바이오스펙테이터

by Jongwon Jang

1. NOX Inhibitor Discovery Platform..Inhibition of ROS Production, Mechanism for Suppression of Inflammation · Fibrosis ... ’Pipeline for 5 Complications of Diabetes Mellitus', 2. ‘Aptamer+DRUG’. N

Aptabio challenges the global market with its innovative ‘First-in-Class’ new drug based on the two original platform technologies aiming at intractable diseases. Based on key technologies of the “NOX Inhibitor Discovery Platform” and the “Aptamer-drug conjugate, the Apta-DC Platform”, the five new candidate materials for complications of diabetes mellitus and the two new candidate materials for anticancer agents aiming at inveterate cancers, are being developed. Aptabio was jointly founded in July 2009 along with congenial professional specialists with over 20 years of experience in the field of development of new drugs.

◇Key Technology 1. NOX Inhibitor Discovery Platform, “Mechanism of Inhibition of Inflammation and Fibrosis by Preventing Excessive Production of ROS”

The first key technology is the “NOX Inhibitor Discovery Platform”. Through the inhibition of NOX (NADPH oxidase), which is involved in the creation of active oxygen (ROX), the oxidative stress is regulated to discover compounds suppressing inflammation and fibrosis. The NOX (NADPH oxidase), residing in the cell membrane, is the key source of ROS production stimulated by external stimuli. Aptabio employs a strategy utilizing the low molecular weight compound, which inhibits NOX for the simultaneous suppression of inflammation and fibrosis due to oxidative stress caused by complications of diabetes mellitus.

Aptabio secured the candidate compounds capable of inhibiting NOX through high throughput screening (HTS) technology and hNOX separation technology and developed the five pipelines for the treatment of complications of diabetes mellitus.

◇pan-NOX Inhibitor ‘APX115’..”Phase 1 Clinical Trial for Diabetic Nephropathy in Europe will be completed within this year"

The lead-off pipeline, ‘APX-115‘, started Phase 1 Clinical trial in Europe in May this year; the trial is scheduled to be completed within this year.

The “APX-115” of Aptabio is a pan-NOX inhibitor; it is an oral low molecular weight compound. He said, “... APX-115 got over all the target issues associated with drug toxicity. It exhibited better efficacy compared to existing NOX1/4 inhibition compound from an animal model; the broad safety margin and excellent in vivo pharmacokinetic behavior thereof were identified.”

APX-115 demonstrated a renal protective effect in an animal model of the diabetic mouse before it was employed in the clinical trial in Europe. The manifestation of NOX1, 2, 4 protein, as well as the oxidative stress, was reduced by the administration of APX-115. Excretion of albumin in urine, which is a problematic symptom of diabetic nephropathy, decreased while the level of creatinine was preserved; the glomerular filtration rate was also restored. Such effects appeared to be excellent compared to the effects of ‘GKT137831’, the dual inhibitor of NOX1/NOX4. Anti-inflammatory and anti-fibrosis effects were also identified through biomarkers.

President Lee added, “... APX-115 exhibits a new mechanism of inhibiting pan-NOX and has demonstrated sufficient efficacy in the animal test. The proof of concept (POC) of the competing NOX1/4 inhibitor was already successfully demonstrated in a clinical trial. Though it did not demonstrate significant excellence in the Phase 2 Clinical Trial, the APX-115 rendered better renal protective effect compared to other competing drugs in the animal model. Thus, we are anticipating positive consequences from the clinical trial.” Apparently, APX-115 is currently employed in the Phase 1 Clinical Trial, which is in progress with 88 healthy subjects in Europe.

Aptabio also develops candidate materials for new drugs such as a new inhibitor having NOX selectivity, ‘APX-5278’, the therapeutic agent for arteriosclerosis, ‘APX-1004’, the therapeutic agent for retinopathy, and ‘APX-311’, the therapeutic agent for NASH etc.

◇Key Technology 2. 'Apta-DC'. Development of New Drugs for Pancreatic Cancer and Blood Cancer

The second key technology is the “Aptamer-drug conjugate, Apta-DC”. Aptamer functions similarly to an antibody, hence referred to as “Chemical Antibody” and embodied in a new combination with the existing drug.

Aptabio derived two pipelines employing Apta-DC technology. “Apta-12” takes a form of Nucleolin targeting Aptamer, fused into the secondary therapeutic agent for pancreatic cancer. “Apta-16” is a candidate material for the therapeutic agent to cure acute myelocytic leukemia (AML) for which the Nucleolin targeting Aptamer is combined with the primary therapeutic agent for treatment of blood cancer. Transference of all pertinent technologies is completed.

Apta-12 is scheduled to complete non-clinical trial next year, whereas Apta-16 will be entering into Phase 1 Clinical Trial next year.

President Lee expressed his aspiration, “... Aptamer intends to be a global leader through the development of “First-in-Class” therapeutic agents for intractable diseases.”