4-1BB agonists(Tumor necrosis factor receptor superfamily member 9 agonists), PDL1 inhibitors(Programmed death-ligand 1 inhibitors), albumin modulators(Serum albumin modulators)

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication

Advanced Malignant Solid NeoplasmColorectal CancerFallopian Tube Carcinoma+ [6]

Originator Organization

Numab Therapeutics AG

Active Organization

Numab Therapeutics AG

Cornerstone Pharmaceutical Co., Ltd

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

Gene Sequence

Sequence Code 319918217

100 Clinical Results associated with ND-021

100 Translational Medicine associated with ND-021

100 Patents (Medical) associated with ND-021

Literatures (Medical) associated with ND-021

31 Dec 2023·OncoImmunology

An engineered T-cell engager with selectivity for high mesothelin-expressing cells and activity in the presence of soluble mesothelin

Article

Author: Kirk, Niels ; Alberti, Alessandra ; Warmuth, Stefan ; Flückiger, Naomi ; Lichtlen, Peter ; Brock, Matthias ; Spiga, Fabio Mario ; Gunde, Tea ; Heiz, Robin ; Wagen, Sandro ; Diem, Dania ; Snell, Daniel ; Hess, Christian ; Weinert, Christopher ; Urech, David ; Johansson, Maria ; Yaman, Yasemin ; Giezendanner, Noreen ; Simonin, Alexandre ; Campos Carrascosa, Lucia ; Chatterjee, Bithi ; Mahler, Dana ; Bassler, Nicole

Mesothelin (MSLN) is an attractive immuno-oncology target, but the development of MSLN-targeting therapies has been impeded by tumor shedding of soluble MSLN (sMSLN), on-target off-tumor activity, and an immunosuppressive tumor microenvironment. We sought to engineer an antibody-based, MSLN-targeted T-cell engager (αMSLN/αCD3) with enhanced ability to discriminate high MSLN-expressing tumors from normal tissue, and activity in the presence of sMSLN. We also studied the in vivo antitumor efficacy of this molecule (NM28-2746) alone and in combination with the multifunctional checkpoint inhibitor/T-cell co-activator NM21-1480 (αPD-L1/α4-1BB). Cytotoxicity and T-cell activation induced by NM28-2746 were studied in co-cultures of peripheral blood mononuclear cells and cell lines exhibiting different levels of MSLN expression, including in the presence of soluble MSLN. Xenotransplant models of human pancreatic cancer were used to study the inhibition of tumor growth and stimulation of T-cell infiltration into tumors induced by NM28-2746 alone and in combination with NM21-1480. The bivalent αMSLN T-cell engager NM28-2746 potently induced T-cell activation and T-cell mediated cytotoxicity of high MSLN-expressing cells but had much lower potency against low MSLN-expressing cells. A monovalent counterpart of NM28-2746 had much lower ability to discriminate high MSLN-expressing from low MSLN-expressing cells. The bivalent molecule retained this discriminant ability in the presence of high concentrations of sMSLN. In xenograft models, NM28-2746 exhibited significant tumor suppressing activity, which was significantly enhanced by combination therapy with NM21-1480. NM28-2746, alone or in combination with NM21-1480, may overcome shortcomings of previous MSLN-targeted immuno-oncology drugs, exhibiting enhanced discrimination of high MSLN-expressing cell activity in the presence of sMSLN.

01 Jan 2021·OncoImmunology

Engineering of a trispecific tumor-targeted immunotherapy incorporating 4-1BB co-stimulation and PD-L1 blockade

Article

Author: Simonin, Alexandre ; Brock, Matthias ; Weinert, Christopher ; Flückiger, Naomi ; Wickihalder, Belinda ; Diem, Dania ; Bommer, Bettina ; Mahler, Dana ; Gunde, Tea ; Snell, Daniel ; Tietz, Julia ; Lichtlen, Peter ; Chatterjee, Bithi ; Wagen, Sandro ; Küttner, Benjamin ; Urech, David ; Spiga, Fabio Mario ; Zeberer, Julia ; Heiz, Robin ; Muntwiler, Simone ; Warmuth, Stefan ; Yaman, Yasemin ; Hess, Christian ; Johansson, Maria

Co-stimulatory 4-1BB receptors on tumor-infiltrating T cells are a compelling target for overcoming resistance to immune checkpoint inhibitors, but initial clinical studies of 4-1BB agonist mAbs were accompanied by liver toxicity. We sought to engineer a tri-specific antibody-based molecule that stimulates intratumoral 4-1BB and blocks PD-L1/PD-1 signaling without systemic toxicity and with clinically favorable pharmacokinetics. Recombinant fusion proteins were constructed using scMATCH3 technology and humanized antibody single-chain variable fragments against PD-L1, 4-1BB, and human serum albumin. Paratope affinities were optimized using single amino acid substitutions, leading to design of the drug candidate NM21-1480. Multiple in vitro experiments evaluated pharmacodynamic properties of NM21-1480, and syngeneic mouse tumor models assessed antitumor efficacy and safety of murine analogues. A GLP multiple-dose toxicology study evaluated its safety in non-human primates. NM21-1480 inhibited PD-L1/PD-1 signaling with a potency similar to avelumab, and it potently stimulated 4-1BB signaling only in the presence of PD-L1, while exhibiting an EC₅₀ that was largely independent of PD-L1 density. NM21-1480 exhibited high efficacy for co-activation of pre-stimulated T cells and dendritic cells. In xenograft models in syngeneic mice, NM21-1480 induced tumor regression and tumor infiltration of T cells without causing systemic T-cell activation. A GLP toxicology study revealed no evidence of liver toxicity at doses up to 140 mg/kg, and pharmacokinetic studies in non-human primates suggested a plasma half-life in humans of up to 2 weeks. NM21-1480 has the potential to overcome checkpoint resistance by co-activating tumor-infiltrating lymphocytes without liver toxicity.

News (Medical) associated with ND-021

21 May 2021

·www.pharmaceutical-technology.com

Numab Therapeutics secures $110m in Series C funding round

Numab plans to use the funds to speed up the clinical development of its lead programme, NM21-1480, for various cancers. Credit: Prasesh Shiwakoti (Lomash) / Unsplash. Numab Therapeutics has raised approximately $110m (CHF100m) through Series C funding to expedite the clinical development of its multi-specific antibody pipeline in oncology and inflammation. The funding round was co-led by new investors Novo Holdings and HBM Partners. New investors Forbion, Cormorant Asset Management, BVF Partners, RTW Investments and BlackRock managed funds and accounts and Octagon Capital Advisors also participated along with the current ones. A Switzerland-based clinical-stage biopharmaceutical company, Numab focuses on developing multi-specific antibody immunotherapies for cancer and inflammation. Numab plans to use the funds to speed up the clinical development of its lead programme, NM21-1480, for various cancer types. NM21-1480 can potentially stabilise anti-tumour immunity with a suitable safety profile by concurrently targeting tumour necrosis factor ligand superfamily member 9 (4-1BB), programmed death-ligand 1 (PD-L1) and human serum albumin (HSA). Numab Therapeutics founder and CEO David Urech said: “Combining PD-L1 blockade with tumour localised 4-1BB co-stimulation in a single molecule emerges as an attractive next-generation therapeutic strategy in solid tumours and Numab’s lead compound NM21-1480 has best-in-class potential. “The financing will help us to maximise the value of this asset by significantly expanding the clinical development programme and accelerating toward Phase II proof-of-concept (PoC).” As part of the financing, HBM Partners Private Equity head Matthias Fehr, Nanna Lüneborg from Novo Ventures and Carlo Incerti from Forbion will join Numab’s board of directors. Fehr said: “We are impressed by the biological insights that went into the engineering of NM21-1480 and by the innovative pipeline that Numab has established. “We believe that Numab’s Lambda-cap and MATCH technologies can provide treatment options with favourable benefit-to-risk profiles.” In May 2019, Numab Therapeutics and CStone Pharmaceuticals signed an exclusive regional licensing agreement to develop and market a monovalent, tri-specific antibody-based molecule, ND021, which targets PD-L1, 4-1BB and HSA. PR: Add:

Antibody

100 Deals associated with ND-021

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Discovery	US	Numab Therapeutics AG	19 Aug 2020
Advanced Malignant Solid Neoplasm	Discovery	ES	Numab Therapeutics AG	19 Aug 2020
Advanced Malignant Solid Neoplasm	Discovery	TW	Numab Therapeutics AG	19 Aug 2020
Fallopian Tube Carcinoma	Discovery	TW	Numab Therapeutics AG	19 Aug 2020
Fallopian Tube Carcinoma	Discovery	ES	Numab Therapeutics AG	19 Aug 2020
Fallopian Tube Carcinoma	Discovery	US	Numab Therapeutics AG	19 Aug 2020
Non-Small Cell Lung Cancer	Discovery	US	Numab Therapeutics AG	19 Aug 2020
Squamous Cell Carcinoma of Head and Neck	Discovery	ES	Numab Therapeutics AG	19 Aug 2020
Squamous Cell Carcinoma of Head and Neck	Discovery	US	Numab Therapeutics AG	19 Aug 2020
Squamous Cell Carcinoma of Head and Neck	Discovery	TW	Numab Therapeutics AG	19 Aug 2020

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

ND-021

Overview

Basic Info

Gene Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation