Axcella Presents Data at The Liver Meeting™ Providing New Mechanistic Insights on Observed Multifactorial Effects of its Liver Product Candidates
- AXA1665 enhances amino acid metabolism and improves ammonia disposal in subjects with mild and moderate hepatic insufficiency
- AXA1125 impacts key biochemical pathways and molecular mediators regulating amino acid catabolism, insulin sensitivity, inflammation and fibrogenesis
- Data reinforce product candidates’ potential to address unmet needs in hepatic encephalopathy (HE) and nonalcoholic steatohepatitis (NASH)
“Simultaneous dysregulation in multiple pathways is a fundamental feature of complex diseases such as hepatic encephalopathy (HE) and nonalcoholic steatohepatitis (NASH),” explains Dr.
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
Abstract Number: #2134
Title: Mechanistic insights into the multimodal effects of AXA1125 in T2D subjects with NAFLD
Presentation Type: Poster
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
Internet Posting of Information
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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