MMP1

Phio's Compound RXI-185 is designed to slow progression of UV induced collagen breakdown Marlborough, Massachusetts--(News - June 18, 2024) - Phio Pharmaceuticals Corp. (NASDAQ: PHIO), a clinical stage biotechnology company whose proprietary INTASYL® siRNA gene silencing technology is designed to make immune cells more effective in killing tumor cells, has been granted a skin care patent in South Korea. The patent, METHODS FOR TREATING AGING AND SKIN DISORDERS USING NUCLEIC ACIDS TARGETING MMP1, covers the INTASYL RXI-185 compound that treats aging and skin disorders, including photo-aging. RXI-185 is a potent silencer of MMP1 expression in the skin, interrupting ultraviolet radiation (UVR) induced collagen breakdown, thereby improving and/or slowing the progression for skin thickening, elasticity and wrinkles. This is an additional patent in a family of patents covering INTASYL compounds that target aging skin disorders. The Phio patent portfolio now consists of 81 issued patents, 77 of which cover the INTASYL siRNA gene silencing technology. The portfolio includes patents and applications broadly covering both the composition and methods of use of INTASYL compounds targeting immune checkpoint, cellular differentiation, and metabolism targets for ex vivo cell-based cancer immunotherapies. "Our patent portfolio for Phio's INTASYL siRNA technology is extensive and robust," said Robert Bitterman, CEO of Phio Pharmaceuticals. "The addition of this recent patent for treatment of photo-aging complements our current initiative in treating skin cancer." About Phio Pharmaceuticals Corp. Phio Pharmaceuticals Corp. (Nasdaq: PHIO) is a clinical stage biotechnology company whose proprietary INTASYL® RNAi technology is designed to make immune cells more effective in killing tumor cells. INTASYL is the only self-delivering RNAi technology focused on immuno-oncology therapeutics. INTASYL drugs precisely target specific proteins that reduce the body's ability to fight cancer, without the need for specialized formulations or drug delivery systems. For additional information, visit the Company's website, . Forward Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as "intends," "believes," "anticipates," "indicates," "plans," "expects," "suggests," "may," "would," "should," "potential," "designed to," "will," "ongoing," "estimate," "forecast," "target," "predict," "could" and similar references, although not all forward-looking statements contain these words. These statements are based only on our current beliefs, expectations and assumptions and are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Examples of forward-looking statements include statements regarding the use of RXI-185 to treat skin disorders and photo-aging. Our actual results may differ materially from those indicated in the forward-looking statements as a result of a number of important factors, including, but not limited to, the impact to our business and operations by inflationary pressures, rising interest rates, recession fears, the development of our product candidates, results from our preclinical and clinical activities, our ability to execute on business strategies, our ability to develop our product candidates with collaboration partners, and the success of any such collaborations, the timeline and duration for advancing our product candidates into clinical development, the timing or likelihood of regulatory filings and approvals, the success of our efforts to commercialize our product candidates if approved, our ability to manufacture and supply our product candidates for clinical activities, and for commercial use if approved, the scope of protection we are able to establish and maintain for intellectual property rights covering our technology platform, our ability to obtain future financing, market and other conditions and those identified in our Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q under the caption "Risk Factors" and in other filings the Company periodically makes with the SEC. Readers are urged to review these risk factors and to not act in reliance on any forward-looking statements, as actual results may differ from those contemplated by our forward-looking statements. Phio does not undertake to update forward-looking statements to reflect a change in its views, events or circumstances that occur after the date of this release, except as required by law. Contact: Phio Pharmaceuticals Corp. ir@phiopharma.com PR Contact Michael Adams Bridge View Media adams@bridgeviewmedia.com To view the source version of this press release, please visit

An essential protein that acts as a gatekeeper for calcium entering cells promotes the growth of oral cancer and generates pain, according to a new study. Targeting this protein -- the ORAI1 calcium channel -- could provide a new approach to treating oral cancer, which causes persistent pain that worsens as it progresses. An essential protein that acts as a gatekeeper for calcium entering cells promotes the growth of oral cancer and generates pain, according to a new study published in Science Signaling led by researchers at NYU College of Dentistry. Targeting this protein -- the ORAI1 calcium channel -- could provide a new approach to treating oral cancer, which causes persistent pain that worsens as it progresses. "Our results show that the ORAI1 channel fuels the growth of oral cancer tumors and produces an abundance of molecules that, once secreted, interact with neurons resulting in an increased sensitivity to pain," said Ga-Yeon Son, a postdoctoral fellow in the Department of Molecular Pathobiology at NYU College of Dentistry and the study's first author. The keepers of the gates of heaven ORAI calcium channels -- named after the three sisters in Greek mythology who guarded the gates of heaven at Mount Olympus -- play an important role controlling how much calcium enters cells. "These calcium channels can be a source of good or bad for cells," said Rodrigo Lacruz, professor of molecular pathobiology at NYU College of Dentistry and the study's senior author. "Calcium entering cells is necessary for many good things, but too much calcium for a long time has the opposite effect." Calcium channels have been linked to various cancers, especially cancer progression, but few studies have looked at the role of ORAI1 in cancer and pain. "Calcium influx through ORAI1 channels has been well known to contribute to the regulation of gene expression by activating gene transcription factors in the cells. Notably, our investigation extends its function in regulating gene expression to altering oral cancer pain," said Son. Less ORAI1, less cancer growth and pain The researchers first analyzed tissue samples from human oral cancer tumors and healthy tongues. They found that the ORAI1 gene, which contains instructions for creating the ORAI1 calcium channel, was heavily overexpressed in the tumors but not in healthy tissue. They then examined human oral cancer cells and found that activating the ORAI1 calcium channel (but not other calcium channels) caused a large influx of calcium into cancer cells. This influx resulted in the increase of a calcium-dependent enzyme called matrix metalloprotease 1 (MMP1) that is secreted outside of cancer cells. MMP1 is abundant in multiple types of cancer, including oral cancer, where its overexpression is associated with metastasis and poor prognosis. Removing the ORAI1 gene from oral cancer cells changed the course of the disease in animal studies. When mice were inoculated with cancer cells lacking the ORAI1 gene, tumors grew more slowly and were less painful. "These findings demonstrate an important role for ORAI1 in oral cancer progression and pain, but what is the mechanism? We wondered if MMP1 could be the messenger relaying pain," said Lacruz. In collaboration with NYU Pain Research Center scientists Rajesh Khanna and Yi Ye, the team looked at the levels of MMP1 expressed in the fluid surrounding oral cancer cells and saw that cells lacking the ORAI1 gene secreted less MMP1 into the surrounding fluid. They combined the fluid with neurons from the trigeminal ganglia, a collection of nerves in the face that transmit pain in oral cancer. The fluid from cancer cells without the ORAI1 gene did not elicit a strong response from the neurons, but the MMP1-rich fluid from cells with ORAI1 evoked an increase in action potentials, the necessary signal for pain transmission. "This gives us evidence that an abundance of MMP1 may generate increased sensitivity to pain," said Lacruz. The researchers also ran experiments with abnormal but non-cancerous cells. When they overexpressed the ORAI1 gene in these non-invasive cells, they became invasive, raising the possibility that ORAI1 could play a role in cells switching from non-cancerous to cancerous cells. Future research: blocking ORAI Several FDA-approved drugs block the ORAI1 calcium channel, but they have not yet been tested in oral cancer. In future studies, the researchers will see whether nanoparticles can be loaded with an ORAI-blocking drug and precisely delivered into the tongues of animal models to stop oral cancer progression and pain. "In light of the ongoing opioid crisis, our study paves the way for validating novel pain treatments in oral cancer," said Rajesh Khanna, director of the NYU Pain Research Center, professor of molecular pathobiology at NYU Dentistry, and a co-author of the study. "Ultimately, our hope is that targeting the ORAI1 channel in oral cancer can prevent or delay the progression from oral epithelial dysplasia to oral cancer tumors and concurrently alleviate the pain burden experienced by oral cancer patients," added Son. Additional study authors include Nguyen Huu Tu, Maria Daniela Santi, Santiago Loya Lopez, and Guilherme H. Souza Bomfim of NYU College of Dentistry; Manikandan Vinu, Ariya Chaloemtoem, Rama Alhariri, and Youssef Idaghdour of NYU Abu Dhabi; and Fang Zhou of NYU Langone Health. The research was supported by the National Institute of Dental and Craniofacial Research (DE027981, DE027679, R01DE029493), National Institutes of Health HEAL Initiative (R01DE032501), National Institute of Neurological Disorders and Stroke (NS098772, NS120663), and National Institute on Drug Abuse (DA042852).

Topical FS2 shows statistically significant improvement versus the market leader VANCOUVER, BC, Jan. 22, 2021 /PRNewswire/ - BirchBioMed Inc., a clinical-stage immunology company focused on the prevention and reduction of immunological fibrotic conditions and defects in the immune system, has announced statistically significant, positive results of a double-blind study into the safety and efficacy of topical FS2 in the treatment of keloid scars. FS2, the active ingredient in BirchBioMed's FS2 cream, has been shown to inhibit the formation of collagen, which is the major component of scars. "The study definitively shows that FS2 has significant efficacy on mature keloid scars as compared not only to the vehicle control but to an active scar treatment (Mederma)," said Dr. Mark Nestor, M.D., Ph.D., the study's principal investigator and director of the Center for Clinical and Cosmetic Research in Aventura, Florida. "Showing significant benefit on mature keloid scars points to significant efficacy for the treatment of hypertrophic scars as well as cosmetic benefit to all post-surgical scars." The prospective randomized double-blind trial compared the safety and efficacy of topical FS2 versus the market leading scar cream (Mederma) and a vehicle (placebo cream) in the treatment of mature keloids in 75 subjects. Trial participants were evaluated using both the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS). The percentage change in VSS scores for FS2 showed a statistically significant improvement when compared to Mederma (p<0.001) and versus vehicle (p<0.05) at the conclusion of the 180-day trial. Secondary data analysis using POSAS showed dramatic patient satisfaction with FS2 patients scoring a 51% improvement with FS2 versus Mederma's 28% (p<0.05) and vehicle 20% (p<0.01). Neither Mederma nor vehicle showed statistically significant improvement according to the subjects' evaluations. "Subjects using FS2 graded the improvement in their scar greater than Mederma and vehicle at every time point culminating in highly significant differences at 180 days," said Dr. Nestor. "This signifies that it wasn't only the appearance of the keloid scar that changed over time with FS2 but more fundamentally the way the subject globally felt about the improvement. Furthermore, there were no safety concerns noted and no significant local skin reactions observed." As BirchBioMed's lead antifibrotic platform therapy, FS2 acts at the molecular level by reducing production of two primary extracellular scar-forming proteins (collagen and fibronectin) and by increasing the production of key scar-degrading enzymes (MMP-1 and MMP-3) to stop the formation of scars and promote the breakdown of existing scars. "We are delighted with the results of FS2 in providing a safe and effective treatment for disfiguring scars that often profoundly affect a patient's quality of life," said Mark S. Miller, chief executive officer of BirchBioMed. "Scarring poses a chronic and growing therapeutic challenge for millions of patients each year. The global cost of treating scars is expected to reach $41.8 billion in 2022, compared with $21.4 billion just three years ago. Moreover, the U.S. National Institutes of Health estimates that 11 million Americans suffer from keloid scars, making it all the more critical that we develop cost-effective and successful treatments." About BirchBioMed BirchBioMed Inc. is a clinical-stage immunology company focused on the prevention and reduction of immunological fibrotic conditions and reversing defects in the immune system. As a University of British Columbia (UBC) spinoff, BirchBioMed holds the exclusive, worldwide pharmaceutical license from UBC for two breakthrough medical technologies in the treatment of scarring and certain autoimmune diseases.