SOT102, a novel CLDN18.2-targeting antibody-drug conjugate, exhibits strong therapeutic potential in solid tumors

Sep 22, 2026

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SOT102 is a novel antibody–drug conjugate designed to target claudin 18.2 (CLDN18.2), a tumor-associated marker predominantly expressed in gastric and pancreatic cancers and also present in multiple other solid tumors. The study evaluates binding, internalization, and cytotoxicity in vitro, then measures antitumor activity in patient- and cell line-derived xenograft models with monotherapy or anti-PD1 combination. Pharmacokinetics and tolerability are assessed in cynomolgus monkeys, supporting further clinical investigation.

LanguageEnglish

CategoryHealthcare

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Pages14

Reading Time35 min

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Abstract

Background

Methods

Results

Conclusions

Background

Valentová et al. BMC Cancer (2026) 26:829 BMC Cancer [https://doi.org/10.1186/s12885-026-16185-x](https://doi.org/10.1186/s12885-026-16185-x) RESEARCH Open Access SOT102, a novel CLDN18.2-targeting antibody-drug conjugate, exhibits strong therapeutic potential in solid tumors Iva Valentová1,2*, Lenka Kyrych Sadílková1, Lukas Bammert3, Lorenz Waldmeier3, Roger Beerli3, Ilona Procházková 1, Filip Jabůrek1, Tatiana Spitzová1, Eliška Kohelová 1, Kati Räsänen 1, Ulrich Moebius 1 and Radek Špíšek1,2 Abstract Background Patients with gastric and pancreatic cancers, as well as other solid tumors including ovarian, lung, liver, and colon cancers, often lack effective therapeutic options. Claudin 18.2 (CLDN18 . 2) is a tumor-associated target that is predominantly expressed in gastric and pancreatic cancers but also found in several other tumor types. SOT102 is a novel antibody–drug conjugate directed against CLDN18.2, developed to provide a new therapeutic strategy for patients with CLDN18 . 2-positive tumors. Methods SOT102, composed of a proprietary monoclonal antibody (mAb) conjugated to the cytotoxic payload PNU-159682, was evaluated for binding, internalization, and cytotoxic effects in vitro. The in vivo antitumor activity was assessed in patient-derived xenograft (PDX) and cell line-derived xenograft (CDX) mouse models, both as monotherapy and the latter in combination with anti-PD1 antibody therapy. SOT102 pharmacokinetics and tolerability were further investigated in cynomolgus monkeys following intravenous administration. Results SOT102 demonstrated selective binding to CLDN18 . 2, with no detectable cross-reactivity to CLDN18 . 1, and efficient internalization into CLDN18 . 2-expressing cell lines, resulting in potent cytotoxic effects against tumor organoids with half-maximal activity ranging from 0.2 nM to 19.4 nM. Antitumor activity against PDX-derived mouse models was observed at a minimum effective dose of 0.2 mg/kg, with enhanced efficacy when combined with anti-PD1 antibody treatment. SOT102 exposure in cynomolgus monkeys was dose-dependent at doses between 0.3 mg/kg and 1 mg/kg with a half-life of approximately 7 days. An acceptable tolerability profile was observed, and the therapeutic window was defined between the minimum effective dose in mice and the highest non-severe toxic dose (HNSTD) of 0.6 mg/kg in cynomolgus monkeys. Conclusions SOT102 exhibited strong antitumor activity in preclinical models of CLDN18 . 2-positive cancers and demonstrated a favorable pharmacokinetic and safety profile in non-human primates. These data were used to support clinical evaluation of SOT102 as a potential treatment option for patients with CLDN18 . 2-expressing solid tumors. Keywords Claudin 18. 2, Antibody-drug conjugate, Gastric cancer, Pancreatic cancer, Solid tumor *Correspondence: Iva Valentová [valentovai@sotio.com](valentovai@sotio.com) 1SOTIO Biotech a. s., Prague, Czech Republic 2Department of Immunology, Charles University, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic 3NBE-Therapeutics AG, Basel, Switzerland © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds

FAQs

What is SOT102 and what target does it address?

SOT102 is a novel antibody–drug conjugate directed against CLDN18.2, developed for patients with CLDN18.2-positive tumors.

How was SOT102 evaluated in the study?

It was tested for binding, internalization, and cytotoxic effects in vitro, then for antitumor activity in PDX and CDX mouse models, including a combination with anti-PD1 therapy.

What did the results show about SOT102 potency and tolerability?

SOT102 showed selective CLDN18.2 binding with efficient internalization and potent cytotoxicity. Antitumor activity was observed at minimum effective doses in mice, while pharmacokinetics in monkeys were dose-dependent with an acceptable tolerability profile.

Sep 22, 2026

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