A Phase I, Open-label, Dose Finding Study of NILK-2301, a Bispecific CEACAM5 X CD3 Engaging Antibody, in Patients with Locally Advanced or Metastatic Low Tumor Volume (LTV) Colorectal Cancer

Study LCB-2301-001 is an open-label, Phase 1, dose escalation (Part A) and expansion (Part B), first-in-human clinical study of NILK-2301 in patients with locally advanced or metastatic low tumor volume (LTV) colorectal cancer.
The dose escalation part (Part A) of the study will evaluate the safety and tolerability of escalating doses of NILK-2301 to determine the maximum tolerated dose (MTD) and non-tolerated toxic dose (NTD) of NILK-2301 monotherapy. The expansion part (Part B) will further evaluate the safety and efficacy of NILK-2301 monotherapy administered at or below the MTD in up to 10 additional subjects in order to determine the recommended Phase 2 dose (RP2D).
Treatments will be administered every two weeks in 28-day cycles for up to 12 months until disease progression, unacceptable toxicity, or Investigator/patient decision to withdraw study consent.

Start Date12 Apr 2024

Sponsor / Collaborator

Novimmune SA

100 Clinical Results associated with NILK-2301

100 Translational Medicine associated with NILK-2301

100 Patents (Medical) associated with NILK-2301

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Frontiers in Immunology

Targeting CEACAM5-positive solid tumors using NILK-2401, a novel CEACAM5xCD47 κλ bispecific antibody

Article

Author: Batista, Claudia ; Salgado-Pires, Susana ; Juan-Bégeot, Flora ; Hose, Dirk ; Buatois, Vanessa ; Daubeuf, Bruno ; Richard, Françoise ; Poitevin, Yves ; Seckinger, Anja ; Moine, Valéry ; Rousset, Emeline ; Chatel, Laurence ; Mougin, Christelle ; Bosson, Nicolas ; Viandier, Alizée ; Masternak, Krzysztof

BackgroundBlocking the CD47 “don’t eat me”-signal on tumor cells with monoclonal antibodies or fusion proteins has shown limited clinical activity in hematologic malignancies and solid tumors thus far. Main side effects are associated with non-tumor targeted binding to CD47 particularly on blood cells.MethodsWe present here the generation and preclinical development of NILK-2401, a CEACAM5×CD47 bispecific antibody (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-2401 is a fully human BsAb binding the CEACAM5 N-terminal domain on tumor cells by its lambda light chain arm with an affinity of ≈4 nM and CD47 with its kappa chain arm with an intendedly low affinity of ≈500 nM to enabling tumor-specific blockade of the CD47-SIRPα interaction. For increased activity, NILK-2401 features a functional IgG1 Fc-part. NILK-2401 eliminates CEACAM5-positive tumor cell lines (3/3 colorectal, 2/2 gastric, 2/2 lung) with EC50 for antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity ranging from 0.38 to 25.84 nM and 0.04 to 0.25 nM, respectively. NILK-2401 binds neither CD47-positive/CEACAM5-negative cell lines nor primary epithelial cells. No erythrophagocytosis or platelet activation is observed. Quantification of the pre-existing NILK-2401-reactive T-cell repertoire in the blood of 14 healthy donors with diverse HLA molecules shows a low immunogenic potential. In vivo, NILK-2401 significantly delayed tumor growth in a NOD-SCID colon cancer model and a syngeneic mouse model using human CD47/human SIRPα transgenic mice and prolonged survival. In cynomolgus monkeys, single doses of 0.5 and 20 mg/kg were well tolerated; PK linked to anti-CD47 and Fc-binding seemed to be more than dose-proportional for Cmax and AUC0-inf. Data were validated in human FcRn TG32 mice. Combination of a CEACAM5-targeting T-cell engager (NILK-2301) with NILK-2401 can either boost NILK-2301 activity (Emax) up to 2.5-fold or allows reaching equal NILK-2301 activity at >600-fold (LS174T) to >3,000-fold (MKN-45) lower doses.ConclusionNILK-2401 combines promising preclinical activity with limited potential side effects due to the tumor-targeted blockade of CD47 and low immunogenicity and is planned to enter clinical testing.

100 Deals associated with NILK-2301

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic Colorectal Carcinoma	Phase 1	ES	Novimmune SA	12 Apr 2024
Solid tumor	Phase 1	CH	Novimmune SA	26 Mar 2024

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