Gefapixant Citrate

Expands Adrenergic Pipeline to Address Neurogenic Orthostatic Hypotension and Major Depressive Disorder in Older Adults SAN CARLOS, Calif.--(BUSINESS WIRE)--CuraSen Therapeutics, Inc., a clinical-stage biopharmaceutical company developing oral, rapid onset, small molecule drugs to treat psychiatric and neurodegenerative diseases, announced today that it has appointed Kathleen Sereda Glaub, MBA, formerly executive chair, as chief executive officer. Dr. Anthony Ford will move to the role of president and chief scientific officer, and continue to lead research and development. Patrick Enright, managing director of Longitude Capital, will become chair of the board. Along with these executive changes, the company announced clinical program updates for its drug candidates that are each designed to restore adrenergic stimulus that declines with age or disease. CuraSen’s most recent development candidate is CuraAX (CST-3056), an alpha-1A adrenoceptor (α 1A -AR) agonist being developed as a treatment for neurogenic orthostatic hypotension (nOH). The company is planning to submit an investigational new drug (IND) application this quarter. A significant orphan indication affecting approximately 120,000-150,000 patients in the U.S., nOH is a dysfunction in the autonomic nervous system common in Parkinson’s disease (PD) and related diseases that causes sudden drops in blood pressure upon standing. This can lead to debilitating dizziness, weakness, cognitive decline and dangerous falls. CuraAX is a selective, CNS-penetrant, α 1A -AR agonist designed to provide cognitive benefit as well as control harmful blood pressure deviations. CuraCN (formerly known as CST-103/CST-107), a beta2 adrenoceptor (β 2 -AR) agonist combination, is targeted for a Phase 2b study in major depressive disorder in adults 65 and older, many of whom also suffer from cognitive decline. These plans are based on the company’s previous Phase 2 clinical study in patients that revealed compelling evidence of anti-depressant efficacy and improvements in cognition tests. CuraXN (formerly known as CST-2032/CST-107), a second β 2 -AR agonist combination, is in development for Alzheimer’s disease (AD) to address both cognitive symptoms and disease progression. All three drug candidates work by restoring adrenergic function that declines with age and, in particular, is lost early in neurodegenerative diseases such as AD & PD. CuraSen’s development candidates have strong potential to improve cognitive function and mood, in addition to addressing specific aspects of disease pathobiology. “We are thrilled to have Ms. Glaub assume the role of chief executive officer as CuraSen seeks to capitalize on the company’s adrenergic platform and clinical data to develop a broad pipeline of drugs for psychiatric and neurodegenerative diseases. These include opportunities for a significant, fast-to-market, orphan opportunity in neurogenic orthostatic hypotension,” said Mr. Enright, board chair. “CuraSen will benefit from the collective and complementary executive experience of both Ms. Glaub and Dr. Ford, both co-founders of the company.” Ms. Glaub brings more than 30 years of experience in biopharmaceutical corporate development, strategy, financing and company-building. She serves on the board of directors of IO Biotech, and previously served on the boards of Codexis, Aligos Pharmaceuticals and Escient Pharmaceuticals. Ms. Glaub was previously chief executive officer of Afferent Pharmaceuticals, which was acquired by Merck in 2016 for $1.25 billion. Under her leadership, the company advanced gefapixant to Phase 3 readiness for the treatment of chronic cough and raised $80 million in additional private funding for Afferent. Previously, she served as president of Plexxikon, and helped develop two FDA-approved drugs, Zelboraf® for metastatic melanoma and Turalio® for tenosynovial giant cell tumor (TGCT). She led Plexxikon’s business and financing strategy, negotiated multimillion-dollar partnerships, and led the sale of the company to Daiichi Sankyo for nearly $1 billion. She previously held positions as senior vice president and chief financial officer of Cell Genesys, treasurer of Genentech, and various finance and treasury roles with Intel Corporation. Ms. Glaub received her BA from the University of California, Berkeley, and her MBA from Northwestern University. “CuraSen’s expertise in adrenergic pharmacology, chemistry and clinical development has led to the discovery of three promising drug candidates focused on some of the most debilitating and common neurodegenerative and psychiatric diseases affecting patients and their families. Our adrenergic target mechanisms are already validated by approved drugs in a range of indications, and we have confirmed the ability to develop CNS-penetrant compounds with a unique approach to safety,” said Glaub. “Given the strong and rapid-onset efficacy signals pointing to an anti-depressant effect in our past studies and our understanding of adrenergic deficits in older adults, we believe there is a unique opportunity to address depression in these patients with CuraCN. With CuraXN, we hope to deliver a transformational treatment for Alzheimer’s disease with our holistic approach to restoring brain functionality and health. Lastly, with CuraAX, we believe we can offer major advantages over current treatments for nOH, including durability of efficacy and cognitive benefit, dosing convenience and improved safety.” About CuraSen Therapeutics CuraSen is focused on the development of new treatments for psychiatric and neurodegenerative diseases, including neurogenic orthostatic hypotension, major depressive disorder and Alzheimer’s disease. CuraSen’s drugs are small molecule, oral tablets designed to activate certain receptor populations in the brain to compensate for decline of the adrenergic system driven by aging and disease. The company has evaluated two β 2 -AR agonist candidates, CuraCN and CuraXN, in multiple Phase 2 clinical studies for effects on memory, attention, executive function and mood, as well as safety and tolerability. CuraSen is planning to submit an IND application by the end of 2024 for its third drug candidate CuraAX, an α 1A -AR agonist, for the treatment of nOH. For more information, please visit . Contacts Susan Kinkead Kinkead Communications susan@kinkeadcomm.com 415-509-3610

VANCOUVER, British Columbia, March 27, 2024 (GLOBE NEWSWIRE) -- Algernon Pharmaceuticals Inc. (the “Company” or “Algernon”) (CSE: AGN) (FRANKFURT: AGW0) (OTCQB: AGNPF), a Canadian clinical stage pharmaceutical development company, is pleased to announce that it has closed on its agreement with Seyltx Inc. (“Seyltx”), a privately owned U.S. based drug development company, for the acquisition of Algernon’s NP-120 (“Ifenprodil”) research program for the purchase price of USD $2M cash and a 20% common share equity position in Seyltx. The Company previously announced on November 22, 2003 that it had signed a Letter of Intent with Seyltx, to acquire Algernon’s Ifenprodil research program. Ifenprodil is an N-methyl-D-aspartate (“NMDA”) receptor antagonist specifically targeting the NMDA type subunit 2B (GluN2B), which prevents glutamate signaling. Ifenprodil is one of Algernon’s lead research programs and represents a novel first-in-class potential treatment for chronic cough. It is thought to interfere with central signalling in the brain, suppressing the urge to cough. “There are multiple converging lines of evidence that define GluN2B as the master regulator of the cough reflex in the deep brain, including human clinical data with the allosteric inhibitor Ifenprodil in the hardest to treat cough population, those with underlying idiopathic pulmonary fibrosis, illustrating dramatic reductions in cough counts. This human efficacy data is complemented by an extensive safety package that de-risks the final phases of clinical development,” said Dietrich A. Stephan, Ph.D. co-founder and CEO of Seyltx. “I have great respect for the Algernon team who have done an outstanding job at maturing the program to this point, and we look forward to completing the clinical development of this exciting agent for a common and debilitating condition.” Seyltx plans to initiate an Ifenprodil multi-center Phase 2b placebo-controlled chronic cough study in CY2024. Algernon’s clinical management team will be available to provide support, oversight, and management of the study. “We are very pleased to have closed this transaction with Seyltx,” said Christopher J. Moreau, Algernon’s Chief Executive Officer. “We believe that Ifenprodil, a first in class potential treatment for chronic cough could outperform all other drugs that have been clinically investigated to date. We look forward to working with Seyltx as they advance Ifenprodil into the Phase 2b clinical trial.” In connection with the transaction, Maxim Group LLC was paid a transaction advisory services fee pursuant to an agreement with Algernon whereby Maxim was retained to identify and evaluate potential M&A and strategic opportunities. Algernon’s Phase 2a Study Data Algernon’s decision to advance to a Phase 2b cough study was based on positive data previously reported from the Company’s proof of concept Phase 2a study of idiopathic pulmonary fibrosis (“IPF”) and chronic cough, where Ifenprodil showed a significant reduction in cough count. Patients with IPF are usually excluded from trials in refractory chronic cough (“RCC”), and cough in this population is regarded as extremely difficult to treat. Key Data: The geometric mean 24-hour cough counts were reduced by 32.0% at 4 weeks(p = 0.023) and 39.5% at 12 weeks (p = 0.001) compared to baselineThe geometric mean awake cough counts were reduced by 30.2% at 4 weeks(p = 0.038) and 37.4% at 12 weeks (p = 0.002) compared to baselineAlgernon previously announced on January 14, 2022, that it had received positive feedback from the U.S. Food and Drug Administration at its pre-Investigational New Drug (pre-IND) meeting for its investigation of Ifenprodil solely for the treatment of chronic cough. About Chronic Cough Chronic cough is defined as a cough lasting for more than eight weeks in duration and in the United States cough continues to be one of the most common reasons that adults consult medical doctors. Some cases of chronic cough are so debilitating that quality of life is severely impacted leading to depression, anxiety, urinary incontinence, dysphonia, sleep interruption, vomiting, and even rib fractures further adding to the decay in socio-familial dynamics. Chronic cough is believed to be the result of a hypersensitivity of the cough reflex within the neuronal circuitry that governs the urge to cough, wherein one or more aspects that regulate cough are over-active to stimulus, triggering a cough at abnormal levels. Trials of cough suppressants (“Antitussives”) have shown differences in response that may reflect differing pathological processes driving cough in different patients. Experimental Antitussives (like gefapixant and camlipixant) often only engage a single receptor, while the overall cough response is governed by multiple receptors triggered by a large variety of stimuli. A compound like Ifenprodil, acting centrally in the brain where all peripheral messages are sent and coordinated, may achieve a better outcome than what has been achieved by others in clinical trials. Chronic Cough Market According to Data Bridge Market Research analyses, the global chronic cough market was valued at USD $6.15B in 2021 and is projected to grow up to USD $11.38B by 2029. Merck & Co. obtained the rights to gefapixant, a P2X3 receptor antagonist, as the lead asset in the acquisition of Afferent Pharmaceuticals in 2016. At the time, gefapixant had interim data from a Phase 2b study in RCC. The deal was worth up to USD $1.25 billion. Bellus Health, which was advancing camlipixant, its own novel P2X3 receptor antagonist, closed a deal on June 16, 2023 with GSK plc which bought all the outstanding shares in Bellus for USD $14.75 per share in cash with a total deal value estimated at USD $2 billion, confirming the need for better therapies for chronic cough. About NP-120 (Ifenprodil) NP-120 selectively inhibits GluN2B receptors which diminish excitability of neurons and prevent the relaying of information along neuronal circuitry, including the cough reflex. NP-120 may also inhibit the neuroplastic enhancement of central and peripheral cough response neurons. About Seyltx Inc. Seyltx is a clinical-stage pharmaceutical company focused on addressing refractory chronic cough by modulating the master switch of the cough reflex in the brain. Refractory chronic cough is a common disorder estimated to affect between 4-5 million individuals in the United States alone, for which there exist no effective therapies. About Algernon Pharmaceuticals Inc. Algernon Pharmaceuticals is a Canadian clinical stage drug development company investigating multiple drugs for unmet global medical needs. Algernon Pharmaceuticals has active research programs for chronic kidney disease and is the parent company of a private subsidiary called Algernon NeuroScience, that is advancing a psychedelic program investigating a proprietary form of DMT for stroke and traumatic brain injury. CONTACT INFORMATION Christopher J. MoreauCEOAlgernon Pharmaceuticals Inc.604.398.4175 ext 701info@algernonpharmaceuticals.com investors@algernonpharmaceuticals.com www.algernonpharmaceuticals.com Neither the Canadian Securities Exchange nor its Market Regulator (as that term is defined in the policies of the Canadian Securities Exchange) accepts responsibility for the adequacy or accuracy of this release. CAUTIONARY DISCLAIMER STATEMENT: No Securities Exchange has reviewed nor accepts responsibility for the adequacy or accuracy of the content of this news release. This news release contains forward-looking statements relating to product development, licensing, commercialization and regulatory compliance issues and other statements that are not historical facts. Forward-looking statements are often identified by terms such as “will”, “may”, “should”, “anticipate”, “expects” and similar expressions. All statements other than statements of historical fact, included in this release are forward-looking statements that involve risks and uncertainties. There can be no assurance that such statements will prove to be accurate and actual results and future events could differ materially from those anticipated in such statements. Important factors that could cause actual results to differ materially from the Company’s expectations include the failure to satisfy the conditions of the relevant securities exchange(s) and other risks detailed from time to time in the filings made by the Company with securities regulations. The reader is cautioned that assumptions used in the preparation of any forward-looking information may prove to be incorrect. Events or circumstances may cause actual results to differ materially from those predicted, as a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the Company. The reader is cautioned not to place undue reliance on any forward-looking information. Such information, although considered reasonable by management at the time of preparation, may prove to be incorrect and actual results may differ materially from those anticipated. Forward-looking statements contained in this news release are expressly qualified by this cautionary statement. The forward-looking statements contained in this news release are made as of the date of this news release and the Company will update or revise publicly any of the included forward-looking statements as expressly required by applicable law.