MT-0169 / Molecular Templates - LARVOL DELTA

Preclinical evaluation of the CD38-targeting engineered toxin body MT-0169 against multiple myeloma. (PubMed, Hemasphere) - "In the preclinical setting, MT-0169 effectively lysed primary MM cells from newly diagnosed and heavily pretreated MM patients, including those refractory to daratumumab, with minimal toxicity against nonmalignant hematopoietic cells. Finally, MT-0169 showed efficient in vivo anti-MM activity in various mouse xenograft models, including one in which MM cells are grown in a humanized bone marrow-like niche. These findings support clinical investigation of MT-0169 in relapsed/refractory MM patients, including those refractory to CD38-targeting immunotherapies."

IO biomarker • Journal • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology • CASP3 • CASP7

Phase I Trial of MT-0169 in CD38+ Acute Leukemia With Relapsed/Refractory or Measurable Residual Disease (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: M.D. Anderson Cancer Center | N=52 ➔ 0 | Trial completion date: Jul 2030 ➔ Oct 2024 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Jul 2028 ➔ Oct 2024

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Hematological Malignancies • Leukemia • Oncology

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

Phase I Trial of MT-0169 in CD38+ Acute Leukemia With Relapsed/Refractory or Measurable Residual Disease (clinicaltrials.gov) - P1 | N=52 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P1 trial • Hematological Malignancies • Leukemia • Oncology

Molecular Templates, Inc. Provides Interim Update (GlobeNewswire) - P1 | N=14 | NCT04017130 | Sponsor: Molecular Templates, Inc. | "MT-0169 (CD38 ETB)....A phase 1 study in patients with relapsed or refractory multiple myeloma was closed on Dec 2023 due to slow patient enrollment in the wake of multiple new approvals in myeloma. This study enrolled 14 patients and no drug-related Grade 4 or 5 adverse events have been observed. One patient with IgA myeloma who was quad-refractory was treated at 5 mcg/kg and had a stringent Complete Response for 16 cycles (1 cycle = 4 weeks) before discontinuing treatment for progression of disease; MTEM plans on initiating an investigator sponsored trial with MD Anderson Cancer Center to evaluate MT-0169 in relapsed or refractory CD38+ AML patients."

New trial • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

MT-0169-001: A Study of MT-0169 in Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=14 | Terminated | Sponsor: Molecular Templates, Inc. | N=54 ➔ 14 | Trial completion date: Dec 2024 ➔ Dec 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Aug 2024 ➔ Dec 2023; Sparse/no patient enrollment

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

MT-0169-001: A Study of MT-0169 in Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=54 | Active, not recruiting | Sponsor: Molecular Templates, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology

MT-0169-001: A Study of MT-0169 in Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: Molecular Templates, Inc. | Active, not recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

TAK-169-1001: A Study of MT-0169 in Participants With Relapsed or Refractory Multiple Myeloma or Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1; N=198; Recruiting; Sponsor: Molecular Templates, Inc.; N=102 ➔ 198; Trial completion date: Jan 2023 ➔ Dec 2024; Trial primary completion date: Jan 2023 ➔ Jan 2024

Clinical • Enrollment change • IO biomarker • Trial completion date • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

MT-0169-001: A Study of MT-0169 in Participants With Relapsed or Refractory Multiple Myeloma or Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=144 | Active, not recruiting | Sponsor: Molecular Templates, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • IO biomarker • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

MT-0169-001: A Study of MT-0169 in Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=54 | Active, not recruiting | Sponsor: Molecular Templates, Inc. | N=144 ➔ 54 | Trial primary completion date: Jan 2024 ➔ Aug 2024

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

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 the FDA Removal of Partial Clinical Hold in the Phase 1 Clinical Trial for MT-0169 and Focuses on Extramedullary Myeloma (GlobeNewswire) - "Molecular Templates, Inc...announced today that the U.S. Food and Drug Administration ('FDA'), after reviewing safety data on the program, has removed the partial clinical hold on patient enrollment for its MT-0169 trial, allowing Molecular Templates to proceed with its plan to evaluate the efficacy of MT-0169, one of its ETBs, which specifically targets CD38, a validated target in Multiple Myeloma."

FDA event • Hematological Malignancies • Multiple Myeloma • Oncology

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

Molecular Templates Announces Partial Clinical Hold for Phase 1 Study of MT-0169 (GlobeNewswire) - "Molecular Templates...announced that the U.S. Food and Drug Administration (the 'FDA') informed MTEM that it has placed a partial clinical hold on the Phase 1 study of MT-0169 based on previously disclosed cardiac adverse events noted in two patients dosed at 50 mcg/kg that prompted the dose reduction to 5 mcg/kg last year. Since then, four patients have been dosed at 5 mcg/kg and three patients have been dosed at 10 mcg/kg with no cardiac adverse events noted....The FDA has asked MTEM to provide narratives on the two patients who experienced cardiotoxicity at 50 mcg/kg, justification for the revised dose of 5 mcg/kg, and data evaluating the clinical benefit-to-risk ratio seen with the lower doses of MT-0169, among other requests."

Trial suspension • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

[VIRTUAL] TAK-169, a Novel Recombinant Immunotoxin Specific for CD38, Induces Powerful Preclinical Activity Against Patient-Derived Multiple Myeloma Cells (ASH 2020) - P1 | "Monoclonal antibodies (daratumumab, anti-CD38; elotuzumab, anti-SLAMF7) and BCMA-targeting T-cell redirecting therapies are highly effective in a large proportion of multiple myeloma (MM) patients. In conclusion, we show that TAK-169 induces powerful lysis of primary MM cells from both ND and RR MM patients, including those refractory to daratumumab. Our findings support the ongoing phase 1 clinical trial evaluating TAK-169 monotherapy in heavily pretreated MM (NCT04017130), and encourage preclinical evaluation of TAK-169 in other CD38-positive malignancies such as AML and T-ALL."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • CD38

A Phase 1, Open-Label, Dose-Escalation and Expansion, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of MT-0169 in Patients with Relapsed or Refractory Multiple Myeloma or Non-Hodgkin Lymphoma (ASH 2022) - P1 | "Prior treatment with an anti-CD38 therapy (including daratumumab) is permitted. The trial is currently recruiting at multiple sites in the United States. (NCT04017130)."

Clinical • P1 data • PK/PD data • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

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

Interim results of a phase 1 study of the novel engineered toxin body TAK-169 in patients with relapsed or refractory multiple myeloma (SITC 2021) - P1 | "Dose escalation is ongoing. Trial Registration Clinicaltrials.gov identifier: NCT04017130"

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

A Phase 1, Open-Label, Dose-Escalation and Expansion, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TAK-169 in Patients with Relapsed or Refractory Multiple Myeloma (ASH 2021) - P1 | "Clinical activity was seen in heavily pre-treated hematological malignancies with a first-generation ETB (MT-3724) targeting CD20...Prior treatment with an anti-CD38 therapy (including daratumumab) is permitted...The trial is currently recruiting at three US sites. (NCT04017130)"

Clinical • P1 data • PK/PD data • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Oncology • CD59

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

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, 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

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

Combination of CD20 targeted engineered toxin body, MT-3724, with chemotherapy or IMiDs for the treatment of non Hodgkin's lymphoma (AACR 2019) - P1, P2, P2a; "...Specifically, in R/R diffuse large B cell lymphoma (DLBCL) patients who had low pre-existing serum levels of rituximab, an objective response rate (ORR) of 30% (3 of 10) and disease control rate of 70% (7 of 10) has been observed thus far (NCT02361346).Given the unique ribosomal inhibition mechanism of action for MT-3724, we hypothesized that combination of MT-3724 with agents possessing a differentiated mechanism of action could result in additive or synergistic cellular cytotoxicity in CD20 positive NHL cell lines. Preclinical studies were conducted to assess MT-3724 in combination with cytotoxic chemotherapeutic agents (doxorubicin, gemcitabine, bendamustine, and vincristine) or an immunomodulatory (IMiD) agent (lenalidomide) on selected NHL cell lines. The combination of MT-3724 with all agents demonstrated additive or synergistic cytotoxicity of NHL cell lines.The single agent clinical activity of MT-3724 in heavily pre-treated R/R NHL patients along with thi

Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology