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Patent has already been issued in other major markets including the U.S. PETACH TIKVA, Israel--(BUSINESS WIRE)-- Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE:CANF), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address oncological and inflammatory diseases, today announced it received a Notice of Allowance from the European Patent Office for its patent application titled “An A3 Adenosine Receptor Ligands For Use in Treatment of a Sexual Dysfunction”. This invention addresses the use of the CF602 drug candidate as an oral or topical drug for patients such as diabetics, who suffer from erectile dysfunction, and cannot use the current drugs on the market. While oral phosphodiesterase type 5 (PDE5) inhibitors are the current standard of care for erectile dysfunction (ED), with brands including Viagra, Cialis, Levitra, and Stendra, an estimated 30% to 35% of ED patients are non-responders, and these drugs can be contraindicated for people living with diabetes. Can-Fite recently published an article in Andrologia, suggesting that CF602 could potentially offer an alternative to the current drugs on market. A full erectile recovery was achieved following a single dose of CF602 with restored muscle collagen ratio and endothelial cell function. Can-Fite’s CF602, an allosteric modulator of the A3 adenosine receptor (A3AR), applied topically or orally in a diabetic rat model, resulted in increased arterial blood flow and significant dose-dependent improvements in intracavernosal pressure (ICM), smooth muscle/collagen ratio, vascular endothelial growth factor and endothelial nitric oxide synthase. treatment to PDE5 inhibitors, particularly to PDE5 non-responders and diabetics. “This additional European patent for erectile dysfunction adds to our growing IP estate for this high-value indication of the CF602 drug candidate. We believe our strong and broad IP, together with the pre-clinical positive data position it as a promising candidate for further development for the treatment of sexual dysfunction,” stated Motti Farbstein, Can-Fite CEO. The Erectile Dysfunction market is expected to reach approximately $6.6 billion by 2030, according to Market Research Future. About Namodenoson Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson is currently being evaluated in a pivotal Phase III trial for advanced liver cancer, a Phase IIb trial for the treatment of steatotic liver disease (SLD), and the Company is planning a Phase IIa study in pancreatic cancer. A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential expression may be one of the important factors that accounts for the excellent safety pro the drug. About Can-Fite BioPharma Ltd. Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CANF) is an advanced clinical stage drug development Company with a platform technology that is designed to address multi-billion dollar markets in the treatment of cancer, liver, and inflammatory disease. The Company's lead drug candidate, Piclidenoson recently reported topline results in a Phase III trial for psoriasis and is expected to commence a pivotal Phase III. Can-Fite's cancer and liver drug, Namodenoson, is being evaluated in a Phase IIb trial for the treatment metabolic dysfunction-associated steatohepatitis (MASH), a Phase III pivotal trial for hepatocellular carcinoma (HCC), and the Company is planning a Phase IIa study in pancreatic cancer. Namodenoson has been granted Orphan Drug Designation in the U.S. and Europe and Fast Track Designation as a second line treatment for HCC by the U.S. Food and Drug Administration. Namodenoson has also shown proof of concept to potentially treat other cancers including colon, prostate, and melanoma. CF602, the Company's third drug candidate, has shown efficacy in the treatment of erectile dysfunction. These drugs have an excellent safety pro experience in over 1,600 patients in clinical studies to date. For more information please visit: . Forward-Looking Statements This press release may contain forward-looking statements, about Can-Fite’s expectations, beliefs or intentions regarding, among other things, its product development efforts, business, financial condition, results of operations, strategies or prospects. All statements in this communication, other than those relating to historical facts, are “forward looking statements”. Forward-looking statements can be identified by the use of forward-looking words such as “believe,” “expect,” “intend,” “plan,” “may,” “should” or “anticipate” or their negatives or other variations of these words or other comparable words or by the fact that these statements do not relate strictly to historical or current matters. Forward-looking statements relate to anticipated or expected events, activities, trends or results as of the date they are made. Because forward-looking statements relate to matters that have not yet occurred, these statements are inherently subject to known and unknown risks, uncertainties and other factors that may cause Can-Fite’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Important factors that could cause actual results, performance or achievements to differ materially from those anticipated in these forward-looking statements include, among other things, our history of losses and needs for additional capital to fund our operations and our inability to obtain additional capital on acceptable terms, or at all; uncertainties of cash flows and inability to meet working capital needs; the initiation, timing, progress and results of our preclinical studies, clinical trials and other product candidate development efforts; our ability to advance our product candidates into clinical trials or to successfully complete our preclinical studies or clinical trials; our receipt of regulatory approvals for our product candidates, and the timing of other regulatory filings and approvals; the clinical development, commercialization and market acceptance of our product candidates; our ability to establish and maintain strategic partnerships and other corporate collaborations; the implementation of our business model and strategic plans for our business and product candidates; the scope of protection we are able to establish and maintain for intellectual property rights covering our product candidates and our ability to operate our business without infringing the intellectual property rights of others; competitive companies, technologies and our industry; risks related to any resurgence of the COVID-19 pandemic and the war between Israel and Hamas; risks related to not satisfying the continued listing requirements of NYSE American; and statements as to the impact of the political and security situation in Israel on our business. More information on these risks, uncertainties and other factors is included from time to time in the “Risk Factors” section of Can-Fite’s Annual Report on Form 20-F filed with the SEC on March 28, 2024 and other public reports filed with the SEC and in its periodic filings with the TASE. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Can-Fite undertakes no obligation to publicly update or review any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by any applicable securities laws. View source version on businesswire.com: Contacts Can-Fite BioPharma Motti Farbstein info@canfite.com +972-3-9241114 Source: Can-Fite BioPharma Ltd. View this news release online at:

First marketing authorization submission for sepiapterin with additional global submissions to follow in 2024 SOUTH PLAINFIELD, N.J., March 28, 2024 /PRNewswire/ -- PTC Therapeutics, Inc. (NASDAQ: PTCT) announced today the submission of the sepiapterin MAA to the European Medicines Agency. The MAA submission is for the treatment of pediatric and adult patients with PKU, including the full spectrum of disease subtypes. "This MAA submission is the first in a series of global submissions for sepiapterin as we move closer to bringing this therapy to children and adults with PKU worldwide," said Matthew B. Klein, M.D., Chief Executive Officer of PTC Therapeutics. "The strength of the sepiapterin data generated in clinical trials substantiate how differentiated sepiapterin is from currently available therapies and support how sepiapterin could address the significant unmet medical need for PKU patients." The sepiapterin MAA includes the results of the phase 3 APHENITY trial in which sepiapterin had a statistically significant and clinically meaningful reduction in blood phenylalanine levels in pediatric and adult PKU patients. Sepiapterin treatment resulted in a mean reduction in Phe levels of 63% in the overall treated population and 69% in the subgroup of subjects with classical PKU. The vast majority of subjects (84%) achieved Phe control in accordance with treatment guidelines, and 22% of subjects had normalization of Phe levels. Data from the ongoing APHENITY open-label extension study demonstrates that these sepiapterin treatment effects are durable. In addition, data from the Phe tolerance sub study demonstrate that subjects are liberalizing their diet, beyond the recommended daily allowance of protein, and maintaining control of Phe within target levels from guidelines. The ability to enable patients to liberalize their highly restrictive diets and still maintain Phe control, is a very meaningful sepiapterin treatment benefit for physicians, payers and patients. PTC expects to submit the sepiapterin NDA to the FDA no later than the third quarter of 2024. Submissions in 2024 are planned in a number of additional key countries where PTC has existing rare disease commercial infrastructure including Brazil and Japan. About Sepiapterin Sepiapterin (formerly PTC923) is an oral formulation of synthetic sepiapterin, a precursor to intracellular tetrahydrobiopterin, which is a critical enzymatic cofactor involved in the metabolism and synthesis of numerous metabolic products. Sepiapterin is a more bioavailable precursor than exogenously administered synthetic BH4 and has the potential to treat the broad range of PKU patients. About Phenylketonuria Phenylketonuria (PKU) is a rare, inherited metabolic disease, which affects the brain.1 It is caused by a defect in the gene that helps create the enzyme needed to break down phenylalanine.1 If left untreated or poorly managed, phenylalanine – an essential amino acid found in all proteins and most foods – can build up to harmful levels in the body. This causes severe and irreversible disabilities, such as permanent intellectual disability, seizures, delayed development, memory loss, and behavioral and emotional problems.1 Newborns with phenylketonuria initially don't have any symptoms, but symptoms are usually progressive, and damage caused by toxic levels of phenylalanine in the first few years of life is irreversible.2,3 Diagnosis of phenylketonuria usually takes place during newborn screening programs.4 There are an estimated 58,000 people with phenylketonuria globally. About PTC Therapeutics, Inc. PTC is a global biopharmaceutical company focused on the discovery, development and commercialization of clinically differentiated medicines that provide benefits to patients with rare disorders. PTC's ability to innovate to identify new therapies and to globally commercialize products is the foundation that drives investment in a robust and diversified pipeline of transformative medicines. PTC's mission is to provide access to best-in-class treatments for patients who have little to no treatment options. PTC's strategy is to leverage its strong scientific and clinical expertise and global commercial infrastructure to bring therapies to patients. PTC believes this allows it to maximize value for all its stakeholders. To learn more about PTC, please visit us at and follow us on Facebook, Instagram, LinkedIn and Twitter at @PTCBio. For More Information: Investors: Kylie O'Keefe +1 (908) 300-0691 kokeefe@ptcbio.com Media: Jeanine Clemente +1 (908) 912-9406 jclemente@ptcbio.com Forward-Looking Statement: This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this release, other than statements of historic fact, are forward-looking statements, including statements regarding: the future expectations, plans and prospects for PTC, including with respect to the expected timing of regulatory submissions and responses, commercialization and other matters with respect to its products and product candidates; PTC's strategy, future operations, future financial position, future revenues, projected costs; the extent, timing and financial aspects of our strategic pipeline prioritization and reductions in workforce; and the objectives of management. Other forward-looking statements may be identified by the words, "guidance", "plan," "anticipate," "believe," "estimate," "expect," "intend," "may," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions. PTC's actual results, performance or achievements could differ materially from those expressed or implied by forward-looking statements it makes as a result of a variety of risks and uncertainties, including those related to: the outcome of pricing, coverage and reimbursement negotiations with third party payors for PTC's products or product candidates that PTC commercializes or may commercialize in the future; expectations with respect to sepiapterin, including any regulatory submissions and potential approvals, commercialization, the potential achievement of development, regulatory and sales milestones and contingent payments that PTC may be obligated to make; significant business effects, including the effects of industry, market, economic, political or regulatory conditions; changes in tax and other laws, regulations, rates and policies; the eligible patient base and commercial potential of PTC's products and product candidates; PTC's scientific approach and general development progress; and the factors discussed in the "Risk Factors" section of PTC's most recent Annual Report on Form 10-K, as well as any updates to these risk factors filed from time to time in PTC's other filings with the SEC. You are urged to carefully consider all such factors. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. There are no guarantees that any product will receive or maintain regulatory approval in any territory, or prove to be commercially successful, including sepiapterin. The forward-looking statements contained herein represent PTC's views only as of the date of this press release and PTC does not undertake or plan to update or revise any such forward-looking statements to reflect actual results or changes in plans, prospects, assumptions, estimates or projections, or other circumstances occurring after the date of this press release except as required by law. Acronyms: EMA: European Medicines Agency FDA: U.S. Food and Drug Administration MAA: Marketing Authorization Application NDA: New Drug Application PKU: Phenylketonuria View original content: SOURCE PTC Therapeutics, Inc. Company Codes: NASDAQ-NMS:PTCT

Researchers are working to understand how protein quality control works in cells.  From plants to animals, all living things depend on proteins to help their cells function properly. In certain cases, like when under stress in response to heat or toxins, some proteins within the cell condense into liquid-like droplets called condensates. This process is hypothesized to occur via phase separation and provides a quick way for the cell to assemble certain components. Research in Syracuse University Professor Carlos Castañeda's lab has recently shown that protein quality control (PQC) components are important for many of these condensates. Castañeda, associate professor of biology and chemistry in the College of Arts and Sciences (A&S), is among a team of researchers working to understand how protein quality control works in cells. Similar to the way computers use coding as a set of instructions, the PQC receives its instructions from polyubiquitin chains. Ubiquitin (Ub) is a regulatory protein found in all eukaryotic cells (cells containing a defined nucleus) and polyubiquitin is an assembly containing at least a few ubiquitin molecules. Under normal operating conditions, condensates form and react to a stressor, and then dissolve after the stress is relieved. But when this system becomes disrupted, it can result in protein clumping or aggregation, which can cause cells, especially those in the nervous system, to die. These abnormal protein aggregates are markers for neurological diseases like amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. By understanding the circumstances that lead to dysregulation of the PQC, scientists hope this research will one day lead to a cure for such neurodegenerative diseases. In a paper published last year in EMBO Reports, Castañeda and his collaborators established a framework for how polyubiquitin chains regulate the formation and disassembly of a condensate made of Ubiquilin-2 (UBQLN2) proteins, whose dysregulation is implicated in ALS. Polyubiquitin is important for UBQLN2 function and the two bind noncovalently, meaning that the interaction between them is weaker than a covalent chemical bond. Following up on that work, the researchers wanted to further explore the specific conditions that affect assembly of these condensates. "While working on the EMBO Reports project, we started to see that more extended polyubiquitin chains favored phase separation (condensate formation) with UBQLN2," says Castañeda. "So, we wondered if this is always true. We decided to make even more extended chains." Through the Research Experience for Undergraduates (REU) program, Castañeda welcomed students Suzanne Enos and Antara Chaudhuri into his lab in 2021. The NSF-sponsored REU program brings undergraduate students from across the country to Syracuse's campus to participate in research over the summer. In Castañeda's lab, the team engineered and designed different types of polyubiquitin chains with variable lengths and topologies. Enos and Chaudhuri then helped test how well these chains phase separated with UBQLN2. After further design-work by Sarasi Galagedera, a former postdoctoral researcher in Castañeda's lab; Thuy Dao, a lab manager in the Department of Chemistry; and Jeremy Schmit, a professor of physics at Kansas State University, the team found there was a "sweet spot" -- or specific spacing between Ub units -- where condensate formation was optimized. Fittingly coined as "goldilocks," the group's findings were recently published in Proceedings of the National Academy of Sciences (PNAS). "We found that there is an arrangements of ubiquitin units in polyubiquitin that is 'just right' for condensates to form," says Castañeda. "Ubiquitin units that are too far apart or too close together don't favor condensate formation as much. Jeremy Schmit used theoretical modeling and polyphasic linkage concepts to generalize these experimental observations." Furthermore, they uncovered that polyubiquitin in excess causes the condensates to disassemble. "In a cell, you can imagine that concentrations of polyubiquitin, as well as the spacing between ubiquitin units within different types of polyubiquitin, can up- or down-regulate condensate formation. You essentially have multiple ways to tune condensate formation with just adding this one polyubiquitin molecule," notes Castañeda. While their research merely scratches the surface of how polyubiquitin chains can regulate phase separation of condensates, Castañeda says it offers proof that these chains will be a main regulator of droplets. Future studies will involve adapting their rules to an in vitro system that models PQC to prove and test their theories in living cells. "This work provides a principle that can be applied to understanding how biomolecular condensates are generally controlled and will have large implications for anyone studying the regulation of their favorite biomolecular condensate," says Castañeda. The team's work was funded by the following grants: NIH R01 GM136946 awarded to Carlos Castañeda; NSF REU grant awarded to the Department of Chemistry; and NIH R01 GM141235 awarded to Jeremy Schmit.