NK1

Pictured: Bayer's office in Berlin, Germany/iStock, Elenasfotos Bayer reported another Phase III win for its menopause drug candidate Tuesday, linking the molecule to improved outcomes in a long-term study and setting the stage for approval filings. The clinical trial evaluated the safety and efficacy of elinzanetant, a dual neurokinin-1,3 (NK-1,3) receptor antagonist, in the treatment of hot flashes associated with menopause over 52 weeks. Bayer reported a pair of 12-week Phase III studies met their coprimary endpoints in January 2024, but still needed a hit on the third trial to show the long-term effects of the molecule. Bayer’s topline readout revealed that the trial met its primary endpoint, which tracked the mean change in the frequency of moderate to severe hot flashes after 12 weeks of oral daily dosing with elinzanetant or placebo. The company also said the safety pro across 52 weeks of dosing was consistent with the results of previously published studies including its Phase 2b dose-finding trial. The company plans to include data from all three clinical trials in applications for approval. If Bayer wins approval, it will face competition from Astellas’ rival NK3 receptor antagonist Veozah (fezolinetant). The FDA approved Veozah for the treatment of vasomotor symptoms, the medical term for hot flashes, due to menopause in May 2023. Bayer is keeping back data from all three trials to present at upcoming scientific congresses, making it impossible to assess how elinzanetant compares to Veozah. Astellas reported 3.6 billion yen ($24 million) of Veozah sales over the first nine months of its financial year and has run ads during the Super Bowl and the Oscars to promote the product. Elinzanetant may have an advantage over Veozah because it targets NK1 and NK3, rather than just the latter receptor. Some studies have suggested NK1 antagonists may improve sleep. Bayer’s long-term trial looked at changes in sleep disturbances, which are frequently associated with hot flashes, but the company has yet to release the data. The details of the readout will shape the prospects of an important molecule for Bayer. The company has 10 programs in Phase III development but CEO Bill Anderson has warned the “late-stage pipeline is thin relative to the patent losses we have in the next years,” telling the Financial Times that the problems stem from historical under-investment. Having stopped a Phase III trial of the investigational factor XIa inhibitor asundexian in November 2023, Bayer is looking to elinzanetant and late-phase prostate cancer and chronic kidney disease prospects to drive growth and offset the upcoming loss of patent protection for Xarelto (rivaroxaban). Nick Paul Taylor is a freelance pharmaceutical and biotech writer based in London. He can be reached on LinkedIn.

HT-ALZ emerges as a promising novel solution for combating neuroinflammation and cognitive deficits associated with Alzheimer's Disease. NEW YORK, March 19, 2024 /PRNewswire/ -- Hoth Therapeutics, Inc. (NASDAQ: HOTH), is pleased to unveil positive pre-clinical research showcasing the potential of HT-ALZ, an innovative Alzheimer's disease therapeutic. Targeting the Substance P/Neurokinin 1 Receptor pathway, HT-ALZ emerges as a promising novel solution for combating neuroinflammation and cognitive deficits associated with Alzheimer's Disease. This pioneering study, conducted by a distinguished team of researchers including Carla Yuede, Kate M. Reardon, Ryan T. Harrigan, and John R. Cirrito, among others, highlights HT-ALZ's profound impact on Alzheimer's pathology. By specifically antagonizing the NK1 receptor, HT-ALZ not only reduces soluble Aβ levels in the brain's interstitial fluid but also significantly diminishes anxiety-like behavior and enhances cognitive function in preclinical models. The research presents compelling evidence of HT-ALZ's capacity to improve memory tasks related to the hippocampus and sensorimotor gating, showcasing an important step forward in Alzheimer's disease treatment. While the effects on plaque deposition and Aβ levels were inconclusive, the treatment's cognitive benefits suggest that HT-ALZ's mode of action may involve a reduction in brain inflammation, thereby improving cognitive outcomes for Alzheimer's patients. HT-ALZ's pre-clinical significance lies in its ability to restore cognitive functions and improve quality of life for subjects suffering from Alzheimer's disease, offering a beacon of hope. Hoth Therapeutics remains committed to further research and development of HT-ALZ, including detailed analyses of its effects on microglial activation and brain inflammation. The company is optimistic about HT-ALZ's path toward. The full manuscript of the study will be published later this year and we look forward to a presentation of the results by the scientists named above who will be sharing this data at an Alzheimer's Research Center group at Washington University in St Louis. For more information on Hoth Therapeutics and our innovative approach to Alzheimer's disease treatment with HT-ALZ, please visit 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 . 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 Phone: (678) 570-6791 Company Codes: NASDAQ-NMS:HOTH

Bayer plans to share the data at upcoming scientific congresses. Bayer has kept up the pressure on Astellas’ hot flash drug Veozah, reporting a clean sweep of coprimary endpoints in a pair of phase 3 trials of its rival molecule elinzanetant. Astellas and Bayer bought spots at the head of the race for the postmenopausal market, respectively paying 500 million euros ($547 million) for Ogeda and $425 million upfront for KaNDy Therapeutics. The deals covered molecules designed to bring relief for hot flashes, known medically as moderate to severe vasomotor symptoms (VMS), without using hormones.  Having seen Astellas win FDA approval for its drug last year, Bayer reported topline data from two pivotal trials of its rival candidate, elinzanetant, Monday. The readout suggests Bayer has a good shot at getting elinzanetant to market without providing much clarity on how the molecule matches up to Veozah. Like Astellas, Bayer tested its candidate against four coprimary endpoints that looked at the severity and frequency of hot flashes after four and 12 weeks of treatment. And, again like Astellas, the drugmaker met all four coprimary endpoints across the two studies. Both molecules acted on hot flashes in the first week of treatment and were linked to improvements in sleep disturbances and quality of life. Bayer is yet to share any numbers from the studies. With Astellas’ Veozah already on the market, the details of the data could go a long way to determining whether Bayer can and establish elinzanetant as a major product. Elinzanetant has a slightly different mechanism than Veozah, acting on neurokinin-1 (NK-1) and 3 rather than just neurokinin-3. Other researchers have linked antagonism of NK-1 to effects on insomnia and mood disorders unrelated to menopause, suggesting that Bayer’s dual-target approach may help improve sleep, but the lack of data in Bayer’s release means the clinical impact of the mechanism remains unclear.  The German drugmaker plans to share the data at upcoming scientific congresses. Preparations for the presentations will proceed alongside work to wrap up a third phase 3 trial, results from which are due in the coming months, and file for approval in the treatment of moderate to severe VMS associated with menopause.