Axcella Presents Data at The Liver Meeting™ Providing New Mechanistic Insights on Observed Multifactorial Effects of its Liver Product Candidates

Axcella Health (Nasdaq: AXLA), a biotechnology company pioneering the research and development of novel interventions to address dysregulated metabolism and support health, today announced that it will present new data on the company’s liver product candidates at The Liver Meeting^TM, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), being held this week in Boston. Two poster presentations highlight mechanistic data from preclinical and non-IND clinical studies of two of its investigational candidates, AXA1665 and AXA1125.

"Simultaneous dysregulation in multiple pathways is a fundamental feature of complex diseases such as hepatic encephalopathy (HE) and nonalcoholic steatohepatitis (NASH),” explains Dr. Manu Chakravarthy, M.D., Ph.D., Axcella’s SVP of Clinical Development and Chief Medical Officer. "In order to effectively address these conditions, a safe, multifactorial approach is required. We are excited to share our latest clinical findings, which both affirm and deepen our mechanistic understanding of the ways in which AXA1665 and AXA1125 may impact key biochemical and molecular pathways.”

Poster #0432 showcases the distinctive pharmacokinetic profile of AXA1665, as compared to a standard protein supplement, with improved nitrogen and ammonia handling by AXA1665 in subjects with hepatic insufficiency.

• AXA1665 enhanced anabolism-associated amino acids (AAs) and the clearance of ammoniagenic aromatic AAs (e.g., phenylalanine and tyrosine, which are inversely related to health consequences in patients with cirrhosis).
• AXA1665 administration, relative to the control group, demonstrated a decrease in fasted plasma ammonia concentration, with increased blood urea nitrogen (within the normal range) suggestive of enhanced ureagenesis.

Poster #2134 further delineates mechanisms underlying the previously reported observations of AXA1125 from a non-IND clinical study.

• No increases were observed in basal plasma branched chain amino acid (BCAA) levels despite the AXA1125 composition containing 24g of BCAAs per day. These findings are at least partially due to increased BCAA catabolism, as shown by the induction of the BCAA metabolite, C5-OH/C3-DC, induced by AXA1125.
• Propensity to improve insulin sensitivity was supported by enhanced insulin-dependent glucose uptake in primary human hepatocytes treated with the components of AXA1125.
• Coordinated effects of AXA1125 to dampen the inflammatory and fibrogenic responses were manifested by decreased proinflammatory (Trp, Kyn, YKL-40) and fibrogenic (Pro, His) markers.

Further information is contained in the aforementioned posters at AASLD:

Abstract Number: #0432
Title: AXA1665, a defined composition of endogenous metabolic modulators, but not dietary protein improved the dysregulated amino acid metabolism and ammonia disposal in Child-Pugh A and B subjects
Presentation Type: Poster
Session Date/Time: November 8, from 8:00 a.m. to 10:00 a.m. ET
Location: Hynes Convention Center, Hall B

Abstract Number: #2134
Title: Mechanistic insights into the multimodal effects of AXA1125 in T2D subjects with NAFLD
Presentation Type: Poster
Session Date/Time: November 10, from 8:00 a.m. to 10:00 a.m. ET
Location: Hynes Convention Center, Hall B

About Endogenous Metabolic Modulators

Endogenous metabolic modulators (EMMs) are a broad family of molecules, including amino acids, which fundamentally impact and regulate human metabolism. Our AXA Candidates are comprised of EMMs that individually have a history of safe use as food. We believe that, unlike conventional targeted interventions currently used to address dysregulated metabolism, EMM compositions have the potential to directly and simultaneously modulate multiple metabolic pathways implicated both in complex diseases and overall health.

About Non-IND Clinical Studies

Axcella conducts Institutional Review Board (IRB)-approved, non-investigational new drug application (Non-IND) clinical studies in humans with its AXA Candidates under U.S. Food and Drug Administration regulations and guidance supporting research with food. In these studies, Axcella evaluates in humans, including in individuals with disease, AXA Candidates for safety, tolerability and effects on the normal structures and functions of the body. Non-IND, IRB-Approved Clinical Studies are not designed or intended to evaluate an AXA Candidate’s ability to diagnose, cure, mitigate, treat or prevent a disease. If Axcella decides to further develop an AXA Candidate as a potential therapeutic, subsequent 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 and 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 Health

Axcella is designing and developing AXA Candidates, compositions of endogenous metabolic modulators, or EMMs, engineered in distinct ratios, designed to target and maximize the fundamental role that EMMs play in regulating multiple metabolic functions. Axcella’s AXA Candidates are generated from its proprietary, human-focused AXA Development Platform. Axcella believes its expertise and capabilities in EMMs position it to become a preeminent biotechnology company reprogramming metabolism to address a diverse set of complex diseases and support health. Axcella’s AXA Development Platform has already produced a pipeline of product candidates in programs targeting liver, muscle and blood. Axcella was founded by Flagship Pioneering. For more information, 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 development potential of AXA Candidates, including AXA1665 and AXA1125, potential expansion into new therapeutic fields, the ability of endogenous metabolic modulators to impact dysregulated metabolism and health and the timing of the company’s clinical studies and the timing of receipt of data from the same. 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 breadth of the company’s pipeline of product candidates, the strength of the AXA Development Platform, the efficiency of the company’s discovery and development approach, the clinical development and safety profile of AXA Candidates and their health or therapeutic potential, whether and when, if at all, AXA Candidates will receive approval from the U.S. Food and Drug Administration and for which, if any, indications, competition from other biotechnology companies, the company’s liquidity, its ability to successfully develop AXA Candidates through current and future milestones on the anticipated timeline, if at all, past results from Non-IND, IRB-Approved Clinical Studies not being representative of future results, and other risks identified in the company’s SEC filings, including Axcella’s 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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