On March 7, 2021 China Oncology Focus Limited (COF), an affiliate of Lee’s Pharmaceutical Holdings Limited (Lee’s Pharm, HKEX: 950) reported that its anti-PD-L1 antibody, Socazolimab, licensed from Sorrento to COF for the greater China territory, has been cleared to begin a multicenter, randomized, double blinded, parallel-group clinical trial of Socazolimab (anti-PD-L1 monoclonal antibody, formerly known as ZKAB001) combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer (Press release, Sorrento Therapeutics, MAR 7, 2021, View Source [SID1234576176]). The clearance is based on the results from an earlier Phase Ib trial in which Socazolimab combined with carboplatin and etoposide showed a promising efficacy and safety profile in patients with extensive-stage small-cell lung cancer. The Principal Investigator for the clinical trial will be Professor Shun Lu from the Shanghai Chest Hospital and the site is expected to initiate patient recruitment in the second quarter of 2021.

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Socazolimab is an in-licensed product from Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento") for the People’s Republic of China, Hong Kong, Macau and Taiwan. Three Phase I clinical trials of Socazolimab monotherapy have been completed: (1) recurrent or metastatic cervical cancer; (2) advanced urothelial carcinoma; and (3) high-grade osteosarcoma after adjuvant chemotherapy for maintenance purposes. For recurrent or metastatic cervical cancer, a pivotal study has been completed and breakthrough therapy designation was granted by the NMPA in February 2021. Lee’s Pharm expects to file the New Drug Application for Socazolimab in recurrent or metastatic cervical cancer in the second quarter of 2021. Apart from monotherapies, several studies of Socazolimab combining with chemotherapy are being conducted in advanced urothelial carcinoma (Phase Ib), extensive-stage small-cell lung cancer (Phase III), and neoadjuvant treatment in esophageal carcinoma (Phase Ib+II).

Dr. Henry Ji, Chairman and CEO of Sorrento Therapeutics, stated, "We at Sorrento are pleased with the collaboration with our colleagues at Lee’s Pharm and with the further advances of our first therapeutic antibody partnership in Socazolimab."

About Socazolimab

Socazolimab is a fully human anti-PD-L1 monoclonal antibody identified by Sorrento using its proprietary G-MAB library platform. COF received exclusive rights to develop and commercialize the antibody for Greater China, which includes Mainland China, Hong Kong, Macau, and Taiwan. Socazolimab has the following potential advantages over its competitors:

Fully human antibody potentially allows it to have minimal immunogenicity; demonstrated by its negative antigen-derived antibody (ADA) generation in humans in studies to date.
Potentially lower dose required to achieve efficacy compared to other anti-PD-L1 antibodies.
Dual mechanism of action observed with both immune-checkpoint inhibition and antibody-dependent cellular cytotoxicity (ADCC) effect.
The antibody has been tested or is being tested in various cancer indications including recurrent or metastatic cervical cancer, maintenance therapy for high-grade osteosarcoma after adjuvant chemotherapy, locally advanced and metastatic urothelial carcinoma, extensive small cell lung cancer in combination with carboplatin and etoposide, and advanced urothelial carcinoma in combination with albumin-bound paclitaxel and esophageal carcinoma.

On March 7, 2021 CMAB Biopharma (Suzhou) Inc’s ("CMAB") partner Shanghai Junshi Biosciences Co., Ltd. ("Junshi Biosciences") (HK: 1877; SH: 688180), reported that a clinical trial application for its PD-1/TGF-β bifunctional fusion protein JS201 injection (JS201) has been accepted by National Medical Products Administration (NMPA) (Press release, CMAB Biopharma, MAR 7, 2021, View Source;bifunctional-fusion-protein-301242062.html [SID1234576171]).

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JS201 is a bifunctional fusion protein developed by Junshi using its proprietary technology that can simultaneously target PD-1 and TGF-β (transforming growth factor-β). JS201 is the first product targeting PD-1/TGF-β approved for a clinical trial application in China. JS201 can effectively block the immunosuppressive pathways of PD-1 and TGF-β which improves the immunomodulatory effect in the tumor microenvironment, thereby promoting the killing effect of the patient’s immune system on tumor cells and reducing the occurrence of immune escape and drug resistance.

"A hearty congratulations to our partner Junshi Biosciences on entering the new phase of JS201", said Dr. Yongzhong Wang, CEO of CMAB, "Utilizing our advanced integrated biological drug development platform, we provided CMC related services including cGMP production of drug substance and drug product for the JS201 project. We wish the JS201 clinical study success as we believe that this novel product can provide significant benefits for cancer patients."

On March 5, 2021 Hengrui Pharmaceutical’s reported its innovative drug SHR6390 tablets was included in the list of proposed breakthrough treatments by the Drug Evaluation Center of the National Medical Products Administration (Press release, Hengrui Pharmaceuticals, MAR 5, 2021, View Source [SID1234633503]).

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Source: CDE
SHR6390 is an oral, high-efficiency and selective small molecule CDK4/6 inhibitor developed by Jiangsu Hengrui, which belongs to the first class of chemical drugs.

Introduction to CDK4/6 Inhibitors
Introduction to CDK4/6 Inhibitors
Cyclin Dependent Kinase (CDK) is a key kinase involved in cell cycle regulation.

CDK4/6 inhibitor approval status

CDK4/6 inhibitor approval status
In recent years, CDK4/6 inhibitors are rapidly changing the treatment pattern of HR+ and HER2- advanced breast cancer.

Pfizer’s piperacillil no longer leads the way, CDK4/6 inhibitor melee is about to start
Pfizer’s piperacillil no longer leads the way, CDK4/6 inhibitor melee is about to start
As the first CDK4/6 inhibitor drug to be marketed, Pfizer’s piperacillil has an obvious first-mover advantage.

It can be said that piperacillil dominates the CDK4/6 inhibitor market, and even if reboxilil and abecilil are listed afterwards, they have not been able to shake its market position.

In fact, on December 18, 2020, Qilu Pharmaceutical’s 4 generic drugs, piperacillil capsules, have been approved for marketing by NMPA, which is the first imitation of this variety, and its indication is the first-line combination of aromatase inhibitors to treat postmenopausal patients.

(Source: CDE)

In short, CDK 4/6 is a star target, and many companies are developing innovative drugs in the country.

Reference source:

Reference source:
1.

3.

4.
Im SA, Lu YS, Bardia A, et al.
Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer.
N Engl J Med.
2019;381(4):307-316.

On March 5, 2021 Lepu Biopharma reported the application for clinical trial of "CG0070 Injection" by Lepu Biopharma Co., Ltd. (hereinafter referred to as"Lepu Biopharma") has been accepted by Center for Drug Evaluation (CDE), NMPA (Acceptance No.: JXSL2100029) and publicized on March 4, 2021 (Press release, CG Oncology, MAR 5, 2021, View Source [SID1234608843]). CG0070 oncolytic virus antineoplastic drug is brought in by Lepu Biopharma fron CG Oncology, Inc., USA., obtaining its product development rights and global supply rights in China.
Oncolytic viruses can selectively replicate in tumor cells and then lyse tumor cells, and could meanwhile try to avoid affecting the growth of normal cells; with the development of cancer immunotherapy, the therapeutic potential of oncolytic viruses in various diseases such as malignant tumors has received more and more attention. Since the US FDA approved Amgen’s T-VEC oncolytic virus antineoplastic drugs in 2015, a number of oncolytic virus antineoplastic drugs have entered clinical studies worldwide. At the same time, a number of clinical studies have also been carried out on the synergistic effect of the combination of oncolytic viruses and other anti-tumor drugs.
CG0070, an oncolytic virus antitumor agent, is a genetically modified adenovirus type 5 (Ad5) that is modified to contain the cancer-selective promoter E2F-1 and the human granulocyte macrophage-colony stimulating factor GM-CSF gene to selectively replicate and lyse tumor cells in tumor cells with defective Rb regulation. Lysis of cancer cells releases tumor-specific antigens and GM-CSF expressed with the virus, which stimulates a systemic anti-tumor immune response.
In recent years, Lepu Biopharma has actively step into the field of oncolytic viruses. In addition to introducing the CG0070 project of CG Oncology, Inc., Lepu Biopharma has also taken a stake in Wuhan Binhui Biopharm Co., Ltd., and has initiated a clinical trial of the combination of immune checkpoint inhibitors and oncolysis virus (OH2).

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On March 5, 2021 BerGenBio ASA (OSE:BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical need, reported the first patient dosed in an international Phase Ib trial investigating its first-in-class fully humanised anti-AXL monoclonal antibody, tilvestamab (BGB149) (Press release, BerGenBio, MAR 5, 2021, View Source [SID1234578613]).

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The objective of the study is to confirm safety, tolerability and determine a recommended phase II dose (RP2D) for use in subsequent clinical trials. It is a multiple ascending dose study, that will focus on establishing tilvestamab’s
safety profile, tolerability and provide an insight into the dose proportional response with respect to its effectiveness at modulating AXL expression, as determined by BerGenBio’s proprietary cAXL biomarker diagnostic assay.

The study will be conducted in patients with platinum resistant high-grade serous ovarian cancer, in which AXL is frequently strongly over expressed. The research will be conducted at specialist ovarian cancer centres able to perform serial biopsies in these patients, and thereby providing a comprehensive understanding of how tilvestamab modulates AXL expression in real time during a treatment period.

Richard Godfrey, Chief Executive Officer of BerGenBio, said: "We understand that AXL plays an important role in mediating the aggressive nature of this treatment resistant cancer. From our Phase Ia study with tilvestamab that was completed last year, we have an insight into its safety profile, and a safe starting dose for this first-in-patient study. I am particularly excited that we are able to conduct this state-of-the-art study collecting serial biopsies from patients with a similar disease, which will provide high quality data on how tilvestamab modulates AXL expression. This will inform how we can best use tilvestamab in a future Phase II program.

About AXL

AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases.

In COVID-19, AXL has two synergistic mechanisms of action, it acts a co-receptor to ACE2, to which the spike protein of the Sars-Cov-2 virus attaches and enters the host cell, and AXL expression is upregulated that leads to suppression of the Type 1 Interferon immune response by host cells and in their environment. Research data confirms bemcentinib inhibits SARS-CoV-2 host cell entry and promotes the anti-viral Type I interferon response.

In cancer, increase in AXL expression has been linked to key mechanisms of drug resistance and immune escape by tumour cells, leading to aggressive metastatic cancers. AXL suppresses the body’s immune response to tumours and drives treatment failure across many cancers. High AXL expression defines a very poor prognosis subgroup in most cancers. AXL inhibitors, such as bemcentinib, therefore, have potential high value as monotherapy and as the cornerstone of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Research has also shown that AXL mediates other aggressive diseases including fibrosis.

About Bemcentinib

Bemcentinib (formerly known as BGB324), is a potential first-in-class, potent and highly selective AXL inhibitor, currently in a broad phase II clinical development programme. It is administered as an oral capsule and taken once per day. Ongoing clinical trials are investigating bemcentinib in COVID-19, and multiple solid and haematological tumours, in combination with current and emerging therapies (including immunotherapies, targeted therapies and chemotherapy), and as a single agent. Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity.