Molecular Templates, Inc. Provides Interim Update
June 03 2024 - 8:11AM
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 Kimgrace.kim@mtem.com
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