SOT106 Receives New FDA FTD and ODD in Sarcoma

SOT106, an investigational antibody-drug conjugate (ADC) targeting leucine-rich repeat-containing 15 (LRRC15), received FDA fast track designation (FTD) for the treatment of osteosarcoma and orphan drug designation (ODD) for the treatment of soft tissue sarcoma (STS), giving the ADC both designations across both sarcoma subtypes.¹

“Patients with sarcoma continue to face limited treatment options, underscoring the need for innovative targeted therapies,” stated Radek Spisek, MD, PhD, chief executive officer of SOTIO, in a news release. “As we advance SOT106 toward the clinic, we believe it has the potential to become an important treatment option for patients in need.”

SOT106 previously received ODD for osteosarcoma in May 2026 and FTD for STS in August 2026.^2,3 SOTIO’s CDH17-targeting ADC, SOT109, received FTD for colorectal cancer in July 2026. FTD is intended to facilitate the development and expedite the review of therapies addressing serious conditions and unmet medical needs, whereas ODD provides incentives intended to support development of therapies for rare diseases.

Mechanism and Target Rationale

LRRC15 is a mesenchymal and stromal antigen associated with tumor invasion and with resistance to chemotherapy and immunotherapy. LRRC15 is broadly expressed across multiple highly prevalent sarcoma subtypes and is a clinically validated target. SOT106 is designed to target LRRC15 and release a payload selectively within the tumor.

In preclinical models, including patient-derived xenograft models of osteosarcoma and STS, SOT106 has demonstrated antitumor activity along with a tolerability profile the company describes as supporting a high therapeutic index.^1,4

Plans for Early-Stage Trial and Company Pipeline

SOTIO expects to initiate a multinational, multicenter open-label first-in-human clinical trial (NCT07801222) of SOT106 later in 2026.⁵ Part A of the trial is a Time-to-event Bayesian Optimal Interval (TITE-BOIN) Design to evaluate the maximum tolerated dose and recommended phase 2 dose of SOT106 in patients with LRRC15-positive advanced or metastatic osteosarcoma or STS. This part will evaluate the safety, pharmacokinetics, and preliminary efficacy of SOT106 in escalating doses given every 21 days intravenously. Patients must have received or be intolerant to all standard-of-care therapy. Patients aged 12 to 17 may be eligible provided certain safety conditions are met for the initial dose levels; otherwise, patients must be 18 or older. At least 1% of biopsied tissue cells must express LRRC15 expression of 1+ by immunohistochemistry.

Part B will be a randomized dose optimization trial of the 2 recommended doses for optimization identified in Part A to determine the dose that provides the best balance between benefit and risk, in the same patient population.

SOT109 is currently being investigated in a phase 1/2 study for colorectal cancer (NCT07693751), whereas SOT201, a next-generation PD-1–targeting immunocytokine, is being evaluated in the phase 1 VICTORIA-01 trial (NCT06163391) in patients with solid tumors. The company has described both SOT106 and SOT109 as potential best-in-class ADCs designed to rapidly advance to clinical proof of concept.¹

REFERENCES

1. SOTIO Advances SOT106 with Dual FDA Designations, Further Positioning the Program as a Potential Best-in-Class ADC for Sarcoma. News release. SOTIO Biotech. September 23, 2026. Accessed September 23, 2026.

2. 1. FDA Grants Fast Track Designation to SOTIO's SOT106 ADC for Soft Tissue Sarcoma Treatment, Accelerating Clinical Development. News release. SOTIO Biotech. August 26, 2026. Accessed August 26, 2026. https://tinyurl.com/47s9dv3m

3. SOTIO Receives U.S. FDA Orphan Drug Designation for SOT106, a Potential Best-in-Class ADC for Sarcoma. SOTIO Biotech. News release. June 3, 2026. Accessed June 4, 2026. https://tinyurl.com/3mn6wbnv

4. Purcell JW, Tanlimco SG, Hickson J, et al. LRRC15 Is a novel mesenchymal protein and stromal target for antibody-drug conjugates. Cancer Res. 2018;78(14):4059-4072. doi:10.1158/0008-5472.CAN-18-0327

5. A Study to Assess Safety and Efficacy of SOT106 in Patients With LRRC15-positive Advanced Unresectable or Metastatic Osteosarcoma or Soft Tissue Sarcoma. ClinicalTrials.gov. Updated September 3, 2026. Accessed September 23, 2026. https://clinicaltrials.gov/study/NCT07801222