Refsum Disease, Infantile

Researchers who work with tiny drug carriers known as lipid nanoparticles have developed a new type of material capable of reaching the lungs and the eyes, an important step toward genetic therapy for hereditary conditions like cystic fibrosis and inherited vision loss. Researchers who work with tiny drug carriers known as lipid nanoparticles have developed a new type of material capable of reaching the lungs and the eyes, an important step toward genetic therapy for hereditary conditions like cystic fibrosis and inherited vision loss. Findings of the study led by Gaurav Sahay and Yulia Eygeris of the Oregon State University College of Pharmacy and Renee Ryals of Oregon Health & Science University were published today in the Proceedings of the National Academy of Sciences. Unlike other types of lipid nanoparticles that tend to accumulate in the liver, the ones in this study, based on the compound thiophene, are able to navigate their way to the tissues of the lungs and retina, where they deliver their therapeutic payload. The researchers refer to these new lipids as Thio-lipids. The collaboration demonstrated, by using animal models, the possibility of using Thio-lipids in lipid nanoparticles to deliver messenger RNA, the technology underpinning COVID-19 vaccines, to combat genetic blindness and pulmonary disease. "These nanoparticles filled with fatty lipids can encapsulate genetic medicines like mRNA and CRISPR-Cas9 gene editors, which can be used to treat and even cure rare genetic diseases," said Eygeris, a senior research associate at OSU. "Chemical structures of the lipids determine how potent are the lipid nanoparticles and which organ they can reach from the bloodstream." Lipids are organic compounds containing fatty tails and are found in many natural oils and waxes, and nanoparticles are tiny pieces of material ranging in size from one- to 100-billionths of a meter. Messenger RNA delivers instructions to cells for making a particular protein. With the coronavirus vaccines, the mRNA carried by the lipid nanoparticles instructs cells to make a harmless piece of the virus' spike protein, which triggers an immune response from the body. As a therapy for vision impairment resulting from inherited retinal degeneration, the mRNA would instruct cells in the retina -- which don't work right because of a genetic mutation -- to manufacture the proteins needed for sight. Inherited retinal degeneration, commonly abbreviated to IRD, encompasses a group of disorders of varying severity and prevalence that affect one out of every few thousand people worldwide. An example of a genetic pulmonary condition is cystic fibrosis, a progressive disorder that results in persistent lung infection and affects 30,000 people in the U.S., with about 1,000 new cases identified every year. One faulty gene -- the cystic fibrosis transmembrane conductance regulator, or CFTR -- causes the disease, which is characterized by lung dehydration and mucus buildup that blocks the airway. The thiophene-based lipid nanoparticle study, which involved mice and non-human primates, stems from a $3.2 million grant to Sahay and Ryals from the National Eye Institute. The grant's purpose is addressing limitations associated with the current primary means of delivery for gene editing: a type of virus known as adeno-associated virus, or AAV. "AAV has limited packaging capacity compared to lipid nanoparticles and it can prompt an immune system response," said Sahay, a professor of pharmaceutical sciences. "It also doesn't do fantastically well in continuing to express the enzymes the editing tool uses as molecular scissors to make cuts in the DNA to be edited." Sahay calls the Thio-lipid findings "highly encouraging" but says more studies are needed, including research on the lipids' long-term impact on retinal health. "But we think our results serve as a proof of concept and we will continue to explore Thio-lipids in potential treatments of pulmonary and retinal genetic diseases," he said. In addition to the National Eye Institute, funding and research support were provided by the Oregon National Primate Research Center and the Casey Eye Institute.

The presentation will review study population data from ONL’s Phase 2 study of ONL1204 Ophthalmic Solution in patients with Macula-Off Rhegmatogenous Retinal DetachmentANN ARBOR, Mich., Jan. 23, 2024 (GLOBE NEWSWIRE) -- ONL Therapeutics, Inc., a clinical-stage biopharmaceutical company developing novel therapies for protecting the vision of patients with retinal disease, announced today that David Zacks, M.D., Ph.D., chief scientific officer and co-founder of ONL Therapeutics, and the Edna H. Perkiss Research Professor of Ophthalmology and Visual Sciences at the Kellogg Eye Center of the University of Michigan, will present an update on the company’s Phase 2 study in patients with rhegmatogenous retinal detachment (RRD) at the upcoming 47th Annual Meeting of the Macula Society, being held February 7 – 10, 2024, at the La Quinta Resort & Club in Palm Springs, California. “We believe our Phase 2 randomized study to assess the safety and efficacy of intravitreal ONL1204 Ophthalmic Solution in patients with macula-off rhegmatogenous retinal detachment (RRD) could play an important role in treating this vision-threatening condition, and we look forward to sharing an update at the Macula Society meeting,” said David Esposito, chief executive officer of ONL Therapeutics. “With the study now fully enrolled we will focus our attention on gathering and analyzing the data with a goal to share topline results in the second quarter of 2024.” Details of the podium presentation are as follows: Title: Fas Inhibition with ONL1204 for Macula-off Rhegmatogenous Retinal Detachment (RRD): Study Population Data on a Phase 2, Multicenter, Randomized, Sham-controlled, Single-Masked, Clinical Trial Presenter: David N. Zacks, M.D., Ph.D.Chief Scientific Officer, ONL TherapeuticsEdna H. Perkiss Research Professor of Ophthalmology and Visual Sciences, Kellogg Eye CenterUniversity of Michigan Date / Time: Saturday, February 10, 2024, at 10:28 a.m. PT Session: Surgery I (Retinal Detachment) About Rhegmatogenous Retinal DetachmentRhegmatogenous retinal detachment (RRD) is an acute and serious vision-threatening condition in which a tear in the retina allows liquefied vitreous to enter the subretinal space, thereby detaching the photoreceptor (PR) layer of the retina from the retinal pigment epithelium (RPE), the principal source of metabolic support for the PR layer. Once detached, PRs undergo a cascade of inflammation and cell death leading to vision loss after RRD. There are nearly 100,000 retinal detachment repairs annually in the US alone. About ONL1204 Ophthalmic SolutionONL1204 is a novel, first-in-class small molecule Fas inhibitor designed to protect key retinal cells, including photoreceptors, from cell death that occurs across a range of retinal diseases and conditions. Death of these retinal cells, through both direct and inflammatory signaling pathways, is the root cause of vision loss and the leading cause of blindness. The company’s later-stage clinical development program for ONL1204 currently includes a Phase 2 study in the U.S. for the treatment of macula-off retinal detachment (NCT05730218), a condition for which the compound has been granted orphan drug designation by the United States Food and Drug Administration (FDA). The company is also conducting a Phase 1b clinical trial in patients with geographic atrophy (GA) associated with age-related macular degeneration (AMD) (NCT04744662) and a Phase 1b clinical trial in patients with progressing open-angle glaucoma (NCT05160805) at sites in Australia and New Zealand. Preclinical work is ongoing to enable clinical trials in other disease indications, including inherited retinal degeneration (IRD; also known as retinitis pigmentosa). About ONL TherapeuticsONL Therapeutics (ONL) is a clinical-stage biopharmaceutical company committed to developing first-in-class therapeutics to protect and improve the vision of patients with retinal disease. By advancing a breakthrough technology designed to protect key retinal cells from Fas-mediated cell death, ONL is pioneering a new approach to preserving vision. ONL is developing a platform of products for use in a wide range of blinding diseases, including retinal detachment, glaucoma, AMD and IRD. For more information about ONL Therapeutics, please visit www.onltherapeutics.com.

Quadri Pharma will cover 50% of the costs of development activity up to a capped dollar contribution Jaguar to host virtual educational webinar on intestinal failure with leading gastroenterologists and nutrition experts November 8th from 1:00 PM to 2:30 PM EST; Click here to register for the webinar SAN FRANCISCO, CA / ACCESSWIRE / November 2, 2023 / Napo Pharmaceuticals, Inc. (Napo), a Jaguar Health, Inc. (NASDAQ:JAGX) family company, today announced that it has entered a revenue sharing license and commercialization agreement (the "Agreement") with Quadri Pharmaceuticals Store LLC (Quadri Pharma) that grants Quadri Pharma exclusive promotional, commercialization, and distribution rights for the rare disease indications of microvillus inclusion disease (MVID), other congenital diarrheal disorders, and short bowel syndrome (SBS) with intestinal failure for a powder formulation of crofelemer for oral solution in multiple Middle East countries, following regulatory approval to market crofelemer for these indications. In addition, the Agreement grants Quadri Pharma exclusive rights to distribute the powder formulation of crofelemer for the specified indications through Named Patient Programs in the specified Middle East countries following regulatory guidelines. SBS can result from surgical resection of a portion of the small intestine, or from disease or injury, or be congenital. MVID is an ultra-rare congenital diarrheal disorder. An estimate of congenital birth defect rates shows a higher incidence of anomalies among live births in Arab countries compared to those in Europe, North America and Australia.1 Many Arab countries display some of the highest rates of consanguineous marriages in the world ranging around 20-50% of all marriages, contributing to a higher-than-normal rate of congenital abnormalities. "We are very happy to have entered this new collaboration with Quadri Pharma, which is distinct from the revenue sharing distribution and license agreement Napo and Quadri Pharma entered in early 2022 that granted Quadri Pharma exclusive promotional, commercialization, and distribution rights to the tablet formulation of crofelemer in certain Middle East countries for specified human indications including HIV-related diarrhea and cancer therapy-related diarrhea (CTD), following regulatory approval," said Karen Brunke, PhD, Jaguar Health's Executive Vice President of Corporate and Business Development. "Under the terms of this new Agreement, Quadri Pharma will cover 50% of the costs of development activity in the specified territory for the powder formulation of crofelemer for the specified rare disease indications for three years, up to a certain total dollar amount. We look forward to continuing our close relationship with Quadri Pharma and their team of experienced professionals as we work together to expand access to crofelemer to intestinal failure patients in need in this region." "We are very happy to enter into this new strategic relationship with Napo," said Dr. Hesham Elbakr, Chief Executive Officer of Quadri Pharma. "We expect crofelemer to be an important treatment option for patients suffering from the devastating rare diseases of SBS with intestinal failure and MVID in the Middle East countries specified in the Agreement. We have expertise in the distribution and marketing of prescription drugs throughout the Middle East, including the introduction and management of early access programs where that medicine does not have marketing approval and critically ill patients have very limited therapy options - such as requests related to Named Patient Programs, which provide access to individual patients ("named" patients) through physician requests." Napo to Host Virtual Educational Webinar on Intestinal Failure with Leading Gastroenterologists and Nutrition Experts November 8, 2023 from 1:00 PM to 2:30 PM Eastern Standard Time Participants in this virtual event, which will be moderated by Pravin Chaturvedi, PhD, Jaguar Health's Chief Scientific Officer and Chair of the Jaguar/Napo Scientific Advisory Board, will define intestinal failure, which is classified as a malabsorptive syndrome, discuss the current standards of care for SBS and MVID patients, including parenteral support, and address the major unmet need for treatment options for the debilitating, chronic, severe watery diarrhea that is associated with intestinal failure. Participants include these distinguished gastroenterologists and nutrition experts from the US, the Middle East and Europe: Professor Mohamad Miqdady, MD, Division Chief, Pediatric Gastroenterology, Hepatology & Nutrition Division, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates Professor Antonella Diamanti, MD, Head of Artificial Nutrition Unit, Bambino Gesù Pediatric Hospital, Rome, Italy Christos Tzivinikos, MD, DCH, FRCPCH, MSc, CEBP, Consultant Pediatric Gastroenterologist, Head of Pediatric Gastroenterology, Hepatology and Nutrition Department, Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates Lindsey Russell, MD, MSc, FRCPC, Department of Gastroenterology, Hepatology and Nutrition and the Digestive Diseases & Surgery Institute, Cleveland Clinic, Ohio Fabrizio Pasanisi, MD, PhD, Director of the Interuniversity Center for Studies and Research on Obesity (CISROD) and Professor of Internal Medicine, University of Naples Federico II, Naples, Italy Carol Wolin, MA, RDN, LD, Public Health Dietitian, Legacy Community Health, Houston, Texas Webinar registration required via Zoom. To register, please click here or email Jaguar@TogoRun.com for more information. MVID is a severe infantile disease characterized by diarrhea, malabsorption, and acid/base instability, requiring intensive parenteral support for nutritional and fluid management, and there are currently no approved drug treatments. MVID patients commonly face intestinal failure - a catastrophic health situation that also often afflicts patients with SBS, a rare and complex condition characterized by diarrhea and/or severe malabsorption of fluids and nutrients. Crofelemer has been granted Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for both MVID and SBS. Jaguar is supporting investigator-initiated and investigator IND proof-of-concept studies of crofelemer for MVID and SBS with intestinal failure in the US, EU, and Middle East/North Africa (MENA) regions, with results expected before the end of 2023 and in 2024. In accordance with the guidelines of specific European Union countries, published data from such clinical investigations could support reimbursed early patient access to crofelemer for SBS or MVID for these debilitating conditions. Napo's Investigational New Drug application for crofelemer for the treatment of MVID was activated by the FDA August 7, 2023. Based in Abu Dhabi and Dubai in the UAE, Quadri Pharma provides services related to the registration, marketing, and distribution of pharmaceutical products in the MENA region in compliance with local and international regulatory standards. About Crofelemer Crofelemer is the only oral FDA-approved prescription drug under botanical guidance. It is plant-based, extracted and purified from the red bark sap of the Croton lechleri tree in the Amazon Rainforest. Napo Pharmaceuticals, a Jaguar family company, has established a sustainable harvesting program, under fair trade practices, for crofelemer to ensure a high degree of quality, ecological integrity, and support for Indigenous communities. About the Jaguar Health Family of Companies Jaguar Health, Inc. (Jaguar) is a commercial stage pharmaceuticals company focused on developing novel proprietary prescription medicines sustainably derived from plants from rainforest areas for people and animals with gastrointestinal distress, specifically associated with overactive bowel, which includes symptoms such as chronic debilitating diarrhea, urgency, bowel incontinence, and cramping pain. Jaguar family company Napo Pharmaceuticals focuses on developing and commercializing human prescription pharmaceuticals for essential supportive care and management of neglected gastrointestinal symptoms across multiple complicated disease states. Napo Pharmaceuticals' crofelemer drug product candidate is the subject of the OnTarget study, an ongoing pivotal Phase 3 clinical trial for preventive treatment of chemotherapy-induced overactive bowel (CIOB) in adults with cancer on targeted therapy. Jaguar family company Napo Therapeutics is an Italian corporation Jaguar established in Milan, Italy in 2021 focused on expanding crofelemer access in Europe and specifically for orphan and/or rare diseases. Jaguar Animal Health is a Jaguar tradename. Magdalena Biosciences, a joint venture formed by Jaguar and Filament Health Corp. that emerged from Jaguar's Entheogen Therapeutics Initiative (ETI), is focused on developing novel prescription medicines derived from plants for mental health indications. For more information about: Jaguar Health, visit Napo Pharmaceuticals, visit Napo Therapeutics, visit napotherapeutics.com Magdalena Biosciences, visit magdalenabiosciences.com Visit Jaguar on LinkedIn: Visit Jaguar on X: Visit Jaguar on Instagram: Forward-Looking Statements Certain statements in this press release constitute "forward-looking statements." These include statements regarding the expectation that Jaguar Health will host a virtual educational webinar on intestinal failure on November 8, 2023, the expectation that crofelemer may be an important treatment option for patients suffering from SBS with intestinal failure and MVID in the Middle East countries specified in the Agreement, the expectation that results from proof-of-concept studies of crofelemer for MVID and SBS with intestinal failure may be available before the end of 2023 and in 2024, and the expectation that, in accordance with the guidelines of specific European Union countries, published data from such clinical investigations could support reimbursed early patient access to crofelemer for SBS or MVID. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "aim," "anticipate," "could," "intend," "target," "project," "contemplate," "believe," "estimate," "predict," "potential" or "continue" or the negative of these terms or other similar expressions. The forward-looking statements in this release are only predictions. Jaguar has based these forward-looking statements largely on its current expectations and projections about future events. These forward-looking statements speak only as of the date of this release and are subject to several risks, uncertainties, and assumptions, some of which cannot be predicted or quantified and some of which are beyond Jaguar's control. Except as required by applicable law, Jaguar does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. 1 Call for improved genetic services in Arab countries, Nature Middle East, Published online May 21, 2014 CONTACT: hello@jaguar.health Jaguar-JAGX SOURCE: Jaguar Health, Inc. View source version on accesswire.com: