Adenosine deaminase deficiency

FDA & EMA approvals for rare genetic diseases are fast and require clinical studies with small number of patients Ramat Gan, Israel, March 19, 2025 (GLOBE NEWSWIRE) -- 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 that a Phase II design is completed and preparatory work is undergoing for the initiation of clinical study in the rare genetic disease Lowe Syndrome. Dr. Franchesca Emma from the Division of Nephrology, Bambino Gesù Children's Hospital - IRCCS Rome Italy, will be the principal investigator of the study. The Phase II open study will enroll 5 patients that will be treated twice daily with 3 mg Piclidenoson for 12 months. The study’s primary end point will be the efficacy of Piclidenoson in increasing 99mTc-DMSA renal uptake. The treatment of this rare genetic disease is based on successful pre-clinical work of Dr. Antonella De Matteis, Professor of Biology, Department of Molecular Medicine and Medical Biotechnology at the University of Naples Federico II, and Program Coordinator of the Cell Biology and Disease Mechanisms at the Telethon Institute of Genetics and Medicine (TIGEM) in Italy. Can-Fite and Fondazione Telethon have signed a collaboration agreement for the clinical development of Piclidenoson for the treatment of Lowe Syndrome, a high medical need with no drug available. Lowe Syndrome, also known as oculo-cerebro- renal syndrome (OCRL), an X-linked genetic condition occurring almost exclusively in males, is a multisystem disorder characterized by vision problems including clouding of the lenses of the eyes (cataracts) that are present at birth, kidney problems (consisting of urinary loss of proteins and solutes) that usually develop in the first year of life, and brain abnormalities associated with intellectual disabilities, and a life span that rarely exceeds 40 years. Lowe Syndrome prevalence is estimated at approximately 1 in 500,000. “Having tested thousands of compounds in search of a treatment for Lowe Syndrome, Piclidenoson is the only compound we’ve found to date that has shown to be effective in pre-clinical studies. Importantly, we observed that Piclidenoson treatment in preclinical models of Lowe syndrome leads to a significant decrease of the urinary loss of proteins,” Dr. De Matteis stated. “We chose to investigate Piclidenoson based on the availability of extensive scientific data showing its excellent safety, coupled with efficacy in this disease in pre-clinical studies which involves renal, cerebral, and ocular manifestations.” Can-Fite CSO&Chairperson Dr. Pnina Fishman commented, “We are very much enthusiastic by the breakthrough research of Dr. De Matteis showing that Piclidenoson is efficacious in treating pre-clinical models of Lowe Syndrome. Her impressive results are the basis for implementing Piclidenoson in the treatment of this rare genetic disease”. stated Dr. Pnina Fishman, Can-Fite CSO & Chairperson”. About Piclidenoson Piclidenoson is a robust anti-inflammatory agent, currently being evaluated in a pivotal Phase III psoriasis clinical study under approval of both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Piclidenoson is a novel, first-in-class, A3 adenosine receptor agonist (A3AR) small molecule, orally bioavailable drug with an excellent safety profile demonstrating evidence of efficacy in Phase II and Phase III clinical studies. The drug’s mechanism of action entails inhibition of the inflammatory cytokines interleukin 17 and 23 (IL-17 and IL-23) and the induction of apoptosis of patients’ skin cell keratinocytes involved with the disease pathogenicity. About Fondazione Telethon Fondazione Telethon ETS is one of the main Italian biomedical charities, founded in 1990 on the initiative of a group of patients suffering from muscular dystrophy. Its mission is to achieve the cure of rare genetic diseases through scientific research of excellence, selected according to the best practices shared internationally. Through a unique method in the Italian panorama, it follows the entire "research chain" dealing with fundraising, selection and funding of projects and the research activity itself carried out in the centers and laboratories of the Foundation. Telethon also develops collaborations with public health institutions and pharmaceutical industries to translate the results of research into therapies accessible to patients. Since its foundation, Telethon has invested more than 660 million euros in research, has funded 2,960 projects with 1,720 researchers involved and 630 diseases studied. To date, thanks to Fondazione Telethon, the first gene therapy with stem cells in the world has been made available, thanks to the collaboration with the pharmaceutical industry. This therapy is intended for the treatment of ADA-SCID, a severe immunodeficiency that compromises the body's defenses from birth. In 2023, Fondazione Telethon became responsible for the production and distribution of the drug to eligible patients in the European Union. Another gene therapy resulting from Telethon research made available is the one for a serious neurodegenerative disease, metachromatic leukodystrophy. This therapeutic approach is in an advanced stage of development for another immunodeficiency, Wiskott-Aldrich syndrome. Other diseases on which the gene therapy developed by Telethon researchers has been evaluated in patients are beta thalassemia and two metabolic diseases of childhood, mucopolysaccharidosis type 6 and type 1. In addition, within the Telethon institutes a targeted therapeutic strategy is being studied or developed for other genetic diseases, such as hemophilia or various hereditary vision defects. In parallel, the study of basic mechanisms and potential therapeutic approaches for diseases still unanswered continues in all laboratories funded by Telethon. About Can-Fite BioPharma Ltd. Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CFBI) 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 liver drug, Namodenoson, is being evaluated in a Phase III trial for hepatocellular carcinoma (HCC), a Phase IIb trial for the treatment of MASH, and in 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 profile with experience in over 1,600 patients in clinical studies to date. For more information please visit: https://www.canfite.com/. 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. Contact Can-Fite BioPharma Motti Farbstein info@canfite.com +972-3-9241114

Results from the first four children to be treated have been detailed in a research paper. Credit: Tom Merton via Getty Images. MeiraGTx is advancing its investigational gene therapy toward expedited approval in the UK after 11 children who were born blind from birth gained significant vision improvements following treatment. The AAV-AIPL1 therapy is designed to address severe sight impairment caused by mutations in the AIPL1 gene. This condition is a form of retinal dystrophy that leads to severe visual impairment from birth, with affected individuals typically only able to distinguish between light and dark. The gene therapy involves injecting functional copies of the AIPL1 gene into the retina using an adeno-associated viral (AAV) vector, aiming to restore retinal cell function and prevent degeneration. Results from four of the 11 children were published in The Lancet on 21 February. The first four children treated were aged one to three years with severe retinal dystrophy linked to mutations in the AIPL1 gene. Each child received the therapy in one eye through subretinal injection. Outcome measures included visual acuity assessments, functional vision evaluations, visual evoked potentials, and retinal structure imaging. Before treatment, the children’s visual acuity was limited to light perception. At an average follow-up of three and a half years post-treatment, the treated eyes showed significant improvement, with visual acuity improving. In contrast, the untreated eyes’ visual acuity deteriorated to unmeasurable levels. Additionally, objective tests confirmed enhanced visual function and electrophysiological assessments indicated increased visual cortex activity specific to the treated eyes. Imaging revealed better preservation of retinal structure in treated eyes compared to untreated ones. MeiraGTx’s CEO Alexandria Forbes said: “These improvements extended outside the meaningful effects on vision and result in life-changing benefits in all areas of development including communication, behaviour, schooling, mood, psychological benefits and social integration.” Following these positive outcomes, a second cohort of seven children received treatment in both eyes. All 11 children treated with AAV-AIPL1 have so far exhibited meaningful visual improvements. One child experienced cystoid macular oedema in the treated eye, which partially improved over time and did not hinder the overall visual gains. No other significant safety concerns have been reported. In light of these findings, MeiraGTx has engaged in discussions with the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) and plans to submit AAV-AIPL1 for expedited approval. The company is also in talks with the US Food and Drug Administration (FDA) to explore accelerated approval pathways in the US. If approved, AAV-AIPL1 would be eligible for a priority review voucher (PRV). While gene therapies hold promise for rare diseases, commercialisation remains a challenge. High development costs, complex manufacturing processes, and limited patient populations often deter investment. Earlier this month, Italian charity Telethon Foundation submitted a marketing authorisation application (MAA) to the European Medicines Agency (EMA) for a gene therapy targeting Wiskott-Aldrich syndrome after the withdrawal of its commercial partner. This marks the second time the foundation has stepped in to support an abandoned gene therapy, following its efforts with simoladagene autotemcel for ADA-SCID. The foundation claims to be the first charity worldwide to take responsibility for drug production and distribution, highlighting the financial and logistical hurdles in bringing gene therapies to market. The incidence of AIPL1-associated severe retinal dystrophy is estimated to be around one in every million live births. During a call with investors, Forbes stated that the company is exploring all options to ensure global access to AAV-AIPL1, noting “strategic interest” in the therapy. Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Optimise your cell therapy process: a guide to cell thawing Typically carried out at the point of care, errors in cell therapy thawing could compromise treatment efficacy, leading to significant patient impact as well as high costs and a compromised reputation for the product’s developer. This guide addresses how cell thawing has historically developed into the new techniques used today, along with the physical and biological implications of key metrics and components such as warming rate and ice structure. Also included are reviews of key studies from scientific literature and a consideration of the interactions between cooling and warming rates, as applicable to cell and gene therapies. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Cytiva Thematic By downloading this Whitepaper, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy

30 patients with Wiskott-Aldrich syndrome have been treated with etuvetidigene autotemcel. Credit: Telethon Foundation via LinkedIn. Italian research charity Telethon Foundation is one step closer to getting a gene therapy to treat rare disease Wiskott-Aldrich syndrome WAS approved in the European Union. The gene therapy, named etuvetidigene autotemcel, was developed by scientists of the San Raffaele-Telethon Institute for Gene Therapy in Milan. Before the Telethon Foundation assumed responsibility for the therapy, it was licensed to Orchard Therapeutics – a biotech specialising in gene therapies for rare diseases. However, in 2022, Orchard withdrew from the programme, citing strategic and commercial reasons. Telethon has submitted a marketing authorisation application (MAA) to the European Medicine’s Agency (EMA) for evaluating the gene therapy. Etuvetidigene autotemcel is designed as a one-time treatment for patients who lack a matched family donor for haematopoietic stem cell transplantation – the current standard of care for Wiskott-Aldrich syndrome. The therapy consists of autologous CD34+ stem and progenitor cells modified with a lentiviral vector encoding the WAS gene. The rare disorder affects platelet production and immune system function, often leading to severe infections, bleeding, and autoimmune complications. To date, 30 patients with Wiskott-Aldrich syndrome have been treated with the therapy – 27 within the clinical development programme, and three through an early access scheme. The therapy has been available in Italy since August 2023 under a determination by the Italian Medicines Agency (AIFA), which allows its use in patients over six months without a matched related donor. Telethon Foundation’s director general Ilaria Villa said that the foundation is also working on a submission to the US Food and Drug Administration (FDA), to make the therapy available in the US. This submission marks the second time the charity has taken over the development of a gene therapy after a commercial partner withdrew. It previously did so with simoladagene autotemcel, a therapy for adenosine deaminase severe combined immunodeficiency (ADA-SCiD). That gene therapy also originated in the laboratories of the San Raffaele-Telethon Institute in Milan and was the subject of an industrial partnership with Orchard. According to Telethon, it is the first charity in the world to assume responsibility for the production and distribution of a drug. One of the key challenges associated with gene therapy development is funding. Due to small patient populations and uncertain commercial returns, venture capitalists and private investors are sometimes hesitant to support such therapies beyond early-stage clinical trials. While grants can help fund initial research, they rarely cover the full development and approval process, which requires significantly more investment. Another barrier is the high cost of commercial-grade manufacturing. The production of gene therapies requires advanced technology, stringent quality controls, and specialised facilities, making them expensive to scale. If a gene therapy is deemed commercially unviable, its development may be paused or abandoned. At the end of 2024, Pfizer terminated its partnership with Sangamo Therapeutics on a haemophilia A gene therapy. Pfizer originally licensed the therapy from Sangamo in 2017, and it successfully passed a Phase III clinical trial meeting its primary goal. However, Pfizer decided not to pursue approval due to questions about its potential commercial performance. To address these challenges, the EMA launched a pilot programme in 2022 to support academic and non-profit developers of advanced therapy medicinal products (ATMPs). While it does not introduce new regulatory mechanisms, the initiative aims to help non-profit organisations navigate existing regulatory pathways. Participants benefit from fee reductions and waivers for scientific advice, MAA submissions, and pre-authorisation inspections. The EMA expects to publish initial results from the pilot this year, outlining key findings and potential areas for regulatory improvement. Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Cell and gene therapies: Pipe dream to pipeline The cell and gene industry is gaining momentum, with a new wave of therapies promising to transform the way doctors treat, and even cure, disease. In this report, Cytiva and GlobalData have collaborated to explore the rise of the cell and gene therapy industries, the current state of the market, present and future opportunities for advancement, and the challenges that lie ahead. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Cytiva Thematic By downloading this Whitepaper, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy