On November 12, 2021 Neoleukin Therapeutics, Inc., "Neoleukin" (NASDAQ:NLTX), a biopharmaceutical company utilizing sophisticated computational methods to design de novo protein therapeutics, reported the presentation of new preclinical data on NL-201, an alpha-independent, de novo-designed IL-2 and IL-15 dual agonist, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 36TH Annual Meeting (SITC 2021) (Press release, Neoleukin Therapeutics, NOV 12, 2021, View Source [SID1234595447]).
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The presentation highlights preclinical data on NL-201 alone and in several combination regimens. NL-201 is a de novo agonist of the IL-2 and IL-15 receptors, designed to expand cancer-fighting CD8 T cells and natural killer (NK) cells without any bias toward cells expressing the IL-2 receptor alpha subunit (CD25).
"The SITC (Free SITC Whitepaper) presentations highlight the broad potential of NL-201, which we believe to be the first fully de novo designed protein to enter clinical trials, to activate the immune system to fight cancer," said Jonathan Drachman, M.D., Chief Executive Officer of Neoleukin. "New data demonstrate that NL-201 can activate the tumor microenvironment and increase T-cell receptor diversity. We also found that local, intratumoral administration can control both the injected and distant tumors with improved tolerability compared to systemic administration in pre-clinical models. We are pleased to share this research as we continue to advance the NL-201 phase 1 clinical trial."
Further details from the presentations are as follows:
Poster/Abstract Number: 716
NL-201 Induces Inflammation in a ‘Cold’ Tumor Microenvironment through Upregulation of MHC-I, Expansion of the TCR Repertoire, and Potent Antitumor Activity when Combined with PD-1 Inhibition
NL-201 turns "cold" tumors "hot" by increasing pro-inflammatory T cells and an immune signature in the tumor microenvironment and upregulating MHC-1 in tumors.
NL-201 stimulates pro-inflammatory tumor reprogramming without the coincident Treg expansion observed with PD-1 antibodies and other immuno-oncology agents.
NL-201 drives anti-tumor efficacy in a manner that is cooperative with PD-1 inhibition, including increasing TCR repertoire diversity.
Poster/Abstract Number: 898
Intratumoral Administration of NL-201, an Alpha-Independent IL-2/15 Receptor Agonist, Inhibits the Growth of Both Injected and Uninjected Tumors in Preclinical Models
Intratumoral NL-201 administration demonstrated:
Dose-dependent antitumor activity in syngeneic murine tumor models;_
Improved tolerability compared to systemic administration at equivalent dose levels and;
Durable tumor-specific immunity.
Results support clinical investigation of intratumoral NL-201 administration to increase NL-201 concentration in accessible lesions and reduce systemic exposure.
Poster/Abstract Number: 509
A First-in-Human Phase 1 Study of NL-201 in Patients with Relapsed or Refractory Cancer (Trials in Progress)
Assessing the safety profile and recommended Phase 2 dose and treatment schedule of NL-201.
Dose escalation and dose expansion cohorts.
Enrollment ongoing at multiple sites in North America and Australia.
Poster/Abstract Number: 563
ICT01, an Anti-BTN3A Monoclonal Antibody, and NL-201, an Alpha-Independent IL-2/IL-15 Agonist, Combine to Elicit a Potent Anti-Tumor Response by Synergistically Stimulating g9d2 T Cell Activation and Proliferation
ICT01 plus NL-201 synergistically triggers gd T-cell activation, expansion and antitumor activity.
Data support clinical evaluation of this novel therapeutic approach.
The poster presentations are available on the Neoleukin website publications page: View Source
About NL-201
NL-201 is a de novo agonist of the IL-2 and IL-15 receptors, designed to expand cancer-fighting CD8 T cells and natural killer (NK) cells without any bias toward cells expressing the alpha receptor subunit (CD25). Previously presented preclinical data has demonstrated the ability of NL-201 to stimulate and expand CD8+ and NK cells at low doses with minimal impact on immunosuppressive regulatory T cells. Furthermore, NL-201 has demonstrated both monotherapy and combination activity across a wide range of preclinical syngeneic tumor models.