apocynin/paeonol (AKL-4) / AKL Therapeutics, Nordic Biosci - LARVOL DELTA

APPA (APOCYNIN AND PAEONOL) REDUCES THE SENESCENCE IN HUMAN ARTICULAR CHONDROCYTES (EULAR 2024) - "A combination between Etoposide (5µM or 20 µM respectively) and 10 ng/ml oncostatin –OSM- (Eto+OSM) was used to induce cellular senescence. APPA reduced the number of senescent cells and increased the number of cells without causing apoptosis, which indicates that APPA may be senomorphic. The data indicated that both components of APPA need to be present to fully obtain these effects."

Immunology • Osteoarthritis • Pain • Rheumatology • ANXA5 • CDKN1A

New data by AKL Therapeutics suggests investigational oral osteoarthritis drug APPA may have a promising senotherapeutic effect with potential in other diseases of ageing (BioSpace) - "New data presented at the 2023 Osteoarthritis Research Society International (OARSI) World Congress in Denver, Colorado (March 17th-20th) suggest that AKL Therapeutics' investigational oral osteoarthritis (OA) drug APPA may have a dual effect on senescence – a process in which cells stop dividing as a natural consequence of ageing. Senescence plays a major role in the development of many age-related diseases, including osteoarthritis (OA)....It found that APPA appears to not only reduce the number of harmful senescent cells which build up in the cartilage causing inflammation (a 'senolytic' effect), but could also potentially reverse the senescence process so cells can function normally again (a 'senomorphic' effect). The study found that APPA significantly reduced the number of senescent cells (p=0.020) and increased the number of cells - indicated by the number of nuclei (p=0.062) - in the chondrocyte cell line in which senescence had been induced."

Preclinical • CNS Disorders • Osteoarthritis • Pain

A Trial of APPA in the Treatment of Knee Osteoarthritis (clinicaltrials.gov) - P2; N=152; Completed; Sponsor: AKL Research and Development; Recruiting ➔ Completed; Trial primary completion date: Mar 2021 ➔ Sep 2021

Clinical • Trial completion • Trial primary completion date • Immunology • Osteoarthritis • Pain • Rheumatology

New data presented at Virtual EULAR 2021 Congress by AKL Research and Development demonstrate its investigational osteoarthritis drug APPA reduces senescence and reactive oxygen species production (PRNewswire) - "AKL Research and Development (AKLRD)...today unveils new data at the Virtual European Congress of Rheumatology (EULAR) 2021 (June 2-5). Findings from the study indicate its investigational oral osteoarthritis (OA) drug APPA can reduce reactive oxygen species (ROS) production and senescence of human articular chondrocytes, both indicators associated with OA pathogenesis....APPA, which is currently in a Phase II clinical trial with results expected in July 2021, is a leading oral new chemical entity (NCE) in the biopharma pipeline that targets multiple signalling pathways to deliver both pain relief and disease modification in OA."

P2 data • Osteoarthritis • Pain

New data presented at OARSI 2021 Virtual World Congress by AKL Research and Development advances understanding of biological effects of its investigational osteoarthritis drug APPA to protect against joint damage (PRNewswire) - "AKL Research and Development (AKLRD)...today unveils new data at the Osteoarthritis Research Society International (OARSI) Virtual World Congress (April 29 – May 1) indicating its investigational oral osteoarthritis (OA) drug APPA can modulate cellular function, reduce inflammation and inhibit bone resorption associated with joint degradation caused by the disease....Results from one study, conducted by Nordic Biosciences using ex vivo tissue explants, found that APPA, an NRf2 and NFkB regulator...Results from a second study...showed that APPA significantly reduces the gene expression induced by inflammatory cytokines IL-1β of IL-8, TNF-α and cartilaginous degrading enzymes MMP-13 and MMP-3."

Preclinical • CNS Disorders • Osteoarthritis • Pain

AKL Research & Development's novel osteoarthritis medicine APPA begins Phase II trial with partner Nordic Bioscience Clinical Development (PRNewswire) - "A novel, oral osteoarthritis (OA) medicine being developed by AKL Research and Development (AKLRD) has recruited its first patient into its Phase II human clinical trial being conducted by its partner Nordic Bioscience Clinical Development (NBCD), following the successful completion of Phase I....The study is a placebo-controlled, double-blind, randomized trial evaluating the efficacy and safety of oral APPA in 150 patients with osteoarthritis of the knee and is being conducted by NBCD at three clinical research centres (Sanos Clinic) in Denmark, with results expected mid-2021....A National Institute for Health Research (NIHR)-approved Phase I study was successfully completed earlier this year...The full study report will be available shortly."

Enrollment status • P1 data • P2 data • CNS Disorders • Osteoarthritis • Pain

Phase update (PRNewswire) - P1➔P2, Osteoarthritis, Pain

Phase shift • Osteoarthritis • Pain

Osteoarthritis: New trial drug has powerful anti-inflammatory effect (Medical News Today) - "Interestingly, some of the cytokines that APPA regulates also play a role in the cytokine storms that researchers have observed in COVID-19 patients....Preventing such cytokine storms in COVID-19 could become an important part of the treatment regimen. The selective approach of a drug such as APPA, which blocks the harmful effects of an overactive immune system without stopping its ability to fight infection, could be a fruitful area of research once clinical trials on this new drug are complete."

Clinical • Cytokine storm • Infectious Disease • Novel Coronavirus Disease

AKL Research & Development and Nordic Bioscience collaborate to take novel osteoarthritis medicine to phase II (PRNewswire) - "AKL Research & Development (AKLRD) and Nordic Bioscience Clinical Development, today announce a risk-share agreement to assess the efficacy of a novel, oral medicine, APPA, in a phase II trial of Osteoarthritis (OA)....The partnership will assess the effectiveness of APPA both in relieving OA pain and in slowing the destruction of cartilage, which has already been demonstrated in animal studies....APPA, developed by AKLRD, is currently undergoing a Phase I trial and is scheduled to finish this summer. The Phase II trial will begin shortly after in Copenhagen, with results expected mid-2020."

Licensing / partnership • New P2 trial • P1 data