ramantamig (JNJ-5322) / J&J - LARVOL DELTA

Ramantamig (JNJ-79635322), a novel T-cell-engaging trispecific antibody targeting BCMA, GPRC5D, and CD3, in multiple myeloma models. (PubMed, Blood) - P1 | "The potent and selective antitumor activity of ramantamig, with a clonal depleting ability in vitro, ex vivo, and in vivo warrants clinical evaluation of its ability to induce durable responses in myeloma. Phase 1 clinical trials are ongoing for patients with relapsed/refractory MM (NCT05652335, NCT06768489)."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • GPRC5D

Updated Safety and Efficacy of Ramantamig (Ram; JNJ-5322) at the Recommended Phase 2 Dose (RP2D), Demonstrating Feasibility of Outpatient Dosing (OPD) in Relapsed/Refractory Multiple Myeloma (RRMM) (IMS 2026) - P1 | "The OPD cohort (subset of RP2D cohort) was to receive all doses outpatient, including SUD and tx dose 1; prophylactic tocilizumab (ppx toci) was recommended. Longer follow-up of Ram monotherapy at the RP2D continues to demonstrate deep, durable responses in TCE RRMM with no new safety signals. OPD at start of tx was feasible with low-gr, manageable CRS using ppx toci. The safety profile and convenient schedule (single SUD dose, fixed Q4W dosing) support use of this novel dual myeloma-antigen targeting Ab across practice settings."

Clinical • First-in-human • P2 data • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Pruritus • Thoracic Cancer

A Study of JNJ-79635322 in Combination With Daratumumab With or Without Lenalidomide for Multiple Myeloma, Newly Diagnosed AL Amyloidosis, and High-risk Smoldering Multiple Myeloma or JNJ-79635322 in Combination With Pomalidomide for Multiple Myeloma (clinicaltrials.gov) - P1 | N=240 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Jan 2029 ➔ Jun 2029

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

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

Updated efficacy and safety results of JNJ-5322, a novel, next-generation BCMA×GPRC5D×CD3 trispecific antibody, in patients with Relapsed/Refractory multiple myeloma (ASH 2025) - P1 | "In cohortswithout (received 100 mg Q4W) and with (received 100 mg Q4W/Q8W) prophylactic tocilizumab, CRSoccurred in 69.2% (gr 2, 15.4%) and 20.0% (gr 2, 0%), respectively. With longer follow-up in part 1 of the phase 1 trial, JNJ-5322 continues to demonstrateresponses comparable to CAR-T therapy (ORR 100.0%) that are durable and continue to deepen (≥CR77.8%), with a safety profile similar or improved compared with BsAbs targeting BCMA or GPRC5D. JNJ-5322 offers off-the-shelf, Q4W dosing and 1 SUD with low rates of gr 2 CRS that may enable an efficientapproach to dual antigen targeting via convenient administration and outpatient treatment. Thesefindings support further evaluation of JNJ-5322 in patients with RRMM."

Clinical • IO biomarker • Trispecific • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Pneumonia • Respiratory Diseases

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 (SOHO 2025) - P1 | "The first clinical data for JNJ-5322 showed a 100% ORR at RP2D in anti-BCMA/-GPRC5D-naïve patients with 1 SUD, with convenient Q4W dosing and manageable tolerability. CRS was mostly gr 1. The first data with JNJ-5322 suggest a paradigm shift, with preliminary efficacy similar to CAR T cells but as an off-the-shelf therapy intended for outpatient dosing."

Clinical • P1 data • Trispecific • Hematological Malignancies • Multiple Myeloma • Oncology

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

CR109234: 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: Aug 2028 ➔ Nov 2030

First-in-human • Trial completion date • Amyloidosis • Hematological Malignancies • Multiple Myeloma • Oncology

TRI Pro: A Study Evaluating the Prophylactic Use of Tocilizumab to Prevent Cytokine Release Syndrome With Ramantamig Administration in Participants With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P2 | N=230 | Recruiting | Sponsor: Janssen Research & Development, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology

Trilogy-4: A Study Comparing JNJ-79635322 and an Anti-B-cell Maturation Antigen (BCMA)xCD3 Bispecific Antibody in Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P3 | N=400 | Not yet recruiting | Sponsor: Janssen Research & Development, LLC

New P3 trial • Hematological Malignancies • Multiple Myeloma • Oncology

A Study of JNJ-79635322 in Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P2 | N=157 | Not yet recruiting | Sponsor: Janssen Research & Development, LLC

New P2 trial • Hematological Malignancies • Multiple Myeloma • Oncology

A Study of JNJ-79635322 in Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P2 | N=157 | Recruiting | Sponsor: Janssen Research & Development, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

TRIlogy-5: A Study Comparing JNJ-79635322 and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P3 | N=700 | Not yet recruiting | Sponsor: Janssen Research & Development, LLC

New P3 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Trilogy-4: A Study Comparing JNJ-79635322 and an Anti-B-cell Maturation Antigen (BCMA)xCD3 Bispecific Antibody in Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: Janssen Research & Development, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

TRIlogy-5: A Study Comparing JNJ-79635322 and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P3 | N=700 | Recruiting | Sponsor: Janssen Research & Development, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • 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=240 | Recruiting | Sponsor: Janssen Research & Development, LLC | N=140 ➔ 240 | Trial primary completion date: Nov 2027 ➔ Jan 2029

Enrollment change • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

TRIlogy-7: A Study of Ramantamig Plus Daratumumab Versus Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone (DVRd) or Daratumumab, Lenalidomide, and Dexamethasone (DRd) in Participants With NDMM For Whom Stem Cell Transplant is Not Planned (clinicaltrials.gov) - P3 | N=1000 | Not yet recruiting | Sponsor: Janssen Research & Development, LLC

New P3 trial • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

BTL-101, A FULLY HUMAN TRISPECIFIC BCMA×GPRC5D×CD3 T-CELL ENGAGER FOR THE TREATMENT OF MULTIPLE MYELOMA (EHA 2026) - "In myeloma co-cultures (H929, MM.1S, U266), BTL-101 mediated potent killing exceeding talquetamab+teclistamab, depleted dual- and single-antigen–positive cells (including low-to-intermediate BCMA expressers), and retained activity against BCMA- or GPRC5D-knockdown targets, consistent with efficacy under heterogeneous antigen expression...In 48-h PBMC–H929 co-cultures (E:T=5:1), BTL-101 showed higher-potency killing with attenuated cytokines and outperformed JNJ-79635322, SIM0500, and MBS-314...Summary/Conclusion BTL-101 demonstrates strong dual-antigen cytotoxicity with an attenuated cytokine profile and resistance to soluble BCMA. A Phase I/II clinical study is currently ongoing to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of BTL-101 in patients with relapsed/refractory multiple myeloma."

IO biomarker • Trispecific • Hematological Malignancies • Multiple Myeloma • CD69 • IL2RA • IL6

79635322MMY3001: A Phase 3 Study Comparing JNJ-79635322 and an anti-BCMAxCD3 Bispecific Antibodynin Participants with Relapsed or Refractory Multiple Myeloma (clinicaltrialsregister.eu) - P2/3 | N=53 | Not yet recruiting | Sponsor: Janssen Cilag International

New P2/3 trial • Hematological Malignancies • Multiple Myeloma • Oncology

TRI Pro: A Study Evaluating the Prophylactic Use of Tocilizumab to Prevent Cytokine Release Syndrome With Ramantamig Administration in Participants With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P2 | N=230 | Not yet recruiting | Sponsor: Janssen Research & Development, LLC

New P2 trial • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology

79635322MMY2001: A Phase 2 Study of JNJ-79635322 in Participants with RRMM (clinicaltrialsregister.eu) - P1/2 | N=28 | Not yet recruiting | Sponsor: Janssen Cilag International

New P1/2 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Talisman: A Study to Evaluate Preventive Treatments for GPRC5D-related Oral Events (clinicaltrials.gov) - P2 | N=210 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Apr 2029 ➔ May 2030 | Trial primary completion date: Apr 2026 ➔ May 2030

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

Updated Results of JNJ-5322, a Next-Generation BCMA×GPRC5D×CD3 Trispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma (BSH 2026) - No abstract available

Clinical • Trispecific • Hematological Malignancies • Multiple Myeloma

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