On April 7, 2022 Synthekine Inc., an engineered cytokine therapeutics company, reported five poster presentations based on research spanning each of its three distinct cytokine engineering platforms at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 taking place in New Orleans, LA from April 8-13, 2022 (Press release, Synthekine, APR 7, 2022, View Source [SID1234611610]).

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"Over the past year, we have made advances with all three of our platforms, including moving our first cytokine partial agonist into the clinic, advancing a novel solid tumor cell therapy program using our orthogonal IL-2 receptor/ligand system into preclinical studies, and establishing our first partnership for surrogate cytokine agonists," said Debanjan Ray, Chief Executive Officer of Synthekine. "We are excited to present updates across all of our platforms at AACR (Free AACR Whitepaper) 2022 to showcase the progress we are making to develop biased cytokine therapeutics and advance cytokine science."

Details are as follows and available on the AACR (Free AACR Whitepaper) online itinerary planner:

Title: Trial in Progress: 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)
Session Title: Phase I Trials in Progress 2
Session Date & Time: April 13, 2022, 9:00 AM – 12:30 PM CT
Location: First floor exhibit hall D-H, poster section 35 (poster board: 5)
Abstract Number: CT244
Summary: A first-in-human, open-label, dose escalation and expansion study in adults with advanced solid tumors (NCT05098132). The objectives of this study are to evaluate the safety, pharmacokinetics, immunogenicity, preliminary efficacy, and pharmacodynamics of STK-012 as monotherapy and in combination with pembrolizumab. We announced dosing of the first patient earlier this year.

Title: Engineered human IL-2/IL-2Rβ orthogonal pairs selectively enhance anti-GPC3 CAR T cells to drive complete responses in solid epithelial tumor models
Session Title: Adoptive Cell Therapy 3
Session Date & Time: April 12, 2022, 9:00 AM – 12:30 PM CT
Location: First floor exhibit hall D-H, poster section 35 (poster board: 15)
Abstract Number: 2824
Summary: Here we demonstrate the ability of our orthogonal IL-2 system to enhance the anti-tumor activity and persistence of anti-glypican 3 (GPC3) CAR T cells in human hepatocellular cancer models leading to tumor rejection in the majority of mice. These findings demonstrate that the orthogonal IL-2 system has the potential to improve the efficacy and durability of CAR T therapy for solid tumor targets such as GPC3 by selectively expanding CAR-T cells in vivo, driving CAR-T cells into the tumor, and activating CAR-T cells in the tumor microenvironment.

Title: Orthogonal IL-2/IL-2Rβ signaling in adoptively transferred T cells controls tumor growth without the need for lymphodepletion in a B16 tumor model
Session Title: Adoptive Cell Therapy 2
Session Date & Time: April 10, 2022, 1:30 PM – 5:00 PM CT
Location: First floor exhibit hall D-H, poster section 37 (poster board: 21)
Abstract Number: 586
Summary: We have previously shown a human orthogonal IL-2 receptor/ligand system can selectively proliferate and activate adoptively transferred T-cells (ACTs) without peripheral expansion of native lymphocytes. We have also developed a mouse orthogonal IL-2 receptor/ligand system to show in immune competent mice that the approach can additionally obviate the requirement of lymphodepletion in adoptive cell therapies to improve cell engraftment, persistence and efficacy of ACTs.

Title: IL-2Rβ/IL-2Rγ synthetic cytokines induce activation of human T and NK cells
Session Title: Immunomodulatory Agents and Interventions 3
Session Date & Time: April 13, 2022, 9:00 AM – 12:30 PM CT
Location: First floor exhibit hall D-H, poster section 38 (poster board: 5)
Abstract Number: 4225
Summary: We have generated a series of functional IL-2Rβ/IL-2Rγ surrogate cytokine agonists comprising dimers of heavy chain single domain antibodies (VHH) specific to IL-2Rβ and IL-2Rγ. The surrogate cytokine agonists show a variety of signaling strengths and bias, demonstrating the diversity of molecules that can be generated with this platform.

Title: IL10/IL2 surrogate cytokine agonists
Session Title: Preclinical Immunotherapy
Session Date & Time: April 8, 2022, 12:00 PM – 1:00 PM CT
Location: E-poster website
Abstract Number: 5544
Summary: Designing surrogate cytokine agonists that pair non-natural cytokine receptors allows for generating molecules that can decouple the pleiotropy of cytokines by preferentially stimulating the desired cell population. Here, we have generated IL10Rα/IL2Rγ surrogate cytokine agonists that are biologically active and signal with varying strengths in T cells with little to no activity on monocytes, thus providing an opportunity to decouple the pleiotropy of IL10 and bias its activity toward cell populations associated with anti-tumor efficacy.

E-posters will be released on April 8, 2022 at 12:00 PM CT, and will be available to registered attendees through July 13, 2022.