FDA Clears IND Application for Phase I/II Study of OBI-999 in Epithelial Cancer

Earlier this week the U.S. Food and Drug Administration (FDA) cleared an investigational new drug (IND) application for OBI-999 to conduct a Phase I/II study of its antibody-drug conjugate therapy targeting Globo H, a glycolipid antigen. The drug is being developed by Taiwan based OBI Pharma.

OBI-999 is a novel first-in-class antibody-drug conjugate with a proprietary Thiobridge® linker technology that provides a consistent drug-to-antibody ratio (DAR) for cancer treatment that is based on Globo H, an antigen expressed in up to 15 epithelial cancers.

The surfaces of cancer cells frequently express specific types of carbohydrate antigens not necessarily found normal, healthy, cells. If they do express these antigen, they generally express them to a lesser extent. This makes antigens, like Globo H, a potential target  for stimulating an active immune response against tumor.

In 1983 Hakomori and colleagues first isolated Globo H as a glycolipid with a ceramide backbone from the human breast cancer cell line MCF-7. It is highly expressed in various types of cancer, such as breast, prostate, and lung. Hence, Globo H was recognized as a potential target for the development of a novel immunotherapeutic treatment against various cancers.

Globo H is a complex hexasaccharide. Lack of an efficient synthesis methods has hindered clinical development. This changed with the development of the One-Pot Synthesis or OPopS™ platform by Professor Chi-Huey Wong, Distinguished Research Fellow and President of Academia Sinica, during his tenure at The Scripps Research Institute (TSRI).

MabPlex
ADC Bio
Lonza
 

Targeted drug delivery
By releasing a small molecule chemotherapeutic drug through the specificity of the antibody, the investigational agent directly deploys cytotoxic therapy at the targeted cancer cells. This Globo H targeting antibody, OBI-888, is currently in a Phase I/II clinical trial to test its safety and efficacy as an immune-oncology therapy.

In pre-clinical xenograft animal models in multiple tumor types (pancreatic, lung, gastric, and breast), OBI-999 has demonstrated profound tumor shrinkage at various doses. In pre-clinical single and repeated dose toxicology studies, OBI-999 was well-tolerated, and achieved a favorable safety margin which warrants further clinical development. OBI Pharma owns global rights to OBI-999.

OBI plans to enroll patients with advanced solid tumors including pancreatic, gastric, colorectal and esophageal cancers in a number of clinical trials.

“These clinical trial intends to verify the safety and preliminary efficacy profile of OBI-999, a novel first-in-class antibody-drug conjugate that selectively targets Globo H. We are delighted to conduct this first-in-human clinical trial at the University of Texas M.D. Anderson Cancer Center, one of America’s leading academic oncology research institutions,” noted Tillman Pearce, MD., OBI Pharma’s Chief Medical Advisor, who has more than twenty-five years of international experience in both large pharma and small biotech affording him experience in the pre- and post-marketing development of therapeutics in the areas of solid tumors, and hematologic malignancies.

“We strive to develop and validate our novel anti-Globo H immuno-oncology pipeline to fulfill unmet medical needs of cancer patients,” added Michael Chang, Ph.D., OBI Pharma Chairman and Chief Executive Officer.

OBI Pharma, established in 2002, develops and licenses novel therapeutic agents for unmet medical needs against various promising cancer targets. In addition to OBI-999 the company is also developing OBI-998, an antibody-drug conjugate (ADC) targeting stage-specific embryonic antigen 4 (SSEA4), a cell surface antigen expressed along with SSEA3, TRA-1-60 associated highly expressed in multiple cancers.

Compared to conventional chemotherapeutic drugs, the company’s SSEA-4-specific monoclonal antibody targets tumors using site-specific release of cytotoxic payload at the targeted sites, which directly shrinks or eradicate tumors, while potentially reducing damage to normal cells and, lowering the chance of side effects.