PAH

Announced Positive Results from the Phase 3 ENERGIZE Study of Mitapivat in Adults with Non-Transfusion-Dependent Alpha- or Beta-Thalassemia Presented Positive Results from Phase 2 Portion of the RISE UP Pivotal Study in Sickle Cell Disease at 65th ASH Annual Meeting and Exposition Two Additional Phase 3 Readouts of Mitapivat Expected in 2024, with a Total of Four Phase 3 Readouts by the End of 2025 U.S. PYRUKYND® (mitapivat) Net Revenue of $7.1 Million in Q4; Cash, Cash Equivalents and Marketable Securities of $806.4 Million as of December 31, 2023 CAMBRIDGE, Mass., Feb. 15, 2024 (GLOBE NEWSWIRE) -- Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in the field of cellular metabolism pioneering therapies for rare diseases, today reported business highlights and financial results for the fourth quarter and year ended December 31, 2023. “The past 12 months have been remarkable for Agios. We reported positive data across our industry-leading pipeline of PK activators, including Phase 3 data in non-transfusion-dependent thalassemia, Phase 2 data in sickle cell disease and clinical proof-of-concept in lower-risk MDS, and expanded our preclinical pipeline by in-licensing a novel siRNA program from Alnylam,” said Brian Goff, chief executive officer at Agios. “In 2024, we expect two additional Phase 3 readouts, including the Phase 3 study of mitapivat in transfusion-dependent thalassemia, and are actively preparing for a potential U.S. launch in thalassemia in 2025. Together with our strong cash position, Agios is poised for significant near- and long-term growth as we progress toward of our vision of becoming a leading rare disease company.” Fourth Quarter 2023 & Recent Highlights PYRUKYND® U.S. Launch: Generated $7.1 million in U.S. net revenue for the fourth quarter of 2023, a 4 percent decrease from the third quarter of 2023, primarily driven by lower customer inventory levels at the end of the fourth quarter of 2023, partially offset by favorable gross-to-net adjustments. A total of 178 unique patients have completed prescription enrollment forms, representing an increase of 11 percent over the third quarter of 2023. A total of 109 patients are on PYRUKYND® therapy, a 9 percent increase from the third quarter of 2023. Thalassemia: Announced positive topline data from the Phase 3 ENERGIZE study of mitapivat in non-transfusion-dependent thalassemia. The study achieved its primary endpoint of hemoglobin response and achieved both key secondary endpoints associated with change from baseline in FACIT-Fatigue Score and hemoglobin concentration. Sickle Cell Disease: Presented positive results from the Phase 2 portion of the RISE UP pivotal study of mitapivat at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition. The study achieved its primary endpoint of hemoglobin response and an improvement in annualized rates of sickle cell pain crises was observed. Lower-risk Myelodysplastic Syndromes: Announced clinical proof-of-concept data in the open-label Phase 2a study of AG-946 for the treatment of anemia in lower-risk myelodysplastic syndromes (LR-MDS). Earlier-stage Pipeline: Filed an Investigational New Drug Application (IND) for AG-181, Agios’ PAH stabilizer for the treatment of phenylketonuria (PKU). Data presentations: Presented broad set of clinical and translational data at the 65th ASH Annual Meeting & Exposition, including positive data from the Phase 2 portion of the RISE UP study of mitapivat in sickle cell disease, as noted above. Anticipated 2024 Milestones Thalassemia: Following the announcement of positive topline data from the Phase 3 ENERGIZE study of mitapivat in non-transfusion-dependent thalassemia in January 2024, Agios plans to report topline data from the Phase 3 ENERGIZE-T study of mitapivat in transfusion-dependent thalassemia (mid-year) and FDA approval of mitapivat in thalassemia (year-end) Sickle Cell Disease: Complete enrollment in the Phase 3 portion of the RISE UP study of mitapivat (year-end) Pediatric PK Deficiency: Complete enrollment in the Phase 3 ACTIVATE-kids study of mitapivat (mid-year). Report topline data from Phase 3 ACTIVATE kids-T study (year-end) Lower-risk Myelodysplastic Syndromes: Dose first patient in Phase 2b study of AG-946 (mid-year) Earlier-stage Pipeline: Dose the first patient in the Phase 1 study of AG-181 for the treatment of PKU (early 2024) Fourth Quarter and Full Year 2023 Financial Results Revenue: Net U.S. product revenue from sales of PYRUKYND® was $7.1 million for the fourth quarter of 2023 compared to $4.3 million for the fourth quarter of 2022, and $26.8 million for the year ended Dec. 31, 2023 compared to $11.7 million for the year ended Dec. 31, 2022. Cost of Sales: Cost of sales was $0.6 million for the fourth quarter of 2023 and $2.9 million for the full year ended Dec. 31, 2023. Research and Development (R&D) Expenses: R&D expenses were $77.5 million for the fourth quarter of 2023 compared to $70.3 million for the fourth quarter of 2022, and $295.5 million for the year ended Dec. 31, 2023 compared to $279.9 million for the year ended Dec. 31, 2022. These changes reflect an increase in development costs for mitapivat and the up-front payment associated with the license agreement with Alnylam, partially offset by a reduction in expenses associated with the evolution of our research organization and the sale of our oncology business to Servier. Selling, General and Administrative (SG&A) Expenses: SG&A expenses were $35.3 million for the fourth quarter of 2023 compared to $32.8 million for the fourth quarter of 2022, and $119.9 million for the year ended Dec. 31, 2023 compared to $121.7 million for the year ended Dec. 31, 2022. Net Income (Loss): Net loss was $95.9 million for the fourth quarter of 2023 compared to a net income of $36.5 million for the fourth quarter of 2022, and net loss was $352.1 million for the year ended Dec. 31, 2023 compared to $231.8 million for the year ended Dec. 31, 2022. The increase in net loss is due to the $127.9 million sale to Sagard in the fourth quarter of 2022 of our rights to future contingent payments associated with royalties on U.S. net sales of TIBSOVO®. Cash Position and Guidance: Cash, cash equivalents and marketable securities as of Dec. 31, 2023, were $806.4 million compared to $1.1 billion as of Dec. 31, 2022. Agios expects that its cash, cash equivalents and marketable securities together with anticipated product revenue, interest income and vorasidenib milestone will enable the company to fund its operating expenses and capital expenditures at least into 2026. This does not include cash inflows which could extend runway beyond 2026 including potential royalties or monetization of royalties from vorasidenib, commercializing mitapivat outside of the U.S. through one or more partnerships, or other potential strategic business or financial agreements. Conference Call Information Agios will host a conference call and live webcast with slides today at 8:00 a.m. ET to discuss fourth quarter and full year 2023 financial results and recent business highlights. The live webcast can be accessed under “Events & Presentations” in the Investors section of the company’s website at The archived webcast will be available on the company's website beginning approximately two hours after the event. About Agios Agios 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, MDS-associated anemia and phenylketonuria (PKU). In addition to its clinical pipeline, Agios is advancing a preclinical TMPRSS6 siRNA as a potential treatment for polycythemia vera. For more information, please visit the company’s website at . Cautionary Note Regarding Forward-Looking Statements This 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 PYRUKYND® (mitapivat), AG-946, TMPRSS6 siRNA and AG-181, Agios’ PAH stabilizer; Agios’ plans, strategies and expectations for its preclinical, clinical and commercial advancement of its drug development, including PYRUKYND®, AG-946 and AG-181, its PAH stabilizer; Agios’ strategic vision and goals, including its key milestones for 2024; and the potential benefits of Agios’ strategic plans and focus. The words “anticipate,” “expect,” “goal,” “hope,” “milestone,” “plan,” “potential,” “possible,” “strategy,” “will,” “vision,” 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 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. 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; competitive factors; 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 its 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 Agios’ cash and cash equivalents; 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. Consolidated Balance Sheet Data (in thousands) (Unaudited) December 31, 2023 December 31, 2022 Cash, cash equivalents, and marketable securities $ 806,363 $ 1,096,993 Accounts receivable, net 2,810 2,206 Inventory 19,076 8,492 Total assets 937,118 1,238,718 Stockholders' equity 811,019 1,100,814 Consolidated Statements of Operations Data (in thousands, except share and per share data) (Unaudited) Years Ended December 31, 2023 2022 2021 Revenues: Product revenue, net $ 26,823 $ 11,740 $ — Milestone revenue — 2,500 — Total revenue 26,823 14,240 — Operating expenses Cost of sales $ 2,881 $ 1,704 $ — Research and development 295,526 279,910 256,973 Selling, general and administrative 119,903 121,673 121,445 Total operating expenses 418,310 403,287 378,418 Loss from operations (391,487 ) (389,047 ) (378,418 ) Gain on sale of contingent payments — 127,853 — Royalty income from gain on sale of oncology business — 9,851 6,639 Interest income, net 33,344 12793 836 Other income, net 6,055 6,749 14,433 Net loss from continuing operations (352,088 ) (231,801 ) (356,510 ) Net income from discontinued operations, net of tax — — 1,961,225 Net (loss) income $ (352,088 ) $ (231,801 ) $ 1,604,715 Net loss from continuing operations per share - basic and diluted $ (6.33 ) $ (4.23 ) $ (5.90 ) Net income from discontinued operations per share - basic and diluted $ — $ — $ 32.45 Net (loss) income per share - basic and diluted $ (6.33 ) $ (4.23 ) $ 26.55 Weighted-average number of common shares used in computing net loss per share from continuing operations, net income per share from discontinued operations and net (loss) income per share – basic and diluted 55,651,487 54,789,435 60,447,346 Contacts: Investor Contact Chris Taylor, VP Investor Relations and Corporate Communications Agios Pharmaceuticals IR@agios.com Media Contact Dan Budwick 1AB dan@1abmedia.com

INCHEON, South Korea, Feb. 7, 2024 /PRNewswire/ -- Zymedi announced today that the first in human dosage of ZMA001, a monoclonal antibody being developed as a first-in-class treatment for Pulmonary Arterial Hypertension (PAH) has been initiated. The placebo-controlled phase 1 trial designed to ascertain the safety and dosage of ZMA001 is a collaborative effort between Zymedi and the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH). In the preceding year, both organizations entered into a Cooperative Research & Development Agreement (CRADA) in order to work together to advance the development of ZMA001. PAH is a serious and life-threatening condition affecting approximately 3 persons per 100,000 globally, with about 500 to 1,000 new cases diagnosed annually in the U.S. It is characterized by the narrowing of pulmonary arteries, a rise in pulmonary vascular resistance, and eventually death due to right heart failure. Current treatments for PAH, such as vasodilators, reduce symptoms but do not treat the underlying cause of the problem. ZMA001 is a first-in-class therapeutic antibody targeting the novel pro-inflammatory factor KARS1 that is specific to monocytes and macrophages. It can improve both the survival rates and the quality of life of PAH patients by eliminating the root pathologic cause of PAH. "We are excited to initiate this first in human trial of ZMA001, which marks a significant milestone for our company and the fight against PAH," said Dr. Sunghoon Kim, CEO and Founder of Zymedi. "We are scheduled to assess the safety and tolerability of ZMA001 through dose escalation clinical trials, systematically observing adverse reactions as dosage increases. Furthermore, we aim to establish the recommended dosage and determine the Maximum Tolerated Dose (MTD) for forthcoming phase 1b/2a clinical trials involving patients." The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. About ZMA001 ZMA001 is a human monoclonal antibody designed to control or inhibit inflammation responses in pulmonary blood vessels by blocking lysyl-tRNA synthetase (KARS1)-dependent infiltration of monocytes and macrophages. ZMA001 specifically targets membrane-exposed KARS1 without affecting its catalytic activity for protein synthesis. It can assure specificity toward response, disease indication, immune system, and target biology without inducing the systemic hypotension frequently observed with other typical treatments using vasodilators. ZMA001 with its novel MOA, is expected to treat PAH by eliminating its root pathologic cause unlike other treatments such as vasodilators that only address the symptoms. About Zymedi Zymedi is a global biopharmaceutical company that is committed to transforming the role of ARSs (Aminoacyl-tRNA Synthetases) and targeting it as a method of discovering and developing innovative treatments for patients with serious and life-threatening conditions that have no standard of care or lack effective therapy. For more information, please visit SOURCE Zymedi

Treatment with JNT-517 demonstrated a statistically significant mean blood phenylalanine reduction of 51% versus baseline JNT-517 was safe and well tolerated with no serious adverse events Jnana has adapted the ongoing trial to accelerate the program and aims to advance JNT-517 directly into a pivotal study in early 2025 BOSTON, Jan. 30, 2024 (GLOBE NEWSWIRE) -- Jnana Therapeutics, a clinical-stage biotechnology company leveraging its next-generation chemoproteomics platform to discover medicines for challenging-to-drug targets, today announced positive, statistically significant interim results from its ongoing clinical study of JNT-517 in individuals with phenylketonuria (PKU). JNT-517, a small molecule inhibitor of the phenylalanine (Phe) transporter SLC6A19, is being evaluated as a potential first-in-class oral treatment for PKU across all ages and genotypes. On the basis of these positive interim results, Jnana has adapted the Phase 1b trial design to support the potential for accelerated progression of JNT-517. “There is an urgent need for an oral, safe, and efficacious therapy for the more than 60% of individuals with PKU not currently on therapy. Across the spectrum of mild to severe disease, our results demonstrate a robust, sustained reduction in blood Phe levels, the registrational endpoint for PKU, giving us high confidence in the path forward for JNT-517,” said George Vratsanos, M.D., Chief Medical Officer and Head of R&D at Jnana Therapeutics. “We are also encouraged by this validation of the power of our RAPID platform to discover small molecules with compelling clinical benefit against challenging-to-drug targets.” JNT-517 is being studied in a randomized, double-blind, placebo-controlled trial in individuals with mild to severe PKU. Following a 28-day screening period focused predominantly on ensuring an average blood Phe level of >600µM, study participants were randomized with no run-in period to 75mg of JNT-517 twice daily (BID) or placebo. The planned interim analysis was based on 13 participants, eight dosed with JNT-517 and five dosed with placebo over 28 days, and demonstrated the following results: JNT-517 led to a statistically significant (p=0.0019 vs. placebo) mean blood Phe reduction from baseline of 51%, measured per-protocol at day 28. A high response rate was seen where seven of eight (88%) treated participants achieved >30% reduction in blood Phe from baseline; five of eight (63%) achieved >45% reduction; and two of eight (25%) achieved >65% reduction. A robust response was seen across participants treated with JNT-517 irrespective of baseline blood Phe levels, which ranged from 593µM to 1,526µM with a mean of 1,124µM. A rapid onset of effect was observed with significant blood Phe reduction achieved within seven days after commencing dosing, which was sustained through the full 28 days of dosing. JNT-517 was safe and well tolerated with no serious adverse events and no clinically significant changes in laboratory parameters, consistent with the safety pro in the Phase 1a healthy volunteer study. “JNT-517 represents a completely new therapeutic approach that could transform the current treatment paradigm in PKU, in particular for individuals with severe, or classical, PKU where there is the highest unmet medical need,” said Cary O. Harding, M.D., study investigator and Professor of Molecular and Medical Genetics at Oregon Health and Science University School of Medicine. “I am encouraged by the clinical results to date and look forward to working with Jnana and the PKU community to continue to advance this program.” Based on these interim results, Jnana has adapted the protocol of the ongoing trial to include dose exploration. Jnana expects topline data from the second dose cohort in mid-2024 and plans to submit full data from the two dose cohorts for presentation at a scientific meeting in the second half of 2024. Jnana anticipates the company will engage regulators in the second half of 2024 and seek to advance JNT-517 directly into a pivotal Phase 3 study in the first half of 2025. JNT-517Phase 1b Clinical Trial The ongoing clinical program includes a randomized, double-blind, placebo-controlled trial evaluating the safety, tolerability, pharmacokinetics, and effect on blood and urinary Phe of JNT-517 dosed over a four-week period in individuals diagnosed with PKU. The study dosed its first participant with PKU in August 2023 and is enrolling individuals aged 18 to 65 at clinical sites in the United States and Australia. For more information about the study, please see clinicaltrials.gov (NCT05781399). About JNT-517 JNT-517 is a selective small molecule inhibitor of the Phe transporter SLC6A19 that has the potential to be a first-in-class oral therapy used to treat any person with PKU, regardless of age or genotype. JNT-517 acts at a novel, cryptic allosteric site to block kidney reabsorption of Phe and offers a promising new approach to reduce blood Phe levels. The U.S. Food and Drug Administration granted JNT-517 Rare Pediatric Disease Designation in late 2022. About PKU PKU is a rare inherited metabolic disorder caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH). This enzyme is required for the breakdown of phenylalanine (Phe), an amino acid found in all protein-containing foods. When PAH is deficient or defective, Phe accumulates to abnormally high levels in the blood. If left untreated, toxic levels of Phe in the blood can result in progressive and severe neurological impairment and neuropsychological complications. The SLC transporter SLC6A19 is responsible for kidney reabsorption of Phe back into the bloodstream, and the inhibition of SLC6A19 offers a novel, oral approach for the treatment of PKU by facilitating urinary excretion of excess Phe. About Jnana Therapeutics Jnana Therapeutics is a clinical-stage biotechnology company leveraging its next-generation RAPID chemoproteomics platform to discover medicines for highly validated, challenging-to-drug targets to treat diseases with high unmet needs. Jnana is focused on developing first- and best-in-class therapies to treat a wide range of diseases, including rare diseases and immune-mediated diseases. Jnana’s wholly owned lead program, JNT-517, which targets an allosteric site on the phenylalanine transporter SLC6A19, is a potential first-in-class oral approach for the treatment of PKU, a rare genetic metabolic disease. Located in Boston, Jnana brings together scientific leaders in small molecule drug discovery and development, a highly experienced management team, and the backing of leading life science investors Bain Capital Life Sciences, RA Capital Management, Polaris Partners, Versant Ventures, Avalon Ventures, Pfizer Ventures, and AbbVie Ventures. For more information, please visit and follow us on Twitter/X and LinkedIn. Media Contact Adam Silverstein Scient PR media@jnanatx.com Investor Relations Josh Rappaport Stern IR ir@jnanatx.com