Iron Overload

MELBOURNE, Australia and SAN FRANCISCO, Oct. 11, 2024 (GLOBE NEWSWIRE) -- Alterity Therapeutics (ASX: ATH, NASDAQ: ATHE) (“Alterity” or “the Company”), a biotechnology company dedicated to developing disease modifying treatments for neurodegenerative diseases, today announced promising new data related to ATH434 were presented at the Society for Neuroscience 2024 in Chicago, USA. The poster entitled, “Potent Antioxidant and Mitochondrial-protectant Effects of ATH434, a Novel Inhibitor of α-Synuclein Aggregation with Moderate Iron-binding Affinity,” demonstrates that the neuroprotective and mitochondrial protectant properties of ATH434 include reducing lipid damage in two distinct and disease-relevant neuronal injury models. Additional studies elucidate the inherent antioxidant properties and benefits of ATH434 in cellular energy usage. ATH434’s antioxidant properties were distinguished from those of another iron binding agent approved for treating iron overload. The study was run under the direction of Dr. Daniel J. Kosman, Distinguished Professor of Biochemistry at the State University of New York at Buffalo. “ These exciting new data further our understanding of ATH434’s potential as a disease modifying treatment for neurodegenerative diseases, including Parkinson’s disease and related disorders,” said, David Stamler, M.D., Chief Executive Officer of Alterity. “The study extended previous findings and demonstrated that ATH434 has intrinsic antioxidant activity. This is key as oxidative injury is an important contributor to the pathology of neurodegeneration. By addressing this injury in two different ways, both directly and by redistributing excess labile iron, ATH434 has excellent potential to treat this group of diseases. The ability of ATH434 to reduce damage to lipid membranes undergoing oxidative stress may augment its ability to slow disease progression. We are grateful for the continued valuable contributions from our collaborators in Dr. Kosman’s laboratory at SUNY-Buffalo.” The study, authored by Dr. Danielle Bailey, investigated the efficacy of ATH434 and comparator agents as lipid peroxidation protectants using a menadione-induced model and a hemin-induced oxidative stress model in a neuronal cell line. In unstressed cells, ATH434 promoted energy production in mitochondria to a pathway less prone to causing oxidative stress. In-solution assays detailed the mechanisms underlying ATH434’s direct antioxidant capacity with respect to potentially damaging charged molecules. These combined properties can serve to protect vulnerable mitochondria in neurodegenerative diseases. The poster presentation can be found on Alterity’s website here . About ATH434 Alterity’s lead candidate, ATH434, is an oral agent designed to inhibit the aggregation of pathological proteins implicated in neurodegeneration. ATH434 has been shown preclinically to reduce α-synuclein pathology and preserve neuronal function by restoring normal iron balance in the brain. As an iron chaperone, it has excellent potential to treat Parkinson’s disease as well as various Parkinsonian disorders such as Multiple System Atrophy (MSA). ATH434 successfully completed Phase 1 studies demonstrating the agent is well tolerated and achieved brain levels comparable to efficacious levels in animal models of MSA. ATH434 is currently being studied in two clinical trials: Study ATH434-201 is a randomized, double-blind, placebo-controlled Phase 2 clinical trial in patients with early-stage MSA and Study ATH434-202 is an open-label Phase 2 Biomarker trial in patients with more advanced MSA. ATH434 has been granted Orphan drug designation for the treatment of MSA by the U.S. FDA and the European Commission. About Alterity Therapeutics Limited Alterity Therapeutics is a clinical stage biotechnology company dedicated to creating an alternate future for people living with neurodegenerative diseases. The Company’s lead asset, ATH434, has the potential to treat various Parkinsonian disorders and is currently being evaluated in two Phase 2 clinical trials in Multiple System Atrophy. Alterity also has a broad drug discovery platform generating patentable chemical compounds to treat the underlying pathology of neurological diseases. The Company is based in Melbourne, Australia, and San Francisco, California, USA. For further information please visit the Company’s web site at . Authorisation & Additional information This announcement was authorized by David Stamler, CEO of Alterity Therapeutics Limited. Investor and Media Contacts: Australia Hannah Howlett we-aualteritytherapeutics@we-worldwide.com +61 450 648 064 U.S. Remy Bernarda remy.bernarda@iradvisory.com +1 (415) 203-6386 Forward Looking Statements This press release contains “forward-looking statements” within the meaning of section 27A of the Securities Act of 1933 and section 21E of the Securities Exchange Act of 1934. The Company has tried to identify such forward-looking statements by use of such words as “expects,” “intends,” “hopes,” “anticipates,” “believes,” “could,” “may,” “evidences” and “estimates,” and other similar expressions, but these words are not the exclusive means of identifying such statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are described in the sections titled “Risk Factors” in the Company’s filings with the SEC, including its most recent Annual Report on Form 20-F as well as reports on Form 6-K, including, but not limited to the following: statements relating to the Company’s drug development program, including, but not limited to the initiation, progress and outcomes of clinical trials of the Company’s drug development program, including, but not limited to, ATH434, and any other statements that are not historical facts. Such statements involve risks and uncertainties, including, but not limited to, those risks and uncertainties relating to the difficulties or delays in financing, development, testing, regulatory approval, production and marketing of the Company’s drug components, including, but not limited to, ATH434, the ability of the Company to procure additional future sources of financing, unexpected adverse side effects or inadequate therapeutic efficacy of the Company’s drug compounds, including, but not limited to, ATH434, that could slow or prevent products coming to market, the uncertainty of obtaining patent protection for the Company’s intellectual property or trade secrets, the uncertainty of successfully enforcing the Company’s patent rights and the uncertainty of the Company freedom to operate. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

- Business Combination Expected to Provide Patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC) Optimal Access to G1’s COSELA® (trilaciclib), the First and Only Proactive Multilineage Myeloprotection Agent - - Pharmacosmos’ Significant Resources and Expertise in Hematology and Supportive Care to Maximize Availability of COSELA for Patients with ES-SCLC - - Transaction Expands and Strengthens Pharmacosmos’ Global Commercial Portfolio - - G1’s Shareholders to Receive U.S. $7.15 per Share in Cash for a Total Equity Value of Approximately $405 Million - RESEARCH TRIANGLE PARK, N.C. and HOLBAEK, Denmark, Aug. 07, 2024 (GLOBE NEWSWIRE) -- G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company focused on delivering next-generation therapies that improve the lives of those affected by cancer, and Pharmacosmos A/S, a leader in the development of innovative treatments for patients suffering from iron deficiency and iron deficiency anemia, today announced that they have entered into a definitive merger agreement under which Pharmacosmos A/S, through its U.S. subsidiary Pharmacosmos Therapeutics Inc., will acquire all outstanding shares of G1 Therapeutics common stock for U.S. $7.15 per share in cash for a total equity value of approximately $405 million, which represents a 68% premium to G1’s closing share price on August 6, 2024 and a 133% premium to G1’s prior 30-day volume weighted average price. The Boards of Directors of the parties have unanimously approved the transaction, which is expected to close late in the third quarter of 2024. G1’s COSELA is the first and only product approved by the U.S. Food and Drug Administration to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC). Together, Pharmacosmos and G1 Therapeutics will execute on the shared vision to grow and accelerate the availability of COSELA for all appropriate patients with ES-SCLC. G1 brings a well-established and successful commercial, sales, and medical platform to Pharmacosmos, which has complementary expertise in commercializing hematology and supportive care products, a robust global commercial presence, and significant resources to maximize the penetration of COSELA into the ES-SCLC market. Together, the combined company will be able to optimize the commercial reach to oncologists and expand the availability of COSELA among patients living with ES-SCLC. “G1 and Pharmacosmos have a shared commitment to people living with cancer; the transaction announced today will enable a more rapid uptake of COSELA into the ES-SCLC market to maximize availability for patients who need this important drug,” said Jack Bailey, Chief Executive Officer of G1 Therapeutics. “Importantly, this acquisition delivers significant value to G1’s stakeholders by providing better and broader access to this important product for the cancer patients we seek to treat and a significant premium to our shareholders. I am proud of all that the G1 team has accomplished over the years, thankful for their great effort, and excited about what’s possible by the combined Pharmacosmos/G1 team as we meet the needs of more cancer patients." “The acquisition of G1 Therapeutics Inc., its intellectual property, and the addition of COSELA® (trilaciclib) to our portfolio of innovative products is transformative for Pharmacosmos. By combining our existing colleagues with the great team at G1 Therapeutics, we will meaningfully expand our organization serving oncologists in the US. This will enable broader and better access for patients in need of COSELA as well as for our existing FDA approved drug, Monoferric® (ferric derisomaltose),” said Tobias S. Christensen, President and Chief Executive Officer of Pharmacosmos A/S. “COSELA is a first-in-class product that brings important benefits to patients and fits very nicely together with our lead product Monoferric® (ferric derisomaltose). While Monoferric is available around the World, COSELA is so far only approved in the US and in China. It will be a focus for us to bring this important product to more patients both in US and worldwide to help minimize the number of lung cancer patients suffering from myelosuppression after chemotherapy.” Transaction Terms Under the terms of the merger agreement, Pharmacosmos has agreed to commence a cash tender offer to acquire all issued and outstanding shares of G1 common stock for US $7.15 per share in cash. The transaction will be fully financed by Pharmacosmos’ existing cash on hand and existing corporate credit facilities. The closing of the tender offer will be subject to customary conditions, including the tender of shares which represent at least a majority of the total number of G1’s outstanding shares of common stock and the expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act. Upon successful completion of the tender offer, Pharmacosmos would acquire all shares not acquired in the tender offer through a second-step merger for the same consideration that the tendering stockholders will receive in the tender offer. It is anticipated the transaction will close late in the third quarter of 2024. Upon completion of the transaction, G1’s common stock will no longer be publicly listed. As previously announced, G1 will be releasing its second quarter 2024 financial results and filing its Form 10-Q Quarterly Report tomorrow. However, due to the pending transaction, we will no longer be hosting a conference call at 8:30 am ET, August 8 to review such results. Advisors For Pharmacosmos, MTS Health Partners, L.P. is serving as exclusive financial advisor, and Arnold & Porter Kaye Scholer LLP is serving as legal counsel. For G1, Centerview Partners LLC is serving as exclusive financial advisor, and Ropes & Gray LLP and Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. are serving as legal counsel. About COSELA® (trilaciclib) for Injection COSELA (trilaciclib) was approved by the U.S. Food and Drug Administration on February 12, 2021. Indication COSELA® (trilaciclib) is indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer. Important Safety Information COSELA is contraindicated in patients with a history of serious hypersensitivity reactions to trilaciclib. Warnings and precautions include injection-site reactions (including phlebitis and thrombophlebitis), acute drug hypersensitivity reactions, interstitial lung disease (pneumonitis), and embryo-fetal toxicity. The most common adverse reactions (>10%) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia. This information is not comprehensive. Please click here for full Prescribing Information. https://www.g1therapeutics.com/cosela/pi/ To report suspected adverse reactions, contact G1 Therapeutics at 1-800-790-G1TX or call FDA at 1-800-FDA-1088 or visit www.fda.gov/medwatch. About Monoferric (ferric derisomaltose) Indication Monoferric (ferric derisomaltose) is indicated for the treatment of iron deficiency anemia (IDA) in adult patients: who have intolerance to oral iron or have had unsatisfactory response to oral ironwho have non-hemodialysis dependent chronic kidney disease (NDD-CKD) Important Safety Information Monoferric is contraindicated in patients with a history of serious hypersensitivity to Monoferric or any of its components. Reactions have included shock, clinically significant hypotension, loss of consciousness, and/or collapse. Warnings and precautions include serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Monoferric. Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. Monitor patients for signs and symptoms of hypersensitivity during and after Monoferric administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Monoferric when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. Monoferric is contraindicated in patients with prior serious hypersensitivity reactions to Monoferric or any of its components. In clinical trials in patients with IDA and CKD, serious or severe hypersensitivity were reported in 0.3% (6/2008) of the Monoferric treated subjects. These included 3 events of hypersensitivity in 3 patients; 2 events of infusion-related reactions in 2 patients and 1 event of asthma in one patient. Excessive therapy with parenteral iron can lead to excess iron storage and possibly iatrogenic hemosiderosis or hemochromatosis. Monitor the hematologic response (hemoglobin and hematocrit) and iron parameters (serum ferritin and transferrin saturation) during parenteral iron therapy. Do not administer Monoferric to patients with iron overload. Adverse reactions were reported in 8.6% (172/2008) of patients treated with Monoferric. Adverse reactions related to treatment and reported by ≥1% of the treated patients were nausea (1.2%) and rash (1%). Adjudicated serious or severe hypersensitivity reactions were reported in 6/2008 (0.3%) patients in the Monoferric group. Hypophosphatemia (serum phosphate <2.0 mg/dL) was reported in 3.5% of Monoferric-treated patients in Trials 1 & 2. To report adverse events, please contact Pharmacosmos at 1-888-828-0655. You may also contact the FDA at www.fda.gov/medwatch or 1-800-FDA-1088. This information is not comprehensive. Please click here for full Prescribing Information. Pharmacosmos Group Pharmacosmos A/S, headquartered in Holbaek, Denmark, and founded in 1965, is a highly specialised company focused on carbohydrate chemistry and a global leader in the development of innovative treatments for patients suffering from iron deficiency and iron deficiency anaemia. With companies in the UK, Ireland, Nordics, Germany, the USA, and China, as well as through partners, Pharmacosmos markets its products around the world. With a strong and ongoing commitment to R&D, Pharmacosmos is able to leverage a unique carbohydrate production platform along with deep expertise in the synthesis of iron-carbohydrate complexes. The Pharmacosmos Group has more than 500 employees. About G1 Therapeutics G1 Therapeutics, Inc. is a commercial-stage oncology biopharmaceutical company whose mission is to develop and deliver next-generation therapies that improve the lives of those affected by cancer, including the Company’s first commercial product, COSELA® (trilaciclib). G1’s goal is to provide innovative therapeutic advances for people living with cancer. G1 is based in Research Triangle Park, N.C. For additional information, please visit www.g1therapeutics.com and follow us on X (formerly known as Twitter) @G1Therapeutics and LinkedIn. G1 Therapeutics® and the G1 Therapeutics logo and COSELA® and the COSELA logo are trademarks of G1 Therapeutics, Inc. Forward-Looking Statements This document contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the proposed acquisition of G1 by Pharmacosmos, the expected timetable for completing the transaction, and G1’s future financial or operating performance. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “seek,” “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 document 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: (i) risks associated with the timing of the closing of the proposed transaction, including the risks that a condition to closing would not be satisfied within the expected timeframe or at all or that the closing of the proposed transaction will not occur; (ii) uncertainties as to how many of G1’s stockholders will tender their shares in the offer; (iii) the possibility that a governmental entity may prohibit, delay or refuse to grant approval for the consummation of the transaction; (iv) the possibility that competing offers will be made; (v) the outcome of any legal proceedings that may be instituted against the parties and others related to the merger agreement; (vi) unanticipated difficulties or expenditures relating to the proposed transaction, the response of business partners and competitors to the announcement of the proposed transaction, and/or potential difficulties in employee retention as a result of the announcement and pendency of the proposed transaction; (vii) G1’s ability to successfully demonstrate the efficacy and safety of its drug or drug candidates, and the preclinical or clinical results for its product candidates, which may not support further development of such product candidates; (viii) comments, feedback and actions of regulatory agencies; (ix) G1’s dependence on the commercial success of COSELA (trilaciclib); (x) the inherent uncertainties associated with developing new products or technologies and operating as commercial stage company; (xi) chemotherapy shortages; and (xii) other risks identified in G1’s SEC filings, including G1’s Annual Report on Form 10-K for the year ended December 31, 2023, and subsequent filings with the SEC. G1 cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. G1 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. Additional Information and Where to Find It The tender offer referred to in this document has not yet commenced. This document is for informational purposes only and is neither an offer to purchase nor a solicitation of an offer to sell shares, nor is it a substitute for the tender offer materials that Pharmacosmos and its acquisition subsidiary will file with the SEC upon commencement of the tender offer. At the time the tender offer is commenced, Pharmacosmos and its acquisition subsidiary will cause to be filed a tender offer statement on Schedule TO with the SEC, and G1 will file a solicitation/recommendation statement on Schedule 14D-9 with respect to the tender offer. THE TENDER OFFER STATEMENT (INCLUDING AN OFFER TO PURCHASE, A RELATED LETTER OF TRANSMITTAL AND OTHER OFFER DOCUMENTS) AND THE SOLICITATION/RECOMMENDATION STATEMENT WILL CONTAIN IMPORTANT INFORMATION THAT SHOULD BE READ CAREFULLY AND CONSIDERED BY G1’S STOCKHOLDERS BEFORE ANY DECISION IS MADE WITH RESPECT TO THE TENDER OFFER. Both the tender offer statement and the solicitation/recommendation statement will be mailed to G1’s stockholders free of charge. A free copy of the tender offer statement and the solicitation/recommendation statement will also be made available to all stockholders of G1 by accessing https://investor.g1therapeutics.com/ or by contacting Investor Relations at ir@g1therapeutics.com. In addition, the tender offer statement and the solicitation/recommendation statement (and all other documents filed with the SEC) will be available at no charge on the SEC’s website: www.sec.gov, upon filing with the SEC. G1’S STOCKHOLDERS ARE ADVISED TO READ THE SCHEDULE TO AND THE SCHEDULE 14D-9, AS EACH MAY BE AMENDED OR SUPPLEMENTED FROM TIME TO TIME, AND ANY OTHER RELEVANT DOCUMENTS FILED WITH THE SEC WHEN THEY BECOME AVAILABLE BEFORE THEY MAKE ANY DECISION WITH RESPECT TO THE TENDER OFFER, BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION ABOUT THE PROPOSED TRANSACTION AND THE PARTIES THERETO. Pharmacosmos A/S Contact: Christian Lundquist MadsenVP Global Marketing & Communication+45 5948 5959 clm@pharmacosmos.com G1 Therapeutics Contacts: John W. Umstead VChief Financial Officer919-747-8419jumstead@g1therapeutics.com Will RobertsCommunications OfficerVice President, Investor Relations and Corporate Communications(919) 907-1944 wroberts@g1therapeutics.com

– ACTIVATE-KidsT is Agios’ First Pediatric Data Readout;Safety Results Consistent with Safety Profile for Mitapivat Previously Observed in Adultswith PK Deficiency Who are Regularly Transfused – – Prespecified Statistical Criterion for the Primary Endpoint in ACTIVATE-KidsT Was Not Met; Results Were Clinically Meaningful, with Observed Response Rates Higher for Mitapivat than Placebo for the Primary Endpoint of Transfusion Reduction Response and for the Secondary Endpoints of Transfusion-Free Response and Normal Hemoglobin Response – – Enrollment Completed for Phase 3 ACTIVATE-Kids Study of Mitapivat in Children with PK Deficiency Who Are Not Regularly Transfused; Topline Data Expected in 2025 – CAMBRIDGE, Mass., Aug. 01, 2024 (GLOBE NEWSWIRE) -- Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in cellular metabolism and pyruvate kinase (PK) activation pioneering therapies for rare diseases, today announced topline results from the global Phase 3 ACTIVATE-KidsT study of mitapivat in children aged 1 to <18 years with PK deficiency who are regularly transfused. Using Bayesian methodology, the prespecified statistical criterion for the primary endpoint in ACTIVATE-KidsT was not met using low or moderate borrowing of data from the ACTIVATE-T study in adults. In the ACTIVATE-KidsT study, 28.1% of patients in the mitapivat arm achieved the primary endpoint of transfusion reduction response, compared to 11.8% of patients in the placebo arm. Transfusion-free response and normal hemoglobin response were secondary endpoints in this study and only observed in patients in the mitapivat arm. In the 32-week double-blind treatment period, mitapivat was generally safe and well-tolerated, with safety results consistent with the safety profile for mitapivat previously observed in adults with PK deficiency who are regularly transfused. “After years of working with the PK deficiency community and caregivers whose children have no disease-modifying therapies, it is gratifying to share encouraging efficacy and safety data that may support the potential of a first-ever pediatric treatment for this rare blood disorder,” said Sarah Gheuens, M.D., Ph.D., chief medical officer and head of R&D at Agios. “We look forward to completing our pediatric PK deficiency clinical development program next year with the readout of the ACTIVATE-Kids study of mitapivat in children who are not regularly transfused. More broadly, the ACTIVATE-KidsT study represents Agios’ first pediatric data readout. With our focus on lifelong, debilitating rare diseases, we hope that this study will be the first of several pediatric studies to make a positive impact in the lives of children facing rare hemolytic anemias, including PK deficiency, thalassemia and sickle cell disease.” “Children with PK deficiency can experience significant disease burden, including fatigue, the need for blood transfusions, and the risk of iron overload. Symptoms of PK deficiency, disease complications, and common supportive therapies can interfere with regular childhood activities,” said Rachael F. Grace, M.D., MMSc; Dana-Farber/Boston Children’s Cancer and Blood Disorder Center, Harvard Medical School, Boston, an investigator in the ACTIVATE-KidsT study. “The ACTIVATE-KidsT trial is the first study of mitapivat in children who are regularly transfused and demonstrates the potential for meaningful clinical benefit, resolving the anemia and need for transfusions in a subset of children.” In addition, Agios has completed enrollment in the ACTIVATE-Kids study of mitapivat in children with PK deficiency who are not regularly transfused, and expects to report topline data in 2025. Topline results for the Phase 3 ACTIVATE-KidsT study were as follows: A total of 49 patients aged 1 to <18 years were enrolled in the study, with 32 randomized to mitapivat twice-daily and 17 randomized to matched placebo. 30 patients (93.8%) in the mitapivat arm and 16 (94.1%) in the placebo arm completed the 32-week double-blind period of the study.The primary endpoint of the study was transfusion reduction response (TRR), defined as ≥33% reduction in the total red blood cell transfusion volume from Week 9 through Week 32 of the double-blind period normalized by weight and actual study drug duration compared with the historical transfusion volume standardized by weight and to 24 weeks. The analysis of the primary endpoint was based on Bayesian statistical methodology whereby the TRR data from the adult ACTIVATE-T study inform and contribute to the analysis of TRR in the ACTIVATE-KidsT study. The analysis was performed using a range of relative weights of borrowing from the adult ACTIVATE-T study, representing the prior degree of belief in the similarity of the treatment effect in the pediatric and adult populations. The prespecified statistical criterion for the primary endpoint in ACTIVATE-KidsT was not met with low or moderate borrowing weights; however, the results were clinically meaningful.28.1% (9/32) of patients in the mitapivat arm achieved a transfusion reduction response, compared to 11.8% (2/17) of patients in the placebo arm. In addition, a higher proportion of patients in the mitapivat arm compared to the placebo arm achieved the secondary endpoints of transfusion-free response and normal hemoglobin response: 6 patients (18.8%) in the mitapivat arm compared to 0 in the placebo arm had a transfusion-free response, defined as no red blood cell transfusions from Week 9 through Week 32 of the double-blind period.4 patients (12.5%) in the mitapivat arm compared to 0 in the placebo arm achieved a normal hemoglobin response, defined as hemoglobin concentrations within normal limits at least once, 8 weeks or more after a transfusion, from Week 9 through Week 32 of the double-blind period. In the 32-week double-blind treatment period of the study, a similar proportion of patients had adverse events (AEs) in the mitapivat and placebo arms and there were no discontinuations of study treatment due to AEs.Safety results in this pediatric study were consistent with the safety profile for mitapivat previously observed for adult patients with PK deficiency who are regularly transfused. Agios plans to present a more detailed analysis of the Phase 3 ACTIVATE-KidsT data at an upcoming medical meeting. About PYRUKYND® (mitapivat)PYRUKYND is a pyruvate kinase activator indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency in the United States, and for the treatment of PK deficiency in adult patients in the European Union. IMPORTANT SAFETY INFORMATIONAcute Hemolysis: Acute hemolysis with subsequent anemia has been observed following abrupt interruption or discontinuation of PYRUKYND in a dose-ranging study. Avoid abruptly discontinuing PYRUKYND. Gradually taper the dose of PYRUKYND to discontinue treatment if possible. When discontinuing treatment, monitor patients for signs of acute hemolysis and anemia including jaundice, scleral icterus, dark urine, dizziness, confusion, fatigue, or shortness of breath. Adverse Reactions: Serious adverse reactions occurred in 10% of adult patients receiving PYRUKYND in the ACTIVATE trial, including atrial fibrillation, gastroenteritis, rib fracture, and musculoskeletal pain, each of which occurred in 1 patient. In the ACTIVATE trial, the most common adverse reactions including laboratory abnormalities (≥10%) in patients with PK deficiency were estrone decreased (males), increased urate, back pain, estradiol decreased (males), and arthralgia. The adverse reactions reported in the population of adult patients who were regularly transfused (ACTIVATE-T) were consistent with that seen in ACTIVATE. Drug Interactions: Strong CYP3A Inhibitors and Inducers: Avoid concomitant use.Moderate CYP3A Inhibitors: Do not titrate PYRUKYND beyond 20 mg twice daily.Moderate CYP3A Inducers: Consider alternatives that are not moderate inducers. If there are no alternatives, adjust PYRUKYND dosage.Sensitive CYP3A, CYP2B6, CYP2C Substrates Including Hormonal Contraceptives: Avoid concomitant use with substrates that have narrow therapeutic index.UGT1A1 Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.P-gp Substrates: Avoid concomitant use with substrates that have narrow therapeutic index. Hepatic Impairment: Avoid use of PYRUKYND in patients with moderate and severe hepatic impairment. Please see full Prescribing Information and Summary of Product Characteristics for PYRUKYND. About AgiosAgios is the pioneering leader in PK activation and is dedicated to developing and delivering transformative therapies for patients living with rare diseases. In the U.S., Agios markets a first-in-class pyruvate kinase (PK) activator for adults with PK deficiency, the first disease-modifying therapy for this rare, lifelong, debilitating hemolytic anemia. Building on the company's deep scientific expertise in classical hematology and leadership in the field of cellular metabolism and rare hematologic diseases, Agios is advancing a robust clinical pipeline of investigational medicines with programs in alpha- and beta-thalassemia, sickle cell disease, pediatric PK deficiency and MDS-associated anemia. In addition to its clinical pipeline, Agios is advancing a preclinical TMPRSS6 siRNA as a potential treatment for polycythemia vera, and a preclinical PAH stabilizer as a potential treatment for phenylketonuria (PKU). For more information, please visit the company’s website at www.agios.com. Cautionary Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding: the potential benefits of mitapivat; Agios’ plans for the future clinical development of mitapivat in pyruvate kinase deficiency; and Agios’ strategic plans and prospects. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “would,” “could,” “potential,” “possible,” “hope” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from Agios’ current expectations and beliefs. For example, there can be no guarantee that any product candidate Agios or its collaborators is developing will successfully commence or complete necessary preclinical and clinical development phases, or that development of any of Agios’ product candidates will successfully continue. Moreover, there can be no guarantee that any medicines ultimately commercialized by Agios will receive commercial acceptance. There can be no guarantee that any positive developments in Agios’ business will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other important factors, including, without limitation: risks and uncertainties related to the impact of pandemics or other public health emergencies to Agios’ business, operations, strategy, goals and anticipated milestones, including its ongoing and planned research activities, ability to conduct ongoing and planned clinical trials, clinical supply of current or future drug candidates, commercial supply of current or future approved products, and launching, marketing and selling current or future approved products; Agios’ results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. FDA, the EMA or other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies; Agios’ ability to obtain and maintain requisite regulatory approvals and to enroll patients in its planned clinical trials; unplanned cash requirements and expenditures; Agios’ ability to obtain, maintain and enforce patent and other intellectual property protection for any product candidates it is developing; Agios’ ability to establish and maintain key collaborations; uncertainty regarding any milestone or royalty payments related to the sale of Agios’ oncology business or its in-licensing of TMPRSS6 siRNA, and the uncertainty of the timing of any such payments; uncertainty of the results and effectiveness of the use of proceeds from the transaction with Servier; competitive factors; and general economic and market conditions. These and other risks are described in greater detail under the caption "Risk Factors" included in Agios’ public filings with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Agios expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Contacts: Investor ContactChris Taylor, VP Investor Relations and Corporate CommunicationsAgios PharmaceuticalsIR@agios.com Media Contact Dan Budwick1AB dan@1abmedia.com