Science

De Novo Protein Design

Proteins are amazing molecular machines that carry out many critical tasks in the human body.

The remarkable function of a protein is guided by its 3-dimensional structure, formed by the intricate folding of linear chains of amino acids.

Traditionally, protein engineers have modified natural proteins to turn them into therapeutics. However, this approach is fundamentally limited by the building blocks that nature provides.

WHAT IF ENTIRELY NEW PROTEINS COULD BE BUILT FROM SCRATCH, custom-designed to overcome the biggest challenges in modern medicine?

That’s the promise of protein design.

By combining innovative algorithms and the power of modern computing, Neoleukin Therapeutics is bringing the protein design revolution to patients.

Designing de novo proteins to address today’s toughest medical challenges

The Neoleukin Platform

A Pioneering Approach to Building Custom Protein Therapeutics

Protein Design image

The Neoleukin Platform is a propriety, computational approach to developing new – de novo – proteins that overcome the limitations of naturally occurring proteins, offering the potential for targeted and precise treatments.

De novo proteins created using the Neoleukin Platform are highly selective and hyper-stable. These biologically active de novo proteins are designed to overcome biological problems that have not been solved using natural proteins.

For example, interleukin-2 has been problematical as a therapeutic due to the biased activation of cells that contain the alpha component of the IL-2 receptor (also known as CD25). Using the Neoleukin Platform, Neoleukin scientists designed a completely de novo protein with the proper intermolecular interactions to recapitulate potent IL-2 signaling while completely eliminating CD25 binding. This approach can be used to create de novo therapeutic proteins with improved efficacy, lower toxicity, increased stability, improved pharmacokinetic properties, or alternate routes of administration.

Publications

NL-201, a de novo IL-2/IL-15 agonist, demonstrates enhanced in vivo antitumor activity in combination with multiple cancer immunotherapies
Walkey et. Al, SITC 2020, Abstract #576, November 2020
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De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2
T. W. Linsky et. al. Science. 10.1126/science.abe0075 (2020)

Pre-clinical development of NL-201: A de novo α-independent IL-2/IL-15 agonist
Walkey et. Al, AACR Virtual Annual Meeting II, Abstract #4518, June 2020
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Access poster/presentation at AACR.org

Engineered variants of Neo-2/15 potently expand CAR-T cells and promote antitumor activity in lymphoma and solid tumor mouse models
Leung, et. Al, AACR Virtual Annual Meeting II, Abstract #222, June 2020
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Access poster/presentation at AACR.org

Conditionally active de novo IL-2 cytokine mimetics for targeted immunotherapy: de novo split technology
Quijano-Rubio et. Al., AACR Virtual Annual Meeting II, Abstract #1075, Jun/2020
Access presentation at AACR.org

De novo design of potent and selective mimics of IL-2 and IL-15
DA Silva et al. Nature. VOL 565, pages 186–191 (2019)

The advent of de novo proteins for cancer immunotherapy
Alfredo Quijano-Rubio, Umut Y. Ulge, Carl D. Walkey, Daniel-Adriano Silva. Current Opinion in Chemical Biology (in press) Available online 1 May 2020.

Collaborations & Partnerships

At Neoleukin, we believe in the power of scientific collaboration. We welcome connections with potential collaborators in academia and industry who share our excitement and passion to explore new applications of our technology.

If you’d like to learn more about potential collaborative opportunities, please contact us.