MT-5111

P1, N=50, Terminated, Molecular Templates, Inc. | N=178 --> 50 | Trial completion date: May 2025 --> Apr 2023 | Recruiting --> Terminated; Study Reprioritization

Three ETBs (MT-0169, MT-5111, and MT-6402) are currently in clinical studies across different targets (CD38, HER2, PD-L1) and across hematologic malignancies, solid tumor, and immuno-oncology indications. ETBs can also deliver additional payloads to drive unique biology like the alteration of tumor immunophenotype. Here we describe three active clinical stage programs with encouraging safety and efficacy data that represent a transformation of the immunotoxin landscape into a more viable therapeutic approach to target validated as well as typically intractable clinical cancer targets.

MT-5111 is a 55kD engineered toxin body targeting HER2 in solid tumors that binds to an epitope distinct from trastuzumab and pertuzumab, offering potential combination strategies with other HER2-targeting agents. sHER2 biomarker data is expected for all cohorts with PK correlation and 23µg/kg safety and efficacy data. PK profile of MT-5111, C1D1 values

P1, N=140, Recruiting, Molecular Templates, Inc. | Phase classification: P1/2 --> P1

Background: MT-5111 is a 55kD engineered toxin body (ETB) targeting HER2 in solid tumors that binds to an epitope distinct from trastuzumab and pertuzumab, offering potential combination strategies with other HER2-targeting agents. MT-5111 is well tolerated to-date with no clinically significant immuno/cardiotoxicity. Dose escalation is ongoing at a dose of 13µg/kg, expected to be required for efficacious exposure.

P1/2, N=178, Recruiting, Molecular Templates, Inc. | Phase classification: P1 --> P1/2

Background : MT-5111 is a 55 kD engineered toxin body (ETB) targeting HER2 in solid tumors that binds to an epitope distinct from trastuzumab and pertuzumab, offering potential combination strategies with other HER2-targeting agents. MT-5111 was well tolerated with no clinically significant immuno/cardiotoxicity. Dose escalation is ongoing and is nearing levels expected to be required for efficacious exposure.

MT-5111 is a 55 kD ETB targeting HER2 in solid tumors that binds to an epitope distinct from trastuzumab and pertuzumab, offering potential combination strategies with other HER2-targeting agents. MT-5111 was well tolerated with no clinically significant immuno- or cardiotoxicity. Dose escalation is ongoing and nearing levels expected to be required for efficacious exposure.

MT‑5111, a de-immunized 55 kD ETB targeting HER2 in solid tumors, also binds to an epitope distinct from trastuzumab and pertuzumab, which may permit combination strategies with other HER2 targeting agents. MT-5111 was well tolerated with no clinically significant cardiotoxicity. Continued dose escalations are ongoing.

MT-5111 binds an epitope on HER2, distinct from trastuzumab or pertuzumab, that may provide for combination potential with other HER2-targeting agents. Pts with evaluable disease may be included in Part 1; in Part 2, all pts must have =1 measurable lesion per Response Evaluation Criteria in Solid Tumors v1.1. Enrollment, which began in September 2019, is ongoing.

MT-5111, a de-immunized 55 kD ETB targeting HER2 in solid tumors, binds to an epitope distinct from and non-competitive with trastuzumab and pertuzumab. MT-5111 appears to be well tolerated at the lowest dose with no apparent cardiotoxicity to date. Drug concentrations are expected to be below the level required for in vitro tumor cell killing. Safety and efficacy data from subsequent dose escalation cohorts are expected by May 2020.

It binds a HER2 epitope distinct from trastuzumab or pertuzumab, could be combined with other HER2 targeting agents, and may have improved tumor penetration. Clinical trial information: NCT04029922. Research Funding: Molecular Templates

MT-5111 binds an epitope on HER2 distinct from trastuzumab or pertuzumab, that may provide for combination potential with other HER2 targeting agents. A Phase 1, first in human, open-label dose escalation and expansion study of MT-5111 (NCT04029922) in subjects with HER2+ solid tumors whose disease has progressed after treatment with other approved therapies is open for enrollment. MT-5111 represents a novel HER2 targeted therapy for patients with HER2+ cancers with potential to overcome mechanisms of tumor resistance to existing therapies. Research Funding: Molecular Templates, INC

MT-5111 is a 55 kilodalton protein and may have improved tumor penetration features in the solid tumor settings.MT-5111 has been designed to bind a HER2 domain distinct from the trastuzumab and pertuzumab binding sites and retains binding to HER2 and cell-kill activity even in the presence of these monoclonal antibodies. This short half-life was confirmed in primates (t1/2 of ~2 to 5 hours).A Phase 1, first in human, open-label dose escalation, and expansion study of MT-5111 (NCT04029922) in subjects with HER2-positive solid tumors whose disease has progressed after treatment with other approved therapies is open for enrollment. In conclusion, MT-5111 represents a novel HER2 targeted therapy which could provide benefit in subjects with HER2-positive cancers and potentially overcome mechanisms of tumor resistance to existing HER2 targeted therapies.