On June 14, 2026 Eli Lilly and Company (NYSE: LLY) reported results from the Phase 3 BRUIN CLL-322 clinical trial of Jaypirca (pirtobrutinib), a non-covalent Bruton tyrosine kinase (BTK) inhibitor, plus venetoclax and rituximab versus venetoclax and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). The study met its primary endpoint of independent review committee (IRC)-assessed progression-free survival (PFS), demonstrating that the addition of pirtobrutinib to a two-year venetoclax plus rituximab regimen reduced the risk of disease progression or death by 45% (HR=0.55 [95% CI, 0.40-0.75]; p=0.0001).

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These data will be highlighted in a late-breaking oral presentation at the 2026 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting taking place in Stockholm, Sweden, as well as featured in the meeting’s press program.

"These results from BRUIN CLL-322 show that the addition of pirtobrutinib as part of a time-limited regimen further enhanced an already effective treatment and extended the duration of remission for patients with previously treated CLL. Importantly, the study provides the first robust evidence for such an approach in patients who received a prior BTK inhibitor," said Matthew S. Davids, M.D., M.M.Sc., Chief of the Division of Lymphoma at Dana-Farber Cancer Institute, who is the lead author on the study. "Time-limited regimens are an important option in CLL care and provide patients with meaningful treatment-free intervals. In the context of the modern CLL treatment landscape, where many patients may only receive two lines of therapy, these results speak to the potential benefits that improving second-line therapy can have. Our study has the potential to establish a new standard of care in this population."

BRUIN CLL-322 enrolled 639 relapsed or refractory patients, with 79.8% having prior covalent BTK inhibitor exposure, who were randomized 1:1 to receive pirtobrutinib plus venetoclax and rituximab (PVR, n=321) or venetoclax and rituximab alone (VR, n=318). Patients in the PVR arm received three cycles of pirtobrutinib and the first three cycles of rituximab before venetoclax was introduced. The efficacy results are based on a Feb. 2, 2026 data cutoff. At a median follow-up of 27.3 months, the primary endpoint of IRC-assessed PFS was significantly improved with the addition of pirtobrutinib to VR compared to VR alone (HR=0.55 [95% CI, 0.40-0.75]; p=0.0001). Median PFS in the PVR arm was not reached (95% CI, 43.3-NE), versus 39.7 months (95% CI, 35.9-NE) in the VR arm. The PFS results were consistent across prespecified subgroups, including patients with prior covalent BTK inhibitor exposure (PVR: not reached [95% CI, 41.5-NE] versus VR: 36.2 months [95% CI, 33.2-NE]), those who discontinued prior covalent BTK inhibitor due to progressive disease (PVR: 43.3 months [95% CI, 39.2-NE] versus VR: 33.2 months [95% CI, 28.3-37.5]), as well as those with high-risk features such as unmutated IGHV, TP53 mutation and/or 17p deletion, and/or complex karyotype. In an exploratory analysis of second-line patients whose disease progressed after a first-line covalent BTK inhibitor, the median PFS was not reached (95% CI, 30.1-NE) in the PVR arm and was 28.3 months (95% CI, 20.5-NE) in the VR arm (HR=0.32 [95% CI, 0.14-0.73]), with 24-month PFS rates of 88% (95% CI, 75.7-94.6) and 52% (95% CI, 34.7-66.2), respectively, and consistent benefit was observed regardless of the specific prior covalent BTK inhibitor received.

Overall survival (OS), a key secondary endpoint, was not yet mature at this analysis (HR=0.89 [95% CI, 0.57-1.40]), and final testing of OS superiority is planned at a future date. An additional secondary endpoint, time to next treatment (TTNT), consistently favored the pirtobrutinib combination regimen (HR=0.50 [95% CI, 0.35-0.70]; nominal p<0.0001).

The overall safety profile of this regimen in BRUIN CLL-322 was consistent with the known safety profile of each medicine, with little additive toxicity observed with the addition of pirtobrutinib to venetoclax and rituximab. Rates of Grade ≥3 adverse events (AEs) were similar with PVR compared to VR (78.8% versus 73.0%, respectively). Low rates of any grade atrial fibrillation/flutter (3.5% versus 2.6%, respectively), hypertension (12.0% versus 7.4%, respectively), and hemorrhage (14.2% versus 10.6%, respectively) were seen with PVR versus VR. Grade ≥3 clinical AEs of interest included neutropenia (50.3% versus 43.7%, respectively) and tumor lysis syndrome (0.9% versus 3.9%, respectively) in the PVR and VR arms. Discontinuation rates due to treatment-related AEs were similar across the PVR and VR study arms (5.4% versus 5.1%, respectively). The addition of pirtobrutinib to VR also allowed for downgrading of tumor lysis risk, with 78% of high-risk patients downgraded to medium (n=20) or low risk (n=18), and 61% of medium-risk patients downgraded to low risk.

"These remarkable findings support the potential addition of two years of Jaypirca to a time-limited venetoclax-based regimen in relapsed or refractory CLL," said Jacob Van Naarden, executive vice president and president of Lilly Oncology. "BRUIN CLL-322 enrolled a mostly covalent BTK inhibitor-pretreated population, ensuring that these results have applicability to the modern CLL treatment landscape where covalent BTK inhibitor use is now common. Additionally, these data further strengthen the unique body of evidence for Jaypirca across the CLL continuum, from monotherapy to combination therapy and across multiple settings where CLL patients need effective treatment."

Lilly plans to submit results from the BRUIN CLL-322 study to global regulatory authorities with the goal of further expanding Jaypirca’s label.

Lilly is studying Jaypirca in CLL/SLL in multiple Phase 3 studies. Details on the trials can be found by visiting clinicaltrials.gov.

About BRUIN CLL-322
BRUIN CLL-322 is a global, randomized, open-label, Phase 3 study comparing time-limited pirtobrutinib plus venetoclax and rituximab versus venetoclax and rituximab in previously treated CLL/SLL patients. The trial enrolled 639 patients, who were randomized 1:1 to receive pirtobrutinib (200 mg, once daily) plus venetoclax and rituximab per their labeled doses or venetoclax and rituximab alone. The primary endpoint is PFS as assessed by blinded IRC. Secondary endpoints include PFS as assessed by investigator, OS, TTNT, event-free survival, overall response rate, time to worsening of CLL/SLL-related symptoms, time to worsening of physical functioning, safety and tolerability.

About Jaypirca (pirtobrutinib)
Jaypirca (pirtobrutinib) (pronounced jay-pihr-kaa) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent inhibitor of the enzyme BTK.1 BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).2,3 Jaypirca is a U.S. FDA-approved oral prescription medicine, 100 mg or 50 mg tablets taken as a once-daily 200 mg dose with or without food until disease progression or unacceptable toxicity.

INDICATIONS FOR JAYPIRCA (pirtobrutinib)
Jaypirca is indicated for the treatment of

Adult patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have previously been treated with a covalent BTK inhibitor.
Adult patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
IMPORTANT SAFETY INFORMATION FOR JAYPIRCA (pirtobrutinib)

Infections: Fatal and serious infections (including bacterial, viral, fungal) and opportunistic infections occurred in Jaypirca-treated patients. Across clinical trials, Grade ≥3 infections occurred (25%), most commonly pneumonia (20%); fatal infections (5%), sepsis (6%), and febrile neutropenia (3.8%) occurred. In patients with CLL/SLL, Grade ≥3 infections occurred (32%), with fatal infections occurring in 8%. Opportunistic infections included Pneumocystis jirovecii pneumonia and fungal infection. Consider prophylaxis, including vaccinations and antimicrobial prophylaxis, in patients at increased risk for infection, including opportunistic infections. Monitor for signs and symptoms, evaluate, and treat. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Hemorrhage: Fatal and serious hemorrhage has occurred with Jaypirca. Across clinical trials, major hemorrhage (Grade ≥3 bleeding or any central nervous system bleeding) occurred (2.6%), including gastrointestinal hemorrhage; fatal hemorrhage occurred (0.3%). Bleeding of any grade, excluding bruising and petechiae, occurred (16%). Major hemorrhage occurred when taking Jaypirca with (2.0%) and without (0.6%) antithrombotic agents. Consider risks/benefits of co-administering antithrombotic agents with Jaypirca. Monitor for signs of bleeding. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca. Consider withholding Jaypirca 3-7 days pre- and post-surgery based on surgery type and bleeding risk.

Cytopenias: Jaypirca can cause cytopenias, including neutropenia, thrombocytopenia, and anemia. Across clinical trials, Grade 3 or 4 cytopenias, including decreased neutrophils (27%), decreased platelets (13%), and decreased hemoglobin (11%), developed. Grade 4 decreased neutrophils (15%) and Grade 4 decreased platelets (6%) developed. Monitor complete blood counts regularly. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Cardiac Arrhythmias: Cardiac arrhythmias occurred in patients taking Jaypirca. Across clinical trials, atrial fibrillation or flutter were reported in 3.4% of Jaypirca treated patients, with Grade 3 or 4 atrial fibrillation or flutter in 1.6%. Other serious cardiac arrhythmias such as supraventricular tachycardia and cardiac arrest occurred (0.4%). Cardiac risk factors such as hypertension or previous arrhythmias may increase risk. Monitor and manage signs and symptoms of arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea). Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Second Primary Malignancies: Across clinical trials, second primary malignancies, including non-skin carcinomas, developed in 9% of Jaypirca-treated patients, most frequently non-melanoma skin cancer (4.4%). Other second primary malignancies included solid tumors (including genitourinary and breast cancers) and melanoma. Advise patients to use sun protection and monitor for development of second primary malignancies.

Hepatotoxicity, Including Drug-Induced Liver Injury (DILI): Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of DILI, has occurred in patients treated with BTK inhibitors, including Jaypirca. Evaluate bilirubin and transaminases at baseline and throughout Jaypirca treatment. For patients who develop abnormal liver tests after Jaypirca, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold Jaypirca. If DILI is confirmed, discontinue Jaypirca.

Embryo-Fetal Toxicity: Jaypirca can cause fetal harm. Administration of pirtobrutinib to pregnant rats caused embryo-fetal toxicity, including embryo-fetal mortality and malformations at maternal exposures (AUC) approximately 3-times the recommended 200 mg/day dose. Advise pregnant women of fetal risk and females of reproductive potential to use effective contraception during treatment and for one week after last dose.

Adverse Reactions (ARs) in Patients Who Received Jaypirca

The most common (≥30%) ARs in the pooled safety population of patients with hematologic malignancies (n=704) were decreased neutrophil count (54%), decreased hemoglobin (43%), decreased leukocytes (32%), fatigue (31%), decreased platelets (31%), decreased lymphocyte count (31%), calcium decreased (30%).

Mantle Cell Lymphoma

Serious ARs occurred in 38% of patients, with pneumonia (14%), COVID-19 (4.7%), musculoskeletal pain (3.9%), hemorrhage (2.3%), pleural effusion (2.3%), and sepsis (2.3%) occurring in ≥2% of patients. Fatal ARs within 28 days of last dose occurred in 7% of patients, most commonly due to infections (4.7%), including COVID-19 (3.1% of all patients).

Dose Modifications and Discontinuations Due to ARs: Dose reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. Permanent discontinuation in >1% of patients included pneumonia.

Most common ARs (≥15%) and Select Laboratory Abnormalities (≥10%) (all Grades %; Grade 3-4 %): hemoglobin decreased (42; 9), platelet count decreased (39; 14), neutrophil count decreased (36; 16), lymphocyte count decreased (32; 15), creatinine increased (30; 1.6), fatigue (29; 1.6), musculoskeletal pain (27; 3.9), calcium decreased (19; 1.6), diarrhea (19; -), edema (18; 0.8), dyspnea (17; 2.3), AST increased (17; 1.6), pneumonia (16; 14), bruising (16; -), potassium decreased (13; 1.6), sodium decreased (13; -), lipase increased (12; 4.4), ALT increased (11; 1.6), potassium increased (11; 0.8), alkaline phosphatase increased (11; -). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (10), platelets decreased (7), lymphocytes decreased (6).

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma from Single-Arm and Randomized Controlled Clinical Trials

Serious ARs occurred in 47-56% of patients across clinical trials. Serious ARs in ≥5% of patients in the single-arm trial were pneumonia (18%), COVID-19 (9%), sepsis (7%), febrile neutropenia (7%). Serious ARs in ≥3% of patients in the randomized controlled trial were pneumonia (21%), COVID-19 (5%), sepsis (3.4%). Fatal ARs within 28-30 days of last Jaypirca dose occurred in 8-11% of patients, most commonly due to infections (7-10%), including sepsis (5%), COVID-19 (2.7-5%), and pneumonia (3.4%).

Dose Modifications and Discontinuations Due to ARs: Dose reductions in 3.6-10%, treatment interruption in 42-51%, and permanent discontinuation of Jaypirca in 9-17% of patients. Permanent discontinuation in >1% of patients included second primary malignancy, pneumonia, COVID-19, neutropenia, sepsis, anemia, and cardiac arrhythmias.

Most common ARs and Select Laboratory Abnormalities (≥20%) (all Grades %, Grade 3-4 %)–in a randomized controlled trial: neutrophil count decreased (54; 26), hemoglobin decreased (45; 10), platelet count decreased (37; 17), pneumonia (28; 16), ALT increased (25; 1.8), creatinine increased (25; -), calcium decreased (23; 0.9), sodium decreased (22; 0.9), bilirubin increased (21; 0.9), upper respiratory tract infections (21; 0.9); in a single-arm trial: neutrophil count decreased (63; 45), hemoglobin decreased (48; 19), calcium decreased (40; 2.8), fatigue (36; 2.7), bruising (36; -), cough (33; -), musculoskeletal pain (32; 0.9), platelet count decreased (30; 15), sodium decreased (30; -), COVID-19 (28; 7), pneumonia (27; 16), diarrhea (26; -), abdominal pain (25; 2.7), lymphocyte count decreased (23; 8), ALT increased (23; 2.8), AST increased (23; 1.9), creatinine increased (23; -), dyspnea (22; 2.7), hemorrhage (22; 2.7), lipase increased (21; 7), alkaline phosphatase increased (21; -), edema (21; -), nausea (21; -), pyrexia (20; 2.7), headache (20; 0.9). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (23).

Drug Interactions

Strong CYP3A Inhibitors: Concomitant use increased pirtobrutinib systemic exposure, which may increase risk of Jaypirca ARs. Avoid using strong CYP3A inhibitors with Jaypirca. If concomitant use is unavoidable, reduce Jaypirca dose according to approved labeling.

Strong or Moderate CYP3A Inducers: Concomitant use decreased pirtobrutinib systemic exposure, which may reduce Jaypirca efficacy. Avoid using Jaypirca with strong or moderate CYP3A inducers. If concomitant use with moderate CYP3A inducers is unavoidable, increase Jaypirca dose according to approved labeling.

Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP Substrates: Use with Jaypirca increased their plasma concentrations, which may increase risk of ARs related to these substrates for drugs sensitive to minimal concentration changes. Follow recommendations for these sensitive substrates in their approved labeling.

Use in Specific Populations

Pregnancy and Lactation: Due to potential for Jaypirca to cause fetal harm, verify pregnancy status in females of reproductive potential prior to starting Jaypirca. Presence of pirtobrutinib in human milk is unknown. Advise women to use effective contraception and to not breastfeed while taking Jaypirca and for one week after last dose.

Geriatric Use: In the pooled safety population of patients with hematologic malignancies, patients aged ≥65 years experienced higher rates of Grade ≥3 ARs and serious ARs compared to patients <65 years of age.

Renal Impairment: Because severe renal impairment increases pirtobrutinib exposure, reduce Jaypirca dose in these patients according to approved labeling.

(Press release, Eli Lilly, JUN 14, 2026, View Source [SID1234668721])

On June 14, 2026 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on developing innovative CAR T-cell therapies, reported poster presentations for CT0596 (an allogeneic CAR T-cell product targeting BCMA), and CT1190B (an allogeneic CAR T-cell product targeting CD19/CD20) at the 2026 Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) ("EHA").

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Data for CT0596 in Relapsed/Refractory Multiple Myeloma and Primary Plasma Cell Leukemia

Eight patients, including 6 relapsed/refractory multiple myeloma (R/RMM) and 2 relapsed/refractory primary plasma cell leukemia (R/R pPCL), received CT0596 at the 4.5×10⁸ CAR⁺ T cell dose level. All patients were heavily pretreated, with a median of 3.5 prior lines of therapy (range 2, 6). Most patients had advanced disease (ISS Stage III: n=5), 1 had extramedullary disease, and 5 patients had high-risk cytogenetics.

All 8 patients reported treatment-emergent adverse events (TEAEs), primarily hematologic toxicities, which are common adverse events following CAR-T infusion. No grade ≥3 cytokine release syndrome (CRS), no immune effector cell-associated neurotoxicity syndrome (ICANS) and no graft-versus-host disease (GVHD) were observed. No treatment-related deaths or study discontinuation due to AE.

As of May 10, 2026, with a median follow-up of 6.97 months, 6 patients maintained responses. All 8 patients were evaluable for efficacy. Six patients achieved stringent complete response (sCR) (n=5) or very good partial response (VGPR) (n=1) following the initial 4.5×10⁸ infusion. One R/R MM patient achieved partial response (PR) and ongoing response at Month 10 after retreatment with 4.5×10⁸, following failure of initial 3.0×10⁸ infusion. One overweight pPCL patient (102 kg) who received reduced intensity lymphodepletion progressed after the initial 4.5×10⁸ infusion, but achieved sCR following retreatment with full-dose lymphodepletion and 6.0×10⁸. By disease subtype analysis, both pPCL patients achieved sCR. Among the 6 MM patients, 4 achieved sCR, 1 achieved VGPR, and 1 achieved PR. All patients achieved MRD negativity at a sensitivity of 10⁻⁶ at 4 weeks after the effective infusion.

Pharmacokinetic results from the 8 infused patients demonstrated robust and persistent cell expansion, with median Cmax of 100,078 copies/µg gDNA and median Tmax of 10.5 days.

Data for CT1190B in Relapsed/Refractory B-cell Non-Hodgkin’s Lymphoma

A total of 13 patients (10 with large B-cell lymphoma [LBCL] and 3 with follicular lymphoma

[FL]) received CT1190B infusion, with 1, 2, 4, and 6 patients dosed with 1.5×10⁸, 3.0×10⁸, 4.5×10⁸, and 6.0×10⁸ cells, respectively. All patients were heavily pretreated, with a median of 3 prior lines of therapy (range 2-7).

The majority of grade ≥3 adverse events were hematological toxicities, of which most recovered within 28 days. No grade ≥3 infections occurred. CRS was observed in 8 patients (7 grade 1-2, 1 grade 3) and all recovered within 11 days. ICANS occurred in 2 patients (one grade ≥3 resolving, one grade 1 resolved). No study discontinuations or deaths due to adverse events.

As of May 11, 2026, 12 patients were evaluable for efficacy. The objective response rate (ORR) was 91.7% (11/12) with complete response (CR) rate of 66.7% (8/12), including: 1 partial response (PR) and 1 CR at 3.0×10⁸; 1 PR and 3 CR at 4.5×10⁸; 1 PR and 4 CR at 6.0×10⁸. All 3 FL patients achieved CR. All 7 LBCL patients under lymphodepletion regimen A achieved response with a CR rate of 71.4%. Notably, responses were observed even in patients with prior CAR T-cell or bispecific antibody therapy exposure, and all patients treated at intermediate or higher doses (≥3.0×10⁸) achieved response. With a median follow-up of 6.62 months, 7 out of 11 responders maintained ongoing response.

CAR T-cell expansion was observed across intermediate and higher doses with a median Tmax of 10 days. At the highest dose level (6.0×10⁸ cells), the median Cmax (reaching 10⁵) and AUC0-t (reaching 6×10⁵) of CT1190B far exceeded those of currently approved autologous CAR‑T products (Cmax: 10³–10⁴; AUC 0-t: 10⁴–2×10⁵).

About CT0596

CT0596 is an allogeneic BCMA-targeted CAR-T therapy developed using CARsgen’s proprietary THANK-u Plus platform. It is currently being evaluated in IITs for R/R MM or PCL. CT0596 demonstrated preliminary favorable tolerability and encouraging efficacy signals. Further investigation is planned in additional plasma cell malignancies and autoimmune diseases mediated by autoreactive plasma cells. The Company plans to initiate Phase Ib clinical trials for R/R MM and primary PCL in 2026.

About CT1190B

CT1190B is a CD19/CD20-targeted allogeneic CAR-T cell therapy developed based on CARsgen’s THANK-u Plus platform. IITs for R/R B-NHL are ongoing. The Company plans to initiate Phase Ib clinical trials for R/R B-NHL in 2026.

(Press release, Carsgen Therapeutics, JUN 14, 2026, View Source [SID1234668724])

On June 13, 2026 Incyte (Nasdaq:INCY) reported updated clinical data from two Phase 1 studies evaluating the safety, tolerability and efficacy of INCA033989, a first-in-class mutant calreticulin (mutCALR)-targeted monoclonal antibody, in patients with mutCALR-expressing myeloproliferative neoplasms (MPNs). INCA033989 demonstrated rapid, clinically meaningful responses and consistent molecular activity across both myelofibrosis (MF) and essential thrombocythemia (ET), with convergent evidence supporting the potential for disease modification.

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These findings are being presented in oral and poster presentations at the European Hematology Association (EHA) (Free EHA Whitepaper) 2026 Congress in Stockholm, Sweden (Session: Myeloproliferative neoplasms – Clinical, Presentation numbers: S216, PS1983, PF884).

"The data presented at EHA (Free EHA Whitepaper) 2026 demonstrate clinically meaningful and consistent responses with INCA033989 across both myelofibrosis and essential thrombocythemia," said Pablo J. Cagnoni, M.D., President of Incyte and Global Head of Research and Development. "What distinguishes INCA033989 is its potential to deliver disease control while targeting the biology that drives it. We remain on track to initiate our pivotal ET study by mid-2026 and are actively engaging regulators on a pivotal MF program."

Results in Patients with Myelofibrosis (MF)

The safety, tolerability, and efficacy of INCA033989 in Type 1 and non-Type 1 patients with MF harboring a CALR mutation is being evaluated in two ongoing Phase 1 studies. Results demonstrate that INCA033989 delivers broad, clinically meaningful improvements across spleen volume, symptom burden and anemia in patients with MF. As a monotherapy and in combination with ruxolitinib, INCA033989 had a manageable safety profile and the majority of patients remained on treatment – no dose-limiting toxicities were observed, and a maximum tolerated dose was not reached.

Monotherapy: INCA033989 was evaluated as monotherapy in patients who were resistant, refractory or intolerant to JAK inhibitor treatment after >12 weeks (JAK R/R/I), or ineligible to JAK inhibitor therapy. The dose escalation cohort evaluated INCA033989 from 24-3500 mg, and the dose expansion cohort evaluated 250 mg and 2000 mg.

INCA033989 monotherapy demonstrated durable clinical benefit, with clinically meaningful improvements across spleen volume, symptoms and anemia across both JAK R/R/I and JAK ineligible patients.

Spleen Volume Reduction (SVR): Rapid and robust spleen volume reductions were observed in patients, with 55% (38/69) and 39% (27/69) of patients achieving the best SVR25 and SVR35 reduction, respectively. At Week 24, 27% (17/62) patients achieved SVR35, including 47% (8/17) JAK ineligible and 20% (9/45) JAK R/R/I. Robust responses were observed in JAK ineligible patients regardless of mutation type (60% [6/10] Type-1 vs. 29% [2/7] non-Type 1). In JAK R/R/I patients, clinically meaningful reductions were observed in 31% (8/26) of Type-1 patients across all evaluated doses at Week 24, and 33% (1/3) of non-Type-1 patients evaluated at 2500 mg, the highest evaluated dose.
Symptom Improvement: Improvements in symptoms were also observed in the majority of patients, with 53% of patients achieving at least a 50% best TSS reduction (TSS50). At Week 24, 32% of patients achieved TSS50, including 29% and 33% of JAK ineligible and JAK R/R/I patients, respectively.
Anemia: Rapid and durable anemia improvements were observed in most patients, with anemia response occurring in 60% of evaluable anemic patients, and 52% of patients achieved a major anemia response. Improvements in anemia were observed across patients regardless of prior JAK exposure, including 63% of JAK R/R/I patients and 55% of JAK ineligible patients.
Molecular: Consistent reductions in variant allele frequency (VAF) were observed across most patients, regardless of prior JAK exposure and mutation type, with 89% of patients achieving a reduction in whole blood mutCALR VAF (Type 1: 90%, Non-Type 1: 88%), and 81% of patients achieving a ≥25% reduction in mutCALR peripheral blood mononuclear cells (PBMC) from baseline (Type 1: 62%, Non-Type 1: 38%).
INCA033989 was generally well-tolerated, with 84% (70/83) of patients remaining on therapy at the time of the data cut off. Treatment emergent adverse events (TEAEs) occurred in 92% (76) of patients, with 27% (22) of patients experiencing Grade ≥3 TEAEs, the most frequent of which were cytopenias. No dose-limiting toxicities were observed, and discontinuations due to TEAEs were limited (n=2).

Combination therapy: INCA033989 (dose range: 70 to 2,500 mg) was evaluated in combination with ruxolitinib in patients with MF who experience a suboptimal response to ruxolitinib monotherapy. INCA033989 demonstrated additive, multi-domain clinical activity in patients when administered in combination with ruxolitinib.

SVR: At Week 24, 55% (11/20) and 30% (6/20) of patients achieved SVR25 and SVR35, respectively.
Symptom Improvement: 31% (5/16) of patients achieved TSS50 at Week 24.
Anemia: Anemia response occurred in 35% (6/17) of evaluable anemic patients.
INCA033989 in combination with ruxolitinib was generally well-tolerated, with 76% (16) of patients remaining on treatment at the time of the data cut off. In the combination arm (n=21), all patients experienced TEAEs. Grade ≥3 TEAEs were reported in 67% (14) of patients, most commonly anemia (33%).

Translational data

Clinical response occurred regardless of mutational complexity with SVR, anemia and molecular responses observed in patients with and without high molecular risk (HMR) mutations.
93% of patients with HMR had a reduction in whole blood mutCALR VAF, as did 88% of those without HMR mutations.
A reduction in mutCALR-positive hematopoietic stem and progenitor cells (HSPCs) was also seen, indicating activity at the level of disease-initiating cells.
"Patients with CALR-mutated MF have distinct disease biology and often respond poorly to available therapies, underscoring the need for treatments targeting the underlying driver of disease," said Claire Harrison, M.D., Professor of MPNs and Deputy Chief Medical Officer, Guy’s and St. Thomas’ NHS Foundation Trust. "What stands out in these data is that INCA033989 produced rapid and robust spleen, symptom and anemia responses, alongside reductions in mutCALR allele burden regardless of HMR mutations, pointing to activity at the level of the disease-initiating clone."

Results in Patients with Essential Thrombocythemia

In patients with ET, INCA033989 demonstrated rapid, deep and durable hematologic and molecular responses across both Type 1 and non-Type 1 CALR patients, supporting potential for disease modification in a population resistant or intolerant to prior cytoreductive therapy.

Hematologic Response:

Across doses, 70% (80/114) of patients achieved a complete hematologic response (CHR, platelet count ≤400 × 109/L and leukocytes <10 × 109/L) and 87% achieved complete or partial hematologic response (CHR/PHR, platelet count ≤600 × 109/L and leukocytes <10 × 109/L).
81% of patients with Type 1 mutCALR achieved a durable (>12 weeks) CHR at 750 mg and above; and 50% of patients with non–Type 1 mutCALR achieved a durable CHR/PHR at 2500 mg. The median time to onset of durable CHR was 2.1 weeks.
Molecular Response and Disease Biology:

≥25% reduction in mutCALR VAF correlated with durable CHR (nominal P<0.0001, n=103).
Of the patients who achieved a CHR and had ≥1 post-baseline VAF assessment, 73% achieved ≥25% reduction in VAF.
Durable molecular response was observed in both Type 1 and non–Type 1 mutCALR.
A reduction in mutCALR megakaryocytes was seen in both Type 1 and non-Type 1 patients treated with INCA033989
INCA033989 was well tolerated with 95% of patients remaining on treatment. The median duration of INCA033989 exposure was 8.1 months (range from 0.59 to 27.0 months). A low incidence of Grade ≥3 adverse events was observed (19%); the most common were neutropenia (4.4%) and lipase increase (3.5%). Grade ≥3 cytopenia TEAEs occurred in 6% (7/114) of patients; no Grade ≥3 thrombocytopenia TEAEs were observed.

"In patients with ET who were resistant to or intolerant of prior cytoreductive therapy, INCA033989 resulted in rapid and durable normalization of platelet counts with accompanying molecular responses, with the majority of patients achieving a CHR," said John Mascarenhas, M.D., Professor of Medicine at the Icahn School of Medicine at Mt. Sinai and Director, Center of Excellence for Blood Cancers and Myeloid Disorders, The Tisch Cancer Institute. "As there are currently no mutation-specific treatments available for patients with ET, this approach is critically important for this high-risk patient population. These results provide a strong foundation for advancing INCA033989 into a registrational Phase 3 study."

In November of 2025, INCA033989 was granted Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with ET harboring a Type 1 CALR mutation who are resistant or intolerant to at least one cytoreductive therapy. A Phase 3 study of INCA033989 in mutCALR positive patients with ET who are resistant or intolerant to at least one prior cytoreductive therapy (EXCALIBUR-ET2, NCT07623200) is being initiated in mid-2026.

More information regarding the EHA (Free EHA Whitepaper) 2026 Congress can be found on the EHA (Free EHA Whitepaper) website: View Source

About Myeloproliferative Neoplasms (MPNs) and Mutations in Calreticulin (mutCALR)

Calreticulin (CALR) is a protein involved in the regulation of cellular calcium levels and normal protein folding. Somatic, or non-inherited, DNA mutations in the CALR gene (mutCALR) can result in abnormal protein function and lead to the development of myeloproliferative neoplasms (MPNs),1 a closely related group of clonal blood cancers in which the bone marrow functions abnormally, overproducing blood cells.2,3 Among two types of MPNs, essential thrombocythemia (ET) and myelofibrosis (MF), mutCALR drives 25-35% of all cases.4 In MF, it is estimated that 70-83% of CALR mutations in the U.S. are identified as Type 1, with 15-30% identified as non-Type 1.4,5 There are currently no targeted therapies for CALR mutations.

Incyte is at the forefront of developing novel therapies for patients with mutCALR ET or MF that target only malignant cells, sparing normal cells, including INCA033989, a first-in-class, mutCALR-specific therapy. INCA033989 received Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with ET harboring a Type 1 CALR mutation who are resistant or intolerant to at least one cytoreductive therapy. A Phase 3 study of INCA033989 in patients with ET with a Type 1 or non-Type 1 CALR mutation who are resistant or intolerant to at least one cytoreductive therapy is being initiated (EXCALIBUR-ET2, NCT07623200).

About the INCA33989-101 & INCA33989-102 Trials

The clinical trial program for INCA033989 includes two multicenter, open-label Phase 1 studies, INCA33989-101 (NCT05936359) and INCA33989-102 (NCT06034002). The studies are evaluating the safety, tolerability and efficacy of INCA033989 in ~455 adult (≥18 years old) patients with mutCALR-expressing myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET) and myelofibrosis (MF).

The primary endpoint of the studies is measured by the number of participants with dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs) and the number of participants with TEAEs leading to dose modification or discontinuation. Secondary endpoints include response rates, mean change of ET total symptom score, percentage of MF patients achieving spleen volume reduction, MF patient anemia response, mean change in disease-related allele burden and various pharmacokinetics measures.

(Press release, Incyte, JUN 13, 2026, View Source [SID1234668725])

On June 13, 2026 Incyte (Nasdaq:INCY) reported positive results from the pivotal Phase 3 frontMIND trial evaluating the efficacy and safety of tafasitamab (Monjuvi/Minjuvi), a humanized Fc-modified cytolytic CD19-targeting monoclonal antibody, and lenalidomide added to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone; Tafa-Len-R-CHOP) versus R-CHOP, the current standard of care, as a first-line treatment for adults with previously untreated diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL). Eligible patients had an International Prognostic Index (IPI) score of 3-5, or, for patients ≤60 years of age, an age-adjusted IPI (aaIPI) of 2-3.

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These data are being highlighted in a prestigious Plenary Abstracts Session at the European Hematology Association (EHA) (Free EHA Whitepaper) 2026 Congress, being held June 11 – 14, 2026, in Stockholm, Sweden (Abstract # S101. Plenary Abstract Session. June 13, 6:00 – 7:30 a.m. ET [12:00-1:30 p.m. CEST]). frontMIND results were also recently published in The Lancet.

"These frontMIND data reinforce the potential of Tafa-Len-R-CHOP to meaningfully change the first-line treatment landscape for patients with high-risk DLBCL or HGBL, for which outcomes have remained unchanged for decades," said Steven Stein, M.D., Executive Vice President, Chief Medical Officer and Head of Late-stage Development, Incyte. "With encouraging efficacy observed across prespecified subgroups regardless of cell-of-origin (COO) molecular subtype, we believe these findings position this therapy as a compelling potential new standard of care and support our continued efforts to bring it to patients who are in need of other efficacious treatment options."

The results, which build on previously reported topline data and also recently announced at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, showed Tafa-Len-R-CHOP resulted in statistically significant and clinically meaningful improvements in progression-free survival (PFS).

Efficacy Data

A 25% reduction in risk of disease progression or death demonstrated with Tafa-Len-R-CHOP compared with R-CHOP (HR 0.75 [P=0.0194]; 95% CI: 0.59, 0.96; median follow-up of 35.2 months).
PFS increase of 8.2% at 2 years (71.1% with Tafa-Len-R-CHOP vs. 62.9% with R-CHOP) and a PFS increase of 6.6% at 3 years (67.3% with Tafa-Len-R-CHOP vs. 60.7% with R-CHOP).
Tafa-Len-R-CHOP trends toward PFS advantage were broadly consistent across prespecified subgroups, including patients with centrally confirmed lymphoma subtypes and across COO molecular subtypes (ABC [Activated B-cell-like] and GCB [Germinal Center B-cell-like]).
Tafa-Len-R-CHOP significantly improved event-free survival (EFS) compared to R-CHOP (HR 0.79 [P=0.0260] 95% CI: 0.64, 0.97; median follow-up of 35.4 months).
Interim overall survival (OS) analysis demonstrated a positive trend toward improvement (HR=0.85 [P=0.2703] 95% CI: 0.63, 1.14, median follow-up of 35.9 months).
Minimal residual disease (MRD)-negativity rate was 81.3% with Tafa-Len-R-CHOP and 66.7% with R-CHOP.
"A key goal in frontline treatment is to potentially prevent relapse, and spare patients from requiring additional therapies later. This is particularly meaningful for high-risk DLBCL and HGBL patients, where new treatment approaches are needed," said Dr. Georg Lenz, University Hospital Münster and principal investigator of the frontMIND study. "The frontMIND results are especially encouraging because the addition of tafasitamab and lenalidomide improved outcomes without compromising delivery of the R-CHOP backbone, which remains fundamental to achieving better outcomes for patients."

Safety Data
Tafa-Len-R-CHOP was generally well tolerated, and safety was consistent with the expected safety profile of adding Tafa-Len to R-CHOP. Safety findings included:

The most common treatment-emergent adverse events (TEAEs) for Tafa-Len-R-CHOP were neutropenia (70.7%), anemia (46.3%) and peripheral neuropathy (40.6%).
Any grade TEAEs were similar in both treatment arms (98.6% vs 97.1%).
More Grade ≥3 TEAEs occurred with Tafa-Len-R-CHOP (86.7%) vs R-CHOP (76.1%).
The most common Grade 3 TEAEs for Tafa-Len-R-CHOP group were anemia (22.8%), thrombocytopenia (13.1%) and neutropenia (12.4%) vs. anemia (15.9%), febrile neutropenia (8.7%) and thrombocytopenia (6.7%) for R-CHOP.
Incremental safety events observed with Tafa-Len-R-CHOP were well managed and did not interfere with the delivery of the R-CHOP backbone.
Rates of TEAEs leading to discontinuation of all study treatment were similar between the two groups (5.2% for Tafa-Len-R-CHOP and 5.4% for R‑CHOP) – a higher rate of fatal TEAEs was observed with Tafa-Len-R-CHOP (5.9% vs 3.8% with R-CHOP), however there were fewer overall deaths with Tafa-Len-R-CHOP (82 [18.5%]) compared to R-CHOP (97 [21.7%]), consistent with the positive trend observed in overall survival.
The frontMIND data support global regulatory applications for tafasitamab and lenalidomide in addition to R-CHOP for previously untreated DLBCL and HGBL.

About DLBCL
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) in adults worldwide, representing 40% of all cases.1 It is characterized as an aggressive, fast-growing type of lymphoma that can emerge in lymph nodes or extranodal sites such as the gastrointestinal tract, skin and brain.2 Each year, approximately 24,000 people in the U.S. and up to 36,000 people in Europe are diagnosed with DLBCL.3,4 With about 40% of these patients not responding to initial therapy or relapsing thereafter5,6, there is a high medical need for new, effective therapies, particularly for high-risk patients.

About frontMIND
The frontMIND trial (NCT04824092) is a randomized, double-blind, placebo-controlled, global Phase 3 study in patients with previously untreated high-risk diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL).

The study enrolled 899 adults (≥18 to ≤80 years) and is evaluating the efficacy and safety of tafasitamab and lenalidomide added to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) compared with R-CHOP.

The primary endpoint of the study is investigator-assessed progression-free survival (PFS) using the Lugano 2014 criteria. Key secondary endpoints include event-free survival (EFS) by investigator assessment and overall survival (OS).

For more information about the frontMIND trial, please visit View Source

About Tafasitamab (Monjuvi/Minjuvi)
Tafasitamab (Monjuvi/Minjuvi) is a humanized Fc-modified cytolytic CD19-targeting monoclonal antibody. Tafasitamab incorporates an XmAb engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP). Incyte licenses exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc.

In the U.S., Monjuvi (tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide and rituximab for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL). Additionally, Monjuvi received accelerated approval in the United States in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT).

Monjuvi is not indicated and is not recommended for the treatment of patients with relapsed or refractory marginal zone lymphoma outside of controlled clinical trials.

In Europe, Minjuvi (tafasitamab) received conditional Marketing Authorization from the European Medicines Agency in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory DLBCL who are not eligible for ASCT. In addition, in December 2025, the EMA approved Minjuvi, in combination with lenalidomide and rituximab, for the treatment of adult patients with relapsed or refractory FL (Grade 1-3a) after at least one line of systemic therapy.

In Japan, Minjuvi is approved in combination with rituximab and lenalidomide for adult patients with relapsed or refractory follicular lymphoma (2L+ FL).

XmAb is a registered trademark of Xencor, Inc.

Monjuvi and Minjuvi are registered trademarks of Incyte.

IMPORTANT SAFETY INFORMATION

What are the possible side effects of MONJUVI?
MONJUVI may cause serious side effects, including:

Infusion reactions. Your healthcare provider will monitor you for infusion reactions during your infusion of MONJUVI. Tell your healthcare provider right away if you get fever, chills, flushing, headache, or shortness of breath during an infusion of MONJUVI.
Low blood cell counts (platelets, red blood cells, and white blood cells). Low blood cell counts are common with MONJUVI, but can also be serious or severe. Your healthcare provider will monitor your blood counts during treatment with MONJUVI. Tell your healthcare provider right away if you get a fever of 100.4°F (38°C) or above, or any bruising or bleeding.
Infections. Serious infections, including infections that can cause death, have happened in people during treatment with MONJUVI and after the last dose. Tell your healthcare provider right away if you get a fever of 100.4°F (38°C) or above, or develop any signs and symptoms of an infection.
The most common side effects of MONJUVI include:

Feeling tired or weak
Diarrhea
Cough
Fever
Swelling of lower legs or hands
Respiratory tract infection
Decreased appetite
These are not all the possible side effects of MONJUVI. Your healthcare provider will give you medicines before each infusion to decrease your chance of infusion reactions. If you do not have any reactions, your healthcare provider may decide that you do not need these medicines with later infusions. Your healthcare provider may need to delay or completely stop treatment with MONJUVI if you have severe side effects.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Before you receive MONJUVI, tell your healthcare provider about all of your medical conditions, including if you:

Have an active infection or have had one recently.
Are pregnant or plan to become pregnant. MONJUVI may harm your unborn baby. You should not become pregnant during treatment with MONJUVI. Do not receive treatment with MONJUVI in combination with lenalidomide if you are pregnant because lenalidomide can cause birth defects and death of your unborn baby.
You should use an effective method of birth control (contraception) during treatment and for at least 3 months after your final dose of MONJUVI.
Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with MONJUVI.
Are breastfeeding or plan to breastfeed. It is not known if MONJUVI passes into your breastmilk. Do not breastfeed during treatment for at least 3 months after your last dose of MONJUVI.
You should also read the lenalidomide Medication Guide for important information about pregnancy, contraception, and blood and sperm donation.

Tell your healthcare provider about all the medications you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Please see the full Prescribing Information for Monjuvi, including Patient Information, for additional Important Safety Information.

(Press release, Incyte, JUN 13, 2026, View Source [SID1234668726])

On June 13, 2026 Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a commercial-stage biopharmaceutical company focused on delivering innovative medicines for patients with rare diseases, reported detailed results from the 52-week double-blind period of the global RISE UP Phase 3 trial of mitapivat, an oral pyruvate kinase (PK) activator, in patients aged 16 years or older with sickle cell disease. These efficacy and safety results, which include new transfusion burden and hemoglobin responder analyses reinforcing the strong anti-hemolytic profile of mitapivat, were presented during the distinguished Plenary Abstracts Session at the 31st European Hematology Association (EHA) (Free EHA Whitepaper) Congress (EHA 2026) in Stockholm, Sweden.

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In November 2025, topline results from RISE UP demonstrated a significant improvement in the trial’s primary endpoint of hemoglobin response with mitapivat compared with placebo. The trial also met two key secondary endpoints, showing rapid and durable improvements in hemoglobin concentration and indirect bilirubin, a marker of hemolysis (red blood cell destruction). Although mitapivat showed a reduction in the annualized rate of sickle cell pain crises (SCPCs) compared with placebo, this primary endpoint did not reach statistical significance, and there was no overall difference between mitapivat and placebo for the key secondary endpoint measuring patient-reported fatigue. However, patients in the mitapivat arm who achieved a hemoglobin response experienced clinically meaningful reductions in the annualized rate of SCPCs and related hospitalizations, as well as improvements in fatigue.

New RISE UP analyses, not previously disclosed by the company, further highlight the potential for mitapivat to offer clinical benefits for patients with sickle cell disease, as evidenced by a clinically meaningful reduction in transfusion burden and, for hemoglobin responders in the mitapivat arm, improvements observed across additional measures of pain and physical function.

"Patients living with sickle cell disease are in critical need of new treatments that can effectively manage the debilitating impact of their condition," said Biree Andemariam, M.D., Professor of Medicine and American Red Cross Endowed Chair in Transfusion Medicine, University of Connecticut Health, and a RISE UP trial investigator. "The RISE UP Phase 3 data presented today showcase the strong anti-hemolytic profile of mitapivat, with rapid and durable improvements in both hemoglobin and indirect bilirubin as well as a meaningful reduction in transfusion burden. Importantly, this anti-hemolytic effect is translating to clear clinical benefits, including improvements for hemoglobin responders across measures of sickle cell pain crises, pain, sleep, and physical function compared with non-responders. Together, these data reinforce the potential for mitapivat to improve the relentless physical toll that comes with living with sickle cell disease."

New RISE UP Phase 3 Trial Results at EHA (Free EHA Whitepaper) 2026
Reduction in Transfusion Burden
New analyses from RISE UP show that mitapivat was associated with a clinically meaningful reduction in transfusion burden compared with placebo. Patients in the mitapivat arm had a 41.1% relative reduction in the proportion of patients requiring blood transfusions compared with placebo (23.9% with mitapivat vs. 40.6% with placebo), as well as a 55.9% relative reduction in average red blood cell units transfused per patient compared with placebo (0.70 units with mitapivat vs. 1.59 with placebo). These benefits were observed regardless of whether patients were also taking hydroxyurea. A reduction in transfusion burden in sickle cell disease can reflect decreased dependence on supportive care.

Hemoglobin Responders Post-Hoc Analysis
As previously reported, 40.6% of patients in the mitapivat arm achieved the primary endpoint of hemoglobin response (≥1.0 g/dL increase from baseline in average hemoglobin from Week 24 through Week 52) compared with 2.9% in the placebo arm, a statistically significant improvement (2-sided p<0.0001). Among these hemoglobin responders, the mean change from baseline in average hemoglobin concentration from Week 24 through Week 52 was 1.6 g/dL.

A post-hoc analysis showed patients in the mitapivat arm who achieved a hemoglobin response also experienced clinically meaningful reductions in pain crises and related hospitalizations, including a 26% reduction in the annualized rate of SCPCs (2.20 for responders vs. 2.98 for non-responders) and 34% fewer related hospitalizations (1.16 for responders vs. 1.76 for non-responders). These patients also had improvements in healthcare utilization, with a 53% reduction in the annualized rate of emergency room visits for SCPCs (1.11 for responders vs. 2.33 for non-responders) and a 37% decrease in the annualized rate of hospitalization days for SCPCs (7.83 for responders vs. 12.34 for non-responders).

Hemoglobin responders in the mitapivat arm also reported greater improvements in patient-reported fatigue scores than non-responders (-5.19 for responders vs. -2.55 for non-responders), as measured by change from baseline in average Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue 13a Short Form scores from Week 24 through Week 52. The magnitude of this improvement in hemoglobin responders exceeded the predefined 4.1-point threshold required to be considered clinically meaningful.

In the mitapivat arm, improvements across several additional patient-reported outcomes, including measures of pain, sleep, and physical function, were observed for hemoglobin responders compared with non-responders:

PROMIS Pain Intensity 1a: The mean change from baseline was -1.63 points for hemoglobin responders and -0.59 for non-responders, with a least squares mean (LSM) difference of -1.04 (95% confidence interval [CI]: -1.66 to -0.42), favoring hemoglobin responders. The LSM difference is used throughout to represent the model-adjusted difference between hemoglobin responders and non-responders.
Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) Pain Impact: The mean change from baseline was 4.09 points for hemoglobin responders and 0.85 for non-responders, with an LSM difference of 3.24 (95% CI: 1.18 to 5.30), favoring hemoglobin responders.
PROMIS Physical Functioning 8a: The mean change from baseline was 5.30 points for hemoglobin responders and 1.79 for non-responders, with an LSM difference of 3.51 (95% CI: 0.62 to 6.39), favoring hemoglobin responders.
ASCQ-Me Sleep Impact: The mean change from baseline was 2.39 points for hemoglobin responders and -0.48 for non-responders, with an LSM difference of 2.87 (95% CI: 0.22 to 5.53), favoring hemoglobin responders.
EuroQol-5 Dimension Visual Analog Scale (EQ-5D VAS): The mean change from baseline was 3.27 points for hemoglobin responders and -6.77 for non-responders, with an LSM difference of 10.04 (95% CI: 2.41 to 17.66), favoring hemoglobin responders.

"Having the opportunity to present these comprehensive results during the EHA (Free EHA Whitepaper) 2026 Plenary Session highlights the strength of the RISE UP Phase 3 data – the first pivotal trial to validate pyruvate kinase activation as a new treatment approach in sickle cell disease," said Sarah Gheuens, M.D., Ph.D., Chief Medical Officer and Head of R&D, Agios. "Building on over a decade of clinical experience with mitapivat across several hemolytic anemias, these results reinforce both its consistent benefits and its well-established safety profile, which is supported by over 1,300 patient-years of data. Taken together, mitapivat represents a differentiated anti-hemolytic approach that can provide meaningful clinical benefits for patients with sickle cell disease – an underserved population in desperate need of innovative therapies."

Safety Profile
Mitapivat was well-tolerated, with a safety profile consistent with previous trials of mitapivat in sickle cell disease. The percentage of patients with any reported treatment-emergent adverse events was similar between the mitapivat and placebo arms (97.1% vs. 98.6%, respectively). No treatment-related deaths occurred during the trial.

EHA 2026 Investor Event
Agios will host a conference call and live webcast during EHA (Free EHA Whitepaper) 2026 today, June 13, 2026, at 9:00 a.m. ET (3:00 p.m. CEST). The live webcast will be accessible on the Investors section of the company’s website (www.agios.com) under the "Events & Presentations" tab. A replay of the webcast will be available on the company’s website approximately two hours after the event.

About Sickle Cell Disease
Sickle cell disease is a rare, inherited blood disorder caused by the production of abnormal hemoglobin that disrupts the ability of red blood cells to carry oxygen throughout the body. As a result, red blood cells become rigid and sickle-shaped, causing deformation of red blood cell membranes and the premature death of the cells. These effects lead to chronic hemolytic anemia, vaso-occlusion, and a cascade of severe and life-threatening complications, including long-term damage to the lungs, kidneys, and cardiovascular system. Due to its physical toll, sickle cell disease imposes a profound burden on patients and their families, marked by increased healthcare needs and early mortality.

About Mitapivat in Sickle Cell Disease
Mitapivat, an oral pyruvate kinase (PK) activator, is designed to enhance the process by which red blood cells produce energy. This approach has the potential to improve red blood cell health by increasing ATP levels to support increased energy demands and lowering levels of a molecule called 2,3-diphosphoglycerate (2,3-DPG). In sickle cell disease, increased stress on red blood cells results in elevated levels of 2,3-DPG, which raises the likelihood that red blood cells develop the abnormal "sickle" shape that triggers vaso-occlusive crises. In May 2026, Agios announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for the accelerated approval of mitapivat in sickle cell disease.

About the RISE UP Phase 3 Trial
The global RISE UP Phase 3 trial (NCT05031780) is evaluating the efficacy and safety of mitapivat in patients with sickle cell disease aged 16 years or older, representative of the global population. The trial included a 52-week, double-blind, randomized, placebo-controlled period, in which 207 participants were randomized 2:1 to receive oral mitapivat (100 mg) twice daily (n=138) or matched-placebo (n=69).

To comprehensively evaluate objective measures of hemolysis alongside other clinically relevant outcomes in sickle cell disease, the double-blind period of RISE UP included two primary endpoints – hemoglobin response and annualized rate of sickle cell pain crises – as well as five key secondary endpoints:

Average change from baseline in hemoglobin concentration from Week 24 through Week 52
Average change from baseline in indirect bilirubin from Week 24 through Week 52
Average change from baseline in Patient Reported Outcome Measurement Information System Fatigue 13a (PROMIS Fatigue) Short Form scores from Week 24 through Week 52
Annualized frequency of hospitalizations for sickle cell pain crises
Average change from baseline in percent reticulocyte levels from Week 24 through Week 52

Of the 176 participants who completed the double-blind period of the trial, nearly all (n=174/176) opted to transition into a 216-week open-label extension (OLE) period, during which all participants receive mitapivat.

(Press release, Agios Pharmaceuticals, JUN 13, 2026, View Source [SID1234668729])