Molecular Templates Announces Partial Clinical Hold for Phase 1 Study of MT-0169

Rhea-AI Summary

Molecular Templates (MTEM) announced a partial clinical hold on its Phase 1 study of MT-0169 due to cardiac adverse events observed at a higher dosage of 50 mcg/kg. The FDA is reviewing safety data from lower doses (5 mcg/kg and 10 mcg/kg) where no cardiac events were reported among eight patients. The hold permits current participants to continue treatment, but new enrollments are paused. Notably, one patient at 5 mcg/kg showed a Very Good Partial Response evolving into a stringent complete response. The FDA has requested additional data to evaluate the benefit-to-risk ratio of the lower doses before lifting the hold, as patient safety remains a priority for MTEM.

Positive

• No cardiac adverse events noted in patients dosed at 5 mcg/kg and 10 mcg/kg.
• One patient at 5 mcg/kg achieved a stringent complete response after more than 7 months of treatment.

Negative

• Partial clinical hold placed on MT-0169 study due to previous cardiac events at 50 mcg/kg dosage.
• FDA requires further justification and data before considering lifting the hold.

Partial hold based on previously disclosed cardiac events at 50 mcg/kg cohort; FDA to review safety data in lower dose cohorts

AUSTIN, Texas, April 07, 2023 (GLOBE NEWSWIRE) -- Molecular Templates, Inc. (Nasdaq: MTEM, “Molecular Templates,” or “MTEM”), today announced that the U.S. Food and Drug Administration (the “FDA”) informed MTEM that it has placed a partial clinical hold on the Phase 1 study of MT-0169 based on previously disclosed cardiac adverse events noted in two patients dosed at 50 mcg/kg that prompted the dose reduction to 5 mcg/kg last year. Since then, four patients have been dosed at 5 mcg/kg and three patients have been dosed at 10 mcg/kg with no cardiac adverse events noted.

Of the patients dosed at 50 mcg/kg, one patient experienced asymptomatic grade 2 myocarditis and one patient experienced asymptomatic grade 3 cardiomyopathy; both patients had full recoveries within two months of these events. No grade 4 or 5 toxicities were observed at 50 mcg/kg. Under the partial clinical hold, current study participants may continue treatment, but no new patients will be enrolled until the partial hold is lifted by the FDA.

After filing a protocol amendment in January 2022, Molecular Templates resumed study treatment in patients with relapsed Multiple Myeloma at 5 mcg/kg, a 90% reduction in dose. Four patients were dosed at 5 mcg/kg with no adverse events greater than grade 1 noted and no cardiac adverse events noted. One patient dosed at 5 mcg/kg had a Very Good Partial Response (“VGPR”) that deepened to a stringent complete response and remains on study for more than 7 months. Three patients were dosed at 10 mcg/kg with no cardiac events noted; one patient dosed at 10 mcg/kg experienced transient grade 2 diarrhea.  

The FDA has asked MTEM to provide narratives on the two patients who experienced cardiotoxicity at 50 mcg/kg, justification for the revised dose of 5 mcg/kg, and data evaluating the clinical benefit-to-risk ratio seen with the lower doses of MT-0169, among other requests.

"Patient safety is our highest priority. The 5 and 10 mcg/kg cohorts have been completed and we have not observed any cardiac adverse events or other serious adverse events at these lower doses. One patient dosed at 5 mcg/kg is in a stringent complete response and is in his seventh month of therapy. We look forward to sharing these data with the FDA and are confident in the benefit-risk profile of MT-0169 at these lower doses," said Roger Waltzman, MD., Chief Medical Officer at MTEM. "We are excited to see early signs of clinical benefit in this difficult-to-treat patient population."

About Molecular Templates

Molecular Templates is a clinical-stage biopharmaceutical company focused on the discovery and development of targeted biologic therapeutics. Our proprietary drug platform technology, known as engineered toxin bodies (“ETBs”), leverages the resident biology of a genetically engineered form of Shiga-like Toxin A subunit to create novel therapies with potent and differentiated mechanisms of action for cancer.

Forward-Looking Statements

This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”). Molecular Templates disclaims any intent or obligation to update these forward-looking statements and claims the protection of the Act’s Safe Harbor for forward-looking statements. All statements, other than statements of historical facts, included in this press release regarding strategy, future operations, future financial position, future revenue, projected expenses, prospects, plans and objectives of management are forward-looking statements. In addition, when or if used in this press release, the words “may,” “could,” “should,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “plan,” “predict” and similar expressions and their variants, as they relate to Molecular Templates may identify forward-looking statements. Examples of such statements include, but are not limited to, statements regarding future benefit-to-risk data regarding MT-0169 expected to be shared with the FDA and our potential plans for MT-0169, statements relating to the potential lifting of the partial clinical hold on Molecular Templates’ MT-0169 clinical trial, the safety or potential efficacy of Molecular Templates’ drug or biologic candidates, including MT-0169; and Molecular Templates’ belief that its proprietary biologic drug platform technology, or ETBs, provides for a differentiated mechanism of action for cancer. Forward-looking statements are not guarantees of future performance and involve risks and uncertainties. Actual events or results may differ materially from those discussed in the forward-looking statements as a result of various factors including, but not limited to the following: the risks associated with Molecular Templates’ ability to satisfactorily respond to requests from the FDA for further information and data regarding MT-0169, uncertainties as to whether Molecular Templates can successfully resolve the partial clinical hold with regard to MT-0169; the uncertainties inherent in the preclinical and clinical development process, including the fact that interim results may not be indicative of future results; Molecular Templates’ ability to timely enroll subjects in its clinical trials; the ability of Molecular Templates’ to protect its intellectual property rights; and legislative, regulatory, political and economic developments, as well as those risks identified under the heading “Risk Factors” in Molecular Templates’ filings with the SEC. Any forward-looking statements contained in this press release speak only as of the date hereof, and Molecular Templates specifically disclaims any obligation to update any forward-looking statement, whether because of new information, future events or otherwise.

Contacts:
Dr. Grace Kim
Head of Investor Relations
grace.kim@mtem.com

FAQ

What is the reason for the partial clinical hold on MT-0169 by Molecular Templates?

The FDA placed a partial clinical hold on MT-0169 due to previously disclosed cardiac adverse events at the 50 mcg/kg dose.

What were the results of the lower dose cohorts in the MT-0169 study?

Patients dosed at 5 mcg/kg and 10 mcg/kg reported no cardiac adverse events, with one patient at 5 mcg/kg achieving a stringent complete response.

How many patients were dosed at the lower doses of MT-0169?

A total of four patients were dosed at 5 mcg/kg and three patients at 10 mcg/kg.

What does the FDA expect from Molecular Templates regarding the MT-0169 trial?

The FDA has requested narratives on previous cardiotoxicity cases, justification for the lower dose, and evaluation of the clinical benefit-to-risk ratio.

What impact does the partial hold have on new patient enrollment for the MT-0169 study?

No new patients will be enrolled in the MT-0169 study until the FDA lifts the partial clinical hold.