How Immatics’ VP of Late-Stage Development Navigating the Transition from Early Development for a TCR-T Therapy
Immatics Biotechnologies VP of Late-Stage Development, Dr Delfi Krishna, talks to us about her work ferrying their TCR-T product from early- to large-stage development, and the impact they hope to have on patients with cutaneous melanoma.
What is the work you’re leading at Immatics as VP of Late-Stage Cell Therapy Development?
I am leading a cross-functional team with the goal to obtain regulatory approval of a PRAME-directed TCR-T autologous cell therapy in cutaneous melanoma. A major challenge of my role is facilitating the strategic, operational and cultural transition from early- to late-stage development for a complex TCR-T product.
"A big challenge is working on how to further develop multiple pipeline candidates that have clinical proof of concept, in a capital-scarce environment."
What are the challenges for your role, related to the stage that Immatics is currently in, and the larger environment-level challenges?
In early development, discussions were focused on the scientific data required to create a clinical proof of concept. Now, we are expanding our focus to include patient, physician, regulatory and payer perspectives in bringing our autologous cell therapies to market.
A big challenge is working on how to further develop multiple pipeline candidates that have clinical proof of concept, in a capital-scarce environment as an organization newly establishing its late-stage identity.
How are you navigating those challenges?
By incorporating diverse perspectives into our work and corporate strategy. Some of our physicians and their patients are willing to share their stories after having administered or having been treated with one of our product candidates. This enables us to benefit from their unique insights and experiences and share them during companywide meetings.
We also request that our physicians and key opinion leaders provide input on study designs and we deliberately put time and effort into learning from the development, regulatory approval and launch of other T-cell therapies. We listen and learn from our investors, too. All in all, I call this a “leadership 360” approach – listening and learning from all angles.
What can you tell us about how you’re approaching success in TCR-Ts differently?
Through early clinical development, we have demonstrated four aspects that are critical for the success of TCR-T in solid tumors:
- highly prevalent and homogeneously expressed targets (e.g. PRAME)
- fine-tuned and specific TCRs
- an optimized manufacturing process to achieve desirable cellular functionality
- understanding the dose-response relationship
This may sound trivial but achieving clarity on these aspects is very important to move beyond clinical proof of concept into late-stage development.
"Tackling pHLA targets enables the identification of otherwise inaccessible intracellular protein targets and thus significantly increases the diversity and novelty of the targets Immatics can pursue."
What gap in treatment or current hurdle of existing cell therapies does this approach mitigate?
Unlike CAR-T therapy and current antibody-based approaches, which can only target cell surface proteins, tackling pHLA targets enables the identification of otherwise inaccessible intracellular protein targets and thus significantly increases the diversity and novelty of the targets Immatics can pursue. Such intracellular targets are generally recognized as one of the most important keys to unlocking hard-to-treat cancers, particularly solid tumors.
Our product candidates are designed to use the potency and specificity of proprietary TCRs to attack and kill cancer cells and, in the case of solid tumors, invade the tumor, overcoming significant hurdles for current immuno-oncology approaches.
What made you passionate about entering this field and keeps you passionate?
I am a science and technology nerd. I get an adrenaline rush by following the journey from ignorance to competence on complicated topics. I find T cells really fascinating and the whole concept of engineering our own cells to conquer cancer is simply mind blowing.
Working in this field, I wake up every morning thinking I can’t believe I get paid to do what I do. Medicine development is done through cross-functional teams pushing and pulling in different directions, and I like to orchestrate them into a creative outcome and encourage them to take bold risks.
I get thrills from contributing to the development of best- or first-in-class medicines. My leadership mission keeps me passionate: inspire colleagues to join me in bringing innovative medicines to patients, and while they do so, to identify their greatest potential, find their most confident voice and have fun while we break boundaries together.
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?
Assemble a “board of directors” advising your career. These are individuals not only willing to champion, sponsor or mentor you but also give you unfiltered feedback to help you grow.
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