JNJ-5322 / J&J - LARVOL DELTA

FIRST-IN-HUMAN STUDY OF JNJ-79635322 (JNJ-5322), A NOVEL, NEXT-GENERATION TRISPECIFIC ANTIBODY, IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: INITIAL PHASE 1 RESULTS (EHA 2025) - P1 | "In the largest data set for a next-generation dual antigen T-cell redirecting trispecific antibody, the first clinical data for JNJ-5322 showed a 100% ORR at the putative RP2D in anti-BCMA/-GPRC5D naïve patients, with convenient Q4W dosing. Tolerability appeared improved, including lower incidence and severity of GPRC5D-associated AEs vs anti-GPRC5D BsAbs and manageable grade 3/4 infection rates. CRS was mostly grade 1 (no grade ≥3 CRS) using 1 SUD."

Clinical • P1 data • Trispecific • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology

A Study of JNJ-79635322 in Combination With Daratumumab With or Without Lenalidomide or in Combination With Pomalidomide for Multiple Myeloma (clinicaltrials.gov) - P1 | N=140 | Recruiting | Sponsor: Janssen Research & Development, LLC | N=100 ➔ 140

Enrollment change • Hematological Malignancies • Multiple Myeloma • Oncology

First-in-human study of JNJ-79635322 (JNJ-5322), a novel, next-generation trispecific antibody (TsAb), in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Initial phase 1 results. (ASCO 2025) - P1 | "In the largest data set for a next-generation dual antigen T-cell redirecting TsAb, the first clinical data for JNJ-5322 showed a 100% ORR at the putative RP2D in anti-BCMA/-GPRC5D naïve patients, with convenient Q4W dosing. Tolerability appeared improved, including lower incidence and severity of GPRC5D-associated AEs vs anti-GPRC5D BsAbs and manageable gr 3/4 infection rates. CRS was mostly gr 1 (no gr ≥3 CRS) using 1 SUD."

Clinical • P1 data • Trispecific • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology

Early results from Johnson & Johnson's trispecific antibody show promising response in heavily pretreated multiple myeloma patients (PRNewswire) - P1 | N=180 | NCT05652335 | Sponsor: Janssen Research & Development, LLC | "Among the 36 patients who received the recommended phase 2 dose (RP2D), the overall response rate (ORR) was 86.1 percent. In the 27 patients who were naive to BCMA and GPRC5D directed therapies, the ORR was 100 percent at the RP2D. Findings were featured in an oral presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #7505). The study will also be featured as one of the six best abstracts during the Plenary Abstracts Session at the 2025 European Hematology Association (EHA) Congress (Abstract #S100)....The most common adverse event was cytokine release syndrome (CRS), occurring in 59 percent of patients, but no events were Grade 3 or higher. Twenty-eight percent of patients experienced Grade 3 or higher infections."

P1 data • Multiple Myeloma

A Study of JNJ-79635322 in Participants With Relapsed or Refractory Multiple Myeloma or Previously Treated Amyloid Light-chain (AL) Amyloidosis (clinicaltrials.gov) - P1 | N=180 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Apr 2025 ➔ Apr 2027

Trial primary completion date • Amyloidosis • Hematological Malignancies • Multiple Myeloma • Oncology

QLS4131, a proprietary T cell engager targeting both BCMA and GPRC5D for the treatment of multiple myeloma (AACR 2025) - P1 | "QLS4131 demonstrated a higher affinity for MM tumor cell lines when compared to JNJ-79635322, which is a clinical stage TCE targeting both BCMA and GPRC5D developed by Janssen Research & Development. In conclusion, the excellent efficacy, favorable PK, and safety profile support the potential of QLS4131 as a novel therapeutic agent to address the significant unmet needs in multiple myeloma. A Phase 1 dose-escalating study of QLS4131 in multiple myeloma is currently underway (NCT06500507)."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • GPRC5D • IL6

VTS105: A novel and potent BCMA/GPRC5D/CD3 trispecific T cell engager (TCE) for the treatment of hematologic malignancies and autoimmune diseases (AACR 2025) - "Recently approved T cell engagers targeting BCMA (e.g., Teclistamab) and GPRC5D (e.g., Talquetamab) have demonstrated clinical responses; however, high relapse rates persist due to suboptimal complete response (CR) rates and minimal residual disease (MRD)...VTS105 exhibits potent human PBMC-mediated tumor cell killing across various heterogeneous MM cell lines, outperforming competitors such as JNJ-79635322, IBI3003, and SCR-8572...Evaluations in this indication are currently underway. Currently VTS105 is advancing into CMC and toxicology studies, with an Investigational New Drug (IND) filing planned for the second half of 2026."

IO biomarker • Late-breaking abstract • Trispecific • Hematological Malignancies • Multiple Myeloma • Oncology • GPRC5D

A Study of JNJ-79635322 in Combination With Daratumumab or Pomalidomide for Multiple Myeloma (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: Janssen Research & Development, LLC

New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology

A Study of JNJ-79635322 in Participants With Relapsed or Refractory Multiple Myeloma or Previously Treated Amyloid Light-chain (AL) Amyloidosis (clinicaltrials.gov) - P1 | N=180 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Apr 2026 ➔ Apr 2027

Trial completion date • Trispecific • Amyloidosis • Hematological Malignancies • Multiple Myeloma • Oncology

A Study of JNJ-79635322 in Participants With Relapsed or Refractory Multiple Myeloma or Previously Treated Amyloid Light-chain (AL) Amyloidosis (clinicaltrials.gov) - P1 | N=170 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: May 2025 ➔ Apr 2026

Trial completion date • Trispecific • Amyloidosis • Hematological Malignancies • Multiple Myeloma • Oncology

Characterization of JNJ-79635322, a Novel BCMAxGPRC5DxCD3 T-Cell Redirecting Trispecific Antibody, for the Treatment of Multiple Myeloma (ASH 2023) - P1 | "JNJ-79635322 is a potential first-in-class trispecific antibody targeting BCMA and GPRC5D with the ability to deplete dual and single target expressing MM clones in preclinical studies vitro and in vivo. A Phase 1 dose-escalating study of JNJ-79635322 in myeloma patients is ongoing (NCT05652335)."

Trispecific • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • GPRC5D

A Study of JNJ-79635322 in Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=169 | Recruiting | Sponsor: Janssen Research & Development, LLC | N=90 ➔ 169

Enrollment change • Trispecific • Hematological Malignancies • Multiple Myeloma • Oncology

A Study of JNJ-79635322 in Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: Janssen Research & Development, LLC

New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology