briquilimab (JSP191) / Amgen, Jasper Therap - LARVOL DELTA

Hematopoietic stem cell transplantation using briquilimab (Anti-CD117 Antibody-Conditioning), immunosuppression and TCRαβ+ T-cell/CD19+ B-cell depleted haploidentical grafts in patients with fanconi anemia: An approach without irradiation, busulfan and calcineurin inhibitors. (ASH 2025) - "FA patients have renal abnormalities and are prone to renal toxicities.Therefore, avoiding calcineurin inhibitors increases the renal safety during transplant.Objective: To reduce acute and long-term treatment-related toxicities, we have developed a first of itskind treatment intended to improve the safety of allo-HSCT using: 1) a TBI- and busulfan-freeconditioning regimen consisting of briquilimab, rabbit ATG (rATG - Thymoglobulin), fludarabine,cyclophosphamide and rituximab - briquilimab is a monoclonal antibody (mAb) that targets humanCD117 to clear host HSCs from their niches enabling blood and immune reconstitution with minimaltoxicity with other agents being used for immune suppression to prevent immunologic rejection; 2)transplantation of TCRαβ+ T-cell/CD19+ B-cell hematopoietic grafts - a stem cell therapy that enhancesdonor hematopoietic and immune reconstitution while decreasing GvHD; and 3) pharmacokineticanalysis for briquilimab, rATG and fludarabine to..."

Clinical • Acute Graft versus Host Disease • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Genetic Disorders • Graft versus Host Disease • Immunology • Transplant Rejection • Transplantation • CD34 • KIT • NCAM1

BEACON Cohort 8 & Cohort 9 Internal Investigation Concluded (GlobeNewswire) - "In response, Jasper’s internal investigation included: switching all US patients to a new lot of drug product for the remainder of their doses on study to determine if drug product played a role, a comprehensive review of all manufacturing records, drug handling, site training/ logs and data handling; recovery and testing by Jasper and independent labs of drug product samples from across the supply chain; a review of all US sites and all US patients, including protocol adherence patient medical histories, patient screening and all pharmacokinetics, pharmacodynamics and efficacy data, and assembling a KOL panel to review the internal investigation findings, including full patient dossiers, which provided its input and conclusions from the findings....'BEACON data expected in Q1 2026 that will enable us to select final doses for the Phase 2b CSU study, planned to commence mid-2026.'"

New P2b trial • P1/2 data • Trial status • Chronic Spontaneous Urticaria

Radiation and Busulfan-Free Hematopoietic Stem Cell Transplantation Using Briquilimab (JSP191) Anti-CD117 Antibody-Conditioning, Transient Immunosuppression and TCRαβ+ T-Cell/CD19+ B-Cell Depleted Haploidentical Grafts in Patients with Fanconi Anemia (ASH 2023) - "Objective: To reduce acute and long-term treatment-related toxicities, we have developed a first of its kind treatment intended to improve the safety of allo-HSCT through: 1) a TBI- and busulfan-free conditioning regimen consisting of briquilimab, rabbit ATG (rATG - Thymoglobulin), fludarabine, cyclophosphamide and rituximab - briquilimab (formerly called JSP191) is a monoclonal antibody (mAb) that targets human CD117 to deplete host HSCs enabling blood and immune reconstitution with minimal toxicity with the other agents being used for transient immune suppression to prevent immunologic rejection; 2) transplantation of TCRαβ+ T-cell/CD19+ B-cell hematopoietic grafts - a stem cell therapy that enhances donor hematopoietic and immune reconstitution while decreasing GvHD; and 3) a pre- and post-transplant monitoring protocol to maximize engraftment. All three patients in the Phase 1b portion of the study show early safety and efficacy of this approach. Briquilimab was..."

Clinical • Acute Graft versus Host Disease • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Genetic Disorders • Graft versus Host Disease • Hematological Disorders • Immunology • Transplant Rejection • Transplantation • CD34 • KIT • NCAM1

ETESIAN Study Design and Preliminary Data Summary (GlobeNewswire) - "The preliminary data includes the results from 14 participants, 8 receiving a single dose of 180mg briquilimab and 6 receiving placebo, who completed at least 6 weeks of allergen challenge testing following initial dosing with investigational product. Compared to baseline, briquilimab reduced the allergen induced LAR (measured by the mean maximum percentage fall in FEV1 (%Max FEV1) and fall in area under the FEV1 time response curve (AUC)) at both 6 and 12 weeks. Patients who received briquilimab showed an improvement in the LAR %Max FEV1 of 10.4% at 6 weeks and 8.7% at 12 weeks compared to baseline and an improvement in the LAR AUC of 25.4% at 6 weeks and 23.3% at 12 weeks."

P1/2 data • Asthma • Immunology

Final Results from Phase 1 Study of Briquilimab, an Anti-CD117 Monoclonal Antibody, in Combination with Low Dose Irradiation and Fludarabine Conditioning, Shows Durable Remissions in Older Adults with Acute Myeloid Leukemia in Complete Remission and Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation (ASH 2023) - "GVHD prophylaxis was tacrolimus, sirolimus, and mycophenolate mofetil. These results demonstrate that targeting CD117 with briquilimab together with TBI/Flu as a novel conditioning regimen is safe, well-tolerated, facilitates full donor myeloid chimerism, and sustained clearance of MRD in older adults with AML in CR and MDS without TP53 undergoing NMA AHCT."

Clinical • Combination therapy • P1 data • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Oncology • Septic Shock • Transplantation • DNMT3A • KIT • TP53

Adding CD117 Antibody to Alemtuzumab, Low Dose Total Body Irradiation (TBI), and Sirolimus for Matched Related Donor (MRD) Hematopoietic Cell Transplant (HCT) in Sickle Cell Disease (SCD): Initial Results (ASH 2024) - "13 patients with homozygous sickle (HbSS) and 1 patient with sickle-beta 0 thalassemia (age range 5-34 years) received briquilimab 0.6 mg/kg on day -11, alemtuzumab 1.0 mg/kg divided over day -7 through -3, 300 cGy TBI on day -2, sirolimus to target trough level of 10 ng/mL starting on day -1, and unmanipulated filgrastim mobilized peripheral blood stem cells on day 0 (10.8-20.4 x 10e6 CD34 cells/kg and 1.9-7.5 x 10e8 CD3 cells/kg). Longer follow-up is needed to detail the trajectory of myeloid and CD3 chimerism. Strategies to increase myeloid and CD3 chimerism are warranted."

Acne Vulgaris • Beta-Thalassemia • Genetic Disorders • Graft versus Host Disease • Hematological Disorders • Hepatology • Immunology • Sickle Cell Disease • Transplantation • CD34 • KIT

Evaluation of Bone Marrow in Fanconi Anemia Patients Treated with Briquilimab Antibody-Based Conditioning and TCRαβ+ T-Cell/CD19+ B-Cell Depleted Haploidentical Grafts (ASH 2024) - P1/2 | "We also observed correction of BMF with DNA-damage resistance in all seven patient BM cells challenged with 10 nM and 50 nM mitomycin C (MMC), and a significant increase in colony counts (P= 0.0238) in patients over 24-52 weeks post-HSCT. Notably, this was accomplished without the use of busulfan or total body irradiation, which is extremely toxic to FA patients. However, additional analyses and assessment of more samples with longer follow-up time points are needed and underway to further understand the full effects of this treatment on the BM microenvironment."

Clinical • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Hematological Disorders • Inflammation • Pediatrics • ANGPT1 • CD34 • CSF2 • FANCA • FANCC • FANCG • FLT3LG • KIT

Allogeneic Hematopoietic Cell Transplantation with Briquilimab (JSP191)-Based Conditioning for GATA2 Deficiency (ASH 2024) - No abstract available

Transplantation

Highlights for Third Quarter 2025 and Recent Weeks (GlobeNewswire) - "Jasper plans to report final conclusions from the investigation in the fourth quarter of 2025, supported by a key opinion leader panel that will review findings and provide clinical and chemistry, manufacturing and controls recommendations for integration into the planned Phase 2b CSU study; Continued to enroll additional patients across the 240mg/180mg Q8W and 240mg Q8W cohorts of the BEACON study, and continued to enroll CSU and CIndU patients in the open-label extension (OLE) study as they rolled off the BEACON and SPOTLIGHT studies. Jasper expects that the additional data from these BEACON cohorts and from the OLE study, anticipated in the first half of the first quarter of 2026, should be adequate to complete dose selection for the planned Phase 2b CSU study, which is now expected to commence mid-2026."

Clinical data • Trial status • Chronic Spontaneous Urticaria • Urticaria

Human KIT Antibody Briquilimab Diminishes Anaphylactic Responses in Mice Expressing Chimeric Human-Mouse KIT. (PubMed, Allergy) - No abstract available

Journal • Preclinical

SPOTLIGHT: A Dose Escalation Trial of Safety, Pharmacokinetic/Pharmacodynamic and Preliminary Clinical Activity of Briquilimab in Adult Patients With Chronic Inducible Urticaria (CIndU) Who Remain Symptomatic Despite Treatment With H1- Antihistamines (clinicaltrials.gov) - P1/2 | N=27 | Terminated | Sponsor: Jasper Therapeutics, Inc. | Trial completion date: Nov 2025 ➔ Jul 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Nov 2025 ➔ Jul 2025; Enrollment was completed and primary efficacy endpoint was completed. Study was terminated before safety follow up was completed due to changes in company priorities and not related to safety concerns

Trial completion date • Trial primary completion date • Trial termination • Dermatology • Immunology • Urticaria

Initial Results from SPOTLIGHT, a Phase 1b/2a Dose Escalation Study of the anti-c-Kit Briquilimab Antibody in Adults with Chronic Inducible Urticaria (CIndU) Who Remain Symptomatic Despite H1-Antihistamine Treatment [WITHDRAWN] (EADV 2025) - No abstract available

Clinical • P1/2 data • Dermatology • Immunology • Urticaria • KIT

Briquilimab Demonstrates Rapid, Clinically Meaningful Reduction in Disease Activity in Adults with Chronic Spontaneous Urticaria (CSU): Results from a Phase 1b/2a Study [WITHDRAWN] (EADV 2025) - No abstract available

Clinical • P1/2 data • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

A Phase 2b, Randomized Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Briquilimab for the Treatment of Chronic Spontaneous Urticaria (CSU) [WITHDRAWN] (EADV 2025) - No abstract available

Clinical • P2b data • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

A Phase 2, Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Briquilimab in Adults with Chronic Urticaria (Trial in Progress) [WITHDRAWN] (EADV 2025) - No abstract available

Clinical • P2 data • Dermatology • Immunology • Urticaria

Briquilimab, an Anti-Human CD117 Antibody, Treats Low-Calcemic Vitamin D3 Analog MC903-Induced Dermatitis in Mouse Model Expressing Chimeric Human/Mouse CD117 [WITHDRAWN] (EADV 2025) - No abstract available

Preclinical • Dermatitis • Dermatology • Immunology • KIT

Briquilimab, an Anti-Human CD117 Antibody, Prevents Epicutaneous Oxazolone-Induced Features of Dermatitis in Mouse Model Expressing Chimeric Human/Mouse CD117 [WITHDRAWN] (EADV 2025) - No abstract available

Preclinical • Dermatitis • Dermatology • Immunology • KIT

Briquilimab Potently Inhibits Stem Cell Factor (SCF)/c-Kit Signaling and Induces Mast Cell Apoptosis (EADV 2025) - "Briquilimab's potent inhibition of SCF/c-Kit signaling and rapid induction of MC apoptosis** may provide a promising treatment option for MC-mediated diseases."

CASP3 • CASP7 • CD34

Briquilimab, an Anti-c-Kit Antibody, Induces Durable Depletion of Mast Cells (MCs) Across Multiple Tissues in Mice Expressing Chimeric Human/Mouse CD117 (c-Kit) (EADV 2025) - "Although HSCs/MCPs return to baseline in BM by 4 weeks post-briquilimab in this model, repopulation of tissue- resident MCs to baseline appears to take significantly longer, and the rate of MC repopulation may vary by tissue. These data suggest that briquilimab can induce durable MC depletion across multiple tissues, and offer insights into potential dosing intervals for MC-mediated diseases."

Preclinical • CD27 • FLT3 • KIT

A Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Safety and Efficacy of Briquilimab in Participants With Allergic Asthma (clinicaltrials.gov) - P1 | N=17 | Terminated | Sponsor: Jasper Therapeutics, Inc. | N=30 ➔ 17 | Active, not recruiting ➔ Terminated; Sponsor Decision - terminated due to changes in company priorities and not related to safety concerns.

Enrollment change • Trial termination • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Irradiation- and busulfan-free stem cell transplantation in Fanconi anemia using an anti-CD117 antibody: a phase 1b trial. (PubMed, Nat Med) - P1/2 | "Here we report a phase 1b clinical trial in patients with FA and bone marrow failure, evaluating safety and efficacy of briquilimab-based conditioning in combination with rabbit anti-thymocyte globulin, cyclophosphamide, fludarabine and rituximab immunosuppression and T cell receptor (TCR)αβ+ T cell-depleted and CD19+ B cell-depleted haploidentical HSCT. These data demonstrate the broad potential of this protocol in maintaining HSCT efficacy while reducing toxicity. The phase 2 trial is ongoing (ClinicalTrials.gov identifier: NCT04784052 )."

Journal • P1 data • Acute Graft versus Host Disease • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Immunology • Mucositis • Transplantation • DRD • KIT

JSP191 Antibody Targeting Conditioning in SCID Patients (clinicaltrials.gov) - P1/2 | N=23 | Terminated | Sponsor: Jasper Therapeutics, Inc. | N=40 ➔ 23 | Trial completion date: Jun 2028 ➔ Jul 2025 | Active, not recruiting ➔ Terminated; Sponsor Decision - terminated due to changes in company priorities and not related to safety concerns.

Enrollment change • Trial completion date • Trial termination • Transplantation • IL7R • JAK3 • PTPRC • RAG1

Study to Assess the Use of JSP191 in Matched Unrelated Donor Transplantation for Chronic Granulomatous Disease (CGD) (clinicaltrials.gov) - P1 | N=7 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Active, not recruiting | N=38 ➔ 7

Enrollment change • Enrollment closed • Immunology • Primary Immunodeficiency • Transplantation

A Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Safety and Efficacy of Briquilimab in Participants With Allergic Asthma (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Jasper Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | Trial primary completion date: Mar 2025 ➔ Aug 2025

Enrollment closed • Trial primary completion date • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Allogeneic Hematopoietic Stem Cell Transplantation With Briquilimab-Based Conditioning in Participants With GATA2 Deficiency (clinicaltrials.gov) - P2 | N=7 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting

Enrollment closed • Bone Marrow Transplantation • Myelodysplastic Syndrome • Transplantation