DNMT1

DUBLIN--( BUSINESS WIRE )--The "Epigenetic Therapeutics: Global Markets" report has been added to ResearchAndMarkets.com's offering. The global epigenetic therapeutics market was valued at $6.4 billion in 2022. The market is expected to reach $9.8 billion by 2028, growing at a compound annual growth rate (CAGR) of 7.7% over the forecast period. Growth factors include aging populations, increased frequency of cancer risk associated with aging and increased prevalence of cancers cases such as acute-T-cell leukemia, breast cancer, ovarian cancer, Non-Small-Cell lung cancers. Epigenetic drug therapy serves as an ultimate treatment option when a cancer patient is not responding to the conventional therapies such as chemotherapy. Technological innovations in epigenetic drug discovery and development are driving increased use of epigenetic therapeutics, which also is pushing market growth. However, loss of exclusivity in the case of a few branded drugs and the entry of generic drugs into the market is the restraining the growth of this market. In 2022, the PRAP inhibitors segment held the largest share of the global market for epigenetic therapeutics, with 51.7% of the market, followed by Kinase inhibitors (37.5%), HDAC inhibitors (5.8%), IDH inhibitors (2.8%), DNMT inhibitors (1.9%) and KMT inhibitors (0.2%). Report Scope This report is a comprehensive study of the global market for epigenetic therapeutics. It describes the epigenetic therapeutics market, which is segmented by product type and region. Based on product type, the market is segmented into PRAP inhibitors, Kinase inhibitors, IDH inhibitors, HDAC inhibitors, DNMT inhibitors and KMT inhibitors. The market is segmented by region into North America, Latin America, Europe, Asia-Pacific, and the Rest of the World (RoW). This report examines the factors driving growth in the epigenetic drugs market, and it reviews major players, established companies and new entrants. The report, however, does not cover epigenetic diagnostic assays and instruments. The report includes: 77 tables A comprehensive overview of the global markets for epigenetic therapeutics Analyses of the global market trends with historical market revenue data (sales figures) for 2020-2022, estimates for 2023, and projections of compound annual growth rates (CAGRs) through 2028 Understanding of the upcoming market potential for epigenetic therapeutics with an emphasis on new products and technologies, and areas of focus to forecast this market into various segments and sub-segments Estimation of the actual market size and revenue forecast for the global epigenetic therapeutics market, and corresponding market share analysis product type and region In-depth information (facts and figures) concerning major market dynamics (DROs), technology advancements, new products and applications in epigenomics, and COVID-19 impact on the industry Coverage of the technological, economic, and business considerations of the market for epigenetic therapeutics, with analyses and growth forecasts through 2028 A look at the recent breakthrough innovations, key technological issues, market regulations, and current status on the intellectual property rights on epigenetic therapeutics Review of patent trends and research publications for innovations in the genome-editing technologies Insight into the recent industry structure, government regulations and policies, development issues, and the vendor landscape Analysis of the competitive environment and market opportunities based on the company's business strategies, product mapping, and operational integration Descriptive company profiles of the leading pharma corporations, including AstraZeneca, Bristol-Myers Squibb, GSK, Ipsen, Seagen, and Incyte Key Attributes Key Topics Covered Chapter 1 Introduction Study Goals and Objectives Reasons for Doing this Study Scope of Report Methodology Information Sources Geographic Breakdown Chapter 2 Summary and Highlights Highlights of the Market for Epigenetic Therapeutics Chapter 3 Market Overview and Definitions Overview Epigenetics Chapter 4 Market Trends Market Drivers Aging Population Risk of Cancer in Major Countries Penetration of Targeted Medicine in Emerging Markets Market Opportunity Market Restraints Chapter 5 Market Breakdown by Product Type Introduction PRAP Inhibitors Kinase Inhibitors IDH Inhibitors HDAC Inhibitors DNMT Inhibitors KMT Inhibitors Chapter 6 Impact of COVID-19 Introduction Impact of COVID-19 on the Medical Devices and Pharmaceutical Industries Decline/Delay in Elective Procedures Impact of COVID-19 on Medical Device and Pharmaceutical Product Segments Impact of COVID-19 on Epigenetic Therapeutics Markets Chapter 7 Market Breakdown by Region Market Overview and Discussion North America Latin America Europe Asia-Pacific Rest of the World Chapter 8 Emerging/Upcoming Technologies CRISPR Antibody Drug Conjugates Multitargeting Agents Chapter 9 Competitive Landscape Industry Scenario Company Shares Chapter 10 Patent Analysis Patent Analysis, by Manufacturer Chapter 11 Pipeline Analysis Clinical Trials Scenario Chapter 12 Company Profiles AstraZeneca Bristol-Myers Squibb Clovis Oncology GSK PLC Incyte Ipsen Seagen Servier Laboratories, Ltd. For more information about this report visit https://www.researchandmarkets.com/r/kdiz64 About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

While Daiichi Sankyo's DS-7300a has been shown to be effective in interim human data from early trials on the drug in castration-resistant prostate cancer, there’s reason to think that it might not work as well on its own in some subtypes. New preclinical research on Daiichi Sankyo’s antibody-drug conjugate DS-7300a suggests it might be more effective against hard-to-treat forms of prostate cancer when used alongside a long-standing chemotherapy drug. According to the results of a study published Nov. 15 in Science Translational Medicine, experiments assessing DS-7300a with and without the blood cancer chemo agent decitabine found that the combo was more effective in mice with neuroendocrine prostate cancer (NEPC) and a form where the tumor suppressor gene RB1 is mutated or lost. The research was sponsored in part by the Japanese pharma and performed by scientists at the Dana-Farber Cancer Institute. In general, prostate cancer is one of the most treatable if detected early. But some advanced types require castration, where hormones or surgery are used to lower testosterone levels and stop the cancer from growing. About 10% to 20% are resistant to treatment with castration—and, of these, a relatively high number have either changes to RB1 or have evolved into NEPC, both of which make them especially tough to treat. “RB1 genomic loss is uncommon at prostate cancer diagnosis but RB1 deletion or mutation is present in approximately 10 to 20% of castration-resistant prostate cancers,” lead author Himisha Beltran, M.D., a genitourinary oncologist and director of translational research within medical oncology at Dana-Farber, explained to Fierce Biotech Research via email. NEPC makes up another 15 to 20%, she added. Both scenarios make the prognosis far more dire. Beltran’s team had previously identified changes in DNA that distinguish NEPC from other forms of prostate cancer, including some that resulted in higher production of enzymes called DNA methyltransferases. Now, they wanted to find out how these DNA changes—also known as DNA methylation—made prostate cancer harder to treat and whether the most highly expressed DNA methyltransferases, DNMT1 and DNMT3A, might be a viable drug target. For that, they turned to decitabine, a chemotherapy drug that has been used for myelodysplastic cancers since the 1980s. Its anti-cancer activity stems from its ability to inhibit DNA methyltransferases, including DNMT1 and DNMT3A. Studies on NEPC patient-derived cell lines and organoids showed the drug could effectively kill cancer cells, findings that were validated in mouse models of the disease. They also saw differences in DNA markers between treated and untreated mouse models that indicated the drug was effectively preventing DNA methylation. These findings led the researchers to wonder whether the benefit from using decitabine to inhibit DNMT1 and DNMT3a could extend beyond NEPC to remedy other types of DNA changes found in advanced prostate cancer. They homed in on RB1, the deletion or mutation of which makes the disease more resistant to treatment as well as more likely to evolve into NEPC. Cell studies and experiments with a mouse model of prostate cancer without the RB1 gene showed that the drug was effective in inhibiting tumor progression, though it didn’t have an effect on cancer in models where the gene was intact. Additional analysis showed that, like in the case of NEPC, it worked by inhibiting the DNMTs. Knowing that DNMT inhibition could lead to the expression of other cancer cell genes, the researchers next focused on seeing whether any of them might make good targets for a combination treatment with decitabine. RNA and DNA sequencing analysis gave them 245 potential candidates, one of which stood out as having some ideal characteristics: the gene for a receptor called B7-H3, the target of prostate tumor treatments under investigation including DS-7300a. While DS-7300a has been shown to be effective in interim human data (PDF) from early trials on the drug in castration-resistant prostate cancer, there’s reason to think that it might not work as well in NEPC or RB1-mutated tumors. That’s because those forms have lower expression of B7-H3 than other types, research shows, which could make them less vulnerable to the drug. Beltran’s lab reasoned that treating NEPC and RB1-mutated tumors with decitabine might make them more susceptible to DS-7300a by raising levels of B7-H3. After showing through cell studies that the combination of decitabine and DS-7300a was indeed synergistic—and that DS-7300a alone wasn’t as effective against cancer cells where B7-H3 expression was low—the researchers tested it out in mouse models. Just as they saw in vitro, DS-7300a had anti-tumor effects in mice with both high- and low-B7-H3-expressing tumors but was more effective against tumors with low levels of B7-H3 when combined with decitabine. The study comes with caveats. It only looked at a limited number of prostate cancer models, the researchers wrote in their report, so it couldn’t assess all the possible relationships between DNA methylation, gene expression and treatment response according to a prostate cancer’s specific genotype and phenotype. On top of that, it’s not clear what level of B7-H3 should be expressed by tumors for them to respond to therapy, Beltran noted. “This can be investigated further in ongoing trials,” she said. Beltran’s team plans to study whether NEPC and prostate cancers with the loss of RB1 respond to monotherapy with decitabine in clinical trials. They also hope to launch a study on the drug in combination with DS-7300a, the effectiveness of which will be assessed in part according to certain biomarkers, she said. 

Webcast of Earnings Call Today, August 9th at 4:30 p.m. ET Topline data from AHFIRM trial expected in Q4 2023 CUPERTINO, Calif., Aug. 9, 2023 /PRNewswire/ -- DURECT Corporation (Nasdaq: DRRX) today announced financial results for the three months ended June 30, 2023 and provided a corporate update. "We are pleased to have completed enrollment in our Phase 2b AHFIRM trial in June and remain on track to report topline data in the fourth quarter of 2023. Assuming a positive outcome from AHFIRM, we plan to review the results with the U.S. Food and Drug Administration (FDA) in the first quarter of 2024. If approved, larsucosterol would be the first FDA-approved treatment for alcohol-associated hepatitis (AH)," stated James E. Brown, D.V.M., President and CEO of DURECT. "We are also excited to announce the expansion of our epigenetic modulator platform into oncology. In conjunction with teams of experienced chemists and biologists, our research and development team have designed new chemical entities (NCE) that are now in preclinical development for multiple oncology indications. With this achievement, DURECT is advancing its mission to be a global leader in the emerging field of epigenetic medicine." Recent Business Highlights: AHFIRM enrollment completed – DURECT announced on June 7, 2023 that it had met the enrollment target in the AHFIRM trial. In total, we randomized and dosed 301 patients at leading hospitals in the U.S., Australia, E.U. and U.K., including prominent transplant centers. We continue to expect to report topline data in the fourth quarter of 2023. AH Key Opinion Leader (KOL) event – DURECT hosted a KOL event for investors on May 16, 2023. The event included presentations by Dr. Paul Gaglio and Dr. Brett Fortune as part of our on-going campaign to build awareness of the mortality rate and unmet patient need in AH, and the role that larsucosterol may play in the treatment of AH. Publication of Phase 2a data in AH – Additional data from DURECT's previously completed Phase 2a trial evaluating larsucosterol in AH were published by the peer-reviewed journal American Journal of Gastroenterology. The publication featured the previously reported safety and efficacy data from the 19-patient, open label Phase 2a trial. It also included cross-study comparisons of severe AH patients from the Phase 2a trial with two matching comparison arms from a contemporaneous study conducted by the DASH (Defeat Alcoholic Steatohepatitis) Consortium. Expanding pipeline with novel anti-cancer NCEs – Building on our knowledge of epigenetic modulation, DURECT has internally developed multiple novel small molecule DNMT inhibitors that exhibit broad spectrum activity against multiple hematologic and solid tumor types. These compounds display unique and desirable physiochemical properties and pharmacokinetic pro as well as favorable tolerability. We intend to select a product candidate by the end of 2023 to advance into clinical trials in cancer patients. Our goal is to be prepared to initiate clinical trials for this product candidate by the end of 2024. Financial Highlights for Q2 2023: Total revenues were $2.1 million and net loss was $11.2 million for the three months ended June 30, 2023 compared to total revenues of $2.1 million and net loss of $11.6 million for the three months ended June 30, 2022. At June 30, 2023, cash, cash equivalents and investments were $34.9 million, compared to $43.6 million at December 31, 2022. Debt at June 30, 2023 was $20.7 million, compared to $21.2 million at December 31, 2022. After the end of the second quarter, in July 2023, we completed a registered direct offering of common stock and warrants which raised net proceeds of approximately $13.8 million. Earnings Conference Call We will host a conference call and webcast today at 4:30 p.m. Eastern Time/1:30 p.m. Pacific Time to discuss second quarter 2023 results and provide a corporate update: Wednesday, August 9 @ 4:30 p.m. Eastern Time / 1:30 p.m. Pacific Time Toll Free: 1-877-407-0784 International: 1-201-689-8560 Conference ID: 13740526 Call meTM: click here Participants can use guest dial-in numbers above to reach an operator or they can click the Call meTM link for instant telephone access to the event (dial-out). The Call meTM link will be made active 15 minutes prior to scheduled start time. Webcast: A live audio webcast of the presentation will be also available by accessing DURECT's homepage at on the "Events" page, under the "Investors" tab. If you are unable to participate during the live webcast, the call will be archived on DURECT's website under "Events" in the "Investors" section. About the AHFIRM Trial Enrollment was completed in June 2023 in our Phase 2b randomized, double-blind, placebo-controlled, international, multi-center study in subjects with severe acute alcohol-associated hepatitis (AH) to evaluate saFety and effIcacy of laRsucosterol treatMent (AHFIRM). The study is comprised of three arms, and 301 total patients were randomized and dosed, with approximately 100 patients in each arm: (1) Placebo plus supportive care, with or without methylprednisolone capsules at the investigators' discretion; (2) larsucosterol (30 mg); and (3) larsucosterol (90 mg). Patients in the larsucosterol arms receive the same supportive care without steroids. In order to maintain blinding, patients in the two active arms receive matching placebo capsules if the investigator prescribes steroids. The primary outcome measure will be the 90-Day incidence of mortality or liver transplantation for patients treated with larsucosterol compared to those treated with placebo. The Company has enrolled patients at clinical trial sites across the U.S., EU, U.K., and Australia. Reflecting the life-threatening nature of AH and the lack of therapeutic options, the U.S. Food and Drug Administration (FDA) has granted larsucosterol Fast Track Designation for the treatment of AH. We believe a positive outcome in the AHFIRM trial could support a New Drug Application filing. For more information, refer to ClinicalTrials.gov Identifier: NCT04563026. About Alcohol-associated Hepatitis (AH) AH is an acute form of alcohol-associated liver disease (ALD), associated with long-term heavy intake of alcohol and often occurs after a recent period of increased alcohol consumption (i.e., a binge). AH is typically characterized by severe inflammation and destruction of liver tissue (i.e., necrosis), potentially leading to life-threatening complications including liver failure, acute kidney injury and multi-organ failure. There are no FDA approved therapies for AH and a retrospective analysis of 77 studies published between 1971 and 2016, which included data from a total of 8,184 patients, showed the overall mortality from AH was 26% at 28 days, 29% at 90 days and 44% at 180 days. A subsequent global study published in December 2021, which included 85 tertiary centers in 11 countries across 3 continents, prospectively enrolled 2,581 AH patients with a median Model of End-Stage Liver Disease (MELD) score of 23.5, reported mortality at 28 and 90 days of approximately 20% and 31%, respectively. Stopping alcohol consumption is necessary, but frequently not sufficient for recovery in many moderate (defined as MELD scores of 11-20) and severe (defined as MELD scores >20) patients and therapies that reduce liver inflammation, such as corticosteroids, are limited by contraindications, have not been shown to improve survival at 90 days or one year, and have demonstrated an increased risk of infection. While liver transplantation is becoming more common for ALD patients, including AH patients, the total number of such transplants is still relatively small. Average charges for a liver transplant exceed $875,000, and patients require lifelong immunosuppressive therapy to prevent organ rejection. About Larsucosterol Larsucosterol is an endogenous sulfated oxysterol and an epigenetic modulator. Epigenetic regulators are compounds that regulate patterns of gene expression without modifying the DNA sequence. DNA hypermethylation, an example of epigenetic dysregulation, results in transcriptomic reprogramming and cellular dysfunction, and has been found to be associated with many acute (e.g., AH) or chronic diseases (e.g., NASH). As an inhibitor of DNA methyltransferases (DNMT1, DNMT3a and 3b), larsucosterol inhibits DNA methylation, which subsequently modulates expression of genes that are involved in cell signaling pathways associated with stress responses, cell death and survival, and lipid biosynthesis. This may ultimately lead to improved cell survival, reduced inflammation, and decreased lipotoxicity. As an epigenetic modulator, the proposed mechanism of action provides further scientific rationale for developing larsucosterol for the treatment of acute organ injury and certain chronic diseases. About DURECT Corporation DURECT is a biopharmaceutical company committed to transforming the treatment of acute organ injury and chronic liver diseases by advancing novel and potentially lifesaving therapies based on its endogenous epigenetic regulator program. Larsucosterol, DURECT's lead drug candidate, binds to and inhibits the activity of DNA methyltransferases (DNMTs), epigenetic enzymes that are elevated and associated with hypermethylation found in alcohol-associated hepatitis (AH) patients. Larsucosterol is in clinical development for the potential treatment of AH, for which FDA has granted a Fast Track Designation; non-alcoholic steatohepatitis (NASH) is also being explored. In addition, POSIMIR® (bupivacaine solution) for infiltration use, a non-opioid analgesic utilizing the innovative SABER® platform technology, is FDA-approved and has been exclusively licensed to Innocoll Pharmaceuticals for commercialization in the United States. For more information about DURECT, please visit and follow us on Twitter . DURECT Forward-Looking Statements This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, relating to: our plans to report topline data in the fourth quarter of 2023, our plans to meet with the FDA to review results of AHFIRM in the first quarter of 2024, the potential FDA approval of larsucosterol for the treatment of AH, the ability of a positive outcome in the AHFIRM trial to support a New Drug Application filing, our plans to commercialize larsucosterol if approved, the commercialization of POSIMIR by Innocoll, the potential to develop larsucosterol for AH, NASH or other indications, our NCE program for oncology and plans to initiate clinical trials related to this program, and the potential benefits, if any, of our product candidates. Actual results may differ materially from those contained in the forward-looking statements contained in this press release, and reported results should not be considered as an indication of future performance. The potential risks and uncertainties that could cause actual results to differ from those projected include, among other things, the risks that the AHFIRM trial does not confirm the results from earlier clinical or pre-clinical trials, or does not demonstrate the safety or efficacy of larsucosterol in a statistically significant manner, the risk that the FDA or other government agencies may require additional clinical trials for larsucosterol before approving it for the treatment of AH even if the results of the AHFIRM trial are successful, risks that Innocoll may not commercialize POSIMIR successfully, and risks related to the sufficiency of our cash resources, our anticipated capital requirements and capital expenditures, our need or desire for additional financing, our ability to obtain capital to fund our operations and expenses and our ability to continue to operate as a going concern. Further information regarding these and other risks is included in DURECT's most recent Securities and Exchange Commission (SEC) filings, including its annual report on Form 10-K for the year ended December 31, 2022 and quarterly report on Form 10-Q for the quarter ended June 30, 2023 when filed under the heading "Risk Factors." These reports are available on our website under the "Investors" tab and on the SEC's website at . All information provided in this press release and in the attachments is based on information available to DURECT as of the date hereof, and DURECT assumes no obligation to update this information as a result of future events or developments, except as required by law. NOTE: POSIMIR® is a trademark of Innocoll Pharmaceuticals, Ltd. in the U.S. and a trademark of DURECT Corporation outside of the U.S. SABER® is a trademark of DURECT Corporation. Other referenced trademarks belong to their respective owners. Larsucosterol is an investigational drug candidate under development and has not been approved for commercialization by the U.S. Food and Drug Administration or other health authorities for any indication. View original content to download multimedia: SOURCE DURECT Corporation Company Codes: NASDAQ-NMS:DRRX