On May 12, 2022 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular Templates," or "MTEM"), a clinical-stage biopharmaceutical company focused on the discovery and development of proprietary targeted biologic therapeutics, engineered toxin bodies (ETBs), reported financial results for the first quarter of 2022 (Press release, Molecular Templates, MAY 12, 2022, View Source [SID1234614480]).

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"We continue to make meaningful progress in advancing our pipeline of ETBs," said Eric Poma, Ph.D., Chief Executive and Chief Scientific Officer of Molecular Templates. "We recently commenced dosing in Cohort 3 of our Phase 1 study of MT-6402 in PD-L1+ patients. We intend to report additional data from this study in the second half of the year. Dose finding in the MT-5111 and MT-0169 programs is ongoing with clinical data expected this year. We look forward to continued momentum across our pipeline in 2022, including filing an IND for MT-8421, our ETB targeting CTLA-4, and advancing our earlier stage pipeline of ETBs targeting TIGIT, TROP-2, and BCMA."

Company Highlights and Upcoming Milestones

Corporate

MTEM expects to provide periodic updates on MT-6402, MT-5111, and MT-0169 throughout 2022.
MTEM hosted a webinar on MT-6402 (PD-L1 ETB with Antigen Seeding Technology) with David Spigel, M.D. of the Sarah Cannon Research Institute on April 13. A replay of the event (including slides) can be accessed here.
Abstracts on MT-6402 and MT-5111 (HER2 ETB) have been accepted for presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, to take place June 3-7, 2022, in Chicago, IL.
Gabriela Gruia, M.D. appointed to Board of Directors.
Megan Filoon promoted to General Counsel.
Immuno-oncology ETBs:

MT-6402 (PD-L1 ETB with Antigen Seeding Technology)

Patient enrollment continues in the Phase 1 study of MT-6402 which began in July 2021. MT-6402 is a 3rd generation ETB designed to induce potent anti-tumor effects via PD-L1 targeting through multiple mechanisms that may overcome the limitations of approved checkpoint inhibitors.
The Phase 1 study is a multi-center, open-label, dose escalation and dose expansion trial in the United States. Patients with confirmed PD-L1 expressing tumors or confirmed PD-L1 expression in the tumor microenvironment (TME) are eligible for enrollment.
As of March 2022, twelve patients with relapsed/refractory tumors that express PD-L1 have been treated to date across two dose cohorts: 16 mcg/kg (n=6) and 24 mcg/kg (n=6). Dosing continues with three patients currently enrolled in the 32 mcg/kg cohort (cohort 3).
One patient in cohort 1 (16 mcg/kg) with non-small cell lung cancer (NSCLC) that had progressed after prior checkpoint therapy (PD-1 and CTLA-4) had evaluable-only multiple sites of bone disease that appeared to have resolved on bone scan with only one remaining site which showed decreased uptake. This patient remained on MT-6402 up to cycle 8 when increased uptake was noted on bone scan and treatment was discontinued.
The 16 mcg/kg cohort was completed with no dose-limiting toxicities (DLTs) observed. One DLT was observed in a single patient in cohort 2 (24 mcg/kg). The patient experienced dermatitis that resolved rapidly with systemic steroids. The patient was rechallenged without incident at 24 mcg/kg. No other DLTs have been reported.
Following determination of the maximum tolerated dose (MTD), MTEM plans expansion cohorts to evaluate MT-6402 as a monotherapy in tumor-specific and PD-L1 positive basket tumor cohorts.
MTEM continues to observe pharmacodynamic (PD) effects including monocyte depletion and T cell activation in the 24 mcg/kg cohort. The extent and timing of these PD effects appear dose-related with patients in the 24 mcg/kg generally showing a more rapid and profound PD effect, including monocyte depletion and T cell activation, potentially in a dose-dependent manner.
These PD effects associated with immune activation were seen across the majority of patients irrespective of HLA type or level of tumor PD-L1 staining. The patient that demonstrated tumor regression was one of two patients treated with high tumor PD-L1 expression and may represent engagement of direct tumor cell-kill and antigen seeding.
MT-8421 (CTLA-4 ETB)

Preclinical data from MTEM’s CTLA-4 program were featured in a poster at the AACR (Free AACR Whitepaper) annual meeting held April 8-13, 2022. In a transgenic mouse model expressing human CTLA-4 and bearing syngeneic subcutaneous tumors, MT-8421 treatment depleted immune suppressive regulatory T cells (Tregs) in the TME.
MT-8421 was well tolerated in a non-human primate toxicology study and achieved serum levels well-above projected IC50 concentrations for Tregs in the TME.
IND filing for MT-8421 is expected in 2H22, with clinical studies expected to commence in 2023.
MT-6402 and MT-8421 represent MTEM’s unique approach to immuno-oncology based on dismantling the TME through direct cell-kill of tumor and immune cells and not just the blocking of ligand-ligand interactions seen with current antibody therapeutics.
Research

MTEM continues to expand its unique approach to immuno-oncology targets with lead optimization on a TIGIT-targeting ETB on-going and additional exploration around new immuno-oncology targets.
Targeted Solid Tumor ETBs:

MT-5111 (HER2 ETB)

The Phase 1 study of MT-5111 in HER2-positive cancers is ongoing with multiple sites open for enrollment.
The HER2-positive breast cancer expansion cohort initiated in November 2021 at a dose of 10 mcg/kg.
As of January 2022, 30 patients had been treated with MT-5111 across eight dose escalation cohorts ranging from 0.5 mcg/kg to 13 mcg/kg without any DLTs. Enrollment in the 17 mcg/kg cohort has been initiated.
Dose escalation will continue to determine the MTD, while the breast cancer expansion cohort collects efficacy and safety data.
No signs of capillary leak syndrome (CLS) or significant cardiotoxicity have been observed to date with MT-5111.
Research

Lead optimization on a 3rd generation ETB targeting TROP-2 continues.
Hematologic Malignancy Targeted ETBs:

MT-0169 (CD38 ETB)

The revised protocol for the ongoing Phase 1 study in patients with relapsed/refractory multiple myeloma or non-Hodgkin’s lymphoma is now open. The revised protocol will explore a lower dose of MT-0169 to reduce the risk of adverse events observed at the initial dose and to enable patients to continue MT-0169 therapy for a longer duration that may drive tumor benefit. Importantly, the robust and rapid NK cell depletion that was observed at the starting dose is expected to be observed at lower doses.
MTEM is opening new sites for the Phase 1 study and anticipates enrollment beginning in the second quarter of 2022.
Research

Lead optimization on BCMA, SLAMF-7, and CD45 continues.
Financial Results

The net loss attributable to common shareholders for the first quarter of 2022 was $21.6 million, or $0.38 per basic and diluted share. This compares with a net loss attributable to common shareholders of $26.8 million, or $0.51 per basic and diluted share, for the same period in 2021.

Revenues for the first quarter of 2022 were $8.5 million, compared to $3.2 million for the same period in 2021. Revenues for the first quarter of 2022 were comprised of revenues from collaborative research and development agreements with Takeda and Bristol Myers Squibb.

Total research and development expenses for the first quarter of 2022 were $21.5 million, compared with $21.4 million for the same period in 2021. Total general and administrative expenses for the first quarter of 2022 were $7.6 million, compared with $8.2 million for the same period in 2021.

As of March 31, 2022, MTEM’s cash and investments totaled $124.5 million. MTEM’s current cash and investments are expected to fund operations to the end of 2023.

For more details on MTEM’s financial results for the first quarter 2022, refer to Form 10Q filed with the SEC.