SOTIO’s lead candidate, SOT109, is generating buzz in the ADC space with its novel target: CDH17. We spoke with Martin Steegmaier, chief scientific officer at SOTIO, to understand why this under-the-radar target is gaining traction—particularly in colorectal cancer (CRC)—and how SOTIO plans to stay ahead in a crowded, competitive field.

The science behind CDH17

What makes CDH17 such a promising target for colorectal cancer compared to previous antigen targets?

CDH17 is overexpressed in more than 90% of colorectal cancers, across all disease stages, and shows similar levels in both primary tumors and metastases. It’s a transmembrane protein that internalizes rapidly—making it well-suited for ADC-mediated delivery.

Despite this, CDH17 has flown under the radar due to concerns over toxicity. It’s also present in healthy gut epithelium, which raised red flags for developers—especially those using highly potent approaches like CAR-T or T-cell engagers. However, normal epithelial CDH17 is far less accessible and internalizes poorly compared to tumor-expressed CDH17. This is because, in healthy tissue, CDH17 resides on the lateral sides of tightly connected epithelial cells, limiting access and uptake.

The key lies in epitope selection. By targeting the right part of the CDH17 molecule, we believe we can exploit its therapeutic potential while maintaining safety.

How does CDH17’s expression in colorectal cancer differ from other tissues, and why is that important for safety?

CDH17 is primarily expressed in gastrointestinal and neuroendocrine tissues. In normal cells, it’s mostly found in intestinal epithelium and pancreatic ducts. That makes it a useful diagnostic marker for GI cancers and, crucially, means off-tumor effects are likely to be confined to the GI tract.

In addition, its limited accessibility and poor internalization in normal tissue—as opposed to the highly exposed, internalizing CDH17 on tumors—suggest a strong therapeutic window for well-designed ADCs.

How did your team identify CDH17 as a viable ADC target?

Existing CRC ADC targets like HER2 and cMET are only expressed in small subsets of patients—around 3% and 30% respectively. CEACAM5 is more widely expressed but doesn’t internalize efficiently.

CDH17 is expressed in nearly all CRC cases, and it’s a strong internalizer in cancer cells. That combination stood out to us immediately and motivated our focus on this target.

SOTIO’s candidate: SOT109

What sets SOT109 apart from other CDH17-targeting ADCs in development?

SOT109 is a fully human antibody optimized for strong internalization. What really differentiates it is our rigorous preclinical strategy. We identified rodent-cross-reactive antibodies and tested them in sophisticated gut epithelial organoids derived from human cells. Mouse cross-reactivity allowed us to assess tolerability early in development—an option not available to teams using non-cross-reactive antibodies.

Our antibody is conjugated using Synaffix’s GlycoConnect and HydraSpace platform, with the SYNtecan E™ linker-payload system—featuring a DAR 4 exatecan payload. This combination showed an excellent balance of efficacy and safety in preclinical studies. Notably, this platform is also used in Innovent’s IBI343, now in Phase 3 trials for gastric and pancreatic cancer, where it has demonstrated strong response rates and good tolerability.

Can you talk us through the preclinical data—what efficacy and safety signals are you seeing?

SOT109 demonstrated potent anti-tumor activity in both cell line-derived and patient-derived CRC xenografts. It induced significant and durable tumor regressions at doses that were well tolerated in mice. Because the antibody is cross-reactive with mouse and non-human primate CDH17, we were also able to confirm its favorable safety profile in both species.

Are any colorectal cancer subtypes showing higher sensitivity to SOT109?

We’ve observed activity across all major CRC subtypes—regardless of KRAS, BRAF, TP53 status, or microsatellite stability. Interestingly, CDH17-directed ADCs with microtubule inhibitors like MMAE often show limited efficacy in CRC due to resistance mechanisms like MDR1 expression. SOT109, with its exatecan payload, appears unaffected by these efflux pumps, which supports its broader applicability.

The broader landscape

Colorectal cancer has been difficult to treat with targeted therapies. Could CDH17 be a turning point?

Yes. CDH17’s restricted expression to the GI tract reduces the risk of systemic toxicity, while its uniform and high expression in CRC (with H-scores between 200–300) makes it a very attractive target. If leveraged correctly, it could lead to safer and more effective therapies for a broader patient population.

There’s growing momentum around CDH17 at AACR. What’s driving this interest?

A lot of CDH17-related drug discovery is being driven by Chinese biotech companies focused on GI cancers. Early exploratory work—particularly with CAR-T and T-cell engagers—generated some buzz a few years ago, and since then, several players have entered the space.

With more companies pursuing CDH17, how will SOTIO stay ahead?

Most of the competition is based in China. In contrast, SOTIO plans to run clinical trials in the US and EU. Our differentiated antibody, strong preclinical validation, and use of a clinically tested payload-linker platform give us a potential best-in-class profile. We’ll move quickly through dose escalation and initiate combination studies early to stay competitive.

Clinical strategy

What’s the timeline for bringing SOT109 into the clinic?

We expect to file an IND in the first half of 2026, with first-in-human trials beginning in the US and EU in the second half of that year.

Are you planning combination strategies with other therapies?

Yes. Our first trial will be a monotherapy dose escalation study in advanced CRC. Once we identify a safe and active dose, we’ll move into earlier lines of therapy in combination with standard-of-care treatments. We’re also evaluating potential use in other GI cancers.

What are the biggest challenges as SOT109 moves into the clinic?

Recruitment shouldn’t be an issue given the high unmet need in CRC. CDH17’s near-universal expression means we won’t need to screen patients in CRC. However, for other indications where CDH17 expression is lower, we’re developing a companion diagnostic (CDx) to select patients more precisely.

The future

Beyond colorectal cancer, where else could CDH17 be relevant?

CDH17 is also highly expressed in gastric, pancreatic, and esophageal cancers, as well as in many neuroendocrine tumors. We’re definitely exploring those opportunities.

How do you see the ADC space evolving in solid tumors like CRC?

We expect a growing focus on novel payloads beyond topoisomerase I inhibitors. With so many ADCs using TOPO1i payloads, resistance is bound to emerge. That’s why SOTIO is also developing new payload classes, including for use with CDH17.

If successful, what impact could SOT109 have on patients with limited treatment options?

We’re aiming for a treatment with superior efficacy, good tolerability, and broader applicability than existing options. SOT109’s ability to bind and internalize CDH17 with high efficiency—combined with a payload that resists resistance mechanisms—could lead to deeper and more durable responses in CRC patients.

If we succeed, we hope to redefine what’s possible in the treatment of colorectal cancer.