MT-3724 / Molecular Templates - LARVOL DELTA

Safety and Efficacy of Engineered Toxin Body MT-3724 in Relapsed or Refractory B-cell Non-Hodgkin's Lymphomas and Diffuse Large B-cell Lymphoma. (PubMed, Cancer Res Commun) - "In a dose expansion study at MTD in serum rituximab-negative patients with diffuse large B-cell lymphoma (DLBCL), primary objectives were safety, tolerability, and pharmacokinetics/pharmacodynamics. This work describes the safety and efficacy of a new pharmaceutical pathway that could provide a treatment option for a subset of patients with a critical unmet therapeutic need. The study drug, MT-3724, is capable of targeting B-cell lymphomas via a unique, potent cell-killing mechanism that appears to be promising."

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

Combinatorial Efficacy and Toxicity of an Engineered Toxin Body MT-3724 with Gemcitabine and Oxaliplatin in Relapsed or Refractory Diffuse Large B Cell Lymphoma. (PubMed, Cancer Invest) - "Two patients experienced grade 2 capillary leak syndrome (CLS). Combination therapy with MT-3724 and GEMOX demonstrated an early efficacy signal but was limited by the incidence of CLS."

Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

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

Improving immunotoxin-based therapeutics for cancer with de-immunized engineered toxin bodies (AACR 2022) - "MT-3724, a 1st gen CD20 targeting ETB comprising wild type SLTA (WT SLTA) genetically fused to a CD20 targeting scFv, displayed efficacy as monotherapy in relapsed/refractory non-Hodgkin lymphoma...These data suggest that cytokines were released in response to WT SLTA and protein aggregates in an off-target manner. This assay will be used to evaluate ETB safety by testing candidate ETBs for likelihood of cytokine release and/or innate immune activation prior to selection as candidates for clinical trials."

Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CCL3 • CSF2 • GZMB • IFNG • IL10 • IL1B • IL6 • TLR4 • TNFA

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

[VIRTUAL] A phase II study of MT-3724, a novel CD20-targeting engineered toxin body, to evaluate safety, pharmacodynamics, and efficacy in subjects with relapsed or refractory diffuse large B-cell lymphoma. (ASCO 2020) - P1/2 | "As rituximab and other CD20-targeting antibodies compete with MT-3724 for the same CD20 domain, minimum washout periods from these agents must be observed. Multiple global sites are enrolling subjects. Research Funding: Molecular Templates, Inc."

Clinical • P2 data • PK/PD data • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Safety and efficacy of anti-CD20 immunotoxin MT-3724 in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) in a phase I study. (ASCO 2018) - P1; "All pts with benefit had undetectable serum rituximab (RTX) level at screening. MT-3724 showed clinical anti-tumor activity in heavily pre-treated pts with R/R B-cell NHL. Consistent with mechanism of action, MT-3724 had the best activity in rapidly growing DLBCL. Safety and efficacy assessment is ongoing at the adjusted MTD of 50 g/kg/dose in DLBCL pts with undetectable screening RTX level."

Clinical • P1 data • Diffuse Large B Cell Lymphoma

[VIRTUAL] Phase 2a/b Dose Escalation and Expansion Study of MT-3724, a Novel CD20-Targeting Engineered Toxin Body, in Subjects with Relapsed or Refractory Follicular Lymphoma (ASH 2020) - "Subjects with Grade 3b FL, central nervous system or leptomeningeal involvement, or recent treatment with rituximab (within 84 days of study initiation; if received within 12-37 weeks of start of treatment, serum rituximab level must be confirmed to be negative [<500 ng/mL]), obinutuzumab (within 184 days), or ofatumumab (within 88 days) are not eligible. Development of and timing of DLTs will be used to identify the RP2D for Part 2, which will comprise a dose expansion cohort. Enrollment is anticipated to initiate in December 2020 globally."

Clinical • P2a data • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Musculoskeletal Pain • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pain • Transplantation • CD20

Monotherapy Activity with the First CD20-Targeted Immunotoxin, MT-3724, in Subjects with Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) (ASH 2019) - P1/2; "As MT‑3724 competes with rituximab (RTX) for the same CD20 binding domain, undetectable or low (< 500 ng/mL) RTX levels (RTX-neg) allow potential response to MT-3724. Twenty-seven subj with NHL (DLBCL:16, composite DLBCL/Follicular Lymphoma (FL): 3, FL: 6, Mantle Cell Lymphoma: 2 were enrolled. Seventeen (63%) were female, mean age was 65 yrs (34-78). Performance status was ECOG 0: 44%, 1: 44%, 2: 11%; median follow-up was 50 (11-372) days; median cycles 2 (1-11)."

Clinical • Monotherapy • CNS Disorders • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hypotension • Immunology • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Obesity • Oncology • Pain • Pneumonia • Respiratory Diseases • Transplantation

[VIRTUAL] MONOTHERAPY (M-TX) ACTIVITY WITH THE FIRST CD20-TARGETED IMMUNOTOXIN, MT-3724, IN SUBJECTS (SBS) WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA (R/R DLBCL) (EHA 2020) - P1/2 | "As MT-3724 competes with rituximab (RTX) for CD20 binding, minimal residual RTX levels (RTX-neg) allow potential response to MT-3724. ADAs did not preclude benefit of MT-3724. A phase 2 M-Tx study to confirm efficacy & safety in RTX-neg sbs with r/r DLBCL (NCT02361346) is ongoing."

Clinical • Monotherapy • CNS Disorders • Diffuse Large B Cell Lymphoma • Fatigue • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Obesity • Oncology • Pain • Pneumonia • Respiratory Diseases • Transplantation

[VIRTUAL] PHASE 2A OPEN-LABEL STUDY OF MT-3724, A NOVEL CD20-TARGETING ENGINEERED TOXIN BODY, IN COMBINATION WITH LENALIDOMIDE (LEN) IN SUBJECTS WITH RELAPSED OR REFRACTORY B-CELL NON-HODGKIN LYMPHOMA (B-NHL) (EHA 2020) - P2a | "Serum rituximab level must be negative (<500 ng/mL) at screening. Conclusion In this analysis of a Phase 2a study of MT-3724+LEN r/r B-NHL, CLS occurred at doses lower than expected, possibly because LEN may modulate the innate immune response to MT-3724; therefore a new schedule of therapy with LEN is under development. The preliminary response data were encouraging."

Clinical • Combination therapy • P2a data • Diffuse Large B Cell Lymphoma • Fatigue • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pain • Small Lymphocytic Lymphoma

A Phase 2a Open-Label Study to Investigate Safety and Tolerability (including the MTD), Efficacy, Pharmacokinetics, Pharmacodynamics and Immunogenicity of MT-3724 in Combination with Lenalidomide in Subjects with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma (ASH 2019) - P2a; "Serum rituximab level must be negative (<500 ng/mL) at screening. The study is currently ongoing. Eligible subjects will be identified and treated through competitive enrollment at multiple study centers in North America."

Clinical • Combination therapy • P2a data • PK/PD data • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

MT-3724NHL001: Safety, PD & Efficacy of MT-3724 for the Treatment of Patients With Relapsed or Refractory DLBCL (clinicaltrials.gov) - P1/2; N=130; Terminated; Sponsor: Molecular Templates, Inc.; Trial completion date: Sep 2022 ➔ Mar 2021; Active, not recruiting ➔ Terminated; Trial primary completion date: Jun 2022 ➔ Mar 2021; Sponsor decision following clinical hold

Clinical • Trial completion date • Trial primary completion date • Trial termination • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • MRI

PK,PD, Safety and Tolerability of Multiple Dose Regimens of MT-3724 With Lenalidomide for the Treatment of Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (MT-3724_NHL_003) (clinicaltrials.gov) - P2a; N=9; Terminated; Sponsor: Molecular Templates, Inc.; N=64 ➔ 9; Trial completion date: Jul 2022 ➔ Mar 2021; Active, not recruiting ➔ Terminated; Sponsor decision

Enrollment change • Trial completion date • Trial termination • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

PK,PD,Safety and Tolerability of Multiple Dose Regimens of MT-3724 With Gemcitabine and Oxaliplatin for the Treatment of Patients With Relapsed/Refractory Diffuse Large B Cell Non-Hodgkin's Lymphoma (clinicaltrials.gov) - P2; N=8; Terminated; Sponsor: Molecular Templates, Inc.; N=64 ➔ 8; Trial completion date: Feb 2023 ➔ Mar 2021; Active, not recruiting ➔ Terminated; Trial primary completion date: Dec 2022 ➔ Mar 2021; Sponsor decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Molecular Templates to Prioritize Next-Generation ETB Candidates (GlobeNewswire) - "Molecular Templates...announced that, following discussion with its co-development partner Takeda, MTEM will assume full rights to TAK-169 including taking control of clinical development from Takeda. In addition, MTEM announced the decision to discontinue development of MT-3724, MTEM’s only first-generation ETB....MTEM anticipates that the transition of TAK-169 development from Takeda to MTEM will be conducted over the next 90 days."

Clinical • Discontinued • Licensing / partnership • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Molecular Templates, Inc. Announces Pricing of $75.9 Million Public Equity Offering (Molecular Templates Press Release) - “Molecular intends to use the net proceeds from the offering, together with its existing cash and cash equivalents, to fund: its Phase II clinical studies for MT-3724 and/or development of other CD20-targeted molecules; its ongoing Phase I clinical study of MT-5111; its share of development expenses in its CD38 collaboration with Takeda; its PD-L1 program (including its anticipated upcoming Phase I clinical study for MT-6402); further preclinical development and drug discovery activities in its other programs; and for working capital and general corporate purposes.”

Commercial • Oncology

[VIRTUAL] A Phase 1 Multicenter Open-Label Study of Escalating Doses of the Novel Anti-CD20-Targeting Engineered Toxin Body MT-3724 in Subjects with Relapsed or Refractory Mantle Cell Lymphoma (ASH 2020) - "Subjects with CNS involvement or recent treatment with rituximab (within 84 days of study initiation; if received within 12-37 weeks of start of treatment, serum rituximab level must be confirmed to be negative [<500 ng/mL]), obinutuzumab (within 184 days), or ofatumumab (within 88 days) will be excluded. A Bayesian optimal interval design will be used to identify the RP2D more accurately (target toxicity rate φ=0.3). Enrollment is anticipated to begin in December 2020."

Clinical • P1 data • Hematological Disorders • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Musculoskeletal Pain • Neutropenia • Oncology • Pain • Transplantation • CCND1

PK,PD, Safety and Tolerability of Multiple Dose Regimens of MT-3724 With Lenalidomide for the Treatment of Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (MT-3724_NHL_003) (clinicaltrials.gov) - P2a; N=64; Active, not recruiting; Sponsor: Molecular Templates, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Combination therapy • Enrollment closed • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Targeted Engineered Toxin Bodies provide a novel mechanism of action against HER2 positive cancers (AACR 2018) - "...Molecular Templates lead compound, MT-3724, has seen clinical activity in heavily pre-treated lymphoma patients, underscoring the potential for this class of agents to work in the refractory/relapsed setting.Current modalities for the targeted treatment of HER2 positive breast cancer include monoclonal antibodies, antibody-drug conjugates, and tyrosine kinase inhibitors...The targeting of MT-5111 to a distinct epitope allows for activity of the ETB on cell lines where the trastuzumab epitope is masked, and allows for combination with targeted agents trastuzumab or T-DM1 without competition for binding to HER2...In vitro and in vivo data will be presented, highlighting the potential for MT-5111 as a novel agent under development for treatment of breast carcinomas, and other malignancies overexpressing the HER2 receptor. Molecular Templates intends to initiate clinical studies with MT-5111 in 2018."

HER2 Breast Cancer • Lymphoma

MT-3724NHL001: Safety, PD & Efficacy of MT-3724 for the Treatment of Patients With Relapsed or Refractory DLBCL (clinicaltrials.gov) - P1/2; N=130; Active, not recruiting; Sponsor: Molecular Templates, Inc.; Recruiting ➔ Active, not recruiting; Trial completion date: Sep 2021 ➔ Sep 2022; Trial primary completion date: May 2021 ➔ Jun 2022

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Molecular Templates: Progress Stalled As Partial Hold Placed On Pivotal ETB Trial (SeekingAlpha) - "A patient death in the company's potentially pivotal trial of lead candidate MT-3724 - targeting DLBCL - has caused the FDA to put a partial clinical hold on the trial."

FDA event • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Oncology

PK,PD,Safety and Tolerability of Multiple Dose Regimens of MT-3724 With Gemcitabine and Oxaliplatin for the Treatment of Patients With Relapsed/Refractory Diffuse Large B Cell Non-Hodgkin's Lymphoma (clinicaltrials.gov) - P2; N=64; Active, not recruiting; Sponsor: Molecular Templates, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

PK,PD,Safety and Tolerability of Multiple Dose Regimens of MT-3724 With Gemcitabine and Oxaliplatin for the Treatment of Patients With Relapsed/Refractory Diffuse Large B Cell Non-Hodgkin's Lymphoma (clinicaltrials.gov) - P2; N=64; Recruiting; Sponsor: Molecular Templates, Inc.; Trial completion date: Feb 2022 ➔ Feb 2023; Trial primary completion date: Jul 2020 ➔ Dec 2022

Clinical • Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Molecular Templates, Inc. Reports Second Quarter 2020 Financial Results (GlobeNewswire) - "MTEM expects to report updates on all three MT-3724 DLBCL studies in 2H20. MTEM also expects to initiate Phase 2 studies for MT-3724 in follicular lymphoma and mantle cell lymphoma in 2H20…MT-5111 (HER2 ETB)...MTEM expects to provide an update on results from the subjects still on treatment as well as higher dose cohorts from the dose escalation portion of the Phase 1 study (including doses that are predicted to be clinically active based on preclinical data) in 4Q20…MTEM expects to file an investigational new drug (IND) application for MT-6402, its ETB targeting PD-L1 (with antigen seeding), in 2H20. MTEM expects to file an IND application for its ETB targeting CTLA-4 in 2021."

Clinical data • IND • New P2 trial • Preclinical • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor