Founder's Vision

One of the most dramatic advances in medicine over the past decade has been the emergence of immunotherapy for cancer. The development of checkpoint blockade therapy by Jim Allison, the development of TIL therapy by Steve Rosenberg and the development of CAR-T therapy by Carl June and others have taught us that autologous T cells are capable of treating and sometimes eradicating cancer. Lyell is a next generation autologous T cell therapy company whose goal is to bring to patients – simply stated – curative therapy for any solid tumor.

While our goal is ambitious, it is actually grounded in the abundant evidence that autologous T cells can eradicate even advanced and refractory cancer, but only occasionally and only in a few cancers. Our goal is therefore not to prove this possibility, but to make it reliably and predictably effective, widely applicable and practicable for any cancer in any patient!

Our approach has been to examine currently available human data to understand the underlying reasons and correlates of why and when autologous T cell therapy against solid tumors is sometimes successful and more often fails.

Through this, we have identified what we believe are the two most important barriers to successful therapy:

• Exhaustion of T cells
• Ability to create the effective and self-renewing – properties which we term durable stemness – therapeutic product in each dose we give to patients

The primacy of these barriers and the solutions for them that we have developed come from the labs of our three scientific founders, Nick Restifo, Stan Riddell and Crystal Mackall. We are striving to overcome these two barriers with our ability to reprogram T cells to adopt those qualities correlated with, and thus necessary for, successful solid tumor eradication. The pursuit to elucidate and overcome these barriers is our foundation and ethos.

We have created T Cell Reprogramming Platforms that we believe can be directed at almost any cancer. While many are exploring new ways to manufacture T cell therapies, we are asking not “how” to manufacture cell preparations, but “what” T cells and their properties we need to manufacture. Our goal is to fundamentally redefine the very composition of adoptive cell therapy preparations, and therefore their reliable efficacy. We believe that these platforms are applicable to any modality for targeting tumors, be they CARs, TILs or cloned TCRs and our clinical programs will incorporate each of these targeting modalities.

Our story is the story of our science. The execution of that science has been the product of one of the most remarkable teams that I have ever worked with. We are committed to continued scientific innovation, and so while our first two T cell reprogramming platforms are ready to be tested in the clinic, we continue to develop next generation reprogramming platforms, including one based on our ability to rejuvenate, or turn back the age of, T cells.

We have built an end-to-end company capable of discovering new science, designed to translate that science into products, manufacture those products and clinically test our science and products.

We believe that the use of living cells as therapies will be a big part of the future of medicine, representing the third evolution in therapeutics, the first being the use of small molecules which defined the pharmaceutical industry, the second, the use of biologic macromolecules which defined the biotech industry and finally, cell therapy – living, dynamic therapy to confront an always-evolving disease. It will be our ability to define and control the identity, fate and function of these cells that will enable us to create cell-based curative therapies and it is within this new paradigm of medicine that we have built Lyell.

For me personally, Lyell represents the culmination of a long journey – from the work in my own lab in the 1980s that helped define how T cells are turned on, and the discovery of the molecular engine that underlies CAR T cells and the activity of all T cells when they see their target antigens; to overseeing the nation’s cancer program as NCI Director in the 1990s; to my co-founding of Juno Therapeutics. The dream of creating curative therapies for cancer for the many patients and families confronting this disease has inspired and motivated me to stay on that journey. It is the privilege of building companies that can take science into the clinic, with aspirations to change the lives of those patients, that I hope will be the beginning of the end of that journey.

Rick Klausner, M.D.

Founder & Board Chair