MT-8421 / Molecular Templates - LARVOL DELTA

MT-8421 Displays Acceptable Safety Profile in First-in-Human Trial for Advanced Solid Tumors (OncLive) - P1 | N=15 | NCT06034860 | Sponsor: Molecular Templates, Inc. | "The maximum tolerated dose (MTD) was not reached. Across all treated patients (n = 15), the most frequently reported treatment-emergent adverse effects (TEAEs), including immune-mediated AEs, were pyrexia/chills (40%; n = 6), infusion-related reactions (IRRs; 33%; n = 5), fatigue (27%; n = 4), pruritus (27%; n = 4), rash (20%; n = 3), nausea (20%; n = 3), and muscle/joint pain (20%; n = 3). Grade 3 TEAEs were infrequent. No grade 4 or 5 TEAEs were reported. Notably, grade 1/2 cytokine release syndrome (CRS) was observed in 7% of patients (n = 1); no grade 3 CRS occurred."

Cytokine release syndrome • P1 data • Oncology • Solid Tumor

MT-8421-001: Study of MT-8421 as Monotherapy and in Combination With Nivolumab in Patients With Selected Advanced Solid Cancer Types (clinicaltrials.gov) - P1 | N=15 | Terminated | Sponsor: Molecular Templates, Inc. | Active, not recruiting ➔ Terminated; Sponsor Termination

Trial termination • Cervical Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Melanoma • Mesothelioma • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • MSI • PD-1 • PD-L1

MT-8421-001: Study of MT-8421 as Monotherapy and in Combination With Nivolumab in Patients With Selected Advanced Solid Cancer Types (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: Molecular Templates, Inc. | Recruiting ➔ Active, not recruiting | N=200 ➔ 15 | Trial completion date: Oct 2026 ➔ Oct 2024 | Trial primary completion date: Jul 2026 ➔ Oct 2024

Combination therapy • Enrollment change • Enrollment closed • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Cervical Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Melanoma • Mesothelioma • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • MSI • PD-1 • 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

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 (Businesswire) - P1 | N=200 | NCT06034860 | Sponsor: Molecular Templates, Inc. | "MT-8421 (CTLA-4 ETB)....Three patients were dosed in the first cohort of the phase I study at 32 mcg/kg. No grade 3 or grade 4 drug-related adverse events were observed. Two patients have stable disease and remain on study at cycle 4 and cycle 2, respectively (1 cycle = 4 weeks). One patient had disease progression at the end of cycle 2; The two patients in stable disease showed peripheral depletion of Tregs and significant elevations in IL-2 while on therapy; Enrollment is on-going in the second cohort of 48 mcg/kg for the phase I study of MT-8421."

P1 data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

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

Molecular Templates Announces First Patient Dosed in Phase 1 Trial Evaluating MT-8421, a Novel Engineered Toxin Body Targeting CTLA-4, in Advanced Solid Tumors (GlobeNewswire) - "Molecular Templates...announced that the first patient has been dosed in the Phase 1 clinical trial evaluating MT-8421, a novel engineered toxin body targeting CTLA-4, for the treatment of advanced solid tumors. The Phase 1 study is a multi-center open-label, dose-escalation, dose-expansion, and...will enroll adult patients with tumors where CTLA-4 inhibitors have been proven to provide benefit and in other select tumor types known to frequently have an immune rich tumor microenvironment ('TME'). This will include melanoma, hepatocellular carcinoma (HCC), non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), Microsatellite Instability-High (MSI-H) / Mismatch Repair Deficient (dMMR) cancer, mesothelioma, esophageal squamous cell carcinoma (ESCC), squamous cell carcinoma of the head and neck (SCCHN), urothelial carcinoma, and cervical carcinoma."

Trial status • Cervical Cancer • Esophageal Squamous Cell Carcinoma • Hepatocellular Cancer • Melanoma • Mesothelioma • Microsatellite Instability • Non Small Cell Lung Cancer • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Study of MT-8421 as Monotherapy and in Combination With Nivolumab in Patients With Selected Advanced Solid Cancer Types (clinicaltrials.gov) - P1 | N=200 | Recruiting | Sponsor: Molecular Templates, Inc.

Combination therapy • Metastases • Monotherapy • New P1 trial • Cervical Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Melanoma • Mesothelioma • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • MSI • PD-1 • PD-L1

Molecular Templates, Inc. Reports Second Quarter 2023 Financial Results and Business Update (GlobeNewswire) - "First-in-human phase I study for MT-8421 targeting CTLA-4-expressing regulatory T-cells ('Tregs') in the tumor microenvironment ('TME') for elimination without affecting Tregs in the periphery to begin in 3Q 2023."

New P1 trial • Oncology • Solid Tumor

"$MTEM Molecular Templates Announces IND Acceptance by FDA for MT-8421 ETB Program Targeting CTLA-4 https://t.co/2iMSJKF1Mq" (@stock_titan)

Molecular Templates Announces IND Acceptance by FDA for MT-8421 ETB Program Targeting CTLA-4 (GlobeNewswire) - "Molecular Templates...has received clearance by the United States Food and Drug Administration ('FDA') following review of its Investigational New Drug Application ('IND') to proceed for clinical testing of its novel MT-8421 ETB program targeting CTLA-4 in patients with relapsed/refractory solid tumors previously exposed to checkpoint inhibitors....MTEM expects to initiate a first-in-human phase I study with MT-8421 by mid-year 2023 at a starting dose of 32 mcg/kg."

IND • New P1 trial • Oncology • Solid Tumor

Engineered toxin body targeting CTLA-4 (MT-8421) depletes Tregs in the tumor microenvironment and synergizes with αPD-1 to enhance T cell immunity (SITC 2022) - "The lack of prolonged peripheral CTLA-4 blockade may reduce toxicity as seen with antibody approaches to CTLA-4. Clinical studies are expected to start in 2023."

Biomarker • Tumor microenvironment • Oncology • CD4 • CD8

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 American Association of Cancer Research (AACR) Annual Meeting 2022 Highlight Potential of ETB Approach (GlobeNewswire) - "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...CTLA-4-targeted ETBs are designed to preferentially deplete regulatory T cells (Tregs), via a direct cell kill mechanism of action that is independent of effector cells, in the tumor microenvironment (TME) to improve efficacy and reduce the toxicity associated with CTLA-4 targeted antibodies. In a transgenic mouse model expressing human CTLA-4 and bearing syngeneic subcutaneous tumors, CTLA-4 ETB treatment depleted Tregs in the TME."

Preclinical • Oncology

A CTLA-4 targeted ETB for Treg depletion shows favorable preclinical efficacy and safety (AACR 2022) - "Overall, the candidate ETB is a unique CTLA-4 targeting modality that is designed to deplete Tregs selectively and directly in the tumor, spare CD8+ CTLs, and represents an alternative treatment option to traditional blocking antibodies. Development activities are underway to support the upcoming IND application."

Preclinical • Oncology • CD4 • CD8 • CTLA4

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

[VIRTUAL] Preclinical characterization of a novel CTLA-4-targeted ETB for direct Treg depletion (AACR 2021) - "Utilizing human CTLA-4 knock in mouse syngeneic tumor models, we show that CTLA-4-ETB-A can reduce the % Tregs and increase the CD8/Treg ratio in the TME. Preclinical assessment of safety and pharmacodynamic signals are underway in cynomolgus studies."

IO biomarker • Preclinical • Oncology • CD8 • CTLA4