Sarcoidosis, Pulmonary

Just five months after closing its $2.9 billion deal for MorphoSys, Novartis has recorded an $800 million impairment on the acquisition after a review of “certain clinical trial data,” the company said in its third-quarter earnings report . A company spokesperson confirmed that the review was triggered by pelabresib, an oncology candidate at the center of the MorphoSys buyout. Novartis shared Tuesday that it’s expecting a delayed regulatory submission for pelabresib, as it needs to follow patients longer to assess concerns about emergent malignancies. The company had initially hoped to file for approval in myelofibrosis this year. Emergent malignancies in patients treated with pelabresib were first reported by STAT earlier this year. Novartis will “look at the data over the course of next year,” and assess the potential need for additional studies, CEO Vas Narasimhan said during its Q3 earnings call with the media. Novartis also disclosed three Phase 2 pipeline cuts Tuesday: a BCMA cell therapy called durcabtagene autoleucel or PHE885 in multiple myeloma; XXB750 in hypertension and heart failure; and an IL-17 inhibitor subbed CMK389 in pulmonary sarcoidosis. Overall, Barclays analysts said Novartis had a “strong” quarter. The company raised its end-of-year guidance, with Narasimhan saying its “pure-play” strategy is starting to pay off. While executives previously expected net sales growth in the high single digits to low double digits, Novartis now says the low end of that range will be in the double digits. “The changes we’ve made to become a focused, pure-play company focused on key therapeutic areas, focused on key geographies, is really working,” Narasimhan told reporters. Elsewhere, Narasimhan also fielded a variety of questions about Novartis’ new structure, legal strategy and manufacturing capacity: On the company’s reorganization: It’s been roughly two years since Novartis announced a global restructuring that impacted thousands of positions and involved the spinout of generics unit Sandoz. The company said it completed its transformation in November 2023, though “additional streamlining” this year brought some cuts on the development side. Narasimhan said Novartis is “always going to be fine-tuning at a low level, but we don’t foresee any other large changes at this time.” On radioligand supply: Novartis applied for a label expansion last quarter to bring Pluvicto into the pre-taxane setting for patients with metastatic castration-resistant prostate cancer. But despite recent shortage concerns across the radiopharma space, Narasimhan said Novartis’ manufacturing plans will enable not only the supply of Pluvicto, but also “a very large pipeline of radioligand therapies moving forward.” He added that Novartis’ supply has been “unconstrained for most of this year,” with the ability to produce volumes that support $7 billion to $8 billion-plus in sales. The company has plans to expand its Indianapolis site, and is putting up new sites in California, China and Japan. On the Inflation Reduction Act and a recent court loss: A New Jersey federal court recently rejected Novartis’ legal challenge to the IRA. The company has appealed, though Narasimhan said it’s “difficult to say” whether Novartis’ case or cases brought by other drugmakers will conclude before negotiated prices take effect in 2026. For now, the CEO said Novartis is pushing for legislative changes, including around a provision that calls for negotiations to occur sooner for small molecule drugs than for biologics. “We are operating under the assumption that we need to work under the rules of the law and rather focus on trying to educate policymakers,” he said. On generic entry: Novartis said it expects generic rivals to Tasigna, Promacta and Entresto to hit the US market in mid-2025. “That will certainly be a headwind we’ll face in the second half of 2025,” Narasimhan said. “We still expect good growth next year, both on the top and bottom line.” Editor’s note: This story has been updated to include comment from Novartis on the MorphoSys impairment.

SAN DIEGO, Oct. 08, 2024 (GLOBE NEWSWIRE) -- aTyr Pharma, Inc. (Nasdaq: ATYR) (“aTyr” or the “Company”), a clinical stage biotechnology company engaged in the discovery and development of first-in-class medicines from its proprietary tRNA synthetase platform, today announced that the Company’s lead therapeutic candidate, efzofitimod, will be featured in the Best of CHEST Journals session at the CHEST 2024 Annual Meeting, which is scheduled to take place October 6 – 9, 2024, in Boston, MA. “We are very pleased to have efzofitimod featured in this year’s Best of CHEST session, which speaks to the high quality of the data from the Phase 1b/2a study that was previously published in the journal,” said Sanjay S. Shukla, M.D., M.S., President and Chief Executive Officer of aTyr. “We believe the findings from this study, which showed the ability of efzofitimod to reduce—and in some cases eliminate— steroid use in patients while controlling symptoms, are an important step forward in developing a potential new treatment for sarcoidosis.” Details of the presentation appears below. Title: Efzofitimod for the Treatment of Pulmonary Sarcoidosis Presenter: Daniel A. Culver, D.O., Chair of the Division of Pulmonary Medicine, Cleveland ClinicSession Title: Best of CHEST Journals, Presented by CHEST, CHEST Critical Care, and CHEST Pulmonary Date and Time: Tuesday, October 8, 2024, from 4:00 p.m. to 4:20 p.m. EDTLocation: Convention Center 256 The presentation will review data supporting the efficacy of efzofitimod in pulmonary sarcoidosis, including findings from a Phase 1b/2a study for key efficacy endpoints including measures of steroid reduction, lung function, sarcoidosis symptoms and inflammatory biomarkers that were published in CHEST and a post hoc analysis of the Phase 1b/2a study that evaluated time-to-first-relapse and relapse rate for steroid use that was published in the European Respiratory Journal. Efzofitimod is currently being investigated in the global pivotal Phase 3 EFZO-FIT™ study in 268 patients with pulmonary sarcoidosis. Topline data from the study are expected in the third quarter of 2025. About Efzofitimod Efzofitimod is a first-in-class biologic immunomodulator in clinical development for the treatment of interstitial lung disease (ILD), a group of immune-mediated disorders that can cause inflammation and fibrosis, or scarring, of the lungs. Efzofitimod is a tRNA synthetase derived therapy that selectively modulates activated myeloid cells through neuropilin-2 to resolve inflammation without immune suppression and potentially prevent the progression of fibrosis. aTyr is currently investigating efzofitimod in the global Phase 3 EFZO-FIT™ study in patients with pulmonary sarcoidosis, a major form of ILD, and in the Phase 2 EFZO-CONNECT™ study in patients with systemic sclerosis (SSc, or scleroderma)-related ILD. These forms of ILD have limited therapeutic options and there is a need for safer and more effective, disease-modifying treatments that improve outcomes. About aTyr aTyr is a clinical stage biotechnology company leveraging evolutionary intelligence to translate tRNA synthetase biology into new therapies for fibrosis and inflammation. tRNA synthetases are ancient, essential proteins that have evolved novel domains that regulate diverse pathways extracellularly in humans. aTyr’s discovery platform is focused on unlocking hidden therapeutic intervention points by uncovering signaling pathways driven by its proprietary library of domains derived from all 20 tRNA synthetases. aTyr’s lead therapeutic candidate is efzofitimod, a first-in-class biologic immunomodulator in clinical development for the treatment of interstitial lung disease, a group of immune-mediated disorders that can cause inflammation and progressive fibrosis, or scarring, of the lungs. For more information, please visit www.atyrpharma.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are usually identified by the use of words such as "anticipate," “believes,” “designed,” “can,” “expects,” “intends,” “may,” “plans,” “potential,” “will,” and variations of such words or similar expressions. We intend these forward-looking statements to be covered by such safe harbor provisions for forward-looking statements and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements include, among others, statements regarding the clinical development for efzofitimod, including the potential of efzofitimod to reduce or eliminate steroid use in patients while controlling symptoms and the potential for efzofitimod to be a new treatment for sarcoidosis. These forward-looking statements also reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects, as reflected in or suggested by these forward-looking statements, are reasonable, we can give no assurance that the plans, intentions, expectations, strategies or prospects will be attained or achieved. All forward-looking statements are based on estimates and assumptions by our management that, although we believe to be reasonable, are inherently uncertain. Furthermore, actual results may differ materially from those described in these forward-looking statements and will be affected by a variety of risks and factors that are beyond our control including, without limitation, uncertainty regarding geopolitical and macroeconomic events, risks associated with the discovery, development and regulation of efzofitimod, risks associated with clinical trials and their resulting data generally, the risk that we or our partners may cease or delay preclinical or clinical development activities for efzofitimod for a variety of reasons (including difficulties or delays in patient enrollment in planned clinical trials), the possibility that existing collaborations could be terminated early, and the risk that we may not be able to raise the additional funding required for our business and product development plans, as well as those risks set forth in our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and in our other SEC filings. Except as required by law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. Contact:Ashlee DunstonDirector, Investor Relations and Public Affairsadunston@atyrpharma.com

Post hoc analysis of Phase 1b/2a study demonstrated statistically significant difference in time-to-first-relapse for corticosteroid use in therapeutic (3.0 and 5.0 mg/kg efzofitimod) vs subtherapeutic (1.0 mg/kg efzofitimod and placebo) groups. 54.4% of patients in the subtherapeutic group relapsed following corticosteroid taper, compared to 7.7% in the therapeutic group. SAN DIEGO, Oct. 02, 2024 (GLOBE NEWSWIRE) -- aTyr Pharma, Inc. (Nasdaq: ATYR) (“aTyr” or the “Company”), a clinical stage biotechnology company engaged in the discovery and development of first-in-class medicines from its proprietary tRNA synthetase platform, today announced the publication of a post hoc analysis of the Phase 1b/2a clinical trial of its lead therapeutic candidate, efzofitimod, in patients with pulmonary sarcoidosis, a major form of interstitial lung disease, in the European Respiratory Journal. The publication, entitled, “Therapeutic Doses of Efzofitimod Demonstrate Efficacy in Pulmonary Sarcoidosis,” is available on the Journal’s website and at: https://doi.org/10.1183/23120541.00536-2024. “Oral corticosteroids are considered first-line therapy in patients with sarcoidosis. However, while they may help improve symptoms, long-term use is often associated with significant toxicity and reduced quality of life,” said Ogugua Ndili Obi, M.D., M.P.H., M.Sc., Associate Professor of Medicine and Clinical Director of the Sarcoidosis Program at the Brody School of Medicine at East Carolina University and lead author of the paper. “Many patients find it difficult to taper and/or maintain reduced steroid doses, as symptoms often flare or disease remains refractory, so the low relapse rate seen for the efzofitimod therapeutic group and a significant difference in time-to-first-relapse in this 24-week study is impressive. The ability of a therapy such as efzofitimod to maintain disease control while decreasing or discontinuing steroid use entirely would be clinically important and very meaningful to patients.” The publication reports findings from a post hoc analysis of a pre-specified endpoint in the Phase 1b/2a randomized, double-blind, placebo-controlled, 24-week study of efzofitimod in 37 patients with pulmonary sarcoidosis receiving oral corticosteroid treatment who underwent a forced steroid taper in the first 8 weeks of the study. In this pooled analysis, the time-to-first-relapse was significantly shorter in the subtherapeutic group (1.0 mg/kg efzofitimod and placebo) than in the therapeutic group (3.0 and 5.0 mg/kg efzofitimod). The median time-to-first-relapse in the subtherapeutic group was 126 days, whereas only one of 17 patients in the therapeutic group had relapsed by the end of the study (p=0.017). Furthermore, 54.4% of patients in the subtherapeutic group relapsed for steroid use following steroid taper, compared to 7.7% of patients in the therapeutic group. “We continue to publish data from our Phase 1b/2a study that further demonstrate the efficacy of efzofitimod in pulmonary sarcoidosis patients and positions this first-in-class immunomodulator as a promising new treatment option that can reduce or avoid steroid-related toxicity,” said Sanjay S. Shukla, M.D., M.S., President and Chief Executive Officer of aTyr. “We believe we are on the cusp of a paradigm shift in the treatment for sarcoidosis, where patients may have the opportunity to receive clinically validated therapies that can treat their underlying disease without incurring added harm.” Efzofitimod is a tRNA synthetase derived therapy that selectively modulates activated myeloid cells through neuropilin-2 to resolve inflammation without immune suppression and potentially prevent the progression of fibrosis. Efzofitimod is currently being investigated in the global pivotal Phase 3 EFZO-FIT™ study in 268 pulmonary sarcoidosis patients (NCT05415137). Efzofitimod has received orphan drug designation in the U.S., E.U. and Japan for sarcoidosis and Fast Track designation in the U.S. for pulmonary sarcoidosis. Phase 1b/2a Clinical Trial in Patients with Pulmonary Sarcoidosis The Phase 1b/2a study was a randomized, double-blind, placebo-controlled, multiple-ascending dose clinical trial in 37 patients with pulmonary sarcoidosis. The trial consisted of three cohorts testing doses of 1.0 mg/kg, 3.0 mg/kg and 5.0 mg/kg of efzofitimod or placebo, dosed intravenously every month for six months. The primary objective of the study was to evaluate the safety, tolerability, immunogenicity and pharmacokinetic profile of multiple doses of efzofitimod compared to placebo. Secondary objectives included the potential steroid-sparing effects of efzofitimod, in addition to other exploratory assessments of efficacy, such as lung function. (NCT03824392) About Pulmonary Sarcoidosis Sarcoidosis is an immune-mediated disease characterized by the formulation of granulomas, clumps of inflammatory cells, in one or more organs of the body, predominantly in the lungs. Almost 200,000 Americans live with pulmonary sarcoidosis and the prognosis ranges from benign and self-limiting to chronic, debilitating disease, with 1 in 5 cases resulting in fibrosis, or scarring, of the lungs, which causes permanent loss of lung function and in many cases death. Current treatment options include corticosteroids and other immunosuppressive therapies, which have limited efficacy and are associated with serious side effects that many patients cannot tolerate long-term. About Efzofitimod Efzofitimod is a first-in-class biologic immunomodulator in clinical development for the treatment of interstitial lung disease (ILD), a group of immune-mediated disorders that can cause inflammation and fibrosis, or scarring, of the lungs. Efzofitimod is a tRNA synthetase derived therapy that selectively modulates activated myeloid cells through neuropilin-2 to resolve inflammation without immune suppression and potentially prevent the progression of fibrosis. aTyr is currently investigating efzofitimod in the global Phase 3 EFZO-FIT™ study in patients with pulmonary sarcoidosis, a major form of ILD, and in the Phase 2 EFZO-CONNECT™ study in patients with systemic sclerosis (SSc, or scleroderma)-related ILD. These forms of ILD have limited therapeutic options and there is a need for safer and more effective, disease-modifying treatments that improve outcomes. About aTyr aTyr is a clinical stage biotechnology company leveraging evolutionary intelligence to translate tRNA synthetase biology into new therapies for fibrosis and inflammation. tRNA synthetases are ancient, essential proteins that have evolved novel domains that regulate diverse pathways extracellularly in humans. aTyr’s discovery platform is focused on unlocking hidden therapeutic intervention points by uncovering signaling pathways driven by its proprietary library of domains derived from all 20 tRNA synthetases. aTyr’s lead therapeutic candidate is efzofitimod, a first-in-class biologic immunomodulator in clinical development for the treatment of interstitial lung disease, a group of immune-mediated disorders that can cause inflammation and progressive fibrosis, or scarring, of the lungs. For more information, please visit www.atyrpharma.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are usually identified by the use of words such as "anticipate," “believes,” “designed,” “can,” “expects,” “intends,” “may,” “plans,” “potential,” “will,” “would,” and variations of such words or similar expressions. We intend these forward-looking statements to be covered by such safe harbor provisions for forward-looking statements and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements include, among others, statements regarding the clinical development for efzofitimod, including the potential benefits and therapeutic application of efzofitimod as compared to the potential benefits and drawbacks of the current standard of care for sarcoidosis, timelines and plans with respect to certain development activities (such as the timing of data from clinical trials) and our publishing of additional data, the potential benefits of efzofitimod to be a new treatment option that can reduce or avoid steroid-related toxicity and certain development goals. These forward-looking statements also reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects, as reflected in or suggested by these forward-looking statements, are reasonable, we can give no assurance that the plans, intentions, expectations, strategies or prospects will be attained or achieved. All forward-looking statements are based on estimates and assumptions by our management that, although we believe to be reasonable, are inherently uncertain. Furthermore, actual results may differ materially from those described in these forward-looking statements and will be affected by a variety of risks and factors that are beyond our control including, without limitation, uncertainty regarding geopolitical and macroeconomic events, risks associated with the discovery, development and regulation of efzofitimod, risks associated with clinical trials and their resulting data generally, the risk that we or our partners may cease or delay preclinical or clinical development activities for efzofitimod for a variety of reasons (including difficulties or delays in patient enrollment in planned clinical trials), the possibility that existing collaborations could be terminated early, and the risk that we may not be able to raise the additional funding required for our business and product development plans, as well as those risks set forth in our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and in our other SEC filings. Except as required by law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. Contact: Ashlee Dunston Director, Investor Relations and Public Affairs adunston@atyrpharma.com