Molecular Templates, Inc. Provides Interim Update
Molecular Templates provided an interim update on its clinical-stage programs focusing on its ETB (Engineered Toxin Bodies) platform. Key highlights include:
MT-6402 (PD-L1-targeting ETB): This drug has shown promising results in heavily pre-treated solid tumor patients, especially those with low PD-L1 expression. Noteworthy outcomes include partial responses in head and neck cancer patients and an unconfirmed partial response in a non-small cell lung cancer patient. The safety profile of MT-6402 remains favorable.
MT-0169 (CD38-targeting ETB): This drug demonstrates strong potential in treating immune-mediated diseases by effectively depleting CD38+ immune cells. It displayed potent activity in pre-clinical and early clinical data, with no grade 3 or higher adverse events reported.
MT-8421 (CTLA-4 ETB): Early Phase 1 data show promising pharmacodynamic effects with no severe drug-related adverse events, although one patient experienced disease progression.
The company emphasizes the potential of its ETB platform across multiple diseases and continues to enroll patients in its ongoing studies.
- MT-6402 displayed promising single-agent activity in heavily pre-treated solid tumor patients.
- Partial responses observed in head and neck cancer and non-small cell lung cancer patients.
- Favorable safety profile for MT-6402 with no drug-related adverse events exceeding grade 3.
- MT-0169 showed potent depletion of CD38+ immune cells in clinical studies.
- No grade 3 or higher adverse events reported for MT-0169.
- MT-8421 demonstrated early pharmacodynamic effects with no severe adverse events.
- Ongoing patient enrollment and dose escalation across multiple studies.
- Disease progression observed in one patient treated with MT-8421.
- Unconfirmed partial response in non-small cell lung cancer patient for MT-6402.
- Two NSCLC patients treated with MT-6402 had progressive disease.
Insights
MT-6402 and MT-0169 from Molecular Templates, Inc. both present promising clinical trial results that could impact treatment paradigms for various cancers and immune-mediated diseases. MT-6402's ability to show monotherapy activity in heavily pre-treated patients, particularly in head and neck squamous cell carcinoma (HNSCC) with low PD-L1 expression, is noteworthy. The fact that two patients achieved partial responses and others had stable disease indicates potential effectiveness even in difficult-to-treat populations.
The novel mechanism of action of MT-0169, targeting CD38+ cells through enzymatic ribosomal destruction and ER stress, offers a potent alternative to existing therapies. This is particularly relevant in multiple myeloma, where resistance to CD38-targeting antibodies is a significant hurdle. The early data showing CD38+ cell depletion without severe adverse events could translate into a new line of therapy for patients with relapsed or refractory multiple myeloma.
From a clinical perspective, the differentiation in mechanisms of action and the promising early results set these therapies apart, potentially leading to more effective and targeted treatments in oncology and hematology.
Molecular Templates' update highlights significant progress in their clinical pipeline, with MT-6402 and MT-0169 showing potential in early trials. MT-6402's effectiveness in patients with low PD-L1 expression stands out, given that this subset of patients often has limited treatment options. The response in a non-small cell lung cancer (NSCLC) patient with high PD-L1 expression further supports the drug's broad applicability and potential to address checkpoint therapy resistance.
MT-0169's unique mechanism of action, which avoids common antibody resistance mechanisms like receptor downregulation, adds a layer of innovation to the treatment of CD38+ related diseases. This could result in more durable responses and complements existing therapies, especially for those who have developed resistance to current treatments.
Additionally, the ongoing development of MT-8421, targeting CTLA-4+ Tregs, demonstrates the company's strategic approach to dismantling the tumor microenvironment, a critical factor in promoting long-term cancer remission. While the clinical data are still early, the pharmacodynamic effects observed are encouraging.
From an investor's standpoint, Molecular Templates, Inc. provides several reasons for optimism, particularly in the context of its recent clinical updates. The observed efficacy and safety profile across multiple indications for MT-6402 and MT-0169 suggest potential market opportunities in oncology and immune-mediated diseases. These advancements could lead to favorable milestones such as further clinical developments, partnerships, or even early regulatory approvals.
The fact that MT-6402 continues to show promising results in heavily pre-treated cancer patients may attract interest from larger pharmaceutical companies looking for acquisition or licensing opportunities. Positive trial results in such challenging patient populations often serve as a strong validation of a therapy's potential market success.
However, it’s essential to consider the typical risks associated with clinical-stage biotech companies, including potential setbacks in trials and regulatory hurdles. Investors should balance the promising data with these inherent risks, while keeping an eye on upcoming data releases and conference presentations that might provide further validation or new insights.
- Continued monotherapy activity in solid tumors with MT-6402 (PD-L1-targeting ETB) in checkpoint-experienced patients.
- Early pre-clinical and clinical data demonstrate the potential of MT-0169 (CD38-targeting ETB) in severe immune-mediated diseases.
AUSTIN, Texas, June 03, 2024 (GLOBE NEWSWIRE) -- Molecular Templates, Inc. (Nasdaq: MTEM, “Molecular Templates,” or “MTEM”), a clinical-stage company focused on the discovery and development of targeted biologic therapeutics with unique mechanisms of action (engineered toxin bodies or “ETBs”) for cancer and immune-mediated disease, today provided an update on its clinical-stage programs.
Eric Poma, PhD., Chief Executive and Chief Scientific Officer of MTEM, stated, “ETBs are a potentially powerful therapeutic approach to selectively depleting immunosuppressive cells in oncology or eliminating self-reacting immune cells in severe immune-mediated diseases. The monotherapy activity we see with MT-6402 in relapsed/refractory solid tumor patients, and the clinical and ex vivo depletion of CD38+ immune cells seen with MT-0169 at well-tolerated doses underscore the potential of this platform across multiple diseases.”
Company Pipeline Highlights
MT-6402 (PD-L1-targeting ETB)
- Promising Single-Agent Activity: MT-6402 has shown monotherapy activity in heavily pre-treated patients who had previously progressed or were refractory to immuno-oncology therapy.
- Head and Neck Cancer Responses: MTEM had previously reported that nine patients (seven evaluable) with head and neck squamous cell carcinoma (“HNSCC”) had been treated in the Phase 1 dose escalation. Two heavily pre-treated patients with low PD-L1 expressing squamous cell carcinoma of the head and neck (HNSCC) had achieved partial responses with MT-6402 monotherapy. These patients remain in response and in good clinical condition, continuing treatment in cycles 21 and 12 (one cycle = 4 weeks), respectively. In addition, four of the HNSCC patients treated with MT-6402 had stable disease with two showing tumor reduction. All patients with tumor responses or tumor reduction had low PD-L1 expression (≤
20% CPS). - New Lung Cancer Response: An unconfirmed partial response was observed in a non-small cell lung cancer (“NSCLC”) patient with high PD-L1 expression in the Phase 1b monotherapy dose expansion study in solid tumor patients with high PD-L1 tumor expression (TPS≥
50% ). The patient achieved a partial response at the end of cycle 8 following sustained tumor reduction in prior assessments. A PET scan in cycle 8 showed no indications of active metastatic disease. This patient had previously progressed on chemotherapy, targeted therapy, and checkpoint therapy, including progression within six months on pembrolizumab + ramucirumab, before enrolling in the study. Three other NSCLC patients with high PD-L1 expression have been dosed in the Phase 1b expansion study. Two of these patients had progressive disease and one passed away from COVID and was not evaluable. - Favorable Safety Profile: To date, MT-6402 appears to be generally well-tolerated, with no drug-related adverse events exceeding grade 3.
- Ongoing Enrollment: 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-0169 (CD38-targeting ETB)
- Clinical proof-of-concept supports the elimination of CD38+ cells in immune-mediated disease. Recent clinical data with CD38 antibodies have demonstrated the therapeutic potential of CD38+ immune cell clearance in several immune-mediated diseases. Despite these promising early data, a more potent mechanism of CD38+ immune cell depletion may provide greater clinical benefit.
- Potent and unique mechanism of action. MT-0169 is designed to destroy CD38+ tumor or immune cells through internalization of CD38 and cell destruction via a novel mechanism of action (enzymatic ribosomal destruction and ER stress). In ex vivo cell kill assays, MT-0169 shows potency against plasma cells with IC50 activity in the picomolar or femtomolar range. Plasma cells are exceptionally sensitive to ER stress, making them uniquely susceptible to the MT-0169 mechanism of action. MT-0169 also shows potent activity against T-cells that express low levels of CD38. HLA-DR CD38+ T-cells have been implicated in many immune-mediated diseases.
- Overcoming antibody resistance. The unique mechanism of action of MT-0169 and its lack of an Fc domain may avoid resistance mechanisms seen with CD38 antibodies like receptor downregulation or trogocytosis while allowing for combination approaches with FcRn-targeting therapies.
- Clinical proof-of-concept with MT-0169. MTEM’s Phase 1 study in patients with relapsed or refractory multiple myeloma dosed at 5, 10, or 15 mcg/kg showed potent depletion of CD38+ immune cells with no drug-related adverse events of grade 3 or higher noted in these patients.
- Planned clinical development with MT-0169. MTEM will continue to develop MT-0169 in hematology and is evaluating the potential of MT-0169 in severe immune-mediated diseases.
MT-8421 (CTLA-4 ETB)
- Tumor microenvironment dismantling. MT-8421 is designed to potently destroy CTLA4+ Tregs, alleviating immunosuppression in the tumor microenvironment.
- Pharmacodynamic effects observed early Phase 1 dose escalation. Three patients were dosed in the first cohort of the Phase 1 study at 32 mcg/kg. No drug-related adverse events of grade 3 or higher were observed. One patient had disease progression at the end of cycle 2. Two patients have stable disease and remain on study at cycle 8 and cycle 7, respectively (one cycle = four weeks). The two patients in stable disease showed peripheral depletion of Tregs and significant elevations in IL-2 while on therapy. One of the patients has a notable decrease in ctDNA.
- Dose escalation continues. Enrollment is on-going in the second cohort of 48 mcg/kg for the Phase 1 study of MT-8421.
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, or 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 and immune-mediated diseases.
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, including, but not limited to those regarding strategy, future operations, the Company’s ability to execute on its objectives, prospects, plans, future clinical development of the Company’s product candidates, any implication that the preliminary results, interim results, or the results of earlier clinical trials or ongoing clinical trials will be representative of the results of future or later clinical trials or final results, the potential benefits, safety or efficacy and any evaluations or judgements regarding the Company’s product candidates, , and future execution of corporate goals. In addition, when or if used in this press release, the words “may,” “could,” “should,” “continue”, “anticipate,” “potential”, “believe,” “estimate,” “appears”, “expect,” “intend,” “plan,” “predict” and similar expressions and their variants, as they relate to Molecular Templates may identify forward-looking statements. 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 continued availability of financing on commercially reasonable terms, whether Molecular Templates’ cash resources will be sufficient to fund its continuing operations; the results of MTEM’s ongoing clinical studies, the ability to effectively operate MTEM and retain key employees post-MTEM’s previously announced reduction in force, the ability of MTEM to maintain the continued listing of its common stock on Nasdaq, and those risks identified under the heading “Risk Factors” in Molecular Templates’ filings with the Securities and Exchange Commission (the “SEC”), including its Quarterly Report on Form 10-Q for the quarter ended March 31, 2024 and any subsequent reports filed 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:
Grace Kim
grace.kim@mtem.com
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