BeiGene announces the clinical data of Sitravatinib combined with Bazeran® at the American Association for Cancer Research (AACR) 2021 Annual Meeting

Data from an ongoing phase 1b clinical trial of sitravatinib combined with Baizian® shows that the combination of drugs targets patients with unresectable or metastatic melanoma that is refractory or resistant to PD-1/PD-L1 therapy and platinum-based drugs Patients with drug-resistant ovarian cancer have preliminary anti-tumor activity and are generally tolerant Beijing time April 12, 2021, BeiGene (Nasdaq code: BGNE; Hong Kong Stock Exchange code: 06160), a company in the commercial stage A biotechnology company that focuses on the development and commercialization of innovative drugs on a global scale.

The company announced today in two oral reports at the American Association for Cancer Research (AACR) 2021 annual meeting that its anti-PD-1 antibody Bezean® (tislelizumab) was jointly developed with Mirati Therapeutics, Inc.
Clinical data of Sitravatinib, a selective kinase inhibitor under investigation.

The data announced at the annual meeting comes from two cohorts of a phase 1b clinical trial (NCT03666143), which are used to treat patients with unresectable or metastatic melanoma who are refractory or resistant to PD-1/PD-L1 therapy And for the treatment of patients with advanced platinum-resistant ovarian cancer (PROC).

BeiGene has previously reached an exclusive cooperation and licensing agreement with Mirati Therapeutics, Inc.
to jointly develop, produce and commercialize sitravatinib in Asia (excluding Japan), Australia and New Zealand.

Ben Yong, MD, Chief Medical Officer of BeiGene Cancer Immunology, said: “From the data released today, we believe that sitravatinib combined with Baizian® is expected to provide clinical benefits for patients with advanced solid tumors and support our ongoing clinical trials.
This combination is further evaluated in the trial.

In addition, we are excited to observe preliminary anti-tumor activity in patients with PD-1/PD-L1 therapy refractory or drug-resistant melanoma.

We will continue to follow up patients and enroll all patients who have completed the trial.
We also look forward to deepening our understanding of the combination of drugs and provide patients all over the world with a new type of cancer therapy.

"This open, multi-center phase 1b clinical trial aims to evaluate the safety/tolerability and preliminary anti-tumor activity of sitravatinib combined with Bezian® in patients with advanced solid tumors.

The primary endpoint of the trial is the combination of drugs.
Safety/tolerability; key secondary endpoints include the objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) assessed by the investigator based on the evaluation criteria for solid tumor efficacy (RECIST 1.
1).

In addition, The trial also evaluates overall survival (OS).
The
results of the trial for patients with unresectable or metastatic melanoma who are refractory or resistant to PD-1/PD-L1 inhibitor therapy, said Professor Cui Chuanliang from Beijing Cancer Hospital : "The emergence of immune checkpoint inhibitors has changed the treatment of advanced melanoma, but due to primary or congenital drug resistance, a large number of patients cannot benefit from it.

In this phase 1b clinical trial, we are very pleased to see that sitravatinib combined with Baizian® is generally well tolerated in patients with PD-1/L1 drug-resistant melanoma and has demonstrated preliminary anti-tumor activity.
The points are encouraging.

"As of the data cut-off point on October 13, 2020, a total of 25 patients with unresectable or metastatic melanoma who were refractory or resistant to previous PD-1/PD-L1 therapy and who have not received other immunotherapy were enrolled.
The Phase 1b trial G cohort includes 12 skin type, 7 acrotype and 4 mucosal type patients.

As of the data cut-off point, 16 patients (64%) are still receiving study treatment.
The
median follow-up time was 5.
5 At the end of the month, the results included: All 25 patients experienced at least one adverse event (TEAE) during treatment of any level.

The most common (≥20%) are elevated alanine aminotransferase (ALT) (76%), aspartate aminotransferase (AST) (68%), cholesterol (56%), and high blood triglycerides ( 52%), hypothyroidism (48%), weight loss (48%), increased blood creatine kinase (BCK; 40%), diarrhea (40%), increased γ-glutamyltransferase (GGT; 40%), proteinuria (40%), elevated blood bilirubin (BB; 36%), abnormal T wave of electrocardiogram (36%), high blood pressure (36%), palm and toe erythema paresthesia syndrome (32%) ), elevated creatine kinase-myocardial isoenzymes (CK-MB; 28%), hyperuricemia (28%), epigastric pain (24%), vomiting (24%) and hypokalemia (20%) ) Twelve patients (48%) experienced at least one TEAE of grade 3 and above, the most common (≥5%) were hypertension (12%), elevated ALT (8%) and elevated GGT (8%)1 One patient (4%) experienced a severe TEAE with anal abscess.
Two patients (8%) were determined to be related to sitravatinib and the trial treatment was discontinued due to TEAE; one patient was discontinued from the treatment of Bazaan due to vaginal bleeding (with Bazaan ® Unrelated), another 1 patient discontinued sitravatinib treatment due to elevated BCK (related to sitravatinib).
18 patients (72%) and 13 patients (52%) respectively experienced sitravatinib dose interruption or reduction.
All 25 patients were included as effective In sexual evaluation, the confirmed ORR was 24% (95% CI: 9.
4, 45.
1), of which 6 patients achieved partial remission (PR), and the DCR was 88% (95% CI: 68.
8, 97.
5).
The median duration of remission was The (DoR) has not yet been reached.
The median PFS assessed by the investigator was 6.
7 months (95% CI: 4.
07, failed to assess).
The results of the trial for patients with advanced PROC, said Jeffrey Goh, Bachelor of General Surgery at the Icon Cancer Center in Australia: " It is very common for ovarian cancer patients to develop resistance or refractory platinum-based therapy after receiving current standard treatment.

Sitravatinib combined with Bezian® for the treatment of advanced PROC patients who have received multiple therapies before has shown preliminary results.
Anti-tumor activity and overall well tolerated.

Although the current patient sample is relatively small, we look forward to further evaluation of this new combination drug in the PROC.

"As of the data cut-off point on October 13, 2020, a total of 60 patients with relapsed PROC who had not previously received anti-PD-1/PD-L1 treatment were enrolled in the Phase 1b trial E cohort, of which 13 cases (22%) Still receiving research treatment.

The median number of treatment lines previously received by these patients was 4 (range: 1, 11).

At a median follow-up time of 6 months, the results included: 58 enrolled patients (97%) Experienced at least one TEAE of any level.

The most common (≥20%) are diarrhea (67%), nausea (57%), fatigue (48%), high blood pressure (40%), decreased appetite (37%), vomiting (37%), abdominal pain (35%) ), constipation (33%), elevated ALT (30%), urinary tract infection (27%), elevated AST (20%), dysphonia (20%), headache (20%), and erythema paresthesia Syndrome (20%) 41 patients (68%) experienced at least one TEAE of grade 3 and above, the most common (≥5%) were hypertension (18%) and abdominal pain (12%) in 42 patients (70%) 23 patients (38%) who had experienced at least one serious TEAE discontinued the trial treatment due to TEAE, of which 9 patients (15%) discontinued the Bezean® treatment, 14 patients (23%) discontinued sitravatinib treatment, 50 patients (83) %) and 30 patients (50%) experienced a dose interruption or reduction of sitravatinib.
4 patients died due to TEAE, all of which were deemed unrelated to the trial treatment.
Among the 53 patients included in the effectiveness evaluation, the confirmed ORR was 26% (95 % CI: 15.
3, 40.
3), of which 14 patients achieved PR, DCR was 77% (95% CI: 63.
8, 87.
7), median DoR was 4.
7 months (95% CI: 2.
8, failed to assess) median PFS And OS were 4.
1 months (95% CI: 4.
0, 5.
1) and 12.
9 months (95% CI: 6.
3, 17.
2), respectively.
About Sitravatinib Sitravatinib is a multi-target receptor tyrosine kinase (RTK) inhibitor under investigation , Can potentially stimulate the body's immune response to fight cancer.

Sitravatinib inhibits VEGFR and TAM (TYRO3, AXL, MERTK) receptor families, which are involved in the coordination of the immunosuppressive tumor microenvironment (TME).

It has been shown that inhibition of these receptors can stimulate anti-tumor immune responses and may re-sensitize patients who were previously resistant to CPI therapy.

Sitravatinib transforms immunosuppressive TME into immune supportive TME by inhibiting specific RTKs.
It is possible to regain immune response in combination with CPI therapy to overcome the resistance of CPI therapy.

A number of clinical trials (including the Phase 3 SAPPHIRE trial) evaluating Sitravatinib for the treatment of CPI-resistant patients with advanced non-small cell lung cancer and specific patients who have not received CPI therapy are ongoing.

For more information, please visit: www.
mirati.
com/science.
About Bezeran® (tislelizumab injection) Bezeran® (tislelizumab injection) is a humanized lgG4 The anti-programmed death receptor 1 (PD-1) monoclonal antibody is designed to minimize binding to Fcγ receptors in macrophages.

Preclinical data indicate that the binding of Fcγ receptors in macrophages activates antibody-dependent cell-mediated killer T cells, thereby reducing the anti-tumor activity of PD-1 antibodies.

Baizian® is the first drug developed by BeiGene's immuno-oncology biological platform.
It is currently undergoing single-agent and combination therapy clinical trials to develop a series of broad indications for solid tumors and hematological tumors.

 Baizean® has been approved in China for combined chemotherapy for the treatment of patients with first-line advanced squamous non-small cell lung cancer (NSCLC).

Baizean® is also conditionally approved for the treatment of patients with relapsed or refractory classic Hodgkin's lymphoma (cHL) who have undergone at least second-line chemotherapy and the failure of platinum-containing chemotherapy with high PD-L1 expression, including neoadjuvant or adjuvant Patients with locally advanced or metastatic urothelial carcinoma (UC) who progressed within 12 months of chemotherapy.

Full approval for the above two indications will depend on the results of ongoing confirmatory randomized controlled clinical trials.

 In addition, three new indications of Baizian® have been accepted in China and are in the review process, including one for combined chemotherapy for the treatment of first-line advanced non-squamous NSCLC patients and one for the treatment of previously received platinum Second or third-line locally advanced or metastatic NSCLC patients with disease progression after chemotherapy, and a patient with unresectable hepatocellular carcinoma that has been treated previously.

 At present, there are 16 registered clinical trials of Baizean® in China and globally, including 13 phase 3 clinical trials and 3 key phase 2 clinical trials.

 In January 2021, BeiGene and Novartis reached a cooperation agreement, authorizing Novartis to develop, manufacture and commercialize Bazeran® in North America, Europe and Japan.

 Bazeran® has not yet been approved in countries and regions outside of China.

About the clinical project of Beizian® (Tilelizumab injection) The clinical trials of tislelizumab include: Tilelizumab vs.
docetaxel for second-line or third-line treatment of non-small cell lung cancer Phase 3 clinical trial of patient safety and effectiveness (clinicaltrials.
gov registration number: NCT03358875) Phase 3 clinical trial of tislelizumab versus rescue chemotherapy for the treatment of patients with relapsed or refractory classic Hodgkin’s lymphoma (Clinicaltrials.
gov registration number: NCT04486391) Phase 3 clinical trial of tislelizumab for the treatment of patients with locally advanced or metastatic urothelial cancer (clinicaltrials.
gov registration number: NCT03967977) tislelizumab combined with chemotherapy Phase 3 clinical trial of contrast chemotherapy for first-line treatment of patients with advanced squamous non-small cell lung cancer (clinicaltrials.
gov registration number: NCT03594747) tislelizumab combined with chemotherapy versus chemotherapy for first-line treatment of advanced non-squamous non-small cell lung cancer Patient Phase 3 clinical trial (clinicaltrials.
gov registration number: NCT03663205) Phase 3 clinical trial of tislelizumab combined with platinum-containing dual-agent chemotherapy for the treatment of patients with non-small cell lung cancer (clinicaltrials.
gov registration number: NCT04379635).
A phase 3 clinical trial of ralizumab/placebo combined with platinum drugs and etoposide for the treatment of patients with extensive-stage small cell lung cancer (clinicaltrials.
gov registration number: NCT04005716) tislelizumab versus sorafenib Phase 3 clinical trial for first-line treatment of patients with hepatocellular carcinoma (clinicaltrials.
gov registration number: NCT03412773) Phase 2 clinical trial of tislelizumab for the treatment of treated patients with unresectable hepatocellular carcinoma (clinicaltrials.
gov registration) No.
: NCT03419897) Phase 2 clinical trial of tislelizumab for the treatment of patients with locally advanced or metastatic urothelial bladder cancer (clinicaltrials.
gov registration number: NCT04004221) tislelizumab versus chemotherapy for second-line treatment Phase 3 clinical trials in patients with esophageal squamous cell carcinoma (clinicaltrials.
gov registration number: NCT03430843) Phase 3 clinical trial of tislelizumab combined with chemotherapy for the first-line treatment of patients with esophageal squamous cell carcinoma (clinicaltrials.
gov registration number: NCT03783442) tislelizumab versus placebo combined with concurrent radiotherapy Phase 3 clinical trial of chemotherapy for the treatment of patients with localized esophageal squamous cell carcinoma (clinicaltrials.
gov registration number: NCT03957590) Phase 3 clinical trial of tislelizumab combined with chemotherapy compared with placebo combined with chemotherapy for the first-line treatment of gastric cancer ( clinicaltrials.
gov registration number: NCT03777657) Phase 2 clinical trial of tislelizumab for the treatment of patients with MSI-H or dMMR solid tumors (clinicaltrials.
gov registration number: NCT03736889) tislelizumab combined with chemotherapy vs.
comfort A phase 3 clinical trial (clinicaltrials.
gov registration number: NCT03924986) for the first-line treatment of patients with nasopharyngeal cancer (Clinicaltrials.
gov registration number: NCT03924986).
About BeiGene BeiGene is a global, commercial-stage biotechnology company focusing on research, development, and To produce and commercialize innovative drugs to improve the efficacy and availability of medicines for patients around the world.

BeiGene currently has more than 5,400 employees worldwide and is accelerating the company's diversified pipeline of new cancer therapy drugs.

At present, two self-developed drugs of BeiGene, the BTK inhibitor Baiyueze® (Zebutinib Capsules) are being sold in the United States and China, and the anti-PD-1 antibody drug Bezean® (Tilelizumab) is being sold in the United States and China.
Injection) is sold in China.

In addition, BeiGene is or plans to sell a number of oncology drugs authorized by Amgen, Xinji Logistics Co.
, Ltd.
(belonging to Bristol-Myers Squibb) and EUSA Pharma in China, and has reached a cooperation agreement with Novartis to authorize Novartis in North America , Europe and Japan developed, produced and commercialized the anti-PD-1 antibody Bezian®.

For more information, please visit www.
beigene.
com.
cn.

Forward-Looking Statement This press release contains forward-looking statements as defined under the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including the phase 1b clinical trial of sitravatinib in combination with Bazeran® Data and clinical benefits that may be confirmed in the future, the statement regarding sitravatinib under the heading "About sitravatinib", as well as BeiGene's progress plans related to Bezeran® and sitravatinib, expected clinical development plans, pharmaceutical regulatory milestones and Commercialization, etc.

Due to various important factors, actual results may differ materially from forward-looking statements.

These factors include the risks of: BeiGene’s ability to prove the efficacy and safety of its drug candidates; the clinical results of the drug candidates may not support further development or marketing approval; the actions of the drug administration department may affect the initiation of clinical trials , Timetable and progress, and drug marketing approval; BeiGene's ability to market drugs and drug candidates (if approved) to achieve commercial success; BeiGene's ability to obtain and maintain the intellectual property protection of its drugs and technologies; BeiGene's reliance on third parties for drug development, production and other services; BeiGene's limited experience in obtaining regulatory approvals and commercialization of pharmaceutical products, and obtaining further working capital to complete the development of drug candidates and realize and maintain profitability Ability; the impact of the global pandemic of COVID-19 on BeiGene's clinical development, supervision, commercial operation, supervision and other businesses; BeiGene has a more comprehensive view in the "Risk Factors" section of Form 10-K in the most recent annual report The various risks discussed; and the discussion of potential risks, uncertainties and other important factors in BeiGene’s subsequent submission to the U.
S.
Securities and Exchange Commission.

All information in this press release is only as of the date of the press release, and BeiGene has no responsibility to update such information unless required by law.

The 2021 QbD 2nd Biological Medicine Quality Science Conference, sponsored by Bioo Valley (a leading biomedicine aggregation community), will be held in Beijing Shengda from May 25th to 26th.
The conference will be "Integrating quality concepts into analysis, R&D and production "Management" is the theme, and Dr.
Yao Yanping, senior quality director of BeiGene (Beijing) Biotechnology Co.
, Ltd.
, is invited to the conference to give a presentation on the theme of "Application of Electronic Technology in Biopharmaceuticals"! For more details of the conference, please poke the QR code below!