S100A7

Scinai’s NanoAbs downregulated key molecular markers overexpressed in plaque psoriasis Stratum corneum regained normal appearance in laboratory 3D skin model Results from ex-vivo study in human psoriatic skin anticipated in Q4 2023; In-vivo animal study results anticipated in early 2024 JERUSALEM, Sept. 13, 2023 (GLOBE NEWSWIRE) -- via IBN – Scinai Immunotherapeutics Ltd. (Nasdaq: SCNI) a biopharmaceutical company focused on developing, manufacturing, and commercializing innovative inflammation and immunology (I&I) biological products primarily for the treatment of autoimmune and infectious diseases, today announces encouraging results in a preclinical study of Scinai’s anti‑interleukin 17 (IL‑17) NanoAbs as a treatment for plaque psoriasis. Scinai’s NanoAbs are alpaca‑derived recombinant variable domain of heavy-chain-only antibodies and are also known as nanobodies or VHH antibodies. The NanoAbs were tested in a 3D biologic skin model constructed out of a scaffold mounted with various skin cells to generate layers that mimic the structure of human skin and induced to express plaque psoriasis. Upon introduction of NanoAbs into the model (either topically or subcutaneously), standard molecular markers for psoriasis that are overexpressed in the disease (S100A7, CXCL1, and CCL20) were downregulated and outer skin layers (stratum corneum) regained normal appearance. These results suggest NanoAbs’ therapeutic potential to relieve symptoms of plaque psoriasis. In earlier laboratory tests the NanoAbs showed not only high affinity to all three IL-17 isoforms relevant for psoriasis (A, F and AF complex), but also significant neutralization of these isoforms in tissue cultures. IL-17 plays a major role in the development of plaque psoriasis and is the molecular target of several recently launched biological treatments, mainly monoclonal antibodies (mAbs), such as Cosentyx (Novartis, NYSE: NVS) and Taltz (Lilly, NYSE: LLY), both of which target IL-17A. Research shows that targeting IL-17F isoform in addition to IL-17A provides higher efficacy in treating plaque psoriasis. The recently launched Bimzelx (UCB, Euronext Brussels: UCB) was the first mAb targeting both IL-17A and F to be approved by the by the European Medicines Agency (EMA). MoonLake Immunotherapeutics (Nasdaq: MLTX, Market Cap $3.1B) is also developing a nanobody targeting both IL-17A and F. Last year, MoonLake reported superior results vs. Cosentyx in a phase 2 plaque psoriasis clinical trial. All the above-mentioned antibodies, indicated only for moderate to severe psoriasis patients, are administered by subcutaneous injection for systemic drug distribution and carry risk of considerable side effects. These drugs are also expensive as they require chronic, life long, bi-weekly injections, each at a cost of several thousand dollars. Mild psoriasis, which accounts for 50% of plaque psoriatic patients, unfortunately has no safe and affordable biological drug available. Experience shows that even the 28% of patients with moderate plaque psoriasis tend to avoid or delay onset of these biological treatments due to the associated risks. Conversely, Scinai’s NanoAbs are designed to be administered locally to the dermis and are engineered to degrade in a way that should prevent systemic side effects. Results of this recent study suggest the potential for a highly efficacious, specific, yet safer and more convenient treatment for the large and underserved population of mild to moderate plaque psoriasis patients. The NanoAb, exclusively licensed to Scinai, was discovered by Professor Dirk Görlich, Director at the Max Planck Institute for Multidisciplinary Sciences and was tested for neutralization at the laboratory of Professor Matthias Dobbelstein at University Medical Center Göttingen (UMG). Görlich and Dobbelstein are Scinai’s lead collaborators for development of a pipeline of NanoAb-based inflammation and immunology (I&I) biological therapeutics for the treatment of autoimmune and infectious diseases such as psoriasis, psoriatic arthritis, asthma, wet AMD and COVID-19. Scinai recently started to evaluate the anti-IL-17 NanoAbs in a full human skin model induced for plaque psoriasis to evaluate the effective dose and schedule of treatment, with in-vivo animal studies anticipated in early 2024. About Scinai Immunotherapeutics Ltd. Scinai Immunotherapeutics Ltd. (Nasdaq: SCNI) is a biopharmaceutical company focused on developing, manufacturing and commercializing innovative inflammation and immunology (I&I) biological products primarily for the treatment of autoimmune and infectious diseases. With a state-of-the-art facility for biopharmaceutical product development and manufacturing and highly experienced pharmaceutical industry leadership, Scinai offers end-to-end boutique CDMO services in parallel to developing its own pipeline of diversified and commercially viable products and platforms beginning with an innovative nanosized VHH antibody (NanoAb) pipeline targeting diseases with large unmet medical needs. Company website: . Contact Details Scinai: Joshua E. Phillipson | +972 8 930 2529 | joshua.phillipson@scinai.com Forward Looking Statements This press release contains forward-looking statements within the meaning of the Private Litigation Reform Act of 1995. Words such as "expect," "believe," "intend," "plan," "continue," "may," "will," "anticipate," and similar expressions are intended to identify forward-looking statements. All statements, other than statements of historical facts, included in this press release regarding strategy, future operations, future financial position, future revenue, projected expenses, prospects, plans and objectives of management are forward-looking statements. Examples of such statements include, but are not limited to, statements regarding the timing of future preclinical studies and the therapeutic and commercial potential of NanoAbs. These forward-looking statements reflect management's current views with respect to certain current and future events and are subject to various risks, uncertainties and assumptions that could cause the results to differ materially from those expected by the management of Scinai Immunotherapeutics Ltd. Risks and uncertainties include, but are not limited to, the risk of a delay in results from ex-vivo study in human psoriatic skin and In-vivo animal study results; the risk that Scinai may not be able to secure additional capital on attractive terms, if at all; the risk that the therapeutic and commercial potential of NanoAbs will not be met; the risk that our business strategy may not be successful; the risk that the European Investment Bank (EIB) may accelerate the loans under its finance contract with Scinai; risks relating to the SARS-CoV-2 (COVID-19) virus; Scinai's ability to acquire rights to additional product opportunities; Scinai's ability to enter into collaborations on terms acceptable to Scinai or at all; timing of receipt of regulatory approval of Scinai's manufacturing facility in Jerusalem, if at all or when required; the risk that the manufacturing facility will not be able to be used for a wide variety of applications and other vaccine and treatment technologies; and the risk that drug development involves a lengthy and expensive process with uncertain outcomes. More detailed information about the risks and uncertainties affecting the Company is contained under the heading "Risk Factors" in the Company's Annual Report on Form 10-K filed with the Securities and Exchange Commission on April 17, 2023. Scinai undertakes no obligation to revise or update any forward-looking statement for any reason. Corporate Communications: InvestorBrandNetwork (IBN) Los Angeles, California 310.299.1717 Office Editor@InvestorBrandNetwork.com

Creating a mutation that inhibits how the bacterial pathogen Neisseria gonorrhoeae causes gonorrhea, a common sexually transmitted infection, could offer a new way to prevent and treat the disease, according to researchers. Creating a mutation that inhibits how the bacterial pathogen Neisseria gonorrhoeae causes gonorrhea, a common sexually transmitted infection, could offer a new way to prevent and treat the disease, according to researchers in the Institute for Biomedical Sciences at Georgia State University. The researchers found that generating a mutation in a key part of the outer membrane transporter that N. gonorrhoeae uses to hijack human immunity proteins and strip them of metals could help to prevent gonorrhea infection. The findings are published in the journal mBio. Gonorrhea, which affects more than 80 million people worldwide each year, is a global threat to public health because of the increasing incidence of antimicrobial drug resistance, rising treatment costs and lack of a protective vaccine. Up to 80 percent of cases in women are asymptomatic, and if left untreated, gonorrhea can lead to serious health consequences, including pelvic inflammatory disease, ectopic pregnancy, infertility and even life-threatening endocarditis and meningitis. Effective treatment options for gonorrhea are decreasing because of evolving antimicrobial resistance to existing drugs. Also, it's challenging to identify suitable vaccine targets because N. gonorrhoeae alters expression of key surface molecules and dampens the immune response. To block invading pathogens from causing disease, humans rely on a process called nutritional immunity to limit the availability of critical nutrients such as iron and zinc and starve invaders. Metal-binding proteins sequester metals and limit the amount of free essential metal ions that pathogens need to flourish and cause disease. To overcome host nutritional immunity efforts, N. gonorrhoeae deploys TonB-dependent transporters (TdTs) to its outer membrane to bind to host nutritional immunity proteins and strip them of their metals. TdTs often play key roles in establishing infections, making them promising vaccine targets. One TdT named TdfJ recognizes human S100A7, a zinc-binding protein that inhibits the replication of pathogens by hiding zinc. N. gonorrhoeae uses TdfJ to extract zinc from S100A7 and internalize the metal. TdfJ contains an alpha-helix finger in extracellular loop 3. A similar alpha-helix in loop 3 of another gonococcal TdT, known as TbpA, plays a critical role in the interaction between TbpA and human transferrin, which is required for the uptake of iron. Based on this information, the researchers hypothesized the TdfJ loop 3 helix (L3H) participates in interactions with S100A7, and they generated a series of mutations in the TdfJ L3H to determine if they blocked theability of N. gonorrhoeae to acquire zinc and therefore to cause disease. "The prospect of untreatable gonococcal infections has spurred efforts to identify targets for novel therapeutic and prevention strategies, and members of the family of outer membrane TonB-dependent metal transporters have emerged as promising candidates because they play a critical role in establishing infection," said Dr. Cynthia Nau Cornelissen, senior author of the study, Distinguished University Professor and director of the Center for Translational Immunology in the Institute for Biomedical Sciences at Georgia State. "Our study revealed that mutagenesis of key residues within the TdfJ L3H reduced S100A7 binding and zinc piracy by the gonococcus, with the most profound effects seen with substitutions at residues K261 and R262. Taken together, these data suggest a key role for the TdfJ L3H in subverting host nutritional immunity." The study characterized the binding interaction between the zinc importer TdfJ and its human zinc source, S100A7, and it also identified a key region of TdfJ that mediates this interaction. "We detailed for the first time, the binding interaction for gonococcal TdfJ and its human ligand S100A7. We also identified several mutations in TdfJ loop 3 that alter S100A7 binding and subsequent zinc extraction," said Stavros A. Maurakis, first author of the study and a Ph.D. graduate of the Institute for Biomedical Sciences at Georgia State."With a more thorough understanding of the intricate relationships between these bacterial nutrient receptors and their host nutrient sources, we may help pave the way toward identifying effective prophylaxis and/or treatment for an important human disease." Co-authors of the study include Stavros A. Maurakis, Julie L. Stoudenmire and Cynthia Nau Cornelissen of the Institute for Biomedical Sciences at Georgia State; and Jeffrey K. Rymer and Walter J. Chazin of Vanderbilt University. The study is funded by the National Institutes of Health (NIH).

Lower immunity and recurring infections are common in type 1 and type 2 diabetes. Researchers now show that the immune system of people with diabetes has lower levels of the antimicrobial peptide psoriasin, which compromises the urinary bladder's cell barrier, increasing the risk of urinary tract infection. Lower immunity and recurring infections are common in type 1 and type 2 diabetes. Researchers at Karolinska Institutet in Sweden now show that the immune system of people with diabetes has lower levels of the antimicrobial peptide psoriasin, which compromises the urinary bladder's cell barrier, increasing the risk of urinary tract infection. The study is published in Nature Communications. Diabetes results from lack of insulin and/or decreased insulin action. Insulin is a hormone that regulates glucose (sugar) and thus energy to the cells. In type 1 diabetes, the body stops producing insulin, while in type 2 diabetes, the cells have become less sensitive to insulin, which contributes to high blood glucose levels. Diabetes is a common disease that affects the health in many ways. One effect is that it compromises the innate immune system, leaving many people with increased susceptibility to regular infections, such as urinary tract infections (UTI)s caused by E. coli bacteria. In people with diabetes, these are more likely to lead to general blood poisoning, sepsis, originating in the urinary tract. An endogenous antibiotic Researchers at Karolinska Institutet have now investigated whether glucose levels in people with diabetes (type 1, type 2, or prediabetes) are linked with psoriasin, an endogenous antibiotic which is a part of the innate immune system. Using urine, urinary bladder cells and blood serum samples from patients, the researchers analysed levels of psoriasin and other peptides necessary for ensuring that the bladder mucosa remains intact and protects against infection. The findings were then verified in mice and urinary bladder cells with and without infection. "We found that high glucose concentrations reduce the levels of the antimicrobial peptide psoriasin, while insulin has no effect," says Annelie Brauner, professor at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet who led the study. "People with diabetes have lower levels of psoriasin, which weakens the cells' protective barrier function and increases the risk of bladder infection." Oestrogen therapy reduced bacterial population Professor Brauner's research group has previously shown that treatment with oestrogen restores the protective function of bladder cells in humans and mice and thereby help to regulate the immune response to a UTI. The researchers therefore tested how oestrogen treatment affects infected cells exposed to high glucose concentrations. They found that the treatment boosted levels of psoriasin and reduced bacterial populations, indicating that the treatment may have an effect also among patients with diabetes. "We now plan to probe deeper into the underlying mechanisms of infections in individuals with diabetes," says the study's lead author Soumitra Mohanty, researcher at the same department at Karolinska Institutet. "The ultimate goal is to reduce the risk of infection in this growing patient group." The study was conducted in collaboration with the Karolinska University Hospital, Region Stockholm, Capio and Uppsala University in Sweden and Universitätsklinikum Schleswig-Holstein in Germany. It was largely financed by the Olle Engkvist Foundation, Region Stockholm (ALF funding), the KI Research Foundation, the Swedish Society of Medicine, the Swedish Society for Medical Research (SSMF), the Clas Groschinsky Memorial Foundation, the Åke Wiberg Foundation and the Magnus Bergvall Foundation. There are no reported conflicts of interest.