Cytokines by Design
 
 
Developing Disease-Optimized Treatments
We believe that engineered, selective cytokine therapeutics can fundamentally improve the treatment paradigm of cancer and inflammatory disease.
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. Leveraging Dr. Garcia’s foundational research and our team’s decades of experience in cytokine discovery, immunology research, and drug development, we have built a differentiated multi-modality product pipeline of specific, selective, and potent therapeutics against a wide range of high-value targets.
Potential of Cytokine Medicines
Cytokines are small proteins that allow immune cells to communicate and are central to the body’s response to diseases, such as cancer, and to the maintenance of immune homeostasis. These naturally occurring, or wild-type, cytokines often exert many different types of responses, often on different or even the same cell types. This pleiotropy has made harnessing the therapeutic potential of these powerful modulators of the immune system difficult, as most cytokines either promote or dampen the body’s innate or adaptive immune response depending on the cell type and activation state of the cell. While several cytokine therapeutics have demonstrated meaningful benefit in the treatment of cancer and other diseases, cytokine pleiotropy has led to limited efficacy, dose-limiting toxicities, and narrow therapeutic windows. Our goal is to utilize our world-class team’s expertise in cytokine biology, immunology, and drug development to harness the potential of cytokine therapeutics and avoid cytokine-mediated toxicities in order to become a leader in developing selective immunotherapies.
 
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:
Cytokine Partial Agonist Platform
Relying on structural information on the cytokine ligand / receptor interaction to engineer the wild type cytokine to alter response and optimize activity
Orthogonal Cytokine Cell Therapy Platform
Engineered derivatives of naturally occurring cytokines to selectively activate immune cells using an orthogonal ligand receptor system
Surrogate Cytokine Agonist Platform
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 surrogate cytokine agonist platform enables us to combinatorially dimerize or multimerize receptor subunits in ways wild-type cytokines or mutein-based approaches cannot. 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. Presented data evaluating STK-009, an orthogonal IL-2 ligand, 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 SYNCAR-001, an orthogonal receptor-modified CD19 targeted CAR-T.
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.
Surrogate Cytokine Agonists
Surrogate cytokine agonists can dimerize or multimerize cytokine receptors and drive new signaling activities without any reliance on the wild-type cytokine. Our novel combinatorial platform provides the potential to leapfrog the current generation of cytokine therapeutics. The company is developing surrogate agonists 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
PRESS RELEASES
April 7, 2022
Synthekine Announces Multiple Poster Presentations Showcasing Its Three Distinct Cytokine Engineering Platforms at American Association for Cancer Research (AACR) 2022 Annual Meeting
February 3, 2022
Synthekine Doses First Patient in Phase 1 Clinical Trial of IL-2 Partial Agonist, STK-012, for Treatment of Solid Tumors
December 23, 2021
Synthekine Announces Publication of Preclinical Data Demonstrating In Vivo Control of CD19 CAR-T Cells with its Orthogonal IL-2 System
November 1, 2021
Synthekine Establishes Collaboration with Merck to Develop Therapeutic Candidates Using its Proprietary Surrogate Cytokine Agonist Platform
October 28, 2021
Synthekine Advances IL-2 Partial Agonist, STK-012, into Clinical Investigation for Treatment of Solid Tumors
June 10, 2021
Synthekine Announces $107.5 Million Oversubscribed Series B Financing to Support Lead Programs to Clinical Proof of Concept, Advance Preclinical Programs and Platform
June 3, 2021
Synthekine Expands Board of Directors, Management Team and Scientific Advisory Board with New Key Appointments
May 3, 2021
Synthekine Appoints Internationally Recognized Cancer Immunotherapy Leader Naiyer Rizvi, M.D., as Chief Medical Officer
April 22, 2021
Synthekine Licenses Additional Cytokine Programs
April 10, 2021
Synthekine Presents Data at AACR Annual Meeting 2021 Demonstrating Selective IL-2 Partial Agonist, STK-012, Promotes Anti-Tumor Response without Related Toxicities
February 4, 2021
Synthekine Strengthens Leadership with Board of Directors Expansion and Scientific Advisory Board Formation
December 7, 2020
Synthekine Presents Data at American Society of Hematology Annual Meeting Showing Orthogonal IL-2 Ligand Drives Deeper and More Durable Response of CD-19 CAR-T
September 17, 2020
Synthekine Launches with $82 Million Series A Financing to Advance Pipeline of Engineered Cytokine Therapeutics Optimized for Cancer and Autoimmune Diseases
IN THE NEWS
Synthekine’s $82M Series A to Support Engineered Cytokine Development
September 17, 2020
Synthekine Launches with $82M to Create New Cytokine Signals
September 21, 2020
PUBLICATIONS
AACR 2022 – IL10/IL2 Surrogate Cytokine Agonists
Mahalakshmi Ramadass, Sandro Vivona, Deepti Rokkam, Heiko Greb, Anu Gangopadhyay, Romina Riener, Rene de Waal Malefyt, Scott McCauley, Patrick Lupardus, Martin Oft and Robert Kastelein
AACR 2022 – IL-2Rβ/IL-2Rγ Synthetic Cytokines Induce Activation of Human T and NK Cells
Rene de Waal Malefyt, PJ Aspuria, Sandro Vivona, Priyanka Balasubrahmanyam, Cindy Buffone, Mahalakshmi Ramadass, Romina Riener, Martin Oft, Patrick Lupardus and Robert Kastelein
AACR 2022 – Orthogonal IL-2/IL-2Rβ signaling in adoptively transferred T cells controls tumor growth without the need for lymphodepletion in a B16 tumor model
Christina Kochel, Meng Sun, Navneet Ratti, Sandro Vivona, Bhargavi Jayaraman, Romina Riener, Marie Semana, Michele Bauer, Mohammed Ali, Jan Emmerich, Rob Kastelein, Patrick Lupardus, Paul-Joseph Aspuria and Martin Oft
AACR 2022 – Engineered human IL-2/IL-2Rβ orthogonal pairs selectively enhance anti-GPC3 CAR T cells to drive complete responses in solid epithelial tumor models
Paul-Joseph Aspuria, Marie Semana, Mahalaksmi Ramadass, Navneet Ratti, Sandro Vivona, Romina Riener, Michele Bauer, Mohammed Ali, Deepti Rokkam, Rob A. Kastelein, Patrick J. Lupardus, and Martin Oft
AACR 2022 – CT244: A Phase 1a/1b study of STK-012, an α/β IL-2 receptor selective partial agonist as monotherapy and in combination with pembrolizumab in advanced solid tumors (NCT05098132)
David Spigel, Alexander Spira, Dmitriy Zamarin, David F. McDermott, Jason Luke, Rebecca Previs, Ryan Sullivan, Kartik Sehgal, Alex Azrilevich, Naiyer Rizvi, Martin Oft, Natalie Busby and Benjamin Izar
An orthogonal IL-2 and IL-2Rb system drives persistence and activation of CAR T cells and clearance of bulky lymphoma
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, Martin Oft
SITC Pre-Conference 2021: OrthoIL2 signaling in ACT controls tumor growth without the need for lymphodepletion
Christina Kochel, Meng Sun, Navneet Ratti, Sandro Vivona, Romina Reiner, Marie Semana, Michele Bauer, Mohammed Ali, Jan Emmerich, Rob Kastelein, Patrick Lupardus, Paul-Joseph Aspuria and Martin Oft
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.
Tuning Cytokine Receptor Signaling by Re-orienting Dimer Geometry with Surrogate Ligands
Ignacio Moraga, Gerlinde Wernig, Jacob Piehler, 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?

NOTE TO RECRUITERS AND EMPLOYMENT AGENCIES:

All of our open positions are managed through our Human Resources department. Any resumes submitted through the website or directly by recruiters or staffing agencies in advance of an executed agreement with Synthekine, will be considered unsolicited and the company will not be responsible for any related fees. Resumes sent directly to employees or hiring managers will also not be accepted as referrals.

Apply for one of our open positions today
Accounting Manager
Accounts Payable Specialist
Clinical Trials Manager
Data Scientist/Senior Data Scientist
Director of Intellectual Property
Director, Program Management
Front Desk Administrative Assistant
Human Resources Director
Medical Director / Senior Medical Director
Payroll & Stock Administration Manager
Principal Scientist / Associate Director, Process Development
Process Engineer Cytokine Biologics
Research Associate I/II, Analytical Development
Research Associate I/II, Mammalian Cell Culture
Research Associate/Senior Research Associate Bioanalytical Translational Sciences
Scientist / Sr. Scientist, Cell Therapy
Scientist I/II, Cytokine Biology
Scientist, Antibody Engineering
Senior Manager / Associate Director, Business Development
Senior/Principal Process Engineer MSAT – Cell Therapy
Sr. Research Associate, Upstream Process Development
Vice President, QA/QC
Vice President, Regulatory Affairs
 
Contact
1505 O’Brien Drive Menlo Park, California 94025 United States
650.271.9888
LinkedIn Twitter