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DRUG:

NL-201

i
Other names: Neo-2/15, NL-201, NL 201
Associations
Trials
Company:
Neoleukin Therap
Drug class:
IL-2 stimulant, IL-15R agonist, IL-2R agonist
Related drugs:
Associations
Trials
1year
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
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IL2 (Interleukin 2) • STING (stimulator of interferon response cGAMP interactor 1) • CGAS (Cyclic GMP-AMP Synthase) • IL15 (Interleukin 15) • ITGAX (Integrin Subunit Alpha X)
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NL-201
almost3years
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
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CD8 (cluster of differentiation 8) • IL2 (Interleukin 2) • GZMB (Granzyme B) • IL15 (Interleukin 15)
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NL-201
3years
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.
Preclinical • Checkpoint inhibition
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CD8 (cluster of differentiation 8) • IL2 (Interleukin 2)
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NL-201
3years
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)
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).
PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • IL2 (Interleukin 2) • GZMB (Granzyme B) • IL15 (Interleukin 15)
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PD-L1 expression • IFNG expression
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nCounter® PanCancer Immune Profiling Panel
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NL-201
3years
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
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IL2 (Interleukin 2)
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NL-201
4years
Neoleukin-2 enhances anti-tumour immunity downstream of peptide vaccination targeted by an anti-MHC class II VHH. (PubMed, Open Biol)
We then used the VHH-peptide platform to evaluate a panel of candidate neoantigens in vivo in a mouse model of pancreatic cancer. None of the candidate neoantigens tested led to protection from tumour challenge; however, we were able to show vaccine-induced CD8 T cell responses to a melanoma self-antigen that was augmented by combination therapy with the synthetic cytokine mimetic Neo2/15.
Journal • PD(L)-1 Biomarker
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CD8 (cluster of differentiation 8)
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NL-201
4years
[VIRTUAL] NL-201, a de novo IL-2 and IL-15 agonist, demonstrates enhanced in vivo antitumor activity in combination with multiple cancer immunotherapies (SITC 2020)
The synergy of NL-201 with TA99 may result from enhanced NK-mediated antibody-dependent cellular cytotoxicity (ADCC), while the synergy with CPIs may result from CD8+ T cell stimulation, which can turn ‘cold’ tumor microenvironments ‘hot’. Conclusions The broad activity of NL-201 across diverse tumor models and its potential to be combined with a variety of established and exploratory cancer immunotherapies to achieve synergistic antitumor activity highlights the opportunity for NL-201 to become a critical component of future immunotherapy regimens.
Preclinical • Combination therapy
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CD8 (cluster of differentiation 8) • IL2 (Interleukin 2)
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NL-201
4years
[VIRTUAL] NL-201, a de novo IL-2 and IL-15 agonist, demonstrates enhanced in vivo antitumor activity in combination with multiple cancer immunotherapies (SITC 2020)
The synergy of NL-201 with TA99 may result from enhanced NK-mediated antibody-dependent cellular cytotoxicity (ADCC), while the synergy with CPIs may result from CD8+ T cell stimulation, which can turn ‘cold’ tumor microenvironments ‘hot’. Conclusions The broad activity of NL-201 across diverse tumor models and its potential to be combined with a variety of established and exploratory cancer immunotherapies to achieve synergistic antitumor activity highlights the opportunity for NL-201 to become a critical component of future immunotherapy regimens.
Preclinical • Combination therapy
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CD8 (cluster of differentiation 8) • IL2 (Interleukin 2)
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NL-201
over4years
[VIRTUAL] Engineered variants of Neo-2/15 potently expand CAR-T cells and promote antitumor activity in lymphoma and solid tumor mouse models (AACR-II 2020)
In a B cell tumor xenograft model, targeted Neo-2/15 effectively increased CAR-T cell expansion and prolonged survival compared to treatment with CAR-T cells and non-targeted Neo-2/15. Together, these results show that engineered versions of Neo-2/15 induce robust expansion of CAR-T cells and can enhance their antitumor activity.
Preclinical • CAR T-Cell Therapy • IO biomarker
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KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8) • IL2 (Interleukin 2)
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TP53 mutation • KRAS mutation • KRAS overexpression
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JCAR024 • NL-201