MT-5111 / Molecular Templates - LARVOL DELTA

MT-5111_001: Study of MT-5111 in HER2-positive Solid Tumors (clinicaltrials.gov) - P1 | N=50 | Terminated | Sponsor: Molecular Templates, Inc. | N=178 ➔ 50 | Trial completion date: May 2025 ➔ Apr 2023 | Recruiting ➔ Terminated; Study Reprioritization

Enrollment change • Metastases • Trial completion date • Trial termination • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

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

A phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+ tumors: interim results (SABCS 2022) - "MT-5111 is a 55kD engineered toxin body targeting HER2 in solid tumors that binds to an epitope distinct from trastuzumab and pertuzumab, offering potential combination strategies with other HER2-targeting agents. sHER2 biomarker data is expected for all cohorts with PK correlation and 23µg/kg safety and efficacy data. PK profile of MT-5111, C1D1 values"

Clinical • P1 data • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • HER2 Breast Cancer • Oncology • EGFR • HER-2

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

Molecular Templates, Inc. to Present Interim Results on MT-5111 at the 45th Annual San Antonio Breast Cancer Symposium (SABCS) and Participate at the 64th American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - "Molecular Templates...announced that they will present a poster on interim clinical results for the MT-5111 program at the San Antonio Breast Cancer Symposium (SABCS) which will take place December 6 - December 10, 2022 at the Henry B. Gonzalez Convention Center in San Antonio, TX. Molecular Templates will also participate in one-on-one meetings at the 64th American Society of Hematology (ASH) Annual Meeting which will take place December 10 - December 13, 2022 at the Ernest N. Morial Convention Center in New Orleans, LA. In-person and virtual meetings may be scheduled directly with Molecular Templates."

P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

A phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+tumors: Interim results. (ASCO-GI 2022) - P1 | "Background : MT-5111 is a 55 kD engineered toxin body (ETB) targeting HER2 in solid tumors that binds to an epitope distinct from trastuzumab and pertuzumab, offering potential combination strategies with other HER2-targeting agents. MT-5111 was well tolerated with no clinically significant immuno/cardiotoxicity. Dose escalation is ongoing and is nearing levels expected to be required for efficacious exposure."

Clinical • P1 data • Biliary Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • HER-2

A phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+ tumors: Interim results. (ASCO 2022) - P1 | "Background: MT-5111 is a 55kD engineered toxin body (ETB) targeting HER2 in solid tumors that binds to an epitope distinct from trastuzumab and pertuzumab, offering potential combination strategies with other HER2-targeting agents. MT-5111 is well tolerated to-date with no clinically significant immuno/cardiotoxicity. Dose escalation is ongoing at a dose of 13µg/kg, expected to be required for efficacious exposure."

Clinical • P1 data • Breast Cancer • Cardiovascular • Esophageal Adenocarcinoma • Esophageal Cancer • Fatigue • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

Interim results of a phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+tumors (SABCS 2021) - P1 | "MT-5111 is a 55 kD ETB targeting HER2 in solid tumors that binds to an epitope distinct from trastuzumab and pertuzumab, offering potential combination strategies with other HER2-targeting agents. MT-5111 was well tolerated with no clinically significant immuno- or cardiotoxicity. Dose escalation is ongoing and nearing levels expected to be required for efficacious exposure."

Clinical • P1 data • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Oncology • HER-2

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

Assessing safety and tolerability of MT-5111 in patients with HER2+ tumors (YouTube) - "Brian A. Van Tine, MD, PhD...discusses results from a Phase I study (NCT04029922) of MT-511, a novel shiga toxin-conjugated recombinant fusion protein targeting HER2 in HER2-expressing solid tumors."

Interview • Video

Molecular Templates' Presentations at the 2022 ASCO Annual Meeting Demonstrate Advancement in PD-L1 and HER2 Programs (GlobeNewswire) - "A phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+ tumors: interim results...Daniel Ahn...Serum concentration of MT-5111 showed predictable and dose-proportional increasing exposure in the last three evaluable dose cohorts."

MT-5111_001: Study of MT-5111 in HER2-positive Solid Tumors (clinicaltrials.gov) - P1 | N=140 | Recruiting | Sponsor: Molecular Templates, Inc. | Phase classification: P1/2 ➔ P1

Phase classification • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

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

MT-5111_001: Study of MT-5111 in HER2-positive Solid Tumors (clinicaltrials.gov) - P1/2 | N=178 | Recruiting | Sponsor: Molecular Templates, Inc. | Phase classification: P1 ➔ P1/2

Phase classification • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

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

89Zr-Trastuzumab PET/CT in Subjects With Previously Treated HER2-Positive Solid Tumors Scheduled to Receive Treatment With MT-5111 (clinicaltrials.gov) - P2; N=0; Withdrawn; Sponsor: Washington University School of Medicine; N=10 ➔ 0; Not yet recruiting ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Oncology • Solid Tumor • FDG PET

Molecular Templates Provides Corporate Update and Outlines 2022 Milestones (GlobeNewswire) - "Key Milestones for 2022:...(i) Continued data read-outs on all three clinical programs; (ii) IND filing for ETB targeting CTLA-4; (iii) Advancement of ETBs targeting TROP2, TIGIT, SLAMF-7."

IND • P1 data • Pipeline update • Head and Neck Cancer • Hematological Malignancies • Lung Cancer • Multiple Myeloma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Molecular Templates, Inc. Reports Third Quarter 2021 Financial Results (GlobeNewswire) - "MTEM expects to provide an update on MT-5111, MT-0169 and MT-6402 by the end of this year and expects to provide periodic updates throughout 2022; Through 2021 and in 2022, MTEM expects to present preclinical data on ETB candidates at medical and scientific conferences."

Clinical • Preclinical • Oncology

[VIRTUAL] A phase I study of the novel immunotoxin, MT-5111, in subjects (subj) with HER-2 positive tumors: Interim results. (ASCO 2020) - P1 | "MT-5111, a de-immunized 55 kD ETB targeting HER2 in solid tumors, binds to an epitope distinct from and non-competitive with trastuzumab and pertuzumab. MT-5111 appears to be well tolerated at the lowest dose with no apparent cardiotoxicity to date. Drug concentrations are expected to be below the level required for in vitro tumor cell killing. Safety and efficacy data from subsequent dose escalation cohorts are expected by May 2020."

Clinical • P1 data • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • HER2 Breast Cancer • Hypertension • Liver Cancer • Oncology • Solid Tumor • HER-2

[VIRTUAL] Phase 1 study of the novel immunotoxin MT-5111 in patients with HER-2+tumors (AACR 2021) - P1 | "MT‑5111, a de-immunized 55 kD ETB targeting HER2 in solid tumors, also binds to an epitope distinct from trastuzumab and pertuzumab, which may permit combination strategies with other HER2 targeting agents. MT-5111 was well tolerated with no clinically significant cardiotoxicity. Continued dose escalations are ongoing."

Clinical • P1 data • Breast Cancer • Esophageal Cancer • Gastric Cancer • GastroEsophageal Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

MT-5111, a novel HER2 targeting engineered toxin body, under clinical development to overcome mechanisms of resistance to existing HER2 targeted therapies (SABCS 2019) - P1; "MT-5111 is a 55 kilodalton protein and may have improved tumor penetration features in the solid tumor settings.MT-5111 has been designed to bind a HER2 domain distinct from the trastuzumab and pertuzumab binding sites and retains binding to HER2 and cell-kill activity even in the presence of these monoclonal antibodies. This short half-life was confirmed in primates (t1/2 of ~2 to 5 hours).A Phase 1, first in human, open-label dose escalation, and expansion study of MT-5111 (NCT04029922) in subjects with HER2-positive solid tumors whose disease has progressed after treatment with other approved therapies is open for enrollment. In conclusion, MT-5111 represents a novel HER2 targeted therapy which could provide benefit in subjects with HER2-positive cancers and potentially overcome mechanisms of tumor resistance to existing HER2 targeted therapies."

Clinical • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • HER-2

MT-5111: A novel HER2 targeting engineered toxin body in clinical development. (ASCO-GI 2020) - P1; "MT-5111 binds an epitope on HER2 distinct from trastuzumab or pertuzumab, that may provide for combination potential with other HER2 targeting agents. A Phase 1, first in human, open-label dose escalation and expansion study of MT-5111 (NCT04029922) in subjects with HER2+ solid tumors whose disease has progressed after treatment with other approved therapies is open for enrollment. MT-5111 represents a novel HER2 targeted therapy for patients with HER2+ cancers with potential to overcome mechanisms of tumor resistance to existing therapies. Research Funding: Molecular Templates, INC"

Clinical • Gastrointestinal Cancer • HER-2

A phase I open-label study to investigate safety and tolerability, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of MT-5111 in subjects with HER-2 positive tumors. (ASCO-GI 2020) - P1; "It binds a HER2 epitope distinct from trastuzumab or pertuzumab, could be combined with other HER2 targeting agents, and may have improved tumor penetration. Clinical trial information: NCT04029922. Research Funding: Molecular Templates"

Clinical • P1 data • PK/PD data • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER-2

[VIRTUAL] A phase I open-label study to investigate safety and tolerability, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of MT-5111 in patients with HER2-positive tumors. (ASCO-GI 2021) - P1 | "MT-5111 binds an epitope on HER2, distinct from trastuzumab or pertuzumab, that may provide for combination potential with other HER2-targeting agents. Pts with evaluable disease may be included in Part 1; in Part 2, all pts must have =1 measurable lesion per Response Evaluation Criteria in Solid Tumors v1.1. Enrollment, which began in September 2019, is ongoing."

Clinical • P1 data • PK/PD data • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • HER-2