CHIT1

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Amylyx Pharmaceuticals, Inc. (Nasdaq: AMLX) (“Amylyx” or the “Company”) today announced the publication of analyses performed on neuroinflammatory biomarkers using plasma samples from participants with amyotrophic lateral sclerosis (ALS) from the Phase 2 CENTAUR trial. These findings were published in the peer-reviewed medical journal, Journal of Neurology, Neurosurgery and Psychiatry. During the CENTAUR trial, plasma samples were prospectively collected from trial participants for future biomarker analyses. Post hoc analyses were conducted to look at the impact of AMX0035 on biomarkers shown to correlate with ALS disease progression, including chitinase biomarkers such as YKL-40 (also known as chitinase-3-like protein 1), chitinase 1 (CHIT1), and the systemic inflammatory biomarker C-reactive protein (CRP). The results of these post hoc analyses demonstrated a significant reduction in plasma concentrations of YKL-40 and CRP, but not CHIT1, over 24 weeks, with reductions observed as early as Week 12 in participants from the CENTAUR trial. “Neuroinflammatory biomarkers are important for assessing disease progression and therapeutic response in ALS with chitinases and CRP emerging as potential treatment response biomarkers. Previous studies have shown that levels of YKL-40 in cerebrospinal fluid correlate with ALS disease progression rate, severity, and survival,” said Robert Bowser, PhD, Chief Scientific Officer of Barrow Neurological Institute. “The learnings from these analyses are an important step linking the biological impact of AMX0035 with potential key biomarkers for ALS.” “Biomarkers linking clinical therapeutic effect with biological changes are of high interest in ALS, and the findings from these analyses suggest that YKL-40 could be a treatment-sensitive biomarker,” said Machelle Manuel, PhD, Head of Global Medical Affairs at Amylyx. “YKL-40 and CRP concentration decreased significantly for the group of participants that received AMX0035 compared to placebo and were correlated with disease progression as measured by the ALSFRS-R, further demonstrating the impact of AMX0035.” Of the 135 participants in the modified intent-to-treat population (ITT) of the CENTAUR trial, 126 had plasma samples available for these analyses. The analyses showed that geometric least squares (LS) mean YKL-40 and CRP plasma concentrations were 10% and 17% lower, respectively, at Week 12 and approximately 20% and 30% lower, respectively, at Week 24 in the AMX0035 versus placebo group. YKL-40 and CRP concentrations correlated with ALSFRS-R total score and ALSFRS-R slope. Geometric LS mean CHIT1 plasma levels were not significantly different between treatment groups. Further analyses of neuroinflammatory biomarkers are planned in the ongoing Phase 3 PHOENIX trial to confirm these results. About RELYVRIO®/ ALBRIOZA™ / ALBRIOZA® / AMX0035 RELYVRIO®, an oral, fixed-dose combination of sodium phenylbutyrate and taurursodiol (known as ursodoxicoltaurine outside of the U.S.), is approved to treat amyotrophic lateral sclerosis (ALS) in adults in the U.S. and approved with conditions as ALBRIOZA™ for the treatment of ALS in Canada. AMX0035 is being studied for the potential treatment of other neurodegenerative diseases, and Amylyx is exploring its treatment in other populations and regions. The formulation of RELYVRIO, ALBRIOZA, and AMX0035 are identical. RELYVRIO® (sodium phenylbutyrate and taurursodiol) Safety Information for United States WARNINGS AND PRECAUTIONS Risk in Patients with Enterohepatic Circulation Disorders, Pancreatic Disorders, or Intestinal Disorders RELYVRIO contains taurursodiol, which is a bile acid. In patients with disorders that interfere with bile acid circulation, there may be an increased risk for worsening diarrhea, and patients should be monitored appropriately for this adverse reaction. Pancreatic insufficiency, intestinal malabsorption, or intestinal diseases that may alter the concentration of bile acids may also lead to decreased absorption of either of the components of RELYVRIO. Because different enterohepatic circulation, pancreatic, and intestinal disorders have varying degrees of severity, consider consulting with a specialist. Patients with disorders of enterohepatic circulation (e.g., biliary infection, active cholecystitis), severe pancreatic disorders (e.g., pancreatitis), and intestinal disorders that may alter concentrations of bile acids (e.g., ileal resection, regional ileitis) were excluded from the study; therefore, there is no clinical experience in these conditions. Use in Patients Sensitive to High Sodium Intake RELYVRIO has a high salt content. Each initial daily dosage of 1 packet contains 464 mg of sodium; each maintenance dosage of 2 packets daily contains 928 mg of sodium. In patients sensitive to salt intake (e.g., those with heart failure, hypertension, or renal impairment), consider the amount of daily sodium intake in each dose of RELYVRIO and monitor appropriately. ADVERSE REACTIONS The most common adverse reactions (at least 15% and at least 5% greater than placebo) with RELYVRIO were diarrhea, abdominal pain, nausea, and upper respiratory tract infection. Gastrointestinal-related adverse reactions occurred throughout the study but were more frequent during the first 3 weeks of treatment. Please click here for RELYVRIO Full U.S. Prescribing Information. About the CENTAUR Trial CENTAUR was a multicenter Phase 2 clinical trial in 137 participants with ALS encompassing a 6-month randomized placebo-controlled phase and an open-label long-term follow-up phase. The trial met its primary efficacy endpoint of reducing functional decline as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). Overall, reported rates of adverse events and discontinuations were similar between AMX0035 and placebo groups during the 24-week randomized phase; however, gastrointestinal events occurred with greater frequency (≥2%) in the AMX0035 group. Detailed data from CENTAUR is published in the New England Journal of Medicine (NEJM) and Muscle & Nerve. The CENTAUR trial was funded, in part, by the ALS ACT grant and the ALS Ice Bucket Challenge, and was supported by The ALS Association, ALS Finding a Cure (a program of The Leandro P. Rizzuto Foundation), the Northeast ALS Consortium, and the Sean M. Healey & AMG Center for ALS at Mass General. About Amylyx Pharmaceuticals Amylyx Pharmaceuticals, Inc. is committed to supporting and creating more moments for the neurodegenerative community through the discovery and development of innovative new treatments. Amylyx is headquartered in Cambridge, Massachusetts and has operations in Canada and EMEA. For more information, visit amylyx.com and follow us on LinkedIn and X, formerly known as Twitter. For investors, please visit investors.amylyx.com. Forward-Looking Statements Statements contained in this press release and related comments in our earnings conference call regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, the potential of AMX0035 (sodium phenylbutyrate and taurursodiol) as a treatment for ALS and other neurodegenerative diseases including Wolfram syndrome and PSP; the Company’s beliefs regarding the benefits of AMX0035 in ALS and other neurodegenerative diseases, the potential of AMX0035 to be a foundational therapy for ALS the link between biomarker data and clinical effect in ALS; the potential for new pipeline programs and clinical indications for AMX0035; statements regarding regulatory developments; the Company’s expectations regarding its financial performance; and expectations regarding the Company’s longer-term strategy. Any forward-looking statements in this press release and related comments in the Company's earnings conference call are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: the success, cost, and timing of Amylyx’ program development activities, Amylyx’ ability to successfully commercialize RELYVRIO in the United States and ALBRIOZA in Canada, Amylyx’ ability to execute on its commercial and regulatory strategy, regulatory developments, expectations regarding the timing of a decision from the EMA regarding AMX0035 for the treatment of ALS, Amylyx’ ability to fund operations, and the impact that global macroeconomic uncertainty, geopolitical instability and public health events, such as COVID-19, will have on Amylyx’ operations, as well as the risks and uncertainties set forth in Amylyx’ United States Securities and Exchange Commission (SEC) filings, including Amylyx’ Quarterly Report on Form 10-Q for the quarter ended September 30, 2023, and subsequent filings with the SEC. All forward-looking statements contained in this press release and related comments in our earnings conference call speak only as of the date on which they were made. Amylyx undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

U.S. Food and Drug Administration (FDA) approval to conduct a Phase II clinical trial for novel chitinase inhibitor OATD-01 in pulmonary sarcoidosis with first patient expected to be dosed in fourth quarter of 2023 Continued enrollment in the Phase I clinical trial of OATD-02, an oral, first in class dual arginase inhibitor for the treatment of cancer with initial data expected early 2024Successful Secondary Public Offering (SPO) raising gross proceeds of approximately PLN50 million (USD12 million) to fund the company through significant development milestones and value inflection points Warsaw, Poland – 31 October 2023 – Molecure S.A. (“Molecure”: WSE: MOC) a clinical stage biotechnology company developing first-in-class small molecule drug candidates that directly modulate unexplored protein and RNA targets to treat multiple incurable diseases announces third quarter results for the period ended 30 September 2023. The full report in Polish can be found here https://molecure.com/pl/informacje-dla-inwestorow/ Marcin Szumowski, CEO and President of the Management Board of Molecure said: “We have made substantial financial and operational progress during 2023 including the completion of a significantly oversubscribed secondary public offering. This will enable the company to deliver meaningful additional data which will be important in fulfilling the longer-term potential of our pipeline. We have also achieved key milestones in clinical development with the dosing of the first cancer patient in our Phase I study with OATD-02 with anticipated initial results in the next few months. Additionally, we expect to dose the first pulmonary sarcoidosis patient in the Phase II study of OATD-01 before the end of the year. Molecure is entering a very exciting stage in its development with a number of near-term value-creating milestones set to be achieved in our pipeline and we look forward to providing meaningful updates on our progress over the next year." Commercial & Operational Highlights in the third quarter Successful Public Offering Molecure successfully raised, through a Secondary Public Offering, gross proceeds of approximately PLN50m (USD12m) from existing and new shareholders, Proceeds and expected grant awards will be used to fund and build Molecure’s first in class sustainable pipeline of breakthrough therapies through significant value inflection points including completion of the Phase II study for OATD-01 in sarcoidosis and completion of the Phase I clinical trial for OATD-02 in oncology patients, with the possibility of expansion into additional indications and combination therapies. US FDA Clearance to conduct Phase II clinical trial – OATD-01 Molecure received US FDA Investigational New Drug (IND) approval for OATD-01 which will allow the company to conduct Phase II clinical trials in the US. The planned Phase II proof-of-concept study will be the first to treat patients suffering from pulmonary sarcoidosis and is expected to start in the fourth quarter 2023. Molecure has submitted applications to the EMA and UK MHRA to initiate a Phase II clinical trial in the European Union and Norway and the UK respectively. Molecure signed an agreement with Simbec-Orion, a leading global Clinical Research Organization which will conduct the clinical trial on behalf of Molecure. The Phase II trial will be conducted in the US and several European Union Countries and enroll 90+ patients with active pulmonary sarcoidosis. Nine Months Financial Highlights Operating income of PLN1.3 million, in line with the same period in 2022.Operating expenses totaled PLN16.3 million, an increase of PLN4.3 million vs the same period last year. This was mainly due to higher research costs as the company’s pipeline advances, higher salaries and costs of external services.Net loss for the first nine months of the year totaled PLN11.5 million vs net loss of PLN9.4 million in the first nine months of the year in 2022. As of September 30, 2023, Molecure had cash of nearly PLN85 million (US$20 million).US$/PLN exchange rate 4.2 as of 30 September 2023. ENDS For further information, please contact: Molecure S.A. (PR & IR) Marta Borkowska Email: m.borkowska@molecure.com +(48) 728 728 143 MEDiSTRAVA Consulting (Financial PR) Frazer Hall, Sandi Greenwood molecure@medistrava.com +44 (0)203 928 6900 About Molecure Molecure S.A. is a biotechnology company discovering and developing drugs to the clinical stage, which uses its own unique competences in the field of medicinal chemistry and biology to search for and develop first-in-class small-molecule drugs that, through direct modulation of previously unexplored protein and RNA targets, can be the therapy of many incurable diseases. Molecure has generated a diverse portfolio of seven distinct programs with the support of leading academic scientific institutions around the world, including Yale University, Rutgers University, the Flemish Institute for Biotechnology (VIB) in Ghent, the University of Michigan, and the International Institute of Molecular and Cell Biology in Warsaw (MIBMiK). The most advanced drug candidate developed by Molecure is OATD-01, a first-in-class CHIT1 inhibitor for use in the treatment of interstitial lung diseases such as sarcoidosis and idiopathic pulmonary fibrosis, which is ready to enter phase II clinical trials. The start of a phase II trial in sarcoidosis patients is expected in Q4 2023. The second drug candidate is OATD-02, an oral, selective, first-in-class, dual arginase inhibitor (ARG1 and ARG2) for use in cancer treatment, whose phase I clinical trial began with its first administration to a patient in Q1 2023. Molecure’s headquarters and laboratories are located in Warsaw and Łódź. The company is listed on the Warsaw Stock Exchange (ticker: MOC). For more information, please visit Molecure LinkedIn: Molecure| Twitter: @molecure_sa | YouTube: Molecure SA

Molecure strategy update for 2023-2025 based on the development of a diversified portfolio of innovative research projects with the potential for breakthrough therapies for incurable diseasesCompleted successful Secondary Public Offering (SPO) of gross proceeds of approximately PLN50 million (USD12 million) Proceeds will fund the company through significant development milestones and value inflection pointsFirst patient dosed in Phase I trial with OATD-02, a novel, first in class dual arginase inhibitor for the treatment of cancer U.S. Food and Drug Administration (FDA) approval to conduct a Phase II clinical trial for OATD-01, a first-in-class inhibitor of chitotriosidase 1 (CHIT1)Applications also submitted to European Medicine Agency and UK MHRA to conduct Phase II clinical testing of OATD-01 Warsaw, Poland – 29 September 2023 – Molecure S.A. (“Molecure”: WSE: MOC) a clinical stage biotechnology company developing first-in-class small molecule drug candidates that directly modulate unexplored protein and RNA targets to treat multiple incurable diseases announces first half results for the period ended 30 June 2023. The full report in Polish can be found here. Marcin Szumowski, CEO and President of the Management Board of Molecure said “Many events of this year were crucial for further development of Molecure. In June, we announced the updated strategy for 2023-2025, the implementation of which will enable us to continue building the company's value. In a very difficult market for biotech, attracting investor interest leading to high oversubscription in our secondary public offering was clearly a great accomplishment in our quest to build a clinical stage biotechnology company able to change the fate of patients. This year we have made excellent progress developing our first in class product portfolio and have achieved key milestones throughout this year including dosing the first cancer patient in our Phase 1 study with OATD-02, and receiving FDA approval to proceed with clinical trials in the US for OATD-01. Bringing two of our most advanced programs to patients opened a new and exciting chapter for Molecure. I would like to thank our shareholders for their trust and the entire Molecure team for their dedication and unwavering commitment to improving the lives of patients. We eagerly await the initial read outs from our clinical trials and look forward to achieving further milestones in the development of our balanced pipeline, which we hope will ultimately lead to commercial success through strategic partnership agreements.” Investor Presentation The Company's first half results presentation for investors will be held on October 3, 2023 at 2:00 PM (CET) in an online meeting. Link https://livingmedia.com.pl/live/molecure/2Q2023-en The meeting will be conducted mainly in Polish and partly in English with simultaneous translation. It is expected to last approximately 90 minutes. Commercial & Operational Highlights in H1 and post-period Significant progress made on OATD-02, an oral, potent and selective first-in-class, dual arginase inhibitor (ARG1 and ARG2) for the treatment of cancer First patient dosed in March 2023 in Phase I clinical trial to assess safety, tolerability and preliminary efficacy of OATD-02 in patients with advanced and/or metastatic solid tumors lnitial clinical data expected at the end of 2023 Publication in Molecular Cancer Therapeutics, a journal of the American Association of Cancer Research, entitled “Arginase 1/2 inhibitor OATD-02: from discovery to first-in-man setup in cancer immunotherapy”. Link hereIn June, the publication of an update to the Strategy for the years 2023-2025. The Company's primary strategic objectives in the areas of R&D and business development are:Continuation of the intensive clinical development of two key projects: completion of the Phase II study for OATD-01 in sarcoidosis and completion of the Phase I clinical trial for OATD-02 involving oncology patients, with the potential for expanding into additional indications and combination therapies,Further advancement of early-stage preclinical projects, including the identification of 1-2 lead compounds (candidates for preclinical development) and the initiation of another program into the clinical trial phase,Acceleration of the development of a groundbreaking small molecule drug platform targeting mRNA, including achieving in vitro Proof of Concept (PoC) and selecting lead molecules.Enhancement of the drug discovery processes efficiency (by reducing time and costs and mitigating the risk of failure) through investments in machine learning technology and generative artificial intelligence (GenAI),Execution of at least 1 high value partnering agreement for at least one project in the clinical phase, as well as the establishment of a series of commercial collaborations, including profit-sharing arrangements, for programs in earlier stages of development,The total investment expenditure to achieve the goals outlined in the Strategy for the period from mid-2023 to the end of 2025 has been estimated at approximately PLN 250 m.In July, Molecure successfully raised, through a Secondary Public Offering, gross proceeds of approximately PLN50m (USD12m) from existing shareholders, These proceeds and expected grant awards will be used to fund and build Molecure’s first in class sustainable pipeline of breakthrough therapies through significant value inflection points including completion of the Phase II study for OATD-01 in sarcoidosis and completion of the Phase I clinical trial for OATD-02 in oncology patients, with the possibility of expansion into additional indications and combination therapies.We continue to make excellent progress with OATD-01: In July Molecure, received US FDA Investigational New Drug (IND) approval for OATD-01 which will allow the company to conduct Phase II clinical trials in the US. The planned Phase II proof-of-concept study will be the first to treat patients suffering from pulmonary sarcoidosis and is expected to start in the fourth quarter 2023. Molecure has also submitted applications to the EMA and UK MHRA to initiate a Phase II clinical trial in the European Union and Norway and the UK respectively. Molecure has signed an agreement with Simbec-Orion, a leading global Clinical Research Organisation which will conduct the clinical trial on behalf of Molecure. The Phase II trial will be conducted in the US and several European Union Countries and enroll approximately 90 patients with active pulmonary sarcoidosis. Key organizational changes to drive the Company through its next phase of growth and clinical development Dr. Samson Fung, Chief Medical Officer appointed to the Company’s Management Board to support the clinical development of OATD-01 and OATD-02Dr. Zbigniew Zasłona, promoted to Chief Scientific Officer from his former position as VP Research Biology. Dr. Zasłona, remains on Molecure’s Management Board First Half Financial Highlights Operating income of PLN1.0 million, in line with 1H 2022.Operating expenses totaled PLN10.9 million, an increase of PLN2.2 million. This was mainly due to increasing research costs as the company’s pipeline advances, higher salaries and costs of external services.Net loss for the first six months of the year totaled PLN7.4 million vs net loss of PLN7.1 million in 1H 2022. As of June 30, 2023, Molecure had cash of nearly PLN50 million (US$11.5 million).As of the publication date of the 1H 2023 report (September 29), the Company's cash position amounted to approximately PLN85 million, taking into account the funds raised from the recently finalized public offering (US$19.5 million).US$/PLN exchange rate 4.35 as of 30 June 2023. ENDS For further information, please contact: Molecure S.A. (PR & IR) Marta Borkowska Email: m.borkowska@molecure.com +(48) 728 728 143 MEDiSTRAVA Consulting (Financial PR) Frazer Hall, Sandi Greenwood molecure@medistrava.com +44 (0)203 928 6900 About Molecure Molecure S.A. is a biotechnology company discovering and developing drugs to the clinical stage, which uses its own unique competences in the field of medicinal chemistry and biology to search for and develop first-in-class small-molecule drugs that, through direct modulation of previously unexplored protein and RNA targets, can be the therapy of many incurable diseases. Molecure has generated a diverse portfolio of seven distinct programs with the support of leading academic scientific institutions around the world, including Yale University, Rutgers University, the Flemish Institute for Biotechnology (VIB) in Ghent, the University of Michigan, and the International Institute of Molecular and Cell Biology in Warsaw (MIBMiK). The most advanced drug candidate developed by Molecure is OATD-01, a first-in-class CHIT1 inhibitor for use in the treatment of interstitial lung diseases such as sarcoidosis and idiopathic pulmonary fibrosis, which is ready to enter phase II clinical trials. The start of a phase 2 trial in sarcoidosis patients is expected in early Q4 2023. The second drug candidate is OATD-02, an oral, selective, first-in-class, dual arginase inhibitor (ARG1 and ARG2) for use in cancer treatment, whose phase I clinical trial began with its first administration to a patient in Q1 2023. Molecure’s headquarters and laboratories are located in Warsaw and Łódź. The company is listed on the Warsaw Stock Exchange (ticker: MOC). For more information, please visit Molecure LinkedIn: Molecure| Twitter: @molecure_sa | YouTube: Molecure SA