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The liver has many critical functions relating to metabolism, including detoxification of a variety of substances, synthesis of key proteins and other intermediary substrates impacting nutrient homeostasis to coagulation, lipid metabolism and amino acid regulation.

We are investigating our AXA Candidates for safety, tolerability and physiological effects across a spectrum of normal liver structures and functions in our Non-IND, IRB Approved Clinical Studies*. Our AXA Candidates may have potential for development under an IND as drug product candidates with applications in conditions from Non-Alcoholic Steatohepatitis (NASH) to HE. If we decide to further develop one or more of our AXA liver Candidates under food regulations under a non-drug development path, we or a strategic partner may decide to develop our AXA liver Candidates as a consumer health product to support liver health.


HE is a type of metabolic encephalopathy with multifactorial causes that is a common complication of cirrhosis. Prevalence of cirrhosis in the United States is approximately 0.27%, corresponding to approximately 633,000 adults, and the estimated prevalence of overt HE (OHE) is 10% to 14% in the general cirrhotic population and 16% to 21% in those with decompensated cirrhosis. OHE refers to the evidence of neurological abnormalities without specialized psychometric testing, while minimal or covert HE requires specialized testing for its diagnosis, including psychometric tests. HE has multiple precipitating factors, such as amino acid imbalance, ammonia handling, muscle wasting, infections, and constipation. HE is well-established as a significant cause of morbidity and mortality in the cirrhotic population and represents a significant unmet medical need. Muscle depletion and muscle fat infiltration independently increase the risk of both overt and minimal HE with increased mortality. Decline in muscle mass can also hamper the alternative pathway of ammonia detoxification, and hyperammonemia may further worsen sarcopenia, generating a vicious cycle. The highly interdependent complications of cirrhosis, sarcopenia and HE constitute a significant disease burden and can have an impact on irreversible morbidity and mortality in cirrhotic patients. Approximately 63,000 to 130,000 individuals may be affected at any given time with both cirrhotic sarcopenia and overt HE in the United States.

+ AXA1665 IN HE

Our lead program is AXA1665 for the treatment of HE, with time to breakthrough of overt HE event as primary endpoint, with key muscle related secondary endpoints. We believe that therapeutic strategies that simultaneously address both sarcopenia and support the ammonia detoxification process will clinically improve outcomes, such as maintaining remission of HE in those with prior overt HE and/or reduce rates of other cirrhosis complications, and ultimately mortality. AXA1665 was designed to target multiple metabolic pathways intersecting key organ systems (liver, muscle and gut) to maintain liver health, and to impact the underlying biology of plasma amino acid imbalance, ammonia handling and muscle wasting. Prior to making a drug development path decision for AXA1665, we completed a Non-IND IRB-approved study with AXA1665 in subjects with mild and moderate hepatic insufficiency in which we observed:

• A cumulative increase of 40% in the Fischer’s ratio, or FR, the molar ratio of branched-chain amino acids, or BCAAs, to aromatic amino acids, or AAAs;

• A lower plasma ammonia area under the curve when sampled over five hours (AUC0-5h); and

• Subjects tended to maintain a leaner phenotype (i.e. increase in dry lean mass and decrease in fat mass as assessed by bioimpedance measurements) and muscle function (as assessed using a liver frailty index score) compared to those on a control regimen.

Prior to making a drug development path decision for AXA1665, we initiated a 12-week, randomized placebo-controlled, Non-IND, IRB-Approved Clinical Study to assess AXA1665’s safety, tolerability and physiological impact on normal liver and muscle structures and functions in approximately 60 subjects with mild and moderate hepatic insufficiency. This study is ongoing and we anticipate the data readout from this study in the first half of 2020.

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Beyond its role in generating contractile force for movement, skeletal muscle is the primary site of glucose disposal, is a large contributor to circulating lipid oxidation, and accounts for a large portion of resting metabolic rate.

When a muscle remains unused, even for a period of several days, it begins to waste away and lose functionality, the pathophysiology of which is complex and multifactorial. We have completed two Non-IND IRB Approved Clinical Studies investigating the safety, tolerability and impact of our AXA muscle Candidate on normal muscle structure and function. If we pursue development of our muscle Candidate under an IND, we believe it could potentially be investigated for multiple indications characterized by disuse-related muscle atrophy, including total knee arthroplasty, total hip arthroplasty, hip fracture related myopenia, rotator cuff repairs or injury, and other musculoskeletal atrophy or injuries. If we decide to further develop our AXA muscle Candidate under food regulations under a non-drug development path, we or a strategic partner may decide to develop our AXA muscle Candidate as a consumer health product to support muscle health.


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In addition to supporting normal structure and function of blood, we believe EMMs have the potential to target and address diseases of the blood such as Sickle Cell Disease (SCD).

Single amino acid-based approaches have been tested and approved for SCD. Glutamine was approved by the FDA in 2017 for the treatment of SCD. We plan to initiate a Non-IND, IRB-Approved Clinical Study with our AXA blood candidate targeting structure and function of the blood in the second half of 2019, and based on our findings will make the appropriate development path decision to develop as a drug or non-drug product. Under a non-drug development path, we or a strategic partner may decide to develop our AXA blood candidate as a dietary supplement to support blood health.


*Axcella conducts Non-IND, IRB-approved Clinical studies to evaluate the safety and tolerability of its AXA candidates in human subjects, or effects on the normal structure or function of the body. Studies intended at the time of initiation to support drug development will be conducted under an IND.