9 July 2020 - - US-based clinical stage biopharmaceutical company JS InnoPharm Ltd has enrolled the first patient in a Phase 1, open-label, monotherapy dose-escalation and expansion study of JSI-1187, the company's lead investigational drug candidate targeting the enzymes ERK1 and ERK2, the company said.

The study is being conducted at 4 NCI-designated Comprehensive Cancer Centers in the US.

JS InnoPharm holds the US IND for JSI-1187, and this trial is being managed by Strategia Pharmaceuticals LLC, JS InnoPharm's clinical development partner in the United States.

Initiation of this clinical trial represents an important step in the company's efforts to discover and develop precision medicine for cancer patients.

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical activity of JSI-1187 in patients with relapsed, refractory solid tumors with MAPK mutations.

The study will comprise three components: a dose escalation phase of JSI-1187 monotherapy for patients with solid tumors, a dose escalation phase of JSI-1187 in combination with BRAF inhibitor, dabrafenib, and an expansion phase for patients with tumors harbouring specific mutations.

MAPK signaling via the RAS-RAF-MEK-ERK cascade plays a critical role in cancer growth and proliferation. Alterations in the MAPK/ERK pathway are found in a range of cancer types, with KRAS mutations in pancreatic, biliary tract (3-50%), colorectal (30-50%), lung (25-30%), ovarian (15-39%) and endometrial cancers; NRAS mutations in 20% of melanoma; and BRAF V600 mutations in 50% of melanoma and 7% of a variety of other tumor types.

Although it has been demonstrated that BRAF/MEK inhibitor-targeted combination therapy provides a significant benefit beyond single agent therapy in melanoma and other cancers, the majority of patients eventually develop resistance and disease progression.

Several mechanisms of acquired resistance have been identified and central to these mechanisms is the reactivation of ERK signaling.

Therefore, ERK inhibition may provide the opportunity to avoid or overcome resistance from upstream mechanisms, as it is the most distal kinase of this signaling pathway.

JSI-1187 is a selective and orally administered small molecule inhibitor of ERK1 and ERK2.

In preclinical studies, it demonstrated high potency against a variety of tumors with MAPK pathway mutations.

JS InnoPharm is a clinical stage biopharmaceutical company, dedicated to the discovery and development of novel chemical entities for cancer therapy, leveraging cutting edge knowledge in mutations, biomarkers, and precision medicine.

JS InnoPharm is building an innovative pipeline by internal R and D as well as global partnering and licensing, and developing multiple clinical candidates with differential clinical strategies.