Resmetirom

Pictured: FDA headquarters with money and pill bottles/Taylor Tieden for BioSpace There has been no shortage of landmark approvals from the FDA this year. From the first tumor-infiltrating lymphocytes therapy to the first gene therapy for a rare pediatric disease to the first targeted therapy for MASH, 2024 has already seen its fair share. Along with being the first TIL therapy, Amtagvi is also the first one-time cell therapy for a solid tumor. Meanwhile, Orchard’s Lenmeldy offers a glimmer of hope to children with metachromatic leukodystrophy, a fatal genetic metabolic disease, and Rezdiffra is Madrigal’s first approved product. While the first half of the year belonged to cell and gene therapy, the second half is dominated by FDA decisions for other modalities in cancer and diseases of the brain. Here are five target action dates to watch for in the second half of 2024: Eli Lilly’s Donanemab Indication: Alzheimer’s disease PDUFA: Unknown Eli Lilly is one step closer to the long-anticipated decision on its Alzheimer’s therapy, donanemab, after an advisory committee voted unanimously in favor of the anti-amyloid antibody. In June, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee deemed donanemab to be an effective treatment for Alzheimer’s patients with mild cognitive impairment and mild dementia and said the benefits outweighed the risks. Donanemab has not had the smoothest regulatory path. The FDA refused accelerated approval for the candidate in January 2023, taking issue with a Phase II trial design that allowed patients to end treatment when amyloid plaques had been cleared past a certain pre-defined level. This meant that fewer than 100 patients were on donanemab for 12 continuous months, something the regulator requested in its Complete Response Letter. Lilly submitted for traditional approval of donanemab in the second quarter of 2023. In the Phase III TRAILBLAZER-ALZ 2 study, study participants with low-medium levels of tau saw their cognitive decline decrease by around 35% on two different clinical rating scales compared to placebo. Across all amyloid-positive early symptomatic participants, these numbers were 22% and 29%, respectively. If approved, donanemab will be a direct competitor of Biogen and Eisai’s Leqembi, which received the FDA’s full nod in July 2023. Adaptimmune’s afami-cel Indication: Advanced synovial sarcoma PDUFA: Aug. 4 Riding the momentum in the cell and gene therapy space, Adaptimmune is anticipating approval of its T cell therapy afami-cel on or before August 4. If approved, afami-cel would be the first engineered T cell therapy for solid tumors and “the first effective treatment option for synovial sarcoma in more than a decade,” according to Adaptimmune. Synovial sarcoma, which makes up 5% to 10% of soft tissue sarcomas, typically affects individuals under 30, with a five-year survival rate of 20% for metastatic cases. In the SPEARHEAD-1 trial, nearly 40% of patients experienced clinical responses, with a median response duration of around 12 months. Median overall survival was approximately 17 months, contrasting with historical data of less than 12 months for those who received two or more prior lines of therapy; 70% of responders to afami-cel were alive two years after treatment. If successful, afami-cel would be the first product in Adaptimmune’s sarcoma franchise. Lykos Therapeutics’ MDMA Indication: Post-traumatic stress disorder PDUFA: Aug. 11 One of the most-watched FDA decisions this summer, an approval for Lykos Therapeutics’ MDMA-assisted post-traumatic stress disorder (PTSD) therapy would be paradigm-changing. However, on June 4, an FDA advisory committee—the first held for a potential new PTSD treatment this century—voted overwhelmingly against such an approval. In a 10-1 tally, the FDA’s Psychopharmacologic Drugs Advisory Committee said the candidate’s potential benefits do not outweigh its risk, even with a strict risk evaluation and mitigation strategy. Seven out of nine external advisors voted that Lykos had not provided sufficient proof of MDMA’s efficacy in PTSD. A key issue highlighted in FDA briefing documents was that of “functional unblinding,” where “the vast majority” of trial participants were able to accurately guess their treatment assignment. Lykos is backing its New Drug Application with two pivotal Phase III studies, MAPP1 and MAPP2, in which the MDMA-assisted regimen “demonstrated clinically meaningful improvements in PTSD symptoms,” according to the company’s briefing documents. If ultimately approved, Lykos’s therapy would be the first psychedelic drug for a neuropsychiatric disease in the U.S. Bristol Myers Squibb’s KarXT Indication: Schizophrenia PDUFA: Sept. 26 By September 26, the FDA will render a decision on another highly anticipated neuropsychiatric treatment: Bristol Myers Squibb’s KarXT (xanomeline-trospium). BMS came into possession of KarXT following its December 2023 acquisition of Karuna Therapeutics. If approved, KarXT, an investigational muscarinic antipsychotic treatment, would represent the first new drug class for schizophrenia in “several decades,” according to a Karuna press release announcing acceptance of the NDA. Unlike existing schizophrenia treatments, KarXT does not directly block dopamine receptors. Instead, it works through the dual activation of the M1 and M4 muscarinic acetylcholine receptors in the central nervous system, a mechanism believed to improve positive, negative and cognitive symptoms in patients with schizophrenia. Combined data from three completed registrational and placebo-controlled trials show “statistically significant and clinically meaningful improvements,” Karuna reported in November. In April, BMS revealed interim data from a fourth study showing the drug can elicit significant and sustained symptom improvement in patients with schizophrenia. More than 75% of KarXT-treated patients saw at least a 30% improvement in symptoms at 52 weeks of follow-up, according to data presented at the Annual Congress of the Schizophrenia International Research Society 2024 conference. Daiichi Sankyo and AstraZeneca’s Dato-DXd Indication: Non-small cell lung cancer PDUFA: Dec. 20 Daiichi Sankyo and AstraZeneca are looking to add Dato-DXd (datopotamab deruxtecan) to a limited club—antibody drug conjugates (ADCs) approved to treat non-small cell lung cancer (NSCLC). The partners are specifically seeking approval for Dato-DXd to treat adults with locally advanced or metastatic nonsquamous NSCLC who have previously received systemic therapy. AstraZeneca and Daiichi Sankyo are backing the Biologics License Application with data from the Phase III Tropion-Lung01 study, in which Dato-DXd reduced the risk of disease progression or death by 25% compared to chemotherapy. Median progression-free survival was 4.4 months, and the overall response rate was confirmed in 26.4% of patients. In terms of overall survival, high-level results “numerically favored” DatoDXd in the overall trial population, but were not statistically significant, the companies reported in May. Clinically significant improvement was demonstrated in a prespecified subgroup of patients. “We’re very optimistic about this, and we think that [Dato-DXd] can be an important drug for non-squamous non-small cell lung cancer patients,” Mark Rutstein, SVP and head of global oncology clinical development at Daiichi Sankyo, told BioSpace in May. If approved, Dato-DXd could be the first TROP2-directed ADC for lung cancer. Heather McKenzie is a senior editor at BioSpace. You can reach her at heather.mckenzie@biospace.com. Also follow her on LinkedIn.

Lille (France), Cambridge (Massachusetts, United States), Zurich (Switzerland), June 17, 2024 - GENFIT (Nasdaq and Euronext: GNFT), a late-stage biopharmaceutical company dedicated to improving the lives of patients with rare and life-threatening liver diseases, today announced the inclusion of NIS2+® as a key tool for detecting at-risk MASH1 in the European Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). The guidelines were developed as a joint effort by the European Association for the Study of the Liver (EASL), the European Association for the Study of Diabetes (EASD), and the European Association for the Study of Obesity (EASO), and provide healthcare providers an update on prevention, screening, diagnosis, follow-up and treatment for MASLD. The new guidelines were presented during the EASL congress 2024, and were released in the Journal of Hepatology2. “The inclusion of NIS2+® in the EASL-EASD-EASO clinical guidelines is a major scientific recognition based on solid evidence that NIS2+® could play an important role in identifying patients that may benefit from emerging treatments for MASH,” commented Dean Hum, Chief Scientific Officer at GENFIT. “Additionally, GENFIT’s diagnostic technology featured as a monitoring treatment response in a Phase 2 study on tirzepatide’s safety and efficacy for MASH, and was recently presented during the Late Breaking session at EASL and jointly published in the New England Journal of Medicine3,” he added. In the new guidelines, NIS2+® is included for the first time as a non-invasive tool to detect at-risk MASH, and is the only blood-based panel mentioned for this condition. With the recent U.S Food and Drug Administration approval of resmetirom in the US, and given that liver biopsy will be used sparingly in routine clinical practice due to its invasiveness and procedure-related limitations, alternative non-invasive panels with high predictive value validated for the detection of at-risk MASH such as NIS2+®, could play an important role in selecting individuals able to benefit from pharmacotherapy. The new Clinical Practice Guidelines on the management of MASLD can be found at: https://www.journal-of-hepatology.eu/article/S0168-8278(24)00329-5/fulltext ABOUT MASH MASH is a liver disease characterized by an accumulation of fat (lipid droplets), along with inflammation and degeneration of hepatocytes. The disease is associated with an increased risk of cardiovascular disease along with long-term risk for progression to cirrhosis, leading to liver insufficiency and potential progression to liver cancer. MASH is a serious disease that often carries no symptoms in its early stages, but if left untreated can result in cirrhosis, cancer, and the need for liver transplant. The prevalence of MASH is rapidly increasing as a result of the growing obesity and diabetes epidemics and is believed to affect as much as 12 percent of people in the U.S. and six percent worldwide. ABOUT NIS2+® NIS2+® is a blood-based diagnostic technology specifically designed to detect at-risk MASH among patients with metabolic risk factors based on an independent 2-biomarker panel. It is an optimization of the NIS4® technology and was developed and validated by GENFIT as a robust technology across characteristics of interest such as type-2 diabetes, age and sex, allowing large-scale implementation in clinical practice. GENFIT continues to explore the possibility of obtaining regulatory approval and CE Certificates of Conformity, for the widespread use of an IVD test powered by NIS2+® technology in both the United States and Europe. ABOUT GENFIT GENFIT is a late-stage biopharmaceutical company committed to improving the lives of patients with rare, life-threatening liver diseases whose medical needs remain largely unmet. GENFIT is a pioneer in liver disease research and development with a rich history and a solid scientific heritage spanning more than two decades. Today, GENFIT has built up a diversified and rapidly expanding R&D portfolio of programs at various stages of development. The Company focuses on Acute-on-Chronic Liver Failure (ACLF). Its ACLF franchise includes five assets under development: VS-01, NTZ, SRT-015, CLM-022 and VS-02-HE, based on complementary mechanisms of action using different routes of administration. Other assets target other serious diseases, such as cholangiocarcinoma (CCA), urea cycle disorder (UCD) and organic acidemia (OA). GENFIT's expertise in the development of high-potential molecules from early to advanced stages, and in pre-commercialization, was demonstrated in the FDA’s accelerated approval of Iqirvo® (elafibranor4) for Primary Biliary Cholangitis (PBC). Beyond therapies, GENFIT also has a diagnostic franchise including NIS2+® in Metabolic dysfunction-associated steatohepatitis (MASH, formerly known as NASH for non-alcoholic steatohepatitis) and TS-01 focusing on blood ammonia levels. GENFIT is headquartered in Lille, France and has offices in Paris (France), Zurich (Switzerland) and Cambridge, MA (USA). The Company is listed on the Nasdaq Global Select Market and on the Euronext regulated market in Paris, Compartment B (Nasdaq and Euronext: GNFT). In 2021, Ipsen became one of GENFIT's largest shareholders, acquiring an 8% stake in the Company's capital. www.genfit.com FORWARD LOOKING STATEMENTS This press release contains certain forward-looking statements, including those within the meaning of the Private Securities Litigation Reform Act of 1995 with respect to GENFIT, including, but not limited to statements about the potential for NIS2+® to play an important role in identifying patients that may benefit from emerging treatments for MASH. The use of certain words, such as "believe", "potential", "expect", “target”, “may”, “will”, "should", "could", "if" and similar expressions, is intended to identify forward-looking statements. Although the Company believes its expectations are based on the current expectations and reasonable assumptions of the Company’s management, these forward-looking statements are subject to numerous known and unknown risks and uncertainties, which could cause actual results to differ materially from those expressed in, or implied or projected by, the forward-looking statements. These risks and uncertainties include, among others, the uncertainties inherent in research and development, including in relation to safety of drug candidates, cost of, progression of, and results from, our ongoing and planned clinical trials, review and approvals by regulatory authorities in the United States, Europe and worldwide, of our drug and diagnostic candidates, potential commercial success of elafibranor if approved, exchange rate fluctuations, and our continued ability to raise capital to fund our development, as well as those risks and uncertainties discussed or identified in the Company’s public filings with the AMF, including those listed in Chapter 2 "Risk Factors and Internal Control" of the Company's 2023 Universal Registration Document filed on April 5, 2024 (no. D.24-0246) with the Autorité des marchés financiers ("AMF"), which is available on GENFIT's website (www.genfit.fr) and the AMF's website (www.amf.org), and those discussed in the public documents and reports filed with the U.S. Securities and Exchange Commission ("SEC"), including the Company’s 2023 Annual Report on Form 20-F filed with the SEC on April 5, 2024 and subsequent filings and reports filed with the AMF or SEC or otherwise made public, by the Company. In addition, even if the results, performance, financial position and liquidity of the Company and the development of the industry in which it operates are consistent with such forward-looking statements, they may not be predictive of results or developments in future periods. These forward-looking statements speak only as of the date of publication of this document. Other than as required by applicable law, the Company does not undertake any obligation to update or revise any forward-looking information or statements, whether as a result of new information, future events or otherwise. CONTACT GENFIT | Investors Tel: +33 3 2016 4000 | investors@genfit.com GENFIT | Media Stephanie Boyer – Press relations | Tel: +333 2016 4000 | stephanie.boyer@genfit.com GENFIT | 885 Avenue Eugène Avinée, 59120 Loos - FRANCE | +333 2016 4000 | www.genfit.com 1 Metabolic dysfunction-associated steatohepatitis2 DOI: https://doi.org/10.1016/j.jhep.2024.04.0313 DOI: https://doi.org/10.1056/NEJMoa2401943 4 Elafibranor will be marketed and commercialized by Ipsen under the trademark Iqirvo and may be prescribed immediately in the U.S. for eligible patients. Attachment GENFIT: New EASL-EASD-EASO Clinical Practice Guidelines for MASLD Include NIS2+® as Key Tool for Detecting At-Risk MASH