Delving into the Latest Updates on Lamkap Bio Alpha AG with Synapse

Overview

Tags

Neoplasms

Digestive System Disorders

Bispecific antibody

Bispecific T-cell Engager (BiTE)

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Neoplasms	2

Top 5 Drug Type	Count

Bispecific antibody	1
Bispecific T-cell Engager (BiTE)	1

Top 5 Target	Count

CD47 x CEA	1
CD3ε x CEACAM5	1

Author: Kallendrusch, Sonja ; Lesnier, Adeline ; Calloud, Sebastien ; Poitevin, Yves ; Magistrelli, Giovanni ; Ngoc, Hoang ; Hose, Dirk ; Daubeuf, Bruno ; Gockel, Ines ; Malinge, Pauline ; Papaioannou, Anne ; Masternak, Krzysztof ; Shang, Limin ; Strein, Klaus ; Pleche, Nicolas ; Cons, Laura ; Seckinger, Anja ; Majocchi, Sara ; Lordick, Florian ; Ravn, Ulla ; Salgado-Pires, Susana ; Chatel, Laurence ; Broyer, Lucile ; Kramer, Sebastian ; Moine, Valery ; Nouveau, Lise

T-cell retargeting to eliminate CEACAM5-expressing cancer cells via CEACAM5xCD3 bispecific antibodies (BsAbs) showed limited clin. activity so far, mostly due to insufficient T-cell activation, dose-limiting toxicities, and formation of anti-drug antibodies (ADA).We present here the generation and preclin. development of NILK-2301, a BsAb composed of a common heavy chain and two different light chains, one kappa and one lambda, determining specificity (so-called κλ body format).NILK-2301 binds CD3ε on T-cells with its lambda light chain arm with an affinity of ≈100 nM, and the CEACAM5 A2 domain on tumor cells by its kappa light chain arm with an affinity of ≈5 nM.FcγR-binding is abrogated by the "LALAPA" mutation (Leu234Ala, Leu235Ala, Pro329Ala).NILK-2301 induced T-cell activation, proliferation, cytokine release, and T-cell dependent cellular cytotoxicity of CEACAM5-pos. tumor cell lines (5/5 colorectal, 2/2 gastric, 2/2 lung), e.g., SK-CO-1 (Emax = 89%), MKN-45 (Emax = 84%), and H2122 (Emax = 97%), with EC50 ranging from 0.02 to 0.14 nM.NILK-2301 binds neither to CEACAM5-neg. or primary colon epithelial cells nor to other CEACAM family members.NILK-2301 alone or in combination with checkpoint inhibition showed activity in organotypic tumor tissue slices and colorectal cancer organoid models.In vivo, NILK-2301 at 10 mg/kg significantly delayed tumor progression in colon- and a pancreatic adenocarcinoma model.Single-dose pharmacokinetics (PK) and tolerability in cynomolgus monkeys at 0.5 or 10 mg/kg i.v. or 20 mg s.c. showed dose-proportional PK, bioavailability ≈100%, and a projected half-life in humans of 13.1 days.NILK-2301 was well-tolerated.Data were confirmed in human FcRn TG32 mice.In summary, NILK-2301 combines promising preclin. activity and safety with lower probability of ADA-generation due to its format compared to other mols. and is scheduled to enter clin. testing at the end of 2023.

Journal of Hematology & Oncology

Development and characterization of NILK-2301, a novel CEACAM5xCD3 κλ bispecific antibody for immunotherapy of CEACAM5-expressing cancers

Article

Author: Krämer, Sebastian ; Malinge, Pauline ; Poitevin, Yves ; Magistrelli, Giovanni ; Kallendrusch, Sonja ; Nouveau, Lise ; Calloud, Sebastien ; Lordick, Florian ; Papaioannou, Anne ; Chatel, Laurence ; Gockel, Ines ; Ngoc, Hoang ; Daubeuf, Bruno ; Moine, Valéry ; Cons, Laura ; Salgado-Pires, Susana ; Ravn, Ulla ; Strein, Klaus ; Hose, Dirk ; Lesnier, Adeline ; Majocchi, Sara ; Seckinger, Anja ; Broyer, Lucile ; Pleche, Nicolas ; Masternak, Krzysztof ; Shang, Limin

AbstractBackgroundT-cell retargeting to eliminate CEACAM5-expressing cancer cells via CEACAM5xCD3 bispecific antibodies (BsAbs) showed limited clinical activity so far, mostly due to insufficient T-cell activation, dose-limiting toxicities, and formation of anti-drug antibodies (ADA).MethodsWe present here the generation and preclinical development of NILK-2301, a BsAb composed of a common heavy chain and two different light chains, one kappa and one lambda, determining specificity (so-called κλ body format).ResultsNILK-2301 binds CD3ɛ on T-cells with its lambda light chain arm with an affinity of ≈100 nM, and the CEACAM5 A2 domain on tumor cells by its kappa light chain arm with an affinity of ≈5 nM. FcγR-binding is abrogated by the “LALAPA” mutation (Leu234Ala, Leu235Ala, Pro329Ala). NILK-2301 induced T-cell activation, proliferation, cytokine release, and T-cell dependent cellular cytotoxicity of CEACAM5-positive tumor cell lines (5/5 colorectal, 2/2 gastric, 2/2 lung), e.g., SK-CO-1 (Emax = 89%), MKN-45 (Emax = 84%), and H2122 (Emax = 97%), with EC50 ranging from 0.02 to 0.14 nM. NILK-2301 binds neither to CEACAM5-negative or primary colon epithelial cells nor to other CEACAM family members. NILK-2301 alone or in combination with checkpoint inhibition showed activity in organotypic tumor tissue slices and colorectal cancer organoid models. In vivo, NILK-2301 at 10 mg/kg significantly delayed tumor progression in colon- and a pancreatic adenocarcinoma model. Single-dose pharmacokinetics (PK) and tolerability in cynomolgus monkeys at 0.5 or 10 mg/kg intravenously or 20 mg subcutaneously showed dose-proportional PK, bioavailability ≈100%, and a projected half-life in humans of 13.1 days. NILK-2301 was well-tolerated. Data were confirmed in human FcRn TG32 mice.ConclusionsIn summary, NILK-2301 combines promising preclinical activity and safety with lower probability of ADA-generation due to its format compared to other molecules and is scheduled to enter clinical testing at the end of 2023.

100 Deals associated with Lamkap Bio Alpha AG

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100 Translational Medicine associated with Lamkap Bio Alpha AG

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Pipeline

Pipeline Snapshot as of 24 Jan 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

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