Pain Insensitivity, Congenital

SAN DIEGO, March 31, 2025 (GLOBE NEWSWIRE) -- Gyre Therapeutics (“Gyre”) (Nasdaq: GYRE), an innovative, commercial-stage biotechnology company focused on organ fibrosis, today announced that the National Medical Products Administration (NMPA) of the People’s Republic of China (“PRC”) has approved its clinical trial application for a potential new indication for pirfenidone in oncology-related pulmonary complications. The trial will evaluate pirfenidone capsules for the treatment of radiation-induced lung injury (RILI), with or without immune-related pneumonitis (CIP). This regulatory milestone marks the expansion of pirfenidone beyond its established role in idiopathic pulmonary fibrosis (IPF) into the oncology supportive care space, offering a novel lung-protective strategy for cancer patients undergoing radiation therapy or immunotherapy. In accordance with the NMPA approval, Gyre intends to pursue an adaptive Phase 2/3 clinical trial design, combining dose exploration with efficacy confirmation, to efficiently evaluate pirfenidone's potential in this new indication. Radiation-Induced Lung Injury (RILI): Radiation therapy is a cornerstone of lung cancer treatment. However, 5%–25% of patients experience lung damage due to radiation exposure, limiting the ability to escalate doses and thereby compromising treatment efficacy. Checkpoint Inhibitor Pneumonitis (CIP): Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but 13%–19% of patients develop CIP. This condition accounts for approximately 35% of immune-related adverse event (irAE) deaths and often necessitates treatment discontinuation. Currently, no targeted therapies exist for lung injuries caused by radiation or immunotherapy. Distinguishing between RILI and CIP is challenging, particularly when both occur concurrently. Corticosteroids remain the standard of care despite significant long-term side effects. By targeting and inhibiting fibrotic pathways, pirfenidone may address the root cause of lung injury progression, offering a new treatment option for patients receiving radiation or immunotherapy. Gyre anticipates initiating the trial in the second half of 2025 at leading academic and oncology centers across the PRC. About PirfenidonePirfenidone is an orally administered small molecule approved for the treatment of IPF. It works by inhibiting TGF-β signaling and fibroblast proliferation. The drug has demonstrated clinical benefit in slowing lung function decline in IPF and is now being evaluated for oncology-related pulmonary complications. Gyre has held first-in-class status for pirfenidone in the PRC since its original approval in 2011, underscoring its pioneering role in treating fibrotic lung diseases. About Gyre TherapeuticsGyre Therapeutics is a biopharmaceutical company headquartered in San Diego, CA, primarily focused on the development and commercialization of F351 (Hydronidone) for MASH-associated fibrosis in the U.S. Gyre’s strategy builds on its experience in mechanistic studies using MASH rodent models and clinical studies in CHB-induced liver fibrosis. In the PRC, Gyre is advancing a broad pipeline through its indirect controlling interest in Gyre Pharmaceuticals, including therapeutic expansions of ETUARY, and development programs for F573, F528, and F230. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, which statements are subject to substantial risks and uncertainties and are based on estimates and assumptions. All statements, other than statements of historical facts included in this press release, are forward-looking statements, including statements concerning: the expectations regarding Gyre’s research and development efforts and timing of expected clinical trials, including timing of a clinical trial initiation in the second half of 2025. In some cases, you can identify forward-looking statements by terms such as “may,” “might,” “will,” “objective,” “intend,” “should,” “could,” “can,” “would,” “expect,” “believe,” “design,” “estimate,” “predict,” “potential,” “plan” or the negative of these terms, and similar expressions intended to identify forward-looking statements. These statements reflect our plans, estimates, and expectations, as of the date of this press release. These statements involve known and unknown risks, uncertainties and other factors that could cause our actual results to differ materially from the forward-looking statements expressed or implied in this press release. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation: Gyre’s ability to execute on its clinical development strategies; positive results from a clinical trial may not necessarily be predictive of the results of future or ongoing clinical trials; the timing or likelihood of regulatory filings and approvals; competition from competing products; the impact of general economic, health, industrial or political conditions in the United States or internationally; the sufficiency of Gyre’s capital resources and its ability to raise additional capital. Additional risks and factors are identified under “Risk Factors” in Gyre’s Annual Report on Form 10-K for the year ended December 31, 2024 filed on March 17, 2025 and in other filings the Company may make with the Securities and Exchange Commission. Gyre expressly disclaims any obligation to update any forward-looking statements whether as a result of new information, future events or otherwise, except as required by law. For Investors:Stephen Jasperstephen@gilmartinir.com

Relief Therapeutics Announces Positive 12-Month Stability Data for Inhaled and Intravenous Preparations of RLF-100 ® (Aviptadil Acetate) Relief to revised provisional patent application for RLF-100 ® based on the new stability results GENEVA, SWITZERLAND / ACCESSWIRE / April 17, 2023 / RELIEF THERAPEUTICS Holding SA (SIX:RLF)(OTCQB:RLFTF)(OTCQB:RLFTY) (Relief Therapeutics, or Relief), a biopharmaceutical company committed to delivering innovative treatment options with the potential for transformative outcomes to benefit those suffering from select specialty and rare diseases, today announced positive 12-month stability data for the liquid and lyophilized preparations of RLF-100 ® , intended for intravenous (IV) and inhaled administration. RLF-100 ® is the company's proprietary, investigational formulation of aviptadil acetate. The data from the stability study showed that both inhaled and IV RLF-100 ® demonstrated high purity levels at 12 months at all temperatures tested, including refrigerated and room temperature environments. The results are consistent with prior data observed at three- and six-month intervals. The stability testing study will continue to determine the maximum shelf life of RLF-100 ® . Based on the latest results, Relief Therapeutics intends to amend its previously filed provisional patent application for RLF-100 ® with the new findings. If granted, this patent could provide exclusivity for RLF-100 ® at least until 2042, without considering Hatch-Waxman extensions or other patent term adjustments. The Hatch-Waxman Act permits a patent extension term of up to five years as compensation for patent term lost during the FDA regulatory review process. "The testing conducted to date has consistently shown that our novel, optimized composition of aviptadil acetate provides better stability results in both the liquid and lyophilized preparations. RLF-100 ® was shown to be shelf stable and active after one year at temperatures suitable for shipping and long-term storage. This is an important milestone toward commercialization to ensure that RLF-100 ® is safe and effective, no matter where in the world it is supplied." said Jack Weinstein, chief executive officer at Relief Therapeutics. "We believe this new, stable formulation has significant clinical and commercial value and our goal is to establish RLF-100 ® as the standard of care for the prevention and treatment of respiratory failure and its complications in both the acute and chronic applications." Stability testing of pharmaceutical products is mandatory for regulatory approvals. If a product fails to meet the standards prescribed by regulatory authorities, the product will not be granted approval for commercialization. Planning, execution and completion of studies in given timelines plays a major role in securing approval and ensuring a product reaches patients who need it. RLF-100 ® is under development for the potential treatment of acute and chronic lung diseases, including pulmonary sarcoidosis, infectious acute respiratory distress syndrome (ARDS), checkpoint inhibitor-induced pneumonitis (CIP) and chronic berylliosis. The U.S. Food and Drug Administration (FDA) granted RLF-100 ® Orphan Drug designation (ODD) to inhaled RLF-100 ® for the potential treatment of pulmonary sarcoidosis in August 2021. About Drug Stability Requirements The purpose of long-term and accelerated stability testing is to determine how long a drug product will maintain the properties and characteristics, such as purity, efficacy and structure, it possessed at the time of manufacture as well as the quality of a drug product over time while under the influence of environmental conditions such as temperature, humidity and light. Under long-term and accelerated stability storage conditions, the drug is evaluated by high performance liquid chromatography (HPLC) to separate, identify and quantify each chemical component to a very high degree of resolution to assess if any changes occur in the chemical composition. Stability studies are conducted during all phases of drug development to satisfy the regulatory requirements for clinical trials. Data from these studies is then used to establish recommended storage conditions, retest intervals and shelf life. Demonstrating long-term stability of a drug to be used in human clinical testing is essential to prove the potency and efficacy of the drug is not affected during prolonged shelf life. Long-term stability is completed over three years, with reporting at 0, 3, 6, 9, 12, 18, 24 and 36 months. Accelerated stability is completed over six months, with reporting at 0, 3 and 6 months. [1] , [2] About RLF-100 ® (aviptadil acetate) Aviptadil acetate is a synthetic form of vasoactive intestinal peptide (VIP) comprising 28 amino acids, which was first discovered in 1970. Although initially identified in the intestinal tract, human VIP is now known to be produced throughout the body and primarily concentrated in the lungs. VIP has shown a multimodal mechanism of action: decrease of inflammatory cytokines release leading to prevention of cytokine storm syndrome and viral replication, immunomodulating effect, vasodilating and bronchodilating effects and prevention of surfactant depletion. Seventy percent of VIP in the body is bound to a less common type of cell in the lung, the alveolar epithelial type II (AT2) cell, which is critical to the absorption of oxygen into the body. Aviptadil acetate has a 20-year history of safe use in humans in multiple human trials for sarcoidosis, idiopathic pulmonary fibrosis, asthma, pulmonary arterial hypertension and sepsis-induced acute respiratory distress syndrome. For example, a combination of aviptadil with phentolamine is approved for the treatment of erectile dysfunction by intra-cavernous injections in countries outside the U.S. In early 2022, an unrelated pharmaceutical company in India received emergency use approval for its own formulation of aviptadil for the treatment of COVID-19 from the Drugs Controller General of India. While their approval does not affect the application for approval of our formulation in other countries, it substantiates our original hypothesis that RLF-100 is a potentially viable treatment for COVID-19-related ARDS. About Relief Therapeutics Relief Therapeutics 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 and disorders. Relief Therapeutics' portfolio offers a balanced mix of marketed, revenue-generating products, our proprietary, globally patented Physiomimic™ and TEHCLO™ drug delivery platform technologies and a highly targeted clinical development pipeline consisting of risk-mitigated assets to address rare metabolic disorders, rare skin diseases and rare respiratory diseases. In addition, Relief Therapeutics is commercializing several legacy products via licensing and distribution partners. Our mission to provide therapeutic relief to those suffering from rare diseases and disorders is being advanced by an international team of well-established, experienced biopharma industry leaders with extensive research, development and rare disease expertise. Relief Therapeutics' headquarters are in Geneva, with additional offices in Balerna, Switzerland, Offenbach am Main, Germany and Rome. Relief Therapeutics 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, please visit our website at or follow Relief Therapeutics on LinkedIn and Twitter . FOR MEDIA/INVESTOR INQUIRIES CONTACT: RELIEF THERAPEUTICS Holding SA Catherine Day Vice President, IR & Communications contact@relieftherapeutics.com LifeSci Advisors Irina Koffler +1-917-734-7387 ikoffler@lifesciadvisors.com DISCLAIMER This press release contains forward-looking statements. Forward-looking statements involve known and unknown risks, uncertainties, and other factors, which could cause the actual results, financial condition, performance or achievements of Relief Therapeutics to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. A number of factors, including those described in Relief Therapeutics' filings with the SIX Swiss Exchange and the U.S. Securities and Exchange Commission (SEC), could adversely affect Relief Therapeutics. Copies of Relief Therapeutics' filings with the SEC are available on the SEC EDGAR database at Relief Therapeutics does not undertake any obligation to update the information contained herein, which speaks only as of this date. REFERENCES [1] International Council for Harmonisation (ICH). Technical Requirements for Pharmaceuticals for Human Use. Quality Guidelines: Q1A - Q1F Stability. Available at: . Accessed on April 14, 2023. [2] U.S. Food and Drug Administration, Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER). May 2021. Guidance For Industry: Pharmaceutical Quality/Chemistry, Manufacturing & Controls (PQ/CMC). Available at: . Accessed on April 14, 2023. SOURCE: Relief Therapeutics Holdings AG View source version on accesswire.com:

Relief Therapeutics Holding SA / Key word(s): Research Update 07-Nov-2022 / 07:00 CET/CEST Release of an ad hoc announcement pursuant to Art. 53 LR The issuer is solely responsible for the content of this announcement. Relief Therapeutics Announces Six-Month Stability Data on a New Formulation of RLF-100® (Aviptadil) This new formulation may have important clinical uses for a variety of rare lung diseases Geneva, Switzerland, November 7, 2022 – RELIEF THERAPEUTICS Holding SA (SIX: RLF, OTCQB: RLFTF, RLFTD) (“Relief”), a Swiss, commercial-stage biopharmaceutical company identifying, developing, and commercializing novel, patent protected products in selected specialty, rare and ultra-rare disease areas on a global basis, today announced promising six-month stability data on a new formulation of RLF-100® (aviptadil). The reported data demonstrated high purity levels at six months at all temperatures tested, including at refrigerated and room temperature environments. The results are consistent with those observed at the three-month time period. Based on these results, Relief has filed a new provisional patent application. “The testing conducted to date has shown our novel RLF-100® formulation to be shelf-stable at temperatures suitable for shipping and long-term storage, a critical step towards commercialization,” stated Raghuram (Ram) Selvaraju, Ph.D., Chairman of the Board of Directors of Relief. “We believe that this new, stable formulation has significant clinical and commercial value, and may allow RLF-100® to be delivered via multiple routes of administration for treatment of several debilitating lung disease indications including pulmonary sarcoidosis, acute respiratory distress syndrome (“ARDS”), berylliosis and checkpoint inhibitor-induced pneumonitis (“CIP”), all of which Relief plans to pursue. As previously reported, we intend to initiate a Phase 2b dose ranging study in 54 patients with pulmonary sarcoidosis using inhaled RLF-100® administered over a 12-week period. A pre-IND meeting with the U.S. Food and Drug Administration (FDA) is planned to confirm the efficacy and safety endpoints as well as the proposed dosing regimen and, based on a positive outcome, the trial is expected to begin during 2023.” ABOUT RLF-100® RLF-100® (aviptadil) is a synthetic form of Vasoactive Intestinal Peptide (“VIP”) consisting of 28 amino acids, which was first discovered in 1970. Although initially identified in the intestinal tract, human VIP is known to be produced throughout the body and to be primarily concentrated in the lungs where it has shown a multimodal mechanism of action: specifically, a decrease of inflammatory cytokines release leading to prevention of cytokine storm syndrome and viral replication, an immunomodulating effect, vasodilating and broncho-dilating effects, and prevention of surfactant depletion. Seventy percent of VIP in the body is bound to a less common type of cell in the lung, the alveolar type 2 cell, which is critical to the transmission of oxygen to the body. RLF-100® has a 20-year history of safe use in humans in multiple human trials for sarcoidosis, idiopathic pulmonary fibrosis, asthma, pulmonary arterial hypertension, and sepsis-induced acute respiratory distress syndrome. A combination of aviptadil with phentolamine is approved for the treatment of erectile dysfunction by intra-cavernous injections in countries outside the U.S. RLF-100® is under development for certain acute and chronic lung diseases, including pulmonary sarcoidosis, for which it was granted an Orphan Drug Designation (“ODD”) by the FDA. RLF-100® is also being explored for treatment of checkpoint inhibitor-induced pneumonitis (“CIP”), an indication in which Relief received Swiss method-of-use patent protection related to the inhaled formulation of RLF-100® into at least 2039. RLF-100® will also be evaluated in treating non-COVID-19-related ARDS with a particular focus on infectious ARDS. There are also plans to conduct European proof-of-concept clinical development of RLF-100® in the treatment of chronic berylliosis, an orphan lung disease for which there are no treatments approved and which is characterized by severe inflammation of the lungs, coughing and increasing breathlessness (dyspnea). ABOUT RELIEF Relief is a Swiss, commercial-stage, biopharmaceutical company focused on identification, development and commercialization of novel, patent protected products intended for the treatment of rare and ultra-rare diseases including metabolic disorders, pulmonary diseases, and connective tissue disorders. Relief’s diversified pipeline consists of assets that have the potential to effectively address significant unmet medical needs, including PKU GOLIKE®, engineered with the proprietary Physiomimic technology, which is the first prolonged-release amino acid product commercialized for the dietary management of phenylketonuria (“PKU”). Relief has a Collaboration and License Agreement with Acer Therapeutics for the worldwide development and commercialization of ACER-001 (sodium phenylbutyrate) for the treatment of various inborn errors of metabolism, including Urea Cycle Disorders (“UCDs”) and Maple Syrup Urine Disease (“MSUD”). Relief also continues to develop aviptadil for several rare pulmonary indications. Further, Relief is in clinical development for APR-TD011, a differentiated acid oxidizing solution of hypochlorous acid intended for the treatment of epidermolysis bullosa (“EB”), a group of rare, genetic, life-threatening connective tissue disorders; APR-TD011 has been granted Orphan Drug Designation by the FDA. Finally, Relief is commercializing several legacy products via licensing and distribution partners. RELIEF THERAPEUTICS Holding SA is listed on the SIX Swiss Exchange under the symbol RLF and quoted in the U.S. on OTCQB under the symbols RLFTF and RLFTD. For more information, visit www.relieftherapeutics.com. Follow Relief on LinkedIn. Disclaimer: This communication expressly or implicitly contains certain forward-looking statements concerning RELIEF THERAPEUTICS Holding SA. Such statements involve certain known and unknown risks, uncertainties and other factors, including (i) whether the new formulation of RLF-100 will continue to be stable beyond six months, (ii) whether Relief's new provisional patent can be successfully prosecuted, (iii) whether Relief will be able to successfully start its Phase 2b dose ranging study in 2023 and whether that study will be successful, and (iv) those risks discussed in RELIEF THERAPEUTICS Holding SA's filings with the SIX and the U.S. Securities and Exchange Commission, which could cause the actual results, financial condition, performance or achievements of RELIEF THERAPEUTICS Holding SA to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. RELIEF THERAPEUTICS Holding SA is providing this communication as of this date and does not undertake to update any forward-looking statements contained herein as a result of new information, future events or otherwise.