firibastat (QGC-001) / Quantum Genomics, Biolab Pharma, Orient Europharma - LARVOL DELTA

Identifying and exploiting molecular abnormalities of glioma vasculature (SNO 2025) - "Log-rank survival analysis revealed that firibastat delivered daily by oral gavage (500mg/kg) significantly extended survival (P = 0.04 vs. vehicle). These results support further study of ENPEP and other novel glioma vascular markers for potential applications as biomarkers and therapeutics."

Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Solid Tumor

Identifying and exploiting molecular abnormalities of glioma vasculature (WFNOS 2025) - "Log-rank survival analysis revealed that firibastat delivered daily by oral gavage (500mg/kg) significantly extended survival (P = 0.04 vs. vehicle). These results support further study of ENPEP and other novel glioma vascular markers for potential applications as biomarkers and therapeutics."

Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Solid Tumor

Orally active brain aminopeptidase A inhibitors on heart failure after myocardial infarction: Their development up to phase II clinical trials (PubMed, Biol Aujourdhui) - "These studies revealed the key role of brain AngIII in blood pressure regulation and cardiac function, highlighting brain aminopeptidase A, the enzyme responsible for brain AngIII formation, as a potential therapeutic target for treating arterial hypertension and myocardial infarction-induced heart failure. This led to the development of two, orally active, centrally acting, aminopeptidase A inhibitors, firibastat and QGC606, which were tested in various experimental models of arterial hypertension and heart failure, and demonstrated therapeutic potentialities up to phase 2 clinical trials in patients after myocardial infarction."

Journal • P2 data • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Myocardial Infarction • Pulmonary Arterial Hypertension

Renal biopsy in diabetic patients – 25 years of a single center experience (ERA 2025) - "Among them, 77 men and 54 women were present with a median age (range) 58 (20-74) years, duration of diabetes 9,0 (0-33) years, duration of nephropathy 8 (1-264) months, serum creatinine in time of RB 150 (56-1000) μmol/l, and proteinuria 7,8 (0,5-34) g/24 h. Nephrotic range proteinuria was present in 110 (84,0 %), hematuria in 79 (60,3 %) and hypertension in 118 (90,1 %) diabetics... Up to 62,4 % of diabetic patients indicated for RB had a nephropathy of non- diabetic origin (either alone or combined with DN). Clinical and laboratory data were of no value in differential diagnostics except for age, diabetes duration and diabetic retinopathy. Properly indicated RB is a valuable tool for the assessment of precise diagnosis, prognosis and focused therapy in these patients."

Biopsy • Clinical • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Diabetic Retinopathy • Glomerulonephritis • Hypertension • IgA Nephropathy • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Metabolic Disorders • Nephrology • Renal Disease • Retinal Disorders • Systemic Lupus Erythematosus • Vasculitis

Novel Antihypertensive Medications to Target the Renin-Angiotensin System: Mechanisms and Research. (PubMed, Rev Cardiovasc Med) - "The current overview presents the latest research findings on the mechanisms through which novel anti-hypertensive medications target the RAS. These include zilebesiran (targeting angiotensinogen), PRO20 (targeting the renin/(pro)renin/PRR axis), sacubitril/valsartan (targeting the renin/ACE/Ang II/AT1R axis), GSK2586881, Ang (1-7) and AVE0991 (targeting the renin/ACE2/Ang (1-7)/MasR axis), alamandine (targeting the alamandine/MrgD receptor axis), C21 and β-Pro7-Ang III (targeting the renin/ACE/Ang II/AT2R axis), EC33, and firibastat and NI956 (targeting brain Ang III)."

Journal • Review • Cardiovascular • CNS Disorders • Hypertension • Vascular Neurology

Rhizospheric microbiota of suppressive soil protect plants against Fusarium solani infection. (PubMed, Pest Manag Sci) - "Rhizospheric microbiota of suppressive soil protects plants against F. solani infection. Antagonistic microorganisms in suppressive soil inhibit pathogen growth and infection. Microbial consortia consisted of keystone taxa well control root rot disease. These findings help control Fusarium wilt."

Journal • Infectious Disease

New trials in resistant hypertension: mixed blessing stories. (PubMed, Clin Kidney J) - "In conclusion, managing RH remains challenging, and new compounds like firibastat, aprocitentan and baxdrostat have shown varied effectiveness. Further research is needed to improve our understanding and treatment of this condition."

Journal • Review • Cardiovascular • Hypertension

New approaches targeting the renin-angiotensin system: inhibition of brain aminopeptidase A, ACE2 ubiquitination, and angiotensinogen. (PubMed, Can J Cardiol) - "It raises the possibility that centrally acting amino peptidase A inhibitors (e.g., firibastat), preventing the conversion of angiotensin II to angiotensin III in the brain, might be particularly useful in African Americans and obese patients...Furthermore, antisense oligonucleotides or small interfering ribonucleic acids suppress hepatic angiotensinogen for weeks-months after one injection, and thus could potentially overcome adherence issues. Finally, interference with ACE2 ubiquitination is emerging as a future option for the treatment of neurogenic hypertension, given that ubiquitination-resistance might upregulate ACE2 activity."

Journal • Review • Cardiovascular • Hypertension • Obesity • Targeted Protein Degradation

Firibastat Versus Ramipril After Acute Mechanical Reperfusion of Anterior Myocardial Infarction: A Phase 2 Study. (PubMed, Am J Cardiovasc Drugs) - P2 | "Firibastat was not superior to ramipril for prevention of left ventricular dysfunction after first acute anterior MI, and their safety profiles were similar."

Clinical • Journal • P2 data • Cardiovascular • Heart Failure • Myocardial Infarction

Randomized Study of Extended Treatment With Firibastat in Treatment-Resistant Hypertension (REFRESH) (clinicaltrials.gov) - P3 | N=419 | Terminated | Sponsor: Quantum Genomics SA | N=750 ➔ 419 | Trial completion date: Jul 2024 ➔ Jan 2023 | Recruiting ➔ Terminated | Trial primary completion date: Sep 2023 ➔ Jan 2023; No Efficacy demonstrated inn the QGC001-3QG1 study

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Cardiovascular • Hypertension

LBS.09. Late-Breaking Science: Resistant HTN: A Pressure Cooker (AHA 2022) - "The landscape of treatment options for resistant hypertension is expanding rapidly with the most recent clinical trials to prove it. This session includes the top line results of the first-in-class aminopeptidase-A inhibitor, firibastat (FRESH), the use of the dual endothelin receptor antagonist aprocitentan to affect underlying mechanisms for resistant HTN (PRECISION), the safety and efficacy of baxdrostat, a highly selective aldosterone synthase inhibitor (BrigHTN), and the anticipated results of radiofrequency renal denervation (SPYRAL HTN-ON)."

Late-breaking abstract • Cardiovascular • Hypertension

Top-Line Results of The First-in-Class Aminopeptidase-A Inhibitor Firibastat in Treatment-Resistant Hypertension (FRESH) Study (AHA 2022) - P3 | "The primary and key secondary results of FRESH will be reported and discussed.Table. Baseline characteristicsTotal (n = 503 with available data)Male, n (%)293 (58.3)Age (years), mean (SD)63.3 (10.9)Obese (BMI >30 kg/m2), n (%)310 (61.6)Race, n (%)White409 (81.3)Black or African American69 (13.7)Asian6 (1.2)Other19 (3.8)Unattended digital SBP/DBP (mmHg), mean (SD)146.0 (12.2)/84.3 (11.8)"

Late-breaking abstract • Cardiovascular • Hypertension • Obesity

"FRESH study failed, firibastat was not effective for treatment resistant HTN. It was an APA inhibitor #aha22" (@u_shakur)

Effects of Firibastat, a First-in-Class Centrally Acting Aminopeptidase Inhibitor on Resistant Hypertension (KIDNEY WEEK 2022) - No abstract available

Cardiovascular • Hypertension

FRESH: Firibastat in Treatment-resistant Hypertension (clinicaltrials.gov) - P3 | N=515 | Completed | Sponsor: Quantum Genomics SA | Recruiting ➔ Completed | Trial completion date: Dec 2021 ➔ Sep 2022 | Trial primary completion date: Dec 2021 ➔ Aug 2022

Trial completion • Trial completion date • Trial primary completion date • Cardiovascular • Hypertension

Efficiency of reciprocating systems reciprocated at different angles in removing root-canals fillings with an MTA-type sealer: an Ex-vivo study. (PubMed, BMC Oral Health) - "The WOG and RB systems removed more MTA-type sealer-based root-canals fillings than the RM system. Lower counterclockwise reciprocating angles improve the retreatment ability of reciprocating systems, especially the WOG system and can reduce the time required for retreatment procedures."

Journal • Preclinical

New and developing pharmacotherapies for hypertension. (PubMed, Expert Rev Cardiovasc Ther) - "Sacubitril/valsartan may emerge as a potential first-line drug due to its superiority over renin angiotensin system inhibitors, and SGLT2 inhibitors can reduce BP in difficult-to-control hypertensive patients with type 2 diabetes. In addition, firibastat and aprocitentan may expand the therapeutic options for resistant hypertension by novel mechanism of actions. As gut dysbiosis not only leads to hypertension but also causes direct target organ damage, prebiotics and probiotics could represent a potential strategy to prevent or reduce the development of hypertension and to contribute to BP control."

Journal • Cardiovascular • Diabetes • Hypertension • Metabolic Disorders • Type 2 Diabetes Mellitus

PRE-RECORDED: EXOPEPTIDASES INVOLVED IN Aβ N-TERMINAL TRUNCATION: IDENTIFICATION, CONTRIBUTION TO AD NEUROPATHOLOGY AND BEHAVIORAL DEFECTS AND ALTERATIONS IN AD BRAINS (ADPD 2022) - "We demonstrate that the pharmacological blockade of APA and DPP4 with theirs selective inhibitors RB150 and sitagliptin restores the density of mature spines and significantly reduced filopodia-like processes in hippocampal organotypic slices cultures virally transduced with the Swedish mutated Aβ-precursor protein (βAPP). Importantly, we demonstrate that, concomitantly to the occurrence of Aβ pE3-42-positive plaques, APA and DPP4 activity are augmented at early Braak stages in sporadic AD brains. Overall, our data indicate that APA and DPP4 are two key exopeptidases involved in Aβ N-terminal truncation and suggest the potential benefit of targeting this proteolytic activity to interfere with Aβ-related AD pathology."

Alzheimer's Disease • CNS Disorders

Current Knowledge about the New Drug Firibastat in Arterial Hypertension. (PubMed, Int J Mol Sci) - "Results from studies show that firibastat is generally well tolerated and safe to use in hypertensive patients. The aim of this review is to investigate the current knowledge about firibastat in the treatment of hypertension."

Journal • Review • Cardiovascular • Hypertension • Hypotension • Pulmonary Arterial Hypertension

QGC606, a best-in-class orally active centrally acting aminopeptidase A inhibitor prodrug, for treating heart failure following myocardial infarction. (PubMed, Can J Cardiol) - "Chronic oral QGC606 administration in post-MI mice showed beneficial effects in improving cardiac function and reducing cardiac remodeling and fibrosis but, unlike ramipril, without lowering BP."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Myocardial Infarction • CTGF

Firibastat: a Novel Treatment for Hypertension. (PubMed, Curr Hypertens Rep) - "This review introduces firibastat as a new therapeutic class of treatment for hypertension focused on the renin angiotensin system in the brain. Early studies have shown a significant reduction in blood pressure with minimal side effects particularly in patients who are difficult to treat."

Journal • Review • Hypertension

European Society of Cardiology (ESC) Congress 2021 (August 27-30, 2021 - Virtual Meeting). (PubMed, Drugs Today (Barc)) - "The 2021 Congress of the European Society of Cardiology (ESC) was again held as a digital experience, providing poster and oral sessions highlighting the latest developments in cardiovascular science, including therapeutics for a range of related conditions and updates on ongoing trials, as well as guideline updates."

Journal • Cardiovascular

Randomized Study of Extended Treatment With Firibastat in Treatment-Resistant Hypertension (REFRESH) (clinicaltrials.gov) - P3; N=750; Recruiting; Sponsor: Quantum Genomics SA; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Hypertension

[VIRTUAL] QUORUM : Quantum Genomics Firibastat (QGC001) or Ramipril after Acute Myocardial Infarction for Prevention of Left Ventricular Dysfunction (ESC 2021) - No abstract available

Late-breaking abstract • Cardiovascular • Heart Failure • Myocardial Infarction

Randomized study of Extended treatment with Firibastat in treatment-RESistant Hypertension Estudio aleatorizado de tratameinto extendido con Firibastat para el tratamiento de Hipertensión RESistente (clinicaltrialsregister.eu) - P3; N=750; Ongoing; Sponsor: Quantum Genomics

New P3 trial • Cardiovascular • Hypertension