Cytokines
by Design
Developing
Disease-Optimized Treatments
Synthekine is a development stage biotherapeutics company focused on the engineering of novel specific, selective and potent cytokine therapies. Our targeted protein engineering guided by our deep experience in immunology provides transformative immunotherapies for the treatment of cancer and autoimmune disorders.
Naturally occurring cytokines play a central role in many key biological processes involved in the mechanism of human diseases, but their pleiotropic activities have complicated their development as pharmaceutical agents. At Synthekine, we leverage our scientific expertise to selectively modulate cytokine agonism and generate new immunotherapies. Synthekine designs differentiated cytokine therapeutics to be both safe and efficacious, and our platform offers a chance to revolutionize how cytokine therapeutics are discovered.
Synthekine was founded, and its core technologies developed, by K. Christopher Garcia, Ph.D., professor of molecular and cellular physiology and structural biology at Stanford University School of Medicine, a Howard Hughes Medical Institute (HHMI) investigator and member of both the National Academy of Sciences and the National Academy of Medicine. His research into the structure-function relationship of cytokines and their receptors provides Synthekine with unique insights essential to the development of these new therapeutic agents with optimized efficacy, larger therapeutic windows and improved safety for patients.
Potential of
Cytokine Medicines

Cytokines are a unique structural class of small messenger molecules that are powerful regulators of the immune system and can stimulate a wide range of different immune cells, primarily driven by their binding and interaction with cell surface receptors. Natural (or wild type) cytokines were evolved to maintain immune system homeostasis. From activating T cells to controlling inflammatory response, cytokines influence countless cellular pathways that are implicated in immunity in humans.

Most cytokines are pleiotropic, meaning that across multiple cell types a given cytokine can exert a range of responses, even opposing responses. This pleiotropy has proven to be a significant obstacle in the development of cytokine therapeutics. Existing cytokine therapeutics – such as aldesleukin and interferons – demonstrate meaningful efficacy in cancer and other diseases, but their applications are limited by significant side effects. However, their critical activities in modulating immune function cannot be overlooked.

Our Science
At Synthekine, we design new molecules that harness these core immunomodulatory activities while minimizing their undesired properties to create new medicines for unmet medical needs.
Our initial focus is on three platform technologies:
Engineered Partial Agonists
Relying on structural information on the cytokine ligand / receptor interaction to engineer the wild type cytokine to alter response and optimize activity
Orthogonal Cell Therapies
Engineered derivatives of naturally occurring cytokines to selectively activate immune cells using an orthogonal ligand receptor system
Synthekine Platform
Unprecedented cytokine engineering platform using surrogate agonists in lieu of mutant cytokines

We are discovering and developing engineered derivatives of therapeutically relevant, naturally occurring cytokines. These carefully engineered proteins provide tunable agonism of cytokine signaling while minimizing undesired activities. Our interleukin-2 (IL-2) partial agonists are based on the deep understanding of the structure-function relationship of this cytokine with its receptors, providing selective activation of particular immune cell types and enabling the development of IL-2-based therapeutics with a unique approach.

Our orthogonal ligand receptor system enables us to selectively activate engineered immune cells both in vitro and in vivo. This core technology enables Synthekine to develop improved versions of adoptive cell therapy products such as CAR-T cells and tumor-infiltrating lymphocyte (TIL) therapies, and it facilitates the use of adoptive cell therapies in therapeutic applications that have proven difficult to treat by conventional methods.

We are currently developing a new CAR-T cell therapy product in combination with this technology, which provides many advantages with respect to available CAR-T products and cell therapies in development.

Our synthekine platform allows us to engineer cytokine agonists that oligomerize cytokine receptors without reliance on the wild-type cytokines. This platform is capable of activating new intracellular pathways, creating new biology and the opportunity for therapeutic intervention beyond what is otherwise possible even with engineered cytokines.

Our Pipeline
STK-009 + SYNCAR-001
Designed to selectively activate CAR-Ts and other adoptive cell therapies (ACTs) in vivo to improve efficacy, persistence and durability of CAR-Ts and other ACTs. Data evaluating STK-009, an orthogonal ligand, with SYNCAR-001, an orthogonal receptor-modified CD-19 targeted CAR-T, were presented at the American Association for Cancer Research Virtual Annual Meeting in 2020. These data show the ability to selectively harness the potent anti-tumoral T-cell effector functions of IL-2 and improve the efficacy, durability and manufacturability of CAR-T cell therapy. Synthekine anticipates filing an IND in 2021 for the STK-009/SYNCAR-001 combination.
Partial Agonists of IL-2
Designed to selectively agonize cancer antigen activated T cells, Synthekine’s lead immuno-oncology IL-2 partial agonist, STK-012, has demonstrated single-agent activity in preclinical tumor models. The company anticipates filing an IND in 2021 for this potent immunotherapy.
Synthekines
Synthekines are agonists that can combine cytokine receptors and drive new signaling activities without any reliance on the wild-type cytokine. This novel combinatorial platform provides the potential to leapfrog the current generation of cytokine therapeutics. The company is developing synthekines across several families of cytokine receptors.
Our Leadership
Synthekine’s leadership has significant experience in cytokine biology and advancing meaningful therapeutic pipelines.
Management Team
Debanjan Ray
Chief Executive Officer
Martin Oft, M.D.
Chief Development Officer
Naiyer Rizvi, M.D.
Chief Medical Officer
Gregory Yedinak
Senior Vice President,
Technical Operations
Robin Knifsend
Senior Vice President,
Finance and Operations
Rob Kastelein, Ph.D.
Vice President of Research,
Head of Discovery
Patrick Lupardus, Ph.D.
Vice President of Research,
Head of Protein Sciences
Richard Murphy, J.D.
Vice President,
Intellectual Property
Christine Rocha
Vice President,
Development Operations
Board of Directors
Srinivas Akkaraju, M.D., Ph.D.
Managing Partner,
Samsara BioCapital
Pablo Cagnoni, M.D.
Independent Director
Mardi Dier
Independent Director
Julie Grant, MBA, MPhil
General Partner,
Canaan Partners
Tim Kutzkey, Ph.D.
Managing Partner,
The Column Group
Nils Lonberg, Ph.D.
Independent Director
Scientific Advisory Board
Christopher Garcia, Ph.D.
Stanford, HHMI
Christopher A. Hunter, Ph.D.
University of Pennsylvania School of Veterinary Medicine
Nils Lonberg, Ph.D.
Biopharma Veteran and Member of Synthekine’s Board of Directors
Antoni Ribas, M.D., Ph.D.
UCLA Jonsson Comprehensive Cancer Center, Parker Institute for Cancer Immunotherapy
Casey Weaver, M.D.
University of Alabama at Birmingham
E. John Wherry, Ph.D.
University of Pennsylvania Institute for Immunology
News
PUBLICATIONS
AACR 2021 – STK-012, an alpha/beta selective IL-2 mutein for the activation of antigen-activated T cells in solid tumors
Jan Emmerich, Navneet Ratti, Michele Bauer, Sandro Vivona, Marie Semana, Bhargavi Jayaraman, Scott McCauley, Romina Riener, Rene De Waal Malefyt, Paul-Joseph Aspuria, Deepti Rokkam, Patrick Lupardus, Rob Kastelein, Martin Oft
AACR 2021 – OrthoCARs: Engineered IL-2/IL-2Rβ orthogonal pairs that selectively enhance CAR T cell function in vivo
Paul-Joseph Aspuria, Sandro Vivona, Michele Bauer, Marie Semana, Navneet Ratti, Scott McCauley, Romina Riener, Rene de Waal Malefyt, Deepti Rokkam, Jan Emmerich, Rob A.Kastelein, Patrick J. Lupardus, and Martin Oft
ASH 2020 – OrthoCARs: Engineered human IL-2/IL-2Rb orthogonal pairs selectively enhance CAR T cell antitumor efficacy
Paul-Joseph Aspuria, Michele Bauer, Sandro Vivona, Steve E. Kauder, Scott McCauley, Romina Riener, Rene de Waal Malefyt, Deepti Rokkam, Jan Emmerich, Rakesh Verma, Patrick J. Lupardus, Rob A. Kastelein, and Martin Oft
AACR 2020 – OrthoCARs: Engineered human IL-2/IL-2Rb orthogonal pairs selectively enhance CAR T cell anti-tumor efficacy and durability of response
Paul-Joseph Aspuria, Michele Bauer, Sandro Vivona, Steven E Kauder, Scott McCauley, Romina Riener, Rene De Waal Malefyte, Navneet Ratti, Deepti Rokkam, Jan Emmerich, Patrick J Lupardus, Rob A Kastelein, Martin Oft
Structure of the IFNγ receptor complex guides design of biased agonists
Juan L. Mendoza, Nichole K. Escalante, Kevin M. Jude, et al.
Selective targeting of engineered T cells using orthogonal IL-2 cytokine-receptor complexes
Jonathan T. Sockolosky, Eleonora Trotta, Giulia Parisi, et al.
Careers

At Synthekine, we adventure beyond conventional scientific thinking. We believe this open mindset — questioning dogma and constantly re-examining the data — is instrumental in discovering and developing transformative medicines.

We are seeking the brightest minds in biology, immunology, pharmacology and protein chemistry to help us advance our cytokine therapeutic pipeline. Are you a scientist hoping to translate your understanding of the complex, unanticipated actions of the immune system into disease-optimized therapies?

Apply for one of our open positions today
Director Supply Chain
Executive Assistant
QC Analyst/Research Associate
Scientist 1 – Cytokine Biology
Scientist 1 – Protein Sciences
Scientist – Molecular Biology
Senior Director/VP – Clinical Development
Senior Scientist/Principal Scientist – Cytokine Biologist
Sr. Process Engineer/Scientist – Cell Therapy
VP – Human Resources
Contact
1505 O’Brien Drive
Menlo Park, California 94025
United States
650.271.9888