Monotherapy activity of long duration in patients who have progressed on checkpoint therapy via a novel immuno-oncology mechanism of action with PD-L1 ETB (MT-6402) program Early indication of monotherapy activity in CTLA-4 ETB (MT-8421) program through T-reg depletion; no drug-related adverse events > grade 2 Novel mechanism of action targeting CD38+ immune cells of B-cell, T-cell, and monocytic lineage representing enhanced potency in I&I without the need for conditioning therapy AUSTIN, Texas, Aug. 14, 2024 (GLOBE NEWSWIRE) -- 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, today reported financial results and business updates for the second quarter of 2024. "ETBs can eliminate immune cells that monoclonal antibodies cannot. Eliminating MDSCs with MT-6402 and Tregs with MT-8421 is a novel approach to immuno-oncology that is demonstrating durable responses in patients who have progressed or were refractory to checkpoint therapy. The elimination of immunosuppressive cells in patients with tumor microenvironments that promote immune evasion may drive long-lasting responses in patients who have exhausted other treatment options," said Eric Poma, PhD., Chief Executive and Chief Scientific Officer of MTEM. "Similarly, we believe MT-0169 can eliminate CD38+ immune cells that antibodies cannot, allowing for potentially greater potency in both hematologic malignancies and autoimmune diseases." Recent Company Highlights MT-6402: Continued monotherapy activity in patients who progressed or were refractory to checkpoint therapyNine patients (seven evaluable) with low PD-L1+ HNSCC were dosed in the MT-6402 phase I dose escalation study. Two patients remain in partial responses at cycle 23 and cycle 14 (one cycle is 4 weeks). Both patients had progressed after multiple lines of checkpoint therapy. In the high PD-L1+ dose expansion cohort, four NSCLC patients (three evaluable) have been enrolled. and one patient is in a partial response at cycle 11; the patient had progressed on chemotherapy, targeted therapy, and checkpoint therapy. All responding patients were heavily pretreated (3 or more lines of previous therapy including checkpoint) and have been on MT-6402 longer than any other previous therapy. MTEM continues to enroll HNSCC patients with low PD-L1 expression (1-49%) and patients with solid tumors with high PD-L1 expression (≥50%). MT-8421: Enrollment in Phase 1 dose escalation ongoing with continued observation of unique pharmacodynamic profile (peripheral and TME Treg depletion) and signs of monotherapy activityFive melanoma patients were evaluable in the first two dose cohorts (32 and 48 mcg/kg); no drug related adverse events > grade 2 were observed. One patient remains on study in cycle 11 with a 27% decrease in tumor volume and reduction in circulating tumor DNA from 3.13 to 0 MTM/mL. This patient had a >90% reduction in peripheral Tregs and a ~66% reduction of Tregs in the TME. The patient had progressed on pembrolizumab in the adjuvant setting and then progressed on ipilimumab (4 doses at 3mg/kg) and nivolumab in the metastatic setting. MT-0169: Potential in severe autoimmune diseases being explored based on clinical demonstration of complete elimination of CD38+ immune cells at dose levels with no drug-related adverse events > grade 2. The potent and unique mechanism of action of MT-0169 is not subject to resistance mechanisms associated with monoclonal antibodies like trogocytosis and can eliminate high-expressing CD38 immune cells like plasma cells as well as low-expressing CD38+ cells like HLA-DR CD38+ T-cells. This mechanism of action does not require conditioning therapy. MTEM will continue to develop MT-0169 in hematologic malignancies and is evaluating the potential of MT-0169 in severe immune-mediated diseases. Upcoming Milestones for 2H 2024 Additional updates from the MT-6402 low PD-L1+ HNSCC and high PD-L1+ solid tumor expansions studies in 3Q24. Additional updates from the MT-8421 dose escalation study in 3Q24. MT-0169 Phase 1 study initiation in CD38+ hematological malignancies and continued evaluation in autoimmune disease. Upcoming Conferences MTEM will participate at the H.C. Wainwright 26th Annual Global Investment Conference taking place at the New York Lotte Palace Hotel, September 9 – 11, 2024. An on-demand presentation will be accessible virtually starting 7:00am ET September 9, 2024 via MTEM corporate website. One-on-one meetings may be scheduled by directly contacting MTEM. Second Quarter 2024 Financial Results The net loss attributable to common shareholders for the second quarter of 2024 was $8.1 million, or $1.23 per basic and diluted share. This compares with a net loss attributable to common shareholders of $10.9 million, or $2.89 per basic and diluted share, for the same period in 2023. Revenues for the second quarter of 2024 were $0.6 million, compared to $6.9 million for the same period in 2023. Total research and development expenses for the second quarter of 2024 were $5.4 million, compared with $13.4 million for the same period in 2023. Total general and administrative expenses for the second quarter of 2024 were $3.5 million, compared with $5.2 million for the same period in 2023. As of June 30, 2024, MTEM's cash and cash equivalents totaled $9.7 million. The Company expects that its cash and cash equivalents for the quarter ended June 30, 2024 will support its ongoing operations into the fourth quarter of 2024. Molecular Templates, Inc.CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS(in thousands, except share and per share data)(unaudited)       Three Months Ended June 30,   Six Months Ended June 30,     2024   2023   2024   2023 Research and development revenue   $ 189     $ 6,627     $ 11,113     $ 40,254   Grant revenue     383       238       545       3,240   Total revenue     572       6,865       11,658       43,494   Operating expenses:                         Research and development     5,402       13,413       12,807       32,455   General and administrative     3,466       5,195       7,197       10,997   Total operating expenses     8,868       18,608       20,004