Results of Axcella’s AXA1665-001 Clinical Study Published in Clinical and Translational Gastroenterology

Axcella (Nasdaq: AXLA), a clinical-stage biotechnology company focused on leveraging endogenous metabolic modulators (EMMs) to pioneer a new approach for treating complex diseases and improving health, today announced the publication of results from the company’s AXA1665-001 clinical study in Clinical and Translational Gastroenterology entitled "Safety, tolerability, and physiological effects of AXA1665, a novel composition of amino acids, in subjects with Child–Pugh A and B cirrhosis.” The AXA1665-001 study, which was completed in late 2018, investigated AXA1665’s effect on safety, tolerability, and biomarkers related to hepatic and muscle metabolism and function. Axcella also recently reported positive top-line data from its second clinical study of AXA1665, AXA1665-002.

"Excess ammonia, amino acid imbalance and muscle wasting are often underlying contributing factors that impact various complications of cirrhosis, including overt hepatic encephalopathy, which is typically marked by significant cognitive dysfunction,” says Dr. Manu Chakravarthy, Chief Medical Officer of Axcella. "We believe that AXA1665 holds the potential to address these metabolic derangements in an integrated and well-tolerated manner. In this paper, we report on the findings from our initial clinical experience with this oral product candidate in subjects with Child-Pugh A and B cirrhosis.”

AXA1665-001 was a domiciled and controlled crossover clinical study that examined two AXA1665 doses (14.7g/day and 44.1g/day), each over a two-week period. Overall, the results showed that both doses of AXA1665 were well tolerated, with no product-related adverse events observed. AXA1665’s effects on hepatic and muscle physiology were measured using clinically relevant biomarkers. Results suggest AXA1665’s potential to mitigate the multifactorial defects of hyperammonemia, dysregulated amino acid metabolism, and physical dysfunction. Key physiological findings in subjects receiving the higher dose of AXA1665 for 15 days as compared to the control group were:

• An increase in Fischer Ratio (branched chain amino acids ÷ aromatic amino acids) of approximately 40%, indicating improved amino acid balance.
• A decreased trend in mean fasted plasma ammonia concentration despite provision of additional nitrogen via the amino acids in AXA1665, suggesting improved nitrogen handling.
• A decrease in the liver frailty index, suggesting improved physical function, accompanied by trends toward a leaner body composition.

"This publication follows our presentations at EASL and AASLD last year and the recent positive data readout for our second clinical study of AXA1665, helping to raise further awareness about Axcella’s pioneering work to develop multi-targeted agents utilizing distinct compositions of EMMs,” explains Bill Hinshaw, President and CEO of Axcella. "The AXA1665-001 study was our first opportunity to demonstrate this product candidate’s multifactorial potential, and we were excited to build on this body of knowledge in AXA1665-002 by also showing positive changes in neurocognitive measures. We look forward to initiating our planned Phase 2 clinical trial of AXA1665 in patients with advanced liver disease in the first half of 2021.”

About Endogenous Metabolic Modulators (EMMs)

EMMs are a broad family of molecules, including amino acids, that regulate human metabolism. Axcella is developing a range of novel product candidates that are comprised of multiple EMMs engineered in distinct combinations and ratios to simultaneously impact multiple metabolic pathways to modify the root causes of various complex diseases and improve health.

About Axcella’s Ongoing Clinical Studies

Each of the company’s clinical studies to date are or have been conducted as non-investigational new drug application (IND) clinical studies under U.S. Food and Drug Administration regulations and guidance supporting research with food. These studies evaluate product candidates for safety, tolerability and effects on the normal structures and functions in humans, including in individuals with disease. They are not designed or intended to evaluate a product candidate’s ability to diagnose, cure, mitigate, treat or prevent a disease. If Axcella decides to further develop a product candidate as a potential therapeutic, as is the case with AXA1665 and AXA1125, any subsequent clinical studies will be conducted under an IND.

Internet Posting of Information

Axcella uses its website, www.axcellahealth.com, as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Such disclosures will be included on the company’s website in the "Investors & News” section. Accordingly, investors should monitor such portions of the company’s website, in addition to following its press releases, SEC filings and public conference calls and webcasts.

About Axcella

Axcella is a clinical-stage biotechnology company focused on leveraging endogenous metabolic modulators (EMMs) to pioneer a new approach for treating complex diseases and improving health. The company’s product candidates are comprised of EMMs and their derivatives that are engineered in distinct combinations and ratios to simultaneously impact multiple biological pathways. Axcella’s pipeline includes lead therapeutic candidates for non-alcoholic steatohepatitis (NASH) and the reduction in risk of overt hepatic encephalopathy (OHE) recurrence. Additional muscle- and blood-related programs are in earlier-stage development. For more information, please visit www.axcellahealth.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the characteristics and development potential of the company’s EMM product candidates and the company’s characterization of the results from its clinical studies and future clinical trials, including for AXA1665, the company’s anticipated program milestones, including the design, status and timing of an IND-enabled clinical trial of AXA1665, the subject and timing of the company’s planned interactions with the FDA on its AXA1665 program, including the timing of IND submissions, and the potential of the company’s product candidates to impact health and/or disease, including AXA1665’s potential in advanced liver disease. The words "may,” "will,” "could,” "would,” "should,” "expect,” "plan,” "anticipate,” "intend,” "believe,” "estimate,” "predict,” "project,” "potential,” "continue,” "target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those related to the potential impact of COVID-19 on the company’s ability to conduct and complete its ongoing or planned clinical studies and IND-enabled clinical trials in a timely manner or at all due to patient or principal investigator recruitment or availability challenges, clinical trial site shutdowns or other interruptions and potential limitations on the quality, completeness and interpretability of data the company is able to collect in its AXA1665-002 clinical study, other potential impacts of COVID-19 on business and financial results, including with respect to the ability to raise additional capital, make planned interactions and submissions to FDA or other regulatory authorities in a timely manner or at all and operational disruptions or delays, changes in law, regulations, or interpretations and enforcement of regulatory guidance, whether data readouts and/or FDA feedback support our IND submission and clinical trial initiation plans and timing, clinical trial design and target indication for AXA1665, whether and when, if at all, the company’s product candidates will receive approval from the FDA or other comparable regulatory authorities, and for which, if any, indications, past results from clinical studies not being representative of future results, and other risks identified in the company’s SEC filings, including Axcella’s Annual Report on Form 10-K, Quarterly Report on Form 10-Q and subsequent filings with the SEC. The company cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. Axcella disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent the company’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. The company explicitly disclaims any obligation to update any forward-looking statements.

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