APL-1202 is an innovative oncology drug developed by Asieris Pharmaceuticals over the past decade after in-licensing the patented technology from Johns Hopkins University in the United States. As the first-in-class oral and reversible methionine aminopeptidase 2 (MetAP2) inhibitor to enter a pivotal/phase III clinical trial, APL-1202 is the world’s first oral targeted therapy for non-muscle invasive bladder cancer (NMIBC) under a pivotal/phase III clinical trial. At the same time, APL-1202 is also being developed for preoperative neoadjuvant treatment of muscle invasive bladder cancer (MIBC).

The APL-1202 project was granted support by National Major New Drug Innovation Programs for the 12th Five-year Plan period and 13th Five-year Plan period in 2015 and 2018, respectively.

Unmet Market Demand

Bladder cancer is a malignant tumor that originates from the urothelium in the bladder tissue. It is caused by uncontrolled growth of abnormal cells in the bladder’s inner lining. It is one of the most common malignant tumors in the urinary system. Based on whether the tumor infiltrates the detrusor muscle, bladder cancer can be divided into non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). The number of new patients with bladder cancer worldwide rose from 506,000 in 2015 to 565,000 in 2019, with a compound annual growth rate of 2.8%. In China, the number of new patients with bladder cancer was 85,000 in 2019, and it is expected to increase to 99,000 by 2024, with a compound annual growth rate of 3.2% during the period. Among the new patients, patients with NMIBC will account for about 75%.

The standard of care for NMIBC is transurethral resection of bladder tumor (TURBT). Because of high tumor recurrence rate after TURBT, intravesical chemo- or immun0-therapies are required after the procedure. However, these therapies have significant limitations. Intravesical instillation therapy is an invasive and painful procedure, which often causes 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 experiencing dysuria, urinary frequency, and hematuria. For high-risk NMIBC patients who have failed intravesical therapies, radical cystectomy is the standard treatment. However, such a surgery lowers a patient’s quality of life tremendously as it requires permanent use of an external container for storing urine.

Therefore, NMIBC patients have significant unmet clinical needs in multiple aspects:

First, after intravesical instillation therapies fail, there is no good second-line treatment option, and radical cystectomy is the only choice;

Second, the safety of intravesical instillation therapies was unsatisfactory. With intravesical chemotherapy and BCG bladder instillation, 30%-50% of patients tend to suffer from irritation to the urethra, and 20% may have systemic adverse reactions;

Third, intravesical instillation is an invasive approach, and patient compliance is poor;

Therefore, patients urgently need new therapeutic drugs with new anti-tumor mechanism, significant efficacy, good safety profile, and convenient administration.

Currently, no oral drug for the treatment of NMIBC is available globally.

Significant Clinical Value

The Phase II clinical trial data showed that the efficacy of APL-1202 is better than intravesical chemotherapy with a significantly superior safety profile in humans. The clinical value of APL-1202 is summarized as follows:

Remarkable therapeutic effect on high-risk NMIBC patients

As a new-generation reversible MetAP2 inhibitor, APL-1202 inhibits both tumor cell proliferation and tumor angiogenesis. Compared with intravesical chemotherapy, APL-1202’s efficacy was superior in patients who have previously failed intravesical chemotherapy, helping some high-risk patients avoid radical cystectomy;

Superior safety profile in humans

There have been no drug-related serious adverse events to date, with major side effects limited to gastrointestinal discomfort at an incidence of <10%. Such a safety profile is significantly superior to those of BCG and intravesical chemotherapy drugs (such as MMC);

Oral administration

Oral administration is convenient, painless, and safe, without causing pain or injury to the urethra. It has obvious advantages in terms of patient compliance.