Harpoon Therapeutics, Inc. (Nasdaq: HARP), a clinical-stage
immuno-oncology company developing novel T cell engagers, today
presented preclinical data on two new development candidates from
the proprietary ProTriTAC™ platform in TROP2- and
ITGB6-expressing solid tumors in poster presentations at the
American Association for Cancer Research (AACR) Annual Meeting
being held in Orlando, Fla., April 14-19, 2023. ProTriTAC is a T
cell engager prodrug platform designed to remain inert systemically
until its activation in the tumor by tumor-associated proteases and
enable the safe targeting of broadly expressed solid tumor
antigens. The first candidate, TROP2 ProTriTAC, is a
protease-activated T cell engager prodrug targeting TROP2. The
second candidate, ITGB6 ProTriTAC, is a protease-activated T cell
engager prodrug targeting integrin-beta6.
“TROP2 and ITGB6 are tumor targets that are overexpressed in
numerous solid tumor types and have demonstrated clinical utility
when targeted as antibody drug conjugates,” said Luke Walker, M.D.,
Chief Medical Officer of Harpoon Therapeutics. “However,
significant unmet needs remain as both the depth and the durability
of response with antibody drug conjugates are typically limited.
The ability to safely target TROP2 and ITGB6 with T cell engagers,
as the preclinical data with our ProTriTAC platform now
demonstrate, warrants further study in the clinic.”
“Our ProTriTAC platform is designed to improve the therapeutic
index of T cell engagers targeting solid tumor antigens,” said S.
Jack Lin, Ph.D., Senior Director, Research and Preclinical
Development, Harpoon Therapeutics. “The data presented at AACR
further demonstrate that the ProTriTAC platform can be applied
broadly to target different solid tumor antigens, which are often
expressed elsewhere on normal tissues, and can achieve potent
anti-tumor activities without incurring significant on-target
off-tumor toxicities at the anticipated therapeutically relevant
dose levels.”
Highlights from the posters include:
Abstract #2927: ITGB6 ProTriTAC™, a protease-activated T
cell engager prodrug targeting Integrin-β6 for the treatment of
solid tumorsITGB6 protein is expressed in multiple tumor
types, including cervical, lung, and head and neck, among others.
In rodent established tumor models, ITGB6 ProTriTAC showed
efficient prodrug activation and potent anti-tumor activity in vivo
with complete tumor eradication at doses as low as 30 µg/kg. In
cynomolgus monkeys, ITGB6 ProTriTAC showed favorable
pharmacokinetic and safety profiles and was well-tolerated up to
540 µg/kg, the highest dose tested. Hematological changes consisted
of minimally to moderately decreased neutrophils at all dose
levels, as well as transient decreases in lymphocytes and basophils
in week three of the study. There were no notable findings in
plasma cytokines (IFNγ, IL-1β, IL-2, IL-6, IL-10, IL-8, TNF-α),
coagulation, clinical chemistry, or urinalysis parameters.
Additionally, there were no notable histopathological findings
based on organ weight, gross and microscopic examination.
Abstract #2928: TROP2 ProTriTAC™, a protease-activated T
cell engager prodrug targeting TROP2 for the treatment of solid
tumorsTROP2 protein is expressed in multiple solid tumor
types, including cervical, prostate and ovarian, among others. In
rodent established tumor models, TROP2 ProTriTAC had highly potent
anti-tumor activity in vivo with complete tumor eradication at
doses as low as 30 µg/kg. In cynomolgus monkeys, TROP2 ProTriTAC
showed favorable pharmacokinetics and was well-tolerated up to 180
µg/kg, whereas 540 µg/kg triggered on-target toxicity with mixed
cell infiltrates in organs where normal tissue expression of TROP2
is expected. There were no notable findings in serum cytokines
(IFNγ, IL-1β, IL-2, IL-6, IL-10, IL-8, TNF-α) throughout the
study.
For more details about the AACR Annual Meeting, please visit:
https://www.aacr.org/meeting/aacr-annual-meeting-2023/
The posters will be available on Harpoon’s website following
today’s presentations.
Harpoon’s three distinct T cell engager platforms are designed
to potentially allow more patients to get maximum clinical benefit
while maintaining the best possible quality of life. Harpoon’s
first platform, the constitutively active TriTAC® (Tri-specific T
cell activating construct), is designed to minimize off-target
toxicities, and is ideal for targets with limited on-target
liabilities. The ProTriTAC platform offers similar advantages and
adds an element of spatial control, with activation directed
primarily to the tumor microenvironment. This spatial control of
activation may address on-target tissue damage, hence enabling an
expansion of the T cell engager target space. The
TriTAC-XR™ platform (extended-release with slow activation in
circulation) adds improved temporal control and is designed to be
activated in the systemic circulation at a predefined rate to
minimize on-target cytokine release syndrome (CRS).
About Harpoon Therapeutics
Harpoon Therapeutics is a clinical-stage immuno-oncology
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 TriTACs initially focused on the treatment of solid
tumors and hematologic malignancies. Harpoon has also developed a
proprietary ProTriTAC™ platform, which applies a prodrug
concept to its TriTAC platform to create a therapeutic T cell
engager that remains inactive until it reaches the tumor. Harpoon’s
third proprietary technology platform, extended release TriTAC-XR,
is designed to mitigate cytokine release syndrome. For additional
information about Harpoon Therapeutics, please visit
www.harpoontx.com.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. Words such as “may,” “expect,” “potential,” “further,”
“will,” and similar expressions (as well as other words or
expressions referencing future events, conditions or circumstances)
are intended to identify forward-looking statements. These
forward-looking statements are based on Harpoon Therapeutics’
expectations and assumptions as of the date of this press release.
Each of these forward-looking statements involves risks and
uncertainties that could cause Harpoon Therapeutics’ clinical
development programs, future results or performance to differ
significantly from those expressed or implied by the
forward-looking statements. Forward-looking statements contained in
this press release include, but are not limited to, statements
about the expected progress, results, and plans pertaining to
Harpoon Therapeutics’ clinical trials, the association of interim
clinical data and preclinical results with potential treatment
outcomes, and other statements that are not historical fact. Many
factors may cause differences between current expectations and
actual results, including unexpected safety or efficacy data
observed during clinical studies, preliminary data and trends may
not be predictive of future data or results, may not
demonstrate safety or efficacy or lead to regulatory approval by
the FDA or other regulatory agencies, clinical trial site
activation or enrollment rates that are lower than expected,
changes in expected or existing competition, changes in the
regulatory environment, the uncertainties and timing of the
regulatory approval process, the timing and results of unexpected
litigation or other disputes, and the sufficiency of Harpoon
Therapeutics’ cash resources. These and other factors that may
cause Harpoon Therapeutics’ actual results to differ from those
expressed or implied in the forward-looking statements in this
press release are discussed in Harpoon Therapeutics’ filings with
the U.S. Securities and Exchange Commission, including under
“Risk Factors” in Harpoon Therapeutics’ annual report on Form 10-K
for the year ended December 31, 2022, and future filings
by Harpoon Therapeutics. Except as required by
law, Harpoon Therapeutics assumes no obligation to update
any forward-looking statements contained herein to reflect any
change in expectations, even as new information becomes
available.
Contacts:
Investors:ICR WestwickeRobert H. UhlManaging
Director858-356-5932 robert.uhl@westwicke.com
Media:Uncapped
Communications303-588-0599kerry.walton@uncappedcommunications.com
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