On November 13, 2023 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"), to create novel therapies with potent differentiated mechanisms of action for cancer, reported financial results and business updates for the third quarter of 2023 (Press release, Molecular Templates, NOV 13, 2023, View Source [SID1234637551]).

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Eric Poma, PhD., Chief Executive and Chief Scientific Officer of MTEM, stated, "ETBs represent a new approach to oncology drug development that continue to show unique biology and monotherapy activity in heavily pre-treated patients. We expect to see substantial additional data across all three of our clinical programs with updates throughout this year and into 2024."

Company Highlights

Initiation of expansion study with MT-6402 (PD-L1) exploring 63 and 83 mcg/kg doses; compelling early evidence of monotherapy activity in patients with relapsed or refractory Head and Neck cancer observed at the 63 and 83 mcg/kg doses observed
First patient dosed in phase I study for MT-8421 targeting CTLA-4-expressing regulatory T-cells ("Tregs") in the tumor microenvironment ("TME") for elimination without affecting peripheral Tregs
MT-0169 (CD38): The company is in the process of declaring the recommended doses that will be further investigated in CD38+ malignancies.
Clinical data for each program continues to demonstrate novel mechanisms of action, unique pharmacodynamic ("PD") effects, and single agent activity in heavily relapsed/refractory patients across immuno-oncology, hematologic, and solid tumor indications observed
No instances of capillary leak syndrome ("CLS") or other manifestations of innate immunity have been observed to date with any next-generation ETB
Focus on preclinical activities related to Bristol Myers Squibb collaboration moves forward
MT-6402 (PD-L1 ETB)

The Part A dose escalation of the phase I for MT-6402 has been completed with no Grade 4 or Grade 5 drug-related adverse events having been observed to date.

In the Part A dose escalation, 10 patients with head and neck cancer were treated at doses of 63, 83, or 100 mcg/kg. Two of these patients were not evaluable for the cycle 1 dose-limiting toxicity ("DLT") period because of early progression and came off study after receiving only one or two doses of MT-6402, respectively. Of the remaining eight head and neck cancer patients, the best responses observed were as follows: two had a partial response (one unconfirmed), and a third patient had evidence of tumor regression. All three patients had progressed after multiple lines of treatment including checkpoint therapy. The unconfirmed partial response was in a patient who was pembrolizumab-refractory.

Three other patients had stable disease of 6, 4, and 2 months, respectively, before disease progression or discontinuation. A fourth patient remains in stable disease at cycle 5. One patient progressed at the end of cycle 2. Of these 8 patients, only one patient (the patient with stable disease through 6 cycles) had a PD-L1 tumor proportion score ("TPS") greater than 50%.

"We are very excited to see responses in heavily pre-treated, checkpoint-experienced, head and neck cancer patients, a setting with high unmet medical need," said Eric Poma. "The TME in head and neck tumors is typically rich with immunosuppressive cells, but current checkpoint monotherapy in I/O-naïve head and neck patients has a ~15% response rate. Here, in patients who have progressed on checkpoint therapy, we believe we are seeing evidence of monotherapy activity of long duration and monotherapy activity in a patient refractory to checkpoint therapy. The responses observed to date were in patients with CPS <20% and showed concomitant increases in cytokines associated with T-cell activation that are not seen with other checkpoint therapies. We believe these data demonstrate a new and potentially best-in-class approach to targeting the PD-1-PD-L1 axis."

"MT-6402 appears generally well-tolerated at the 63 and 83 mcg/kg doses with no Grade 4 or Grade 5 adverse events and no instances of CLS seen at any dose," said Dr. Maurizio Voi, Chief Medical Officer of Molecular Templates. "The irAE profile of MT-6402 appears to be consistent with that seen with other checkpoint therapies."

The Part B dose expansion is ongoing, with three patients currently on treatment but not yet evaluable for efficacy. The 63 and 83 mcg/kg doses will be studied in the expansion cohort in patients with >50% tumor expression of PD-L1, allowing for the potential of direct tumor cell-kill. Additionally, in patients with the HLA-A*02 haplotype and who are CMV+, the antigen seeding mechanism of MT-6402 may be engaged.

MT-8421 (CTLA-4 ETB)

MT-8421, along with MT-6402, represent our unique approach to immuno-oncology based on dismantling the TME through, and the elimination of, immunosuppressive cells in the TME.
MT-8421 is designed to potently destroy CTLA4+ Tregs via enzymatic ribosome destruction but does not have activity against low CTLA-4 expressing peripheral Tregs.
Clinical sites are open and enrollment has commenced on this program.
MT-0169 (CD38 ETB)

MT-0169 was designed to destroy CD38+ tumor cells through internalization of CD38 and cell destruction via a novel mechanism of action (enzymatic ribosomal destruction and immunogenic cell death).
MT-0169 will continue to be studied in CD38 hematological malignancies. No adverse events ≥ Grade 3 have been observed.
One patient with extra medullary IgA myeloma treated at 5 mcg/kg has had a marked reduction in IgA serum protein, conversion from immunofixation positive to negative and resolution of uptake on bone scan of skeletal lesions demonstrating a stringent Complete Response.
The patient’s disease was quad-agent refractory, including CD38-targeting antibody, proteosome inhibitor, IMiD, and a BCMA bispecific antibody.
The patient continues on study in a response at cycle 16.
Research and Collaboration

MTEM continues to make progress in the drug discovery collaboration with Bristol Myers Squibb.
Key Upcoming Milestones

Accelerating enrollment across all clinical programs.
Advancement of Bristol Myers Squibb research collaboration across multiple targets. Under terms of the agreement, Molecular Templates received $70M upfront and will undertake research responsibilities for the discovery of next-generation ETBs for multiple undisclosed targets.
MTEM expects to provide a year-end update and periodic updates on MT-6402, MT-8421, and MT-0169 throughout 2024.
Upcoming Conferences

Stifel Annual Health Care Conference

Format: Live Presentation and One-on-One Meetings
Date: Wednesday, November 15, 2023
Time: 10:55 am Eastern Time
Location: Lotte New York Palace Hotel, New York, NY
Webcast: The live-streamed webcast can be accessed here
Meetings: To be scheduled by contact with Stifel representative
The presentation link will be archived for 90 days here in the "News and Media" section of the corporate website.

Evercore ISI 6th Annual HealthCONx Conference

Format: One-on-one meetings
Dates: November 28 – 30, 2023
Location: Kimpton Epic Hotel, Miami, FL
Meetings: To be scheduled directly with Molecular Templates
Financial Results

The net loss attributable to common shareholders for the third quarter of 2023 was $4.2 million, or $0.82 per basic share and per diluted share. This compares with a net loss attributable to common shareholders of $24.6 million, or $6.56 per basic and diluted share, for the same period in 2022.

Revenues for the third quarter of 2023 were $6.8 million, compared to $4.2 million for the same period in 2022. Revenues for the third quarter of 2023 were comprised of revenues from the collaborative research and development agreement with Bristol Myers Squibb and grant revenue from CPRIT.

Total research and development expenses for the third quarter of 2023 were $7.6 million, compared with $22.0 million for the same period in 2022. Total general and administrative expenses for the third quarter of 2023 were $4.3 million, compared with $5.9 million for the same period in 2022.

As of September 30, 2023, MTEM’s cash and cash equivalents totaled $15.8 million. MTEM anticipates cash runway to the end of the second quarter of 2024.