronic wounds, psoriasis, asthma, acne, mast-cell derived cancers & anaphylaxis and pneumonia. Hoth has also entered into two different agreements to further the development of two therapeutic prospects to prevent or treat COVID-19. 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, 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, 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 entitled "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
Phone: (678) 570-6791

Media Relations Contact:
Email: hoth-mak@makovsky.com


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SOURCE Hoth Therapeutics, Inc.