We focus on immuno-oncology and precision medicine with a well-balanced oncology portfolio of 15 innovative assets. CStone has received five NDA approvals. Among them, GAVRETO® (pralsetinib), AYVAKIT® (avapritinib) and Cejemly® (sugemalimab) have been approved by the National Medical Products Administration (NMPA) of China, AYVAKIT® has been approved by the Taiwan Food and Drug Administration and AYVAKIT® (avapritinib) has been approved by the Department of Health, Hong Kong, China.
Sugemalimab is an investigational anti-PD-L1 monoclonal antibody discovered by CStone. As a fully human, full-length anti-PD-L1 monoclonal antibody, sugemalimab mirrors the natural G-type immunoglobulin 4 (IgG4) human antibody, which reduces the risk of immunogenicity and potential toxicities in patients, a unique advantage over similar drugs.
Sugemalimab is being investigated in a number of ongoing clinical trials, including one Phase II registration study for lymphoma and four Phase III registrational studies in stage III NSCLC, stage IV NSCLC, gastric cancer, and esophageal cancer, respectively. In November 2021, China’s NMPA accepted the New Drug Application for anti-PD-L1 monoclonal antibody sugemalimab in first-line advanced NSCLC.
In August 2021, China’s NMPA has accepted its new drug application for sugemalimab in the treatment of stage III NSCLC. CStone will work closely with EQRx on regulatory discussions for new drug applications for the indication of stage III NSCLC in multiple countries.
Sugemalimab was granted Orphan Drug Designation for the treatment of T-cell lymphoma and Breakthrough Therapy Designation for the treatment of R/R ENKTL by the U.S. Food and Drug Administration. It has also been granted Breakthrough Therapy Designation by the National Medical Products Administration of China. The proposed indication is R/R ENKTL.
In August 2021, the China registrational study CS3010-101 of TIBSOVO® (ivosidenib tablets) has met the pre-specified endpoints. The National Medical Products Administration (NMPA) of China has accepted the new drug application (NDA) of TIBSOVO® (ivosidenib tablets) for the treatment of adults with R/R AML with a susceptible IDH1 mutation and this NDA has been granted priority review.
In the same month, CStone's partner Servier announced positive topline data from the global Phase 3 study of TIBSOVO® (ivosidenib tablets) in combination with azacitidine in patients with previously untreated idh1-mutated acute myeloid leukemia
In 2020, TIBSOVO® (ivosidenib tablets) was selected in the list of the third batch of Overseas New Drugs Urgently Needed in Clinical Settings by the Center for Drug Evaluation, NMPA, and granted for fast-track designation.
TIBSOVO® (ivosidenib tablets) is currently approved in the U.S. since 2018 as monotherapy for the treatment of adults with susceptible IDH1-mutant relapsed or refractory acute myeloid leukemia (AML). In 2019, the indication was extended by the U.S. FDA to include the treatment of newly diagnosed susceptible IDH1-mutant AML adult patients who are ≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy.
The U.S. FDA has granted Breakthrough Therapy Designation for TIBSOVO® (ivosidenib tablets) in combination with azacytidine for the treatment of adult patients with newly-diagnosed IDH1-mutant AML who are ≥75 years old or who have comorbidities that preclude use of intensive induction chemotherapy and Breakthrough Therapy Designation for TIBSOVO® (ivosidenib tablets) for the treatment of adult patients with relapsed and refractory myelodysplastic syndrome (MDS) with a susceptible IDH1 mutation.
In August 2021, the U.S. FDA approved TIBSOVO® (ivosidenib tablets) for the treatment of adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma with an IDH1 mutation as detected by an FDA-approved test. The supplemental New Drug Application for TIBSOVO® (ivosidenib tablets) received Priority Review, which accelerated the review timeline. TIBSOVO® (ivosidenib tablets) is the first and only targeted therapy approved for patients with previously treated IDH1-mutated cholangiocarcinoma.
CS1003 is a humanized recombinant IgG4 monoclonal antibody targeting human programmed cell death protein 1 (PD-1) being developed for immunotherapy of various tumors. Compared to most of the monoclonal antibodies that bind human and monkey PD-1 that have been approved or are currently under clinical development, CS1003 can not only be cross-reactive to both human and murine PD-1, but also shows a unique competitive advantage in the efficacy test of homologous mouse tumor models.
A global phase III trial of CS1003 in combination with LENVIMA® (lenvatinib) is being conducted, a standard-of-care TKI in patients with advanced hepatocellular carcinoma (“HCC”).
CS1003 was granted an ODD by U.S. FDA for the treatment of patients with HCC in July 2020.
In preclinical studies, lorlatinib demonstrated potent and selective inhibitory activity against ROS1/ALK rearrangements, crizotinib-resistant ROS1 mutations, as well as acquired ALK mutations that are resistant to crizotinib, alectinib, ceritinib and brigatinib. Lorlatinib can also efficiently penetrate the blood-brain barrier.
Lorlatinib was approved in the United States as a first line treatment for adults with metastatic NSCLC whose tumors are ALK-positive as detected by an FDA-approved test. In the European Union, lorlatinib is approved as a monotherapy for the treatment of adult patients with ALK-positive advanced NSCLC whose disease has progressed after alectinib or ceritinib as the first ALK TKI therapy, or crizotinib and at least one other ALK TKI. Previously, Pfizer conducted multiple clinical studies of lorlatinib in ALK-positive lung cancer in China and submitted an NDA for the treatment of patients with ALK-positive advanced NSCLC in March 2021. In Jun 2021, CStone Pharmaceuticals announced that it would work with Pfizer to jointly conduct study and develop lorlatinib for ROS1-positive advanced NSCLC in Greater China.
Fisogatinib is an orally available, potent, irreversible inhibitor of FGFR4. Fisogatinib was specifically designed to inhibit FGFR4 with exquisite selectivity, thereby sparing the paralogs FGFR1, FGFR2 and FGFR3 and preventing potential adverse effects. Preclinical data has validated FGFR4 as an oncogenic driver for a subset of patients with advanced HCC.
Fisogatinib is under development for the treatment of patients with FGFR4-activated HCC. The U.S. Food and Drug Administration has granted orphan drug designation to fisogatinib for the treatment of HCC.
A biosimilar of ipilimumab (Yervoy) ; In Phase Ia study, CS1002 monotherapy was well tolerated up to 10 mg/kg Q3W, and the overall clinical profile was consistent with that of ipilimumab (data presented at CSCO 2019)
An orally available, small molecule inhibitor of mitogen-activated extracellular signal regulated kinases 1 and 2 (MEK1 and MKE2)
CDK4/6 inhibitors prevent G1-S phase cell cycle transition and induce cell cycle arrest of tumor cells. Small molecule inhibitors of CDK4/6 have become a standard treatment for certain solid tumors.
Selective inhibition of HDAC6 may lead to better efficacy in multiple myeloma with an improved safety profile