Theratechnologies TH1902 Study Published in Pharmaceutics Demonstrates Inhibition of Human Sortilin (SORT1)-Positive Ovarian and Triple-Negative Breast Cancer Stem-Like Cells and Tumor Growth
September 12 2022 - 6:30AM
Theratechnologies Inc. (“Theratechnologies” or the “Company”) (TSX:
TH) (NASDAQ: THTX), a biopharmaceutical company focused on the
development and commercialization of innovative therapies, today
announced the publication of a preclinical study demonstrating the
in vitro and in vivo efficacy of TH1902, an investigational
sortilin (SORT1)-targeted peptide-drug conjugate, in inhibiting
ovarian cancer and triple-negative breast cancer (TNBC) stem-like
cells’ (CSCs) tumor growth. The study, published as part of the
special issue of Pharmaceutics “Targeting Drug Resistance and
Metastatic Pathways for Cancer Therapy”, reports that TH1902
appears to exert anticancer activity that is superior to
unconjugated docetaxel in preclinical models, in part by
circumventing the chemoresistance phenotype that is often
responsible for treatment failure and cancer recurrence.
SORT1 is a scavenger receptor protein that binds to circulating
proteins and peptides prior to their intracellular internalization.
It is upregulated in several types of cancer. TH1902, now being
investigated across at least eight solid tumor types in a Phase 1
clinical trial, has been shown in preclinical models to recognize
and exploit SORT1 function, to efficiently trigger in vitro cell
death through apoptosis, to inhibit in vitro cell cycling by
trapping cells into the G2/M phase, and to inhibit in vivo growth
of CSCs from gynecological cancers including ovarian cancer and
TNBC. The Pharmaceutics paper provides the first evidence for
TH1902 targeting of human breast and ovarian CSCs, both in vitro
and in vivo. The limited ability of docetaxel, a widely used cancer
chemotherapeutic agent, to inhibit the growth of CSCs from TNBC and
ovarian cancer may be one mechanism of resistance and limit the
effectiveness of the drug in controlling tumor growth and
spread.
“The development of resistance to chemotherapy is a major
obstacle to successful anticancer treatment, and the presence of
cancer stem-like cells within tumors is believed to play an
important role in that process,” said Dr. Christian Marsolais,
Chief Medical Officer, Theratechnologies. “The Pharmaceutics
publication provides important insights into the ability of TH1902
to inhibit the growth of these cells.”
In the Pharmaceutics paper, researchers at Theratechnologies and
the Molecular Oncology Laboratory at Université du Québec à
Montréal (UQAM) describe the activity of TH1902 against CSCs and
its ability to circumvent some of the known resistance phenotypes
associated with CSCs. Their findings suggest that TH1902 targets
cancer cells overexpressing the sortilin receptor – an effect that
is absent in healthy cells. Additionally, at doses equivalent to
docetaxel, single-agent TH1902 exhibited superior efficacy against
breast and ovarian CSCs, compared to docetaxel alone. Finally, when
combined with carboplatin in an ovarian tumor model, the efficacy
of TH1902 was also superior to that of paclitaxel- or
docetaxel-carboplatin combinations. In TNBC and ovarian CSCs animal
models, TH1902 decreased tumor growth by 80%, compared to roughly
35% in docetaxel-treated mouse models.
“Given our enhanced understanding of the association of SORT1
and cancer resistance to chemotherapy, using TH1902 to exploit
SORT1 function within cancer stem-like cells may further offer a
path to bypassing the chemoresistance phenotype often responsible
for cancer recurrence,” stated Dr. Borhane Annabi, Professor of
Biochemistry and Chair in Cancer Prevention and Treatment at UQAM.
“TH1902 thus appears to offer a promising strategy for targeting
cancer cells that exhibit plasticity, metastatic potential, and
resistance to chemotherapy.”
The U.S. Food and Drug Administration (FDA) granted TH1902
Fast-Track Designation in February 2021. The basket portion of the
Phase 1a/1b trial is currently enrolling at sites across the United
States (TH1902 in Patients With Advanced Solid Tumors - Full Text
View - ClinicalTrials.gov).
About TH1902 and SORT1+ Technology™
Theratechnologies is currently developing a platform of
proprietary peptides called SORT1+ TechnologyTM for cancer drug
development targeting SORT1 receptors. The SORT1 receptor plays a
significant role in protein internalization, sorting and
trafficking. It is highly expressed in cancer cells compared to
healthy tissue, which makes SORT1 an attractive target for cancer
drug development. Expression of SORT1 is associated with aggressive
disease, poor prognosis and decreased survival. It is estimated
that the SORT1 receptor is expressed in 40% to 90% of cases of
endometrial, ovarian, colorectal, triple-negative breast and
pancreatic cancers.
TH1902 is currently Theratechnologies’ lead investigational
peptide-drug conjugate (PDC) candidate for the treatment of cancer
derived from its SORT1+ Technology™. It is the company’s
proprietary peptide linked to docetaxel – a commonly used cytotoxic
agent used to treat many cancers. The FDA granted fast track
designation to TH1902 as a single agent for the treatment of all
sortilin-positive recurrent advanced solid tumors that are
refractory to standard therapy.
About Theratechnologies
Theratechnologies (TSX: TH) (NASDAQ: THTX) is a
biopharmaceutical company focused on the development and
commercialization of innovative therapies addressing unmet medical
needs. Further information about Theratechnologies is available on
the Company's website at www.theratech.com, on SEDAR at
www.sedar.com and on EDGAR at www.sec.gov.
Forward-Looking Information
This press release contains forward-looking statements and
forward-looking information (collectively, “Forward-Looking
Statements”), within the meaning of applicable securities laws,
that are based on our management’s beliefs and assumptions and on
information currently available to our management. You can identify
Forward-Looking Statements by terms such as "may", "will",
"should", "could", “would”, "outlook", "believe", "plan",
"envisage", "anticipate", "expect" and "estimate", or the negatives
of these terms, or variations of them. The Forward-Looking
Statements contained in this press release include, but are not
limited to, statements regarding the development of a treatment for
patients with Sortilin positive solid tumors, the development of
our SORT1+ Technology™ platform and the conduct and recruitment of
patients for the basket trial using TH1902. Although the
Forward-Looking Statements contained in this press release are
based upon what the Company believes are reasonable assumptions in
light of the information currently available, investors are
cautioned against placing undue reliance on these statements since
actual results may vary from the Forward-Looking Statements.
Certain assumptions made in preparing the Forward-Looking
Statements include that: the pre-clinical results obtained using
TH1902 will be replicated into humans, we will be able to continue
recruiting patients to conduct the basket trial using TH1902, no
dose limiting toxicities will be observed in patients comprising
the basket trial, our manufacturer of TH1902 will be able to supply
the required quantity of TH1902 in due time to advance the basket
trial, and we will see signs of efficacy of TH1902 in the conduct
of the basket trial across all patients forming part of the trial.
Forward-Looking Statements assumptions are subject to a number of
risks and uncertainties, many of which are beyond
Theratechnologies’ control that could cause actual results to
differ materially from those that are disclosed in or implied by
such Forward-Looking Statements. These risks and uncertainties
include, but are not limited to, our inability to recruit patients
for the conduct of the basket trial, the observation of adverse
safety issues, the lack of demonstration of efficacy in many or in
all of the patients forming part of the trial, issues regarding the
manufacture and supply of TH1902, and conflicts with third party
suppliers in the conduct of our basket trials. We refer current and
potential investors to the “Risk Factors” section of our Annual
Information Form dated February 23, 2022 available on SEDAR at
www.sedar.com and on EDGAR at www.sec.gov as an exhibit
to our report on Form 40-F dated February 24, 2022 under
Theratechnologies’ public filings for additional risks related to
the Company. The reader is cautioned to consider these and other
risks and uncertainties carefully and not to put undue reliance on
Forward-Looking Statements. Forward-Looking Statements reflect
current expectations regarding future events and speak only as of
the date of this press release and represent our expectations as of
that date. We undertake no obligation to update or revise the
information contained in this press release, whether as a result of
new information, future events or circumstances or otherwise,
except as may be required by applicable law.
Contacts:
Media inquiries:Julie SchneidermanSenior Director,
Communications & Corporate
Affairscommunications@theratech.com1-514-336-7800
Investor inquiries:Elif McDonaldSenior Director, Investor
Relationsir@theratech.com1-438-315-8563
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