▎WuXi AppTec Content Team Report

On April 8, Phanes announced that the U.S. FDA grantedDLL3/CD47 Bispecific Antibody PT217Fast Track Designation, for the treatment of disease progression following platinum-based chemotherapyPatients with Extensive-Stage Small Cell Lung Cancer (ES-SCLC), regardless of whether they have received combination therapy with immune checkpoint inhibitors.Last month, PT886, the Claudin18.2/CD47 bispecific antibody product developed by Phanes, received FDA approval.Fast Track Designation，

Small Cell Lung Cancer (SCLC) is an aggressive cancer.The disease is characterized by high incidence and mortality rates. SCLC is difficult to diagnose at an early stage, progresses very rapidly, and is usually already at an advanced stage when diagnosed.DLL3The full Chinese name is delta-like canonical Notch ligand 3, which is expressed on the surface of tumor cells in approximately 85% of patients with small cell lung cancer and large cell neuroendocrine carcinoma.CD47It is a transmembrane protein expressed on tumor cells. Blocking the CD47-SIRPα interaction can promote the phagocytosis of tumor cells by macrophages.

PT217 is a bispecific antibody with a natural IgG structure, targeting DLL3 and CD47., intended for the development of treatments for SCLC, large cell neuroendocrine carcinoma of the lung (LCNEC), and extrapulmonary neuroendocrine carcinomas (EP-NECs), etc. This productThe multi-center Phase 1 clinical trial, SKYBRIDGE study, is currently being conducted in the United States to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of PT217 in patients with advanced or refractory cancers expressing DLL3. 

According toPhanesIntroduction to Public Information，PT217It can directly kill tumor cells through the ADCP activity of macrophages and the ADCC activity of NK cells, and expand the scope of tumor killing by simultaneously targeting the overexpressed DLL3 and CD47 on the surface of tumor cells.In addition, PT217 is expected to induce the presentation of tumor neoantigens by guiding tumor cells into phagocytic antigen-presenting cells (APCs), and indirectly activate T cells to kill tumor cells with low or no DLL3 expression by recognizing tumor neoantigens, thereby stimulating the acquired immune system. The anti-CD47 arm of PT217 is highly differentiated and has been shown in preclinical models to maintain strong binding activity to CD47 on tumor cells while exhibiting reduced binding to human red blood cells.

According to the Phanes press release, PT217 was granted orphan drug designation by the FDA in 2022.Drug Qualification,For the treatment of small cell lung cancer.In addition, on April 8, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration showed that PT217 has also received implied clinical trial approval in China, and is proposed to initiate...Development of treatments for advanced solid tumors.

Founder and CEO of PhanesDr. Wang MinghanPT217 has the potential to become a new treatment option for patients with SCLC, LCNEC, and EP-NECs in various clinical settings. Currently, two products in Phanes' R&D pipeline have received FDA Fast Track designation. Last month, the Claudin18.2/CD47 bispecific antibody product PT886 received FDA...Fast Track Designation, for the treatment of patients with metastatic Claudin18.2-positive pancreatic cancer. Both PT217 and PT886 are derived from Phanes' optimized anti-CD47 bispecific antibody series and are currently undergoing clinical trials. It is believed that this optimized anti-CD47 bispecific antibody treatment can unlock more potential of the innate immune system to target and attack solid tumors.

References

[1] Phanes' PT217 Granted FDA Fast Track Designation for TreatmentPatients with Extensive-Stage Small Cell Lung Cancer. Retrieved April 8, 2024 fromhttps://mp.weixin.qq.com/s/vB-hfIPbQgmWkb7KGgsYZw