On August 2, 2022, the Company reported topline results from the
Phase 2a randomized, double-blind, placebo-controlled investigation to evaluate the efficacy and safety of AXA1125 in patients with fatigue
related to Long COVID.
In the study, 41 subjects were enrolled and randomized to receive either
67.8 grams per day of AXA1125 (N=21) or a matched placebo (N=20) in two divided doses for 28 days, with a one-week safety follow-up period.
All 41 subjects who started the study remained in the study to completion. Endpoints included phosphocreatine recovery time (PCrτ)
following moderate exercise as assessed by 31P-magnetic resonance spectroscopy (MRS), which was included to assess mitochondrial function,
and most importantly, clinically relevant endpoints including self-reported mental and physical fatigue as assessed by the Chalder Fatigue
Questionnaire (CFQ-11), 6 minute walk test (6MWT) as well as serum lactate levels. The CFQ-11 is a validated patient reported outcome
measure of fatigue that has been used in measuring patient impact in fatigue states such as chronic fatigue syndrome.
Subjects who received AXA1125 had improvements in measures of mental
and physical fatigue that were both highly statistically significant and clinically relevant compared to those who received placebo. Mean
changes in total, physical and mental scores in the CFQ-11 versus placebo were -4.30 (p=0.0039), -2.94 (p=0.0097) and -1.32 (p=0.0097),
respectively. Clinically meaningful shifts in the severity of physical and mental fatigue were also noted in subjects who received AXA1125
compared to those who received placebo. There was a statistically significant correlation of improvement in fatigue score and greater
distance achieved in the 6MWT (p=0.0027), an objective measure of physical ability, only observed in subjects who received AXA1125 when
compared to those receiving placebo.
Baseline PCrτ among all subjects was significantly higher
and had a higher degree of inter-subject variability (92.46 S + 35.3 S) than previously reported in the literature. These findings
support the hypothesis that there is significant mitochondrial dysfunction in these patients but limits the utility of this
parameter in a clinical trial. The trial did not meet its exploratory primary endpoint of showing a change from baseline to week
four in the PCrτ recovery rate following moderate exercise between subjects receiving AXA1125 and placebo. There was a notable
trend toward significant improvement in serum lactate levels after a 6MWT in AXA1125 subjects (p=0.0730). AXA1125 was safe and well
tolerated with no significant emergent adverse events or serious adverse events reported by study subjects.
Cautionary Note Regarding
Forward-Looking Statements
This Form 8-K contains forward-looking statements within the meaning
of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding interest that
may ensue in the Company’s product candidates or securities following announcement of the Company’s recent clinical trial
results and the timing of the Company’s clinical trial data readouts and next steps for its clinical programs, including a potential
registration trial of AXA1125 for the treatment of Long COVID. 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 Form 8-K 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 Form 8-K, including, without limitation, those
related to the belief that mitochondrial dysfunction is a key driver of Long COVID induced fatigue, potential impact of COVID-19 on the
Company’s ability to conduct and complete its ongoing or planned clinical studies and 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 clinical
trials of AXA1125, other potential impacts of COVID-19 on the Company’s business and financial results, including with respect to
its ability to raise additional capital and operational disruptions or delays, changes in law, regulations, or interpretations and enforcement
of regulatory guidance, whether data readouts support the Company’s clinical trial plans and timing, clinical trial design and target
indications for AXA1125, the clinical development and safety profile of AXA1125 and its therapeutic potential, whether and when, if at
all, the Company’s product candidates will receive approval from the FDA or other comparable regulatory authorities, potential competition
from other biopharma companies in the Company’s target indications, and other risks identified in the company’s SEC filings,
including Axcella’s Annual Report on Form 10-K, Quarterly Reports 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 Form 8-K 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.