FDA Grants SOTIO's SOT106 ADC Orphan Drug and Fast Track Designations for Sarcoma

The FDA has granted Orphan Drug Designation to SOTIO Biotech's investigational antibody-drug conjugate (ADC) SOT106 for the treatment of soft tissue sarcoma (STS) and Fast Track Designation for the treatment of osteosarcoma, the company announced on September 23, 2026.¹ With these additions, SOT106 now holds both designations in both indications.¹ The latest Fast Track Designation follows one the FDA granted SOT106 in STS in August 2026.²

According to SOTIO, Fast Track and Orphan Drug Designations are intended to support development of therapies for rare diseases and areas of high unmet need, providing opportunities for enhanced regulatory engagement and other incentives.¹ SOTIO, a clinical-stage company owned by PPF Group, expects to initiate a first-in-human trial of SOT106 later this year.¹ All efficacy and tolerability data reported for the program to date are preclinical.¹

How does SOT106 work?

SOT106 combines SOTIO's proprietary antibody against leucine-rich repeat-containing 15 (LRRC15) with LigaChem Biosciences' ConjuAll site-specific conjugation technology and a beta-glucuronidase-cleavable linker.¹ SOTIO said the linker is designed to remain stable in circulation and release the payload selectively within the tumor.¹ The release does not identify the payload.

LRRC15 is a member of the leucine-rich repeat superfamily found on cancer-associated fibroblasts and stromal cells, and its expression is upregulated by the cytokine TGF-β.³ In a 2020 analysis of 711 STS cases, Ben-Ami and colleagues reported that, unlike the pattern seen in epithelial tumors, LRRC15 was expressed not only by stromal cells but also by cancer cells in multiple STS subsets, with significant variation between histological subtypes.³ Overexpression of LRRC15 correlated with tumor grade and was independently associated with adverse outcomes.³

SOTIO described LRRC15 as a clinically validated target broadly expressed across multiple highly prevalent sarcoma subtypes.¹ The target has been tested in humans before. In a first-in-human Phase 1 study of AbbVie's LRRC15-targeted ADC ABBV-085, which carried a monomethyl auristatin E payload, the overall response rate among patients with osteosarcoma or undifferentiated pleomorphic sarcoma treated at 3.6 mg/kg was 20%, including four confirmed partial responses.⁴ Investigators reported that ABBV-085 appeared safe and tolerable at that dose every 14 days.⁴

For SOT106, SOTIO reported that preclinical data, including patient-derived xenograft models of both osteosarcoma and STS, indicate the ADC is potent and well tolerated, with a high therapeutic index and strong anti-tumor activity.¹

Why does linker design matter in ADCs?

SOT106 pairs SOTIO's own target-specific antibody with LigaChem's linker and conjugation technology, and SOTIO's stated rationale for the linker is stability in circulation and selective payload release in the tumor.¹ Speaking about ADC design generally rather than SOT106 specifically, Paul Romness, chair, chief executive officer, and president of OS Therapies, described the linker's role in a Q&A with BioPharm International. "The linker is responsible for ensuring the payload reaches the tumor while limiting exposure to healthy tissue," Romness said. "In many ways, it's the weakest link in an ADC, because if the payload is released too early or in the wrong place, you lose precision and potentially increase toxicity."

What is the unmet need in sarcoma?

The American Cancer Society estimates that about 13,910 new STS cases will be diagnosed in the US in 2026 and that about 5,400 people will die of the disease.⁵ The most common STS types in adults are undifferentiated pleomorphic sarcoma, liposarcoma, and leiomyosarcoma.⁵ Ben-Ami and colleagues noted that STS represents approximately 1% of cancers in adults and 15% in children.³

"Patients with sarcoma continue to face limited treatment options, underscoring the need for innovative targeted therapies," said Radek Spisek, MD, PhD, chief executive officer of SOTIO.¹

What happens next?

SOTIO expects to begin first-in-human testing of SOT106 later in 2026.¹ The company has not yet disclosed the trial's design, dosing, or which sarcoma subtypes it will enroll first. SOT106 is one of two lead ADC programs at SOTIO, alongside SOT109, a CDH17-targeting ADC in a Phase 1/2 study for colorectal cancer that has also received Fast Track Designation.¹ The company is also evaluating SOT201, a PD-1-targeting immunocytokine, in the Phase 1 VICTORIA-01 study in patients with solid tumors.¹

References

1. SOTIO Biotech. SOTIO Advances SOT106 with Dual FDA Designations, Further Positioning the Program as a Potential Best-in-Class ADC for Sarcoma. Press release. Published September 23, 2026. Accessed September 24, 2026.
2. SOTIO Biotech. FDA Grants Fast Track Designation to SOTIO's SOT106 ADC for Soft Tissue Sarcoma Treatment, Accelerating Clinical Development. Press release. Published August 26, 2026. Accessed September 24, 2026.
3. Ben-Ami E, Perret R, Huang Y, et al. LRRC15 targeting in soft-tissue sarcomas: biological and clinical implications. Cancers (Basel). 2020;12(3):757.
4. Demetri GD, Luke JJ, Hollebecque A, et al. First-in-human phase I study of ABBV-085, an antibody-drug conjugate targeting LRRC15, in sarcomas and other advanced solid tumors. Clin Cancer Res. 2021;27(13):3556-3566.
5. American Cancer Society. Key Statistics for Soft Tissue Sarcomas. Accessed September 2026.