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])

On June 12, 2026 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported the U.S. Food and Drug Administration (FDA) approved KEYTRUDA (pembrolizumab) and KEYTRUDA QLEXTM (pembrolizumab and berahyaluronidase alfa-pmph), Merck’s anti-PD-1 therapies, each in combination with WELIREG (belzutifan), Merck’s first-in-class, oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, for the adjuvant treatment of adult patients with renal cell carcinoma with a clear cell component (ccRCC) at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. These approvals represent the first approval for WELIREG in earlier-stage ccRCC and the first approvals for PD-1 and HIF-2α inhibitor combination regimens.

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The approvals are based on results from the pivotal Phase 3 LITESPARK-022 trial. LITESPARK-022 enrolled 1,841 patients and demonstrated that KEYTRUDA in combination with WELIREG significantly improved disease-free survival (DFS), the trial’s primary endpoint, reducing the risk of disease recurrence, metastasis or death by 28% (HR=0.72 [95% CI 0.59-0.87]; p=0.0003) for patients with ccRCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions compared to KEYTRUDA plus placebo. The estimated 24-month DFS rate was 81% (95% CI 0.78-0.83) with KEYTRUDA plus WELIREG compared to 74% (95% CI 0.71-0.77) with KEYTRUDA plus placebo. Median DFS was not reached in either arm. Overall survival (OS) results were not yet mature at this interim analysis. The effectiveness of KEYTRUDA QLEX for its approved indications has been established based upon evidence from the adequate and well-controlled studies conducted with KEYTRUDA and additional data from MK-3475A-D77 comparing the pharmacokinetic, efficacy, and safety profiles of KEYTRUDA QLEX and KEYTRUDA.

The WELIREG prescribing information contains a boxed warning that exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception. WELIREG can render some hormonal contraceptives ineffective. WELIREG can cause severe anemia that can require blood transfusion. Monitor for anemia before initiation of, and periodically throughout, treatment with WELIREG. WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen or hospitalization. Monitor oxygen saturation before initiation of, and periodically throughout, treatment with WELIREG. For more information, see "Selected Safety Information" below.

KEYTRUDA QLEX is contraindicated in patients with known hypersensitivity to berahyaluronidase alfa, hyaluronidase or to any of its excipients. KEYTRUDA and KEYTRUDA QLEX are associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions in any or multiple organs, which can occur during or after treatment, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, other transplant (including corneal graft) rejection; severe and life-threatening infusion or injection-related reactions; fatal and other serious complications in patients who receive allogeneic hematopoietic stem cell transplantation before or after beginning treatment; embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when KEYTRUDA or KEYTRUDA QLEX is added to a thalidomide analogue plus dexamethasone, which is not recommended outside of controlled trials. Immune-mediated adverse reactions listed here may not include all such possible severe or fatal reactions. For more information, see "Selected Safety Information" below.

"Patients with earlier-stage renal cell carcinoma at high risk of recurrence after surgery may see their cancer return, frequently as metastatic disease," said Dr. Toni K. Choueiri, director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and Jerome and Nancy Kohlberg professor of medicine, Harvard Medical School. "The results of the LITESPARK-022 trial demonstrated the ability of pembrolizumab in combination with belzutifan to reduce the risk of disease recurrence, metastasis, or death by 28%, which represents an important new option for these patients to help keep their clear cell renal cell carcinoma from coming back."

"Reflecting on my own experience as a clinical oncologist, I know the significant impact that improved disease-free survival can have on the lives of patients," said Dr. M. Catherine Pietanza, vice president, global clinical development, Merck Research Laboratories. "These approvals demonstrate Merck’s commitment to pursuing innovative treatment options that may help these patients experience longer periods without disease."

"The FDA approval of the novel KEYTRUDA and WELIREG combination is exciting news for the kidney cancer community," said Bryan Lewis, CEO and co-founder, KidneyCan. "This progress reflects an important step in addressing the needs of patients with earlier-stage renal cell carcinoma."

Study design and additional data from LITESPARK-022

LITESPARK-022 is a multicenter, randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT05239728) evaluating WELIREG in combination with KEYTRUDA compared to placebo plus KEYTRUDA for the adjuvant treatment of ccRCC post nephrectomy. Eligible patients had intermediate-high or high risk of recurrence of RCC, or M1 no evidence of disease (NED). Patients must have undergone a partial or radical nephrectomy, and if indicated, metastasectomy within two years of nephrectomy, within ≥4 weeks prior to the time of screening. Patients were excluded from the trial if they had received prior systemic therapy for advanced RCC. The trial enrolled 1,841 patients who were randomized (1:1) to receive either:

WELIREG (120 mg orally once daily) plus KEYTRUDA (400 mg intravenously [IV] every six weeks) for up to 9 cycles (54 weeks) until disease recurrence or unacceptable toxicity (n=921), or;
KEYTRUDA (400 mg IV every six weeks) plus oral placebo for up to 9 cycles (54 weeks) until disease recurrence or unacceptable toxicity (n=920).
The major efficacy outcome measure was investigator-assessed DFS and an additional outcome measure was OS.

The safety of WELIREG in combination with KEYTRUDA was evaluated in LITESPARK-022. A total of 915 patients received WELIREG in combination with KEYTRUDA and a total of 913 patients received oral placebo in combination with KEYTRUDA. The median duration of exposure to WELIREG was 12.4 months (range 1 day to 20.1 months). The median duration of exposure to KEYTRUDA in the treatment arm was 11.1 months (range: 1 day to 16.1 months).

Serious adverse reactions occurred in 30% of patients who received WELIREG in combination with KEYTRUDA. The most frequently reported serious adverse reactions (≥1%) were pneumonia (2%), hypoxia (1.9%), pneumonitis (1.6%), arrhythmia (1.5%), diarrhea (1.1%), and acute kidney injury (1.1%). Fatal adverse reactions occurred in 1.1% of patients who received WELIREG in combination with KEYTRUDA, including sepsis (0.1%).

WELIREG was permanently discontinued due to adverse reactions in 27% of patients. Adverse reactions which resulted in permanent discontinuation of WELIREG in ≥1% of patients included anemia (4%), fatigue (2.2%), rash (2%), increased alanine aminotransferase (ALT) (1.7%), hypoxia (1.6%), diarrhea (1.4%), pneumonitis (1.3%), increased aspartate aminotransferase (AST) (1.1%), and hepatic function abnormal (1%).

KEYTRUDA was permanently discontinued due to adverse reactions in 23% of patients. Adverse reactions which resulted in permanent discontinuation of KEYTRUDA in ≥1% of patients included increased ALT (4.5%), increased AST (3%), pneumonitis (2.4%), diarrhea (2.4%), and rash (1.5%).

Dosage interruptions of WELIREG due to an adverse reaction occurred in 52% of patients. Of the patients who received WELIREG in combination with KEYTRUDA, 30% were ≥65 years old and 5% were ≥75 years old. Dose interruptions of WELIREG occurred in 57% of patients ≥65 years of age and in 49% of younger patients. Adverse reactions which required dosage interruption of WELIREG in ≥2% of patients included anemia (25%), fatigue (3.7%), increased ALT (3.5%), diarrhea (3.4%), increased AST (3.4%), COVID-19 (2.6%), hypoxia (2.5%), pyrexia (2.5%), musculoskeletal pain (2.1%), and rash (2.1%).

Dose interruptions of KEYTRUDA due to an adverse reaction occurred in 29% of patients. Adverse reactions which required dosage interruption of KEYTRUDA in ≥2% of patients included anemia (3.2%), diarrhea (3%), increased ALT (3%), and increased AST (2.5%).

Dose reductions of WELIREG due to an adverse reaction occurred in 34% of patients. Dose reductions of WELIREG occurred in 39% of patients ≥65 years of age and in 32% of younger patients. Adverse reactions which required dose reduction in ≥3% of patients included anemia (17%), hypoxia (3.5%), increased ALT (3.2%), and fatigue (3.1%).

The most common (≥25%) adverse reactions, including laboratory abnormalities, in patients who received WELIREG in combination with KEYTRUDA were decreased hemoglobin (95%), increased ALT (57%), fatigue (49%), increased AST (46%), decreased lymphocytes (38%), and increased alkaline phosphatase (29%).

About renal cell carcinoma

Renal cell carcinoma (RCC) is the most common type of kidney cancer, with about nine out of 10 kidney cancer diagnoses being RCC. In 2022, there were about 435,000 new cases of kidney cancer diagnosed and approximately 156,000 deaths from the disease worldwide. In the U.S., it is estimated there will be more than 80,000 new cases of kidney cancer diagnosed and more than 15,000 deaths from the disease in 2026. Renal cell carcinoma is about twice as common in men as in women. Cases of RCC might be discovered incidentally during imaging tests for other reasons. Clear cell renal cell carcinoma, which accounts for 70% of RCC diagnoses, is the most common subtype.

(Press release, Merck & Co, JUN 12, 2026, View Source [SID1234666606])

On June 12, 2026 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported detailed and updated clinical results from the registration-directed APEX clinical trial of bezuclastinib in patients with advanced systemic mastocytosis (AdvSM) demonstrating clinically meaningful results as measured by consensus criteria used to assess patient response. The company also shared a more detailed review of the pathobiology data in AdvSM patients from the APEX trial, reinforcing the rapid and deep clinical benefit bezuclastinib has demonstrated in these patients. The data will be presented at the 2026 European Hematology Association (EHA) (Free EHA Whitepaper) Congress taking place in Stockholm, Sweden, June 11-14, 2026.

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"We are excited to share updated and detailed results from the APEX trial in AdvSM patients, building upon previously announced results from bezuclastinib in the SUMMIT trial in NonAdvSM patients," said Andrew Robbins, Cogent’s President and Chief Executive Officer. "The results shown across these two trials demonstrate that a selective, potent KIT D816V inhibitor like bezuclastinib will have tremendous opportunity to become the new standard of care and change the lives of patients living with systemic mastocytosis. We are on track to complete the APEX NDA submission in the very near future and plan to launch bezuclastinib later this year in both systemic mastocytosis and GIST following FDA approval."

As of the updated data cutoff of March 31, 2026 in Part 2 of the APEX trial, 81 AdvSM patients were treated with 150 mg of bezuclastinib, including 57 patients with SM-AHN, 11 patients with ASM and 13 patients with MCL. The primary endpoint of response per mIWG-MRT-ECNM was assessed on 68 evaluable patients and showed 65% ORR (CR+CRh+PR+CI), including 57% of patients who achieved CR, CRh or PR as best response.

Additional highlights include:

Key secondary endpoint of response per pure pathological response (PPR) criteria was assessed on 81 patients which showed an 81% ORR (CR+CRh+PR).
Bezuclastinib demonstrated reversal of bone marrow pathobiology including rapid and deep reductions in aberrant CD25 and CD30 expression, normalization of mast cell morphology, normalization of bone marrow cellularity, and improvement in myelofibrosis.
Bezuclastinib demonstrated durable clinical activity and prolonged PFS with a 12-month PFS rate of 79% and a 12-month OS rate of 87%. Median duration of PFS and OS were immature at the time of the data cutoff.
Bezuclastinib achieved clear and clinically significant reductions in objective disease markers for these AdvSM patients:
Outcome measure Bezuclastinib
Proportion with ≥50% reduction in serum tryptase (n=80) 89 %
Proportion with ≥50% reduction in bone marrow mast cells or clearance of aggregates (n=80) 89 %
Proportion with ≥50% reduction in KIT D816V variant allele frequency (n=43) 91 %

"The results from the APEX trial demonstrate clear evidence of bezuclastinib’s rapid and deep clinical activity in patients with advanced systemic mastocytosis," said Daniel J. DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at the Dana-Farber Cancer Institute and Professor of Medicine, Harvard Medical School. "Coupled with an impressive safety and tolerability profile minimizing off-target toxicities that allows for long-term therapeutic dosing, bezuclastinib will become an important treatment option for patients with advanced SM."

Pathobiology Data

Cogent will also present new data highlighting the impact bezuclastinib has at a cellular level in patients with AdvSM. In the APEX study, bezuclastinib demonstrated robust improvement in disease pathology, with effects observed as early as eight weeks, including high PPR rates, improvement (including normalization) in bone marrow mast cell distribution, improvement in broader bone marrow characteristics and a majority of patients achieving normalization of serum tryptase. In addition, approximately one-third of patients treated with bezuclastinib achieved undetectable levels of KIT D816V VAF, signifying modification of the underlying AdvSM disease with bezuclastinib treatment.

APEX Safety and Tolerability

As of the data cutoff, bezuclastinib continued to be well-tolerated, with infrequent need for dose reduction or discontinuation for treatment-related adverse events (TRAEs). The most frequent TRAEs reported on bezuclastinib treatment were hair color change (31%), neutropenia (31%), altered taste (28%), thrombocytopenia (25%), and ALT/AST elevations (21%). The majority of transaminase elevations were of low grade, asymptomatic and reversible. Of the two patients who experienced Grade 3 transaminase elevation, one discontinued treatment and one remains on therapy following dose reduction.

The EHA (Free EHA Whitepaper) posters and presentation will be available on the Cogent website at: View Source

Bezuclastinib – Expanded Access Program

Working with the FDA, Cogent has established active Expanded Access Programs (EAPs) for U.S. patients SM or GIST who meet disease-specific criteria and could benefit from treatment with bezuclastinib or the combination of bezuclastinib and sunitinib. For more information please visit: View Source

(Press release, Cogent Biosciences, JUN 12, 2026, View Source [SID1234666607])