On November 14, 2022 Orionis Biosciences, a life sciences company pioneering innovation of highly selective and tunable therapeutics for cancer and beyond, reported that preclinical data supporting its A-Kine platform for rational design of cis-acting immuno-cytokines at the 14th Annual PEGS Europe Protein & Antibody Engineering Summit, taking place November 14 – 16 in Barcelona, Spain (Press release, Orionis Biosciences, NOV 14, 2022, View Source [SID1234624017]). The data demonstrate potent anti-tumor activity across multiple classes of targeted cytokines.

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Cytokines are powerful regulators of the immune system and attractive therapeutic effector candidates. However, their sites of action must be restricted to avoid systemic toxicity. To achieve spatial control of cytokine bioactivity, Orionis has developed a proprietary biologics platform that integrates a strategic "plug-and-play" assembly of modular biomolecular building blocks into therapeutic agents with unique conditional effector functions and cell-target selectivity. These conditionally active, cis-acting cytokines aim to trigger anti-tumor immune responses even in cold tumors that lack prevalent immune involvement and are refractory to checkpoint inhibitor and other therapies.

"Today we shared preclinical data that represent exciting progress for our proprietary A-Kine platform. Our R&D engine, inspired by nature’s intrinsic mechanisms for disease control, has the potential to address some of the biggest challenges in oncology drug discovery and beyond," said Nikolai Kley, Ph.D., Founder, President and Chief Executive Officer of Orionis Biosciences. "As we look ahead, we anticipate IND submission and the start of a conditionally active cytokine Phase 1 trial in 2023."

Orionis’ deep and diversified A-Kine pipeline comprises multiple cytokine classes, including re-engineered interferons (IFNs), interleukins (ILs) and tumor necrosis factors (TNFs). In conjunction with an arsenal of cell-targeting strategies, Orionis is harnessing the therapeutic potential of these cytokines to reprogram immune cells and reactivate the cancer immunity cycle, and thereby the immune system’s natural mechanisms of disease control.

The company presented its advances and breakthroughs in design, engineering and development of exquisitely target-selective A-Kines incorporating:

Cis-acting Interferons to promote immune system recognition and infiltration of tumors
Cis-acting Interleukin-2 to directly activate CD8+ tumor cytotoxic T cells
These unique agents exhibit potent, single agent anti-tumor activity in multiple preclinical cancer models, mediated by targeting of key immune cells, including subtypes of myeloid cells and tumor cytotoxic CD8+ T cells, and PD-1/PD-L1 checkpoint mechanisms. Orionis’ A-Kine pipeline reflects multiple protein engineering innovations and contains an array of programs in lead optimization and IND-enabling phases.

Details of today’s presentation are as follows:

14th Annual PEGS Europe Protein & Antibody Engineering Summit, November 14–16, 2022, Barcelona, Spain

Title: A-Kine Platform: On-Target Cytokines to Reprogram Cell Targets for Immuno-Oncology
Date and Time: Monday, November 14, 11:45 a.m. CET
Presenter: Erik Depla, Ph.D., Director of Biology, Orionis Bio
Orionis recently announced a $55 million financing to support entry of its lead A-Kine cancer immunotherapy programs into the clinic. The company anticipates IND submission and start of a Phase 1 study of a conditionally active cytokine in 2023. In addition to the A-Kine platform, Orionis has developed the Allo-Glue protein degradation platform for discovery and rational design of small molecule molecular glues. These types of conditionally active small molecules are designed to tackle traditionally undruggable or elusive drug targets by harnessing nature’s cellular machinery to degrade and dispose of proteins that cause and/or promote disease.