CStone Pharmaceuticals (Cstone), a biopharmaceutical company, announced dosing of the first patient in a phase I clinical trial in Australia for CS1003, an investigational anti-programmed death-1 (PD-1) monoclonal antibody (mAb). The open-label, first-in-human (FIH) study is initiated at Scientia Clinical Research Ltd in Australia and will investigate the safety, tolerability, and preliminary efficacy of CS1003 in patients with advanced solid tumors.

"We are excited to announce initiation of clinical development for PD-1 inhibitor CS1003, our second pipeline candidate to enter Phase I studies in Australia after the CTLA-4 mAb CS1002 within one month," said Dr. Frank Jiang, chief executive officer at CStone. "CS1003 is cross-reactive with human and mouse PD-1 which enables quick pre-clinical proof of concept experiments in combination with novel targets, leading to global first-in-combination potential. Because of this unique feature, CS1003 is critical to CStone's combination strategy in cancer immunotherapy."

The launch of clinical studies for CS1003 is a key milestone for CStone, which now has three important checkpoint inhibitors for cancer therapy under clinical development. Alongside CS1001 (PD-L1) and CS1002 (CTLA-4), CS1003 will provide the backbone for CStone's pipeline development of oncology combination therapies.

As noted by Dr. Jason Yang, chief medical officer of CStone, "In preclinical studies, CS1003 demonstrated high affinity and selectivity for PD-1, as well as synergistic anti-tumor effects with multiple small-molecule drugs in animal models. The launch of this clinical program will allow us to gather important safety and efficacy data on CS1003. This will lay the foundation for future development of this molecule, in particular as the basis of combination therapies."

"We are excited to be enrolling our first patient treated with CS1003 and are hopeful that this novel immunotherapy drug will add to the available therapeutic options for advanced-stage tumors, either by itself or in combination with other drugs," said Dr. Charlotte Lemech, MBBS, BSc, FRACP, MD, lead investigator for this trial at Scientia Clinical Research Ltd.

The phase Ia/Ib study includes a dose-escalation stage followed by a dose-expansion stage. Additional information on the trial can be found here.

CS1003 is a humanized anti-PD-1 IgG4 monoclonal antibody developed by CStone using an internationally leading hybridoma platform. CS1003 has shown good tolerability and efficacy profile in preclinical in vivo studies.

PD-1, or programmed death-1, is an inhibitory checkpoint receptor expressed on T cells. Under normal circumstances, it binds with its ligands, programmed death ligand-1 or ligand 2 (PD-L1/PD-L2), inhibiting T cell and cytokine activation, serving to dampen the immune response in order to prevent damage to healthy tissues. However, studies have shown that PD-L1 can be abundantly expressed on the surface of many solid tumors as well as hematological malignancies. Cancer cells can therefore make use of the PD-1/PD-L1 pathway to successfully avoid immune system recognition and attack. Targeting of the PD-1/PD-L1 checkpoint by anti-tumor drugs can block the "tumor immune evasion mechanism" and restore anti-cancer immune ability in patients.

Currently, there are two anti-PD-1 antibodies approved globally: Opdivo® (nivolumab) from Bristol-Myers Squibb and Keytruda® (pembrolizumab) from Merck, Sharp & Dohme. Unlike other anti-PD-1 mAbs, CS1003 recognizes both human and murine PD-1, providing a unique competitive advantage during efficacy testing in syngeneic mouse tumor models particularly for development of effective combination therapies.

CStone Pharmaceuticals is a biopharmaceutical company devoted to the development of innovative drugs. With a broad oncology pipeline, the company is focused on the development of immuno-oncology based combination therapies.