Werewolf Therapeutics, Inc. (the “Company” or “Werewolf”)
(Nasdaq: HOWL), an innovative biopharmaceutical company pioneering
the development of conditionally activated therapeutics engineered
to stimulate the body’s immune system for the treatment of cancer,
today announced preliminary first-in-human clinical data from
initial monotherapy dose-escalation cohorts in the Company’s lead
clinical program, WTX-124x2101. This clinical program is an
ongoing, multi-center Phase 1/1b clinical trial of WTX-124,
Werewolf’s interleukin 2 (IL-2) INDUKINE molecule, in patients with
advanced or metastatic solid tumors. The preliminary data will be
presented today at the Society for Immunotherapy of Cancer’s (SITC)
38th Annual Meeting in San Diego, California.
Study WTX-124x2101 is evaluating WTX-124 as a monotherapy and in
combination with pembrolizumab in patients with immunotherapy
sensitive advanced or metastatic solid tumors who have failed
standard of care treatment, including checkpoint inhibitor therapy.
The preliminary data include data collected as of October 18, 2023,
from 16 heavily pretreated patients from the first four monotherapy
dose escalation cohorts (1, 3, 6, 12 mg). The preliminary data
established proof of mechanism for WTX-124 and proof of concept for
Werewolf’s INDUKINE design.
“We are encouraged by these preliminary data demonstrating that
WTX-124 was generally well tolerated while delivering a wild-type
IL-2 to the tumor microenvironment and eliciting monotherapy
biomarker and clinical activity, including two patients with
ongoing unconfirmed partial responses in the 12 mg cohort,” said
Daniel J. Hicklin, Ph.D., President and Chief Executive Officer of
Werewolf. “We look forward to sharing additional data to inform our
recommended dose to proceed into monotherapy expansion arms in the
first half of 2024.”
The preliminary data include assessments of safety and
tolerability, pharmacokinetics, relevant biomarkers and preliminary
antitumor activity. Data as of the October 18, 2023, cutoff date
are summarized as follows:
WTX-124 was generally well-tolerated at all doses tested
up to and including 12 mg in the outpatient setting.
- All treatment-emergent adverse
events (TEAEs) were Grade 1 or Grade 2, and arthralgias and fatigue
were the most common TEAEs. Vascular leak syndrome was not
observed, and there were no dose limiting toxicities,
treatment-related serious adverse events (SAEs) or
treatment-related study discontinuations.
- WTX-124 was delivered intravenously
once every two weeks (Q2W).
WTX-124 showed expected pharmacokinetics with evidence
of wide therapeutic index allowing for continued dose
escalation.
WTX-124 demonstrated both translational biomarker
activity and early evidence of monotherapy antitumor activity at 6
mg and 12 mg doses.
- CD8+ T and NK cell proliferation and
activation in the tumor microenvironment and immune cell gene
expression changes were seen at 6 mg and 12 mg dose levels.
- Among five patients treated at 12
mg, one patient achieved an unconfirmed partial response (uPR), one
patient had a restaging scan that was consistent with a partial
response as of November 1, 2023, and one other showed evidence of
anti-tumor activity.
“IL-2 is a well-validated cytokine, but the challenges
associated with administering high-dose IL-2 have limited its use.
Next-generation approaches have not been successful to date in
demonstrating monotherapy activity at well-tolerated doses,” said
Randi Isaacs, M.D., Chief Medical Officer of Werewolf. “Although
still early in the trial, today’s presentation at SITC of
preliminary data from monotherapy dose escalation highlights
WTX-124’s potential to deliver this important mechanism with
limited toxicity and to provide another therapeutic option to
cancer patients.”
Dose escalation is ongoing in the monotherapy and combination
therapy arms of the trial with additional data from monotherapy
dose-escalation cohorts informing declaration of recommended dose
for expansion (RDE) and opening of the monotherapy expansion arms
expected in the first half of 2024.
In addition, five preclinical posters further supporting the
INDUKINE hypothesis, WTX-124 properties, and other INDUKINE
molecules are being presented at the meeting, including:
Title: PK/RO Modeling of WTX-124, a Tumor-Activated IL-2
Prodrug, Highlights the Potential for a Substantially Improved
Therapeutic Index Compared to Other IL-2 Molecules (Abstract
#1074)
- Plasma and tumor data from mice were
used to perform pharmacodynamic and receptor occupancy modeling to
predict IL-2 receptor occupancy on peripheral lymphocytes and tumor
infiltrating lymphocytes (TILs) suggesting WTX-124 has a
substantially improved, best-in-class therapeutic index as compared
to other IL-2 molecules investigated, including a half-life
extended non-alpha IL-2 and a non-alpha IL-2 tumor-activated
prodrug.
Title: Optimal Antitumor Immunity Triggered by WTX-124, a
Clinical Stage Conditionally Activated INDUKINETM Molecule that
Releases Fully Potent IL-2 in the Tumor Microenvironment (Abstract
#1058)
- WTX-124 generated robust anti-tumor
activity in a MC38 tumor bearing mouse model and promoted the
expansion and activation of tumor specific CD8+ T cells as compared
to a variant Non-Alpha IL-2 containing INDUKINE molecule which
failed to generate anti-tumor activity, to drive tumor specific
CD8+ T cell expansion, or to activate tumor infiltrating immune
cells even when dosed up to 28 times higher than the active dose of
WTX-124. In addition, while both molecules protected tumor
infiltrating CD8+ T cells from exhaustion, only treatment with
WTX-124 was able to induce an effector phenotype in tumor specific
CD8+ T cells and drive clustering of CD8+ T cells with CD103+ cross
presenting dendritic cells within the tumor.
Title: Spatial Analysis of Tumor Infiltrating Lymphocyte
Populations in Syngeneic Mouse Tumor Models After Treatment with
IL-12 (mWTX-330) and IL-2 (WTX-124) INDUKINETM Molecules (Abstract
#1059)
- Combination treatment with WTX-124
and alpha PD-1 generated robust anti-tumor activity in a CT26 model
resulting in widespread tumor infiltration by CD8+ T cells driving
immune activation in the tumor microenvironment. In addition,
detection of structured and unstructured lymphoid aggregates,
including the clustering of various adaptive and innate immune
cells within the tumor microenvironment suggests a zone of
cytotoxic cell education within the tumor microenvironment.
Title: The Combination of ACT and INDUKINETM Therapy Leads to
Improved Antitumor Immunity in Solid Tumors (Abstract # 252)
- Systemic WTX-124 was shown to
preferentially expand CD4 CAR T cells while WTX-330 expanded CD8
CAR T cells, demonstrating that the administration of INDUKINE
proteins with adoptive cell therapy could reinvigorate donor cell
function leading to improved immunity, engraftment and long-term
responses in solid tumors.
Title: Development of WTX-712, a Conditionally Activated IL-21
INDUKINETM Molecule for the Treatment of Cancer (Abstract #
1075)
- WTX-712 was shown to be peripherally
inactive in preclinical studies, releasing IL-21 selectively within
the tumor microenvironment while driving CD8+ T cell
polyfunctionality and promoting immune cell interactions. In
addition, WTX-712 demonstrated enhanced activity when combined with
immune checkpoint inhibitors, blocking PD-1/PD-L1 or CTLA-4
pathways, indicating further evaluation of WTX-712 is
warranted.
The posters will be available on the ‘Scientific Resources’
section of Werewolf Therapeutics website at
https://investors.werewolftx.com/news-and-events/scientific-resources.
Conference Call Information:Management will
host a call to review the preliminary data today, November 3, at
8:30 AM ET. Details for the call can be found here and at
https://investors.werewolftx.com/news-and-events/events.
About Werewolf
Therapeutics:
Werewolf Therapeutics, Inc. is an innovative clinical-stage
biopharmaceutical company pioneering the development of
therapeutics engineered to stimulate the body’s immune system for
the treatment of cancer. We are leveraging our proprietary
PREDATOR™ platform to design conditionally activated molecules that
stimulate both adaptive and innate immunity with the goal of
addressing the limitations of conventional proinflammatory immune
therapies. Our INDUKINE™ molecules are intended to remain inactive
in peripheral tissue yet activate selectively in the tumor
microenvironment. Our most advanced product candidates, WTX-124 and
WTX-330, are systemically delivered, conditionally activated
Interleukin-2 (IL-2), and Interleukin-12 (IL-12) INDUKINE molecules
for the treatment of solid tumors. WTX-124 is in development as a
monotherapy and in combination with KEYTRUDA® (pembrolizumab) in
multiple solid tumor types. WTX-330 is in development as a single
agent in refractory and/or immunotherapy unresponsive or resistant
advanced or metastatic solid tumors and non-Hodgkin lymphoma.
Cautionary Note Regarding Forward-Looking
Statements
This press release contains forward-looking statements that
involve substantial risk and uncertainties. All statements, other
than statements of historical facts, contained in this press
release, including statements regarding Werewolf’s future
operations, prospects, plans, objectives of management, the
expected timeline for the clinical development of product
candidates and availability of data from such clinical development,
and the potential activity and efficacy of product candidates in
preclinical studies and clinical trials constitute forward-looking
statements within the meaning of The Private Securities Litigation
Reform Act of 1995. The words “aim,” “anticipate,” “believe,”
“contemplate,” “continue,” “could,” “design,” “designed to,”
“estimate,” “expect,” “goal,” “intend,” “may,” “might,”
“objective,” “ongoing,” “plan,” “potential,” “predict,” “project,”
“promise,” “should,” “target,” “will,” or “would,” or the negative
of these terms, or other comparable terminology are intended to
identify forward-looking statements, although not all
forward-looking statements contain these identifying words. The
Company may not actually achieve the plans, intentions or
expectations disclosed in these forward-looking statements, and you
should not place undue reliance on these forward-looking
statements. Actual results or events could differ materially from
the plans, intentions and expectations disclosed in these
forward-looking statements as a result of various important
factors, including: uncertainties inherent in the development of
product candidates, including the conduct of research activities,
the initiation and completion of preclinical studies and clinical
trials; uncertainties as to the availability and timing of results
from preclinical studies and clinical trials; the timing of and the
Company’s ability to submit and obtain regulatory approval for
investigational new drug applications; whether results from
preclinical studies will be predictive of the results of later
preclinical studies and clinical trials; whether preliminary data
from a clinical trial will be predictive of the results of the
trial and future clinical trials; the Company’s ability to obtain
sufficient cash resources to fund the Company’s foreseeable and
unforeseeable operating expenses and capital expenditure
requirements; as well as the risks and uncertainties identified in
the “Risk Factors” section of the Company’s most recent Form 10-Q
filed with the Securities and Exchange Commission (“SEC”), and in
subsequent filings the Company may make with the SEC. In addition,
the forward-looking statements included in this press release
represent the Company’s views as of the date of this press release.
The Company anticipates that subsequent events and developments
will cause its views to change. However, while the Company may
elect to update these forward-looking statements at some point in
the future, it specifically disclaims any obligation to do so.
These forward-looking statements should not be relied upon as
representing the Company’s views as of any date subsequent to the
date of this press release.
Investor Contact:Josh
Rappaport Stern IR 212.362.1200Josh.Rappaport@sternir.com
Media Contact:Amanda
SellersVERGE Scientific Communications
301.332.5574asellers@vergescientific.com
Company Contact:Ellen
LubmanChief Business Officer Werewolf Therapeutics
elubman@werewolftx.com
Werewolf Therapeutics (NASDAQ:HOWL)
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부터 4월(4) 2024 으로 5월(5) 2024
Werewolf Therapeutics (NASDAQ:HOWL)
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부터 5월(5) 2023 으로 5월(5) 2024