On April 18, 2021 Sirnaomics, Inc., a biopharmaceutical company engaged in the discovery and development of RNAi therapeutics against cancer and fibrotic diseases, reported the initiation of a Phase 2 study of the company’s lead drug candidate, STP705, for Keloid scar prevention (Press release, Sirnaomics, APR 18, 2021, View Source [SID1234578167]). The Phase 2, multi-center, randomized, double-blind, multiple-arm, controlled study is designed to evaluate the safety and efficacy of various doses of STP705 in reducing post-keloidectomy keloid recurrence.
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The primary endpoint of this trial is to measure the rate of recurrence in patients who have undergone surgery alone (receiving placebo) versus surgery and STP705 at three months, six months, and 12 months post-surgical excision.
"We anticipate that this important study should render additional data on STP705’s unique mechanism of action on skin fibrotic scarring, following the promising results in previous studies," said Patrick Lu, Ph.D., founder, President and CEO of Sirnaomics. "This approach for Keloid scar prevention is indicative of our strategy to leverage STP705’s dual-targeted inhibitory property and polypeptide nanoparticle-enhanced delivery to develop improved options for treating different cancer indications."
"Keloid scarring is a serious medical condition resulting in abnormal scar formation and pain along with having a very negative psychological impact on patients who suffer from the disease," said Michael Molyneaux M.D., Chief Medical Officer. "There is currently no treatment apart from surgical removal and this carries a very high recurrence rate. We seek to offer patients a viable alternative to prevent recurrence after surgical resection."
Sirnaomics expects to report initial clinical data from the Phase 2 trial in the second half of 2021. Additional information about this clinical trial is available at clinicaltrials.gov using the identifier: NCT04844840.
About Keloid Scar
Keloids form as a result of aberrations of physiologic wound healing and may arise following any insult to the deep dermis. By causing pain, pruritus and contractures, excessive scarring significantly affects the patient’s quality of life, both physically and psychologically. Multiple studies on keloid formation have been conducted for decades and have led to a plethora of therapeutic strategies to prevent or attenuate excessive scar formation. However, most therapeutic approaches remain clinically unsatisfactory, most likely owing to poor understanding of the complex mechanisms underlying the processes of scarring and wound contraction.
Pathophysiology of keloids entails a prolonged inflammatory and proliferative phase of wound healing after injury. Among various cytokines promoting keloids formation, TGF-β1 is known as a key regulator of the aberrant fibrogenic response, while COX-2 acts a potent proinflammatory and proliferative mediator. When STP705 was locally injected into the human hypertrophic scar tissues, which were surgically removed from patients and implanted onto nude mice, the company observed scar size reductions, accompanying with not only target gene silencing but down regulation of fibrogenic markers including α-SMA, hydroxyproline, Collagen 1, and Collagen 3. Further analysis revealed that STP705 is able to induce fibroblast apoptosis both in vitro and in vivo. Therefore, the synergistic effect of simultaneous silencing of TGF-β1 and COX-2 may reverse skin fibrotic scarring through minimizing inflammation and activating fibroblast apoptosis. This mechanism of action of STP705 can be widely applied for treatment of many fibrotic conditions.
About STP705
Sirnaomics’ leading product candidate, STP705, is a siRNA (small interfering RNA) therapeutic that takes advantage of a dual-targeted inhibitory property and polypeptide nanoparticle (PNP)-enhanced delivery to directly knock down both TGF-β1 and COX-2 gene expression. The product candidate has received multiple IND approvals from both the US FDA and Chinese NMPA, including treatments of cholangiocarcinoma, nonmelanoma skin cancer and hypertrophic scar. STP705 has also received Orphan Drug Designation for treatment of cholangiocarcinoma and primary sclerosing cholangitis. A Phase 2a study of STP705 for treatment of squamous cell skin cancer (isSCC) in adult patients demonstrated positive efficacy and safety results, with 76% of all patients (19/25) achieving complete histologically clearance and the two optimal dosing ranges achieving 90% histological clearance of tumor cell in the lesion. No significant or serious adverse events, including no significant cutaneous skin reactions, were reported in the study, and the company was able to define a clear therapeutic window in advance of later stage studies.