Myocardial fibrosis

- Company completed Late-Cycle review meeting with FDA - FDA no longer intends to hold Advisory Committee meeting - FDA Review of NDA continues to proceed as planned with PDUFA target action date of November 28, 2024 NEW YORK, Sept. 18, 2024 (GLOBE NEWSWIRE) -- Applied Therapeutics, Inc. (Nasdaq: APLT), a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates against validated molecular targets in indications of high unmet medical need, today announced an update on the ongoing New Drug Application (NDA) review of govorestat for the treatment of Classic Galactosemia. The Company recently completed its late-cycle review meeting with the United States Food and Drug Administration (FDA). The FDA communicated that an Advisory Committee meeting would no longer be required, which was previously tentatively scheduled for October 9, 2024. The FDA informed the Company that the Priority Review of the NDA is continuing as planned with alignment on post-marketing requirements expected in October 2024. The previously announced Prescription Drug User Fee Act (PDUFA) target action date remains on track for November 28, 2024. “We are incredibly pleased by the ongoing collaborative dialogue with the FDA during the NDA review process, and we look forward to continuing to work together with the agency to bring the first potential treatment to Classic Galactosemia patients,” said Shoshana Shendelman, PhD, Founder and CEO of Applied Therapeutics. “Galactosemia is a progressive disease in urgent need of treatment, and the potential approval of govorestat will be transformative for the many patients and families living with this serious disease. Our commitment to the Classic Galactosemia community is further supported by our thoughtful commercial preparation, focused on establishing an effective patient access program, high physician awareness and strong payor engagement.” About Galactosemia Galactosemia is a rare genetic metabolic disease resulting in an inability to metabolize the simple sugar galactose. Galactose is found in foods, but is also produced endogenously by the body. When not metabolized properly, galactose is converted to the toxic metabolite, galactitol, which causes neurological complications, including deficiencies in speech, cognition, behavior, and motor skills, and also results in juvenile cataracts and ovarian insufficiency (in women). There are approximately 3,000 patients with Galactosemia in the US and 80 new births per year, and approximately 4,000 patients with Galactosemia in the EU and 120 new births per year. Newborn screening for Galactosemia is mandatory in the US and most EU countries, leading to rapid identification of affected patients. About Govorestat (AT-007) Govorestat is a central nervous system (CNS) penetrant Aldose Reductase Inhibitor (ARI) in development for the treatment of several rare neurological diseases, including Galactosemia, SORD Deficiency, and PMM2-CDG. In a study in children with Galactosemia aged 2-17, treatment with govorestat demonstrated clinical benefit on activities of daily living, behavioral symptoms, cognition, fine motor skills and tremor. Govorestat also significantly reduced plasma galactitol levels in both adults and children with Galactosemia. Galactitol is a toxic metabolite responsible for tissue damage and long-term complications in Galactosemia. In the Phase 3 INSPIRE trial in patients with SORD Deficiency, an interim analysis at 12 months demonstrated a statistically significant reduction in blood sorbitol levels with govorestat treatment as compared to placebo, as well as a statistically significant correlation of sorbitol with change in clinical outcomes, such as 10-meter walk run test, dorsiflexion and 6-minute walk test. Govorestat also demonstrated highly statistically significant effects on the CMT Health Index (CMT-HI) patient reported outcome measure, with benefit of govorestat shown on lower limb function, mobility, fatigue, pain, sensory function, and upper limb function. Govorestat has received Orphan Medicinal Product Designation from the European Medicines Agency (EMA) for both Galactosemia and SORD Deficiency. Govorestat has also received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of Galactosemia, PMM2-CDG, and SORD Deficiency; Pediatric Rare Disease designation for Galactosemia and PMM2-CDG; and Fast Track designation for Galactosemia. About Applied Therapeutics Applied Therapeutics is a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates against validated molecular targets in indications of high unmet medical need. The Company’s lead drug candidate, govorestat, is a novel central nervous system penetrant Aldose Reductase Inhibitor (ARI) for the treatment of CNS rare metabolic diseases, including Galactosemia, SORD Deficiency, and PMM2-CDG. The Company is also developing AT-001, a novel potent ARI, for the treatment of Diabetic Cardiomyopathy, or DbCM, a fatal fibrosis of the heart. The preclinical pipeline also includes AT-003, an ARI designed to cross through the back of the eye when dosed orally, for the treatment of Diabetic retinopathy. To learn more, please visit www.appliedtherapeutics.com and follow the company on Twitter @Applied_Tx. Forward-Looking Statements This press release contains “forward-looking statements” that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. Any statements, other than statements of historical fact, included in this press release regarding the strategy, future operations, prospects, plans and objectives of management, including words such as “may,” “will,” “expect,” “anticipate,” “plan,” “intend,” “predicts” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are forward-looking statements. These include, without limitation, statements regarding (i) the likelihood that the Company’s ongoing NDA and MMA submissions will be approved and the timing of any decision and (ii) statements related to the scheduling or timing of any potential FDA or EMA meetings, interactions or submissions. Forward-looking statements in this release involve substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by the forward-looking statements, and we, therefore cannot assure you that our plans, intentions, expectations or strategies will be attained or achieved. Such risks and uncertainties include, without limitation, (i) our plans to develop, market and commercialize our product candidates, (ii) the initiation, timing, progress and results of our current and future preclinical studies and clinical trials and our research and development programs, (iii) our ability to take advantage of expedited regulatory pathways for any of our product candidates, (iv) our estimates regarding expenses, future revenue, capital requirements and needs for additional financing, (v) our ability to successfully acquire or license additional product candidates on reasonable terms and advance product candidates into, and successfully complete, clinical studies, (vi) our ability to maintain and establish collaborations or obtain additional funding, (vii) our ability to obtain and timing of regulatory approval of our current and future product candidates, (viii) the anticipated indications for our product candidates, if approved, (ix) our expectations regarding the potential market size and the rate and degree of market acceptance of such product candidates, (x) our ability to fund our working capital requirements and expectations regarding the sufficiency of our capital resources, (xi) the implementation of our business model and strategic plans for our business and product candidates, (xii) our intellectual property position and the duration of our patent rights, (xiii) developments or disputes concerning our intellectual property or other proprietary rights, (xiv) our expectations regarding government and third-party payor coverage and reimbursement, (xv) our ability to compete in the markets we serve, (xvi) the impact of government laws and regulations and liabilities thereunder, (xvii) developments relating to our competitors and our industry, (xviii) our ability to achieve the anticipated benefits from the agreements entered into in connection with our partnership with Advanz Pharma and (xiv) other factors that may impact our financial results. In light of the significant uncertainties in these forward-looking statements, you should not rely upon forward-looking statements as predictions of future events. Although we believe that we have a reasonable basis for each forward-looking statement contained in this press release, we cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur at all. Factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in our filings with the U.S. Securities and Exchange Commission, including the “Risk Factors” contained therein. Except as otherwise required by law, we disclaim any intention or obligation to update or revise any forward-looking statements, which speak only as of the date they were made, whether as a result of new information, future events or circumstances or otherwise. Contacts Investors: Julie Seidel/Andrew Vulis646-970-0543appliedtherapeutics@argotpartners.com Media:media@appliedtherapeutics.com

Eli Lilly is pairing up with a so-called “dark genome” biotech startup to hunt for a new generation of obesity and metabolic drugs. The Indianapolis-based drugmaker is betting up to $1 billion on seed-stage biotech HAYA Therapeutics, the companies said Wednesday morning. The Swiss and US startup is working on an RNA dark genome platform that complements Lilly’s growing efforts in genetic medicines , which now comprise about one-third of its pipeline. HAYA will get an upfront payment and equity investment from Lilly, but both companies declined to disclose those figures. Initial checks are becoming a smaller portion of overall biotech-pharma pacts, according to a recent JP Morgan report . Like a handful of other startups, HAYA is exploring the dark genome, which informs how cells respond to an environment and mediates disease-driving cell state effects, CEO Samir Ounzain said in an interview. The company considers the dark genome a vastly untapped area of drug R&D. Proteins comprise less than 2% of your genome, and have small therapeutic windows and safety liabilities, but dark genome RNAs are “exquisitely specific,” Ounzain said. “You can discover these RNAs that are only active in a diseased cell in a specific tissue,” Ounzain said. “So once you develop a medicine to target that RNA, you have really unprecedented precision in disease-modifying activity, and that’s really the reason why we’re so excited about the long non-coding RNAs and the regulatory genome as a new biological target space for drug development.” Another startup in the space, NextRNA, teamed up with Bayer last week with a focus on two cancer programs. HAYA’s lead internal program is in cardiac fibrosis in heart failure and is entering the GLP toxicology phase, Ounzain said. Further down the pipeline, it has projects in pulmonary fibrosis and the tumor microenvironment in oncology, he said. The company is still working off an approximately $20 million seed round announced in May 2021, Ounzain said. It emerged about a year after another startup in the area, ROME Therapeutics, had launched with $50 million in Series A funds from GV and ARCH Venture Partners, among others. At the time of the seed financing, Ounzain told Endpoints News that HAYA could be in the clinic in two to three years. He declined to give an updated timeframe. “We’re actually very proud of that, that what we’ve been able to build with our seed financing has validated the value proposition around the platform and the target space,” Ounzain said. The company has about 35 employees across its operations in Lausanne, Switzerland, and San Diego, where it works out of Johnson & Johnson’s JLABS. As Lilly runs clinical trials of at least half a dozen other experimental obesity medications, with two of those in late-stage testing, the pharma giant is seeking to build out its fourth, fifth and beyond generations of treatments for weight loss and various associated metabolic conditions. It also teamed up with Fauna Bio last December to apply the California startup’s research on the 13-lined ground squirrel, whose annual six-month dormancy could offer insights into new approaches to the chronic condition. That deal also came with an undisclosed upfront and equity portion and up to $494 million in milestones.

On August 28, Bayer and NextRNA Therapeutics, Inc. announced a collaboration and licensing agreement. Under the agreement, the two companies will jointly develop two small molecule therapies targeting long non-coding Rnas (lncrnas), with the aim of further strengthening Bayer's R&D pipeline in precision oncology. NextRNA Therapeutics is a biotechnology company dedicated to developing innovative drugs to treat diseases driven by lncRNA. Under the terms of the agreement, Bayer and NextRNA will jointly advance two programs targeting oncology indications where there is currently a significant unmet medical need. The first project involves small molecule therapies targeting lncrnas and is currently in early preclinical development of NextRNA. In the second project, NextRNA will propose lncRNA targets identified by its platform, while Bayer will have the right to select one of these targets for co-development. Bayer will provide up to $547 million in financial support for both projects, which includes upfront and late-stage milestone payments, research funding, development and commercial milestone payments, and tiered royalties based on net sales.   Founded in 2021, NextRNA Therapeutics' research and development direction is based on the pioneering research of Dr. Carl Novina at Dana-Farber Cancer Institute. The company is focused on developing small molecule drugs that can selectively modulate lncRNA interactions with proteins. Under pathological conditions, dysregulated lncrnas recruit RNA-binding proteins (RBP), thereby driving the pathological process of the disease. NextRNA Therapeutics mainly disrupts the interaction between lncRNA and RBP through small molecule drugs to inhibit the function of lncRNA associated with disease. NextRNA Therapeutics' competitive advantage lies in its unique NextMap computational engine, which combines deep lncRNA biology expertise with multiple biochemical, biophysical and chemical technologies to build a powerful R&D platform.   In March 2022, NextRNA Therapeutics successfully closed A $9.3 million seed round and a $46.8 million Series A round. CobroVentures and Lightchain Capital led both rounds of funding, CircleAlternative Investments, Evans Capital, Jefferies, Rivas Capital and Willett Advisors also participated. NextRNA Therapeutics is being backed by a number of international investors. The funds will be used to strengthen NextRNA Therapeutics' target and drug discovery engine, expand the product pipeline, and advance pilot programs.   Bayer's collaboration with NextRNA Therapeutics not only strengthens NextRNA's leading position in lncRNA targets, but also underscores its value as an ideal partner for developing innovative small molecule drugs across disease domains. In living organisms, non-coding Rnas (Ncrnas) are a class of RNA molecules that are not involved in protein coding. They fall into two main categories: short-chain micrornas (mirnas) and long-chain lncrnas. Numerous studies have shown that although Ncrnas do not encode proteins, they are closely involved in a variety of complex biological processes, such as immune cell development and function, immune disorders, neurodevelopment, and neurological diseases. Therefore, lncrnas and other Ncrnas and their interacting proteins constitute a vast and underexplored field of novel therapeutic targets.   In recent years, in addition to NextRNA, many emerging companies are also working to develop targeted therapies for long non-coding RNA (lncRNA). Laronde was one of the pioneers in the early deployment of lncRNA therapeutics, building a technology platform based on circular RNA (circRNA). Because circRNA, as a type of lncRNA, is more stable, Laronde plans to take advantage of this property to achieve more durable expression of therapeutic proteins such as peptides, enzymes and antibodies in the body. In May 2021, the company received a $50 million investment from Flagship Pioneering; In August 2021, Laronde closed a $440 million funding round.   Transine Therapeutics was founded by Prof. Piero Carninci, a pioneer in the field of functional genomics and lncRNA, and Prof. Stefano Gustincich. Transine's SINEUP platform is a lncrNA-specific technology that specifically enhances the translation efficiency of targeted mrnas. SINEUP consists of an mRNA binding domain and a functional domain, in which the binding domain is responsible for identifying targeted mrnas and is the core of platform specificity. The functional domain is responsible for directly recruiting the ribosome and enhancing the expression of the protein through the insertion of the reverse SINEB2 repeat, hence the name of the technique. Transine closed a £9.1 million seed round in June 2021 and an additional £4.6 million seed round in May 2022.   HAYA Therapeutics uses lncRNA as a drug target, identifies tissue - and cell-specific lncrnas from the dark genome through its proprietary technology platform, and develops RNA-targeted therapies targeting these lncrnas to inhibit their expression. Examples include the use of modified antisense oligonucleotides (ASO) to prevent and reverse fibrosis, providing more effective treatment options for diseases such as cardiac fibrosis. In addition, HAYA Therapeutics has established the world's largest lncRNA database to explore lncrnas associated with disease, tissue and cell specificity, and species conservation. In September 2022, the company closed A $40 million Series A funding round.   Cardior is focused on developing non-coding RNA (ncRNA) -based therapies for patients with heart disease. Unlike NextRNA, which is focused on developing small molecule therapies, Cardior's flagship program, CDR132L, is an oligonucleotide ncRNA inhibitor targeting micro-RNA-132, which is capable of affecting multiple key disease signaling pathways simultaneously, resulting in synergistic therapeutic effects targeting key features of heart disease. Cardior has successfully raised $76 million in Series B funding.   In China, lncTAC is a leader in the field of long-chain non-coding RNA (lncRNA) drug research and development. Founded in 2021, the company is dedicated to the research and development of innovative nucleic acid drugs based on lncRNA. At present, lncTAC has established a nucleic acid drug stabilization platform and an extra-hepatic targeted delivery platform with fully independent intellectual property rights.   In addition to lncTAC, there are Hanbio, Novogene, OBiO Technology and other enterprises in the field of lncRNA layout.   In fact, lncrnas are the most abundant class of regulatory RNA molecules in the human body. More than 72% of the human genome is transcribed as lncrnas, which far outnumber proteins, indicating the existence of more potential drug targets. lncRNA can regulate epigenetic, chromatin modification, transcriptional activation and other key life processes, and can play a role in the extracellular, cellular membrane and intracellular. Therefore, disease therapy by targeting lncrnas is considered to be a promising strategy. At present, domestic and foreign enterprises are in the initial stage of development in this field, and we expect relevant enterprises to make breakthroughs in the field of lncRNA as soon as possible.