The US Food and Drug Administration (FDA) has approved Biocytogen Pharmaceuticals’ Investigational New Drug (IND) application to commence the Phase I study of YH008.

Biocytogen’s wholly owned subsidiary Eucure Biopharma completed the IND application.

The dose-escalation, open-label Phase I study has been designed for assessing the pharmacokinetics, safety, preliminary anti-tumour activity, and tolerability of YH008 as a monotherapy in PD-(L)1-resistant advanced solid tumours or haematological malignancies patients

YH008 is an anti-PD-1 x CD40 bispecific antibody and exerts antagonistic and agonistic activities on PD-1 and CD40, respectively.

Preclinical studies demonstrated that YH008 has stronger in vivo anti-tumour activity compared to the benchmark mAb and anti-PD-L1 x CD40 bispecific antibody in multiple syngeneic models.

It also showed superior anti-tumour activity than parental monoclonal antibodies (mAbs) or combination therapy in vivo.

Biocytogen Pharmaceuticals vice-president, Eucure Biopharma chief medical office and CEO Dr Rong Chen said: “YH008 is a first-in-class bispecific antibody discovered through large-scale in vivo efficacy screening, where it demonstrated excellent anti-tumour activity, even in cold tumours.

“With this IND clearance for YH008, the company will have more products with diversified modalities entering the clinic to benefit patients.”

YH008 was engineered with an Fc-silent IgG1 isotype for avoiding Fc-receptor-mediated non-specific immune activation.

It can conditionally activate CD40 pathway without systemic CD40 non-specific activation, in the tumour microenvironment where tumour specific PD-1+ T cells are enriched.

Biocytogen Pharmaceuticals chief scientific officer Dr Yi Yang said: “The CD40 agonistic activity of YH008 is PD-1-dependent, which allows for more targeted immune cell activation and synergies.

“These characteristics prevent occurrence of liver toxicity, even at high doses, while enhancing anti-tumour activity, giving YH008 high clinical potential.”

In August this year, the company and TRACON Pharmaceuticals received approval for the IND application from the US FDA to start the Phase I/II clinical trial of YH001 plus envafolimab and doxorubicin for the treatment of sarcoma patients.