Bowen's Disease

Published: Tietze JK, et al. Clin Nucl Med. 2023;48(10):869–876. MUNICH, Oct. 25, 2023 /PRNewswire/ -- Results from a recently completed study show topical rhenium-188 skin cancer therapy to be a highly effective option for treating non-melanoma skin cancer (NMSC) of up to 3 mm thickness.1 NMSCs are the most common cancers seen in the European population and their incidence are rising all over the world,2,3 with 7.7 million cases reported globally in 2017.4 In Australia, 2 in 3 people will be diagnosed with skin cancer in their lifetime and this is likely to increase as the population ages.5 Typically, treatment options for NMSCs include surgery, radiation, and cryotherapy. Surgical intervention is currently the most common treatment for invasive tumors, but it can lead to unfavorable cosmetic outcomes for some presentations.6 A team of researchers in Germany, led by dermatologist Professor Julia Tietze, and funded by OncoBeta® GmbH, Germany, investigated the efficacy and safety of topical rhenium-188 ionizing radiation therapy for the treatment of invasive NMSC. Research lead, Professor Tietze from the University Medical Center, Rostock says, "The study found rhenium skin cancer therapy to be a highly effective treatment for NMSCs, in particular, the cosmetic outcomes on the head and face. The overall conclusion is, while surgery is the gold standard therapy for NMSCs, rhenium skin cancer therapy may be suitable for large tumors, and tumors located on sensitive areas such as nose, ear, or lips; or where surgery would be challenging." The study involved 22 patients with 40 histologically confirmed NMSCs (57.5% basal cell carcinomas (BCCs), 12.5% cutaneous squamous cell carcinomas (cSCCs), 30% Bowen's disease lesions). Following the rhenium-188 single-session treatment, the response rate, adverse events, and cosmetic outcomes were assessed at 14 days, 4 months, and 12 months. The key findings included: Response rate at 12 months was 97.5% with 95.0% complete responses (clinically or histologically proven). No adverse events reported during the application of rhenium-188. Most patients (62.5%) did not experience an adverse event during the trial period. Most adverse events were reported at 14 days post-treatment, with 20% of lesions itching, 12.5% were painful (mostly minor pain) and 7.5% had a burning sensation. The majority of treated lesions were not reported to be painful. At 4 months: Most lesions (35/40) were clinically healed. One lesion that only partly responded to treatment and was found to be outside the study inclusion criteria (being 3.8 mm thick). Beneficially, the size of that tumor was decreased by 75% which meant a reduced surgical procedure. At 12 months: Only 3/39 lesions remained potentially suspect, with one confirmed as a newly developed Bowen's disease. 41% of lesions were graded as either cosmetically superior to the expected result after surgery and/or as barely detectable. 51% of lesions were graded as comparable to successful surgery and/or as detectable but aesthetically appealing, even though 49% of the lesions showed hypopigmentation. "Surgery for the removal of NMCSs has a high clearance rate of 95% after 5 years, however depending on the size and localization of the lesion, treatment may be painful and it may also lead to disfigurement. This study shows the efficacy of rhenium skin cancer therapy demonstrating a 97.5% response rate with 37 of the 39 lesions showing complete response at 12 months," adds Professor Tietze. The full report and results of the study have been published in the Journal Clinical Nuclear Medicine – available to healthcare professionals via this link: Study Design and Ethics Approval Patients were eligible if they had a histologically confirmed BCC or cSCC with an area of <5 cm2 and thickness <3 mm, they were least 18 years of age and were not suitable or not willing to undergo surgery due to comorbidities, specific anatomic location or unsuccessful previous surgical procedures. Exclusion criteria included known primary melanoma near the treatment area, they were undergoing treatment for non-resectable or metastatic melanoma (including BRAF- or MEK-Kinase inhibition), they had significant impaired blood circulation in the treatment area or if they were pregnant. Patients were treated once with 188Re resin with a targeted dose of 50 Gy. The response rate (RR), adverse events (AEs) and cosmetic outcome were assessed at 14 days, 4- and 12-months post-treatment. All procedures performed in this study were in accordance with the 1964 Helsinki declaration and its later amendments. The study was approved by the local Ethical Committee (A2020-0178). Patients signed written informed consent to participate. About the Rhenium-SCT® (Skin Cancer Therapy) Non-melanoma skin cancer (NMSC) is the most common form of cancer in humans.3 The most common cause of NMSC is sun exposure, while other predisposing factors include genetic skin conditions and immunosuppressive diseases or treatments.7 The Rhenium-SCT is a painless*, single session†, non-invasive‡ therapy that provides aesthetic results, even in cases otherwise considered difficult to treat8-10 The Rhenium-SCT utilizes the radioisotope Rhenium-188 in an epidermal application with optimal properties for the treatment of NMSCs. The Rhenium-SCT is a precise, personalised8,11 therapy that is only applied to the area needed to treat without affecting the healthy tissue. The specially designed device ensures the Rhenium-SCT compound never comes in direct contact with the patient's skin and the application is safe and simple for the applying physician. Most cases of NMSCs (basal cell carcinoma, squamous cell carcinoma, Bowen's disease, and Queyrate Erythroplasia) can be treated using the Rhenium-SCT in one single session.8-10† Scar-free healing of the treated lesion area and the regeneration of healthy tissue occurs usually within a few weeks after treatment.8 About OncoBeta® OncoBeta® with its headquarters located in Garching near Munich, Germany, is a privately held medical device company, specializing in the development and commercialization of state-of-the-art, innovative therapies. Since its foundation, OncoBeta® has concentrated its efforts on the development, regulatory approval(s) and commercialization of the epidermal radioisotope therapy Rhenium-SCT® (Skin Cancer Therapy), targeting non-melanoma skin cancers and keloid scars. OncoBeta® has perfected the customized application and device management system in conformity with all health, safety, and environmental protection regulatory standards. Find out more about the Rhenium-SCT® at Follow us on social media: LinkedIn: Facebook: Instagram: Forward-looking Statements This announcement includes forward-looking statements that involve risks, uncertainties, and other factors, many of which are outside of OncoBeta's control, and which could cause actual results to differ materially from the results discussed in the forward-looking statements. Forward-looking statements include statements concerning OncoBeta's plans, objectives, goals, future events, performance and/or other information that is not historical information. All such forward-looking statements are expressly qualified by these cautionary statements and any other cautionary statements which may accompany the forward-looking statements. OncoBeta® undertakes no obligation to publicly update or revise forward-looking statements to reflect subsequent events or circumstances after the date made, except as required by law. *No pain reported during procedure.8,10 †Complete tumor regression in 98.5% of lesions treated.9 ‡A procedure is considered non-invasive when no break or cut in the skin is created.11 References Tietze JK, et al. Clin Nucl Med. 2023;48(10):869–876. Hu W, et al. BMC Cancer. 2022;22(1):836. Ciążyńska M, et al. Sci Rep. 2021;11(1):4337. Urban K, et al. JAAD Int. 2021;2:98–108. Olsen CM, et al. Public Health Res Pract. 2022;32(1):3212203. Callan P, et al. Clinical practice guidelines for keratinocyte carcinoma: Surgical treatment. Cancer Council Australia. Last modified 25 November 2019. Available from: (accessed September 2023). Cancer.net. Skin Cancer (Non-Melanoma): Risk Factors and Prevention. February 2022. (accessed September 2023). Cipriani C, et al. J Dermatol Treat. 2022;33(2):969–975. Epub 22 Jul 2020. Cipriani C, et al. In Therapeutic Nuclear Medicine. 2014. RP Baum (Ed), New York: Springer. Castellucci P, et al. Eur J Nucl Med Mol Imaging. 2021;48(5):1511–1521. Australian Therapeutic Goods Administration. ARTG Public summary 400142. Contact: ***@moreymedia.com.au Photos: Press release distributed by PRLog SOURCE OncoBeta GmbH

GAITHERSBURG, Md. and SUZHOU, China, June 16, 2022 /PRNewswire/ -- Sirnaomics Ltd. (" Sirnaomics", stock code: 2257.HK), a leading biopharmaceutical company in discovery and development of RNAi therapeutics, announced the peer-reviewed publication of Phase IIa clinical study results of its lead therapeutic candidate, STP705, for the treatment of skin cancer, in the May 2022 issue of the Journal of Drugs in Dermatology (the " JDD"). The study, titled "Safety and Efficacy of TGF-β1/COX-2 Silencing Therapeutic in Adults with Cutaneous Squamous Cell Carcinoma In Situ," showed that STP705 was safe and well-tolerated in patients with Cutaneous Squamous Cell Carcinoma In Situ (isSCC). The key results from the publication indicate that this single-center, open label, dose escalation cohort study evaluated the safety and efficacy of various doses of intralesional injections of STP705, a therapeutic of TGF-β1/COX-2 combined with histidine-lysine polypeptide (siRNA/HKP) nanoparticle silencing, in patients with cutaneous cell carcinoma. The primary endpoint was the proportion of patients with complete histological clearance. Twenty-five patients received STP705 where nineteen of them (76%) achieved histological clearance. In the 30 µg/treatment group and 60 µg/treatment group, 80% and 100% of them achieved histological clearance, respectively. As a result of the study, STP705 appears to be noninvasive, safe and efficacious in treating cutaneous in situ squamous cell carcinoma. The recommended doses for future study of the investigational product are 30 µg/treatment and 60 µg/treatment. At last fall's Clinical Dermatology Conference 2021, Brian Berman, MD, PhD, Professor of Dermatology at The University of Miami Miller School of Medicine, a member of the Board of Directors of the American Academy of Dermatology, and the principal investigator of the clinical study of STP705 for treatment of isSCC, gave a presentation on the details of the clinical development and study results. Following his presentation, an audience survey was conducted among 2000+ clinical dermatologists, with questions about whether STP705 fulfilled a need for clinical practices for the treatment of isSCC. The survey results provided a strong favorable opinion regarding the clinical application potential of STP705. Through the Gore Range Capital Skin Health Innovation Competition during the conference, Sirnaomics STP705 was selected as one of the top three finalists. "A limited number of approved, non-surgical treatments for isSCC currently exist. Our results suggest that STP705 has the potential to be a viable option for patients with skin lesions due to this form of non-melanoma skin cancer, and publication and survey results further validated the clinical application potential of this novel siRNA therapeutic," said Michael Molyneaux M.D., Executive Director and Chief Medical Officer at Sirnaomics and lead author of the study. "The overexpression of TGF-β1 and COX-2 genes are strongly associated with SCC development, with TGF-β1 having a prominent role in tumor progression. By using RNAi based therapeutics such as STP705 that silence these genes, we have the potential to block the proliferation of isSCC through non-invasive means. This study supports this thesis, and we plan to continue to evaluate 30 µg and 60 µg doses in future studies." "The peer-reviewed publication of our Phase IIa STP705 clinical study results for treating isSCC in the JDD, 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, Ph.D., founder, Chairman of the Board, Executive Director, President and CEO of Sirnaomics. "This is a prevalent type of cancer, with over five million new diagnoses in the U.S. 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." About Non-melanoma Skin Cancer and Squamous Cell Carcinoma In Situ Non-melanoma skin cancers (NMSC) are the most common forms of human neoplasia. NMSC constitute a large group of skin cancers that are not melanoma, including squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Extramammary Paget's Disease (EMPD), Merkel cell carcinoma (MCC), and skin adnexal carcinomas. Among these, BCC and SCC account for the majority of NMSC with more than 5 million newly diagnosed cases estimated to occur in the U.S. every year. Squamous cell carcinoma in situ, also called Bowen disease, is the earliest form of SCC. Along with BCC, SCC is one of two major subtypes of NMSC. According to Incidence Estimate of Non-melanoma Skin Cancer (Keratinocyte Carcinomas) in the U.S. Population, 2012, the number of new cases of isSCC in the U.S. was 1.3 million in 2020 and is projected to increase to 3.4 million in 2030. In China, according to Chinese Society of Clinical Oncology, the number of new cases of isSCC is 11 thousand in 2020 and is projected to increase to 26 thousand in 2030. A World Health Organization authorized report from "International Agency for Research on Cancer" (2019) has demonstrated that the number of deaths in 2018 globally for both men and women from NMSC is 65,155, where the mortality of NMSC patients in Asia represents 41.9% of the global total, significantly more than other individual areas. Surgery is the currently the most common treatment option for the treatment of NMSC. 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 U.S. Food and Drug Administration (FDA) approved local injection therapy that is safe and effective. 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 U.S. FDA and Chinese National Medical Products Administration, 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. STP705 is currently in five clinical trials for different indications: a Phase IIa for isSCC, a Phase II for BCC, a Phase I/II for keloid scarring, a Phase I/II for hypertrophic scar, and a Phase I for liver cancer (basket). About Sirnaomics Sirnaomics is an RNA therapeutics biopharmaceutical company with product candidates in preclinical and clinical stages that focuses on the discovery and development of innovative drugs for indications with medical needs and large market opportunities. Sirnaomics is the first clinical-stage RNA therapeutics company to have a strong presence in both China and the United States, and also the first company to achieve positive Phase IIa clinical outcomes in oncology for an RNAi therapeutics for its core product, STP705. Learn more at . CONTACT: Michael Molyneaux, MD, MBA Executive Director and Chief Medical Officer, Sirnaomics Email: [email protected] Investor Relations: Nigel Yip Chief Financial Officer, China, Sirnaomics Email: [email protected] US Media Contact: Alexis Feinberg Tel: +1 203 939 2225 Email: [email protected] Asia Media Contact: Bunny Lee Tel: +852 3150 6707 Email: [email protected] SOURCE Sirnaomics Ltd.

Sirnaomics Doses First Patient in Phase Ⅱb Study of STP705 for Treatment of Squamous Cell Skin Cancer Company Expects to Report Interim Clinical Data of the Phase 2 in Second Half of 2021 Sirnaomics, Inc., a biopharmaceutical company engaged in the discovery and development of RNAi therapeutics against cancer and fibrotic diseases, today announced dose administration for the first patient in a Phase 2b study of the company’s drug candidate, STP705, for the treatment of squamous cell skin cancer in situ (isSCC). 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 randomized, double-blind, placebo-controlled Phase 2b study is evaluating the safety and efficacy of intralesional injection of STP705 in up to 100 adult patients with isSCC. This portion of the trial will further evaluate the two most efficacious dosing regimens of 30 ug and 60 ug. The primary endpoint of this trial is the proportion of participants with histological clearance of treated isSCC lesion at the end of treatment. Histological clearance will be defined as the absence of detectable evidence of isSCC tumor cell nests as determined by central pathology review. “For many patients with isSCC, surgery is still considered the only viable treatment option, so with our first patient dosed in this Phase 2b study, we’ll be able to observe the efficacy of STP705, which has to the potential to be a non-surgical, non-invasive alternative,” said Michael Molyneaux M.D., Chief Medical Officer. “Our interim readout later this year will guide our clinical development for this indication.” “After a high rate of patients achieved histological clearance in the Phase 2a study of STP705 for isSCC, we’re looking forward to seeing the results of our Phase 2b study as we begin patient dosing,” said Patrick Lu, Ph.D., founder, President and CEO of Sirnaomics. “The anticipated clinical readout in the second half of 2021 will provide more insights into the potential of STP705 for the treatment of non-melanoma skin cancer and the impact of RNAi therapeutics in oncology.” Additional information about this clinical trial is available at clinicaltrials.gov using the identifier: NCT04844983. About Non-melanoma Skin Cancer and Squamous Cell Carcinoma In Situ 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 non-melanoma skin cancer (NMSC) along with 5.43 million people that are currently living with cancer lesions. 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 subtypes 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. Surgery is the currently the most common treatment option for the treatment of NMSC. 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. About STP705 Sirnaomics’ 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. Read the original news release. 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 and corporate partnerships. 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.