The financing was co-led by Canaan Partners, Samsara BioCapital and The Column Group, with participation from other undisclosed investors. Synthekine was founded by K. Christopher Garcia, Ph.D., to leverage discoveries showing that cytokines can be tuned to enhance their therapeutic effects.

Synthekine combines strengths in immunology, structural insights on cytokines and multiple engineering technologies to create optimized therapeutics against new and validated cytokine targets for the treatment of cancer and autoimmune disorders. Proceeds from this Series A financing will be used to advance Synthekine's lead therapeutic programs into clinical studies, expand its discovery pipeline and hone its proprietary cytokine engineering platforms. The company currently has two lead programs in IND-enabling development: STK-012, an engineered Interleukin-2 (IL-2) partial agonist for the treatment of cancer, and the combination of STK-009 and SYNCAR-001, an orthogonal IL-2 ligand and a CD-19 CAR-T-cell therapy being studied in combination.

"Cytokines have a fundamental role in the immune system and represent an enormous opportunity for innovative therapeutics. However, most cytokines broadly activate a wide range of cells that can simultaneously stimulate and suppress the immune system, making drug development against these targets challenging," said Debanjan Ray, chief executive officer of Synthekine. "Chris Garcia has shown, for a wide range of therapeutically important cytokines, that cytokine efficacy and toxicity can be decoupled through structure-based protein engineering. These findings mean that many cytokines previously thought to be unsuitable as therapeutics can be transformed into safe and effective drugs. In addition to our highly differentiated IL-2-based programs, we have assembled multiple best-in-class technologies and an accomplished team to develop cytokine therapeutics by engineering them at the molecular level to enhance their activity and selectivity."

Unlocking cytokine therapeutics through unique structural biology insights

Cytokines are small, soluble proteins that are powerful regulators of the immune system and can stimulate a wide range of immune cells, primarily driven by their binding and interaction with cell surface receptors. Most cytokines are pleiotropic, meaning that a given cytokine can exert a range of responses across multiple cell types. Pleiotropy has proven to be a significant obstacle in the development of cytokine therapeutics. Existing cytokine therapeutics, such as aldesleukin (Proleukin®) and interferons, demonstrate meaningful efficacy in cancer and other diseases but are limited by significant side effects.

Synthekine has licensed several cytokine programs and platforms from Stanford University. Research conducted in the Garcia lab at Stanford led to insights into the interaction of cytokines and their receptors, allowing researchers to engineer modified cytokines to deliver selective activity to particular cell types of therapeutic interest, giving them the potential for optimized efficacy, a larger therapeutic window and improved safety for patients. This research has been responsible for determining the three-dimensional structures for many different cytokine/receptor complexes, including IL-1, IL-2, IL-4, IL-6, IL-13, IL-15, IL-17, IL-23 and the three different classes of interferons.

A deep preclinical pipeline and proprietary platform

Synthekine is advancing several preclinical programs and innovative platform technologies. These include:

STK-012 - Partial Agonist of IL-2: Designed to selectively agonize T cells that recognize tumor antigens, 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.

STK-009 - Orthogonal IL-2 System: 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 IL-2 ligand, with SYNCAR-001, an orthogonal IL-2 receptor-modified CD-19 targeted CAR-T, were presented at the American Association for Cancer Research Virtual Annual Meeting in 2020 and showed 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.

Synthekine platform: Designed as a combinatorial engineering platform, synthekines are surrogate cytokine agonists that can combine cytokine receptors and drive new signaling activities without reliance on the wild type cytokine. The company is developing synthekines across several families of cytokines receptors.

A collaborative company formation effort and seasoned leadership team

The founding members of Synthekine's board of directors include Tim Kutzkey, Ph.D., managing partner of The Column Group; Srinivas Akkaraju, Ph.D., founding partner of Samsara BioCapital; and Julie Grant, general partner at Canaan Partners. Synthekine has also appointed biopharma veteran Nils Lonberg as an independent member of its board of directors.

Synthekine's executive team is led by Debanjan Ray as chief executive officer. Mr. Ray was previously chief financial officer and head of business development at CytomX Therapeutics, where he was responsible for leading financing efforts and securing multiple strategic collaborations with major pharmaceutical companies that generated more than $400 million in upfront payments and up to $4 billion in milestones. The executive team also includes Martin Oft, M.D., as chief development officer, Rob Kastelein, Ph.D., as head of therapeutic discovery and Gregory Yedinak as senior vice president of technical operations.

Synthekine's scientific advisory board is led by its founder, 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 a member of both the National Academy of Sciences and the National Academy of Medicine.

About Synthekine

Synthekine is an engineered cytokine therapeutics company developing disease-optimized treatments. The company uses immunological insights to guide targeted protein engineering to generate transformative medicines for cancer and autoimmune disorders. Using the principles of cytokine partial agonism and immunological specificity, Synthekine designs differentiated therapeutics to be both safe and efficacious. Its lead programs have shown promising efficacy and tolerability in preclinical studies, and it is developing additional cytokine partial agonists that selectively modulate key pathways of the immune system. For more information, visit www.synthekine.com.