Sirnaomics Advances Dual-Targeting RNAi Therapy STP705 into Phase 2 Trial for Keloid Scar Prevention

On July 14, 2021, Sirnaomics announced that the first patient has been dosed in its Phase 2 clinical trial of the drug candidate STP705 for the prevention of keloid scars. STP705 is a small interfering RNA (siRNA) therapeutic that utilizes dual-targeting inhibition and peptide nanoparticle (PNP)-enhanced delivery technology to directly knock down the expression of TGF-β1 and COX-2, thereby reducing abnormal tissue fibrosis.

Keloids result from an abnormal wound healing process and may occur following any injury to the deep dermis. Excessive scarring significantly impairs patients' quality of life by causing pain, pruritus, and contracture. Currently, most treatment modalities remain clinically unsatisfactory, most likely due to an insufficient understanding of the complex mechanisms underlying scar formation and wound contraction.

The pathophysiology of keloids involves the prolongation of the inflammatory and proliferative phases of wound healing following injury. Among the various cytokines that promote keloid formation, TGF-β1 is one of the key regulators of the aberrant fibrotic response, while COX-2 is a potent mediator of pro-inflammatory processes and tissue proliferation.

STP705 is an siRNA therapeutic that leverages dual-targeting inhibition and peptide nanoparticle (PNP)-enhanced delivery to directly knock down the expression of TGF-β1 and COX-2. It has received multiple Investigational New Drug (IND) approvals from the U.S. FDA and China’s NMPA, including for the treatment of cholangiocarcinoma, non-melanoma skin cancer, and hypertrophic scars.

▲Mechanism of Action of siRNA (Image source: Official website of Sirnaomics, Inc.)

When STP705 was locally injected into human hypertrophic scar tissue grafted onto nude mice, experimental results demonstrated a reduction in scar size, along with the downregulation of fibrotic biomarkers including α-SMA, hydroxyproline, collagen I, and collagen III.

Further analysis revealed that STP705 induces fibroblast apoptosis in both *in vitro* and *in vivo* studies. Consequently, the synergistic effect of simultaneously silencing TGF-β1 and COX-2 may reverse cutaneous fibrotic scarring by minimizing inflammation and activating fibroblast apoptosis. This mechanism of action of STP705 holds broad potential for the treatment of various fibrotic diseases.

This Phase 2 clinical trial is a multicenter, randomized, double-blind, multi-arm, controlled study designed to evaluate the safety and efficacy of different doses of STP705 in reducing keloid recurrence following surgical excision. The study plans to enroll a total of 50 patients. The primary endpoint of the trial is the recurrence rate at 3, 6, and 12 months post-excision in patients treated with surgery plus placebo versus surgery plus STP705.

Note: The original text has been abridged.

References:

[1] Sirnaomics Doses First Patient in Phase 2 Study of STP705 for Keloid Scar Prevention. Retrieved July 14, 2021, from https://www.prnewswire.com/news-releases/sirnaomics-doses-first-patient-in-phase-2-study-of-stp705-for-keloid-scar-prevention-301333779.html

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