Harbour BioMed Gets FDA Nod to Start US Trials of 2 Immunotherapies

The U.S. Food and Drug Administration (FDA) has approved Harbour BioMed’s investigational new drug applications to initiate U.S. clinical trials testing two of its immunotherapy candidates — HBM9167 and HBM4003 — in several cancers.

HBM9167 and HBM4003 are immune checkpoint inhibitors designed to boost the body’s anti-tumor responses by blocking the proteins that cancer cells use to evade immune system attack. HBM9167 targets the PD-L1 protein on cancer cells, and HBM4003 targets the CTLA-4 protein on T-cells (immune cells with the ability to fight tumors).

With these approvals, Harbour BioMed can move forward with its plans for a Phase 2 clinical trial evaluating HBM9167 in people with metastatic or relapsed nasopharyngeal cancer, and a Phase 1 clinical study of HBM4003 in people with advanced solid cancers.

The FDA also granted orphan drug designation to HBM9167 as a treatment for nasopharyngeal cancer. This designation is intended to provide regulatory support and financial benefits to accelerate HBM9167’s clinical development and review, and to ensure a seven-year period of marketing exclusivity in the U.S. upon regulatory approval.

“Nasopharyngeal cancer is a tumor type for which patients remain in need of effective treatment options,” Jingsong Wang, MD, PhD, Harbour BioMed’s founder, chairman, and CEO, said in a press release.

“We were also able to work with the FDA to enable a direct entry into a Phase 2 clinical study in patients with metastatic or recurrent disease,” he added.

In 2018, Harbour BioMed signed a partnership and licensing agreement with Kelun-Biotech — HBM9167’s developer — for exclusive rights to develop and commercialize HBM9167 worldwide, except in Greater China.

To date, Kelun-Biotech has evaluated the safety and effectiveness of HBM9167 in Phase 1 and ongoing Phase 2 clinical trials in China, involving more than 300 individuals, including those with nasopharyngeal cancer. Preliminary data from these trials have highlighted HBM9167’s tolerable safety profile.

HBM4003 — Harbour BioMed’s next-generation, fully-human antibody against CTLA-4 — was developed using the company’s heavy chain only (HCAb) technology, that results in smaller, stable, and highly-specific antibodies.

Pre-clinical studies have shown that HBM4003 boosts anti-tumor immune responses through two mechanisms: the binding and block of CTLA-4 in T-cells — rescuing their ability to kill cancer cells — and the elimination of immunosuppressive regulatory T-cells in tumor tissues.

Notably, potent anti-tumor activity was achieved with much lower exposure to HBM4003 than with other anti-CTLA-4 antibodies, suggesting a potentially significant advantage in its therapeutic profile.

According to the company, HBM4003’s new and distinct mechanism of action can potentially improve its effectiveness while significantly lowering its toxicity.

The future U.S. Phase 1 trial will evaluate HBM4003’s safety, tolerability, pharmacokinetics (uptake, distribution, and elimination in the body), and anti-tumor activity in patients with advanced solid tumors.

It follows an ongoing pilot trial in Australia (NCT04135261) — the first clinical study of a fully human antibody based on HCAb technology — initiated in November 2019.

The approval of HBM4003’s investigational new drug application is an important next step in Harbour BioMed’s global program to develop “this exciting molecule,” Wang said in a separate press release.

“HBM4003 is the first in a portfolio of mono- and bi-specific antibodies based on our patented, heavy chain only (HCAb) technology against various immuno-oncology and immunology targets that are advancing toward clinical trials,” he said.