NL-201 / Neoleukin Therap - LARVOL DELTA

Radiation Synergizes with IL-2/IL-15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity. (PubMed, Mol Cancer Ther) - "The immune stimulatory mechanisms triggered by NL-201 and RT resulted in superior tumor growth inhibition and survival benefit in both localized and metastatic cancers. Our results support further preclinical and clinical investigation of this novel synergism regimen in locally advanced and metastatic settings."

Journal • Breast Cancer • Oncology • Solid Tumor • CGAS • IL15 • IL2 • ITGAX • STING

NL-201 upregulates MHC-I expression and intratumoral TCR diversity, and demonstrates robust antitumor activity as monotherapy and in combination with PD-1 blockade. (PubMed, Cancer Immunol Res) - "In the B16F10 model, treatment with NL-201 plus anti-PD-1 increased the abundance of CD4+ and CD8+ effector T cells in the tumor microenvironment. These findings reveal an important mechanistic basis for the antitumor activity of NL-201 both as a monotherapy and in combination with PD-1 antagonists, and provide further context for the role of IL2Rα-based signaling in ICI-resistant tumors."

Combination therapy • IO biomarker • Journal • Monotherapy • Immune Modulation • Oncology • CD4 • CD8 • IFNG • IL15 • IL2RA

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 (SITC 2021) - P1 | "The demonstration that NL-201 can convert 'cold' tumors to immunologically 'hot' tumors may provide a novel therapeutic option for patients unresponsive to current standard of care checkpoint inhibitors. A Phase 1 study of NL-201 in patients with advanced solid tumors is currently underway (NCT04659629)."

Biomarker • IO biomarker • Tumor microenvironment • Oncology • Solid Tumor • CD8 • GZMB • IFNG • IL15 • IL2

ICT01, an anti-BTN3A mAb, and NL-201, an alpha-independent IL-2/IL-15 agonist, combine to elicit a potent anti-tumor response by synergistically stimulating Vg9Vd2 T cell activation and proliferation (SITC 2021) - P1 | "Previous studies have shown that IL-2 (Proleukin®) promotes γ9δ2 T-cells expansion following ICT01 stimulation, which may be clinically useful given that γ9δ2 T-cells are normally <5% of total T-cells [5]. Expanded γ9δ2 T-cells in the combination groups display an effector memory phenotype, confirming our in vitro results. Conclusions These results demonstrate the ability of the ICT01+NL-201 combination to synergistically trigger γ9δ2 T-cell activation, expansion and anti-tumor activity and support clinical evaluation of this combination as a novel therapeutic approach for cancer patients."

Oncology • CD8 • IL15 • IL2 • IL2RA

NL-201 Monotherapy and in Combination With Pembrolizumab in Patients With Relapsed or Refractory Cancer (clinicaltrials.gov) - P1 | N=310 | Active, not recruiting | Sponsor: Neoleukin Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Monotherapy • Oncology • Prostate Cancer • Solid Tumor

Neoleukin Therapeutics Announces Third Quarter 2022 Financial Results and Corporate Update (GlobeNewswire) - P1 | N=310 | NCT04659629 | Sponsor: Neoleukin Therapeutics, Inc. | "Neoleukin announced today that it is discontinuing development of NL-201, its first de novo cytokine mimetic to be tested in patients. Preliminary monotherapy data from the Phase 1 study of NL-201 demonstrated engagement of the target receptor, expected pharmacodynamic changes for a potent IL-2/IL-15 agonist, and did not demonstrate significant immunogenicity even after multiple cycles of therapy....Neoleukin determined that the resources required to continue development would be better applied to advancing the next generation of de novo protein therapeutics."

Discontinued • P1 data • Oncology • Solid Tumor

A first-in-human Phase 1 study of NL-201 in patients with relapsed or refractory cancer (SITC 2021) - P1 | "Clinicaltrials.gov identifier: NCT04659629. Trial Registration Clinicaltrials.gov identifier: NCT04659629."

Clinical • P1 data • Brain Cancer • Oncology • Solid Tumor • CD8 • IL15 • IL2

A first-in-human phase 1 study of NL-201 in patients with relapsed or refractory cancer (AACR 2022) - P1 | "Key exclusion criteria include history of brain cancer or active brain metastases, carcinomatous meningitis, neurologic autoimmune disease; patients previously receiving CAR-T or IL-2-based therapies are not eligible. Recruitment of Part 1 began in April 2021, and the trial is actively enrolling."

Clinical • P1 data • Brain Cancer • Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • CD8 • IL15 • IL2

Neoleukin Therapeutics Announces First Patient Treated in Combination Arm of Phase 1 Trial Evaluating NL-201 in Combination with KEYTRUDA (pembrolizumab) (GlobeNewswire) - "Neoleukin Therapeutics, Inc...announced treatment of the first patient in a combination arm evaluating the safety and efficacy of Neoleukin’s NL-201 in combination with Merck’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab), as part of Neoleukin’s ongoing Phase 1 trial in patients with relapsed or refractory solid tumors....Up to 132 patients will be enrolled in the combination arm of the study, which is being conducted through a clinical collaboration and supply agreement with Merck (known as MSD outside the United States and Canada)."

Trial status • Oncology • Solid Tumor

NL-201, a de novo agonist of IL-2 and IL-15 receptors, demonstrates antitumor activity in preclinical B cell lymphoma models (AACR 2022) - "The NL-201 enhancement of cytotoxicity by CD8+ T cells and NK cells supports additional exploration aimed at optimizing combinatorial approaches. These findings will inform the design of planned clinical studies with NL-201 in patients with B-cell lymphomas and other hematological malignancies."

Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • CD8 • GZMB • IL15 • IL2 • STAT5

NL-201, a de novo engineered IL2/IL15 mimic, synergizes with radiation to generate potent antitumor immunity (AACR 2022) - "Furthermore, we identify a unique mechanism in which NL-201 synergizes with RT, likely via the direct activation of STING in DCs. Taken together, the results provided herein support further preclinical and clinical investigation of this novel combination regimen in both localized and metastatic settings."

Brain Cancer • Breast Cancer • Oncology • Solid Tumor • CGAS • IL15 • IL2 • STING

Neoleukin Therapeutics Announces Preclinical Data for NL-201 at American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "Neoleukin Therapeutics...announced the presentation of preclinical data and a trial in progress overview for its immunotherapy candidate NL-201, an IL-2 and IL-15 agonist, at the American Association for Cancer Research (AACR) Annual Meeting....NL-201 monotherapy demonstrates antitumor activity in the human Pfeiffer xenograft lymphoma model....NL-201 in combination with radiation therapy enhances activation of the cytosolic DNA sensor cyclic GMP-AMP synthase stimulator of interferon genes (cGAS-STING) pathway....The multinational, first-in-human, open-label Phase 1 trial of NL-201 monotherapy is assessing the safety profile, recommended Phase 2 dose and treatment schedule in patients with advanced and/or refractory solid tumors....Enrollment is ongoing at sites in North America and Australia."

Preclinical • Trial status • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

Neoleukin Therapeutics Announces Year End 2021 Financial Results and Corporate Update (GlobeNewswire) - "The open label Phase 1 trial of NL-201 is active at participating sites in the United States, Australia and Canada. Enrollment in the trial is progressing. Dose escalation is currently underway and will continue through 2022. Interim data is expected to be reported in the second half of 2022."

P1 data • Oncology • Solid Tumor

NL-201 in Patients With Relapsed or Refractory Cancer (clinicaltrials.gov) - P1 | N=252 | Recruiting | Sponsor: Neoleukin Therapeutics, Inc. | N=120 ➔ 252

Enrollment change • Oncology • Solid Tumor

Neoleukin Therapeutics Announces Clinical Collaboration with Merck to Evaluate NL-201 in Combination with KEYTRUDA (pembrolizumab) (GlobeNewswire) - "Neoleukin Therapeutics, Inc...announced a clinical trial collaboration and supply agreement with Merck (known as MSD outside the United States and Canada). The agreement will allow for the evaluation of safety and efficacy of Neoleukin’s NL-201, a de novo protein designed to mimic the therapeutic activity of natural cytokines IL-2 and IL-15, in combination with Merck’s anti-PD-1 therapy KEYTRUDA^® (pembrolizumab) in an ongoing Phase 1 trial."

Licensing / partnership • Oncology • Solid Tumor

Seattle Cancer Care Alliance Clinicians Present New Research at 63rd Annual Meeting of the American Society of Hematology (Businesswire) - "Seattle Cancer Care Alliance (SCCA)...announced that more than 20 of the organization’s clinicians will showcase new research at the 63rd Annual Meeting of the American Society of Hematology (ASH), taking place December 11-14, 2021, in Atlanta....Clinicians will discuss findings on CAR-T therapies targeting CD20 cells, multiple myeloma and chronic lymphocytic leukemia. Key research also includes findings on hematopoietic stem cell transplant (HCT) and outcomes and utilization for a range of treatments."

Clinical data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology

NL-201, a De Novo Agonist of IL-2 and IL-15 Receptors, Demonstrates Synergistic Antitumor Activity with Anti-PD-1 Checkpoint Inhibitor Therapy in a Preclinical Non-Hodgkin Lymphoma Model (ASH 2021) - "Additional in vitro and in vivo NHL models are being tested to enhance understanding of the interaction between NL-201 and other approved therapies within the hematopoietic tumor microenvironment. These data will be used to design future clinical trials of NL-201 in novel regimens to treat hematological malignancies."

Checkpoint inhibition • Preclinical • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD8 • IL15 • IL2

Neoleukin Therapeutics Announces Preclinical Data Highlighting Activity of NL-201 in Hematologic Malignancies at 63rd American Society of Hematology Annual Meeting (ASH 2021) (GlobeNewswire) - "The preclinical multiple myeloma data...demonstrate the ability of NL-201 to prevent relapse in murine myeloma models following autologous stem cell transplant....NL-201 treated mice had an increase in bone marrow T-cells expressing granzyme B and a decrease in the T-cell exhaustion phenotype."

Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology

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 (SITC 2021) - "Rechallenged animals failed to develop tumors, demonstrating durable tumor-specific immunity after IT NL-201 treatment. Results of this study support planned clinical investigation of IT NL-201 administration to increase NL-201 concentrations in accessible lesions."

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • IL15 • IL2

ImCheck Provides Promising Updated Patient Response Data from the Phase I/IIa EVICTION Trial with ICT01 at SITC Meeting 2021 (GlobeNewswire) - P1/2a, N=150; EVICTION (NCT04243499); Sponsor: ImCheck Therapeutics; "In efficacy evaluable patients (n=8) treated with the combination of low dose ICT01 plus pembrolizumab who previously failed at least one prior checkpoint inhibitor regimen, 62% showed disease control by RECIST1.1 criteria. Two patients demonstrated a preliminary positive durable response at 24 and 32 weeks. In one metastatic melanoma patient with a brain metastasis, which would typically be unresponsive to standard of care treatments, a complete response of the brain metastasis was observed at week 27 of treatment; a preclinical study of ICT01 plus NL-201 treatment suggests favorable results from the synergistic activity of both candidates through enhanced γ9δ2 T cell activation, expansion and anti-tumor activity in comparison with monotherapy. The synergistic effect of this combined treatment makes a strong case for further investigation of this therapeutic approach"

P1/2 data • Preclinical • Melanoma • Oncology

Neoleukin Therapeutics Presents NL-201 Preclinical Data at Society for Immunotherapy of Cancer’s 36th Annual Meeting (SITC 2021) (GlobeNewswire) - "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; 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."

Preclinical • Oncology

Neoleukin Therapeutics Announces Third Quarter 2021 Financial Results and Corporate Update (GlobeNewswire) - "NL-201 is currently in a phase 1 clinical trial for patients with relapsed and refractory solid tumors. A second trial for patients with hematologic malignancies is expected to begin next year....Neoleukin and collaborators will present four abstracts at SITC 2021."

Clinical data • New trial • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

ImCheck to Present Updated Patient Response Data from the EVICTION Trial and Additional ICT01 Results at the SITC Annual Meeting 2021 (GlobeNewswire) - "ImCheck Therapeutics today announced that it will present updated clinical data from the ongoing EVICTION Phase I/IIa trial evaluating ICT01, a first-in-class Butyrophilin (BTN) 3A-targeting monoclonal antibody, alone and in combination with pembrolizumab in patients with advanced, relapsed/refractory solid and hematological cancers, in one oral presentation and one poster, as well as an additional poster covering preclinical evaluation of ICT01 in combination with a novel IL-2/IL-15 agonist, at the 36th Society for Immunotherapy of Cancer (SITC) Annual Meeting being held both in person and virtually from November 10 - 14, 2021."

P1/2 data • Preclinical • Oncology • Solid Tumor

Neoleukin Therapeutics Announces Multiple Abstracts Accepted for Presentation at the Society for Immunotherapy of Cancer’s 36th Annual Meeting (SITC 2021) (GlobeNewswire) - "Neoleukin Therapeutics, Inc...announced the acceptance of four abstracts to be presented at the upcoming Society for Immunotherapy of Cancer’s 36th Annual Meeting (SITC 2021) taking place November 10-14, 2021, at the Walter E. Washington Convention Center in Washington, D.C."

Clinical • Preclinical • Oncology • Solid Tumor

Neoleukin Therapeutics Announces Second Quarter 2021 Financial Results & Provides Corporate Update (GlobeNewswire) - “While certain factors, including COVID-19, have had an impact on site activation for our Phase 1 trial of NL-201, we are accelerating site start-up activities to increase the pace of enrollment. Interim data from the ongoing systemic Phase 1 trial of NL-201 is currently anticipated in 2022.”

Enrollment status • P1 data • Oncology