Asieris’ APL-1202 has been awarded as recipient of the “National 12th & 13th Five-Year Major New Drug Innovation Program” in China. Asieris licensed the global rights of this technology from the Johns Hopkins University, and evaluate independently its potential as a therapy for the treatment of NMIBC. APL-1202 is the first and only oral methionine aminopeptidase Ⅱ type (MetAP2) inhibitor currently under clinical development in the world. It has novel mechanisms of action of inhibiting both tumor cell growth and angiogenesis.

We have completed a single arm, open-label, multi-center Phase II clinical trial for the treatment of high risk non-muscle-invasive bladder cancer patients who have failed intravesical chemotherapy or BCG. The Phase II data suggested that the efficacy of APL-1202 is better than intravesical chemotherapywith a significantly superior human safety profile. The convenient oral route of administration is considered a breakthrough in the field of bladder cancer treatment.

We are currently conducting a multi-center, randomized, placebo-controlled phase III clinical study of APL-1202 in China.

Unmet Medical Needs

The standard of care for NMIBC is Trans-Urethral Resection of Bladder Tumor (TURBT). Because of high tumor recurrence rate after TURBT, intravesical chemo- or immune-therapies are required after the procedure. However, these therapies have significant limitations.

Intravesical instillation therapy is an invasive and painful procedure, often causing bleeding and inflammation to a patient’s urinary tract. Due to a short drug exposure time (1-2 hours each time, once a week), the efficacy is poor, with 30-50% of patients experience dysuria, urinary frequency , and hematuria.

For high-risk NMIBC patients who have failed intravesical therapies, radical Cystectomy is the standard treatment. However, such surgery lowers a patient’s quality of life tremendously as it requires permanent use of an external container for storing urine.

There has been no new drug approved for the treatment of NMIBC over the past two decades worldwide, nor under clinical development in China.

Significant Clinical Value

The Phase II data has shown that APL-1202 is superior to the current intravesical chemotherapy and with an excellent human safety profile. The clinical value of APL-1202 is summarized as follows:

● Clinical efficacy likely attributable to a novel Moa

As a new generation of reversible MetAP2 inhibitor, APL-1202 inhibits both tumor cell proliferation and tumor angiogenesis.

APL-1202’s efficacy in reducing recurrence rates and extending recurrence-free survival appears to be superior to chemotherapies, helping some high-risk patients avoid radicalcystectomy.

● Superior human safety

There have been no drug-related serious adverse events to date, with major side effects limited to gastrointestinal discomfort at an incidence of <10%.

● Convenient oral administration

The treatment regimen with APL-1202 is convenient and safe, without causing pain or injury to the urethra.

Advances in Clinical Research

Summary of Phase II Study

APL-1202 has been evaluated in a single-arm, open-label, and multi-center Phase II clinical study in Chinafor the treatment of high-risk NMIBC patients who have failed intravesical chemo or BCG therapy. This clinical trial was led by Fudan University Shanghai Cancer Center and the Principal Investigator was Professor Dingwei Ye, who is the elected Chairman of the Genitourinary Tumor Committee of theChinese Anti-Cancer Association, the Vice President of Shanghai Cancer Center,  and the Chair of the Urology Department of Fudan University. Results from this Phase II study have shown promising efficacy and safety for APL-1202 and were well recognized by the participating doctors and patients.

APL-1202 is superior to the current repeat intravesical chemotherapy, with efficacy comparable or superior to first time chemotherapy. In high-risk NMIBC patients (EORTC risk score≥ 10) who have failed intravesical chemotherapy, there was a significant reduction in 1-year recurrence rate after APL-1202 treatment.

Results from this trial also indicates that the drug has a superior safety profile, with gastrointestinal irritation being the primary side effect at an incidence of less than 10%. Such safety profile is significantly superior to those of intravesical chemotherapy drugs (such as MMC) and immunotherapy drugs (such as BCG) currently used in clinical treatment.

Overview of Phase III Pivotal Trial

Protocol Title: “APL-1202 in combination with intravesical instillation chemotherapy versus intravesical instillation chemotherapy alone for the treatment of recurrent non-muscle invasive urethral bladder cancer patients”.

Shanghai Fudan Cancer Center and Peking Union Medical College Hospital are leading this trial, with approximately 40 to 50 participating hospitals nationwide. The co-Principal Investigators are Professor Dingwei Ye of Shanghai Fudan Cancer Center and Professor Hanzhong Li of Peking Union Medical College Hospital.

Currently this trial is near completion of enrollment. We thank the participating patients and their relatives, the investigators and their stuff for their support to this clinical trial.