On September 21, 2019 CStone Pharmaceuticals ("CStone" or the "Company", HKEX: 2616) reported results from the microsatellite instability high/deficient mismatch repair (MSI-H/dMMR) solid tumor cohort in the GEMSTONE-101 Phase Ib study of the Company’s investigational anti-PD-L1 antibody CS1001 for the first time in an oral presentation at the 22nd Annual Meeting of the Chinese Society of Clinical Oncology (CSCO, 2019 CSCO Annual Meeting) (Press release, CStone Pharmaceauticals, SEP 21, 2019, View Source [SID1234539681]).

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The objectives of the MSI-H/dMMR cohort study were to assess CS1001’s preliminary anti-tumor efficacy as a second-line or later monotherapy, and to further evaluate the safety and tolerability of CS1001.

Microsatellites (MS) are repetitive genetic sequences consisting of repeated DNA motifs. Defective DNA mismatch repair pathway causes instability in the length of DNA motifs, resulting in a phenomenon that is called microsatellite instability (MSI). MSI‐H indicates a high level of MSI, which is predictive of the loss of mismatch repair function and the possible presence of a large amount of mutation-derived tumor antigens that produce good responses to immunotherapies. Published data suggests MSI-H/dMMR is most common in patients with endometrial cancer, gastric adenocarcinoma, malignant small intestine tumor, and colorectal adenocarcinoma.

Professor Lin Shen, Vice President of Beijing Cancer Hospital, and the presenter of the results, commented: "Preliminary efficacy data from this study cohort indicates CS1001’s promising anti-tumor activity in patients with MSI-H/dMMR solid tumors. Also shown in the results are CS1001’s good safety and tolerability."

Dr. Frank Jiang, Chairman and CEO of CStone, commented: "I am pleased that CS1001, our core PD-L1 drug candidate, has achieved favorable preliminary results in this MSI-H/dMMR study cohort. At present, no PD-L1 inhibitor has been approved worldwide for the treatment of this type of solid tumors. We hope in future studies CS1001 will demonstrate its therapeutic potential in more tumor types and become the most rapidly developed immuno-oncology drug for MSI-H/dMMR solid tumors."

CStone’s Chief Medical Officer, Dr. Jason Yang, noted: "In view of the good responses to immunotherapies in MSI-H/dMMR solid tumors, effective immuno-oncology treatments will hopefully bring survival benefits to such patient population. The results from this study has shown CS1001’s therapeutic potential, and its 38% overall response rate (ORR), with 28.6% confirmed, in these heavily pretreated patients is remarkable compared to some of the approved PD-1 drugs. CS1001 is the monoclonal antibody that most closely mirrors natural G-type immune globulin 4 (IgG4) human antibody, which hopefully can lead to the demonstration of its unique safety advantage in subsequent clinical studies."

Overview of the MSI‐H/dMMR cohort of the GEMSTONE-101 Phase Ib ≥2L study
This study cohort included unresectable or metastatic MSI‐H/dMMR solid tumor patients who failed to achieve satisfactory outcomes from prior treatments and lacked alternative treatment options. A total of 21 patients were enrolled in this cohort, 18 of whom had colorectal cancer, 2 with pancreatic cancer, and 1 with small intestine cancer. 13 of the enrolled patients had previously been treated with second line or later therapies. During the study, patients were administered with 1,200 mg CS1001 once every three weeks, until disease progression or intolerance.

Demographics and baseline characteristics

Of the 21 enrolled patients, 9 remained on treatment, 12 discontinued treatment.
Main reasons for discontinuation were disease progression (n=8), patient’s decision (n=2), death due to disease progression (n=1), and other reasons (n=1).
No patient discontinued due to AEs.
Preliminary efficacy data

CS1001 has shown promising anti-tumor activity in patients with MSI-H/dMMR solid tumors. 21 patients who received the treatment were included in efficacy analysis, and 8 (38.1%) of them achieved partial response (PR, per RECIST V1.1), 6 (28.6%) were confirmed PRs.
The disease control rate was 57.1% (12/21).
The duration of response (DOR) ranged from 0.03+ to 8.6+ months, and the median DOR was not reached.
Safety data

CS1001 has shown a good safety profile

The median treatment duration of the 21 treated patients was 137 days (21-377).
During treatment, 20 patients (95.9%) developed adverse events (AEs), and close to 1/4 of those patients had Grade 3 or higher AEs.
18 patients (85.7%) developed AEs that were related to the CS1001 treatment, and only 1 patient (4.8%) developed an AE that was Grade 3 or higher in severity.
2 patients (9.5%) developed serious adverse events (SAEs) and neither was related to the CS1001 treatment.
9 patients (42.9%) developed immune-related adverse events (irAEs) that were Grade 1-2 in severity.
No discontinuation or death occurred due to AEs.
About CS1001
CS1001 is an investigational monoclonal antibody directed against PD-L1 being developed by CStone. Authorized by the U.S. based Ligand Corporation, CS1001 is developed by the OMT transgenic animal platform, which can generate fully human antibodies in one step. As a fully human, full-length anti-PD-L1 monoclonal antibody, CS1001 mirrors natural G-type immune globulin 4 (IgG4) human antibody, which can reduce the risk of immunogenicity and potential toxicities in patients, potentially representing a unique advantage over similar drugs.

CS1001 has completed a Phase I dose-escalation study in China, in which CS1001 showed good tolerability and produced sustained clinical benefits during the Phase Ia stage of the study.

CS1001 is being investigated in a number of ongoing clinical trials, including one Phase I bridging study in the U.S. In China, its clinical program includes one multi-arm Phase Ib study, two pivotal Phase II studies, and three Phase III studies for several tumor types.

On September 20, 2019 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it has obtained regulatory approval for its humanized anti-PD-L1 monoclonal antibody, Tecentriq [generic name: atezolizumab (genetical recombination)] from the Ministry of Health, Labour and Welfare (MHLW) for an additional indication of PD-L1-positive, hormone receptor-negative and HER2-negative inoperable or metastatic breast cancer (Press release, Chugai, SEP 20, 2019, View Source [SID1234539661]). It has also obtained approval for an additional formulation of Tecentriq 840 mg. Tecentriq 840 mg was developed to provide an optimal formulation for breast cancer for which approved dosage is 840 mg once every 2 weeks.

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VENTANA OptiView PD-L1 (SP142), a pathological testing kit marketed by Roche Diagnostics K.K., should be used to detect PD-L1 expression. An expanded use of VENTANA OptiView PD-L1 (SP142) as a companion diagnostic of Tecentriq was approved on August 20, 2019 to allow physicians to identify patients with PD-L1-positive breast cancer who could benefit from Tecentriq.

"We are very pleased that Tecentriq has been approved as the first immune checkpoint inhibitor for the treatment of PD-L1-positive triple-negative breast cancer (TNBC) in Japan," said Dr. Yasushi Ito, Chugai’s Executive Vice President, Co-Head of Project & Lifecycle Management Unit. "This approval provides a novel cancer immunotherapy-based treatment for TNBC, a rapidly-progressing cancer with limited therapeutic options. We are committed to contribute to patients through the treatment."

This approval is based on the results from the phase III IMpassion130 study. Tecentriq in combination with nab-paclitaxel (albumin-bound) met primary endpoint with a significant reduction in the risk of disease worsening or death (PFS) compared with nab-paclitaxel (albumin-bound) alone in the intention-to-treat (ITT) population (median PFS=7.2 vs 5.5 months; hazard ratio [HR]=0.80, 95%CI: 0.69-0.92, p=0.0025) and in people who were tested positive for PD-L1 expression (median PFS=7.5 vs 5 months; hazard ratio [HR]=0.62, 95% CI: 0.49-0.78, p<0.0001). Tecentriq and nab-paclitaxel (albumin-bound) showed a clinically meaningful improvement in the co-primary endpoint of overall survival (OS) in the PD-L1-positive population (median OS=25.0 vs 18.0 months; HR=0.71, 95% CI: 0.54-0.93) at the second interim analysis. OS results in the PD-L1-positive population were not formally tested due to the hierarchical design of the study as statistical significance was not met for OS in the intention-to-treat (ITT) population (median OS=21.0 vs 18.7 months; HR=0.86, 95% CI: 0.72-1.02, p=0.078). Follow-up will continue until the next planned analysis. The safety profile of Tecentriq in combination with chemotherapy was consistent with the known safety profiles of the individual medicines, and no new safety signals were identified.

About the IMpassion130 study
The IMpassion130 study is a Phase III, multicenter, randomized, double-blind study evaluating the efficacy, safety and pharmacokinetics of Tecentriq plus nab-paclitaxel (albumin-bound) compared with nab-paclitaxel (albumin-bound) in people with unresectable locally advanced or metastatic TNBC who have not received prior systemic therapy for metastatic breast cancer. The co-primary endpoints are PFS per investigator assessment (RECIST 1.1) and OS in the ITT population and in the PD-L1-positive population.

Roche’s Tecentriq in combination with Abraxane improves outcomes as an initial treatment for people with PD-L1-positive metastatic triple-negative breast cancer (Press release issued by Roche on October 20, 2018)
View Source

Chugai Files for Additional Indication and Additional Formulation of Anti-PD-L1 Antibody TECENTRIQ for Breast Cancer (Press release issued by Chugai on December 21, 2018)
View Source

Roche presents data from across its breast cancer portfolio at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release issued by Roche on June 3, 2019)
View Source

Free Offering of Tecentriq 840 mg prior to the Listing in the NHI Reimbursement Price List
Under the system for healthcare services provided combining insurance-covered and non-covered services provided by MHLW, Chugai will offer Tecentriq for free to respond to requests for emergency use from patients with PD-L1-positive, hormone receptor-negative and HER2-negative inoperable or metastatic breast cancer with very limited treatment options. In the context of proper use, Tecentriq will be offered for free only to medical institutions participated in the clinical study of IMpassion130 study for development of the drug as clinical sites on condition that; 1) they would use the drug in accordance with the approved indications and dosage and administration and 2) they would corporate with us in implementing various safety measures to promote proper use, including activities based on Early Post-Marketing Phase Vigilance conducted by Chugai during the free offering period. The offering will start immediately after the date of regulatory approval and end on the day before the listing in the NHI reimbursement price list.

Sites for implementation of free offering of the drug Medical institutions participated in the clinical study of IMpassion130 study in Japan
Period for implementation of free offering of the drug From date of regulatory approval through the day before the listing in the NHI reimbursement price list
As a top pharmaceutical company in the field of oncology in Japan, Chugai is committed to contribute to patients and medical professionals by offering Tecentriq as a new treatment option and accordingly, to improve access of medications and their proper use.

Prescribing Information *The underlined parts were newly added.

Product name Tecentriq Intravenous Infusion 840 mg
Tecentriq Intravenous Infusion 1200 mg
Generic name atezolizumab (genetical recombination)
Indications Tecentriq Intravenous Infusion 840 mg
PD-L1-positive, hormone receptor-negative and HER2-negative inoperable or metastatic breast cancer
Tecentriq Intravenous Infusion 1200 mg
Unresectable, advanced or recurrent non-small cell lung cancer
Extensive-stage small cell lung cancer
Dosage and administration
In case of patients with untreated unresectable, advanced or recurrent non squamous non-small cell lung cancer.
The usual adult is 1200 mg atezolizumab (genetical recombination) in combination with carboplatin, paclitaxel and bevacizumab (genetical recombination) by intravenous infusion over 60 minutes once every 3 weeks. If the initial infusion is well tolerated, subsequent infusions can be delivered over 30 minutes.
In case of patients with unresectable, advanced or recurrent non squamous non-small cell lung cancer who has undergone chemotherapy.
The usual adult dosage is 1200 mg atezolizumab (genetical recombination) administered by intravenous infusion over 60 minutes once every 3 weeks. If the initial infusion is well tolerated, subsequent infusions can be delivered over 30 minutes.
In case of patients with extensive-stage small cell lung cancer.
The usual adult dosage is 1200 mg atezolizumab (genetical recombination) in combination with carboplatin and etoposide by intravenous infusion over 60 minutes once every 3 weeks. If the initial infusion is well tolerated, subsequent infusions can be delivered over 30 minutes.
In case of patients with PD-L1-positive, hormone receptor-negative and HER2-negative inoperable or metastatic breast cancer.
The usual adult dosage is 840 mg atezolizumab (genetical recombination) in combination with nab-paclitaxel (albumin-bound) administered by intravenous infusion over 60 minutes once every 2 weeks. If the initial infusion is well tolerated, subsequent infusions can be delivered over 30 minutes.
Drug price Tecentriq Intravenous Infusion 840 mg Not listed in the NHI price list
Tecentriq Intravenous Infusion 1200 mg JPY 625,567/per vial
Conditions for approval
A risk management plan should be created and appropriately implemented.
In case of patients with unresectable, advanced or recurrent non squamous non-small cell lung cancer who has undergone chemotherapy.
Because the number of participants in Japanese clinical trials was very limited, post-marketing drug use surveillance of all patients receiving Tecentriq treatment should be conducted until data for a certain number of patients have been accumulated, in order to understand background information on people using Tecentriq as well as to collect safety and efficacy data on Tecentriq promptly, and take necessary measures for the appropriate use of Tecentriq.
About Triple-Negative Breast Cancer
In Japan, 86,500 women (2018 predicted value) are estimated to be afflicted with breast cancer each year. 14,800 women in Japan (2018 predicted value) die as a result of the disease. Triple-negative breast cancer accounts for 15% of all breast cancer cases and, is more common in women under the age of 50, compared with other forms of breast cancer. Triple-negative breast cancer is defined by the lack of expression of hormone receptors (estrogen and progesterone receptors) and the overexpression of human epidermal growth factor receptor 2 (HER2). In general, triple-negative breast cancer has a high tumor-proliferative capacity and shorter overall survival, compared with other forms of breast cancer.

About approval status of Tecentriq in Japan
Tecentriq was launched in April 2018 with an indication of unresectable, advanced or recurrent NSCLC, followed by an approval for the additional dosing for the treatment of untreated unresectable, advanced or recurrent NSCLC in December 2018. In addition, an approval of extensive-stage small cell lung cancer has been obtained in August 2019.

Trademarks used or mentioned in this release are protected by law.

Sources

Cancer Registry and Statistics. Cancer Information Service, National Cancer Center Japan from: View Source Accessed August, 2019
Abramson VG et al. Subtyping of triple-negative breast cancer: implications for therapy. Cancer. 2015;121(1):8-16. 3.
Cancer Center. Triple negative breast cancer risk factors. [Internet; cited 2018 May 24]. Available from: View Source Accessed October 2018.
Pal SK et al. Triple negative breast cancer: unmet medical needs. Breast Cancer Res Treat. 2011;125(3):627-636.
American Cancer Society. Breast Cancer Facts & Figures 2013-2014
Lehmann BD et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121(7):2750-67.

On September 20, 2019 Amyris, Inc. (Nasdaq:AMRS), a leader in the development and production of sustainable ingredients for the Health & Wellness, Clean Beauty and Flavors & Fragrances markets, reported that management will be presenting at the B. Riley FBR Annual Consumer & Media Conference to be held October 3, 2019, at the Sofitel New York Hotel in New York City (Press release, Amyris Biotechnologies, SEP 20, 2019, View Source;media-conference-on-october-3-2019-300922357.html [SID1234539677]).

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Amyris will provide an update on its business and discuss its solid financial results for the first half of 2019 during the presentation, which is scheduled for Thursday, October 3, at 11:00 a.m. ET. A live webcast of the presentation including slides and a replay will be available on the investor relations section of the company’s website at View Source

On September 20, 2019 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending the oral once-daily therapy XOSPATA (gilteritinib) as a monotherapy for the treatment of adult patients who have relapsed or refractory (resistant to treatment) acute myeloid leukemia (AML) with a FLT3 mutation (FLT3mut+) (Press release, Astellas, SEP 20, 2019, View Source [SID1234539662]).2 If approved by the European Commission (EC), gilteritinib has the potential to improve treatment outcomes for AML patients with the most common mutations – FLT3 internal tandem duplication (ITD) and FLT3 tyrosine kinase domain (TKD) – and would be one of the few advances for the treatment of AML in Europe over the past 40 years.1,3 Gilteritinib received accelerated assessment from the EMA, which allowed the CHMP to reduce the timeframe for approval.4

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"The data are encouraging, showing a significant improvement in overall survival (OS), and one-year survival rates doubled when comparing gilteritinib to the current standard of care," said Giovanni Martinelli, M.D., Institute of Hematology, S.Orsola-Malpighi University Hospital, Bologna, Italy, a study investigator. "For relapsed or refractory FLT3mut+ AML patients the current prognosis is poor, with median OS of less than six months following treatment with salvage chemotherapy. If approved by the EC, gilteritinib has the potential to change the treatment landscape."

The CHMP decision is based on results from the Phase 3 ADMIRAL trial, which investigated gilteritinib versus salvage chemotherapy in patients with relapsed or refractory FLT3mut+ AML.5 Patients treated with gilteritinib had significantly longer OS than those who received salvage chemotherapy.5 Median OS for patients who received gilteritinib was 9.3 months, compared to 5.6 months for patients who received salvage chemotherapy (Hazard Ratio = 0.64 (95% CI 0.49, 0.83), P=0.0004).5,6 Rates of one-year survival were 37% for patients who received gilteritinib, compared to 17% for patients who received salvage chemotherapy.5

"There is a high unmet need in AML and Astellas is committed to improving treatment options. Gilteritinib offers a potential new alternative for patients with relapsed or refractory FLT3mut+ AML, with data showing improved survival outcomes," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Global Therapeutic Area Head, Oncology Development, Astellas. "Subject to EC approval, gilteritinib has the potential to provide new hope for clinicians, patients and their families."

The positive opinion from the CHMP will now be reviewed by the EC, which has the authority to approve medicines for the 28 European Union member countries, and is also valid in Iceland, Norway and Liechtenstein.7 In late 2018, gilteritinib was approved by regulatory agencies in the U.S. and Japan for the treatment of adult patients who have relapsed or refractory FLT3mut+ AML.8,9

About Gilteritinib
Gilteritinib was discovered through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and Astellas has exclusive global rights to develop, manufacture and commercialize gilteritinib. Last year gilteritinib received an Orphan Designation from the European Commission and received accelerated assessment from the EMA.4,10

In the U.S., gilteritinib was previously granted Orphan Drug Designation and Fast Track Designation by the Food and Drug Administration (FDA), and was approved in November 2018 for the treatment of adult patients with relapsed or refractory FLT3mut+ AML, based on interim complete remission/complete remission with partial hematologic recovery (CR/CRh) data from the Phase 3 ADMIRAL trial.8 Gilteritinib has also received approval for a supplemental New Drug Application (sNDA) from the FDA, adding Overall Survival (OS) data from the Phase 3 ADMIRAL trial in relapsed or refractory FLT3mut+ AML to the gilteritinib label.6 Full results from the ADMIRAL trial were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2019.5

In Japan, gilteritinib received Orphan Drug Designation and SAKIGAKE Designation from the Japanese Ministry of Health, Labour and Welfare and was approved for the treatment of adult patients with relapsed or refractory FLT3mut+ AML in September 2018.9,11 In August 2019, the Japanese package insert for gilteritinib was revised to include information regarding OS data from the ADMIRAL trial.12

Astellas is currently investigating gilteritinib in various FLT3mut+ AML patient populations through several Phase 3 trials.

About the ADMIRAL Trial13
The Phase 3 ADMIRAL trial (NCT02421939) was an open-label, multicenter, randomized study of gilteritinib versus salvage chemotherapy in adult patients with FLT3mut+ who are refractory to or have relapsed after first-line AML therapy. The co-primary endpoints of the trial were OS and CR/CRh rates. The study enrolled 371 patients with relapsed or refractory AML and FLT3mut+ present in bone marrow or whole blood. Subjects were randomized in a 2:1 ratio to receive gilteritinib (120 mg5) or salvage chemotherapy.

The most common adverse events (AEs) across both treatment arms of the ADMIRAL trial were febrile neutropenia (43.7%), anemia (43.4%), and pyrexia (38.6%).5 Common grade ≥3 AEs related to gilteritinib were anemia (19.5%), febrile neutropenia (15.4%), thrombocytopenia (12.2%), and decreased platelet count (12.2%).5 Adjusted for exposure duration, serious treatment-emergent AEs per patient year were less common with gilteritinib (7.1%) than salvage chemotherapy (9.2%).5

On September 20, 2019 CStone Pharmaceuticals ("CStone" or the "Company", HKEX: 2616) reported the preliminary data from the Phase I bridging study of the Company’s investigational anti-PD-1 monoclonal antibody CS1003 for the first time, in an oral presentation at the 22nd Annual Meeting of the Chinese Society of Clinical Oncology (CSCO, 2019 CSCO Annual Meeting) (Press release, CStone Pharmaceauticals, SEP 20, 2019, View Source;cstone-releases-preliminary-results-from-the-phase-ia-trial-of-cs1003-in-chinese-patients-with-advanced-tumors-300922487.html [SID1234539678]).

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CS1003-102 is a multi-center, open-label, dose-escalation and indication-expansion Phase I clinical trial being conducted in China. Initiated in November 2018, the trial is designed to evaluate the safety, pharmacokinetics, immunogenicity, and preliminary anti-tumor efficacy of CS1003 in patients with advanced tumors.

Professor Lin Shen, Vice President of Beijing Cancer Hospital and the presenter of the results, commented: "Data from the dose escalation phase of the trial demonstrated CS1003’s favorable safety and tolerability in Chinese patients with advanced tumors. Furthermore, preliminary yet noticeable anti-tumor activities were also observed in multiple tumor types."

Dr. Frank Jiang, Chairman and CEO of CStone, commented: "CS1003 is one of CStone’s three backbone immuno-oncology drug candidates. I am very pleased about the encouraging initial data from this Phase Ia trial, as it provides a solid foundation for the continued development of this asset. We will continue to vigorously advance the clinical development of CS1003 around the world. In addition to the on-going programs in China and Australia, we have received IND approval for CS1003 in the U.S. With a robust pipeline and core strategy centering on combination cancer immunotherapy, we will further exploit CS1003’s unique advantages and its vast application potential in combination with multiple drugs."

Dr. Archie Tse, Chief Translational Medicine Officer at CStone, noted: "CS1003 is a high-affinity monoclonal antibody that potently blocks the binding of PD-1 to its ligands. It is worth noting that CS1003’s ability to cross-react with both human PD-1 and mouse PD-1 will allow us to significantly accelerate the preclinical proof-of-concept of CS1003 in combination with new targeted drugs in syngeneic tumor models. Through clinical development, we will further explore the potential of CS1003 as cancer immunotherapy."

CS1003-102 study results

The CS1003-102 study data presented at this year’s CSCO Annual Meeting was generated from 19 patients with advanced tumors, who were enrolled during the dose escalation phase of the study. As of June 15, 2019, 3 patients with gastric adenocarcinoma, 2 with esophageal squamous cell carcinoma, 2 with leiomyosarcoma, and 12 with other advanced tumors were enrolled. 7 patients were administered with CS1003 once every three weeks, at a fixed dose of 60 mg; 12 patients were administered with CS1003 once every three weeks, at a fixed dose of 200 mg. The median treatment duration was 9.1 weeks (range, 3.0-29.3) and 9.0 weeks (range, 4.9-21.7) at 60 mg and 200 mg dose, respectively.

Preliminary safety data on CS1003

No dose-limiting toxicity was observed at either 60 mg or 200 mg, and the maximum tolerated dose was not reached.
Of the 18 patients (94.7%) who developed treatment-related adverse events (TRAEs), 3 reported Grade 3 or higher TRAEs, and the rest were all Grade 1-2 in severity. The common TRAEs included fatigue (26.3%), elevated serum bilirubin levels (15.8%), hypothyroidism (15.8%), and anemia (15.8%).
Nine patients reported at least one immune-related adverse event (irAE), and the most common irAEs included fatigue (15.8%), hypothyroidism (15.8%), hyperthyroidism (10.5%), and rash (10.5%).
The pharmacokinetic characteristics of CS1003

In the on-going Phase I trial in China, CS1003 demonstrated dose-proportional systemic exposure. Comparable pharmacokinetic characteristics were observed between patients in China and Australia.
The immunogenicity of CS1003

The preliminary analysis of anti-drug antibody (ADA) data suggests CS1003 has relatively low immunogenicity. No treatment-induced and enhanced ADA responses (ADA-positive) were observed.
Preliminary efficacy data on CS1003

Of the 16 efficacy-evaluable patients, 7 remained on the treatment, with a median treatment duration of 21.3 weeks (range, 5.6–29.3).
At 60 mg, 1 patient with esophageal squamous cell carcinoma and 1 patient with uterine leiomyosarcoma had a confirmed partial response (PR) per RECIST v1.1; At 200 mg, 1 patient with laryngeal squamous cell carcinoma was determined to be in PR awaiting confirmation.
One patient treated at 200 mg was evaluated as having disease progression per RECIST v1.1 during the first post-baseline tumor assessment and continued to receive CS1003 beyond progression; Noticeable tumor reduction compared to baseline was observed during the following tumor assessment, and the patient remained on treatment as of the data cut-off date.
# # #

About CS1003 and the PD-1/PD-L1 pathway

CS1003 is a humanized IgG4 anti-PD-1 monoclonal antibody developed by CStone using a state-of-the-art hybridoma platform. CS1003 has shown good tolerability and efficacy profile in preclinical in vivo studies. Unlike other anti-PD-1 mAbs, CS1003 recognizes both human and murine PD-1, providing a unique competitive advantage during efficacy evaluation in syngeneic mouse tumor models and the development of combination therapies.

PD-1, or programmed death-1, is an inhibitory checkpoint receptor expressed on T cells. Under normal conditions, PD-1 binds to 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 utilize the PD-1/PD-L1 pathway to avoid immune system recognition. Targeting of the PD-1/PD-L1 checkpoint by anti-tumor drugs can block the "tumor immune evasion mechanism" and restore anti-cancer immunity in patients.