The siRNA STP705 by Sirnaomics Has Promise for Treating in situ Squamous Cell Carcinoma (isSCC)

Sirnaomics has revealed that their leading siRNA therapeutic candidate STP705 has shown promising anti-cancer activity in adults with cutaneous in situ squamous cell carcinoma (isSCC).

The human body’s largest organ, the skin, has three layers and the outermost layer that protects against germs is the epidermis. Squamous cells form the thick layer of the epidermis and shed continuously as new ones are made. Squamous cell carcinoma (SCC) is the second most common form of skin cancer characterized by an accelerated and abnormal growth of squamous cells. Around 1.8 million cases of SCC are diagnosed each year in the US and over 15,000 Americans die each year from SCC.

Overexpression of the multifunctional cytokine TGF-β1 (transforming growth factor beta1) and the enzyme COX-2 (cyclooxygenase-2) is strongly linked with SCC development.

Small interfering RNAs (siRNAs) are a promising class of therapeutic modalities that involve a double-stranded RNA molecule (20 to 25 bp long) which can target and cease the translation of a disease-related mRNA. The siRNA is absorbed into targeted cells by endocytosis and the siRNA then unwinds and forms a complex with the specific mRNA. The binding of the siRNA to the target mRNA silences the expression of that mRNA and thereby leads to tumor suppression of oncogenes.

Sirnaomics, a biopharmaceutical innovator of RNA therapeutics, has revealed that their leading therapeutic candidate STP705 has shown promising anti-cancer activity in adults with cutaneous in situ squamous cell carcinoma (isSCC). The results of their Phase IIa STP705 clinical study were published in the Journal of Drugs in Dermatology, a peer-reviewed medical journal of dermatology that was established in 2002.

STP705 — A Promising siRNA Candidate Against isSCC

STP705 is comprised of two siRNA oligonucleotides targeting TGF-β1 and COX-2 and is formulated with polypeptide nanoparticle technology using a histidine-lysine polypeptide (HLP). The mechanism of action of STP705 is simultaneous inhibition of COX-2 and TGF-β1 expression.

Overexpressed TGF-β1 is seen in tumors and this impairs extracellular matrix remodeling and angiogenesis (the formation of new blood vessels) and contributes to immune evasion which promotes tumor development. When cancer has progressed, TGF-β1 signaling can aid tumor cell migration and metastasis. COX-2 is overexpressed in many malignant tumors in humans. Silencing COX-2 expression will downregulate prostaglandin E2 production and this can inhibit tumor cell proliferation.

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Clinical Trial Outcomes of isSCC Treatment with STP705

The Phase IIa clinical trial was designed to analyze the safety and efficacy of varying doses of STP705 (10 µg, 20 µg, 30 µg, 60 µg and 120 µg dose levels) in a single-center, open label, dose escalation cohort study. There were 25 adult patients with isSCC enrolled in the study and they were divided into five cohorts with five subjects each to match the number of dose levels administered. The patients received injections of STP705 once a week for up to six weeks. The primary endpoint was the proportion of subjects with histological clearance of treated isSCC lesion by the end of the treatment period.

Histological clearance was observed in 19 individuals (76 percent of the participants). The participants in the 30 µg/treatment and 60 µg/treatment groups had 80 percent and 100 percent histological clearance, respectively.

The recommended doses of STP705 for isSCC treatment in future studies are 30 µg/treatment and 60 µg/treatment.

“The peer-reviewed publication of our Phase IIa STP705 clinical study results for treating isSCC in the JDD [Journal of Drugs in Dermatology], together with strong favorable opinion among the clinical dermatologists, further strengthens our confidence in moving forward with STP705 clinical studies for applications in various types of the non-melanoma skin cancers,” said Patrick Lu, PhD, founder, Chairman of the Board, Executive Director, President and CEO of Sirnaomics in the company’s press release.

“This is a prevalent type of cancer, with over five million new diagnoses in the US each year, and after surgical removal patients can have an increased risk of tumor progression, metastasis and recurrence as well as risk of infection, hematoma and scarring. These patients need an alternative, non-invasive treatment option, which is why we are evaluating STP705,” added Lu.

Sirnaomics’ Current Research

Sirnaomics specializes in RNA therapeutics, and they currently have 16 drug candidates in the preclinical to Phase II clinical trial stages for a wide range of diseases. Sirnaomics is the first biopharma to obtain positive Phase IIa clinical outcomes in oncology for an RNA interference (RNAi) therapeutic.

Their leading drug candidate, STP705, is currently in five clinical trials for different indications: Phase IIa for isSCC, Phase II for basal cell carcinoma (BCC), Phase I/II for keloid scarring, Phase I/II for hypertrophic scar and Phase I for liver cancer.