INCA033989 / Incyte - LARVOL DELTA

QIAGEN and Incyte Announce Precision Medicine Collaboration to Develop Companion Diagnostics for Patients With Mutant CALR-expressing Myeloproliferative Neoplasms (MPNs) (Businesswire) - "QIAGEN N.V...and Incyte...announced a new global collaboration to develop a novel diagnostic panel to support Incyte’s extensive portfolio of investigational therapies for patients with myeloproliferative neoplasms (MPNs), a group of rare blood cancers, including Incyte’s monoclonal antibody INCA033989, targeting mutant calreticulin (mutCALR), which is being developed in myelofibrosis (MF) and essential thrombocythemia (ET). Under the terms of the Master Collaboration Agreement with Incyte, QIAGEN will develop a multimodal panel using next-generation sequencing (NGS) technology for detecting clinically relevant gene alterations in hematological malignancies."

Diagnostic • Licensing / partnership • Essential Thrombocythemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

Positive Late-Breaking Data for Incyte’s First-in-Class mutCALR-targeted therapy INCA033989 in Essential Thrombocythemia Presented at EHA2025 (Yahoo Finance) - P1 | N=230 | NCT06034002 | P1 | N=225 | NCT05936359 | Sponsor: Sponsor: Incyte Corporation | "Results as of April 4, 2025, showed rapid and durable normalization of platelet counts across all dose levels, with a trend toward improved responses in higher doses (>400 mg), in patients with ET treated with INCA033989. Notably, 86% of patients at doses 400 mg and above achieved a complete or partial hematologic response, with the majority (82%) of patients achieving complete response. Eighty-nine (89) percent of evaluable patients (34/38) showed a reduction in mutCALR VAF from baseline....Additional data from the INCA033989 study in patients with myelofibrosis will be submitted for presentation at a future medical meeting. Discussions with regulatory authorities are planned with the goal to initiate a Phase 3 study by early 2026."

Late-breaking abstract • New P3 trial • P1 data • Essential Thrombocythemia

Incyte Announces Multiple Presentations, Including New Late-Breaking Data for its mutCALR-Directed Monoclonal Antibody (INCA033989), Accepted for Presentation at EHA 2025 (Businesswire) - "Late-breaking oral presentation will highlight new data from a trial of INCA033989, an anti-mutant calreticulin (mutCALR)-directed monoclonal antibody, in patients with essential thrombocythemia (ET); Incyte to host an in-person analyst and investor event highlighting the mutCALR data at EHA on Sunday, June 15, 2025, from 6:00 - 7:30 a.m. EDT (12:00 - 1:30 p.m. CEST)."

Clinical data • Chronic Graft versus Host Disease • Essential Thrombocythemia • Follicular Lymphoma • Marginal Zone Lymphoma • Myelofibrosis • Myeloproliferative Neoplasm

INCA33989 IS A NOVEL, FIRST IN CLASS, MUTANT CALRETICULIN-SPECIFIC MONOCLONAL ANTIBODY THAT DEMONSTRATES SAFETY AND EFFICACY IN PATIENTS WITH ESSENTIAL THROMBOCYTHEMIA (ET) (EHA 2025) - P1 | "INCA33989-101 (NCT05936359) and -102 (NCT06034002) are phase 1, first-in-human, multicenter, open-label studies evaluating INCA33989 in patients with ET or myelofibrosis (monotherapy or in combination with ruxolitinib). INCA33989 monotherapy in ET patients who were resistant/intolerant to prior therapy was well-tolerated with no DLTs, and 98% of patients remain on treatment. Rapid and durable normalization of blood counts and reduction of mutCALR VAF was observed in most patients, and the potential for disease modification was evidenced by 25% of patients achieving an early PMR."

Clinical • Late-breaking abstract • Anemia • Cardiovascular • Essential Thrombocythemia • Fatigue • Hematological Disorders • Infectious Disease • Myelofibrosis • Myeloproliferative Neoplasm • Neutropenia • Pancreatitis • Respiratory Diseases • Thrombocytopenia • Thrombocytosis • Thrombosis • CALR

A Study to Evaluate INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms (clinicaltrials.gov) - P1 | N=230 | Recruiting | Sponsor: Incyte Corporation | N=140 ➔ 230

Enrollment change • Monotherapy • Essential Thrombocythemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • CALR

Incyte Reports 2024 Fourth Quarter and Year-End Financial Results, Provides 2025 Financial Guidance and Highlights 2025 R&D Milestones (Businesswire) - "Key Recent Company Updates: In December 2024, Incyte shared additional data from its BET inhibitor (INCB057643) in patients with relapsed or refractory myelofibrosis and other advanced myeloid neoplasms at the 2024 ASH Annual Meeting....Incyte plans to initiate a Phase 3 monotherapy study in the post Jakafi patient population in 2025. In December 2024, the supplemental Biologics License Application (sBLA) submission for retifanlimab (Zynyz) in advanced/metastatic squamous cell anal carcinoma was filed with the FDA with approval anticipated in the second half of 2025....The Phase 1 studies evaluating mutCALR in myelofibrosis (MF) and essential thrombocythemia (ET) and JAK2V617Fi in MF are ongoing and enrolling patients. Initial proof of concept data for both studies are anticipated in 2025."

FDA approval • FDA filing • New P3 trial • P1 data • Anal Carcinoma • Essential Thrombocythemia • Myelofibrosis • Squamous Cell Carcinoma

INCA033989: the first shot on goal for MPNs? (PubMed, Blood) - "In this issue of Blood, Reis et al1 identify a monoclonal antibody, INCA033989, that selectively targets mutant calreticulin (mutCALR) in myeloproliferative neoplasms (MPNs), inhibiting its oncogenic activity without affecting normal hematopoiesis."

Journal • Hematological Disorders • Myeloproliferative Neoplasm • Oncology • CALR

Incyte Reports 2024 Third Quarter Financial Results and Provides Updates on Key Clinical Programs (Businesswire) - "Additional Pipeline Updates: A bioequivalence study of ruxolitinib extended-release (XR) is enrolling. The data are anticipated in the first half of 2025....Trials of ruxolitinib twice daily (BID) with BETi and zilurgisertib are ongoing. Additional data for BETi and zilurgisertib are anticipated in the fourth quarter of 2024. The Phase 1 studies evaluating mCALR and JAK2V617Fi are ongoing and enrolling patients. Initial data for both studies are anticipated in 2025."

Clinical data • P1 data • Myelofibrosis • Myeloproliferative Neoplasm

Selective targeting of mutated calreticulin by the monoclonal antibody INCA033989 inhibits oncogenic function of MPN. (PubMed, Blood) - "INCA033989 reduced the pathogenic self-renewal of mutCALR-positive disease-initiating cells in both primary and secondary transplantations, illustrating its disease-modifying potential. In summary, we describe a novel mutCALR-targeted therapy for MPNs, a monoclonal antibody that selectively inhibits the oncogenic function of MPN cells without interfering with normal hematopoiesis."

Journal • Hematological Disorders • Myeloproliferative Neoplasm • Oncology • Thrombocytosis • Transplantation • CALR • CD34

Incyte Reports 2024 Second Quarter Financial Results and Provides Updates on Key Clinical Programs (Businesswire) - "Jakafi: Net product revenues for the second quarter 2024 of $706 million (+3% Y/Y): Paid demand increased 9% in the second quarter of 2024 versus the same quarter in the prior year, with growth across all indications. Year over year net product revenue growth was lower than paid demand growth due to higher channel inventory levels at the end of the second quarter of 2023 versus the same period of 2024. Channel inventory at the end of the second quarter of 2024 was within the normal range....The Phase 1 studies evaluating mCALR and JAK2V617Fi are ongoing and enrolling patients. Initial data for both studies is anticipated in 2025."

P1 data • Sales • Graft versus Host Disease • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera

EFFICACY OF INCA033989 IN CHRONIC AND ADVANCED FORMS OF CALRDEL52 AND CALRINS5 MYELOPROLIFERATIVE NEOPLASMS (MPN) MODELS (EHA 2024) - "Together, our results show INCA efficiently targets CALRdel52 and CALRins5 cells in chronic and advancedforms of MPNs, demonstrating therapeutic potential and warranting further investigation."

Clinical • Metastases • Acute Myelogenous Leukemia • Essential Thrombocythemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • Oncology • Thrombocytosis • CALR • CD34 • HSP90AA1

Incyte to Highlight Data From its Oncology Portfolio at the 2024 ASCO Annual Meeting and EHA2024 Congress (Businesswire) - "Incyte...announced that several abstracts featuring data from its oncology portfolio will be presented at the upcoming 2024 American Society of Clinical Oncology (ASCO) Annual Meeting held May 31 - June 4 in Chicago, and at the European Hematology Association 2024 (EHA2024) Congress held on June 13-16 in Madrid, Spain, and virtually."

Clinical data • Myelofibrosis • Myeloproliferative Neoplasm • Solid Tumor

A Study to Evaluate INCA033989 Administered in Participants With Myeloproliferative Neoplasms (clinicaltrials.gov) - P1 | N=140 | Recruiting | Sponsor: Incyte Corporation | Not yet recruiting ➔ Recruiting

Enrollment open • Essential Thrombocythemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • CALR

Incyte Reports 2023 Third Quarter Financial Results and Provides Updates on Key Clinical Programs (Businesswire) - "The Phase 1 study evaluating INCA033989 (mCALR) is ongoing and enrolling patients. In October, we announced the development of a new program targeting the JAK2V617F mutation, which is present in 55-60% of myelofibrosis (MF) and essential thrombocythemia (ET) patients, and in 95% of polycythemia vera (PV) patients. INCB100658 is a small molecule inhibitor, targeting the JAK2V617F mutation and we expected to file the IND by year-end 2023."

IND • Trial status • Essential Thrombocythemia • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera

A Study to Evaluate INCA033989 Administered in Participants With Myeloproliferative Neoplasms (clinicaltrials.gov) - P1 | N=140 | Not yet recruiting | Sponsor: Incyte Corporation

New P1 trial • Essential Thrombocythemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • CALR

A Study to Evaluate INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms (clinicaltrials.gov) - P1 | N=225 | Recruiting | Sponsor: Incyte Corporation

Combination therapy • Monotherapy • New P1 trial • Myeloproliferative Neoplasm • Oncology • CALR

Incyte Reports 2022 Fourth Quarter and Year-end Financial Results, Provides 2023 Financial Guidance and Updates on Key Clinical Programs (Businesswire) - "Parsaclisib + ruxolitinib in myelofibrosis (MF): A Phase 3 trial evaluating parsaclisib as an add-on to ruxolitinib in suboptimal responders is ongoing with results expected at the end of 2023....Zilurgisertib (ALK2) ± ruxolitinib in MF: Updated combination data with ruxolitinib are expected later this year....INCA33989 (mCALR) in MF and essential thrombocythemia (ET): INCA33989 is expected to enter the clinic later this year."

New P1 trial • P2 data • P3 data • Essential Thrombocythemia • Hematological Disorders • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Oncology