Molecular Templates, Inc. provided an update on its programs. The Part A dose escalation of the phase I study for MT-6402 has been completed with no Grade 4 or Grade 5 drug-related adverse events observed to date. In the Part A dose escalation, 10 patients with head and neck squamous cell cancer (HNSCC) 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 or for efficacy 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: three had a partial response and a fourth patient had evidence of tumor regression. All four patients had progressed on their previous therapies after multiple lines of treatment including checkpoint antibodies. Additional details on each of these participant?s clinical profile and response to the investigational treatment are provided below.

1 patient with a PD-L1 TPS of 2% who had progressed after chemotherapy, radiation therapy, and pembrolizumab had a confirmed PR with 70% tumor reduction and remains on study in cycle 18 (1 cycle = 4 weeks). 1 patient with a PD-L1 CPS of 10% who had progressed after three previous lines of therapy, including progression on Ipi/Nivo within 4 months, showed deepening tumor reduction over time of 3%, 9%, and 15% at the end of cycles 2, 4, and 6, respectively. At the end of cycle 8, the patient had an unconfirmed PR with a 37% reduction in tumor size.

The patient remains on study in cycle 9. 1 patient with a PD-L1 CPS of 5% who had progressed after six prior lines of therapy and was refractory to pembrolizumab received 2 doses of MT-6402 before coming off treatment due to the treating physician?s concerns around an asymptomatic grade 1 high sensitivity troponin elevation and hyponatremia related to excessive alcohol intake. The patient discontinued treatment, but a subsequent CT scan assessed by an external radiology review showed that the patient had a 36% tumor reduction (an unconfirmed PR). 1 patient with a PD-L1 CPS of 10% with pre-existing cardiac risk factors of hypertension, hyperlipidemia, and hypercholesterolemia received three doses of MT-6402 before presenting with asymptomatic grade 1 high sensitivity troponin elevation and dosing was held.

A CT scan showed a 13% reduction in tumor size, but disease progression occurred during treatment interruption and patient discontinued at the end of cycle 6. The three other HNSCC patients enrolled in the Part A dose escalation had stable disease of 6, 4, and 2 months, respectively, before disease progression or study discontinuation. 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 greater than 50%. MT-8421 (CTLA-4 ETB) MT-8421, along with MT-6402, represent unique approach to immuno-oncology based on dismantling the TME through 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. Three patients were dosed in the first cohort of the phase I study at 32 mcg/kg. No grade 3 or grade 4 drug-related adverse events were observed.

Two patients have stable disease and remain on study at cycle 4 and cycle 2, respectively (1 cycle = 4 weeks). One patient had disease progression at the end of cycle 2. The two patients in stable disease showed peripheral depletion of Tregs and significant elevations in IL-2 while on therapy. Enrollment is on-going in the second cohort of 48 mcg/kg for the phase I study of MT-8421.

MT-0169 (CD38 ETB) MT-0169 is 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). A phase 1 study in patients with relapsed or refractory multiple myeloma was closed on December 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. Research and Collaboration MTEM continues to make progress in the drug discovery collaboration with Bristol Myers Squibb.

Previously Announced Process to Explore Strategic Alternatives Previously, Molecular Templates announced that it has retained Stifel, Nicolaus & Company to assist Molecular Templates in initiating a comprehensive evaluation of strategic alternatives, including, but not limited to, potential financing/recapitalization opportunities, the sale of all, or part, of the company, or a merger, or other strategic transactions. A timetable for completion of this strategic review process has not been set, and there can be no assurance that this strategic review will result in any completed transaction.