APL-1202
Product Pipeline
Therapeutic Areas
R&D Strategy
Therapeutic Areas
Asieris currently focuses on and welcomes collaborations in the following therapeutic areas.

Bladder cancer and other genitourinary tumors

  • Bladder Cancer ranks 9th in the most common malignant tumors, with nearly 430,000 new cases and over 165,000 death in 2012. In China, the numbers of new BC patients and death in 2012 were 71,000 and 25,000 respectively. In recent years, the incidence has been increasing with a compounded annual growth rate near 5%.

    Non-muscle invasive bladder cancer (NMIBC, tumors confined to the bladder mucosa and submucosa layers without invasion to the muscle layer) accounts for 70-80% of newly diagnosed bladder cancer patients.

    The most common treatment of non-muscle invasive bladder cancer is Trans-Urethral Resection of Bladder Tumor (TURBT). Because of high recurrence (60-70%) after TURBT surgery, intravesical chemotherapy or immunotherapy drugs are usually required after the surgery. However, intravesical therapy is quite painful and chemotherapy may result in drug resistance. Therefore, there is an urgent need for drugs with novel mechanism and treatment regimen.

    In addition to bladder cancer, urogenital cancers include penile cancer, testicular cancer, male urethral carcinoma, prostate cancer, female urethral carcinoma, tumors of the renal pelvis, ureter tumor, renal cancer, prostatic sarcoma, urogenital malignant tumor, kidney tumor, carcinoma of the renal pelvis, etc. Bladder cancer is most common in China while prostate cancer most common in western countries, though the incidence of the later is increasing significantly in China recently. In recent years, the incidence and mortality of all urogenital tumors have showed an upward trend.

    Asieris' APL-1202 is the world's first oral metaP2 enzyme inhibitor and its efficacy and safety for the treatment of bladder cancer has been demonstrated in a Phase II trial. It is expected to fill the void of new drug for bladder cancer treatment for the past 20 years. In addition, APL-1301, an optimized derivative of APL – 1202, has shown promising efficacy for prostate cancer treatment in preclinical studies.


Tumor immunotherapy

  • The concept of inhibiting tumor growth by immune system was introduced in 1890s, when William B. Coley observed bacterial infection was often accompanied by tumor remission. He suggested that postoperative infection could generate immune response in patients to control tumor growth. Subsequently, Coley reported the successful use of the filtered mixture of bacteria and bacterial lysates to treat cancer. Although research in this area was slow in the 20th century, enormous progress has been made in the past two decades. PD-1 and its ligand PD-L1, and cytotoxic T lymphocyte-associated
    protein 4 (CTLA-4), are the most notable of many protein targets. Clinical results have demonstrated that monoclonal antibodies (such as Opdivo and Keytruda, etc.) for these targets activate the patient's immune system to target and remove cancer cells.

    These findings have achieved unprecedented success in certain cancer therapies and have established clinical guidelines for cancer immunotherapy. However, clinical studies have also showed that a large number of tumors could not be treated by PD-1 and CTLA-4 targeted therapies; therefore new targets and mechanisms of action must be explored.

    Asieris has established an independent drug development platform to screen new immuno-oncology drugs. Currently selected candidates have been proved to showed high response rate in those patients who have failed chemotherapy, and some candidates have the advantage of crossing the blood-brain barrier. Asieris expects to submit US Investigational New Drug (IND) and initiate international clinical research in 2018.

     

Multi drug resistant infection

  • Currently, the lack of antibiotics against antimicrobial resistance (AMR) has become a daunting challenge worldwide. In Europe and the United States, AMR is accountable for approximately 50,000 deaths annually.  In recent years, many cases of death related to untreatable "superbug" infections have been reported. The situation of AMR is more severe in China. The percentage of drug-resistant bacterial strains detected is very high in nationwide survey. According to the "National Bacterial Resistance Surveillance Report 2015", the detected rates of Methicillin Resistant Staphylococcus Aureus (MRSA) and Methicillin Resistant Coagulase Negative Staphylococci (MRCNS) were 35.8% and 79.4%,
    respectively. The resistance rate of Escherichia coli to third-generation cephalosporin was 59.0% and 53.5% for quinolones. The resistance rate of Klebsiella pneumoniae to third-generation cephalosporins was 36.5%. Escherichia coli and Klebsiella pneumoniae resistant to the last line of antibiotics carbapenems drug were 1.9% and 7.6%, respectively. Therefore, there is an urgent need for antibiotics with novel mechanism of action to battle multi-drug resistance infections.
    There has been limited success globally in the development of antibiotics with novel antimicrobial mechanism of action. Since the 1960s, only three new classes of antibiotics have been introduced into the market. Over the past decade, despite many governments in the world have increased supports for new antibiotic research and development, there has been no significant breakthrough to date. In the United States, for example, as of September 2016, there were about 40 drugs (including two pending for approval) in the antibiotic development pipeline. Among them, only five molecules were representative of new targets (i.e., first-in-class drugs), and they were in the early
    clinical development stage. There are thirty antibiotic candidates currently under registration in China; however, all of them belong to the established antibiotic classes. Development of antibiotics with novel mechanism of action will not only meet the urgent need for new antibiotics, but also provide technical platform for research and discovery of next generation antibiotics.

    Studies have shown that methionine aminopeptidase (metaP) is responsible for the cleavage of the initiator methionine from newly synthesized proteins. Knockout of metaP1 enzyme gene in S. typhimurium and E. coli can lead to bacterial death or growth inhibition, suggesting that metaP1 represent a new enzymatic target for antibacterial drugs. Asieris has designed and synthesized a series of metaP inhibitors. Through antibacterial activity screening, APL-1501 has been identified as our lead candidate, which is currently under preclinical development, including pharmacodynamics, pharmacokinetics and toxicology evaluation.