GlobeNewswire Inc | Oct 19, 2021 09:24AM EDT

October 19, 2021

BOCA RATON, Fla., Oct. 19, 2021 (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 forgastrointestinal (GI) diseases, announced today that the U.S. Food and Drug Administration (FDA) has reviewed the Investigational New Drug (IND) application and provided a Study May Proceed letter for the Companys Phase 2a PASSPORT trial investigating FW-ICI-AC as a treatment for Grade 1 and Grade 2 colitis and diarrhea in oncology patients receiving treatment with immune checkpoint inhibitors (ICIs). FW-ICI-AC is a proprietary oral immediate-release tablet formulation of niclosamide, a prescription small molecule with anti-inflammatory and anti-viral properties.

The Phase 2a PASSPORT clinical trial is designed as a double-blind, placebo-controlled study to determine the safety, tolerability, and preliminary efficacy of FW-ICI-AC in the treatment of immune checkpoint inhibitor-associated colitis (ICI-AC) and diarrhea in advanced cancer patients. 60 patients will be enrolled in the trial and divided into two arms (30 patients per arm). One arm will receive FW-ICI-AC three times daily for two weeks, while the other arm will receive placebo three times daily for two weeks. Following treatment, each patient will enter a four-week evaluation period. The primary endpoint of the trial is safety and tolerability of FW-ICI-AC. Additional endpoints will measure early signals of efficacy, including resolution of the patients diarrhea, sparing of steroids, and prevention of disease progression.

We are very pleased to have received IND clearance to initiate the PASSPORT clinical trial investigating FW-ICI-AC as a potential treatment for immune-checkpoint associated colitis and diarrhea. Importantly, the approved IND protocol includes an amended trial protocol that is expected to enable accelerated patient enrollment and a more efficient time to trial completion, stated James Sapirstein, President and CEO of First Wave BioPharma. As many as 30 percent of cancer patients treated with checkpoint inhibitors develop diarrhea that can progress to colitis, a condition that can be debilitating and, at times, life-threatening due to the compromised health of the patient and the impact if patients are forced to halt their cancer treatment. We believe our proprietary formulation of niclosamide has the potential to be the first drug specifically for early-stage Grade 1 and Grade 2 ICI-AC.

First Wave BioPharmas proprietary formulation of niclosamide is also the subject of a Phase 2 clinical trial (RESERVOIR) as a potential treatment for COVID-19-related gastrointestinal (GI) infections and a Phase 2b clinical trial in patients with ulcerative proctitis (UP) and ulcerative proctosigmoiditis (UPS), two forms of ulcerative colitis an inflammatory bowel disease (IBD).

James Pennington, M.D., Chief Medical Officer of First Wave BioPharma, commented, The revised clinical trial protocol should allow us to accelerate patient enrollment and also shorten the time it takes to complete the trial and report data. This is one of several clinical programs we are advancing to explore the potential of niclosamide in the gastrointestinal space, and we look forward to a number of milestones in the coming months.

About FW-ICI-AC FW-ICI-AC is a niclosamide-based, small molecule, anti-inflammatory inhibitor therapy for the treatment of immune checkpoint inhibitor-associated colitis (ICI-AC) and diarrhea in advanced cancer patients. FW-ICI-AC (formerly FW-420) will be supplied to the PASSPORT clinical trial as a proprietary oral immediate-release tablet formulation. The standard care for treating inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohns disease, corticosteroids and other immunosuppressive agents can cause problems when used for check point inhibitor patients due to their immunosuppressant effects. FW-ICI-AC has the potential to safely treat Grade 1 and Grade 2 ICI-associated colitis and diarrhea and prevent its progression to more serious and potentially fatal later stages. The overall goal of early niclosamide treatment is to enable oncology patients to remain on, or spend minimal time off, their ICI treatment programs without interruption. Niclosamide is a prescription small molecule drug listed as an essential medicine by the World Health Organization (WHO). Niclosamide has been safely used on millions of patients for other clinical indications.

About the PASSPORT StudyThe Phase 2a PASSPORT clinical trial is designed as a double-blind, placebo-controlled study to determine the safety, tolerability, and preliminary efficacy of FW-ICI-AC in the treatment of immune checkpoint inhibitor-associated colitis (ICI-AC) and diarrhea in advanced cancer patients. 60 patients will be enrolled in the trial and divided into two arms (30 patients per arm). One arm will receive FW-ICI-AC three times daily for two weeks, while the other arm will receive placebo three times daily for two weeks. Following treatment, each patient will enter a four-week evaluation period. The primary endpoint of the trial is safety and tolerability of FW-ICI-AC. Additional endpoints will measure early signals of efficacy, including resolution of the patients diarrhea, sparing of steroids, and prevention of disease progression.

About Immune Checkpoint Inhibitor-Associated ColitisImmune checkpoint inhibitors (ICIs) are monoclonal antibodies that target down-regulators of the anti-cancer immune response and have revolutionized the treatment of a variety of malignancies. The global market for ICIs was over $22 billion in 2019 and growing rapidly.1 However, many immune-related adverse events, especially diarrhea and colitis, limit their use. The incidence of ICI-AC with diarrhea ranges from 1% to 30% depending on the type of ICI and whether they are used in combination.2 The onset of diarrhea in ICI-AC patients occurs within 6-7 weeks after starting treatment and progressively worsens, and the progression to colitis is rapid and unpredictable. For example, in patients taking ipilimumab (Yervoy), between 25% and 30% of patients developed diarrhea and roughly 8% to 12% developed colitis proven by endoscopy.3 Moreover, the trend is towards the use of combination ICI therapies (e.g., Yervoy and Opdivo) and this will lead to a concomitant increase in both diarrhea and colitis. Administration of corticosteroids, or treatment with certain immunosuppressive biologics, while withholding ICI therapy are recommended for Grade 2 or more severe colitis (National Cancer Institute 2020). The impact of this colitis complication and treatment may reduce the goal of progression free cancer survival. An oral, non-systemic therapeutic, such as niclosamide, for Grade 1 or 2 colitis with diarrhea may prevent progression to even more severe Grades of colitis. There currently is no approved treatment for Grade 1 colitis.

About First Wave BioPharma, Inc.First Wave BioPharma, Inc. is a clinical-stage biopharmaceutical company specializing in the development of targeted, non-systemic therapies for gastrointestinal (GI) diseases. First Wave BioPharma is currently advancing a therapeutic development pipeline populated with multiple clinical stage programs built around its two proprietary technologies niclosamide, an oral small molecule with anti-viral and anti-inflammatory properties, and the biologic adrulipase, a recombinant lipase enzyme designed to enable the digestion of fats and other nutrients. First Wave BioPharmas niclosamide portfolio is led by three clinical programs: FW-COV, for COVID-19 gastrointestinal infections; FW-UP, for ulcerative proctitis (UP) and ulcerative proctosigmoiditis; and FW-ICI-AC, for Grade 1 and Grade 2 Immune Checkpoint Inhibitor-associated colitis and diarrhea in advanced oncology patients. Two additional formulations of niclosamide, FW-UC (ulcerative colitis) and FW-CD (Crohns disease) are expected to enter the clinic in 2022 and 2023, respectively. First Wave BioPharma is also advancing FW-EPI (adrulipase) for the treatment of exocrine pancreatic insufficiency (EPI) in patients with cystic fibrosis and chronic pancreatitis. The Company is headquartered in Boca Raton, Florida with clinical operations in Hayward, California. For more information visit www.firstwavebio.com.

Forward-Looking StatementThis press release may contain certain statements relating to future results which are forward-looking statements. It is possible that the Companys 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 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; the size of the potential markets for the Companys drug candidates and its ability to service those markets; the effects of the First Wave Bio, Inc. acquisition and its announcement on the Companys business, operating results and financial prospects; the integration of the First Wave Bio, Inc. business with the Companys own business; and the Companys 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 Companys financial results are contained in the Companys Annual Report on Form 10-K for the year ended December 31, 2020 under the headingRisk Factors,as well as the Companys 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 502Boca Raton, FL 33431Phone: (561) 589-7020info@firstwavebio.com

Media contact:Tiberend Strategic Advisors, Inc.David Schemelia / Ingrid Mezo(609) 468-9325 / (646) 604-5150dschemelia@tiberend.com / imezo@tiberend.com

References:1 Immune Checkpoint Inhibitors Market, ResearchAndMarkets.com, 2020.2 Wang et al. Patients with ICPI-induced diarrhea or colitis have improved survival outcomes.J Immunother Cancer. 2018; 6: 37. Som et al., World J Clin Cases. Feb 26, 2019; 7(4): 405-4183 Wang DY, Ye F, Zhao S, et al. Incidence of immune checkpoint inhibitor-related colitis in solid tumor patients: a systematic review and meta-analysis. Oncoimmunology 2017; 10: e1344805; Som et al., World J Clin Cases. Feb 26, 2019; 7(4): 405-418