2021 AACR | Chinese companies such as BeiGene, Corning Jerry, and Tianjing Bio will make their debut

Transfer from | Pharmaceutical Mission Hills

The American Association for Cancer Research (AACR) is one of the largest cancer research conferences in the world, with a history of over 100 years.

1.

At this conference, BeiGene will announce a number of clinical data on its anti-PD-1 antibody Bezean (tislelizumab) and the selective kinase inhibitor sitravatinib under investigation in the form of an oral report.

Baizean is a humanized lgG4 anti-PD-1 monoclonal antibody, which has been approved for 3 indications in China, involving advanced squamous NSCLC, relapsed or refractory classic Hodgkin’s lymphoma, advanced or metastatic disease Three types of urothelial carcinoma.

It is worth mentioning that in November 2020, BeiGene has announced that the RATIONALE 303 clinical trial has reached the primary endpoint of overall survival (OS) in the pre-planned interim analysis.

Sitravatinib is a tyrosine kinase inhibitor under development that can effectively inhibit receptor tyrosine kinases (RTKs).

2.

KN046 is a bispecific antibody independently developed by Corning Jereh that can simultaneously target PD-L1 and CTLA-4 immune checkpoints, which can more effectively activate T cells and enhance immune anti-tumor capabilities.

At this conference, Corning Jerry will announce the data of an open, multi-center Phase 1b/2 clinical study (study number: KN046-203) of KN046 combined with paclitaxel in the treatment of patients with advanced triple-negative breast cancer in the form of a poster.

Phase 2 clinical interim data showed that the patient’s median PFS (Progressive Free Survival) was 7.

3.

Uliledlimab is a highly differentiated CD73 humanized monoclonal antibody.

At this conference, Tianjing Bio will display the new protein structure of uliledlimab and CD73, as well as a series of preclinical data when it is used as a single agent and PD-1/PD-L1 antibody.

Research believes that: TJD5 is a humanized anti-CD73 antibody with a unique C-terminal domain epitope, which can realize a novel dimer binding mode in vivo, which distinguishes it from other CD73 antibodies in terms of mechanism of action and inhibitory efficacy.
Currently, TJD5 is undergoing phase 1 clinical trials in the United States and China to verify these differentiated properties and anti-tumor activity.

4.
Developing the pharmaceutical industry: GT19077, GT19506

Mechanism of action: c-Myc targeted therapy

c-Myc is an oncogenic transcription factor, which plays a major role in tumorigenesis, cancer cell survival, proliferation and immune escape.
Studies have found that the IGH/Myc genome translocation can be identified in B-cell lymphoma (15-100%), and Myc family members are amplified in approximately 20% of small cell lung cancer (SCLC) patients.
Therefore, it is necessary to discover and develop new c-Myc inhibitors that target c-Myc.
GT19077 is a c-Myc/Max protein-protein interaction small molecule inhibitor being developed by Pioneer Pharmaceuticals, and GT19506 is a c-Myc targeted therapy developed by protein degradation therapy (PROTAC).

At this AACR annual meeting, Pioneer Pharmaceuticals will publish the results of a preclinical study of GT19077 and GT19506 for c-Myc-driven blood cancer and small cell lung cancer (SCLC).
In this study, the researchers explored the anti-tumor effects of GT19077 and GT19506 in c-Myc-driven blood cancers and small cell lung cancer.
The results show that the two therapies can inhibit the proliferation of B-cell malignant tumors and SCLC cells, and have the potential to treat c-Myc genome mutation-dependent tumors.
Currently, GT19077 and GT19506 are in the lead compound optimization stage.

5.
Yasheng Pharmaceutical: APG-2449, Oribatinib/APG-2575, APG-1387, etc.

Mechanism of action: focal adhesion kinase (FAK) inhibitor, FLT3 inhibitor/BCL-2 inhibitor, IAP inhibitor, etc.

Ascent Pharmaceuticals has 6 latest preclinical advancements of 5 original innovative drugs selected for this conference.
These achievements are mainly focused on the transformational research of many important varieties of Ascent Pharmaceuticals that have entered the clinical development stage.
Here are an excerpt from 3 studies for introduction.

APG-2449 is a new type of FAK/ALK/ROS1 inhibitor with high oral bioavailability under development by Yasheng Pharmaceutical.
Researchers will share the study of APG-2449 by down-regulating CD44 to enhance the sensitivity of ovarian cancer to chemotherapy.
Researchers explored the anti-tumor activity of APG-2449 in combination with chemotherapy for ovarian cancer.
The results show that the inhibitory effect of APG-2449 on FAK makes ovarian cancer sensitive to chemotherapeutics in preclinical tumor models, and the down-regulation of CD44 or ALDH1 of the cancer stem cell population mediates synergistic anti-tumor activity.
These findings promote the clinical development of APG-2449 combined with chemotherapy for the treatment of ovarian cancer.

The other is a study on the synergy of FLT3 inhibitor auribatinib (HQP1351) and BCL-2 selective inhibitor APG-2575 in a preclinical model of FLT3 mutant AML.
The results showed that the inhibition of FLT3 by HQP1351 would down-regulate the expression of the anti-apoptotic protein MCL-1, and could cooperate with APG-2575 to enhance the apoptosis of FLT3 mutant AML.

In addition, researchers will also share the results of the therapeutic potential of IAP inhibitor APG-1387 combined with DR5 agonist CTB-006 in preclinical models of solid tumors.
The results showed that in vitro, the combination therapy showed a dose-dependent synergistic effect in various cancer cell lines.
In the MDA-MB-231 and 2LMP TNBC xenograft models, APG-1387 or CTB-006 single drugs show limited anti-tumor activity, and the combination of the two can enhance this effect.

6.
Qiyu Bio: QP34563457

Mechanism of action: trastuzumab/pertuzumab/IL-15 trifunctional fusion protein

IL-15 is a member of the IL-2 superfamily, and has similar biological activities as IL-2, and has the ability to stimulate the proliferation of T cells and natural killer (NK) cells.
HER2 is overexpressed in approximately 10% to 20% of breast cancers, and its expression is associated with a worse prognosis of patients.
At this AACR annual meeting, Qiyu Bio will announce the results of a preclinical evaluation study of the three-functional fusion protein QP34563457 for the treatment of HER2-positive cancer.

QP34563457 is a trastuzumab/pertuzumab/IL-15 trifunctional fusion protein developed by Qiyu Biologics using its bispecific antibody platform.
Trastuzumab (trastuzumab) and Pertuzumab (pertuzumab) are both HRE2 targeted therapy, among which Pertuzumab can inhibit HER2 receptor dimerization.
In vivo and in vitro studies have shown that the trifunctional fusion protein QP34563457 has higher biological activity than the HER2 antibody trastuzumab or pertuzumab and its combination, indicating that the candidate drug may have a higher biological activity in HER2-positive cancers.
Good therapeutic potential.

7.
Jikai Pharmaceutical: B13.
14.
1 TCR-T, B8.
2.
4 TCR-T

Mechanism of action: TCR-T targeted therapy for RasG12V and RasG13D

RAS is the first oncogene identified in human tumors.
The currently known RAS family has three genes, KRAS, NRAS, and HRAS.
They are the most common oncogenes in cancer-about 20% of human tumors There is a RAS mutation.
Among them, KRAS mutations account for about 80% of the total RAS mutations, and the most common mutations are RasG12V and RasG13D.
However, no drug for RAS has been successfully developed and approved, and there are a large number of unmet medical needs in the treatment of cancers that carry RAS mutations.

At this AACR conference, Jikai Medicine will announce the results of a preclinical study using TCR to target the treatment of RAS mutant cancers.
In this study, the researchers developed two TCR-Ts through engineering modifications that can recognize RASG12V and RASG13D that appear on HLA-matched tumor cell lines, and induce strong INFγ release.
In addition, the researchers also observed effective and specific tumor cell lysis in multiple RASG12V and RASG13D tumor cell lines.
The researchers said that its TCR-T targeted therapy for RasG12V and RasG13D has great potential in the treatment of cancers driven by RAS mutations.

8.
Jiahe Bio: GB261, GB262, GB263, GB264

Mechanism of action: CD20/CD3 T cell adaptor, PD-L1/CD5 double antibody, etc.

According to the Jiahe Biologics press release, the preclinical progress of the company's four drug candidates on the dual antibody/trier antibody platform will be published at the AACR conference in 2021.
These studies are: 1) the new CD20/CD3 T cell engager targeting CD20+ cancer has multiple mechanisms; 2) the new bispecific antibody targeting PD-L1 and CD55 for cancer treatment Development; 3) Application of cMET/cMET/EGFR trispecific antibody in the treatment of non-small cell lung cancer; 4) Claudin 18.
2/CD3 bispecific antibody can maintain effector function to develop better cancer therapy.

For more than 100 years, AACR has attracted researchers in this field with its scientific breadth and excellent reputation, promotes the exchange of new knowledge and new ideas among scientists in the field of cancer research, and provides training opportunities for the next generation of researchers to increase public awareness Cancer awareness.
We will continue to track the information of this AACR conference and share more cutting-edge developments in the field of cancer research with you.

Reference materials:

[1]AACR official website.
From https://#!/9325/

[2] Tianjing Bio will announce the mechanism of action and preclinical research data of its differentiated CD73 antibody Uliledlimab at the 2021 AACR (American Association for Cancer Research) annual meeting.
Retrieved Mar 11, 2021, from https:// -mabbiopharma.
com/cn/article-617.
aspx

[3] Corning Jerry will announce the clinical research data of PD-L1/CTLA-4 double antibody KN046 combined with paclitaxel in the treatment of triple-negative breast cancer at the AACR 2021 meeting.
Retrieved Mar 11, 2021, from http:// .
com/html/news/2281.
html

[4] BeiGene will announce a number of clinical and preclinical data at the American Association for Cancer Research (AACR) 2021 annual meeting.
Retrieved Mar 10, 2021, from https://ir.
beigene.
com/static-files/ 827d6c34-3ea5-4ad1-a1a3-62df61b03812

[5] Jiahe Biotech announced that it will announce the four latest preclinical progress at AACR 2021.
Retrieved Mar 11, 2021, from https:// -latest-preclinical-progress-to-be-presented-at-aacr-2021/