MT-6402 / Molecular Templates - LARVOL DELTA

MT-6402-001: Study of MT-6402 in Subjects With Advanced Solid Cancer That Expresses PD-L1 (clinicaltrials.gov) - P1 | N=64 | Terminated | Sponsor: Molecular Templates, Inc. | N=138 ➔ 64 | Active, not recruiting ➔ Terminated; Terminated by Sponsor

Enrollment change • IO biomarker • Metastases • Trial termination • Head and Neck Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

MT-6402-001: Study of MT-6402 in Subjects With Advanced Solid Cancer That Expresses PD-L1 (clinicaltrials.gov) - P1 | N=138 | Active, not recruiting | Sponsor: Molecular Templates, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: May 2026 ➔ Oct 2024 | Trial primary completion date: Apr 2025 ➔ Oct 2024

Enrollment closed • IO biomarker • Metastases • Trial completion date • Trial primary completion date • Head and Neck Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Molecular Templates, Inc. Reports Second Quarter 2024 Financial Results and Corporate Update (GlobeNewswire) - "Upcoming Milestones for 2H 2024: (i) Additional updates from the MT-6402 low PD-L1+ HNSCC and high PD-L1+ solid tumor expansions studies in 3Q24; (ii) Additional updates from the MT-8421 dose escalation study in 3Q24; (iii) MT-0169 Phase 1 study initiation in CD38+ hematological malignancies..."

P1 data • Trial initiation date • Leukemia • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck

First-in-human, dose escalation and expansion study of MT-6402, a novel engineered toxin body (ETB) targeting PD-L1, in patients with PD-L1 expressing relapsed/refractory advanced solid tumors: Interim data (AACR 2024) - "These results describe a novel approach to checkpoint modulation by MT-6402 with targeted cell killing and altered tumor immunophenotype, particularly in HLA-A*02/CMV+ pts. These results provide rationale for continued development of MT-6402."

Clinical • Metastases • P1 data • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4 • CD8 • HLA-A • IL2 • TNFA

Molecular Templates Presents Interim Data from MT-6402 Phase I Study in Patients with PD-L1+ Solid Tumors at the 2024 American Association for Cancer Research (AACR) Annual Meeting; Monotherapy Activity in Checkpoint-Experienced Head and Neck Cancer Patients Observed Through Novel Immuno-oncology Mechanism (GlobeNewswire) - P1 | N=138 | NCT04795713 | Sponsor: Molecular Templates, Inc. | "MT-6402 has been well tolerated with no drug-related Grade 4 or Grade 5 adverse events observed. MT-6402 acts uniquely from other approved checkpoint agents. MT-6402 depletes immunosuppressive PD-L1+ immune cells and tumor cells, activates a T-effector phenotype, and remodels the tumor microenvironment to restore T-cell surveillance of the tumor....An early monotherapy efficacy signal in head and neck squamous cell carcinoma (HNSCC) was identified. Nine patients with recurrent and metastatic heavily pre-treated and checkpoint-experienced HNSCC were treated in the phase I dose escalation of which two patients have confirmed durable PRs....Tumor reductions were observed in other patients including an unconfirmed PR."

P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Molecular Templates, Inc. Reports Fourth Quarter 2023 Financial Results and Business Update (GlobeNewswire) - "Key Milestones for 2024: Clinical data on MT-6402 expansion cohorts in low and high PD-L1+ HNSCC patients; Clinical data from dose escalation study for MT-8421 Treg depleting agent in solid tumors....MTEM will present an abstract, 'First-in-human, dose escalation and expansion study of MT-6402, a novel engineered toxin body (ETB) targeting PD-L1, in patients with PD-L1 expressing relapsed/refractory advanced solid tumors: Interim Data', Tuesday, April 9, 2024, 9am – 12:30pm ET (Section 48, Poster #19, Abstract #CT191), at the American Association for Cancer Research ('AACR') Annual Meeting taking place in San Diego, CA."

P1 data • Cervical Cancer • Esophageal Squamous Cell Carcinoma • Hepatocellular Cancer • Lung Cancer • Mesothelioma • Microsatellite Instability • Non Small Cell Lung Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Molecular Templates, Inc. Provides Interim Update (GlobeNewswire) - P1 | N=138 | NCT04795713 | Sponsor: Molecular Templates, Inc. | "Molecular Templates, Inc...today provided an update on its programs...The Part A dose escalation of the phase I study for MT-6402 has been completed with no Grade 4 or Grade 5 drug-related adverse events observed to date...In the Part A dose escalation, 10 patients with head and neck squamous cell cancer (HNSCC) were treated at doses of 63, 83, or 100 mcg/kg. Two of these patients were not evaluable for the cycle 1 dose-limiting toxicity ('DLT') period or for efficacy because of early progression and came off study after receiving only one or two doses of MT-6402, respectively...The three other HNSCC patients enrolled in the Part A dose escalation had stable disease of 6, 4, and 2 months, respectively....The Part B dose expansion portion of the phase I study in patients with high PD-L1 is ongoing."

P1 data • Trial status • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Molecular Templates, Inc. Reports Third Quarter 2023 Financial Results and Business Update (GlobeNewswire) - "MTEM expects to provide a year-end update and periodic updates on MT-6402, MT-8421, and MT-0169 throughout 2024."

Clinical • Oncology

MT-6402, an engineered toxin body (ETB) targeting PD-L1: Interim efficacy and safety data. (ASCO 2023) - P1 | "MT-6402 utilizes three PD-L1-targeted and unique MOAs: direct cell-kill, reduced immunosuppression, and increased immunorecognition. As of Feb 2023, 5 dose cohorts have completed. MT-6402 was well tolerated without CLS or payload-derived toxicity as is observed with traditional immunotoxins and ADCs, respectively."

Clinical • IO biomarker • Cytomegalovirus Infection • Lung Cancer • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • HLA-A • IFNG • IL2 • TNFA

Molecular Templates to Present on Phase I Dose Escalation Study of MT-6402 at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - P1 | N=138 | NCT04795713 | Sponsor: Molecular Templates, Inc. | "Molecular Templates...announced today the presentation of a poster at the American Society of Clinical Oncology ('ASCO') Annual Meeting...The poster will highlight interim efficacy and safety data on MT-6402, MTEM’s ETB program designed to activate T-cells through direct cell-kill of immunosuppressive PD-L1+ immune cells....MT-6402 continues to demonstrate pharmacodynamic effects and monotherapy activity in heavily pre-treated checkpoint therapy experienced patients. To date, no instances of capillary leak syndrome or other manifestations of innate immunity have been observed with any next-generation ETB."

P1 data • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer

Molecular Templates, Inc. Reports First Quarter 2023 Financial Results and Business Update (GlobeNewswire) - P1 | N=138 | NCT04795713 | Sponsor: Molecular Templates, Inc. | "Highlights from the on-going Phase I study: As of May 2023, patients have been treated across six dose escalation cohorts of 16 mcg/kg, 24 mcg/kg, 32 mcg/kg, 42 mcg/kg, 63 mcg/kg and 83 mcg/kg in the MT-6402 study of patients with relapsed/refractory tumors that express PD-L1. Dose escalation continues with patients being recruited at 100 mcg/kg....One patient in cohort 5 (63 mcg/kg) with metastatic squamous cell nasopharynx carcinoma with disease progression after radiation therapy, chemotherapy, and pembrolizumab had a Partial Response ('PR') (RECIST) with a 63% reduction in the index lesion after cycle 2. The patient remains in a confirmed response at cycle 7."

P1 data • Head and Neck Cancer • Lung Cancer • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer

Engineered Toxin Bodies (ETBs): Clinical stage immunotoxins with a safer and differentiated profile (AACR 2023) - "Three ETBs (MT-0169, MT-5111, and MT-6402) are currently in clinical studies across different targets (CD38, HER2, PD-L1) and across hematologic malignancies, solid tumor, and immuno-oncology indications. ETBs can also deliver additional payloads to drive unique biology like the alteration of tumor immunophenotype. Here we describe three active clinical stage programs with encouraging safety and efficacy data that represent a transformation of the immunotoxin landscape into a more viable therapeutic approach to target validated as well as typically intractable clinical cancer targets."

Clinical • Hematological Malignancies • Oncology • Solid Tumor • HER-2

Altering tumor immunophenotypes with PD-L1 engineered toxin bodies (AACR 2022) - P1 | "These cytokines overlap with cytokine signatures observed after dosing MT-6402 in HLA:A*02 patients. Preclinical assessment of the safety profile of candidates is ongoing and further development is slated for 2021."

IO biomarker • Oncology • Solid Tumor • PD-L1

Engineered toxin bodies specific for TROP2 positive cancers (SABCS 2022) - "Three ETBs are in clinical development (MT-5111 targeting HER2, MT-0169 targeting CD38, and AST enabled MT-6402 targeting PD-L1)...TROP2 is a clinically validated target in metastatic triple-negative breast cancer (mTNBC) and other cancers such as metastatic urothelial carcinoma (mUC) using antibody drug conjugate (ADC) therapies such as sacituzumab govitecan (Trodelvy®)...In vivo, TROP2 targeted ETBs demonstrate good tolerability in a murine HCC1806 triple-negative breast cancer xenograft model and significantly reduce tumor burden relative to vehicle control. These pre-clinical in vitro and in vivo data suggest AST enabled Trop2 targeted ETBs have the potential to deplete Trop2 positive malignancies through multiple unique mechanisms of action."

Breast Cancer • HER2 Breast Cancer • Oncology • Triple Negative Breast Cancer • Urothelial Cancer • HER-2 • TACSTD2 • TROP2

First-in-human, dose escalation and expansion study of MT-6402, a novel engineered toxin body (ETB) targeting PD-L1, in patients with PD-L1 expressing relapsed/refractory advanced solid tumors: Interim Data (SITC 2022) - P1 | "Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal."

Clinical • IO biomarker • P1 data • Oncology • Solid Tumor • CCL2 • CD14 • CD8 • CXCL8 • HLA-A • IL2 • TNFA

A clinical stage engineered toxin body (ETB) targeting PD-L1 (MT-6402) induces peripheral pharmacodynamic responses unique from PD-L1 monoclonal antibodies (SITC 2022) - P1 | "Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal."

Clinical • IO biomarker • PK/PD data • Oncology • Solid Tumor • CD14 • HLA-A • ITGAM

First-in-human dose escalation and expansion study of MT-6402, a novel engineered toxin body (ETB) targeting PD-L1, in patients with PD-L1 expressing relapsed/refractory advanced solid tumors: Interim data. (ASCO 2022) - P1 | "Dose escalation is ongoing. The results hold promise for development of MT-6402 for solid tumors, including in the R/R setting. Data for additional patients will be presented at the meeting."

Clinical • IO biomarker • P1 data • Cytomegalovirus Infection • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCL2 • CD14 • CD8 • HLA-A • IL2

Phase I study of MT-6402, a novel engineered toxin body (ETB) targeting PD-L1, in patients with PD-L1 expressing advanced solid tumors (AACR 2022) - "These results describe a novel approach to checkpoint modulation, leveraging direct PD-L1 cell kill and antigen seeding technology by the ETB. The results support further dose escalation and hold promise for development of MT-6402 for solid tumors, including in the R/R setting."

Clinical • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD14 • HLA-A

Molecular Templates, Inc. to Present Interim Data and Host R&D Day at The Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting (GlobeNewswire) - "Molecular Templates, Inc...announced that it will present four abstracts and host an in-person Research & Development Day, Friday, November 11, 2022, at The Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting which will be held November 8 – 12, 2022 at the Boston Convention and Exhibition Center in Boston, MA. The R&D Day event will include in-person presentations by the senior leadership team of Molecular Templates reviewing the technology of next-generation ETBs, the clinical highlights informing development strategies, and the data presented at SITC around its PD-L1 targeting MT-6402 and CTLA-4 targeting MT-8421 programs."

Clinical data • Oncology • Solid Tumor

Molecular Templates, Inc. Reports Second Quarter 2022 Financial Results (GlobeNewswire) - "MTEM expects to provide periodic updates on MT-6402, MT-8421, MT-5111, and MT-0169 throughout 2022. Data presentations are expected at the 2022 Society for Immunotherapy of Cancer (SITC) and 2022 San Antonio Breast Cancer Symposium (SABC). MTEM expects to file an IND for MT-8421 (CTLA-4 ETB) at year-end 2022. MTEM is advancing momentum on the development of its additional ETB candidates (TROP2, TIGIT, and BCMA)."

Clinical data • IND • Oncology • Solid Tumor

Molecular Templates’ Presentations at the 2022 ASCO Annual Meeting Demonstrate Advancement in PD-L1 and HER2 Programs (GlobeNewswire) - "Molecular Templates...announces highlights from the two poster presentations on its clinical programs that were presented on June 5th at the 2022 American Society of Clinical Oncology (ASCO) annual meeting....Pharmacodynamic (PD) effects including PD-L1+ dendritic cell and monocyte cell depletion and T cell activation have been observed in the majority of patients. The extent and timing of these PD effects appear dose-related with patients in the 24 mcg/kg cohort generally showing a more rapid and profound PD effect....Higher MT-5111 doses (6.75 mcg/kg and above) appear to saturate circulating soluble HER2 (sHER2) receptors with patients’ HER2 levels stabilizing or decreasing at higher doses."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Engineered toxin bodies (ETBs) targeting Trop2 (AACR 2022) - "This MOA allows for the intracellular processing of antigen and subsequent surface MHC-I presentation required for activation of a re-directed T lymphocyte response and the capacity to restore a functional immune clearance program against the tumor.Three ETBs are in clinical development (MT-5111 targeting HER2, MT-0169 targeting CD38, and AST enabled MT-6402 targeting PD-L1). AST enabled Trop2 targeted ETBs are capable of delivering viral antigens for multiple HLA types and inducing cytokine secretion and T-cell mediated killing in a co-culture assay of Trop2 target cells with antigen matched HLA type and antigen specific T-cells. These pre-clinical in vitro data suggest AST enabled Trop2 targeted ETBs have the potential to deplete Trop2 positive malignancies through multiple unique mechanisms of action."

Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer • HER-2 • TROP2

Molecular Templates’ Presentations at the American Association of Cancer Research (AACR) Annual Meeting 2022 Highlight Potential of ETB Approach (GlobeNewswire) - P1 | N=138 | NCT04795713 | Sponsor: Molecular Templates, Inc. | "Molecular Templates...reviews highlights from the six poster presentations on its pipeline programs that were presented at the American Association of Cancer Research (AACR) Annual Meeting 2022....Twelve patients with PD-L1+ relapsed/refractory disease have been treated to date across two dose cohorts: 16 mcg/kg (n=6) and 24 mcg/kg (n=6). Pharmacodynamic (PD) effects including monocyte and myeloid-derived suppressor cell depletion and T cell activation have been observed in the majority of patients....One patient in the first cohort with non-small cell lung cancer (NSCLC) (osseous non-measurable disease only) that had progressed after prior checkpoint therapy (PD-1 and CTLA-4) showed qualitative reduction in tumor burden."

P1 data • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Molecular Templates to Host Webinar on a Unique Approach to Immuno-Oncology for Solid Tumors (GlobeNewswire) - "Molecular Templates, Inc...announced that it will host a webinar on a unique approach to immuno-oncology for solid tumors on Wednesday, April 13, 2022 at 8:00 am Eastern Time...The webinar will feature a presentation from medical expert David Spigel, MD, of the Sarah Cannon Research Institute, who will discuss Molecular Templates’ program, MT-6402 (targeting PD-L1), and the implications of the Phase 1 data as it relates to treating patients with a variety of PD-L1-expressing solid tumors. MT-6402 is the first of the Company’s 3rd generation ETBs to enter the clinic."

Clinical • P1 data • Oncology • Solid Tumor

Molecular Templates, Inc. Reports Fourth Quarter 2021 Financial Results (GlobeNewswire) - "'MT-6402 with additional data expected throughout 2022. We continue dose finding for the MT-5111 and MT-0169 programs with clinical data expected this year. We plan to file an IND in 2H22 for our CTLA-4 program and are moving forward with our earlier stage pipeline of ETBs in preclinical development targeting TIGIT, TROP-2, and BCMA'"

Clinical data • IND • P1 data • Preclinical • Hematological Malignancies • Lung Cancer • Lymphoma • Multiple Myeloma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor