LAVA-051 / LAVA Therap - LARVOL DELTA

MODULE 5: Chimeric Antigen Receptor (CAR) T-Cell Therapy and Other Novel Strategies for CLL (ASH 2024) - "This program is supported by educational grants from AstraZeneca Pharmaceuticals LP, BeiGene Ltd and Eli Lilly.Biological rationale for the investigation of CD19- directed CAR T-cell therapy for CLL Published efficacy and safety findings with lisocabtagene maraleucel (liso-cel) for R/R CLL from the Phase I/II TRANSCEND CLL 004 trial FDA approval of liso-cel for CLL previously treated with a BTK inhibitor and a Bcl-2 inhibitor; current clinical role and optimal patient selection Early findings with other CAR T-cell-based approaches (eg, liso-cel in combination with ibrutinib, brexucabtagene autoleucel, rapcabtagene autoleucel) for heavily pretreated CLL Antitumor activity observed with bispecific antibody therapy (eg, epcoritamab, NVG-111, LAVA-051) for CLL, including in patients with Richter's transformation Other promising agents and strategies under investigation for CLL"

Chronic Lymphocytic Leukemia • Oncology • Richter's Syndrome

Trial of LAVA-051 in Patients with Relapsed/refractory CLL, MM, or AML (clinicaltrials.gov) - P1 | N=16 | Terminated | Sponsor: Lava Therapeutics | Phase classification: P1/2 ➔ P1 | N=102 ➔ 16 | Active, not recruiting ➔ Terminated; The decision to discontinue LAVA-051clinical trial follows a recent review of the competitive landscape that has continued to evolve (Business decision). The decision is not due to safety concerns.

Enrollment change • Phase classification • Trial termination • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

LAVA Provides Business Updates and Reports First Quarter 2024 Financial Results (GlobeNewswire) - "LAVA-1207 – In Phase 1/2a (NCT05369000) – Next update H2 2024: Monotherapy: Enrolling patients at dose level 10. No ≥ Grade 2 Cytokine Release Syndrome (CRS) since the implementation of step dosing in Q1 2024; KEYTRUDA (pembrolizumab) Combination: Expecting to enroll the first patient in Q2 2024 in the LAVA-1207 + pembrolizumab dose-escalation arm (KEYNOTE-F73)....Research and development expenses were $6.0 million and $9.9 million for the quarters ended March 31, 2024 and 2023, respectively. The decrease was primarily due to lower pre-clinical and clinical trial expenses due to the discontinuation of LAVA-051, announced in June 2023, and reduced personnel-related expenses due to a reduction in research and development headcount in the second half of 2023."

Commercial • Trial status • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

LAVA Therapeutics Provides Business Update and Reports Second Quarter 2023 Financial Results (GlobeNewswire) - "Research and development expenses were $12.6 million and $8.4 million for the quarters ended June 30, 2023 and 2022, respectively, and $22.5 million and $15.9 million for the six months ended June 30, 2023 and 2022, respectively. The increase for both periods was primarily due to increased manufacturing scale-up costs and ongoing activities of the clinical trials. In the three months ended June 30, 2023, we have also included $1.4 million in expenses for discontinuance of the activities for LAVA-051."

Commercial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

Trial of LAVA-051 in Patients With Relapsed/Refractory CLL, MM, or AML (clinicaltrials.gov) - P1/2 | N=102 | Active, not recruiting | Sponsor: Lava Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

LAVA Therapeutics Provides Updates on Clinical Programs and Extends the Cash Runway (GlobeNewswire) - "LAVA Therapeutics N.V...announced its decision to rationalize its pipeline and prioritize its lead solid tumor program. The Company will continue to advance LAVA-1207, its Gammabody program designed to target the prostate-specific membrane antigen (PSMA) as well as earlier stage programs. The ongoing clinical trial of LAVA-051 targeting CD1d expressing hematological tumors, including multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and acute myeloid leukemia (AML) will be discontinued (NCT04887259)....The Company expects that the discontinuation of this LAVA-051 trial and its focus on the LAVA-1207 program will result in cost savings that will extend its cash runway further into 2026."

Financing • Trial termination • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

LAVA Therapeutics Provides Business Update and Reports Fourth Quarter and Year-End 2022 Financial Results (GlobeNewswire) - "Research and development expenses were $10.5 million and $6.6 million for the quarters ended December 31, 2022 and 2021, respectively, and $40.1 million and $36.9 million for the years ended December 31, 2022 and 2021, respectively. The higher quarterly and full-year expense was due to ongoing activities of the clinical trials for LAVA-051 and LAVA-1207, which were offset by a one-time license fee of $14.4 million triggered in the first quarter of 2021 by the IPO."

Commercial • Oncology

PHASE I DOSE ESCALATION OF LAVA-051, A NOVEL BISPECIFIC GAMMA-DELTA T-CELL ENGAGER (GAMMABODY™), IN RELAPSED/REFRACTORY HEMATOLOGICAL MALIGNANCIES (EHA 2022) - P1/2 | "Updated results will be presented at the congress. Conclusion LAVA-051 has been well tolerated early in dose escalation with on-mechanism pharmacodynamics consistent with Vγ9Vδ2-T cell engagement."

IO biomarker • P1 data • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Inflammation • Leukemia • Multiple Myeloma • Oncology • Pain

Bispecific Vγ9Vδ2-T and Type 1 NKT Cell Engager Lava-051 As First-in-Class Clinical Candidate to Target CD1d Expressing CLL, MM and AML (ASH 2021) - P1/2 | "In this study, we demonstrate that the CD1d-Vδ2 bsVHH LAVA-051 triggers activation of both type 1 NKT and Vγ9Vδ2-T cells, which translates directly into antitumor activity. Based on the expression of CD1d in CLL, MM, and AML, the strong preclinical activity of LAVA-051 against CD1d-expresssing tumors, and the favorable tolerability profile of the surrogate engager in NHP, LAVA-051 is currently evaluated in a first-in-human clinical Phase 1/2a study in patients with CD1d-expressing CLL, MM, or AML refractory to prior therapy (NCT04887259)."

Clinical • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Oncology • T Acute Lymphoblastic Leukemia

Lava-051, a Novel Bispecific Gamma-Delta T-Cell Engager (Gammabody), in Relapsed/Refractory MM and CLL: Pharmacodynamic and Early Clinical Data (ASH 2022) - P1/2 | "LAVA-051 has been well tolerated early in dose escalation with pharmacodynamics and early clinical signs reflective of its intended MoA. The differentiating importance of these pharmacodynamic parameters with any correlating preliminary antitumor activity will be further elucidated with continued dose escalation by the IV and SC route and in the determination of the RP2D and schedule."

Clinical data • IO biomarker • PK/PD data • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Inflammation • Leukemia • Leukopenia • Multiple Myeloma • Oncology • Pulmonary Disease • CD1D • CD69 • IL2RA • IL6

A bispecific T cell engager recruits both type 1 NKT and Vγ9Vδ2-T cells for the treatment of CD1d-expressing hematological malignancies. (PubMed, Cell Rep Med) - "Evaluation of a surrogate CD1d-γδ bsTCE in NHPs shows Vγ9Vδ2-T cell engagement and excellent tolerability. Based on these results, CD1d-Vδ2 bsTCE (LAVA-051) is now evaluated in a phase 1/2a study in patients with therapy refractory CLL, MM, or AML."

Journal • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • T Acute Lymphoblastic Leukemia

Trial of LAVA-051 in Patients With Relapsed/Refractory CLL, MM, or AML (clinicaltrials.gov) - P1/2 | N=102 | Recruiting | Sponsor: Lava Therapeutics | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Sep 2023 ➔ Sep 2024

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Oncology

LAVA Therapeutics Announces Updated Data from the Phase 1/2a Clinical Trial of LAVA-051 at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition (GlobeNewswire) - P1/2 | N=102 | NCT04887259 | Sponsor: Lava Therapeutics | "'To date, the Phase 1 data, as presented, showed that dose escalation of LAVA-051 up to 200 µg could be achieved in patients with R/R MM and CLL without evidence of dose-limiting toxicity and cytokine release syndrome (CRS). Often, such toxicities are a significant safety challenge for T-cell engager therapies,'...In addition to the favorable safety profile demonstrated as of the data cutoff (November 11, 2022), LAVA-051 showed predictable and linear pharmacokinetics and on-mechanism pharmacodynamic parameters consistent with Vγ9Vδ2-T cell engagement, including increasing occupancy of patient Vγ9Vδ2-T cells with LAVA-051 and consistent increases in the expression of T-cell activation markers."

P1 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

"$LVTX #ASH22 presentation likely to focus on sc LAVA-051 dosing. Not much on efficacy - 2 pts showed initial hints of activity but both caught covid #Jefferies22" (@JacobPlieth)

Clinical • Novel Coronavirus Disease

Mechanism of action of LAVA-051, a bispecific Vγ9Vδ2 T-cell engager (bsTCE), confirmed in the clinical setting (SITC 2022) - P1/2 | "Trial Registration NCT04887259 Ethics Approval This study has been approved by relevant ethics committees in the Netherlands, Spain and Italy (EUDRACT: 2020-004583-26). Informed consent was obtained from all patients prior to their participation."

Clinical • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Oncology • CD69 • IL2RA

Phase I dose escalation of LAVA-051, a novel bispecific gamma-delta T-cell engager (Gammabody), in relapsed/refractory hematological malignancies. (ASCO 2022) - P1/2 | "LAVA-051 has been well tolerated early in dose escalation with on-mechanism pharmacodynamics consistent with Vγ9Vδ2-T cell engagement."

IO biomarker • P1 data • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Inflammation • Leukemia • Multiple Myeloma • Oncology • Pain

LAVA Therapeutics to Present Updated Data from the Phase 1/2a Clinical Trial of LAVA-051 at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition (GlobeNewswire) - "LAVA Therapeutics N.V...announced the Company will present updated data including safety, pharmacodynamics and pharmacokinetics from the ongoing Phase 1/2a clinical trial of LAVA-051 during the 64th American Society of Hematology (ASH®) Annual Meeting and Exposition, taking place in New Orleans, Louisiana and virtually December 10-13, 2022. First data from subcutaneous administration will be presented, along with updates on the intravenous dosing-cohorts."

P1/2 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

Analyst Says This Small Cap Stock Might Be ’Game Changer’ In Bispecific T Cell Engagers Space (Yahoo Finance) - "The lead candidate, LAVA-051, is being evaluated in a Phase 1/2a study in multiple blood cancer settings; Initial Phase 1 data showed a favorable safety profile and early signs of clinical activity; Additional dose-escalation data is expected in 2H22, and initial Phase 2a data from the expansion cohorts in 1H23....LAVA is also evaluating LAVA-1207 in a Phase 1/2a study in metastatic castration-resistant prostate cancer (mCRPC) therapy, with initial data expected in 4Q22/1Q23; 'We believe Gammabody could be a game changer in the bispecific T cell engagers space. We currently project LAVA to generate risk-adjusted peak revenues of $391 million in 2032, growing from $4 million in 2026,' the analyst writes."

Commercial • P1 data • P1/2 data • P2a data • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Genito-urinary Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Prostate Cancer

LAVA Therapeutics to Present On-Mechanism Pharmacodynamics Data from the Phase 1/2a Clinical Trial of LAVA-051 at the Society for Immunotherapy of Cancer (SITC) 2022 Annual Meeting (GlobeNewswire) - "LAVA Therapeutics N.V...announced the Company will present data demonstrating on-mechanism pharmacodynamics for LAVA-051 in the clinic during the Society for Immunotherapy of Cancer’s 37th Annual Meeting, taking place in Boston, Massachusetts and virtually from November 8-12, 2022."

Preclinical • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

LAVA Therapeutics Provides Business Update and Reports Second Quarter Financial Results (GlobeNewswire) - "Recent Pipeline and Business Highlights: (i) LAVA-051: Additional clinical data are expected in the fourth quarter of 2022; (ii) LAVA-1207: Initial Phase 1 data readout is expected in the fourth quarter of 2022; (iii) LAVA-1266, a CD123 Gammabody for the treatment of hematologic malignancies: A CTA and/or IND is planned for late 2023."

IND • P1 data • Genito-urinary Cancer • Hematological Malignancies • Oncology • Prostate Cancer • Solid Tumor

LAVA Therapeutics Announces FDA IND Clearance for LAVA-051 for the Treatment of Hematologic Malignancies (GlobeNewswire) - "LAVA Therapeutics N.V...announced that the U.S. Food and Drug Administration (FDA) has cleared its investigational new drug (IND) application for LAVA-051, the Company’s lead product candidate for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL), multiple myeloma (MM) and acute myeloid leukemia (AML)....The Phase 1/2a clinical trial currently includes patients with relapsed or refractory CLL and MM. AML patients will be included later in the study..."

IND • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

Trial of LAVA-051 in Patients With Relapsed/Refractory CLL, MM, or AML (clinicaltrials.gov) - P1/2 | N=102 | Recruiting | Sponsor: Lava Therapeutics | N=55 ➔ 102

Enrollment change • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Oncology

"#ASCO22 Rewind: Dose-Escalation Data of LAVA-051 in #CLL & #MultipleMyeloma: https://t.co/R5AfCiP6EJ #HemOnc" (@OncologyTimes)

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

LAVA Therapeutics Highlights Encouraging Clinical Updates on Lead Program, LAVA-051, in Chronic Lymphocytic Leukemia and Multiple Myeloma Patients (GlobeNewswire) - P1/2 | N=55 | NCT04887259 | Sponsor: Lava Therapeutics | "LAVA Therapeutics...hosted a clinical update call focused on encouraging initial Phase 1/2a clinical data for LAVA-051 in patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) patients following poster presentations at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting held June 3-7, 2022, and the European Hematology Association (EHA) 2022 Congress, held June 9-12, 2022."

P1/2 data • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

LAVA Therapeutics to Present Initial Phase 1/2a Clinical Trial Dose Escalation Data of LAVA-051 in Chronic Lymphocytic Leukemia and Multiple Myeloma Patients at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - P1/2a | N=55 | NCT04887259 | Sponsor: Lava Therapeutics | "In addition to the favorable safety profile demonstrated to date, LAVA-051 showed predictable and linear pharmacokinetics and on-mechanism pharmacodynamic parameters consistent with Vγ9Vδ2-T cell engagement, including increasing occupancy of LAVA-051 on patient Vγ9Vδ2-T cells and consistent increases in the expression of T-cell activation markers. In these initial data, potential signs of clinical anti-tumor activity were also observed: a CLL patient experienced early enlargement and tenderness of several CLL-affected lymph nodes followed by a regression of those lymph nodes, resulting in a stable disease assessment after 12 weeks of therapy in combination with a reduction in the peripheral blood leukemic cell count over five cycles of LAVA-051; a MM patient showed a 23% reduction in myeloma cell-produced M-protein levels in the blood."

P1/2 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Multiple Myeloma • Oncology