Photosensitivity Disorders

April 2, 2025 Manuscript in the Journal of Inherited Metabolic Disease indicates increased survival in patients treated with fosdenopterin Solana Beach, CA – April 2, 2025 – Sentynl Therapeutics, Inc. (“Sentynl”), a U.S.-based biopharmaceutical company wholly-owned by Zydus Lifesciences, Ltd. (“Zydus Group”), is pleased to announce the publication of NULIBRY’s three clinical studies comparing the treatment effect of NULIBRY versus a natural history study in the Journal of Inherited Metabolic Disease. Fosdenopterin gained its approval by the United States Food and Drug Administration (FDA) in February 2021, the Israeli Ministry of Health (MoH) in July 2022, the European Medicines Agency (EMA) in September 2022, and the Medicines and Healthcare products Regulatory Agency (MHRA) in April 2024 for the treatment of MoCD Type A. These data represent the first comprehensive body of clinical research in the only approved treatment for MoCD Type A patients, as well as the most abundant findings on the natural progression of the disease. The results showed statistically significant prolonged survival in treated versus untreated patients, as well as genotype-match controls with the risk of death at 5.1 times higher in the untreated patients (Cox proportional hazards 5.1; 95% CI 1.32-19.36; p=0.01). Additionally, significant improvements were seen in cognitive and motor functioning in the treated versus the untreated patients. Fosdenopterin-treated patients experienced mild to moderate treatment emergent adverse events with the most common adverse events being catheter-related complications and infections. There were no discontinuations or dose modifications due to adverse events. MoCD Type A is an ultra-rare, autosomal recessive disease caused by variants in the MOCS1 gene. It typically presents at birth or shortly thereafter and if left untreated causes rapid, irreversible neurogeneration due to a build up of toxic sulfite levels in the brain, and ultimately a premature death. Fosdenopterin, a synthetic form of cPMP, restores normal sulfite levels thereby reducing the toxic sulfite concentration. “This publication marks the end of a truly collaborative and enthusiastic path from basic research to the bedside that started 21 years ago, when we reported the successful treatment of a mouse model of MoCD type A with cPMP (cyclic pyranopterin monophosphate, fodenopterin),” said Guenter Schwarz, Professor, Institute of Biochemistry, Department of Chemistry and Biochemistry & Center for Molecular Medicine, Cologne University, Germany. “Increased awareness and expeditious testing upon suspicion of MoCD are critical to improve neurological outcomes and overall survival in patients with MoCD Type A who can be treated early with fosdenopterin.” “It is important that clinicians consider the diagnosis of MoCD type A in neonates with intractable seizures, encephalopathy, feeding difficulties or increased startle response as earlier treatment appeared to improve achievement of developmental milestones,” said Liza Squires, MD, Sentynl Medical Consultant. Sentynl Therapeutics is committed to treating rare genetic diseases, which often present in infancy and early childhood. “The publication of these data in JIMD is a huge milestone for MoCD Type A patients, caregivers, and the medical community,” said Matt Heck, CEO, Sentynl. “It is the culmination of four companies’ commitment in NULIBRY’s clinical development program spanning over two decades.” About Molybdenum Cofactor Deficiency (MoCD) Type A MoCD Type A is an autosomal recessive, inborn error of metabolism caused by mutations in the molybdenum cofactor synthesis 1 gene and characterized by a deficiency in molybdenum cofactor production, leading to a lack of molybdenum-dependent enzyme activity.1,2 The lack of activity leads to decreased sulfite oxidase activity with buildup of sulfite and secondary metabolites (such as S-sulfocysteine) in the brain, which causes irreversible neurological damage.2 MoCD Type A is an ultra-rare disease. The incidence and prevalence of MoCD Type A in the United States are not known, but the estimated incidence is 1 per 342,000 to 411,000 live births (0.24 and 0.29 per 100,000).3 Based on these estimates, MoCD Type A is likely to be underdiagnosed. The most common presenting symptoms of MoCD Type A are seizures, feeding difficulties and encephalopathy. Patients with MoCD Type A who survive beyond infancy typically suffer from progressive brain damage, which presents in characteristic patterns on magnetic resonance imaging (MRI). This damage leads to severe psychomotor impairment and an inability to make coordinated movements or communicate with their environment. Mechler K et al. Genet Med. 2015;17(12):965-970. Veldman A et al. Pediatrics. 2010;125(5):e1249-e1254 Mayr SJ, et al. Forecasting the incidence of rare diseases: an iterative computational and biochemical approach in molybdenum cofactor deficiency type A. Presented at the 2019 SSIEM meeting; September 3-6, 2019; Rotterdam, The Netherlands. About NULIBRY® (fosdenopterin) for Injection NULIBRY (fosdenopterin) for Injection is a substrate replacement therapy that provides a synthetic source of cPMP, which is converted to molybdopterin. Molybdopterin is then converted to molybdenum cofactor, which is needed for the activation of molybdenum-dependent enzymes, including sulfite oxidase, an enzyme that reduces levels of neurotoxic sulfites. NULIBRY was approved by the U.S. FDA in February 2021, and by the Israel Ministry of Health in July 2022 and is indicated to reduce the risk of mortality in patients with MoCD Type A. NULIBRY was also approved by the EMA in September 2022, with an indication for treatment of patients with MoCD Type A. Important Safety Information Warnings and Precautions Potential for Photosensitivity NULIBRY can make the patient oversensitive to sunlight. NULIBRY-treated patients or their caregivers are advised to avoid or minimize patient exposure to sunlight and artificial UV light and adopt precautionary measures when exposed to the sun, including wearing protective clothing and sunglasses, and use broad-spectrum sunscreen with high SPF in patients 6 months of age and older. If photosensitivity occurs, caregivers/patients are advised to seek medical attention immediately and consider a dermatological evaluation. Adverse Reactions The most common adverse reactions in NULIBRY-treated patients were infusion catheter–related complications (89%), pyrexia (fever) (78%), viral infection (56%), pneumonia (44%), otitis media (ear infection) (44%), vomiting (44%), cough/sneezing (44%), viral upper respiratory infection (33%), gastroenteritis (33%), diarrhea (33%) , and bacteremia (33%). Adverse reactions for rcPMP-treated patients were similar to the NULIBRY-treated patients. Patient Counseling Information Please read the FDA-approved NULIBRY Prescribing Information and Instructions for Use and follow the instructions on how to prepare and administer NULIBRY. NULIBRY has a potential for photosensitivity; see Warnings and Precautions. Seek medical attention immediately if the patient develops a rash or if they notice symptoms of photosensitivity reactions (redness, burning sensation of the skin, blisters). You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. About Sentynl Therapeutics Sentynl Therapeutics, Inc. (“Sentynl”) is a U.S.-based biopharmaceutical company focused on bringing innovative therapies to patients living with rare diseases. The company was acquired by the Zydus Group in 2017. Sentynl’s experienced management team has previously built multiple successful pharmaceutical companies. With a focus on commercialization, Sentynl looks to source effective and well-differentiated products across a broad spectrum of therapeutic areas to address unmet needs. Sentynl is dedicated to ensuring no patient is overlooked, and is committed to the highest ethical standards and compliance with all applicable laws, regulations and industry guidelines. For more information, visit https://sentynl.com. About Zydus Group Zydus Lifesciences Ltd. with an overarching purpose of empowering people with freedom to live healthier and more fulfilled lives, is an innovative, global life sciences company that discovers, develops, manufactures, and markets a broad range of healthcare therapies. The group employs over 27,000 people worldwide, including 1,400 scientists engaged in R & D, and is driven by its mission to unlock new possibilities in life sciences through quality healthcare solutions that impact lives. The group aspires to transform lives through path-breaking discoveries. For more information, visit https://www.zyduslife.com/zyduslife. Contacts: Media: Maureen Roberts, maureen.roberts@fleishman.com Sentynl: Michael Hercz, ir@sentynl.com For U.S. Audiences Only < Back This website uses cookies for data analytics. This website may also use cookies to enhance your experience with the website. We do not use cookies to sell or share your personal information. By selecting “Accept all,” you agree to our use of cookies. By selecting “Reject all,” you agree to a single strictly necessary cookie to prevent the use of data analytics cookies. For more information, please read our privacy statement.

Relief Therapeutics Holding SA / Key word(s): Patent Relief Therapeutics Announces European Patent Office Decision to Grant Patent for RLF-TD011 11.02.2025 / 07:00 CET/CEST Relief Therapeutics Announces European Patent Office Decision to Grant Patent for RLF-TD011 Patent Secures Protection for RLF-TD011 in Epidermolysis Bullosa Wound Treatment GENEVA (FEB. 11, 2025) – RELIEF THERAPEUTICS Holding SA (SIX: RLF, OTCQB: RLFTF, RLFTY) (Relief, or the Company), a biopharmaceutical company committed to delivering innovative treatment options for select specialty, unmet and rare diseases, today announced that the European Patent Office (EPO) has issued a Decision to Grant for its patent application titled “Therapeutic Uses of Oxidizing Hypotonic Acid Solutions.” This patent will protect therapeutic applications of Relief’s proprietary, highly pure hypochlorous acid solutions, including its investigational drug RLF‑TD011 for the treatment of wounds caused by epidermolysis bullosa (EB) in key European countries. The EPO is expected to formally issue the patent on February 26, 2025, under patent number EP 3993811. The patent will remain in effect until 2040, as anticipated by the Notice of Allowance received in October 2024. Corresponding patent applications are under review in other major markets, including the United States and China. RLF-TD011 has previously received orphan drug designation (ODD) from the U.S. Food and Drug Administration (FDA) for the treatment of EB. The Company also intends to seek qualified infectious disease product (QIDP) designation from the FDA. These designations would provide potential incentives such as market exclusivity upon approval. Relief continues to advance the development of its lead program and recently reported positive results from its investigator-initiated clinical trial evaluating RLF-TD011 for the treatment of EB. The Company is currently preparing a pre-IND meeting package for submission to the FDA to finalize the remaining clinical development and regulatory strategy for RLF-TD011. ABOUT RLF-TD011 RLF-TD011 is a highly pure, stabilized hypochlorous acid solution developed using Relief's proprietary TEHCLO™ technology. With strong antimicrobial properties, RLF-TD011 is a sprayable, self-administered solution for targeted wound application while avoiding skin contact and cross-contamination. RLF-TD011 has demonstrated efficacy in accelerating wound closure and reducing infections in certain clinical trials on non-EB wounds. In an investigator-initiated trial (NCT05533866), RLF-TD011 has also shown promising results in infection control and wound healing in EB patients with the most severe forms of the disease. RLF-TD011 aims to address unmet needs in EB care by efficiently controlling infection and inflammation while reducing antibiotic use and easing the intensive, time-consuming wound care routine required by current treatments. ABOUT EPIDERMOLYSIS BULLOSA Epidermolysis bullosa (EB) is a group of rare, inherited connective tissue disorders characterized by extreme skin fragility, leading to blistering and wounds from minor friction or injury. In severe cases, blisters can develop into chronic wounds or form in internal organs such as the mouth or esophagus, leading to painful wounds, recurrent infections, and a deeply impacted quality of life. EB is classified into several major inherited subtypes, each defined by the depth of blister formation within the skin’s layers: epidermolysis bullosa simplex (EBS), dystrophic epidermolysis bullosa (DEB), junctional epidermolysis bullosa (JEB) and Kindler syndrome (KS). Treatment is intensive and includes wound care, infection prevention, and pain management. Approximately 500,000 individuals worldwide are affected by EB. ABOUT RELIEF Relief is a commercial-stage biopharmaceutical company committed to advancing treatment paradigms and delivering improvements in efficacy, safety, and convenience to benefit the lives of patients living with select specialty and rare diseases. Relief’s portfolio offers a balanced mix of marketed, revenue-generating products, proprietary, globally patented TEHCLO™ and Physiomimic™ platform technologies and a targeted clinical development pipeline consisting of risk-mitigated assets focused in three core therapeutic areas: rare skin diseases, rare metabolic disorders, and rare respiratory diseases. In addition, Relief is commercializing several legacy products via licensing and distribution partners. Headquartered in Geneva, Relief is listed on the SIX Swiss Exchange under the symbol RLF and quoted in the U.S. on OTCQB under the symbols RLFTF and RLFTY. For more information, visit www.relieftherapeutics.com. CONTACT: RELIEF THERAPEUTICS Holding SA Jeremy Meinen Chief Financial Officer contact@relieftherapeutics.com DISCLAIMER This press release contains forward-looking statements, which may be identified by words such as "believe," "assume," "expect," "intend," "may," "could," "will," or similar expressions. These statements are based on current plans and assumptions and are subject to risks and uncertainties that could cause actual results, financial condition, performance, or achievements to differ materially from those expressed or implied. Such factors include, but are not limited to, changes in economic conditions, market developments, regulatory changes, competitive dynamics, and other risks or changes in circumstances. This communication is provided as of the date hereof, and Relief undertakes no obligation to update any forward-looking statements contained herein as a result of new information, future events or otherwise. End of Media Release

EPP is a rare genetic disorder that causes severe burn injuries on the skin following exposure to visible light. Credit: Cavan Images via Getty Images. Disc Medicine has raised $225.5m through an upsized public offering to support the company’s pipeline, including its lead investigational drug, bitopertin. The therapy targets erythropoietic protoporphyria (EPP), a rare genetic disorder that causes extreme light sensitivity. Disc is preparing to file a new drug application (NDA) for the therapy this year, seeking accelerated approval from the US Food and Drug Administration (FDA). The drug candidate is designed to reduce levels of protoporphyrin IX (PPIX), a phototoxic compound that accumulates in the blood of EPP and X-linked protoporphyria (XLP) patients, causing severe pain and burns from even brief sun exposure. Earlier this week, Disc announced feedback from a Type C meeting with the FDA, where the agency finalised its agreement with the design of the upcoming Phase III APOLLO trial, which will evaluate the safety and efficacy of bitopertin. The meeting resulted in the addition of a co-primary endpoint to the trial, which will now assess both changes in PPIX levels and the average time patients can spend in sunlight without pain at the end of six months of treatment. These endpoints are designed to demonstrate bitopertin’s ability to improve a patient’s quality of life by reducing sensitivity to sunlight. This follows an earlier end-of-Phase II meeting with the FDA in which Disc secured support for an accelerated approval pathway based on existing clinical data. At that meeting, the regulator agreed that PPIX reduction could serve as a surrogate endpoint for efficacy. The agency also approved key elements of the Phase III trial design, including its randomised, double-blind, placebo-controlled structure, a six-month treatment duration, and a primary endpoint focused on pain-free sunlight exposure during the final month of treatment. Disc’s prior Phase II study showed that bitopertin was well-tolerated at 20mg and 60mg daily doses over 24 weeks in 22 patients, with no serious adverse events reported. Patients who opted to continue into an open-label extension study for another 24 weeks demonstrated further positive outcomes. These data supported Disc’s decision to pursue accelerated approval and informed the design of the Phase III APOLLO trial, which is set to begin in mid-2025. The APOLLO study will enrol patients aged 12 years and older with EPP or XLP and will include additional secondary endpoints such as cumulative time in sunlight without pain, reductions in phototoxic reactions, and patient-reported global impressions of change. If accelerated approval is granted, data from APOLLO would serve as a confirmatory trial to convert the conditional approval into a full approval. Bitopertin could become the second FDA-approved treatment for EPP, following Clinuvel Pharmaceuticals ’ Scenesse (afamelanotide). Scenesse increases skin pigmentation and protects against light-induced skin damage, allowing patients to spend an additional 20 minutes in sunlight daily without pain as demonstrated in a pivotal trial (NCT01605136). A patient with EPP highlighted the ethical challenges in EPP trials at the Outsourcing in Clinical Trials (OCT) DACH 2024 conference, in Zurich, Switzerland, between 29 and 30 October. EPP trials have to reckon with the potential for phototoxic burns in participants randomised to control groups, and the risk of a bias in patient selection, as more severely affected patients may hesitate to participate. However, this risk is met with the drive for new treatments and the unmet need for EPP patients.