Full Press Release Details
Werewolf Therapeutics Presents Preliminary Monotherapy Data from Phase 1/1b Clinical Trial Establishing
Proof of Mechanism for WTX-124 at the Society for Immunotherapy of Cancer s (SITC) 38th Annual Meeting
- Preliminary data on WTX-124 provide compelling early evidence of dose-dependent biomarker and
antitumor activity in patients with advanced or metastatic solid tumors relapsed or refractory to standard of care therapy, including two patients with ongoing unconfirmed partial responses (uPR) in the highest dose tested to date, cohort 4 (12 mg)
- Safety data indicate WTX-124 is generally well-tolerated through cohort 4 with no dose limiting toxicities and no indication of
vascular leak syndrome (VLS) or other typically severe IL-2-mediated toxicities -
- Preliminary data support the potential of WTX-124 to be a differentiated next-generation IL-2 compound by showing immune cell activation in the tumor microenvironment (TME) and monotherapy clinical activity in an
outpatient setting -
- Wide therapeutic index supportive of continued dose escalation with cohort 5 (18 mg) fully enrolled and with
additional interim data from monotherapy dose escalation arm and recommended dose for expansion arm expected in the first half of 2024 -
- Five additional posters showcasing preclinical data from Werewolf pipeline, including WTX-330, WTX-712 and novel adoptive cell therapy approaches, will also be available in the poster sessions -
Company to host webcast today at 8:30 AM ET -
WATERTOWN, Mass., November 3, 2023 (GLOBE NEWSWIRE) 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.
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 12mg 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.
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.
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)
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)
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)
Title: The Combination of ACT and INDUKINETM Therapy Leads to Improved Antitumor Immunity
in Solid Tumors (Abstract # 252)
Title: Development of WTX-712, a
Conditionally Activated IL-21 INDUKINETM Molecule for the Treatment of Cancer (Abstract # 1075)
The posters will be available on the Scientific Resources section of Werewolf Therapeutics
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
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
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.
Communications 301.332.5574
Chief Business Officer
Werewolf Therapeutics