FDA Grants Orphan Drug Designation to PT217 for SCLC

The FDA has granted an orphan drug designation to PT217 for use as a potential therapeutic option for patients with small cell lung cancer.

The FDA has granted an orphan drug designation to PT217 for use as a potential therapeutic option for patients with small cell lung cancer (SCLC), according to an announcement from Phanes Therapeutics.1

A first-in-class bispecific antibody, PT217 is designed to target DLL3 and CD47 in patients with SCLC and other neuroendocrine cancers.

“PT217 has the potential to be a transformative treatment option for SCLC patients whose initial response to chemotherapy is short-lived and inevitably becomes resistant to chemotherapeutic agents,” Ming Wang, PhD, MBA, chief executive officer of Phanes Therapeutics, stated in a press release. “We have built a strong pipeline in immuno-oncology by leveraging our proprietary technology platforms and expect to file an [investigational new drug application] for PT217 by the third quarter of this year.”

Both DLL3 and CD47 are clinically validated targets and are highly expressed in SCLC. PT217 was designed to mediate robust antibody-dependent cellular cytotoxicity for tumor cells by NK cells and block the interaction of CD47 with SIRPα.2 CD47 expression is typically significantly higher than DLL3 on cancer cells, and in preclinical models, PT217 demonstrated increased total selective binding when compared with anti-DLL3 monoclonal antibodies.

Additionally, PT217 stimulated antibody-dependent cellular phagocytosis of tumor cells by macrophage. Initial results suggest that the macrophages eventually engulf the tumor cells targeted by NK cells.

With elevated phagocytosis of the tumor cells by macrophages and dendritic cells, investigators expect to see an increase in the presentation of tumor neoantigens. This increase would then lead to T cell-mediated killing of tumor cells, irrespective of DLL3 expression.

In preclinical mouse xenograft models, PT217 displayed robust rumor suppression activity, and non-human primate (NHP) and rat GLP toxicity studies supported a first-in-human clinical trial. At PT217 doses of 3 mg/kg, 10 mg/kg, and 30 mg/kg , investigators found that red blood cell, hemoglobin, white blood cell, and reticulocyte counts remained within normal range during the first21 days of treatment in an NHP model.

In a presentation at the 2022 AACR Annual Meeting, investigators proposed the structure of a phase 1 dose-escalation trial to investigate PT217 in patients with DLL3-positive SCLC, large cell neuroendocrine carcinoma, and neuroendocrine prostate cancer. The dose escalation–guided 3+3 design would evaluate PT217 administered in weekly doses at 5 different dose levels.

The orphan drug designation for PT217 follows 2 investigation new drug applications clearances for Phanes Therapeutics, including an anti-CD73 monoclonal antibody, PT199, and an anti-Claudin 18.2/anti-CD47 bispecific antibody, PT886.


  1. Phanes Therapeutics' PT217 receives orphan drug designation for small cell lung cancer from the FDA. News release. Phanes Therapeutics. June 21, 2022. Accessed June 21, 2022. https://prn.to/3n5FsXP
  2. Jia H, Fang D, Lobsinger M, et al. PT217, an anti-DLL3/anti-CD47 bispecific antibody, exhibits anti-tumor activity through novel mechanisms of action. Presented at: 2022 AACR Annual Meeting; April 8-13, 2022; New Orleans, LA. Abstract 2908