What is the work you’re leading at Werewolf Therapeutics as Chief Medical Officer?
On a day-to-day basis, I lead the activities of the clinical development and operations team. That includes the ongoing development and translational strategy of two active programs in the clinic, WTX-124 (IL-2) and WTX-330 (IL-12), as well as a broad pipeline of molecules.
"Cytokines are potent modulators of the immune system that work locally in the body, but when administered systemically have poor pharmaceutical properties and severe toxicities that limit their clinical usage."
What can you tell us about Werewolf Therapeutics’ conditionally active immune modulator approach?
Cytokines are potent modulators of the immune system that work locally in the body, but when administered systemically have poor pharmaceutical properties and severe toxicities that limit their clinical usage. Werewolf was formed in 2017 to address the challenges associated with systemic administration of cytokine therapeutics in oncology.
Our approach involves creating unique protein-engineered prodrugs, termed INDUKINE™ molecules. These molecules incorporate the wild-type cytokine (a half-life extension domain for increasing drug exposure), a blocking or masking domain (to prevent peripheral receptor binding and improve the therapeutic index), and protease-cleavable linkers (to deliver the fully potent cytokine immune mechanism to the tumor microenvironment).
What gap in current cytokine therapies does this approach mitigate?
Cytokines are potent, active molecules with important untapped anti-tumor activity. High-dose IL-2 (aldesleukin), for example, was the first immunotherapy to demonstrate durable responses in a small number of patients with metastatic cutaneous melanoma and renal cell carcinoma, leading to its approval in the 1990s. Unfortunately, due to severe toxicities and the requirement for ICU monitoring during administration, it is seldom used now as cancer monotherapy.
Our approach allows for safe, outpatient administration of cytokines to a broad population of patients, not limited by age, performance status, or organ function, and potential usage in any immunotherapy sensitive indication and in combination with standard of care.
If Werewolf’s work is successful, what could the impact be for the broader community?
For patients, this approach provides them with a potential curative therapy. For oncologists, it broadens the options they can give, when they can easily utilize these molecules as part of their therapeutic armamentarium, as monotherapy and in combination.
"Our approach allows for safe, outpatient administration of cytokines to a broad population of patients."
What was your chief priority as CMO, working with a conditionally active agent?
It was critical that we established proof of concept for the INDUKINE design, in order to move forward in development. We have now done that with both of our lead clinical programs by demonstrating a marked improvement in the therapeutic index of these molecules, along with monotherapy anti-tumor and biomarker activity.
What keeps you passionate about this field?
As an oncologist, I went into drug development in order to improve the lives of patients with cancer. I’ve been working in the field of immunotherapy for my entire career and have watched it become one of the mainstays of cancer treatment. I still feel tremendous excitement with every new molecule I put into the clinic and find joy in every patient who responds on trial.
I have an incredible team of drug development, medical, and scientific professionals behind me at Werewolf who come to work everyday because we all want to make a difference. We have devoted sites and investigators who have personal experience now with our active molecules, so we continue to tell our story and present our data.
What was a piece of career advice that helped you during your career that you would pass on to young people, particularly young women, entering careers in science?
Find a mentor, someone with whom you can discuss anything. Do what you love and then just persevere.
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