JNJ-88549968 (novel investigational agent for CALR-mutated MPN)

Current understanding

To be populated as evidence accumulates.

Evidence log

• 2026-09-24 — Selective dependency of CALR-mutant myeloproliferative neoplasms on TYK2 signaling.: cross-connection with deucravacitinib-tyk2-mpn: Parallel CALR-mutant-selective therapeutic strategies — TYK2 pathway dependency vs. direct anti-CALR agent. (novelty: 5)
• 2026 (rece — Mutant Calreticulin in MPN: Mechanistic Insights and Therapeutic Implications: cross-connection with inca033989-mpn: Both agents target the surface-exposed mutant CALR C-terminus of the CALR–MPL tetramer complex described in this review, validating the shared structural basis for CALR-neoepitope-directed therapy. (novelty: 3)
• May 1, 202 — Mutant calreticulin–directed immunotherapies in myeloproliferative neoplasms: cross-connection with inca033989-mpn: Review groups both as antibody-based mutant-CALR-directed immunotherapies leading the CALR neoepitope-targeting field. (novelty: 3)
• June 12-15 — Advancing Frontiers in Myeloproliferative Neoplasms - EHA 2025 Congress Review: cross-connection with inca035784-mpn: EHA 2025 review situates INCA035784 within the emerging CALR-mutation-directed therapeutic class alongside JNJ-88549968 and INCA033989. (novelty: 3)
• 2026-06-03 — A Phase 3 Study of INCA033989 Versus Best Available Therapy in Participants With Essential Thrombocythemia: cross-connection with inca033989-mpn: Both are CALR mutation–directed agents advancing in clinical development; INCA033989 is now in a Phase 3 ET trial, establishing the late-phase benchmark for mutant-CALR-targeted therapy. (novelty: 4)
• May 21, 20 — CALR Mutation–Directed Agents and Targeted Therapies Represent Key Research Avenue in MPN Management: cross-connection with inca033989-mpn: Both are CALR mutation–directed agents (antibody vs. small molecule) advancing the precision-targeting strategy against the CALR-mutant clone in MPN; review groups them as the leading CALR-directed therapeutic avenue. (novelty: 3)
• May 22, 20 — All Eyes Are on Novel Combination Therapies and Molecular Targets in MPN at ASH 2025: ASH 2025 review highlights mutant CALR-targeted therapies (including JNJ-88549968) as a major emerging molecular-target focus in MPN alongside maturing BET-inhibitor combination data. (novelty: 3)
• March 24, — ASH 2025: Myelofibrosis Roundup: cross-connection with inca033989-mpn: Both are mutant-CALR-directed investigational agents for MPN, representing the emerging class of neoepitope-targeted immunotherapies distinct from JAK inhibition. (novelty: 5)
• May 12, 20 — CALR Mutation–Directed Agents and Targeted Therapies Represent Key Research Avenue in MPN Management: cross-connection with inca033989-mpn: Both are investigational agents discussed within the emerging CALR/driver-mutation–directed therapy avenue for MPN; JNJ-88549968 is explicitly CALR-targeted while INCA033989 is part of the same precision-medicine pipeline. (novelty: 3)
• 2026-05-15 — Identification of MPN-specific Antigens and Anti-MPN TCRs in Myeloproliferative Neoplasm: cross-connection with tcr-based-immunotherapy-mpn: Mutant CALR is a leading candidate MPN-specific neoantigen; TCR discovery efforts may overlap with CALR-directed therapeutic targeting. (novelty: 4)
• 2026-04-14 — A Study of JNJ-88549968 for the Treatment of Calreticulin (CALR)-Mutated Myeloproliferative Neoplasms: Trial-early (Phase 1/2 dose-escalation/expansion): JNJ-88549968 entering first-in-human evaluation as monotherapy and in combination with ruxolitinib or momelotinib in CALR-mutated ET and MF, with primary objectives of safety, RP2D, and optimal dosing schedule — represents a CALR-mutation-directed therapeutic approach, a defined molecular subpopulation strategy. (novelty: 4)

Open questions

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