Agios Pharmaceuticals, Inc.

– Completed Enrollment of the Phase 3 RISE UP Study of Mitapivat in Sickle Cell Disease; Topline Data from 52-Week Study Expected in Late 2025 – – Received $1.1 Billion in Payments from Royalty Pharma and Servier, Following FDA Approval of Vorasidenib – – Commenced Enrollment of the Phase 2b Study of Tebapivat in Lower-Risk Myelodysplastic Syndromes (LR-MDS); Granted FDA Orphan Drug Designation for Treatment of MDS – – PYRUKYND® (Mitapivat) Net Revenue of $9.0 Million in Q3; Cash, Cash Equivalents and Marketable Securities of $1.7 Billion as of September 30, 2024 – CAMBRIDGE, Mass., Oct. 31, 2024 (GLOBE NEWSWIRE) -- Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in cellular metabolism and pyruvate kinase (PK) activation pioneering therapies for rare diseases, today reported business highlights and financial results for the third quarter ended September 30, 2024. “We had a strong quarter, marked by several important advancements across our pipeline. We completed enrollment of our Phase 3 RISE UP study of mitapivat in sickle cell disease, on our way to sharing topline results in late 2025. Our Phase 2b study of tebapivat in lower-risk MDS was initiated, and we received orphan drug designation from the FDA to support the development of tebapivat in this indication,” said Brian Goff, chief executive officer of Agios. “Our cash position was further strengthened by the receipt of $1.1 billion in payments. This will allow us to maintain this great momentum and fuel our next phase of growth, building towards a franchise with multi-billion-dollar potential. We remain focused on progressing our promising clinical programs to address the critical needs of rare disease patients and look forward to sharing our progress in the coming months.” Third Quarter 2024 and Recent Highlights PYRUKYND® Revenues: Generated $9.0 million in net revenue for the third quarter of 2024, a 4 percent increase from the second quarter of 2024, primarily driven by increased patient demand. A total of 211 unique patients have completed prescription enrollment forms, representing an increase of 5 percent over the second quarter of 2024. A total of 127 patients are on PYRUKYND® therapy, inclusive of new prescriptions and continued therapy.Sickle Cell Disease: Completed enrollment of the 52-week Phase 3 RISE UP study of mitapivat in sickle cell disease, with more than 200 patients enrolled worldwide, and topline data expected in late 2025. Lower-risk Myelodysplastic Syndromes: Initiated patient enrollment in the Phase 2b study of tebapivat (AG-946).Granted Orphan Drug Designation from the FDA to tebapivat for the treatment of myelodysplastic syndromes (MDS). Presented topline data from Agios’ Phase 3 ACTIVATE-KidsT trial of mitapivat in pediatric patients with PKD. Observed transfusion reduction response rates were higher in the mitapivat arm compared to placebo and were clinically meaningful despite not meeting prespecified statistical criterion for the primary endpoint; secondary endpoints of transfusion-free response and normal hemoglobin response were observed only in the mitapivat arm.Safety was consistent with the profile observed in adults with PK deficiency who are regularly transfused. Presented data from the Phase 3 ENERGIZE trial as an encore session at the 19th Annual Academy for Sickle Cell and Thalassemia (ASCAT) Conference.Corporate Development: The FDA approved Servier’s vorasidenib for the treatment of IDH-mutant diffuse glioma. As a result, Agios received a $200 million milestone payment from Servier and a $905 million payment from Royalty Pharma in connection with the purchase agreement announced in May 2024.Entered into a distribution agreement with NewBridge Pharmaceuticals to advance commercialization of PYRUKYND® in the Gulf Cooperation Council (GCC) region. NewBridge, a leading specialty company headquartered in Dubai, will commercialize PYRUKYND® in Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and the United Arab Emirates. Key Upcoming Milestones & Priorities Agios expects to achieve the following key milestones by the end of 2024: Thalassemia: File sNDA for mitapivat in thalassemia based on the positive results from the Phase 3 ENERGIZE and ENERGIZE-T clinical trials.Present additional clinical data at the 66th Annual American Society of Hematology (ASH) Congress, taking place December 7-10, 2024, in San Diego. Third Quarter 2024 Financial Results Revenue: Net product revenue from sales of PYRUKYND® for the third quarter of 2024 was $9.0 million, compared to $7.4 million for the third quarter of 2023. Cost of Sales: Cost of sales for the third quarter of 2024 was $0.8 million. Research and Development (R&D) Expenses: R&D expenses were $72.5 million for the third quarter of 2024, compared to $81.8 million for the third quarter of 2023. The year-over-year decrease was primarily driven by the $17.5 million upfront payment associated with the license agreement with Alnylam, which was recorded in the prior year. Selling, General and Administrative (SG&A) Expenses: SG&A expenses were $38.5 million for the third quarter of 2024 compared to $25.8 million for the third quarter of 2023. The year-over-year increase was primarily attributable to an increase in commercial-related activities as the company prepares for the potential approval of PYRUKYND® in thalassemia. Net Income (Loss): Net income was $947.9 million for the third quarter of 2024 compared to a net loss of $91.3 million for the third quarter of 2023, reflecting the milestone and royalty agreement income recorded in the third quarter of 2024. Cash Position and Guidance: Cash, cash equivalents and marketable securities as of September 30, 2024, were $1.7 billion compared to $806.4 million as of December 31, 2023. Agios expects that its cash, cash equivalents and marketable securities, together with anticipated product revenue and interest income, will provide the financial independence to prepare for potential PYRUKYND® launches in thalassemia and sickle cell disease, advance existing programs, and to opportunistically expand its pipeline through both internally and externally discovered assets. Conference Call Information Agios will host a conference call and live webcast with slides today at 8:00 a.m. ET to discuss third quarter 2024 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 www.agios.com. 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, myelodysplastic syndromes (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 www.agios.com. 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), tebapivat (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®, tebapivat, and AG-181; Agios’ use of proceeds from the transaction with Royalty Pharma; potential U.S. net sales of vorasidenib and potential future royalty payments; Agios’ strategic vision and goals, including its key milestones for 2024 and 2025; 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 royalty payments related to the sale of its oncology business or any milestone or royalty payments related to 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) September 30, 2024 December 31, 2023Cash, cash equivalents, and marketable securities $1,660,646 $806,363Accounts receivable, net 3,118 2,810Inventory 26,429 19,076Total assets 1,791,794 937,118Stockholders' equity 1,626,672 811,019 Consolidated Statements of Operations Data(in thousands, except share and per share data)(Unaudited) Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Revenues: Product revenue, net$8,964 $7,399 $25,768 $19,720 Total revenue 8,964 7,399 25,768 19,720 Operating expenses: Cost of sales$783 $633 $2,905 $2,295 Research and development 72,455 81,841 218,476 218,037 Selling, general and administrative 38,537 25,822 105,087 84,598 Total operating expenses 111,775 108,296 326,468 304,930 Loss from operations (102,811) (100,897) (300,700) (285,210)Gain on sale of contingent payments 889,136 — 889,136 — Milestone payment from gain on sale of oncology business 200,000 — 200,000 — Interest income, net 13,059 8,375 30,068 24,720 Other income, net 1,651 1,198 4,864 4,342 Net income (loss) before taxes 1,001,035 (91,324) 823,368 — (256,148)Income tax expense 53,120 — 53,120 — Net income (loss)$947,915 $(91,324) $770,248 $(256,148)Net income (loss) per share - basic$16.65 $(1.64) $13.58 $(4.61)Net income (loss) per share - diluted$16.22 $(1.64) $13.38 $(4.61)Weighted-average number of common shares used in computing net income (loss) per share – basic 56,939,403 55,803,663 56,709,318 55,559,766 Weighted-average number of common shares used in computing net income (loss) per share – diluted 58,432,796 55,803,663 57,581,382 55,559,766 Contacts: Investor ContactChris Taylor, VP, Investor Relations and Corporate CommunicationsAgios PharmaceuticalsIR@agios.com Media ContactEamonn Nolan, Senior Director, Corporate CommunicationsAgios Pharmaceuticalsmedia@agios.com

– Topline Data from 52-week Phase 3 Study Expected in Late 2025 – CAMBRIDGE, Mass., Oct. 23, 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 that enrollment is complete for the Phase 3 RISE UP study. This global, double-blind, randomized, placebo-controlled trial is evaluating the efficacy and safety of mitapivat, an oral, small molecule PK activator, in sickle cell disease patients who are 16 years of age or older. Agios expects to report topline results from this 52-week Phase 3 study in late 2025. Sickle cell disease is an inherited, lifelong blood disorder caused by mutations in hemoglobin, the major protein that carries oxygen in red blood cells. In sickle cell disease, red blood cells are sickle-shaped due to a gene mutation that affects the hemoglobin molecule. When red blood cells sickle, they do not bend or move easily and can block blood flow to the rest of the body, resulting in chronic hemolytic anemia, pain, poor quality of life, organ damage and early mortality. In sickle cell disease there is an increased energy demand of adenosine triphosphate (ATP) to support red blood cell function and increased 2,3-diphosphoglycerate (2,3-DPG) concentrations that increase the likelihood of red blood cell sickling. Mitapivat is designed to optimize the glycolytic pathway, which has a dual effect of increasing ATP levels and decreasing 2,3-DPG concentrations in red blood cells. “There is a critical need for novel regimens that elevate the standard of care for patients suffering from sickle cell disease, a burdensome and debilitating disease,” said Sarah Gheuens, M.D., Ph.D., chief medical officer and head of R&D at Agios. “We sincerely thank the patients, study investigators and patient advocates for their instrumental support and partnership in helping us complete enrollment of the Phase 3 RISE UP study. With enrollment now complete, we look forward to completing the trial and sharing topline results with the community in late 2025.” The Phase 3 RISE UP study enrolled more than 200 patients worldwide. The trial’s primary endpoints are hemoglobin response, defined as a ≥1.0 g/dL increase in average hemoglobin concentration from Week 24 through Week 52 compared with baseline, and annualized rate of sickle cell pain crises. These are important clinical endpoints in sickle cell disease because anemia and pain episodes are the hallmark symptoms of the disease that severely impact a patient’s quality of life. The positive results from the double-blind period of the RISE UP Phase 2 study, which were presented at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition in December 2023, supported Agios’ further exploration of mitapivat’s risk-benefit profile in sickle cell disease in the Phase 3 study. About Phase 2/3 RISE UP StudyThe RISE UP Phase 2 and 3 studies are evaluating the efficacy and safety of mitapivat in sickle cell disease patients who are 16 years of age or older, have had between two and 10 sickle cell pain crises in the past 12 months, and have hemoglobin within the range of 5.5 to 10.5 g/dL during screening. The Phase 2 and Phase 3 studies are conducted under a single operationally seamless Phase 2/3 protocol. The two studies enrolled different participants and achieved operational efficiency through leveraging the same sites, vendors and other resources. The Phase 2 study included a 12-week randomized, placebo-controlled period in which participants were randomized in a 1:1:1 ratio to receive 50 mg mitapivat twice daily, 100 mg mitapivat twice daily or matched placebo. The primary endpoints were hemoglobin response, defined as ≥1.0 g/dL increase in average hemoglobin concentration from Week 10 through Week 12 compared to baseline, and safety. The Phase 3 study includes a 52-week randomized, placebo-controlled period in which participants will be randomized in a 2:1 ratio to receive 100 mg of mitapivat twice daily or matched placebo. The primary endpoints are hemoglobin response, defined as a ≥1.0 g/dL increase in average hemoglobin concentration from Week 24 through Week 52 compared with baseline, and annualized rate of sickle cell pain crises. Participants who complete the double-blind period of the Phase 2 or Phase 3 studies will have the option to move into a 216-week open-label extension period to receive mitapivat. 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 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. 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, myelodysplastic syndrome (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 www.agios.com. 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); Agios’ plans, strategies and expectations for its preclinical, clinical and commercial advancement of its drug development, including PYRUKYND®; Agios’ strategic vision and goals, including its key milestones for 2024 and 2025; 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. Contacts: Investor ContactChris Taylor, VP, Investor Relations and Corporate CommunicationsAgios PharmaceuticalsIR@agios.com Media ContactEamonn Nolan, Senior Director, Corporate CommunicationsAgios PharmaceuticalsMedia@agios.com

iStock/ YuLi4ka In the wake of Pfizer’s voluntary market withdrawal of the popular sickle cell disease therapy, BioSpace looks at five investigational drugs currently making their way through the pipeline. A recent fumble has left the sickle cell disease community reeling . Last month, Pfizer abruptly pulled Oxbryta from all global markets after new data showed a higher risk of deaths and complications in treated patients. “[Oxbryta] was one of four medications which we would describe as disease-modifying,” Clifford Takemoto, director of clinical hematology at St. Jude Children’s Research Hospital, told BioSpace . Since the approval of Bristol Myers Squibb’s hydroxyurea for sickle cell disease (SCD) in 1998, only three disease-modifying medications have entered the market, he said. Oxbryta, which won FDA accelerated approval in November 2019, was one of these. Another, Novartis’ Adakveo, has also been called into question after failing to reduce vaso-occlusive crises (VOC) in people with SCD in a Phase III trial last year. EU regulators formally revoked Adakveo’s approval in August 2023, but it remains available in the U.S. “We were optimistic that things were changing,” Takemoto said. “People had hoped that these medications would make a difference.” SCD affects more than 100,000 people in the U.S. and 8 million worldwide. With so few treatment options, it remains a seriously underserved population . Takemoto said the Oxbryta withdrawal has left some patients a “bit angry” and distrustful of new medications, and the question for the community remains: “What’s next?” For Takemoto, the ultimate hope for SCD treatment lies in next-gen transplantation and gene therapy. With the approval of bluebird bio’s Lyfgenia and Vertex and CRISPR Therapeutics’ Casgevy, the potential for gene therapies in SCD is there, even if the rollout is slow and for most, not very accessible, he said. St. Jude is developing its own gene therapy, which the research hospital hopes to move into clinical trials sometime next year. Takemoto also pointed to work being done in bone marrow transplantation intended to reduce toxicity and improve success rates. St. Jude is working on a process that will utilize a “half match,” where a parent’s bone marrow can be used instead of a sibling. These treatments could be transformative, Takemoto said. Here, BioSpace looks at five investigational therapies making their way through the SCD pipeline. Pfizer’s Inclacumab and Osivelotor Oxbryta is not the only SCD asset Pfizer brought onboard with its 2022 acquisition of Global Blood Therapeutics . Two other investigational therapies, inclacumab and osivelotor, were also part of the deal. Inclacumab, a P-selectin inhibitor, is currently being assessed in a Phase III trial to determine its safety and efficacy in reducing VOC. The drug works by binding to P-selectin, a cell adhesion molecule found on platelets. According to Pfizer, this prevents platelets from aggregating, which in turn, is expected to help maintain normal blood flow. Like Oxbryta, osivelotor is a sickle hemoglobin polymerization inhibitor, but with a next-generation design. The asset is currently being studied in a Phase II/III study slated for completion in 2028. While Pfizer has not stated whether the recent findings related to Oxbryta will impact the development of osivelotor, Leerink Partners noted that a Phase II study raised safety concerns, with treatment-emergent adverse events seen in 8 out of 35 patients. Agios Pharmaceuticals’ Mitapivat Agios Pharmaceuticals is developing mitapivat, a pyruvate kinase (PK) activator that is already approved for the treatment of hemolytic anemia in adults with PK deficiency, for SCD. Red blood cells require the PK enzyme for energy, Takemoto explained. In December 2023, the company presented positive data from the Phase II portion of its pivotal RISE UP study. The annualized rate of sickle cell pain crises for patients in the higher dose treatment arm was 0.51 compared to 1.71 for participants in the placebo arm. Takemoto said the oral medication seems to benefit red blood cell health in general and noted that the data look favorable for patients with SCD and other hemolytic anemias. But not everyone is as convinced. Leerink Partners analysts wrote last month of concerns that similar physiological effects could be seen with both Oxbryta and mitapivat. A Phase III readout is expected next year, and the company is targeting a label expansion in 2026. Novo Nordisk’s Etavopivat In 2022, Novo Nordisk paid $1.1 billion to acquire Forma Therapeutics, gaining a lead SCD asset, etavopivat, in the deal. Like mitapivat, etavopivat is also a PK activator, but Novo’s candidate comes with a potential advantage —once daily dosing, versus mitapivat’s twice daily regimen. Etavopivat is currently being studied in a Phase III trial slated for completion in 2026. Phase I data presented by Forma at the American Society of Hematology’s annual meeting in 2021 showed a “sustained increase in hemoglobin and improvement in biomarkers of hemolysis and red blood cell health.” The results, from 15 patients dosed for up to 12 weeks, also showed a trend toward decreasing VOC compared to the 12 months prior to their entering the trial. Takemoto said the candidate “looks very promising” so far but acknowledged that “there are things we don’t know about it. We may learn new side effects as it’s used.” St. Jude will serve as a site for the Phase III trial. Fulcrum Therapeutics’ Pociredir Fulcrum Therapeutics ’ pociredir, a polycomb repressive complex 2 (PRC2) inhibitor, is designed to induce expression of fetal hemoglobin to compensate for the mutated hemoglobin that occurs in SCD. The development path for pociredir has not been without bumps. In February 2023, the FDA slapped Fulcrum with a clinical hold based on previously submitted preclinical data and non-clinical and clinical evidence of hematological malignancies observed with other PRC2 inhibitors. The hold was released six months later. The small molecule, which is currently being studied in a Phase Ib trial, has been well-tolerated in people with SCD with no treatment-related adverse events reported after up to three months exposure, according to a press release announcing the lifted clinical hold.