ADM

With a mortality rate of 20-30% for sepsis and 30-50% for septic shock in developed countries, sepsis represents an enormous public health burden and is responsible for almost 20% of all deaths worldwide Enibarcimab has the potential to become the first treatment addressing the under-lying pathophysiology of sepsis. Combined with precision medicine to identify patients most likely to respond to treatment, this approach is the way towards an effective treatment, after development failures of “one-size-fits-all” therapies AdrenoMed is preparing a confirmatory clinical trial to confirm the reduced septic shock mortality under enibarcimab treatment employing precision medicine In the AdrenOSS-2 Phase II trial, the respective patient subgroup had a statistically significant >60% relative reduction in 28-day mortality vs. placebo HENNIGSDORF, Germany and BERLIN, April 10, 2024 (GLOBE NEWSWIRE) -- Adrenomed AG, the vascular integrity company, today announced that the US Food and Drug Administration (FDA) has granted Fast Track designation to its lead product candidate enibarcimab, a first-in-class non-neutralizing monoclonal antibody, for the treatment of septic shock. AdrenoMed is now preparing a confirmatory Phase IIb/III clinical trial to confirm the reduced septic shock mortality under enibarcimab treatment employing a precision medicine approach. AdrenoMed’s CEO Dr. Richard Jones commented: “We are very pleased that enibarcimab has received Fast Track designation from the FDA, recognizing its potential as an innovative biomarker-guided treatment against septic shock to fill the unmet medical need in this very serious condition with a high death toll. This is a great confirmation of AdrenoMed’s efforts to reduce patient heterogeneity and develop effective treatments by bringing precision medicine also to intensive care units.” Enibarcimab is a non-blocking antibody binding to the vasoprotective hormone adrenomedullin. Applying AdrenoMed’s precision medicine approach, enibarcimab treatment of patients with septic shock resulted in improved organ dysfunction and a relevant reduction of day 28 all-cause mortality from 24% to 8% in the patient population defined by the two biomarkers adrenomedullin and DPP3 in the AdrenOSS-2 trial. With a mortality rate of 20-30% for sepsis1 and 30%-50% for septic shock in developed countries,2 sepsis represents an enormous public health burden and is responsible for almost 20% of all deaths worldwide. Fast Track is a process designed by the FDA to facilitate the development of promising drugs for the treatment of serious conditions that fill an unmet medical need and to accelerate review by the regulatory authority, aimed at getting important new drugs to the patient earlier. A drug that receives Fast Track designation is eligible for more frequent meetings with FDA to discuss development plans for the drug regarding collection of data needed to support its approval; more frequent communication about such things as the design of the proposed clinical trials and use of biomarkers; eligibility for Accelerated Approval and Priority Review, if relevant criteria are met; and Rolling Review. Dr. Stephan Witte, CMO of AdrenoMed, said: “We are very confident that the use of enibarcimab in combination with two biomarkers, Adrenomedullin (bio-ADM) and circulating dipeptidyl peptidase 3 (cDPP3), holds the promise to become the first effective targeted treatment against septic shock. With AdrenoMed’s biomarker-guided approach it is possible to clearly define the patient population benefitting most from enibarcimab, resulting in a more pronounced treatment effect and leading to improved mortality in septic shock.” This was the conclusion also drawn by Prof. Peter Pickkers from the Department of Intensive Care Medicine and Radboud Center for Infectious Diseases (RCI), Nijmegen, Netherlands, in a poster session during the recent ISICEM 2024, which took place in Brussels, Belgium, from March 19 – 22, 2024, where he presented previously unpublished data from a prespecified subgroup of the AdrenOSS-2 trial.3 About AdrenOSS-2 The double-blind, randomized, placebo-controlled, biomarker-guided Phase II trial AdrenOSS-2 (n = 301) had included a prespecified analysis of the role of cDPP3 as a second biomarker (next to ADM) to exclude patients who are unlikely to respond to enibarcimab treatment. DPP3 is a cytosolic enzyme involved in the degradation of various cardiovascular and endorphin mediators. High levels of cDPP3 indicate a high risk of organ dysfunction and mortality. This pathway is mechanistically independent from the loss of vascular integrity, which is known to be the main driver of mortality in septic shock and is indicated by elevated plasma levels of ADM (>70 pg/mL). Consequently, the aim of additional analyses was to investigate the impact of different cDPP3 levels on the treatment effect (28-day all-cause mortality) and to identify a suitable cut-off level. It was shown that the effect of enibarcimab on mortality improves with lower cDPP3 values and that the patients with elevated ADM, but non-elevated baseline cDPP3 (below the upper normal range, ≤ 30-50 ng/mL), benefitted the most from enibarcimab treatment. At 28 days, this patient subgroup had a statistically significant >60% relative reduction in mortality compared to placebo. About AdrenoMed AdrenoMed AG is a German privately financed, clinical-stage biopharmaceutical company. AdrenoMed’s mission is to rescue vascular integrity in order to save the lives of critically ill patients with limited treatment options. Founded in 2009 by a management team with decades of in-depth experience in sepsis and deep knowledge in diagnostics and drug development, the company’s lead product candidate enibarcimab (formerly adrecizumab) is a first-in-class non-blocking monoclonal antibody. Enibarcimab targets the vasoprotective peptide Adrenomedullin, an essential regulator of vascular integrity. Enibarcimab has successfully completed a biomarker-guided, double-blinded, placebo-controlled, randomized, multicenter proof-of-concept Phase II trial with 301 patients suffering from septic shock. For further information, please visit and follow us on LinkedIn and Twitter. Contact AdrenoMed AG Martina Kalle-Brune, Ph.D. phone: +49 (0)3302 207780 bd@adrenomed.com Media Inquiries MC Services AG Eva Bauer / Julia von Hummel phone: +49 (0)89 2102280 adrenomed@mc-services.eu __________________________ 1 Global report on the epidemiology and burden of sepsis: current evidence, identifying gaps and future directions. Geneva: World Health Organization; 2020. . 2 Rudd KE et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the global burden of disease studyThe Lancet 2020;395(10219):200–211. (19)32989-7. 3 Pickkers P, Van Lier D, Knothe C, Struck J, Witte S, Laterre PF, Mebazaa A. Precision medicine in septic shock with enibarcimab – biomarker guided definition of target population, 43rd International Symposium on Intensive Care and Emergency Medicine, Poster A284.

DUBLIN--( BUSINESS WIRE )--The "Sepsis - Pipeline Insight, 2024" clinical trials has been added to ResearchAndMarkets.com's offering. This report provides comprehensive insights about 30+ companies and 35+ pipeline drugs in Sepsis pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space. The report outlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Sepsis pipeline landscape is provided which includes the disease overview and Sepsis treatment guidelines. The assessment part of the report embraces, in depth Sepsis commercial assessment and clinical assessment of the pipeline products under development In the report, detailed description of the drug is given which includes mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Sepsis collaborations, licensing, mergers and acquisition, funding, designations and other product related details. Report Highlights The companies and academics are working to assess challenges and seek opportunities that could influence Sepsis R&D. The therapies under development are focused on novel approaches to treat/improve Sepsis. Sepsis Emerging Drugs Chapters This segment of the Sepsis report encloses its detailed analysis of various drugs in different stages of clinical development, including phase II, I, preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases. Sepsis Emerging Drugs Thymosin alpha 1: SciClone Pharmaceuticals Thymosin alpha 1, referred to as thymalfasin, is a synthetic 28-amino acid peptide with multiple biological activities primarily directed towards immune response enhancement. SciClone developed and launched Thymosin alpha 1, under the trade name Zadaxin, for the treatment of hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infections. The drug is also being developed for the treatment of COVID 2019 infections. Scientific and clinical studies have shown that Thymosin alpha 1 helps to stimulate and direct the body's immune response to eradicate infectious diseases, such as HBV, HCV, bacterial, and fungal infections; to fight certain cancers such as melanoma and liver cancer; and to enhance response to vaccines. Clinical trials have shown that Thymosin alpha 1 improves survival in patients in intensive care units being treated for sepsis from severe bacterial infections. The therapy is being evaluated in Phase III stage to treat Sepsis. Currently, the drug is in Phase III stage of its development for the treatment of sepsis. Enibarcimab: AdrenoMed AG Enibarcimab (HAM8101; former name: Adrecizumab) a clinical-stage, first-in-class drug targeting loss of vascular integrity. The strong rationale for Enibarcimab is supported by the elegance of its mode of action, a monoclonal antibody that on binding to its target Adrenomedullin preserves its functionality as regulator of vascular integrity. Enibarcimab targets Adrenomedullin (ADM), a vasoprotective peptide hormone. ADM that remains in the bloodstream, however, has a different effect, one that helps mitigate sepsis: promoting stability of the endothelial barrier by restoring the cell junctions between endothelial cells that ordinarily regulate molecule transport and leakage. In health, levels of ADM in the bloodstream and extravascular space are in equilibrium so that endothelial barrier integrity is maintained and blood pressure remains normal. Currently, the drug is in Phase II stage of its development for the treatment of sepsis. M 6229: Matisse Pharmaceuticals Matisse's platform technology is based on the discovery that in many patients suffering from sepsis, proteins called histones are released by the innate immune system and dying cells into the blood stream, where they are toxic to other cells. Due to a self-enforcing cascade, people may die from organ failure within one or two days. Preclinical results have shown that by neutralizing the toxic histones with Matisse's product M6229, the negative cascade is terminated by neutralization of cationic histones by anionic M6229. Matisse claims to have identified an elegant solution for treating one of the major complications in sepsis by using a non-anticoagulant fraction of heparin called M6229 to neutralize toxic circulatory histones .Currently, the drug is in Phase I stage of its development for the treatment of sepsis. SNIPR 001: SNIPR Biome SNIPR001 is a novel, orally-administered antibiotic that is designed to precisely target difficult-to-treat bacterial infections. It is developed using SNIPR Biome's CRISPR-Guided VectorsT (CGVT Technology), which is designed to deliver CRISPR reagents into target bacterial cells. SNIPR001 is designed to target certain E. coli bacteria in the gut and thus prevent their translocation to the bloodstream, without affecting beneficial bacteria in the microbiome. It contains four CRISPR-armed phages that selectively target and eliminate E. coli strains that are resistant to fluoroquinolone, with demonstrated efficacy in animal disease models. Currently, the drug is in preclinical stage of its development for the treatment of sepsis. Sepsis: Pipeline Development Activities The report provides insights into different therapeutic candidates in phase II, I, preclinical and discovery stage. It also analyses Sepsis therapeutic drugs key players involved in developing key drugs. Pipeline Development Activities The report covers the detailed information of collaborations, acquisition and merger, licensing along with a thorough therapeutic assessment of emerging Sepsis drugs. Sepsis: Therapeutic Assessment Phases Late stage products (Phase III) Mid-stage products (Phase II) Early-stage product (Phase I) along with the details of Pre-clinical and Discovery stage candidates Discontinued & Inactive candidates Route of Administration Products have been categorized under various ROAs such as Oral Intravenous Subcutaneous Parenteral Topical Molecule Type Products have been categorized under various Molecule types such as Recombinant fusion proteins Small molecule Monoclonal antibody Peptide Polymer Gene therapy Product Type Sepsis Report Insights Sepsis Pipeline Analysis Therapeutic Assessment Unmet Needs Impact of Drugs Sepsis Report Assessment Pipeline Product Profiles Therapeutic Assessment Pipeline Assessment Inactive drugs assessment Unmet Needs Key Players SciClone Pharmaceuticals AdrenoMed AG Matisse Pharmaceuticals SNIPR Biome Tianjin Chase Sun Pharmaceutical Beijing Scitech-Mq Pharmaceuticals Recce Pharmaceuticals Inotrem Octapharma Shaperon Shionogi Pharmazz Seres Therapeutics Key Products Thymosin alpha 1 Enibarcimab M 6229 SNIPR 001 Kukoamine B ST-1830 RECCE 327 Nangibotide OctaplasLG HY209 Cefiderocol Centhaquine SER 155 For more information about this clinical trials report visit https://www.researchandmarkets.com/r/ixi7k5 About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. 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Patient population benefitting most from enibarcimab treatment in septic shock can clearly be defined by two biomarkers, as shown by data presented todayIn the AdrenOSS-2 trial, the respective patient subgroup had a statistically significant >60% relative reduction in 28-day mortality vs. placebo. Adrenomed is preparing a confirmatory trialEnibarcimab is targeting loss of vascular integrity, a previously unaddressed pathophysiological mechanism1Adrenomed presenting on individualized precision medicine treatment at the World Sepsis Day Event, Berlin, September 122 HENNIGSDORF, Germany and BERLIN, Sept. 08, 2023 (GLOBE NEWSWIRE) -- Adrenomed AG, the vascular integrity company, today announced new findings on the biomarker-guided treatment of septic shock with enibarcimab. New data analyses of the phase II clinical trial AdrenOSS-2 validate the precision medicine approach applied by Adrenomed in the development of its non-neutralizing antibody enibarcimab for the treatment of septic shock. It shows that the patient population benefitting most from enibarcimab can clearly be identified by the biomarkers Adrenomedullin (ADM) with elevated levels, and low levels of circulating dipeptidyl peptidase 3 (cDPP3). During the 11th Weimar Sepsis Update3, the data were presented in a scientific talk4 given today by Prof. Matthijs Kox, Department of Intensive Care Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands, and in a poster presentation5 from the working group of critical care physician Prof. Peter Pickkers, Nijmegen. In preparation of a confirmatory clinical trial, the double-blind, randomized, placebo-controlled, biomarker-guided phase II trial AdrenOSS-2 (n = 301) included a prespecified analysis of the role of cDPP3 as a second biomarker (next to ADM) to exclude patients who are unlikely to respond to enibarcimab treatment. DPP3 is a cytosolic enzyme involved in the degradation of various cardiovascular and endorphin mediators. High levels of circulating DPP3 (cDPP3) indicate a high risk of organ dysfunction and mortality.6 This pathway is mechanistically independent from the loss of vascular integrity, which is known to be the main driver of mortality in septic shock and is indicated by elevated plasma levels of ADM (>70 pg/mL). Consequently, the aim of additional analyses was to investigate the impact of different cDPP3 levels on the treatment effect (28-day all-cause mortality) and to identify a suitable cut-off level. It was shown that the effect of enibarcimab on mortality improves with lower cDPP3 values and that the patients with elevated ADM, but non-elevated baseline cDPP3 (below the upper normal range, ≤ 30-50 ng/mL), benefitted the most from enibarcimab treatment.7 At 28 days, this patient subgroup had a statistically significant >60% relative reduction in mortality compared to placebo.8 Adrenomed’s CMO Dr. Stephan Witte commented: “We are very pleased with these findings. They underpin Adrenomed’s hypothesis that there is an interplay between baseline DPP3 levels and treatment effects of enibarcimab in patients with septic shock. After many failures with other potential treatments in development, the use of biomarkers for the identification of patients most likely to respond to treatment is the appropriate way towards an effective treatment. It is therefore a great confirmation of Adrenomed’s efforts to bring precision medicine – which has been long established in other disease areas like oncology – also to intensive care units to reduce patient heterogeneity and develop effective treatments.” Dr. Richard Jones, CEO of Adrenomed, added: “These compelling clinical data results, presented at this very important sepsis congress strongly enhance our belief that enibarcimab can make a real difference to saving or improving the lives of the many patients suffering from septic shock. The AdrenOSS-2 trial has marked an important step forward in bringing our precision medicine approach to patients. Adrenomed is now using these findings for the confirmatory development trial and subsequent marketing authorization of enibarcimab.” Adrenomed’s participation in further meetings: In addition to the Sepsis Update meeting in Weimar Adrenomed’s representatives can be met at the following events: (1) Dr. Joachim Struck, Head of Research & Development, Adrenomed AG, will talk about ”Precision Medicine in New Therapies for Septic Shock” at the World Sepsis Day Event which will be held on September 12, 2023, in Berlin and virtually.9 (2) David Germonpré, Chief Financial Officer of Adrenomed, will attend the 23rd Annual Biotech in Europe Forum (Sachs Conference) on September 20-21, 2023, in Basel, Switzerland. About AdrenomedAdrenomed AG is a German privately financed, clinical-stage biopharmaceutical company. Adrenomed’s mission is to rescue vascular integrity in order to save the lives of critically ill patients with limited treatment options. Founded in 2009 by a management team with decades of in-depth experience in sepsis and deep knowledge in diagnostics and drug development, the company’s lead product candidate enibarcimab (formerly adrecizumab) is a first-in-class non-blocking monoclonal antibody. Enibarcimab targets the vasoprotective peptide Adrenomedullin, an essential regulator of vascular integrity. Enibarcimab has successfully completed a biomarker-guided, double-blinded, placebo-controlled, randomized, multicenter proof-of-concept Phase II trial with 301 patients suffering from septic shock. For further information, please visit www.adrenomed.com and follow us on LinkedIn and Twitter. Contact Adrenomed AGMartina Kalle-Brune, Ph.D.phone: +49 (0)3302 207780bd@adrenomed.com Media Inquiries MC Services AGEva Bauer / Julia von Hummelphone: +49 (0)89 2102280adrenomed@mc-services.eu _________________ References: 1 Precision medicine focuses on the identification of therapeutic strategies that are effective for a group of patients based on similar unifying characteristics. Shah FA et al. Am J Respir Crit Care Med. 2021 Oct 15;204(8):891-901.2 World Sepsis Day Event 2023, Sept. 12, 2023, 18:00 h: “Precision medicine in new therapies for septic shock”, Joachim Struck, Adrenomed, Germany.3 11th Weimar Sepsis Update of the German Sepsis Society (GSS), Weimar (Germany), Sept. 6-8, 2023.4 11th Weimar Sepsis Update, Session 10 Immunmodulation – advances and adaptions 3, Lecture “Non-neutralizing adrenomedullin antibody”, Matthijs Kox, Nijmegen, Netherlands.5 11th Weimar Sepsis Update, Poster Session 2: Clinical Sepsis / COVID-19 Research – Therapy, Poster “Biomarker-guided treatment of septic shock with enibarcimab – cut-off selection to overcome patient heterogenicity”.6 https://doi.org/10.1186/s13054-021-03471-2.7 https://doi.org/10.3389/fmed.2022.1058235.8 Van Lier D., Knothe C., Struck J., Witte S., Pickkers P. “Biomarker-guided treatment of septic shock with enibarcimab – cut-off selection to overcome patient heterogenicity”, 11th Weimar Sepsis Update, Poster Session 2023.9 WSD Event 2023 — World Sepsis Day – September 13 (attendance is free of charge, sign-up here).