Nerve Degeneration

- Based on topline results from the Phase 3 PHOENIX trial of AMX0035 in ALS, Amylyx has started a process with the FDA and Health Canada of voluntarily discontinuing the marketing authorizations for RELYVRIO/ALBRIOZA - RELYVRIO/ALBRIOZA will no longer be available for new patients as of today; Patients currently on therapy in the U.S. and Canada who, in consultation with their physician, wish to continue can be transitioned to a free drug program; PHOENIX Open Label Extension is ongoing - Amylyx continues to advance AMX0035 in Wolfram syndrome and in progressive supranuclear palsy (PSP), and AMX0114 in ALS - Interim data from the Phase 2 HELIOS trial of AMX0035 for the treatment of Wolfram syndrome are expected this month and will be presented during a webcast on April 10, 2024 - Restructuring plan reduces workforce by approximately 70% to focus resources on key clinical and preclinical programs and extends expected cash runway into 2026, through anticipated data readouts for AMX0035 in Wolfram syndrome and PSP, and AMX0114 in ALS CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Amylyx Pharmaceuticals, Inc. (NASDAQ: AMLX) (“Amylyx” or the “Company”) today announced the Company has started a process with the U.S. Food and Drug Administration (FDA) and Health Canada to voluntarily discontinue the marketing authorizations for RELYVRIO®/ALBRIOZA™ (sodium phenylbutyrate and taurursodiol [also known as ursodoxicoltaurine]; also known as AMX0035) and remove the product from the market in the U.S. and Canada based on topline results from the Phase 3 PHOENIX trial. RELYVRIO/ALBRIOZA will no longer be available for new patients as of today. Patients currently on therapy in the U.S. and Canada who, in consultation with their physician, wish to stay on treatment can be transitioned to a free drug program. “While this is a difficult moment for the ALS community, we reached this path forward in partnership with the stakeholders who will be impacted and in line with our steadfast commitment to people living with ALS and other neurodegenerative diseases. The decision to remove RELYVRIO/ALBRIOZA from the market and provide therapy free of charge for those who wish to continue was informed by the PHOENIX trial results, engagement with regulatory authorities, and discussions with the ALS community. Thank you to each and every person who shared feedback with us and continues to support our commitment to the ALS community,” said Joshua Cohen and Justin Klee, Co-CEOs of Amylyx. Amylyx will continue to evaluate and share learnings from PHOENIX to help inform future ALS research. At this time, Amylyx intends to continue to collect available data on survival at the encouragement of ALS specialists. The PHOENIX Open Label Extension (OLE) is ongoing. Topline data from PHOENIX will be presented at the American Academy of Neurology (AAN) Annual Meeting in Denver and online, taking place April 13-18, 2024. The presentation is scheduled to occur on April 16, 2024, during the Clinical Trials Plenary Session (9:15 a.m. – 11:30 a.m. MT) and will be made available on the “Publications and Presentations” section of the Company’s website following the conclusion of the presentation. As part of the Company’s purpose to discover and develop innovative new treatment options for neurodegenerative diseases, Amylyx continues to advance two key programs investigating its lead asset AMX0035 in Wolfram syndrome and progressive supranuclear palsy (PSP), and AMX0114, an antisense oligonucleotide targeting calpain-2, in ALS. “Our pipeline is supported by compelling clinical and preclinical science demonstrating the potential of AMX0035 and AMX0114 in neurodegenerative diseases. AMX0035 was designed to slow or mitigate neurodegeneration by targeting endoplasmic reticulum stress and mitochondrial dysfunction, two connected central pathways that lead to cell death and neurodegeneration. We are investigating AMX0035 in diseases where these two pathways are implicated, which includes Wolfram syndrome and progressive supranuclear palsy,” said Camille L. Bedrosian, MD, Chief Medical Officer of Amylyx. “We look forward to presenting interim data from our Phase 2 HELIOS study of AMX0035 in Wolfram syndrome, a rare, genetic, fatal neurodegenerative disease with no FDA-approved treatment options, later this month. In addition, our Phase 3 ORION study remains ongoing to evaluate AMX0035 for the treatment of progressive supranuclear palsy, a rare neurodegenerative disorder characterized as a tauopathy. We continue to plan for an interim analysis to evaluate the data from ORION that is now expected in mid-2025.” Dr. Bedrosian continued, “We also remain focused on ALS and believe AMX0114 has strong potential for the treatment of ALS and other diseases. Calpain-2 is considered an essential protein in the process of axonal degeneration and has been repeatedly linked to neurofilament biology in published studies. In our preclinical studies of AMX0114 and in multiple independent published studies, inhibition of calpain-2 has reduced cell death and degeneration and decreased neurofilament levels. We expect to initiate a clinical trial studying AMX0114 in ALS in the second half of this year.” Amylyx also announced a restructuring to focus the Company’s financial resources on upcoming clinical milestones. The Company will reduce its workforce by approximately 70% and decrease external financial commitments outside of its priority areas. With these changes, Amylyx expects to have cash runway into 2026, which will allow the organization to deliver on key upcoming milestones, including data readouts from HELIOS (AMX0035 in Wolfram syndrome), ORION (AMX0035 in PSP), and its planned trial of AMX0114 in ALS. “We are so thankful and grateful to our Amylyx team for their contributions and steadfast dedication,” said Cohen and Klee. “Together, the work we have accomplished across the world has helped build a vital foundation to achieve our mission of one day ending the suffering caused by neurodegenerative diseases, which continue to have critical, unaddressed needs.” HELIOS Interim Data in Wolfram Syndrome Investor Webcast Details Amylyx will host a virtual webcast with Dr. Fumihiko Urano, Principal Investigator of the Phase 2 HELIOS clinical trial in Wolfram syndrome and Professor Medicine in the Division of Endocrinology, Metabolism & Lipid Research at Washington University School of Medicine, to discuss interim HELIOS data on April 10, 2024, at 1:30 p.m. ET. A live webcast of the presentation can be accessed under “Events and Presentations” in the Investor section of the Company’s website, , and will be available for replay for 90 days following the event. About AMX0035 AMX0035 is an oral, fixed-dose combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO; also known as ursodoxicoltaurine outside of the U.S.). AMX0035 was designed to slow or mitigate neurodegeneration by targeting endoplasmic reticulum (ER) stress and mitochondrial dysfunction, two connected central pathways that lead to cell death and neurodegeneration. We believe that our proprietary combination of PB and TURSO and their complementary mechanisms of action will allow us to synergistically target abnormal cell death to better prevent neurodegeneration than treatment targeted at either mechanism of action alone. AMX0035 is being studied as a potential treatment for Wolfram syndrome and progressive supranuclear palsy, two neurodegenerative diseases. About AMX0114 AMX0114 is an antisense oligonucleotide designed to target the gene encoding calpain-2, a key contributor to the axonal (Wallerian) degeneration pathway. Axonal degeneration has been recognized as an important early contributor to the clinical presentation and pathogenesis of ALS and other neurodegenerative diseases. Calpain-2 has been implicated in the pathogenesis of ALS based on findings of elevated levels of calpain-2 and its cleavage products in postmortem ALS tissue, therapeutic benefit of calpain-2 modulation in animal models of ALS, and the role of calpain-2 in cleaving neurofilament, a broadly researched biomarker in ALS. Preclinical studies completed to date have shown that AMX0114 achieves potent, dose-dependent, and durable knockdown of CAPN2 mRNA expression and calpain-2 protein levels in human motor neurons. Moreover, in preclinical efficacy studies, treatment with AMX0114 reduced extracellular neurofilament light chain levels following neurotoxic insult in induced pluripotent stem cell (iPSC)-derived human motor neurons, and improved survival of iPSC-derived human motor neurons harboring ALS-linked, pathogenic TDP-43 mutations. About ALS Amyotrophic lateral sclerosis (ALS, also known as motor neuron disease) is a relentlessly progressive and fatal neurodegenerative disorder caused by motor neuron death in the brain and spinal cord. Motor neuron loss in ALS leads to deteriorating muscle function, the inability to move and speak, respiratory paralysis, and eventually, death. More than 90% of people with ALS have sporadic disease, showing no clear family history. ALS affects around 30,000 people in the U.S., and more than 30,000 people are estimated to be living with ALS in Europe (European Union and the United Kingdom). People living with ALS have a median survival of approximately two years from diagnosis. About the HELIOS Trial The HELIOS trial (NCT05676034) is a 12-participant, open-label, proof of biology, Phase 2 trial designed to study the effect of AMX0035 on safety and tolerability, and various measures of endocrinological, neurological, and ophthalmologic function in adult participants living with Wolfram syndrome. About Wolfram Syndrome Wolfram syndrome is an autosomal recessive neurodegenerative disease characterized by childhood-onset diabetes, optic nerve atrophy, and neurodegeneration. Common manifestations of Wolfram syndrome include diabetes mellitus, optic nerve atrophy, central diabetes insipidus, sensorineural deafness, neurogenic bladder, and progressive neurologic difficulties. Genetic and experimental evidence suggests that endoplasmic reticulum (ER) dysfunction is a critical pathogenic component of Wolfram syndrome. The prognosis of Wolfram syndrome is poor, and many people with the disease die prematurely with severe neurological disabilities. About the ORION Trial The ORION trial (NCT06122662) is a global, randomized, double-blind, placebo-controlled Phase 3 clinical trial designed to assess the efficacy, safety, and tolerability of AMX0035 compared to placebo in people living with progressive supranuclear palsy (PSP). The ORION Phase 3 trial was designed and planned in collaboration with key global academic leaders, people living with PSP and their caregivers, and industry advocacy organizations. About PSP Progressive supranuclear palsy (PSP) is a sporadic, rare, and adult-onset neurodegenerative disorder that affects walking and balance, eye movement, swallowing, and speech. People living with PSP have a life expectancy of six to eight years after initial diagnosis, and its epidemiology is similar to that of amyotrophic lateral sclerosis (ALS). PSP typically begins in late-middle age and rapidly progresses over time. The disease affects approximately seven in 100,000 people worldwide, and there are currently no disease-modifying therapies approved for the treatment of PSP. PSP is characterized by abnormal tau inclusions and is consequently also known as a tauopathy. Similar to other neurodegenerative diseases, pathophysiologic changes underlying PSP are multifactorial, with several genetic and environmental factors likely contributing to tau dysfunction and aggregation. Multiple pathways, including genetic mutations, endoplasmic reticulum (ER) stress, and the activation of unfolded protein response, mitochondrial dysfunction, and neuroinflammation have been implicated as contributors to tau dysfunction and aggregation. About Amylyx Pharmaceuticals Amylyx Pharmaceuticals, Inc. is committed to supporting and creating more moments for the neurodegenerative disease community through the discovery and development of innovative new treatments. Amylyx is headquartered in Cambridge, Massachusetts. For more information, visit amylyx.com and follow us on LinkedIn and X, (formerly Twitter). For investors, please visit investors.amylyx.com. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, Amylyx’ expectations regarding: interactions with regulatory authorities; the availability of RELYVRIO/ALBRIOZA for patients currently taking RELYVRIO/ALBRIOZA; the timing and significance of learnings from the PHOENIX trial, the PHOENIX survival analysis and the Open Label Extension; the continued evaluation of AMX0035 in other neurodegenerative diseases, including the timing for expected data readouts in the ORION and HELIOS studies; the potential for AMX0114 as a treatment for ALS and the planned initiation of a trial evaluating AMX0114 in ALS; and the impact of resource-conserving measures on extending the Company's cash runway, including the restructuring plan. Any forward-looking statements in this press release are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include the risks and uncertainties set forth in Amylyx’ United States Securities and Exchange Commission (SEC) filings, including Amylyx’ Annual Report on Form 10-K for the year ended December 31, 2023, and subsequent filings with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Amylyx undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- The Assignee of Civetta Therapeutics, LLC, a trailblazer in the field of biotechnology with a focus on β-propeller protein research, is inviting bids for the company's rich portfolio of intellectual property. Following the cessation of operations on December 22, 2023, and its transition into an Assignment for the Benefit of Creditors, the Assignee is seeking competitive offers for Civetta's extensive collection of innovative research and assets in biotechnology. Civetta Therapeutics has been at the forefront of biotechnological innovation, specializing in the exploration of β-propeller proteins, which present over 600 target opportunities for various diseases. The company's groundbreaking approach has opened new paths in addressing challenges in oncology, neurodegeneration, inflammation, and monogenic diseases. With a skilled team based in Cambridge, MA, and advanced research facilities, Civetta has developed a novel class of therapies and a robust platform for drug discovery in this promising area of biotechnology. Investment Opportunity: The available intellectual property portfolio offers a unique opportunity to invest in a cutting-edge area of biotechnology. Highlights of the portfolio include a late-stage chemically enabled oncology program, validated small molecule hits for another oncology initiative, and comprehensive tools and methodologies for advancing B-propeller protein research and drug discovery. This is a rare opportunity to acquire a comprehensive portfolio of intellectual property in a field with immense therapeutic and commercial potential. Interested parties are encouraged to act promptly to participate in this unique acquisition process. Bid Submission Details: Interested parties are invited to submit their bids for Civetta Therapeutics' intellectual property by April 30, 2024, 5:00 PM Central Time. A confidentiality and non-disclosure agreement will grant qualified bidders access to a virtual data room for due diligence. The bid process is structured to ensure fairness and transparency, with detailed submission guidelines available upon request. All inquiries should be directed to representatives of the Assignee, Development Specialists, Inc. For inquiries and further information regarding the bid submission process, please contact William G. Brandt at (312) 263-4141 or wgbrandt@dsiconsulting.com or Matthew Sorenson at msorenson@dsiconsulting.com About DSI Development Specialists, Inc. (DSI) is one of the leading providers of management consulting and financial advisory services, including turnaround consulting, financial restructuring, litigation support, fiduciary services and forensic accounting. Our clients include business owners, private-equity investors, corporate boards, financial institutions, secured lenders, bondholders and unsecured creditors. View source version on businesswire.com: Contacts Media Contact: Mark Fleming mfleming@dsiconsulting.com Source: Development Specialists, Inc. View this news release online at:

Meeting to discuss potential of IkT-001Pro as a disease modifying treatment for Pulmonary Arterial HypertensionBOSTON and ATLANTA, April 03, 2024 (GLOBE NEWSWIRE) -- Inhibikase Therapeutics, Inc. (Nasdaq: IKT) (“Inhibikase” or “Company”), a clinical-stage pharmaceutical company developing protein kinase inhibitor therapeutics to modify the course of Parkinson's disease, Parkinson's-related disorders and other diseases of the Abelson Tyrosine Kinases, today announced that the Company will meet with the Office of Cardiology, Hematology, Endocrinology and Nephrology (OCHEN) in the Division of Cardiology and Nephrology (DCN) at the U.S. Food and Drug Administration (FDA) for a Pre-IND meeting to discuss IkT-001Pro (“Pro”) as a treatment for Pulmonary Arterial Hypertension (PAH). The meeting will be held on April 5, 2024, with meeting results to be reported following receipt of the formal meeting minutes. “Following our pre-NDA discussion with the FDA related to the path to approval for IkT-001Pro in up to 11 blood and stomach cancers in January, we requested an additional FDA meeting with the Division of Cardiology and Nephrology to discuss Pro as a treatment for Pulmonary Arterial Hypertension,” said Dr. Milton Werner, President and Chief Executive Officer of Inhibikase. “PAH is a rare condition that primarily afflicts women between the ages of 30 and 60 and can lead to premature heart failure and death. Previous clinical research with imatinib, the active ingredient in Pro, was shown to be potentially disease-modifying for PAH, however, the adverse event profile of imatinib mesylate in this patient population could not support approval by the FDA. We believe that Pro may be a be a safer and better tolerated therapeutic option for imatinib treatment in PAH. We look forward to the FDA’s input on a proposed late-stage trial design and to the FDA’s viewpoint on if Pro could be treated as a branded product for this indication.” Pulmonary Arterial Hypertension is a rare disease of the pulmonary microvasculature. PAH can arise spontaneously, or can be caused by genetic mutations, drugs or environmental toxins. PAH is also associated with connective tissue disease (CTD), congenital heart disease, HIV infection and other insults that could affect the right side of the heart. Most treatments for PAH attempt to address symptoms of this progressive disorder, but the recent approval of Winrevair® highlights that disease-modification is possible. There are approximately 30,000 cases of PAH in the U.S. The global PAH market size was valued at $7.66 billion in 2023 and is estimated to grow at a compound annual growth rate of 5.4% between 2024 to 2030. Imatinib has been shown to have efficacy on par with Winrevair® (doi: 10.1164/rccm.201001-0123OC), however its side effect profile precluded approval in this patient population. Changes in the standard-of-care for these patients suggests that the serious adverse events which arose from treatment with imatinib mesylate in the 2010s may not occur when imatinib is delivered as IkT-001Pro; the Company has yet to conduct any clinical studies to validate this hypothesis. The Pre-IND meeting will review our proposed late-stage trial design to reproduce efficacy and evaluate the safety and tolerability of imatinib delivered by IkT-001Pro in patients with WHO Class I PAH, as well as seek regulatory advice or clarity on FDA orange book exclusivity, approval pathways, special designations. Based on the meeting outcome, the Company will evaluate whether to proceed with filing the IND for IkT-001Pro in this indication and undertake a strategic review and business development initiative to define the Company’s path forward with this product. About Inhibikase (www.inhibikase.com) Inhibikase Therapeutics, Inc. (Nasdaq: IKT) is a clinical-stage pharmaceutical company developing therapeutics for Parkinson's disease and related disorders. Inhibikase's multi-therapeutic pipeline has a primary focus on neurodegeneration and its lead program risvodetinib, an Abelson Tyrosine Kinase (c-Abl) inhibitor, targets the treatment of Parkinson's disease inside and outside the brain as well as other diseases that arise from Abelson Tyrosine Kinases. Its multi-therapeutic pipeline is pursuing Parkinson's-related disorders of the brain and GI tract, orphan indications related to Parkinson's disease such as Multiple System Atrophy, and drug delivery technologies for kinase inhibitors such as IkT-001Pro, a prodrug of the anticancer agent imatinib mesylate that the Company believes will provide a better patient experience with fewer on-dosing side-effects. The Company's RAMP™ medicinal chemistry program has identified several follow-on compounds to risvodetinib that could potentially be applied to other cognitive and motor function diseases of the brain. Inhibikase is headquartered in Atlanta, Georgia with offices in Lexington, Massachusetts. Social Media DisclaimerInvestors and others should note that the Company announces material financial information to investors using its investor relations website, press releases, SEC filings and public conference calls and webcasts. The Company intends to also use X, Facebook, LinkedIn and YouTube as a means of disclosing information about the Company, its services and other matters and for complying with its disclosure obligations under Regulation FD. Forward-Looking StatementsThis press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking terminology such as "believes," "expects," "may," "will," "should," "anticipates," "plans," or similar expressions or the negative of these terms and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based on Inhibikase's current expectations and assumptions. Such statements are subject to certain risks and uncertainties, which could cause Inhibikase's actual results to differ materially from those anticipated by the forward-looking statements. Important factors that could cause actual results to differ materially from those in the forward-looking statements include our ability to to enroll and complete the 201 Trial evaluating risvodetinib in untreated Parkinson’s disease, to successfully apply for and obtain FDA approval for IkT-001Pro in blood and stomach cancers or other indications, to successfully conduct clinical trials that are statistically significant and whether results from our animal studies may be replicated in humans, as well as such other factors that are included in our periodic reports on Form 10-K and Form 10-Q that we file with the U.S. Securities and Exchange Commission. Any forward-looking statement in this release speaks only as of the date of this release. Inhibikase undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by any applicable securities laws. Contacts: Company Contact:Milton H. Werner, PhDPresident & CEO678-392-3419info@inhibikase.com Investor Relations:Alex LoboStern Investor Relations, Inc.alex.lobo@sternir.com