Agios Pharmaceuticals, Inc.

Agios与Oscotec就其免疫性血小板减少症资产SYK抑制剂cevidoplenib达成合作，预付2500万美元，高达1.4亿美元的开发和监管里程碑。 Servier与Edgewise就其Myosin ATPase抑制剂sevasemten达成合作，适应症：贝克型和杜氏肌营养不良，15.5亿美元预付现金及最高11亿美元额外里程碑付款。 Travere与Everest就其可逆共价BTK抑制剂Civorebrutinib达成合作，适应症：原发性膜性肾病等，1.125亿美元的前期付款，高达10.3亿美元的开发、监管及商业里程碑付款。

Fulcrum Therapeutics has begun a strategic review that may result in it getting sold, a move made after the companys main medicine hit a possibly insurmountable obstacle.On Tuesday, Fulcrum disclosed that, late last month, it received the official record from a recent meeting with the Food and Drug Administration. The meeting revolved around next steps for pociredir, an experimental treatment for sickle cell disease that Fulcrum had ushered through early-stage human testing.According to the company, FDA staff were worried about pociredirs safety, given emerging data that showed higher-than-expected rates of secondary blood cancers in patients who had received an Ipsen drug, Tazverik, which was pulled from the market in March. Fulcrums drug works in a similar-but-different way, and the company tried to make the case that these differences are important to assessing overall benefits and risks. The FDA, though, still concluded the potential hazards were too great and left no viable regulatory path forward.Fulcrum has therefore made the very difficult decision to discontinue development of pociredir, said CEO Alex Sapir. The company is now exploring strategic alternatives, including potentially merging or selling either assets or the entire business. Its also started efforts to significantly reduce operating expenses and preserve capital, though specific details werent provided. Fulcrum had a third of a billion dollars in cash, cash equivalents, and marketable securities as of March 31.Fulcrums stock price, which had already fallen significantly since late last year, cratered following Tuesdays update. Shares were down more than 50%, to just above $3 apiece.With limited visibility into future value creation beyond strategic alternatives and cost-cutting initiatives, we are moving to the sidelines, wrote Leerink Partners analyst Joseph Schwartz, who also downgraded his rating on Fulcrums stock to Market Perform.Schwartz noted, however, that his team was surprised by this outcome due to the effects pociredir demonstrated in that early-stage study. There, the drug boosted fetal hemoglobin levels one of the most proven methods for treating sickle cell and improved red blood cell health in adults with severe disease. Schwartz highlighted how the trial also hadnt reported any new clinical safety signals.Pociredir is designed to inhibit a large protein complex, PRC2, that helps turn off fetal hemoglobin production. It does this by latching onto a specific piece of the protein that, notably, is distinct from where Tazverik binds. Recent clinical data pointing to an increased incidence of hematologic malignancies among patients given Tazverik appears to have led the FDA to draw a hard line regarding the risk/benefit profile of all PRC2 inhibitors regardless of mechanistic differences, Schwartz wrote.The FDA previously put a so-called full clinical hold on Fulcrums program in early 2023, in part because of concerns with the wider class of PRC2-targeting drugs. The hold was lifted that summer, with Fulcrum agreeing to tailor the type of patients who were eligible to participate in its Phase 1 study. Schwartz argues the FDA position regarding pociredir seems to have been biased by malignancy observations seen in preclinical testing.Luca Issi, an analyst at RBC Capital Markets, claims his team wasnt entirely surprised by this outcome. While its unfortunate for the many [sickle cell] patients looking for therapeutic alternatives, we do believe that discontinuing the program is the right pragmatic decision given the FDA clearly believes that this is a class effect, Issi wrote in his own note to clients.Fulcrums is the latest in a string of setbacks for sickle cell drugmakers. In 2023, development was discontinued for three experimental treatments from Intellia Therapeutics, Sangamo Therapeutics and Graphite Bio. Two years later, Pfizer and Agios Pharmaceuticalseach delivered disappointing clinical results.Pfizers study was for a drug that the pharmaceutical giant picked up through the $5.4 billion acquisition of Global Blood Therapeutics. In 2024, Pfizer removed from the market another asset from that deal, the approved sickle cell therapy Oxbryta, because of safety concerns.The year prior, Novartis withdrew Adakveo from the European market after authorities there formally revoked the sickle cell disease drugs authorization.The World Health Organization estimates that, as of 2021, close to 8 million people had sickle cell. The disease causes “vaso-occlusive crises,“ a sudden, brutal wave of pain brought on by the crescent-shaped blood cells block small blood vessels. It can also make patients more vulnerable to infections and trigger chronic damage. Often, the life expectancy for people with sickle is 20 or so years less than their peers. '

Oscotec’s phase 2 trial missed its primary goal of demonstrating that cevidoplenib could double a patient’s platelet count after 12 weeks of treatment.\n Days after its lead clinical-stage drug suffered a setback, Agios Pharmaceuticals has rebounded by buying a blood disorder drug that flunked a phase 2 study.The prize is an oral spleen tyrosine kinase (SYK) inhibitor called cevidoplenib, which has been developed by Korea’s Oscotec. The biopharma has already taken cevidoplenib into a phase 2 study of 60 patients with a rare autoimmune blood disorder called immune thrombocytopenia (ITP).ITP affects around 200,000 people worldwide, including 90,000 in the U.S. alone, according to Agios. The condition is characterized by an immune system that destroys platelets, leading to an increased risk of bleeding.Oscotec’s phase 2 trial missed its primary goal of demonstrating that cevidoplenib could double a patient’s platelet count after 12 weeks of treatment. But Agios was undeterred, pointing to “durable and clinically meaningful platelet responses observed in the cevidoplenib arm compared with placebo across multiple secondary endpoints that align with primary endpoints used in ITP registrational trials.”Agios’ plan is to take the therapy into phase 3 trials in the first half of 2028, once it has completed additional chemistry, manufacturing, and controls (CMC) development work.Many patients with ITP receive steroids or thrombopoietin receptor agonists, such as Amgen’s Nplate or Novartis’ Promacta. Roche’s Rituxan is also used off-label to treat the condition in the U.S., though the antibody comes with some trade-offs when deployed against ITP. Meanwhile, Sanofi’s Wayrilz became the first BTK inhibitor to score an FDA approval for the clotting disease last year.Agios claimed that while current standard-of-care therapies are focused on increasing platelet counts and reducing bleeding risk, they are “often associated with limitations, including delayed onset of response, lack of durable efficacy, and class-specific adverse events, such as decreased blood counts and an increased risk of infections.”In return for the exclusive global rights to cevidoplenib, the Cambridge, Massachusetts-based biopharma is paying $25 million upfront and is liable for up to a further $140 million in development and regulatory milestones across up to three indications in the U.S. and Europe. If the drug secures an approval, Oscotec could also be in line for commercial milestone payments as well as royalties ranging from high single digit to mid-teens.Once the drug has cleared a phase 3 trial, Seongnam-based Oscotec has the option to secure the right to commercialize cevidoplenib on its home turf of South Korea.Cevidoplenib’s focus on ITP falls within Agios’ comfort zone of blood disorders. The biopharma’s sole commercial product is Pyrukynd, a PK activator that won approval in 2022 as the first therapy indicated for hemolytic anemia in adults with PK deficiency and has since expanded to treat anemia in adults with alpha- or beta-thalassemia under the brand name Aqvesme. Last week, Agio’s next-gen PK drug tebapivat failed a phase 2 study in lower-risk myelodysplastic syndromes, but the company is still persevering with the therapy in sickle cell disease.