Sirnaomics, Inc., a biopharmaceutical company engaged in the discovery and development of RNAi therapeutics against cancer and fibrotic diseases, announced dose administration for the first patient in a Phase 2a clinical study of the company's lead drug candidate, STP705, for the treatment of cutaneous basal cell carcinoma.

The open label, dose escalation study is designed to evaluate the efficacy and safety of intralesional injection of STP705 in adult patients with cutaneous basal cell carcinoma confirmed with biopsy samples. The objective is to determine the safe and effective recommended dose of STP705 for the treatment of basal cell carcinoma (BCC), as well as analysis of biomarkers common to BCC formation pathway including TGF-β1 and COX-2. The trial is comprised of three dose escalation cohorts ranging from 30 μg to 90 μg with five patients in each group, and a total of 15 patients will be enrolled in the trial. Participants will receive injections of STP705 once a week for up to six weeks.

The primary endpoint of this trial is to evaluate patients for complete histological clearance of the tumour cells within the treated BCC lesion with secondary endpoints, evaluating subjects for investigational product treatment related adverse events, as well as serious adverse events, and cutaneous skin reactions.

"This marks another significant milestone as we continue to leverage our polypeptide nano-particle technology for siRNA drug delivery to advance our pipeline of oncology therapeutic candidates," said Patrick Lu, PhD., the founder, President and CEO of Sirnaomics. "We look forward to obtaining important clinical readouts in this trial and increasing the probability of success, while continuing to demonstrate our leadership in RNAi therapeutic development for skin cancers."

"This is an important study and milestone for Sirnaomics, the STP705 program, and potentially for patients with BCC, as it could offer an alternative to surgical excision of these lesions," said Michael Molyneaux M.D., Chief Medical Officer. "The company recognizes that there is a high unmet need for non-surgical treatments for various types of nonmelanoma skin cancers that reduce scarring and achieve high rates of histological clearance."

The Company expects to report initial clinical data from the trial in 2021.

Basal cell carcinoma (BCC) is a type of nonmelanoma skin cancer that occurs most often on areas that are exposed to the sun, such as head and neck. The most commonly found clinical feature of BCC is an elevated tumor with a pearly and translucent margin and telangiectasia. The color may vary widely from nearly normal skin color to erythematous to violaceous and may also be pigmented. BCC may also resemble noncancerous skin conditions such as eczema or psoriasis. The majority of these cancers occur on areas of skin that are regularly exposed to sunlight or other ultraviolet radiation. It is believed that development of BCC is linked closely to overexpression of TGF-β1 and COX-2.

Surgery is the currently the most common treatment option for the treatment of nonmelanoma cancer. The various forms of surgical modalities carry significant cutaneous adverse events, risk of scar, infection and bleeding. Surgery can also have a significant recurrence rate. As a result, there is a high unmet need for an FDA approved local injection therapy that is safe and effective.

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. Preclinical animal models using STP705 have demonstrated a dramatic improvement in T-cell penetration into tumours in the liver with single agent action as well as improvement in the efficacy of an anti-PD-L1 antibody checkpoint inhibitor in an HCC model. This effect may improve other immune checkpoint inhibitor efficacies in addition to those targeting the PD-1/PD-L1 axis.