SMAD7

SAN DIEGO, Nov. 13, 2023 (GLOBE NEWSWIRE) -- Gyre Therapeutics (“Gyre”) (NASDAQ: GYRE), a clinical-stage biotechnology company developing anti-fibrotic therapeutics for a variety of chronic liver diseases, today announced the presentation of a poster at the American Association for the Study of Liver Diseases’ (AASLD) Annual Liver Meeting, November 10-14, 2023, in Boston, Massachusetts. Gyre’s lead asset, Hydronidone, is currently being investigated for the treatment of Metabolic Dysfunction Associated Steatohepatitis (MASH)-associated liver fibrosis in the United States. Gyre’s poster presented the potential antifibrotic effects of Hydronidone and its expected mode of action in mouse hepatic fibrosis models. “We are encouraged by these preclinical results that support Hydronidone’s candidacy as a potential treatment for liver fibrosis,” said Charles Wu, Ph.D., Chief Executive Officer of Gyre Therapeutics. “Our team and collaborators showed Hydronidone’s ability to ameliorate liver fibrosis by inhibiting the activation of hepatic stellate cells (HSCs) via Smad7-mediated Tumor Growth Transforming (TGF)- degradation. Activation of the HSCs is recognized as a central event in the process of liver fibrogenesis with the TGF as one of the key mediators. The obtained mechanistic data support the potential of Hydronidone for the treatment of liver fibrosis associated with a spectrum of chronic liver diseases. We look forward to initiating the clinical program of Hydronidone in the United States in 2024.” Key highlights from the poster presentation are below: Hydronidone significantly improved liver damage in carbon tetrachloride (CCL4) and 3,5-diethoxycarbonyl-1,4-dihydropyridine (DDC) mouse hepatic fibrosis models and reduced the accumulation of collagenHydronidone inhibited the activation of hepatic stellate cells via Smad7-mediated TGF- degradation and decreased the expression of fibrosis genes in hepatic stellate cellsIn a ubiquitin-proteasome dependent pathway, Hydronidone promoted the Caveolin-1 mediated TGFβRI degradation via Smad7Specific knockdown of Smad7 in vivo blocked the antifibrosis effect of Hydronidone Full details for the poster presentations are below: Title: Hydronidone ameliorates liver fibrosis by inhibiting activation of hepatic stellate cells via Smad7-mediated degradation of TGFβRIPresenting Authors: Xianjun Xu, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaPoster Number: 3417-A Date and Time: Sunday, November 12, 2023 from 1:00 p.m. to 2:00 p.m. ETLocation: Poster Hall A A copy of the poster will be made available on the Gyre website at www.gyretx.com following the conclusion of the meeting. About Gyre Therapeutics Gyre Therapeutics (“Gyre”) is a biopharmaceutical company headquartered in San Diego, CA, with a primary focus on the development and commercialization of Hydronidone (F351) for the treatment of Metabolic Dysfunction Associated Steatohepatitis (MASH)-associated fibrosis, formerly known as Nonalcoholic Steatohepatitis (NASH) in the United States. Hydronidone’s development strategy in MASH is based on results obtained in mechanistic studies in MASH rodent model and results of a chronic Hepatitis-B induced liver fibrosis Phase 2 clinical study in China which met the primary endpoints of safety and efficacy and led recently to the designation of a breakthrough therapy by the New Medicines Product Administration of China (NMPA). Gyre is also advancing a diverse pipeline China through its indirect controlling interest in Beijing Continent Pharmaceuticals Ltd., Co., including pirfenidone, 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, including statements concerning the progress and future expectations and goals of Gyre’s research and development efforts, including the timing of the clinical program of Hydronidone, are forward-looking statements. 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: risks associated with the possible failure to realize certain anticipated benefits of the business combination with Catalyst Biosciences, Inc., including with respect to future financial and operating results; positive results from a clinical study may not necessarily be predictive of the results of future or ongoing clinical studies; 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 filed on March 30, 2023 and subsequent reports filed with the SEC, and identified under “Risk Factors” in the Proxy Statement. 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 Jasper stephen@gilmartinir.com

Nogra Pharma announces out-licensing agreement with Torii Pharmaceutical for Japan for New Chemical Entity topical acne treatment NAC-GED-0507 is aPhase III-ready New Chemical Entity (NCE), potentialfirst-in-class treatment, selective PPARγ modulator for topical treatment of acne Phase IIb trial demonstrated a superior safety and efficacy profile compared to standard of care. Results were published in the British Journal of Dermatology in October 2022 Dublin, Ireland, 26 January 2023, Nogra Pharma (“Nogra” or “the Company”), a clinical stage biotechnology company developing innovative therapeutics for immune-inflammatory-mediated diseases, today announces it has entered into an out-licensing agreement with Torii Pharmaceutical Co., Ltd. (Torii) (TSE:4551), to further develop and commercialise NAC-GED-0507 in Japan for the treatment of acne vulgaris. Under the agreement, [for which financial terms are not being disclosed], Torii Pharmaceuticals will gain exclusive development and commercialisation rights for NAC-GED-0507 in Japan. NAC-GED-0507 is an IP protected, Phase III-ready, small molecule selective modulator of the peroxisome proliferation-activated receptor γ (PPARγ), which has been developed by Nogra Pharma in a gel formulation, ideal for topical treatment of acne vulgaris. NAC-GED-0507 has a novel mechanism of action, which acts on the primary pathogenetic factors of acne, with demonstrated: anti-inflammatory activity in both sebocytes and keratinocytes, sebogenesis-modulating activity in sebocytes, capability to “normalize” keratinocytes proliferation/differentiation process, altered by pro-inflammatory cytokines, and effect of induction of sebocytes differentiation. The late-stage clinical development plan has been agreed with the US Food & Drug Administration (FDA) and the European Medicines Agency (EMA). Acne vulgaris is a skin condition that affects 85% of the adolescent and young adult population and is one of the most common skin diseases, with an estimated global prevalence (for all ages) of nearly 10% of the population 1. Despite its high prevalence, innovation in the space has been limited in recent years with NAC-GED-0507 being the first innovative treatment, based on its pharmacological properties, developed in the last 25 years. Leopoldo Zambeletti, Director of Nogra Pharma Ltd, commented: “The agreement with Torii Pharmaceuticals is a testament to the high quality of our scientific network and our development and formulation expertise.At Nogra Pharma, we are committed to using this expertise to develop novel therapeutics agents for the treatment of immune-inflammatory-mediated diseases with high unmet medical need and this agreement is a good step towards this goal. “We’re particularly excited to be exploring innovative pathways in acne, a significant unmet need.If approved, NAC-GED-0507 will be the first new drug for acnein decades,which acts via a novel mechanism of action and has the potential to be the first “disease-modifying agent” for millions of patients affected by the condition worldwide. We’re delighted to be working with Torii, which has a leading position and reputation in dermatology, and look forward to progressing this molecule into development.” Goichi Matsuda, Representative Director, President and Chief Executive Officer of Torii, commented:“We are excited to partner with Nogra and add NAC-GED-0507 to Torii’s growing portfolio of products to treat dermatologic skin diseases with significant unmet need. “The development of NAC-GED-0507 for the treatment of acne is a unique and new approach. Given the promising clinical data, we are confident that NAC-GED-0507 will provide a new treatment option for acne patients. We look forward to collaborating with Nogra and developing NAC-GED-0507 for the Japanese market.” A double-blinded, randomised, vehicle-controlled, multi-centre Phase IIb study conducted on 450 patients with moderate-to-severe acne (registered on EudraCT 2018‐003307‐19) demonstrated statistically superior efficacy of NAC-GED-0507 5% gel over placebo (p < 0.0001) in terms of IGA success rate and total lesion count and was well tolerated. Results of the study, which were published in the British Journal of Dermatology in October 2022, can be found here. - Ends – References J.K.L. Tan, K. Bhate: A global perspective on the epidemiology of acne. British Journal of Dermatology (2015)172(Suppl. 1), pp 3–12 Nogra Pharma Ltd Consilium Strategic Communications Leopoldo Zambeletti Director Phone: +44 7788 183112 Email: lz@nographarma.com Jessica Hodgson/Stella Lempidaki/Andrew Stern Phone: +44 (0)20 3709 5700 Email: nogra@consilium-comms.com About Nogra Pharma Nogra Pharma is a private, clinical stage biotechnology company developing innovative therapeutics for immune-inflammatory-mediated diseases. Led by a highly experienced team with expertise in drug development, Nogra Pharma in collaboration with its subsidiary PPM Services, identifies high-value targets and develops innovative medicines through partnerships with world-leading academic partners. Through a deep understanding of immuno-inflammation, combined with formulation and manufacturing expertise the Company has generated a promising, diversified, commercial pipeline comprising three highly differentiated technology platforms, which can yield multiple assets in a range of indications with high unmet medical need. The oligonucleotide platform has yielded the first oral formulation in the drug class for the treatment of inflammatory bowel disease (an antisense oligonucleotide to Smad7 mRNA which will re-enter clinical development under Nogra’s lead), while the small molecule platforms AhR and SPARMM have yielded promising candidates for the treatment of immune-inflammatory conditions and fibrosis, in skin, gastrointestinal and pulmonary disease. Headquartered in Dublin, Ireland, the Company operates a lean business model of early drug development, up to Phase IIb, before outsourcing assets to pharma partners. About Torii Pharmaceutical Torii Pharmaceutical Co., Ltd. operate business from day to day in line with Torii Pharmaceutical’s Purpose: “We are committed to sincerely serving patients, their families, and those involved in medical care. We contribute to the healthy recovery of patients, as well as to a happy, enriched life free from fear of illness. We will flexibly change and adapt to meet the needs of the times and the environment, while retaining the trust we have earned over our long history, and we will continue to take on the challenge of contributing to healthcare that only we can make.” Torii focuses on Renal diseases, Hemodialysis, Allergy and Skin diseases as its therapeutic areas of importance. Torii is a member of Japan Tobacco Inc. (JT) group. Collaboration with JT takes the form of functional focus, with JT undertaking R&D on new compounds and Torii integrating manufacture and marketing. In addition to Torii’s independent activities, Torii‘s partnership with JT includes in-licensing of high-quality pharmaceuticals.

SOUTH SAN FRANCISCO, Calif., June 24, 2022 (GLOBE NEWSWIRE) -- Pliant Therapeutics, Inc. (Nasdaq: PLRX), a clinical stage biotechnology company focused on discovering and developing novel therapeutics for the treatment of fibrosis, today announced the presentation of two scientific posters at the International Liver Congress™ (ILC) 2022 of the European Association for the Study of the Liver (EASL), taking place June 22-26, 2022, in London, United Kingdom. “Our presentations at this year’s International Liver Congress summarize the translational research findings supporting the hepatic antifibrotic activity of PLN-74809, an oral dual αvß6 / αvß1 integrin inhibitor,” said Éric Lefebvre, M.D., Chief Medical Offer at Pliant Therapeutics. “Preliminary safety data from the INTEGRIS-PSC study continue to show a favorable tolerability profile for PLN-74809.” The poster “Rationale for Evaluation of PLN-74809 Treatment in Participants with Primary Sclerosing Cholangitis in Phase a Study INTEGRIS-PSC” summarized preclinical data on the antifibrotic activity of PLN-74809 in two preclinical models of biliary fibrosis as well as in precision-cut liver slices from patients with primary sclerosing cholangitis (PSC) or primary biliary cirrhosis (PBC). Results showed dose-dependent reductions of key drivers of fibrosis in a mouse model of biliary fibrosis including hepatic collagen, collagen proportionate area, TGF-β signaling and cholestasis. In precision-cut liver slices, PLN-74809 reduced TGF-β-driven COL1A1 and COL1A2 gene expression in a dose-dependent manner. In addition, PLN-74809 demonstrated a favorable tolerability profile based on available blinded safety data and pharmacokinetic findings from participants with PSC enrolled in Part 1 of the ongoing Phase 2a INTEGRIS-PSC study (NCT04480840) that evaluated a once-daily dose of 40 mg. The evaluation of PLN-74809 at doses of 80 mg and 160 mg is currently underway. The poster “Dual Inhibition of Integrins αvß6 and αvß1 Decreases Portal Pressure and Liver Fibrosis in Rats with Biliary Cirrhosis” reviewed preclinical data showing that PLN-75068, a dual αvß6 / αvß1 inhibitor tool compound, reduced TGF-β signaling in the livers of rats with biliary cirrhosis as measured by the reduction of SMAD2 phosphorylation. In addition, a dose-dependent decrease in liver fibrosis, as assessed by collagen proportionate area (CPA), was observed along with dose-dependent inhibitory effects on the TGF-β target genes Ctgf, Serpine1 and SMAD7. Lastly, PLN-75068 improved portal hypertension in this biliary cirrhosis model. Posters presented at the ILC 2022 are available under the Publications section of Pliant’s website at www.PliantRx.com. About Pliant Therapeutics, Inc. Pliant Therapeutics is a clinical stage biopharmaceutical company focused on discovering and developing novel therapies for the treatment of fibrosis. Pliant's lead product candidate, PLN-74809, is an oral small molecule dual selective inhibitor of αvß6 and αvß1 integrins that is in development in the lead indications for the treatment of idiopathic pulmonary fibrosis, or IPF, and primary sclerosing cholangitis, or PSC. PLN-74809 has received Fast Track Designation and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) in IPF and Orphan Drug Designation from the FDA and European Medicines Agency in PSC. Pliant is currently conducting Phase 2a trials of PLN-74809 in the lead indications of IPF and PSC. Pliant has also developed PLN-1474, a small molecule selective inhibitor of αvß1 for the treatment of nonalcoholic steatohepatitis, or NASH with liver fibrosis, which Pliant has transferred to Novartis pursuant to our development partnership. In addition to clinical stage programs, Pliant currently has two preclinical programs targeting oncology and muscular dystrophies. For additional information about Pliant Therapeutics, visit www.pliantrx.com and follow us on Twitter, LinkedIn, Facebook and YouTube. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "anticipate," "estimate," "intend," and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are intended to identify forward-looking statements. These statements include those regarding the de-risking of our development of PLN-74809 and the efficacy and safety profile of our product candidates. Because such statements deal with future events and are based on our current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Pliant Therapeutics could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including those related to the development and commercialization of our product candidates, including any delays in our ongoing or planned preclinical or clinical trials, the impact of the ongoing COVID-19 pandemic on our business, operations, clinical supply and plans, our reliance on third parties for critical aspects of our development operations, the risks inherent in the drug development process, the risks regarding the accuracy of our estimates of expenses and timing of development, our capital requirements and the need for additional financing, and our ability to obtain and maintain intellectual property protection for our product candidates. These and additional risks are discussed in the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" in our Annual Report on Form 10-K filed for the year ended December 31, 2021 with the SEC on March 1, 2022, as updated by our Quarterly Report on Form 10-Q filed for the quarter ended March 31, 2022 with the SEC on May 9, 2022, each available on the SEC's website at www.sec.gov. Unless otherwise noted, Pliant is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise. Investor and Media Contact: Christopher KeenanVice President, Investor Relations and Corporate CommunicationsPliant Therapeutics, Inc.ir@pliantrx.com