FDA Grants Orphan Drug Designation to PT886 for Pancreatic Cancer

PT886 was granted orphan drug designation by the FDA for the treatment of patients with pancreatic cancer.

The FDA has granted orphan drug designation to PT886 for the treatment of patients with pancreatic cancer, according to Phanes Therapeutics, Inc.1

Earlier this month, PT886 received an investigational new drug (IND) application by the FDA.2 Additionally, orphan drug designation was granted by the FDA to another one of the company's products, PT217, for the treatment of patients with small cell lung cancer, and an IND clearance for PT199.

"PT886 has the potential to be a transformative treatment option for pancreatic cancer patients whose current standard of care is severely limited," said Ming Wang, PhD, MBA, founder and chief executive officer of Phanes Therapeutics, in a press release. "This orphan drug designation comes in the same month with our recent IND clearance for PT886, which we are rapidly progressing into the clinic. These important milestones the company has achieved in Q2 this year follow the March IND clearance for PT199, an anti-CD73 monoclonal antibody for the treatment of multiple solid tumors."

PT886 is a first-in-class, bispecific antibody which works to target claudin 18.2 (CLDN18.2) and cluster of differentiation 47 (CD47). The drug is being developed for use in patients with pancreatic, gastric, and gastroesophageal cancers.

The goal of the bispecific antibody is to block the CD47-SIRPα interaction, stimulate phagocytosis of tumor cells by macrophages, and deliver robust effects mediated by the functional Fc of the bispecific antibody.

Findings presented at the 2022 American Association for Cancer Research meeting showed PT886 to have high affinity monovalent binding to cell surface CLDN18.2 and low affinity monovalent binding to cell surface CD47.3 By doing so, PT886 can preferentially bind to tumor cells which overexpress CLDN18.2 and CD47, and reduce its binding to normal cells exclusively express CD47.

However, PT886 exhibits higher activity to tumor cells expressing CLDN18.2 and close to no activity toward normal cells that do not express CLDN18.2. This was shown in a phagocytosis assay as PT886 stimulates stronger phagocytosis in the presence of CLDN18.2 binding in vitro.

Along with targeting CLDN18.2 and CD47, PT886 has a fully functional Fc to directly recruit the tumor cell killing activities of NK cells and macrophages. The anti-tumor activity of PT886 was potent and demonstrated in vivo in a pancreatic cancer xenograft model. Here, treatment with PT886 resulted in a complete tumor clearance at doses as low as 1 mg/kg.

In NHP studies, PT886 also demonstrated a good safety profile. These data support the phase 1 clinical trial of the bispecific antibody planned for 2022.

  1. Phanes therapeutics' PT886 granted orphan drug designation for the treatment of pancreatic cancer by the FDA. News release. Phanes Therapeutics. June 30, 2022. Accessed July 1, 2022. https://prn.to/3OFsbBE
  2. Phanes Therapeutics announces FDA IND clearance for PT886, an anti-claudin18.2/anti-CD47 bispecific antibody being developed for patients with gastric, gastroesophageal junction, and pancreatic cancers. News release. Phanes Therapeutics, Inc. June 15, 2022. Accessed July 1, 2022. https://prn.to/3ntsCD9
  3. Li J, Jia H, Ramsey E, et al. PT886, an anti-claudin18.2/anti-CD47 bispecific antibody constructed with the PACbody࣪ and SPECpair࣪ technology platforms, exhibits robust anti-tumor activity in a pancreatic cancer xenograft model. Presented at: 2022 AACR Annual Meeting; April 8-13, 2022; New Orleans, LA. Abstract 4260.