Sirnaomics Inc., a leading biopharmaceutical company engaged in the discovery and development of RNAi therapeutics against cancer and fibrotic diseases, today announced topline results from the interim analysis of its ongoing clinical Phase II study evaluating STP705 for treatment of non-melanoma skin cancer, specifically squamous cell carcinoma in situ (isSCC). Analysis of the first three cohorts revealed a large portion of patients achieved complete histological clearance of SCC in situ after treatment with STP705, meeting the primary endpoint of the study.
This open label, dose escalation study is designed to evaluate the safety, tolerability and efficacy of various doses of STP705 administered as an intralesional injection in patients with cutaneous squamous cell carcinoma in situ (isSCC). The trial is comprised of five dose escalation cohorts ranging from 10 μg to 120 μg with five patients in each group, and a total of 25 patients will be enrolled in the trial. Participants receive injections of STP705 once a week for up to six weeks. The interim analysis is based on the completion of dosing the first three groups that received the 10 μg, 20 μg, and 30 μg dose levels of STP705. The interim analysis had a data cut-off date of March 2, 2020.
The primary end point of this trial is to evaluate patients for complete histological clearance of treated isSCC lesion. Based upon the analysis of the first three groups, 66% of all patients (10/15) achieved complete histologically clearance. Three patients (60%, 3/5) in both the 10 µg and 20 µg treated groups achieved histological clearance of lesion, while in the 30 µg treated group, four patients (80.0%, 4/5) achieved histological clearance of lesion, with a dose-dependent manner.
STP705 showed promising results in key secondary safety endpoints. There were no investigational product treatment related adverse events as well as no serious adverse events reported in the study. Of particular importance is the fact that there were no significant cutaneous skin reactions noted in the treatment groups. A further evaluation with two additional groups using dosages of 60 µg and 120 µg is ongoing with an attempt to define a clear therapeutic window.
“It is very exciting to unveil the results from the interim analysis from our first clinical oncology study. This marks a significant milestone as evidenced by the large portion of the patients treated with STP705 for isSCC meeting the primary endpoint with a dose dependent manner. This interim clinical readout not only demonstrates the potential of RNAi therapeutics in the oncology application, but also illustrates the potential safety and efficacy of polypeptide nanoparticle delivery for siRNA therapeutics. In addition, the profound therapeutic efficacy further validates TGF-β1 and COX-2 as an important cancer drug target and our dual-targeting strategy for novel RNAi cancer therapeutics,” said Patrick Lu, Ph.D., President and CEO of Sirnaomics. “These efficacy and safety results from the interim report stalwartly demonstrates our leadership position at the forefront of RNAi cancer therapeutics.”
“The results of this study are very encouraging based on the fact that we were able to demonstrate high rates of histological clearance, which is the gold standard for skin cancer. This was combined with an excellent safety profile and most importantly, a lack of local cutaneous skin reactions, which is very important to both patients and clinicians as they look for alternatives to surgical excision of these lesions,” stated Dr. Michael Molyneaux M.D., Chief Medical Officer of Sirnaomics.
“The standard of care for the treatment of squamous cell carcinoma in situ is either surgical excision or destruction or radiation therapy. The advent of a non-surgical, scarless option using a simple series of injections with high cure rates will change the paradigm for the treatment of this common non melanoma skin cancer,” said Mark Nestor, M.D., Ph.D., Principal Investigator and Co-Director of Center for Clinical and Cosmetic Research.
About Non-Melanoma Skin Cancer (NMSC) and Squamous Cell Carcinoma in situ (isSCC)
Skin cancer is the most common type of all cancers diagnosed each year in the United States. It is estimated that nearly half of cancers diagnosed every year will be skin cancers. Over the past decade, the incidence of skin cancers has increased dramatically. According to the JAMA Dermatology paper (Rogers, et. al. JAMA Dermatol. 2015151(10):1081-1086), an estimated 3.3 million people in the US suffer from NMSC along with 5.43 million people that are currently living with cancer lesions. Data on specific types of NMSC cancer were 2.55 million cases for Basal cell carcinoma (47%): 2.57 million cases for squamous cell carcinoma including squamous cell carcinoma in situ (46.7%), plus another 332,000 cases of unspecified type of skin cancers. By Indication type, non-melanoma cancer accounts for the most significant market value due to a large number of patients. According to the Market Research Report from “Datamintelligence.com”, the market potential for NMSC is estimated about USD 4.8 billion.
Squamous cell carcinoma in situ, also called Bowen disease, is the earliest form of squamous cell skin cancer (SCC). Along with basal cell carcinoma, SCC is one of two major subtype of NMSC. The key driver for development of SCC is Ultraviolet rays from the sun. It is believed that development of SCC is linked closely to genomic perturbations, genetic mutations, and altered expression of key molecules (e.g., overexpression of TGF-β1 and COX-2) that impacts squamous cell lineage commitment and terminal differentiation. The most common areas for SCC to occur are the face, neck, bald scalp, extensor forearms, dorsal hands, and shins.
Surgery is the currently the most common treatment option for the treatment of non-melanoma 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. An injectable therapy could be preferable to surgery due to scarring, bleeding, infection risk associated with surgery as well as related collateral considerations/costs.
Additional information about this clinical trial is available at clinicaltrials.gov using the identifier: NCT04293679.
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, Non-Melanoma 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 tumors 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.
Sirnaomics, Inc., a leading privately held biopharmaceutical company for discovery and development of RNAi therapeutics, is a Delaware corporation headquartered in Gaithersburg, Maryland, USA, with subsidiaries in Suzhou and Guangzhou, China. The Company’s mission is to develop novel therapeutics to alleviate human suffering and advance patient care in areas of high unmet medical need. The guiding principles of the company are: Innovation, Global Vision with a Patient Centered focus. Members of the senior management team have a great deal of combined experience in the biopharmaceutical industry, financial, clinical and business management in both the USA and China. The company is supported by funding from institutional investors, corporate partnerships and government grants. Sirnaomics has developed a strong portfolio of intellectual property with an enriched product pipeline. The therapeutic areas of focus include oncology and anti-fibrotic therapeutics. Learn more at www.sirnaomics.com.