Malabsorption Syndromes

Industry veteran with late-stage clinical development, medical affairs, and regulatory experience; well-positioned to advance losmapimod towards a potential regulatory submission and approval Interim Chief Medical Officer, Iain Fraser, MBChB, DPhil, will continue to serve on Fulcrum’s executive leadership team as senior vice president (SVP) of early development CAMBRIDGE, Mass., March 18, 2024 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc.® (Fulcrum) (Nasdaq: FULC), a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with genetically defined rare diseases, today announced the appointment of Patrick Horn, M.D., Ph.D., as chief medical officer, effective immediately. Dr. Horn is a seasoned executive with over 20 years of end-to-end drug development experience spanning multiple therapeutic areas, with an emphasis on rare diseases, across both large pharmaceutical and biotech companies. Interim chief medical officer, Iain Fraser, MBChB, DPhil, will continue to serve on Fulcrum’s executive leadership team as SVP of early development. Together, Drs. Horn and Fraser will be responsible for leading clinical development and overseeing regulatory strategy and execution. “I am very pleased to enrich our leadership team with Pat, an accomplished industry veteran who has successfully guided multiple therapies—including rare disease programs lacking existing regulatory pathways—through late clinical development, regulatory approval, and commercial launch,” said Alex C. Sapir, Fulcrum’s president and chief executive officer. “This is a key moment for Fulcrum as we continue to advance our Phase 3 REACH trial of losmapimod for patients with facioscapulohumeral muscular dystrophy and reinitiate our Phase 1b PIONEER trial of pociredir in sickle cell disease. We believe both Pat and Iain’s complementary expertise will be invaluable as we near several pivotal milestones for our two key clinical programs and advance our early-stage pipeline.” Dr. Horn added, "Joining Fulcrum is an exciting opportunity to bring potentially transformative therapies to patients especially as we advance towards near-term inflection points for losmapimod, a late-stage clinical program with first-to-market potential, and pociredir, a highly differentiated oral treatment option that may shift the current standard of care. Building on the encouraging clinical data generated to date, I, alongside Iain, look forward to working with the management team to deliver on the promise of Fulcrum’s differentiated pipeline of rare disease programs.” Dr. Patrick Horn is a distinguished professional with over 20 years of experience in the field of rare disease drug development, encompassing all stages from initial research to regulatory approval and commercial launch. His most recent role was as the Chief Medical Officer at HemoShear Therapeutics, specializing in rare metabolic diseases. Previously, he held the position of Chief Medical Officer at Albireo Pharma where he led the team that achieved marketing approvals in the US and Europe for Bylvay™ in progressive familial intrahepatic cholestasis (PFIC). Before his tenure at Albireo, he served as the Senior Vice President of Medical and Clinical Development at Orphan Technologies, directing the advancement of novel treatments for homocystinuria. Prior to this, he was the Chief Medical Officer at Tetraphase Pharmaceuticals, where he oversaw the clinical development of antibiotic candidates, including the program leading to the New Drug Application for eravacycline. Before Tetraphase, Dr. Horn led the clinical program at Dyax Corp. that resulted in the approval of Kalbitor® for the treatment of hereditary angioedema. Dr. Horn received his M.D., and Ph.D., from the University of Chicago and completed his pediatric residency at Boston Children’s Hospital. Prior to transitioning to industry, Dr. Horn was a practicing pediatrician at major academic institutions in Chicago. About Fulcrum Therapeutics Fulcrum Therapeutics is a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with genetically defined rare diseases in areas of high unmet medical need. Fulcrum’s two lead programs in clinical development are losmapimod, a small molecule in development for the treatment of facioscapulohumeral muscular dystrophy (FSHD), and pociredir (formerly known as FTX-6058), a small molecule designed to increase expression of fetal hemoglobin and in development for the treatment of sickle cell disease (SCD). Fulcrum uses proprietary technology to identify drug targets that can modulate gene expression to treat the known root cause of gene mis-expression. For more information, visit and follow us on Twitter/X (@FulcrumTx) and LinkedIn. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this press release are forward-looking statements, including express or implied statements regarding advancement of losmapimod towards regulatory submission and approval;; reinitiation of the Phase 1b trial; advancement of Fulcrum’s early-stage pipeline; Fulcrum’s ability to deliver an FDA-approved therapy for FSHD patients; and the potential for pociredir to shift the standard of care;; among others. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements 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. These risks and uncertainties include, but are not limited to, risks associated with Fulcrum’s ability to continue to advance its product candidates in clinical trials; initiating and enrolling clinical trials on the timeline expected or at all; obtaining and maintaining necessary approvals from the FDA and other regulatory authorities; replicating in clinical trials positive results found in preclinical studies and/or earlier-stage clinical trials of losmapimod, pociredir and any other product candidates; obtaining, maintaining or protecting intellectual property rights related to its product candidates; managing expenses; managing executive and employee turnover, including integrating a new CMO; and raising the substantial additional capital needed to achieve its business objectives, among others. For a discussion of other risks and uncertainties, and other important factors, any of which could cause Fulcrum’s actual results to differ from those contained in the forward-looking statements, see the “Risk Factors” section, as well as discussions of potential risks, uncertainties, and other important factors, in Fulcrum’s most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent Fulcrum’s views as of the date hereof and should not be relied upon as representing Fulcrum’s views as of any date subsequent to the date hereof. Fulcrum anticipates that subsequent events and developments will cause Fulcrum’s views to change. However, while Fulcrum may elect to update these forward-looking statements at some point in the future, Fulcrum specifically disclaims any obligation to do so. Contact: Chris Calabrese LifeSci Advisors, LLC ccalabrese@lifesciadvisors.com 917-680-5608

Poster presentations to highlight new quantitative and serologic diagnostic methods for Celiac Disease detection and determination of intestinal mucosal health New tools may serve as companion diagnostics for identifying seroactive patients and for monitoring the efficacy of Latiglutenase, the Company’s Celiac Disease therapeutic program BOCA RATON, Fla., March 18, 2024 (GLOBE NEWSWIRE) -- First Wave BioPharma, Inc., (NASDAQ: FWBI), (“First Wave BioPharma” or the “Company”), a clinical-stage biopharmaceutical company specializing in the development of targeted, non-systemic therapies for gastrointestinal (GI) diseases, today announced that two abstracts have been accepted for presentation at the 2024 Digestive Disease Week Conference (DDW 2024) taking place May 18-21, 2024, in Washington, D.C. The first presentation, titled, “A Composite Mucosal Scale for Celiac Disease Encompassing both Morphology and Inflammation,” will highlight VCIEL, a new quantitative composite scale, combining the histologic scales of villus height to crypt depth ratio (Vh:Cd) and density of intraepithelial lymphocytes (IEL), designed to enhance the accuracy and precision for measuring small intestinal mucosal health of celiac disease (CeD) patients with particular benefit for histologic endpoint measurements in clinical trials. The second presentation, titled, “Dynamics of Serologic Change to Gluten in Celiac Disease Patients,” will report research involving the largest database of CeD clinical results and will explore key issues related to the diagnostics of CeD, such as the effects of resuming a gluten-containing diet on seropositivity and the correlation between two different tTG-IgA assays. “The abstracts accepted for presentation at DDW 2024 showcase significant advancements in the field of gastroenterology, particularly in the precision diagnosis and management of celiac disease through the innovative VCIEL scale that our team has developed,” stated James Sapirstein, Chairman and CEO of First Wave BioPharma. “The invitation to present our findings on the VCIEL scale for measuring mucosal health of the small intestine as well as our research on the impact of gluten reintroduction as a diagnostic intervention for serologic measurements at one of the most influential meetings on gastrointestinal disease validates the potential for our work to advance better understanding and treatment of celiac disease,” said Jack Syage, PhD, President and Chief Operating Officer of First Wave. Details on the presentations are as follows: Presentation Title: A Composite Mucosal Scale for Celiac Disease Encompassing both Morphology and Inflammation Presenters: Jack Syage, PhD. President & Chief Operating Officer, First Wave BioPharma Jennifer Sealy-Voyksner, PhD., Vice President R&D, First Wave BioPharma Session Title: Celiac Disease and Gluten Related Disorders Date and Time: May 19, 2024, from 12:30 PM to 1:30 PM EDT Presentation Title: Dynamics of Serologic Change to Gluten in Celiac Disease Patients Presenters: Jack Syage, PhD. President & Chief Operating Officer, First Wave BioPharma Jennifer Sealy-Voyksner, PhD., Vice President R&D, First Wave BioPharma Session Title: Celiac Disease and Gluten Related Disorders Date and Time: May 19, 2024, from 12:30 PM to 1:30 PM EDT About Celiac Disease Celiac disease is a chronic, hereditary autoimmune and inflammatory disease triggered by gluten consumption. Celiac disease is characterized by damage to the lining of the small intestine, causing malabsorption, gastrointestinal dysfunction and debilitating symptoms. Over the course of a lifetime, untreated or poorly managed celiac disease is often associated with deteriorating general health, multiple serious intestinal and extra-intestinal medical complications, and increased morbidity and mortality. Celiac disease is a global disease and affects approximately 1% of the population worldwide and is increasing in prevalence with improved diagnostic tools and improved awareness. About First Wave BioPharma, Inc. First Wave BioPharma is a clinical-stage biopharmaceutical company specializing in the development of targeted, non-systemic therapies for gastrointestinal (GI) diseases. The Company is currently advancing a therapeutic development pipeline with multiple late-stage clinical programs built around three proprietary technologies – latiglutenase, a Phase 3-ready, potentially first-in-class, targeted, oral biotherapeutic for celiac disease; capeserod, a selective 5-HT4 receptor partial agonist being developed for gastroparesis; and adrulipase, a recombinant lipase enzyme designed to enable the digestion of fats and other nutrients in cystic fibrosis and chronic pancreatitis patients with exocrine pancreatic insufficiency. First Wave BioPharma is headquartered in Boca Raton, Florida. For more information visit . Forward-Looking Statements This press release may contain certain statements relating to future results which are forward-looking statements. It is possible that the Company’s actual results and financial condition may differ, possibly materially, from the anticipated results and financial condition indicated in these forward-looking statements, depending on factors including whether any financing or licensing transaction may be completed, completed with different terms, in an untimely manner, or not at all; whether the Company will be able to realize the expected benefits of its acquisition of ImmunogenX; the Company’s ability to integrate the assets and contemplated commercial operations acquired from ImmunogenX into the Company’s business; whether results obtained in preclinical and nonclinical studies and clinical trials will be indicative of results obtained in future clinical trials; whether preliminary or interim results from a clinical trial will be indicative of the final results of the trial; whether the Company will be able to maintain compliance with Nasdaq’s continued listing criteria and the effect of a delisting from Nasdaq on the market for the Company’s securities; the size of the potential markets for the Company’s drug candidates and its ability to service those markets; the effects of the First Wave Bio, Inc. acquisition, the related settlement and their effect on the Company’s business, operating results and financial prospects; and the Company’s current and future capital requirements and its ability to raise additional funds to satisfy its capital needs. Additional information concerning the Company and its business, including a discussion of factors that could materially affect the Company’s financial results are contained in the Company’s Annual Report on Form 10-K for the year ended December 31, 2022, under the heading “Risk Factors,” as well as the Company’s subsequent filings with the Securities and Exchange Commission. All forward-looking statements included in this press release are made only as of the date of this press release, and we do not undertake any obligation to publicly update or correct any forward-looking statements to reflect events or circumstances that subsequently occur or of which we hereafter become aware. For more information: First Wave BioPharma, Inc. 777 Yamato Road, Suite 502 Boca Raton, FL 33431 Phone: (561) 589-7020 info@firstwavebio.com Media contact: Tiberend Strategic Advisors, Inc. David Schemelia (609) 468-9325 dschemelia@tiberend.com

Latiglutenase is a potentially first-in-class oral biotherapeutic for the treatment of celiac disease James Sapirstein, Chairman and Chief Executive Officer, to continue leading First Wave BioPharma; Jack Syage, Ph.D., named President and Chief Operating Officer A strategic U.S. commercial license agreement with a global pharmaceutical company and concurrent institutional investment expected to close in 2H’24 Conference Call Scheduled for Today at 8:30 a.m. ET BOCA RATON, Fla., March 14, 2024 (GLOBE NEWSWIRE) -- First Wave BioPharma, Inc., (NASDAQ: FWBI), (“First Wave BioPharma” or the “Company”), a clinical-stage biopharmaceutical company specializing in the development of targeted, non-systemic therapies for gastrointestinal (GI) diseases, today announced it has acquired ImmunogenX in an all-stock transaction with the combined company focused on advancing a GI pipeline comprised of multiple, late-stage clinical assets, including latiglutenase, a potentially first-in-class, near Phase 3-ready, targeted, oral biotherapeutic for celiac disease. James Sapirstein will continue to serve as Chairman and Chief Executive Officer of First Wave BioPharma with Jack Syage, Ph.D., previously the Chief Executive Officer and Co-Founder of ImmunogenX, assuming the role of President and Chief Operating Officer of First Wave BioPharma. Dr. Syage and Dr. Chaitan Khosla will also join the board of directors of First Wave BioPharma. First Wave BioPharma intends to license the commercial rights to latiglutenase in the United States and Canada to a strategic global pharmaceutical company which will commercialize latiglutenase following receipt of marketing approval. First Wave BioPharma will also seek to secure financing commitments from a syndicate of institutional healthcare investors to fund the ongoing development of latiglutenase. The closing of a strategic licensing agreement and any other financings would be contingent upon the satisfaction of a number of conditions, including customary due diligence, the negotiation and execution of definitive agreements, Board approval and receipt of all required third-party (including governmental) approvals, licenses, consents, and clearances, as and when applicable. Latiglutenase, an oral biotherapeutic composed of two gluten-specific recombinant proteases, has demonstrated effectiveness in reducing intestinal damage and alleviating symptoms of celiac disease in two Phase 2 trials involving approximately 200 patients. The Phase 3 clinical plan for latiglutenase has been reviewed by the GI Division of the U.S. Food and Drug Administration (FDA) and the trials are anticipated to begin in early 2025. “Completion of the acquisition of ImmunogenX and the addition of latiglutenase to our clinical pipeline is a transformative event for First Wave BioPharma as it provides our company with a Phase 3-ready asset in a multibillion-dollar GI market – celiac disease – for which no approved pharmacologic treatment currently exists,” stated Mr. Sapirstein. “Given this enormous potential, we are working with Dr. Syage and his team to advance the regulatory, manufacturing, and clinical processes that would enable the initiation of the pivotal Phase 3 clinical trials of latiglutenase in 2025. To that end, we will seek to develop latiglutenase by completing an agreement with a global pharmaceutical company to provide First Wave with non-dilutive financing in exchange for U.S. and Canadian rights to the drug and to obtain financing with a syndicate of leading institutional healthcare funds in 2H’24. We expect to finalize these agreements prior to initiating preparatory work for the Phase 3 latiglutenase trials.” Dr. Syage commented: “I am excited to join First Wave BioPharma and advance the company’s mission to become a leading developer of targeted, orally delivered therapeutics for GI diseases. We believe latiglutenase has the potential to transform the treatment of celiac disease with data from two prior Phase 2 trials indicating the therapy is well tolerated and effective in degrading the key gluten proteins responsible for intestinal damage and celiac disease symptoms. This merger with First Wave will provide the support needed to propel the development of latiglutenase, a program that has already received significant NIH grant funding and encouragement from the FDA.” Mr. Sapirstein concluded: “First Wave BioPharma now possesses a GI-development pipeline unrivaled by other companies of similar size. In addition to latiglutenase, our product portfolio includes capeserod, a selective 5-HT4 receptor partial agonist in-licensed from Sanofi, which is being developed for an anticipated Phase 2 trial in gastroparesis, and Phase 2-ready adrulipase, a recombinant lipase designed to enable the digestion of fats and improve nutritional health in cystic fibrosis patients with exocrine pancreatic insufficiency.” Upon closing of the acquisition, the Company issued 365,162 shares of its common stock to the shareholders (including option and warrant holders) of ImmunogenX equal to 19.02% of its currently issued and outstanding common stock and 11,777.418 shares of its newly issued Series G Convertible Preferred Stock (with a conversion ratio of Preferred to Common at 1:1000) representing on a fully diluted basis 81.9% for ImmunogenX and 18.1% for First Wave Biopharma (excluding transaction fees) with a combined fully diluted equity value of $104 million. The shares of the Company’s common stock issuable upon conversion of the Series G Preferred Stock shall be subject to stockholder approval in compliance with the rules of the Nasdaq Stock Market. Tungsten Advisors served as the exclusive financial advisor to First Wave BioPharma. Conference Call Information: First Wave BioPharma will host a conference call and live audio webcast today, March 14, 2024, at 8:30 a.m. ET, to discuss the definitive merger agreement with ImmunogenX and provide a strategic outlook for company. Webcast Access: The audio webcast of the conference call will be accessible via the Investors section of the First Wave website: and from the following URL: . An archive of the webcast will remain available for 90 days beginning at approximately 10:30 a.m. ET, on March 14, 2024. Telephone Access: Additionally, interested participants and investors may access the conference call telephonically by registering via the following online form: Once registered, all individuals will be provided with a participant dial-in number, a passcode, and a registrant ID, which can then be used to access the conference call. About Latiglutenase Latiglutenase is an orally administered mixture of two minimally systemically absorbed gluten-specific recombinant proteases being developed as an oral biotherapeutic for celiac disease. In Phase 2a and 2b clinical trials, latiglutenase was shown to mitigate gluten-induced intestinal mucosal injury as well as reduce the severity and frequency of symptoms in celiac disease patients. The Phase 3 clinical development plan for latiglutenase has been reviewed by the GI Division of the U.S. Food and Drug Administration (FDA) at the End of Phase 2 meeting with an agreed plan forward, with initiation of the Phase 3 trials expected in 2025. About Celiac Disease Celiac disease is a chronic, hereditary autoimmune and inflammatory disease triggered by gluten consumption. Celiac disease is characterized by damage to the lining of the small intestine, causing malabsorption, gastrointestinal dysfunction, and debilitating symptoms. Over the course of a lifetime, untreated or poorly managed celiac disease is often associated with deteriorating general health, multiple serious intestinal and extra-intestinal medical complications, and increased morbidity and mortality. Celiac disease is a global disease and affects approximately 1% of the population worldwide and is increasing in prevalence with improved diagnostic tools and improved awareness. About First Wave BioPharma, Inc. First Wave BioPharma is a clinical-stage biopharmaceutical company specializing in the development of targeted, non-systemic therapies for gastrointestinal (GI) diseases. The Company is currently advancing a therapeutic development pipeline with multiple late-stage clinical programs built around three proprietary technologies – latiglutenase, a Phase 3-ready, potentially first-in-class, targeted, oral biotherapeutic for celiac disease; capeserod, a selective 5-HT4 receptor partial agonist being developed for gastroparesis; and adrulipase, a recombinant lipase enzyme designed to enable the digestion of fats and other nutrients in cystic fibrosis and chronic pancreatitis patients with exocrine pancreatic insufficiency. First Wave BioPharma is headquartered in Boca Raton, Florida. For more information visit . About Tungsten Advisors Tungsten Advisors ( ) is an investment banking firm focused on strategic advisory and corporate finance for healthcare and technology companies. Tungsten provides transactional services including financings (private placements/PIPEs), corporate licensing and mergers and acquisitions (M&A). Tungsten also focuses on company incubation and makes direct investments alongside the creation of new companies in healthcare and technology. Securities offered through Finalis Securities LLC Member FINRA/SIPC. Tungsten Partners LLC d/b/a Tungsten Advisors and Finalis Securities LLC are separate, unaffiliated entities. Forward-Looking Statements This press release may contain certain statements relating to future results which are forward-looking statements. It is possible that the Company’s actual results and financial condition may differ, possibly materially, from the anticipated results and financial condition indicated in these forward-looking statements, depending on factors including whether any financing or licensing transaction may be completed with different terms, in an untimely manner, or not at all; whether the Company will be able to realize the benefits of the completed transaction described herein; the Company’s ability to integrate the assets and commercial operations contemplated acquired from ImmunogenX into the Company’s business; whether results obtained in preclinical and nonclinical studies and clinical trials will be indicative of results obtained in future clinical trials; whether preliminary or interim results from a clinical trial will be indicative of the final results of the trial; whether the Company will be able to maintain compliance with Nasdaq’s continued listing criteria and the effect of a delisting from Nasdaq on the market for the Company’s securities; the size of the potential markets for the Company’s drug candidates and its ability to service those markets; the effects of the First Wave Bio, Inc. acquisition, the related settlement and their effect on the Company’s business, operating results and financial prospects; and the Company’s current and future capital requirements and its ability to raise additional funds to satisfy its capital needs. Additional information concerning the Company and its business, including a discussion of factors that could materially affect the Company’s financial results are contained in the Company’s Annual Report on Form 10-K for the year ended December 31, 2022, under the heading “Risk Factors,” as well as the Company’s subsequent filings with the Securities and Exchange Commission. All forward-looking statements included in this press release are made only as of the date of this press release, and we do not undertake any obligation to publicly update or correct any forward-looking statements to reflect events or circumstances that subsequently occur or of which we hereafter become aware. For more information: First Wave BioPharma, Inc. 777 Yamato Road, Suite 502 Boca Raton, FL 33431 Phone: (561) 589-7020 info@firstwavebio.com Media contact: Tiberend Strategic Advisors, Inc. David Schemelia (609) 468-9325 dschemelia@tiberend.com