FDA Grants ODD to LRRC15-Targeting ADC SOT106 for Osteosarcoma

The FDA has granted orphan drug designation (ODD) to SOT106, an antibody-drug conjugate (ADC) targeting leucine-rich repeat-containing 15 (LRRC15), for the treatment of osteosarcoma, according to a news release from SOTIO Biotech. The designation comes ahead of a planned first-in-human clinical trial expected to initiate in the second half of 2026.¹

A High-Unmet-Need Target

Osteosarcoma is the most common bone cancer in children and adolescents and has seen minimal therapeutic advancement over the past 4 decades. Current treatment relies on intensive chemotherapy regimens that carry significant toxicity burdens and offer limited long-term benefit, with a meaningful proportion of patients requiring limb amputation in aggressive cases. Sarcomas as a class encompass more than 70 distinct subtypes arising in bones and soft tissues; their rarity and biological heterogeneity have historically hindered the development of targeted therapies, including ADCs.

“Osteosarcoma is a devastating disease that has seen little therapeutic innovation over the past four decades,” Radek Spisek, MD, PhD, chief executive officer of SOTIO, stated in a news release. “We are encouraged by this recognition from the FDA and look forward to advancing SOT106 into the clinic later this year.”

SOT106: Mechanism and Preclinical Profile

SOT106 is a next-generation ADC directed against LRRC15, a clinically validated target with broad expression across sarcoma subtypes and in tumor-associated stroma. It is associated with tumor spread and invasion and can contribute to resistance to chemotherapy and immunotherapy.^2-4

Preclinical data demonstrate strong antitumor activity in both soft tissue and osteosarcoma models, with a tolerability profile that the company describes as supporting a high therapeutic index. The program is designed to yield an early and actionable clinical signal, with potential for expansion across multiple solid tumor indications.¹

Another antibody-drug conjugate that targeted LRRC15, samrotamab vedotin (ABBV-085), was investigated in a phase 1 clinical trial in advanced sarcomas and other solid tumors, and yielded an overall response rate of 20% for patients with osteosarcoma and undifferentiated pleomorphic sarcoma who were treated at the expansion dose; no other responses were observed in other cancers.⁵

Implications of Orphan Drug Designation

ODD confers several regulatory and commercial incentives for rare disease drug development, including up to 7 years of market exclusivity upon approval, waivers of certain regulatory fees, and enhanced FDA guidance throughout the development process. For SOT106, the designation reinforces both the unmet medical need in osteosarcoma and the FDA’s recognition of the therapeutic rationale underlying SOTIO’s ADC platform.

“[ODD] for SOT106 underscores both the urgent need for new treatment options in osteosarcoma and the strength of our ADC platform,” Spisek stated.

REFERENCES

1. 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

2. 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

3. Dominguez CX, Müller S, Keerthivasan S, et al. Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15⁺ Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy. Cancer Discov. 2020;10(2):232-253. doi:10.1158/2159-8290.CD-19-0644

4. Zhu X, You S, Du X, et al. LRRC superfamily expression in stromal cells predicts the clinical prognosis and platinum resistance of ovarian cancer. BMC Med Genomics. 2023;16(1):10. Published 2023 Jan 18. doi:10.1186/s12920-023-01435-9

5. 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. doi:10.1158/1078-0432.CCR-20-4513