SOTIO Biotech, a clinical-stage biopharmaceutical company owned by PPF Group, has unveiled promising preclinical data on SOT109, a next-generation antibody-drug conjugate (ADC) targeting cadherin-17 (CDH17). These findings reinforce the strong therapeutic potential of SOT109 in treating colorectal cancer (CRC) and other gastrointestinal (GI) malignancies. The preclinical results were presented at the 15th World ADC London 2025, held from March 3 to 6 at Novotel London West, London, UK.
A New Hope for Gastrointestinal Cancers
Colorectal cancer remains one of the most prevalent and deadly cancers worldwide, with current treatment options often falling short in terms of efficacy and long-term outcomes. SOTIO’s novel ADC, SOT109, represents a significant step forward in addressing this unmet medical need. By specifically targeting CDH17, a protein overexpressed in more than 90% of colorectal cancers and other GI tumors, SOT109 aims to deliver highly potent cytotoxic agents directly to cancer cells while minimizing damage to healthy tissues.
“We are excited to share groundbreaking data on SOT109, an innovative ADC designed to treat colorectal cancer and other GI malignancies,” said Martin Steegmaier, Ph.D., Chief Scientific Officer of SOTIO. “CDH17 has long been recognized as a highly compelling therapeutic target, yet previous non-ADC and ADC approaches have faced significant obstacles. Our cutting-edge design overcomes these challenges, utilizing state-of-the-art linker-payload technology and an optimized antibody backbone to enhance efficacy and tumor selectivity. Preclinical data indicate that our candidate not only delivers potent tumor cell killing but does so with an excellent safety profile and high therapeutic index.”
Understanding CDH17 as a Target
CDH17 is a transmembrane protein that plays a critical role in the development and maintenance of intestinal epithelial tissue. In cancer, CDH17 is aberrantly overexpressed in CRC and other GI tumors, including gastric, pancreatic, and esophageal cancers. Importantly, CDH17 is minimally expressed in normal adult tissues outside of the GI tract, making it an attractive target for therapeutic intervention.
The ability of CDH17 to rapidly internalize upon binding further strengthens its viability as an ADC target, as it allows efficient delivery of cytotoxic payloads directly into tumor cells. Unlike conventional chemotherapy, which indiscriminately affects both healthy and malignant cells, ADCs like SOT109 are designed to selectively attack tumor cells while sparing normal tissues, thereby reducing systemic toxicity and improving the therapeutic window.
SOT109: A Cutting-Edge ADC with Best-in-Class Potential
SOT109 is a fully human and highly specific ADC designed to optimize binding and internalization properties against CDH17. The drug is developed using Synaffix’s clinically validated ADC platform, incorporating the SYNtecan E™ proprietary linker-payload system. This system employs an exatecan-based payload, known for its potent cytotoxic activity, minimal resistance development, and enhanced bystander effect due to high cell permeability.
Key advantages of SOT109’s design include:
- Targeted Delivery: Strong binding affinity to CDH17 ensures precise delivery of the payload to tumor cells.
- High Potency: The exatecan payload is expected to demonstrate superior anti-tumor activity compared to other ADC payloads currently in use.
- Bystander Effect: The high cell permeability of the payload allows it to diffuse into neighboring cancer cells, even those not directly bound by the ADC, improving overall tumor eradication.
- Enhanced Safety Profile: The proprietary linker technology ensures controlled drug release, reducing off-target toxicity and improving tolerability.
Preclinical Data: Strong Efficacy and Favorable Safety Profile
The preclinical results presented at World ADC London 2025 demonstrated that SOT109 exhibits robust anti-tumor activity across multiple in vivo models of CRC and GI cancers. In mouse xenograft models, SOT109 achieved complete tumor regression in several cases, showcasing its potent efficacy.
Furthermore, a tolerability study in mice demonstrated that SOT109 could be administered at doses up to 150 mg/kg with minimal toxicity. Subsequent non-human primate (NHP) toxicity studies confirmed that SOT109 possesses a favorable therapeutic index, meaning the drug has a strong balance between efficacy and safety.
These findings suggest that SOT109 holds immense potential as a transformative therapy for patients with advanced colorectal and GI cancers, where treatment options remain limited.
Future Clinical Development and Regulatory Pathway
Building upon these promising preclinical results, SOTIO is now preparing for the next crucial step: clinical evaluation. The company aims to file an Investigational New Drug (IND) application for SOT109 with regulatory authorities in the second quarter of 2026. If approved, this will enable the initiation of first-in-human clinical trials to further assess the drug’s safety, tolerability, pharmacokinetics, and therapeutic efficacy in patients.
“The preclinical data for SOT109 provide a strong rationale for advancing this program into clinical development,” said Dr. Steegmaier. “We are optimistic about the potential of SOT109 to fill a critical gap in the treatment landscape for colorectal and GI cancers. Our goal is to deliver a best-in-class ADC that improves patient outcomes and extends survival for those battling these aggressive diseases.”
The Broader Impact of ADCs in Oncology
Antibody-drug conjugates are rapidly emerging as one of the most promising therapeutic modalities in oncology. By combining the specificity of monoclonal antibodies with the potency of cytotoxic drugs, ADCs offer a more effective and targeted approach to cancer treatment. Over the past decade, several ADCs have gained regulatory approval and have revolutionized the management of hematologic and solid tumors.
However, despite the success of existing ADCs, significant challenges remain, including improving tumor penetration, overcoming drug resistance, and minimizing adverse effects. Innovations such as those incorporated into SOT109’s design—enhanced target specificity, novel linker technology, and optimized payload selection—represent the next frontier in ADC development.
