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 that a poster describing interim first-in-human
clinical results from initial monotherapy dose-escalation cohorts
in the ongoing Phase 1/1b study of WTX-124 will be presented at the
Society for Immunotherapy of Cancer’s (SITC) 38th Annual Meeting,
taking place November 1-5, 2023 in San Diego, California.
Additional posters with preclinical data supporting the PREDATOR
platform and INDUKINE product candidates will also be presented at
the meeting.
“At SITC, we look forward to sharing first-in-human clinical
results from our lead candidate, WTX-124, including initial
assessments of safety, pharmacokinetics, relevant biomarkers and
preliminary antitumor activity from the ongoing monotherapy
dose-escalation portion of our Phase 1/1b study in solid tumors.
These data will provide early insight into the profile of WTX-124
and preferential activation through our INDUKINE design, including
additional data since the abstract submission in June,” said Randi
Isaacs, M.D., Chief Medical Officer of Werewolf. “Several
preclinical abstracts were also accepted for poster presentation,
collectively reinforcing distinct immune activating potential of
our INDUKINE molecules across various mechanisms, including IL-2,
and as a complement to other anti-cancer approaches, including
checkpoint inhibitors and cell therapy.”
All posters will be available at
https://investors.werewolftx.com/news-and-events/scientific-resources
at 12:00 pm ET on Friday, November 3, 2023. The posters
corresponding to the first three abstracts described below will be
presented at SITC on Friday November 3rd and the posters
corresponding to the second three abstracts described below will be
presented on Saturday November 4th.
Abstract Highlights:
Highlights of the abstracts, which are now available on the SITC
website, include:
Abstract Title: A Phase 1/1b Study of the
Tumor-Activated IL-2 Prodrug WTX-124 Alone or in Combination with
Pembrolizumab in Patients with Immunotherapy-Sensitive Locally
Advanced or Metastatic Solid Tumors Abstract
Number: 737
- This Phase 1/1b, multi-center,
open-label clinical trial is designed to evaluate WTX-124 as a
monotherapy and in combination with KEYTRUDA® (pembrolizumab) in
patients with immunotherapy sensitive advanced or metastatic solid
tumors who have failed standard of care, including prior checkpoint
inhibitor therapy.
- As of June 22, 2023, 11 patients
with relapsed/refractory solid tumors, including non-small cell
lung cancer, cutaneous melanoma and renal cell carcinoma were
treated with WTX-124 in three monotherapy dose escalation cohorts
of 1, 3 and 6 mg administered intravenously every two weeks.
- WTX-124 was well-tolerated with no
dose limiting toxicities at doses up to 6mg.
- Pharmacokinetic data as of June 22,
2023, demonstrated WTX-124 sustained prodrug exposure in plasma
with low levels of active IL-2.
- These results support the potential
of WTX-124 to deliver a potent, wild-type IL-2 to the tumor
microenvironment in patients with solid tumors with limited
toxicities.
Abstract 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
MoleculesAbstract Number: 1059
- Tumor growth over time was measured
in mice bearing syngeneic tumors treated with either mWTX-330 (a
chimeric IL-12 containing INDUKINE TM molecule) or WTX-124 (a human
IL-2 containing INDUKINE molecule) using various techniques,
including high-plex immunofluorescence, resulting in significant
remodeling of immune cell populations found within the tumor tissue
and simultaneously increased immune cell infiltration generating a
potent activation of effector cells.
- These results were further amplified
in combination with PD-1 pathway inhibitors, highlighting the
potential for INDUKINE TM treatments to improve the effects of
checkpoint inhibition therapies.
Abstract Title: Development of WTX-712, a
Conditionally Activated IL-21 INDUKINETM Molecule for the Treatment
of CancerAbstract Number: 1075
- Human IL-21 receptor knock-in
(hIL-21R KI) mice bearing syngeneic tumors were treated with
WTX-712, an IL-21 INDUKINETM molecule, or half-life extended human
IL-21 to monitor tumor growth and body weight over time via flow
cytometry, tissue pharmacokinetics and high-plex
immunofluorescence.
- WTX-712 exhibited activity with an
expanded therapeutic window compared to half-life extended IL-21 in
mouse syngeneic tumor models including complete regressions and
protection against tumor growth upon rechallenge.
Title: The Combination of ACT and INDUKINETM
Therapy Leads to Improved Antitumor Immunity in Solid
TumorsAbstract Number: 252
- The ability of INDUKINE molecules to
improve the engraftment and antitumor activity of adoptive cell
therapy (ACT) products was evaluated using a pmel-1 transgenic
mouse model and a human CD19 CAR-T cell model.
- The combination of pmel-1 ACT and
INDUKINETM polypeptides enhanced antitumor activity and animal
survival compared to either pmel-1 or INDUKINE treatment alone,
including increased donor cell engraftment and persistence of
long-term effector memory T cells in both the periphery and the
tumor microenvironment.
Title: Optimal Antitumor Immunity Triggered by
WTX-124, a Clinical Stage Conditionally Activated INDUKINETM
Molecule that Releases Fully Potent IL-2 in the Tumor
MicroenvironmentAbstract Number: 1058
- The potential benefits of full
activation of IL-2 were evaluated to determine antitumor response
in syngeneic tumor models of WTX-124 as compared to non-alpha forms
of IL-2 designed to reduce dose limiting toxicities associated with
current cytokine therapy.
- Systemic administration of WTX-124
resulted in robust antitumor immunity and preferentially activated
tumor-infiltrating immune cells as compared to a non-alpha IL-2
version of the INDUKINE demonstrating that the full activity of
IL-2 contained in WTX-124 is required to activate potent antitumor
responses.
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
MoleculesAbstract Number: 1074
- A pharmacokinetic model was
developed to evaluate peripheral and tumor lymphocyte IL-2 receptor
occupancy for tumor-activated IL-2 molecules such as WTX-124 as
compared to non-alpha IL-2 molecules.
- WTX-124 was found to be more likely
to improve the therapeutic index by maximizing receptor occupancy
on tumor-infiltrating CD8+ T cells than comparable doses of
non-alpha IL-2 molecules and substantially higher doses of the
non-alpha IL-2 molecule were required to attain the same receptor
occupancy.
Conference Call & Webcast Details
Werewolf management will host a conference call and webcast at
8:30 am ET on Friday, November 3, 2023, to review initial clinical
results from the ongoing Phase 1/1b study of WTX-124 that will be
presented at SITC. The event can be accessed live at
https://investors.werewolftx.com/news-and-events/events. An
archived replay will be available for approximately 90 days
following the event.
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, the expected timeline for the
clinical development of product candidates and availability of data
from such clinical development, and the potential activity,
efficacy and safety 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
interim 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
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