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

概览

疾病领域	数量

肿瘤	1

排名前五的药物类型	数量

双特异性抗体	1

排名前五的靶点	数量

CD47 x CEA	1

关联

1

项与 Lamkap Bio Alpha AG 相关的药物

NI-2401

靶点

CD47 x CEA

作用机制

CD47抑制剂 [+3]

在研机构

Lamkap Bio Alpha AG [+1]

原研机构

Novimmune SA

在研适应症

实体瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

100 项与 Lamkap Bio Alpha AG 相关的临床结果

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0 项与 Lamkap Bio Alpha AG 相关的专利（医药）

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2

项与 Lamkap Bio Alpha AG 相关的文献（医药）

Journal of Hematology & Oncology

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

Article

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

Journal of Hematology & Oncology

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

作者: 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 ; Chatel, Laurence ; Lordick, Florian ; Majocchi, Sara ; Salgado-Pires, Susana ; Moine, Valery ; Ravn, Ulla ; Kramer, Sebastian ; Broyer, Lucile ; 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.

100 项与 Lamkap Bio Alpha AG 相关的药物交易

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100 项与 Lamkap Bio Alpha AG 相关的转化医学

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