Molecular Templates Announces Poster Presentations on its Engineered Toxin Bodies at the American Association of Cancer Resea...
April 12 2021 - 7:00AM
Molecular Templates, Inc. (Nasdaq: MTEM, “Molecular Templates,” or
“MTEM”), a clinical-stage biopharmaceutical company focused on the
discovery and development of proprietary targeted biologic
therapeutics, engineered toxin bodies (ETBs), today reported that
three posters featuring data on its pipeline programs and
technology platform will be presented at the AACR Virtual
Annual Meeting I, taking place April 10-15, 2021.
Title: |
Phase 1 Study of the Novel Immunotoxin MT-5111 in Patients
with HER2+ Tumors |
Authors: |
Zev A. Wainberg, MD; Monica M. Mita, MD; Minal A. Barve, MD; Erika
P. Hamilton, MD; Andrew J. Brenner, MD, PhD; Frances Valdes, MD;
Daniel Ahn, DO; Joleen Hubbard, MD; Jason Starr, DO; Christine
Burnett, PhD; Joshua Pelham; Eric T. Williams, PhD; Aimee Iberg,
PhD; Thomas Strack, MD; Andrés Machado Sandri, MD; Brian A. Van
Tine, MD, PhD |
Abstract # |
CT130 |
This poster summarizes results from a data cut
in December 2020 for an ongoing Phase 1, first in human,
open-label, dose escalation and expansion study
of MT-5111 in subjects with HER2+ solid tumors. MT-5111
has a novel mechanism of action that may not be subject to
resistance mechanisms that exist for current HER2 therapies, binds
a distinct epitope on HER2 that allows for potential combination
with trastuzumab-based therapies, and, at 55kDa, is significantly
smaller than other HER2 antibody or ADC therapies. As of the data
cut in December 2020, 16 study subjects had been treated in the 3+3
cohort escalation. The cancer types included biliary tract (n=6),
breast (n=6), pancreatic (n=2), gastric (n=1), and colon (n=1).
Results to date show that MT-5111 has been well tolerated at
escalated doses up to Cohort 5 (4.5 µg/kg), which allowed for the
progression to Cohort 6 (6.75 µg/kg). There have not been any dose
limiting toxicities nor any signs of cardiotoxicity to date, and
the MTD has not been reached. Pharmacokinetic data for the first 5
cohorts matched simulations based on non-human primate studies.
Exposures at 4.5 µg/kg have reached approximately 5x the IC 50 of
HER2-expressing cell lines.
Three patients experienced stable disease as best response per
RECIST 1.1 criteria (1 pancreatic at 4.5 µg//kg, 1 breast at 2
µg//kg, 1 biliary tract at 2 µg/kg). As previously reported, one
subject with metastatic breast cancer in cohort 2 (1 µg/kg)
remained on treatment for 10 cycles with stable disease; although
she had unmeasurable disease by RECIST criteria, she had three
sub-centimeter hepatic lesions that disappeared at the end of cycle
8 before she discontinued for clinical progression/symptomatic
deterioration at cycle 10. This subject had received three
prior HER2 targeting regimens which initially included pertuzumab
plus trastuzumab followed by trastuzumab and TDM1 as monotherapies.
Dose escalation continues and no dose limiting toxicities have been
observed to date at 6.75 µg/kg (Cohort 6).
The HER2+ breast cancer expansion cohort is planned to be
initiated in 2Q21 at a dose of 10 μg/kg (anticipated to be a
therapeutic dose level), pending adequate safety from the 10 μg/kg
dose escalation cohort. Dose escalation in all HER2+ tumor types
will continue (including potential cohorts beyond 10 µg/kg) to
determine the recommended Phase 2 dose while the breast cancer
expansion cohort collects efficacy and safety data. As doses higher
than 10 μg/kg are considered to be tolerable in the dose escalation
cohort, the dose will be increased in the breast cancer cohort
accordingly.
Title: |
Preclinical Characterization of a Novel CTLA-4-Targeted ETB
for Direct Treg Depletion |
Authors: |
Khanna, Caleigh Howard, Lilia A. Rabia, Alvaro Aldana, Jay Zhao,
Asis Sarkar, Eric Williams, Banmeet Anand, Betty Chang, Chris
Moore, Hilario J. Ramos, Aimee Iberg -- Molecular Templates Inc.,
Austin, TX. |
Abstract # |
1627 |
Current CTLA-4 antibodies have shown efficacy in
oncology but have been limited by toxicity issues and an inability
to clear regulatory T cells (Tregs) from the tumor microenvironment
(TME). CTLA-4-targeted ETBs are designed to preferentially deplete
Tregs in the TME to improve efficacy and reduce the toxicity
associated with CTLA-4 targeted antibodies. This study explored the
preclinical characterization of a lead candidate CTLA-4-targeted
ETB. CTLA-4-ETB-A directly binds and specifically kills CTLA-4
positive cells in vitro and induces apoptosis of ex-vivo expanded
Tregs. CTLA-4-ETB-A is designed to bind CTLA-4 in a manner unique
from classic blocking antibodies and is not expected to have
sustained blocking ability in vivo due to the relatively short
half-life of an ETB compared to a neutralizing monoclonal antibody.
The authors predict this will allow for focused Treg depletion in
the TME based on target expression levels, while sparing
autoreactive T cell activation in the periphery to reduce or
eliminate the toxicity seen with CTLA-4 antibodies. In a transgenic
mouse model expressing human CTLA-4 and bearing syngeneic
subcutaneous tumors, CTLA-4 expression was highest on the Treg
cells within the tumor microenvironment compared to other T cell
populations and compartments. In this model, it was demonstrated
that ETB treatment depletes Tregs in the TME, supporting the
overall hypothesis. Peripheral CD4+ T cell proliferation was
observed in response to ETB treatment. Initial tox assessment was
performed in a non-human primate (NHP) model. ETB candidate A was
well tolerated up to 450 μg/kg. An increase in proliferating CD4+
and CD8+ central memory T cells was observed and is a potential
pharmacodynamic effect.
Title: |
Engineered Toxin Bodies Targeting PD-L1 to Alter Tumor
Immunophenotypes and Delivery Broad Antigenic Diversity and Patient
Coverage |
Authors: |
Swati Khanna, Elizabeth Saputra, Wenzhao Dong, Lindsey Aschenbach,
Lilia A. Rabia, Garrett L. Cornelison, Michaela Sousares, Jay Zhao,
Lee Robinson, Betty Chang, Hilario J. Ramos, Joseph D.
DekkerMolecular Templates Inc., Austin, TX |
Abstract # |
1628 |
MT-6402 is an ETB designed to deliver a unique
and dual mechanisms of action approach for directly targeting
tumors that express PD-L1 on the tumor and/or the TME. Unlike
current checkpoint inhibitors which only bind PD-L1 and sterically
block interactions with PD-1, MT-6402 directly destroys PD-L1+
tumor and TME immune cells. MT-6402 has dual mechanisms of action
that include the enzymatic destruction of ribosomes and the
delivery of a viral class I antigen derived from CMV (pp65) into
the targeted tumor, referred to as Antigen Seeding Technology
(AST), for presentation on the target tumor cell surface to alter
the tumor immunophenotype and induce a CMV specific T-cell
response. MT-6402’s antigen seeding CMV pp65 payload covers the
largest MHC haplotype in the US. Delivery of foreign antigens that
are restricted to additional MHC haplotypes could broaden the
patient population that could benefit from AST. ETBs
based on MT-6402 that deliver additional antigens retain expected
potency and target binding, while also activating donor CTLs with
matched haplotypes. ETBs delivering antigens to a broader
population are under investigation for in vivo safety, efficacy and
function. The MT-6402 IND filing has been accepted by the FDA with
the Phase 1 first-in-human study expected to begin dosing in
2Q21.
About Molecular Templates
Molecular Templates is a clinical-stage 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 other serious 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 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 the safety or
potential efficacy of Molecular Templates’ drug or biologic
candidates; statements relating to the development of MT-5111,
MT-6402 and CTLA-4; the expected timing of submitting various IND
applications, initiating and completing enrollment of cohorts,
initiating and conducting studies and generating data; the expected
participation and presentation at upcoming conferences; the
anticipated effects of the COVID-19 pandemic on Molecular
Templates’ ongoing clinical studies, manufacturing and preclinical
development; and Molecular Templates’ belief that its proprietary
biologic drug platform technology, or ETBs, provides for a
differentiated mechanism of action that may address some of the
limitations associated with currently available cancer
therapeutics.
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 uncertainties inherent in the
preclinical and clinical development process; whether Molecular
Templates’ cash resources will be sufficient to fund its continuing
operations for the periods and/or trials anticipated; the ability
of Molecular Templates’ to protect its intellectual property
rights; risks from global pandemics including COVID-19; 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. There can be no
assurance that any of Molecular Templates’ drug or biologic
candidates will be successfully developed, manufactured or
commercialized, that final results of clinical trials will be
supportive of regulatory approvals required to market products, or
that any of the forward-looking information provided herein will be
proven accurate. 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.
Contact:Adam CutlerChief Financial
Officeradam.cutler@mtem.com 862-204-4006
Molecular Templates (NASDAQ:MTEM)
Historical Stock Chart
From Aug 2024 to Sep 2024
Molecular Templates (NASDAQ:MTEM)
Historical Stock Chart
From Sep 2023 to Sep 2024