UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

 

FORM 8-K

 

 

 

CURRENT REPORT

Pursuant to Section 13 OR 15(d)

of The Securities Exchange Act of 1934

 

Date of Report (Date of earliest event reported): May 6, 2020

 

 

 

AXCELLA HEALTH INC.

(Exact name of registrant as specified in its charter)

 

 

 

 

Delaware   001-38901   26-3321056
(State or other jurisdiction
of incorporation)
  (Commission
File Number)
  (IRS Employer
Identification No.)

 

840 Memorial Drive
Cambridge, Massachusetts
02139
(Address of principal executive offices) (Zip Code)

 

Registrant's telephone number, including area code: (857) 320-2200

 

Not Applicable

(Former name or former address, if changed since last report)

 

 

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions ( see General Instruction A.2. below):

 

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
   
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
   
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
   
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class Trading Symbol(s) Name of each exchange on which registered
Common Stock, $0.001 Par Value AXLA Nasdaq Global Market

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

 

Emerging growth company x

 

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨

 

 

 

 

 

 

Item 8.01. Other Events

 

On May 6, 2020, Axcella Health Inc. issued a press release announcing positive top-line data from its clinical study showing multifactorial activity in adult subjects with NAFLD and hosted a conference call and webcast to discuss such top-line data. A copy of the press release is attached hereto as Exhibit 99.1 and a copy of the accompanying presentation used during the conference call and webcast is attached hereto as Exhibit 99.2.

 

Item 9.01. Financial Statements and Exhibits.

 

(d) Exhibits:

 

Exhibit
No.
  Description
   
99.1   Press release issued by Axcella Health Inc., dated May 6, 2020
99.2   Presentation of Axcella Health Inc., dated May 6, 2020

 

 

 

 

SIGNATURES

 

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

  AXCELLA HEALTH INC. 
     
Date: May 6, 2020 By: /s/ William R. Hinshaw, Jr.
    William R. Hinshaw, Jr.
    Chief Executive Officer, President and Director

 

 

 

 

Exhibit 99.1

 

 

 

Axcella Announces Positive Top-Line Data from AXA1125-003 Clinical Study
Showing Multifactorial Activity in Adult Subjects with NAFLD

 

Clinically relevant reductions in liver fat content, insulin resistance and fibroinflammation markers observed with AXA1125 along with favorable tolerability, supporting its potential to be a first-line NASH therapy

 

Greater activity in key markers seen among subjects with type 2 diabetes receiving AXA1125

 

Company plans to engage with FDA regarding IND submission for AXA1125, proposed Phase 2b clinical trial in adult NASH and pediatric development program

 

Conference call to be held today at 8:30 a.m. ET

 

Cambridge, Mass., May 6, 2020Axcella (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 positive top-line data from AXA1125-003.

 

AXA1125-003 is a placebo-controlled, randomized, multi-arm clinical study assessing the impact of AXA1125 and AXA1957 on safety, tolerability and effects on structures and functions of the liver, as measured by a comprehensive panel of imaging and soluble biomarkers related to metabolism, inflammation and fibrosis. Both of these distinct product candidates are proprietary compositions of amino acids and derivatives that have been designed to support liver health. In this non-IND study, 102 adult non-alcoholic fatty liver disease (NAFLD) subjects with presumed nonalcoholic steatohepatitis (NASH), based on inclusion criteria, were enrolled and dosed in a 2:2:2:1 ratio to receive AXA1125, one of two AXA1957 doses, or placebo administered twice daily for 16 weeks. Study subjects were stratified based on the presence or absence of type 2 diabetes.

 

Results from the study showed that AXA1125 and AXA1957 were generally well-tolerated, with sustained reductions noted for both product candidates versus placebo in key biomarkers of metabolism, inflammation and fibrosis over 16 weeks. Overall, as compared to placebo, AXA1125 demonstrated larger and more consistent reductions in clinically relevant biomarkers than AXA1957. Among subjects receiving AXA1125, 39% achieved a ≥30% relative reduction in liver fat content (MRI-PDFF), 39% achieved a ≥17 U/L reduction in alanine aminotransaminase (ALT), and 35% achieved a ≥80 mSec reduction in corrected T1 (cT1). Among the 11 subjects with type 2 diabetes receiving AXA1125, a greater proportion achieved each of these thresholds. Emerging evidence suggests that these thresholds of activity increase the likelihood of histopathological improvement in NASH subjects. Notably, the above results were seen without impacting mean body weight or serum lipids.

 

Manu Chakravarthy, M.D., Ph.D., Chief Medical Officer of Axcella, said, “In AXA1125-003, we were seeking to evaluate safety and tolerability while also determining what differential responses may be seen from AXA1125 and AXA1957 across markers of metabolism, inflammation and fibrosis. It is gratifying that multifactorial activity and a favorable tolerability profile were noted for AXA1125 in this multi-arm, placebo-controlled randomized study, which replicates findings from our previous clinical study in subjects with NAFLD and type 2 diabetes. We believe that these data, coupled with AXA1125’s oral route of administration and favorable tolerability profile to date, reinforce its potential to meaningfully improve the lives of patients with NASH.”

 

“These data indicate that AXA1125 holds the potential to be a first-line therapy in NASH, with impressive, concordant metabolism, inflammation and fibrosis activity as well as a favorable tolerability profile with no meaningful changes to serum lipids and body weight,” said Stephen A. Harrison, M.D., Medical Director of Pinnacle Clinical Research in San Antonio, TX, visiting professor of Hepatology at the University of Oxford, UK and the principal investigator of AXA1125-003. “Additionally, in the majority of subjects with type 2 diabetes receiving AXA1125, clinically relevant thresholds of activity were observed in non-invasive tests that suggest a higher probability of positive outcomes histopathologically. This is a potential differentiator and is particularly encouraging given that nearly 40% of the NASH population is diabetic and the disease is known to be more severe in these patients.”

 

 

 

 

Select Measures of Relevance at 16 Weeks

 

Measure   Placebo     AXA1125     AXA1957
Low
    AXA1957
High
 
Subjects dosed     15       29       26       32  
Mean relative reduction in liver fat content (MRI-PDFF)     -6 %     -23 %     -20 %     -8 %
Subjects with ≥30% relative reduction in liver fat content     8 %     39 %     23 %     19 %
Mean relative reduction in ALT     -7 %     -22 %     -19 %     -21 %
Subjects with ≥17 U/L reduction in ALT     25 %     39 %     32 %     37 %
Subjects with ≥80 mSec reduction in cT1     17 %     35 %     23 %     23 %
Mean absolute change in proC3 (ng/mL)     -0.7       -3.4       -3.1       -4.1  

 

* Mean values and percentages above only include subjects for whom data was available at the week 16 timepoint.

 

AXA1125 and AXA1957 were both generally well tolerated in the study. The adverse events (AEs) experienced in ≥10% of subjects were gastrointestinal (diarrhea, nausea, reduced appetite) and upper respiratory infection. Gastrointestinal AEs were generally mild and transient, self-resolving in two to three weeks on average. Two serious adverse events were reported, both of which were determined to be unrelated to study product administration.

 

“The findings from this clinical study further validate the strength of our EMM platform and its ability to identify product candidates with the potential to address complex diseases in a multi-targeted manner,” said Bill Hinshaw, President and Chief Executive Officer of Axcella. “Given the strength and consistency of data on AXA1125, we have selected it as our product candidate for NASH and have decided that we will not reinitiate our AXA1957-002 pediatric study, which had recently been suspended due to COVID-19. In the months ahead, we plan to engage with the U.S. Food and Drug Administration (FDA) to discuss our investigational new drug (IND) application for AXA1125, proposed Phase 2b clinical trial in adults and pediatric development program. We give our thanks to the many subjects and investigators who participated in AXA1125-003 and will continue working diligently toward our goal of providing them with an effective and safe treatment option.”

 

Conference Call Information

 

Axcella will host a conference call today at 8:30 a.m. ET to discuss the top-line data from AXA1125-003. The conference call webcast and accompanying slides will be made available shortly before the start of the call on the company’s website at www.axcellahealth.com in the Investors & News. To access the call via telephone, please dial (866) 652-5200 (U.S. toll free) or (412) 317-6060 (international) five minutes prior to the start time. For those unable to listen in live, a webcast archive will be available on the company’s website for 30 days following the call.

 

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 Clinical Studies

 

Each of the company’s clinical studies to date, including AXA1125-003, 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 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

 

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, competitive position and development potential of the company’s EMM product candidates, including AXA1125, the design, status and timing of the company’s ongoing clinical studies and planned IND-enabled clinical trials, including with respect to the company’s planned adult and pediatric clinical trials for AXA1125, the subject and timing of the company’s interactions with the FDA, including with respect to an IND application, Phase 2b clinical trial in adults and pediatric development plans for AXA1125, and the potential of the company’s product candidates to impact health and/or disease, including AXA1125’s potential in NASH. 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 planned 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 we are able to collect, other potential impacts of COVID-19 on our business and financial results, including with respect to our ability to raise additional capital 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 planned timing for an IND filing, clinical trial design and target indication for AXA1125, the clinical development and safety profile of the company’s product candidates and their health or therapeutic potential, 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, competition from other biotechnology companies, 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.

 

###

 

Company/Investor Contact Media Contact
Jason Fredette Azeem Zeekrya
jfredette@axcellahealth.com HDMZ
(857) 320-2236 azeem.zeekrya@hdmz.com
  (312) 506-5244

 

 

 

Exhibit 99.2

 

© 2020 Axcella Health Inc. All rights reserved. NASDAQ: AXLA AXA1125 - 003 Top - Line Data May 6, 2020

 

 

© 2020 Axcella Health Inc. All rights reserved. 2 This presentation 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, competitive position and development potential of the company’s EMM pro duc t candidates, including for AXA1125 and AXA1665, the design, status and timing of the company’s ongoing clinical studies and planned IND - enabled clinical tr ials, the company’s anticipated program milestones, including the timing of AXA1665 - 002 and AXA4010 top line data readouts, the subject and timing of the compan y’s planned interactions with the FDA on the AXA1665 and AXA1125 programs, including potential timing of IND application submissions, and the potential of the company’s product candidates to impact health and/or disease, including AXA1125’s potential in NASH and AXA1665’s potential in OHE. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and sim ilar expressions are intended to identify forward - looking statements, although not all forward - looking statements contain these identifying words. Any forward - looking sta tements in this presentation are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important fact ors that may cause actual events or results to differ materially from those expressed or implied by any forward - looking statements contained in this presentation, i ncluding, 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 stu dies and IND enabled clinical trials and planned interactions and submissions to FDA or other regulatory authorities in a timely manner or at all due to patient o r p rincipal investigator recruitment or availability challenges, clinical trial site shutdowns or other interruptions and potential limitations on the quality, compl ete ness and interpretability of data we are able to collect in our ongoing AXA1665 - 002 and AXA4010 - 001 clinical studies and potential delays in disclosure of the same, othe r potential impacts of COVID - 19 on our business and financial results, including with respect to our ability to raise additional capital and operational disr upt ions or delays, changes in law, regulations, or interpretations and enforcement of regulatory guidance, whether data readouts and/or FDA feedback support our IN D submission and clinical trial initiation plans and timing, clinical trial design and target indication for AXA1125 and AXA1665, the clinical development an d s afety profile of the company’s product candidates and their health or therapeutic potential, whether and when, if at all, the company’s product candidates w ill receive approval from the FDA or other comparable regulatory authorities, and for which, if any, indications, competition from other biotechnology companies, pas t results from clinical studies not being representative of future results, and other risks identified in the company’s SEC filings, including Axcella’s Annual R epo rt 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 state ments, 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 chan ge 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 wil l differ from those set forth in the forward - looking statements. Any forward - looking statements contained in this presentation 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 an y forward - looking statements. Forward - Looking Statements

 

 

© 2020 Axcella Health Inc. All rights reserved. 3 About Axcella’s Development Model and Clinical Approach EMMs have a fundamental role in biology and function. Using the Axcella Knowledge Base, Axcella designs and develops novel EM M c ompositions to engage identified biologies and pathways. Axcella then selects whether to evaluate a product candidate in a non - investigational new drug application (non - IND) clinical study under U.S. Food and Drug Administration regulations and guidance supporting research with food, or unde r an IND clinical trial. Axcella’s non - IND clinical studies evaluate product candidates for safety, tolerability and effects on the normal structures and functions in humans, including in individuals with disease. The company’s non - IND clinical studies include a substantial number of biomarkers that ma y inform biologies relevant to health but are not designed or intended to evaluate a product candidate’s ability to diagnose, cure, mitigate, tr eat or prevent a disease or other health condition. They are conducted at reputable medical centers following Good Clinical Practices (GCPs), including I nst itutional Review Board (IRB) approval, and utilize qualified investigators. Using a combination of data from these studies and/or other relevant inf orm ation, the company decides whether to advance a product candidate’s development as a therapeutic or supplement (independently or in partnership) , o r terminate its development. To date, Axcella has evaluated its current product candidates as investigational food products in non - IND clinical studies. Axce lla has determined its lead compounds – AXA1665 and AXA1125 – to be therapeutic product candidates, meaning that pending and subject to final data readouts from ongoing non - IND clinical studies and FDA feedback, any future development of these product candidates will be under IND clinical trials. These IND clinical trials would therefore be designed to evaluate each product candidate’s ability to diagnose, cure, mitigate, treat or prevent target ed diseases. The company’s current plans are to target OHE with AXA1665 and NASH with AXA1125 in IND clinical trials. In the future, if Axcella decides to pursue therapeutic development for a new product candidate, it will initiate clinical de vel opment under an IND - enabled trial. This presentation refers to Axcella’s non - IND clinical studies as “Clinical Studies” and its planned IND - enabled clinical trials as “Clinical Trials.”

 

 

© 2020 Axcella Health Inc. All rights reserved. 4 EMM, Endogenous Metabolic Modulator; FDA, U.S. Food and Drug Administration; NASH, nonalcoholic steatohepatitis. AXA1125: A Potential First - Line NASH Therapy • AXA1125 - 003 findings further validate Axcella’s platform and approach utilizing EMMs • Multifactorial activity observed for both AXA1125 and AXA1957, while being well tolerated • AXA1125 generated more clinically relevant reductions in liver fat content, insulin resistance and fibroinflammation markers when compared with AXA1957 – Greater activity in key markers seen among subjects with type 2 diabetes receiving AXA1125 • Plan to engage with FDA to discuss an IND application for AXA1125, a proposed Phase 2b clinical trial in adults and Axcella’s pediatric development program

 

 

© 2020 Axcella Health Inc. All rights reserved. 5 Axcella’s Focus: Endogenous Metabolic Modulators (EMMs) EMMs Act as Signaling Agents and Master Regulators in Human Biology • EMMs, including amino acids, are well established agents used to support health • Single EMMs and simple EMM combinations have been approved as treatments for various diseases • Leveraging advances in machine learning and systems biology, Axcella is developing novel EMM compositions that: – Include up to 10 amino acids and derivatives – Are designed to affect multiple biological pathways simultaneously – Have disease - modifying potential Circulatory System Liver Adipose Tissue GI Tract Central Nervous System Immune System Kidneys Skeletal Muscle

 

 

© 2020 Axcella Health Inc. All rights reserved. 6 1. Company estimates based on Decision Resources Group (DRG). Non - alcoholic Steatohepatitis Landscape & Forecast. DRG 2. Cusi , K. Diabetologia . 2016 NASH: A Complex Disease with High Unmet Needs Metabolism Fibrosis Inflammation State of the market: • >15 million U.S. patients and growing 1 • Similar prevalence in the European Union 5 • 30 - 40% of the population is diabetic 2 • Expected to be the leading liver transplant cause this year • U.S. market expected to reach at least $8 billion by 2027 1 State of development: • No approved therapies in the U.S. • Single - target mechanisms for most agents in development • Safety/tolerability challenges (lipids, pruritis, etc.) • Combination therapy already an area of focus • Very limited pediatric development activity Potential Axcella Differentiators: • Oral candidate for first - line therapy • Multi - targeted approach • Favorable safety/tolerability profile to date • Amenable to combination approaches • Planning for pediatric development

 

 

© 2020 Axcella Health Inc. All rights reserved. 7 Hypothesized mechanisms depicted above. AAs, amino acids; AMPK, AMP - activated protein kinase; Arg , arginine; Gln , glutamine; GSH, glutathione; Hif1 α, hypoxia - inducible factor 1 alpha; GSH, glutathione; Ile, isoleucine; Leu, leucine; Nac , N - acetylcysteine; NASH, nonalcoholic steatohepatitis; NF κ B, nuclear factor kappa - light - chain - enhancer of activated B cells; NH3, ammonia; NO, nitric oxide; PPAR α, peroxisome proliferator - activated receptor alpha; ROS, reactive oxygen species; TGF β, transforming growth factor beta; Val, valine. AXA1125 - A Novel Oral Product Candidate for NASH Designed to target multiple metabolic pathways; potential for multifactorial activity relevant to NASH 1125 Prevent Fibrosis Progression Reduce Inflammation/Injury Improve Metabolism Leu Gln Arg Nac Ile Val Lipotoxicity Leu Ile Val Ketones Carnitines PPAR a AMPK Arg NO NH3 Glucose uptake Insulin sensitivity Non - dosed AAs Urea Gln Gut barrier/ tight junction Inflammation Nac GSH ROS Hif1 a NF k B TGF b Hepatic stellate cell activation & fibrogenesis Arg Endotoxin Urea cycle

 

 

© 2020 Axcella Health Inc. All rights reserved. 8 1. Non - IND Clinical Study initiated prior to therapeutic development path decision. Please refer to slide 3 for further detail. 23 subjects received AXA1125 24 g TID and had baseline PDFF >10%; 5 received AXA1125 24 g TID with baseline PDFF <10%; 4 rece ive d AXA1125 6 g TID. ALT, alanine aminotransferase; IND, investigational new drug; MRI - PDFF, magnetic resonance imaging proton density fat fraction; NAFLD, n on - alcoholic fatty liver disease ; ProC3, propeptide of type III collagen; TID, 3 times a day. Positive Results Seen in Previous Clinical Study of AXA1125 AXA1125 - 002: A single - arm Clinical Study of 32 subjects with type 2 diabetes and NAFLD Reduced ProC3 (fibrogenic marker) 0 30 Day 1 n=22 Week 12 n=18 Mean proC3 (ng/mL) Reduced ALT ( inflammation marker) 0 60 Day 1 n=22 Week 12 n=13 Mean ALT (U/L) 0 20 Day 1 n=22 Week 12 n=13 Reduced Liver Fat (MRI - PDFF) Mean PDFF (%) Inflammation Fibrosis Metabolism

 

 

© 2020 Axcella Health Inc. All rights reserved. 9 1. Non - IND Clinical Study initiated prior to therapeutic development path decision. Please refer to slide 3 for further detail. 2. C alorie - matched placebo control. BID, 2 times a day; BMx , biomarkers; D, Day; cT1, corrected T1; IND, investigational new drug; MRI - PDFF, magnetic resonance imaging proton density fat fraction; oGTT , oral glucose tolerance test; T2D, type 2 diabetes; W, Week. Design of AXA1125 - 003 Screening 2:1 Randomization (N = 102) AXA1957 20.3g BID (40.6g/d) (n =32 ) AXA1125 24.0g BID (48.0g/d) (n =29 ) Placebo 24.0g BID 2 (48.0g/d) (n=15) Follow - up 16 WEEKS 2 WEEKS D1: MRI, oGTT, BMx W2 W12 W16: MRI, oGTT, BMx W8: MRI, oGTT, BMx W1 AXA1957 13.5g BID (27.0g/d) (n =26 ) W4 W18 - 6W STUDY DESIGN Multicenter (Summit Network), 16 - week, randomized, placebo - controlled Clinical Study of AXA1125 and AXA1957 Key inclusions: >10% fat by MRI - PDFF, cT1 >830 mSec Stratified by T2D and non - diabetic subjects STUDY BACKGROUND 1 Primary endpoint: Safety & tolerability Key assessments include: • Liver structure by MRI - PDFF and cT1 • Liver function: Markers of glucose and lipid homeostasis, inflammation, apoptosis, and fibrosis Not powered for statistical significance

 

 

© 2020 Axcella Health Inc. All rights reserved. 10 All values are mean (SE) unless otherwise noted. ALT, alanine aminotransferase; AST, alanine transaminase; BMI, body mass index; cT1, corrected T1; HOMA - IR, homeostasis model as sessment of insulin resistance; MRI - PDFF, magnetic resonance imaging proton density fat fraction; ProC3, propeptide of type III collagen; SD, standard deviation; SE, standard error. Demographics Indicative of a Population with Presumed NASH Baseline Demographic/Metric Placebo (n=15) AXA1125 (n=29) AXA1957 high (n=32) AXA1957 low (n=26) Age, mean (SD), years 53.2 (9.62) 49.2 (12.79) 50.1 (12.79) 49.6 (10.74) Sex Female, n (%) 10 (66.7) 17 (58.6) 19 (59.4) 16 (61.5) Male, n (%) 5 (33.3) 12 (41.4) 13 (40.6) 10 (38.5) Weight, mean (SD), kg 118.25 (31.75) 102.86 (23.82) 102.31 (26.14) 106.24 (23.50) BMI, mean (SD), kg/m 2 42.0 (9.39) 36.8 (7.32) 38.5 (8.49) 37.4 (6.11) Diagnosed type 2 diabetes, n (%) 6 (40.0) 12 (41.4) 12 (37.5) 10 (38.5) Metabolism Liver fat content by MRI - PDFF, % 21.19 (1.51) 22.35 (0.93) 22.27 (0.93) 21.01 (1.16) HOMA - IR 8.59 (1.23) 13.51 (3.39) 10.82 (1.78) 9.62 (1.35) Inflammation ALT, U/L 50.5 (8.73) 55.2 (4.89) 50.5 (4.11) 60.6 (5.66) AST, U/L 41.3 (34.3) 37.3 (22.7) 40.6 (21.0) 34.9 (16.6) cT1, mSec 1022.3 (41.35) 960.6 (16.84) 1017.2 (24.30) 959.5 (21.67) Fibrosis Fibroscan score, mean (SD), kPa 13.51 (5.69) 11.73 (6.67) 11.18 (3.82) 16.31 (15.76) ProC3, ng/mL 15.85 (1.82) 17.07 (1.56) 16.76 (1.73) 17.02 (1.90)

 

 

11 © 2020 Axcella Health Inc. All rights reserved. Activity Seen in Subjects Receiving AXA1125 vs. Placebo

 

 

© 2020 Axcella Health Inc. All rights reserved. 12 - 0.7 - 3.4 -6 -4 -2 0 Absolute change, mean (SE), ng/mL - 1.9 - 7.5 -14 -7 0 Relative change, mean (SE), % *p<0.05 versus placebo. ALT, alanine aminotransferase; cT1, corrected T1; FIB - 4, fibrosis 4; HOMA - IR, homeostasis model assessment of insulin resistance ; MRI - PDFF, magnetic resonance imaging proton density fat fraction; ProC3, propeptide of type III collagen; SE, standard error. AXA1125: Reductions Noted in Key Biomarkers Changes from baseline at week 16 Inflammation Fibrosis Metabolism - 5.7 - 22.9 -30 -20 -10 0 Relative change, mean (SE), % - 7.2 - 21.9 -30 -20 -10 0 Relative change, mean (SE), % 18.3 - 69.6 -90 -70 -50 -30 -10 10 30 50 Absolute change, mean (SE), mSec * 0.7 - 4.4 -9 -6 -3 0 3 Absolute change, mean (SE) MRI - PDFF ALT ProC3 HOMA - IR cT1 FIB - 4 Placebo AXA1125 n = 12 26 n = 12 26 n = 12 26 n = 11 25 n = 12 26 n = 10 24

 

 

© 2020 Axcella Health Inc. All rights reserved. 13 - 21.4 - 16.2 -45 -30 -15 0 Relative change, mean (SE), % ALT, alanine aminotransferase; cT1, corrected T1; FIB - 4, fibrosis 4; HOMA - IR, homeostasis model assessment of insulin resistance ; MRI - PDFF, magnetic resonance imaging proton density fat fraction; ProC3, propeptide of type III collagen; SE, standard error. AXA1125: Even Greater Activity Seen in Subjects with Diabetes Changes from baseline at week 16 Inflammation Fibrosis Metabolism - 8.3 - 31.2 -40 -20 0 Relative change, mean (SE), % - 13.9 - 34.6 -50 -25 0 Relative change, mean (SE), % - 42.7 - 105.1 -150 -120 -90 -60 -30 0 Absolute change, mean (SE), mSec - 3.5 - 5.3 -9 -6 -3 0 Absolute change, mean (SE), ng/mL - 0.8 - 9.2 -18 -15 -12 -9 -6 -3 0 Absolute change, mean (SE) Placebo AXA1125 MRI - PDFF ALT ProC3 HOMA - IR cT1 FIB - 4 n = 3 11 n = 3 11 n = 3 11 n = 3 10 n = 3 11 n = 2 10

 

 

© 2020 Axcella Health Inc. All rights reserved. 14 HbA1c, glycated hemoglobin; SE, standard error. AXA1125: Insulin and Glucose Changes in Type 2 Subjects with Diabetes Changes from baseline at week 16 - 4.0 - 14.0 -30 -25 -20 -15 -10 -5 0 Absolute change, mean (SE), mIU/L Fasting Insulin - 0.3 - 0.7 -1 -0.9 -0.8 -0.7 -0.6 -0.5 -0.4 -0.3 -0.2 -0.1 0 Absolute change, mean (SE), % HbA1C - 9.0 - 23.4 -40 -35 -30 -25 -20 -15 -10 -5 0 Absolute change, mean (SE),mg/dL/L Fasting Glucose n = 3 11 n = 3 11 Placebo AXA1125 n = 3 11

 

 

15 © 2020 Axcella Health Inc. All rights reserved. Activity Seen in Subjects Receiving AXA1125 and AXA1957 vs. Placebo

 

 

© 2020 Axcella Health Inc. All rights reserved. 16 HOMA - IR, homeostasis model assessment of insulin resistance; MRI - PDFF, magnetic resonance imaging proton density fat fraction; S E, standard error. Greater Metabolism Activity with AXA1125 Changes from baseline at week 16 Metabolism Placebo AXA1125 AXA1957 High AXA1957 Low - 5.7 - 22.9 - 8.1 - 20.3 -30 -25 -20 -15 -10 -5 0 Relative change, mean (SE), % 8.3 38.5 19.2 22.7 0 10 20 30 40 Subjects, % - 1.2 - 5.2 - 2.1 - 3.6 -7 -6 -5 -4 -3 -2 -1 0 Absolute change, mean (SE), % Relative Reduction in MRI - PDFF ≥30% Relative Reduction in MRI - PDFF Absolute Reduction in MRI - PDFF 0.7 - 4.4 8.4 1.4 -8 -4 0 4 8 12 16 Absolute change, mean (SE) Absolute Reduction in HOMA - IR n = 12 26 26 22 n = 12 26 26 22 n = 12 26 26 22 n = 12 26 25 22

 

 

© 2020 Axcella Health Inc. All rights reserved. 17 n = 12 26 26 22 25.0 38.5 37.0 31.8 0 10 20 30 40 Subjects, % *p<0.05 versus placebo. ALT, alanine aminotransferase; cT1, corrected T1; SE, standard error . Greater Impact on Inflammation with AXA1125 Changes from baseline at week 16 Inflammation Placebo AXA1125 AXA1957 High AXA1957 Low - 7.2 - 21.9 - 20.7 - 19.2 -30 -25 -20 -15 -10 -5 0 Relative change, mean (SE), % 18.3 - 69.6 - 34.7 - 39.7 -90 -70 -50 -30 -10 10 30 50 Absolute change, mean (SE), mSec Relative Reduction in ALT ≥17 U/L Reduction in ALT Absolute Reduction in cT1 16.7 34.6 23.1 22.7 0 5 10 15 20 25 30 35 Subjects , % ≥80 mSec Reduction in cT1 * n = 12 26 27 22 n = 12 26 27 22 n = 12 26 26 22

 

 

© 2020 Axcella Health Inc. All rights reserved. 18 FIB - 4, fibrosis 4; ProC3, propeptide of type III collagen; SE, standard error. Equivalent Activity on Fibrosis Markers with AXA1125 Changes from baseline at week 16 Fibrosis - 0.7 - 3.4 - 4.1 - 3.1 -6 -5 -4 -3 -2 -1 0 Absolute change, mean (SE), ng/mL - 1.9 - 7.5 - 3.3 - 4.4 -14 -12 -10 -8 -6 -4 -2 0 Relative change, mean (SE), % - 3.6 - 13.6 - 15.6 - 9.4 -25 -20 -15 -10 -5 0 Relative change, mean (SE), % Relative Reduction in proC3 Relative Reduction in FIB - 4 Absolute Reduction in ProC3 Placebo AXA1125 AXA1957 High AXA1957 Low n = 10 24 25 22 n = 10 24 25 22 n = 11 25 27 22

 

 

© 2020 Axcella Health Inc. All rights reserved. 19 33.0 45.5 0 10 20 30 40 50 Subjects , % 33.0 63.6 0 10 20 30 40 50 60 70 Subjects, % 0.0 54.5 0 20 40 60 Subjects, % 1. Loomba, R. et al. Hepatology. January 2020 2. Loomba, R. et al. Gastroenterology. January 2019 ALT, alanine aminotransferase; cT1, corrected T1; MRI - PDFF, magnetic resonance imaging proton density fat fraction; NASH, nonalc oholic steatohepatitis; NAFLD, n on - alcoholic fatty liver disease; SE, standard error. AXA1125: Meaningful Thresholds of Activity Achieved Increasing evidence linking PDFF, ALT and cT1 with improved histological outcomes Placebo AXA1125 ≥17 U/L Reduction in ALT 16.7 34.6 0 7 14 21 28 35 Subjects , % ≥80 mSec Reduction in cT1 25.0 38.5 0 10 20 30 40 Subjects, % n = 12 26 n = 12 26 ≥30% Reduction in MRI - PDFF 8.3 38.5 0 10 20 30 40 Subjects, % n = 12 26 All Subjects Diabetic Subjects 0 n = 3 11 n = 3 11 n = 3 11 ALT cT1 PDFF ≥17 U/L reduction associated with histologic response in NASH 2 >80 mSec reduction may correlate with a 2 pt. NAFLD score improvement ≥30% reduction associated with histologic response in NASH 1

 

 

© 2020 Axcella Health Inc. All rights reserved. 20 1. Safety based on what subject received on day 1 of dosing. Subjects counted only once if they had more than one event repor ted during the product administration period. AE, adverse event; GI, gastrointestinal; SAE, serious adverse event; PEAEs, product - emergent adverse events AXA1125 and AXA1957 were Generally Well Tolerated • AEs were mild to moderate • Most frequent AEs for AXA1125 involved GI issues: – These AEs were generally mild and transient, self - resolving in two to three weeks on average • Only one discontinuation due to AEs for placebo and AXA1125 • Two SAEs reported; both assessed as unrelated to study product administration • No meaningful changes seen in lipids or weight in active arms Subjects with product - emergent AEs, n (%) 1 Placebo (n=15) AXA1125 (n=29) AXA1957 High (n=32) AXA1957 Low (n=26) All PEAEs 10 (66.7) 24 (82.8) 19 (59.4) 19 (73.1) All PEAEs reported in >10% for any arm: Diarrhea 1 (6.7) 10 (34.5) 6 (18.8) 3 (11.5) Nausea 1 (6.7) 4 (13.8) 3 (9.4) 3 (11.5) Upper respiratory infection 1 (6.7) 4 (13.8) 2 (6.3) 0 Decreased appetite 0 3 (10.3) 1 (3.1) 2 (7.7) Headache 1 (6.7) 1 (3.4) 2 (6.3) 4 (15.4) Severity of product - emergent AEs, n (%) 1 Placebo (n=15) AXA1125 (n=29) AXA1957 High (n=32) AXA1957 Low (n=26) Diarrhea Mild 1 (6.7) 6 (20.7) 5 (15.6) 3 (11.5) Moderate 0 4 (13.8) 1 (3.1) 0 Severe 0 0 0 0 Nausea Mild 1 (6.7) 3 (10.3) 2 (6.3) 1 (3.8) Moderate 0 1 (3.4) 1 (3.1) 2 (7.7) Severe 0 0 0 0

 

 

© 2020 Axcella Health Inc. All rights reserved. 21 EMM, Endogenous Metabolic Modulator; FDA, U.S. Food and Drug Administration; NASH, nonalcoholic steatohepatitis. AXA1125: A Potential First - Line NASH Therapy • AXA1125 - 003 findings further validate Axcella’s platform and approach utilizing EMMs • Multifactorial activity observed for both AXA1125 and AXA1957, while being well tolerated • AXA1125 generated more clinically relevant reductions in liver fat content, insulin resistance and fibroinflammation markers when compared with AXA1957 – Greater activity in key markers seen among subjects with type 2 diabetes receiving AXA1125 • Plan to engage with FDA to discuss an IND application for AXA1125, a proposed Phase 2b clinical trial in adults and Axcella’s pediatric development program

 

 

© 2020 Axcella Health Inc. All rights reserved. 22 AXA1665 and AXA4010 are being investigated in Non - IND Clinical Studies. Please refer to slides 3 for further detail. 1. Timing based on current expectations and subject to risks associated with the COVID - 19 pandemic. 2. We believe that this has the potential to serve as a registrational Clinical Trial, contingent upon final data readout from o ngo ing Clinical Study and allowance by the FDA. Multiple Anticipated Milestones in 2020 THERAPEUTIC PRODUCT CANDIDATES AREA OF FOCUS PRODUCT CANDIDATE POTENTIAL INDICATION Q1 2020 Q2 2020 Q3 2020 1 Q4 2020 1 LIVER AXA1125 NASH AXA1665 Reduction in Risk of Overt Hepatic Encephalopathy Recurrence EARLY - STAGE PIPELINE AREA OF FOCUS PRODUCT CANDIDATE SUBJECTS STUDIED Q1 2020 Q2 2020 Q3 2020 1 Q4 2020 1 BLOOD AXA4010 Sickle Cell Disease x Completed enrollment in AXA1665 - 002 Report top - line data from AXA1665 - 002 Submit IND application to FDA and initiate potential Phase 2b/3 Clinical Trial 2 x Reported top - line data from AXA1125 - 003 Report top - line data from Cohort 1 of AXA4010 - 001 x Reported interim findings from AXA1125 - 003 Engage with FDA regarding potential Phase 2b Clinical Trial and pediatric development program

 

 

© 2020 Axcella Health Inc. All rights reserved. Participating Sites: Arizona Liver Health Kansas City Research Institute Chandler & Tucson, AZ Kansas City, MO Bioclinical Research Liver Center of Texas Orlando, FL Dallas, TX Cataline Research Institute National Research Institute Montclair, CA Los Angeles, Huntington Park & Panorama City, CA Doctors Hospital at Renaissance Pinnacle Clinical Research Edinburg, TX San Antonio & Austin, TX Excel Medical Clinical Trials Southern Therapy & Advanced Res. Boca Raton, FL Jackson, MS Florida Research Institute Texas Digestive Disease Consultants Lakewood Ranch, FL Fort Worth, TX Gastro One Germantown, TN Our thanks to the subjects and investigators who participated in AXA1125 - 003