On June 14, 2026 Zymeworks Inc. (Nasdaq: ZYME), a biotechnology company managing a portfolio of licensed healthcare assets while developing a diverse pipeline of novel, multifunctional biotherapeutics, reported new clinical data from the dose-escalation portion of its ongoing Phase 1 study evaluating ZW191, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Gynaecological Cancers Congress 2026.

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The presentation highlights compelling anti-tumor activity in patients with platinum-resistant ovarian cancer (PROC) and in patients with endometrial cancer, including patients with both positive and negative FRα expression. The results further support the potential of ZW191 to address limitations of currently available and investigational FRα-targeted therapies and broaden treatment opportunities for patients with gynecologic cancers.

"We are highly encouraged by these data, which continue to demonstrate the differentiated profile of ZW191 and its potential to deliver meaningful clinical benefit across a broad population of patients with ovarian and endometrial cancers," said Sabeen Mekan, M.D., Senior Vice President and Chief Medical Officer of Zymeworks. "The response rate observed in FRα-positive ovarian cancer patients compares favorably with currently available therapies, while maintaining meaningful activity in patients with negative FRα expression. Together these encouraging data on durability, progression-free survival, and manageable safety profile further strengthen our confidence in the program and reinforce the ability of our ADC platform to generate differentiated therapeutics."

The analysis included efficacy data by FRα expression level from Part 1 of the ongoing Phase 1 study as of the March 9, 2026, data cutoff. FRα expression was assessed by immunohistochemistry and categorized using the Proportion and Staining Intensity, defined as the percentage of cells with 2+/3+ staining. Tumors were categorized as FRα-negative (<75%) or FRα-positive (≥75%).

Key Findings

Among response-evaluable PROC patients, ZW191 demonstrated a cORR of 78.6% in patients with FRα-positive tumors and 47.4% in patients with FRα-negative tumors across all dose levels. Disease control rates were 100.0% and 89.5%, respectively. Confirmed ORR in the overall PROC population was 58.8% across all dose levels studied and 65.2% in dose range of 6.4-9.6 mg/kg. These findings demonstrate meaningful anti-tumor activity across both FRα-positive and FRα-negative tumors as well as in the overall population.

In endometrial cancer patients with FRα-negative tumors, ZW191 demonstrated a cORR of 40.0% and a disease control rate of 80.0% across all doses evaluated.

Across both ovarian and endometrial cancer cohorts, responses were observed early and continued to deepen over time. Median duration of response was not reached at the time of data cutoff, and median progression-free survival was 7.6 months.

ZW191 continued to demonstrate a favorable tolerability profile. Treatment-emergent adverse events (TEAEs) occurred in 98% of patients, with grade ≥3 TEAEs reported in 55% of patients. The most common grade ≥3 adverse events were neutropenia (24%), anemia (20%), and thrombocytopenia (12%). Serious TEAEs occurred in 35% of patients, and 20% of patients discontinued treatment due to adverse events. Overall, the safety profile was manageable and consistent with continued clinical development.

"These results further demonstrate the potential of ZW191 to provide meaningful clinical benefit for patients with difficult-to-treat gynecologic cancers," said Kosei Hasegawa, M.D., Ph.D., Saitama Medical University International Medical Center and presenting author. "The robust activity observed in FRα-positive ovarian cancer, together with encouraging responses in tumors with lower FRα expression, suggests ZW191 could expand the benefit of FRα-targeted therapy to a broader patient population."

Part 2a, the dose optimization portion of the Phase 1 study evaluating ZW191 in ~60 PROC patients randomized to either 6.4 mg/kg every three weeks or 9.6 mg/kg every three weeks, has completed enrollment. Data from Part 2a will be presented at a future medical meeting and are expected to inform dose selection for potential future development.

ZW191’s differentiated profile, including its novel FRα-targeting antibody, ZD06519 payload, and high drug-to-antibody ratio, supports its potential to address key limitations of current therapies and broaden the applicability of FRα-targeted treatment approaches across multiple tumor types.

About ZW191

ZW191 is an antibody-drug conjugate engineered to target a protein called folate receptor-⍺ found in ~75% of high-grade serous ovarian carcinomas1, over 50% of endometrial cancers2,3 and ~70% of lung adenocarcinomas4. ZW191’s differentiated design strongly supports its ability to internalize into FR⍺-expressing cells with the potential to release bystander active topoisomerase-1 inhibitor (ZD06519), a novel proprietary payload developed by Zymeworks to kill tumor cells.

(Press release, Zymeworks, JUN 14, 2026, View Source [SID1234668728])

On June 14, 2026 CEL-SCI Corporation ("CEL-SCI" or the "Company") (NYSE American: CVM), a clinical stage cancer immunotherapy company, reported the pricing of a best-efforts offering of 2,500,000 shares of common stock at an offering price of $1.00 per share. Total gross proceeds from the offering, before deducting the placement agent’s fees and offering expenses, are expected to be $2.5 million. The offering is expected to close on June 16, 2026, subject to satisfaction of customary closing conditions.

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The Company intends to use the proceeds for the continued development of Multikine*, general corporate purposes, and working capital.

ThinkEquity is acting as the sole placement agent for the offering.

The securities will be offered and sold pursuant to a shelf registration statement on Form S-3 (File No. 333-288515), including a base prospectus, filed with the U.S. Securities and Exchange Commission (the "SEC") on July 3, 2025, and declared effective on August 12, 2025. The offering will be made only by means of a written prospectus. A final prospectus supplement and accompanying prospectus describing the terms of the offering will be filed with the SEC on its website at www.sec.gov. Copies of the prospectus supplement and the accompanying prospectus relating to the offering may also be obtained, when available, from the offices of ThinkEquity, 17 State Street, 41st Floor, New York, New York 10004.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

(Press release, Cel-Sci, JUN 14, 2026, View Source [SID1234668727])

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 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 The Menarini Group ("Menarini"), a leading international pharmaceutical and diagnostics company, and Stemline Therapeutics, Inc. ("Stemline"), a wholly-owned subsidiary of the Menarini Group focused on bringing transformational oncology treatments to cancer patients, reported that new data related to the pivotal Phase 3 SENTRY trial will be presented as a late-breaking oral[i] at The European Hematology Association (EHA) (Free EHA Whitepaper) 2026 Congress.

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SENTRY (NCT04562389), a pivotal Phase 3 trial, is a randomized, double-blind, placebo-controlled trial of 60 mg selinexor in combination with ruxolitinib in frontline myelofibrosis (MF) (n=353), versus ruxolitinib monotherapy. Conducted by Karyopharm Therapeutics, Inc., in collaboration with the Menarini Group, SENTRY was designed to evaluate two co-primary endpoints: spleen volume reduction of 35% or more (SVR35) and absolute total symptom score (Abs-TSS).

The trial met the first co-primary endpoint, demonstrating that patients who were treated with the combination of selinexor plus ruxolitinib achieved a clear and statistically significant improvement in SVR35, compared to patients who received ruxolitinib alone. These results highlight that the combination arm enabled rapid, deep and sustained spleen volume reductions.

selinexor plus ruxolitinib (n=235)

placebo + ruxolitinib (n=118)

SVR35 at week 12

49.4% (n=116)

20.3% (n=24)

SVR35 at week 24

49.8% (n=117)

28.0% (n=33)

SVR35 at week 36*

46.9% (n=97)

23.0% (n=23)

*Analysis conducted in those patients who completed a spleen assessment or discontinued the study prior to week 36

"Achievement of spleen reduction is the essential goal of myelofibrosis treatment. Importantly, the spleen reduction results seen in SENTRY were rapid, deep and durable, and associated with potential overall survival benefit for the patients receiving the combination," said Dr. Claire Harrison, Professor of Myeloproliferative Neoplasms and Deputy Chief Medical Officer at Guy’s and St. Thomas’ NHS Foundation Trust. "We are encouraged that these results represent a potential new therapeutic advance for our patients who are in dire need of better options."

Other key highlights include:

Absolute Total Symptom Score (Abs-TSS): The combination arm demonstrated a comparable benefit to ruxolitinib alone, with a 9.9 point improvement in Abs-TSS at week 24, in patients who received the combination, compared to a 10.9 point improvement in patients who received ruxolitinib alone. The difference across the two arms was not statistically significant, and the combination arm did not meet this second co-primary endpoint.
Overall Survival (OS): While these data were immature at the time of analysis, a promising early OS signal, a pre-specified secondary endpoint, was observed with the selinexor combination compared to ruxolitinib alone. The study showed a greater than 50% reduction in the risk of death for patients receiving the selinexor combination (HR 0.43).
Spleen Volume Reduction: Consistent SVR35 benefit was observed across prespecified subgroups. Notably, at week 24, superior spleen volume reduction was achieved by the selinexor combination, regardless of the ruxolitinib dose, including by patients receiving less than 15 mg of ruxolitinib per day.
Variant Allele Frequency (VAF) Reduction: This pre-specified exploratory endpoint, which is associated with SVR35, was observed in 32% of patients in the selinexor plus ruxolitinib arm at week 24 versus 23.9% of patients treated with ruxolitinib alone, indicating the combination’s potential for disease modification.
Safety and Tolerability: The combination demonstrated a manageable safety and tolerability profile consistent with the known profile of selinexor and ruxolitinib individually. No new safety signals were observed.
"The strength of the spleen response and the encouraging early overall survival data observed in the SENTRY study creates hope for a potential new treatment option for patients suffering from this devastating disease with dismal outcomes," said Elcin Barker Ergun, CEO of the Menarini Group. "Our dedication and commitment to bring transformational treatments to patients facing cancer is stronger than ever."

About Myelofibrosis (MF)

Myelofibrosis (MF) is a type of blood cancer that belongs to a group of diseases called Myeloproliferative Neoplasms (MPNs). These diseases are caused by the overgrowth of abnormal blood-forming cells in the bone marrow, which leads to the formation of scar tissue. This scarring makes it difficult for the body to produce healthy blood cells. The incidence of MF is rare, with only about one or two people diagnosed each year for every 100,000 individuals, and the median survival after diagnosis is six years. Additionally, for people living with MF, their quality of life can be compromised by symptoms including fatigue, an enlarged spleen, and low blood counts, all of which are caused by the disease.

(Press release, Menarini, JUN 14, 2026, View Source [SID1234668720])