Preclinical Proof-of-Concept Data Presented at the 2018 Society for
Immunotherapy of Cancer (SITC) Annual Meeting
First ProTriTAC Product Candidate Expected to Enter IND-Enabling
Studies in 2019
WASHINGTON–(BUSINESS WIRE)–Harpoon Therapeutics, Inc. (“Harpoon”), a clinical-stage immunotherapy
company developing a novel class of T cell engagers that harness the
power of the body’s immune system to treat patients suffering from
cancer and other diseases, today presented preclinical data supporting
the development of a new Protease-activated Tri-specific T cell
Activating Construct (“ProTriTAC”) platform. The new ProTriTAC platform
is based on Harpoon’s Tri-specific T cell Activating Construct
(“TriTAC™”) technology, which is designed to bind a patient’s immune
cells to cancer cells. This binding leads to activation of the immune
cell, which then attacks and kills the cancer cell. Data were presented
at the 2018 Society for Immunotherapy of Cancer (SITC) Annual Meeting in
Washington, D.C., held November 9-11, 2018.
Therapeutics derived from the new ProTriTAC platform are intended to be
administered as T cell inactive prodrugs and are optimized for serum
exposure to ensure delivery to solid tumor tissues. At the site of the
tumor, these prodrugs can be locally activated by tumor-associated
proteases. This induces T cells to kill tumor cells expressing target
antigen without affecting other tissues.
“We are very pleased to launch our ProTriTAC platform, which retains the
advantages of our TriTAC platform, including activity at low levels of
target expression, extended serum half-life and conventional
manufacturing. Our ProTriTAC platform allows us to access
tumor-associated antigens that have been historically challenging
because they are expressed in both tumors and non-tumor tissues.
ProTriTAC therapeutics are designed to be serum half-life extended, but
do not engage T cells until they are clipped by tumor-associated
proteases. Once clipped, a T cell activator is released at the site of
the tumor. However, this T cell activator now has a short half-life and
is quickly removed from circulation before it can impact non-tumor
tissues,” said Holger Wesche, PhD, Chief Scientific Officer of Harpoon.
“Harpoon plans to bring its first ProTriTAC product candidate into
IND-enabling studies in 2019.”
“ProTriTAC is an important extension of Harpoon’s proprietary TriTAC
platform, a T cell engager platform designed to harness the natural
power of the patient’s own immune system to fight cancer and other
diseases,” said Jerry McMahon, PhD, President and CEO of Harpoon.
“ProTriTAC product candidates have the potential to increase the number
of possible tumor antigen targets for Harpoon’s emerging pipeline.”
The poster entitled “ProTriTAC: A Protease-Activatable T Cell Engager
Platform That Links Half-Life Extension to Functional Masking” can
be found on the Publications
page of Harpoon’s website. Key proof-of-concept data include:
Biological Activity Dependent on Protease Activation
Intact ProTriTAC proteins can block binding to T cells by more than
500-fold, but they can become fully active after a single proteolytic
cleavage event, enabling T cell binding and activity in the tumor
Potent Anti-Tumor Activity In Vivo Is Protease-Dependent
When administered to tumor-bearing mice, ProTriTAC molecules can
completely inhibit tumor growth with doses as low as 0.03 mg/kg. These
data imply that this activity depends on proteolytic activation of the
ProTriTAC in the tumor.
Reduced T Cell Binding and Rapid Clearance of the Active Drug in
Pharmacokinetic data derived from non-human primates confirm that
ProTriTACs exhibit long serum half-life and support that T cells are not
being engaged by the prodrug form.
About Harpoon Therapeutics
Harpoon Therapeutics is a clinical-stage immunotherapy company
developing a novel class of T cell engagers that harness the power of
the body’s immune system to treat patients suffering from cancer and
other diseases. T cell engagers are engineered proteins that direct a
patient’s own T cells to kill target cells that express specific
proteins, or antigens, carried by the target cells. Using its
proprietary Tri-specific T cell Activating Construct (TriTAC) ™
platform, Harpoon is developing a pipeline of novel T cell engagers, or
TriTACs, and is initially focused on the treatment of solid tumors and
hematologic malignancies. Harpoon has also invented a ProTriTAC platform
that applies a prodrug concept to TriTAC to create T cell engagers
designed to be preferentially active in the tumor microenvironment.
For more information, please visit www.harpoontx.com.