More than 10 new drugs have been approved for clinical use!

Text|Pharmaceutical Mission Hills

The Center for Drug Evaluation (CDE) of the State Food and Drug Administration of China recently announced that a number of new drugs have obtained implied approval for clinical trials

1.

Indications: advanced malignant solid tumor

PARP inhibitors are the first class of drugs that use the concept of "synthetic lethality" to achieve clinical success

AZD5305 is a next-generation PARP inhibitor specifically designed for PARP1.

2.

Indications: High-risk HER2-positive early breast cancer

DS-8201a (trastuzumab deruxtecan) is an antibody conjugate drug targeting HER2 jointly developed by Daiichi Sankyo and AstraZeneca

It is worth mentioning that DS-8201a was previously included in the breakthrough therapy category by CDE.

3.

Indications: advanced solid tumor

Because bifunctional antibodies can bind to two antigens at the same time to regulate two signal pathways related to the treatment of cancer, this type of therapy has received widespread attention in the industry in recent years

BJ-005 is a recombinant bifunctional fusion protein, which is formed by the fusion of PD-L1 targeting IgG1 monoclonal antibody with a part of the extracellular domain of TGF-β receptor II

4.

Indications: advanced malignant solid tumors, advanced hepatocellular carcinoma and other solid tumors

HBM4003 is a new generation of anti-CTLA-4 fully human heavy chain antibody that can significantly enhance antibody-dependent cell-mediated cytotoxicity (ADCC) and specifically eliminate Treg cells with high CTLA-4 expression in the tumor microenvironment

At the 2021 European Society of Medical Oncology (ESMO) annual meeting, Harmonicare will announce the results of a phase 1 clinical trial of HBM4003 monotherapy for advanced solid tumors
.
The research data showed that HBM4003 showed good effectiveness, safety and tolerability
.
The study also showed that the immunogenicity of HBM4003 in humans was extremely low, and confirmed the unique PK/PD characteristics and new mechanism of action found in preclinical studies
.

5.
Hutchison Medicine: HMPL-453 tartrate tablets

Mechanism of action: FGFR 1/2/3 inhibitor

Indications: Combination chemotherapy or anti-PD-1 monoclonal antibody for patients with advanced solid tumors

HMPL-453 is a highly selective small molecule FGFR 1/2/3 inhibitor under research.
It targets the target area to block the FGFR-mediated signal pathway, thereby achieving the purpose of inhibiting tumor growth
.
At present, the product has launched a phase 2 clinical trial for advanced malignant mesothelioma in China, and a phase 2 study for patients with advanced intrahepatic cholangiocarcinoma
.
This time, HMPL-453 was approved for clinical use in China, and the proposed development indications are: combined chemotherapy or anti-PD-1 monoclonal antibody for patients with advanced solid tumors
.

According to the 2021 interim results and the latest business developments announced by Hutchison Pharmaceuticals, HMPL-453 is expected to start research on combination therapies with other anti-cancer therapies in China at the end of 2021 or early 2022
.

6.
Qilu Pharmaceutical: QLF31907 for injection

Mechanism of action: PD-L1/4-1BB bispecific antibody

Indications: Malignant tumor

According to Qilu Pharmaceutical’s earlier press release, QLF31907 is a bispecific antibody developed by Qilu that can simultaneously target PD-L1 and 4-1BB (CD137)
.
On the one hand, the product can block the PD1/PD-L1 immunosuppressive pathway by binding to PD-L1
.
On the other hand, it can activate the downstream immune activation signal of 4-1BB and promote the killing of tumor cells by immune cells
.
This dual-targeting mechanism is expected to greatly enhance the anti-tumor efficacy of candidate drugs
.

In preclinical trials, QLF31907 performed better in terms of safety and effectiveness, and was significantly more effective than anti-PD-L1 monoclonal antibody
.
This time the product has been approved for clinical use and is intended to be developed for use in malignant tumors
.

7.
Dino Medicine: DN1508052-01 for injection

Mechanism of action: TLR8 agonist

Indications: advanced malignant solid tumor

DN1508052-01 is a highly effective small molecule Toll-like receptor 8 (TLR8) agonist for cancer immunotherapy
.
TLR receptors are an important part of the innate immune system.
Activation of these receptors can improve the antigen presentation of dendritic cells and macrophages in the tumor microenvironment, and promote the proliferation of CD8+ T cells
.
There are 13 types of TLRs in the TLRs family.
Among them, TLR8 is closely related to autoimmune diseases and is mainly expressed in monocytes, macrophages, and myeloid dendritic cells.
It has a broad application prospect and is a new star in the field of tumor immunotherapy.

.

Prior to this, DN1508052-01 has been clinically approved in the United States and China
.
Among them, the indications for which the product has been approved for clinical research in China are: for the treatment of advanced solid tumors that have progressed after standard treatment or have no standard treatment
.
This time, DN1508052-01 was once again approved for clinical use, and it is planned to be developed for advanced malignant solid tumors
.
According to the ClinicalTrials website, Dino Medicine has initiated an open, multi-center phase 1 clinical trial to initially evaluate the safety tolerance, pharmacokinetic properties and anti-drug properties of the product for single-drug subcutaneous injection in patients with solid tumors.
Tumor activity
.

8.
Yiyi Bio: F-652

Mechanism of action: Recombinant human interleukin 22-Fc fusion protein for injection

Indications: chronic and acute liver failure

According to the announcement of Efan Pharmaceuticals, F-652 is a class 1 innovative biologic drug with independent intellectual property rights owned by its subsidiary EiBio.
It is a recombinant human interleukin 22-Fc (IgG2) fusion protein expressed through CHO cells using genetic engineering technology.

.
According to the announcement, the product completely mimics the activity mechanism of human interleukin 22.
The Fc fragment greatly prolongs the half-life of interleukin 22, and has a significant improvement in drug efficacy
.

Up to now, F-652 has completed 5 clinical studies worldwide
.
Among them, there are two phase 2a clinical trials conducted in the United States for acute graft-versus-host disease (GvHD) and acute alcoholic hepatitis (AH)
.
These trials have reached the preset goals, indicating that the candidate drug has good safety and effectiveness
.
F-652 has also been granted orphan drug designation by the FDA for the treatment of GvHD
.
The clinical study approved for F-652 is a phase 2 clinical trial of F-652 combined with conventional regimens for the treatment of chronic acute liver failure
.

9.
Kangfang Biology: AK112 injection

Mechanism of action: PD-1/VEGF bispecific antibody

Indications: Extensive stage small cell lung cancer

AK112 is a new tumor immunotherapy drug developed by Kangfang Biological.
It is a PD-1/VEGF bispecific antibody
.
The product can block the combination of PD-1 and PD-L1 and PD-L2, as well as the combination of VEGF and VEGF receptor, so it has the curative effect of immunotherapy drugs and anti-angiogenesis drugs at the same time
.
Early studies have shown that AK112 blocks these two targets at the same time, and may block these two pathways more effectively than combination therapy, thereby enhancing anti-tumor activity
.

Prior to this, AK112 has carried out a phase 1 clinical study of dose climbing and expansion in China, Australia and other countries
.
In May 2021, Kangfang Biopharmaceuticals will carry out a number of single-drug or combination-drug clinical trials, with indications covering non-small cell lung cancer, recurrent ovarian cancer, and gynecological tumors
.
This time the product was again approved for clinical use, and it is planned to be developed for use in extensive-stage small cell lung cancer
.

10.
Jiayue Medicine: JYP0061 tablets

Indications: Autoimmune diseases

According to the announcement on the CDE official website, JYP0061 is a new class 1 small molecule drug under development by Jiayue Pharmaceutical.
This is the first time that the product has been clinically approved in China and is intended to be developed for use in autoimmune diseases such as moderate to severe rheumatoid arthritis
.
Jiayue Pharmaceutical is committed to the research and development of innovative drugs, focusing on the development of tumors and autoimmunity, metabolism and infectious diseases
.
At present, the company has established a diversified R&D pipeline, and more than a dozen clinical trials are in progress simultaneously
.

Reference materials:

[1] Center for Drug Evaluation (CDE) of China National Medical Products Administration.
Retrieved Sep 8, 2021, from http:// and property-based drug design of AZD5305, a highly selective PARP1 inhibitor and trapper.
Retrieved April 10, 2021, from https://#!/9325/presentation /1338

[3] Dino Pharmaceutical's official website.
from http:// ENHERTU® Granted Priority Review in the US for Treatment of HER2 Positive Metastatic Gastric Cancer.
Retrieved October 28, 2020, from https:// Prospectus of Hutchison Medicine.
from https://www1.
hkexnews.
hk/listedco/listconews/sehk/2021/0618/2021061800170_e.
pdf

[6] Targeting PD-L1/TGF-β, BJ Bio's bifunctional fusion protein was approved by the FDA.
Retrieved Jun 21, 2021, from http://en.
bjbioscience.
com/blog/_836274_326210.
html

[7] Announcement on the approval of the clinical trial approval notice for the newly-added indications of chronic and acute liver failure of F-652, a newly developed product of the holding subsidiary.
Retrieved Sep 8, 2021, from http:// new/disclosure/detail?stockCode=002019&announcementId=1210983215&orgId=gssz0002019&announcementTime=2021-09-08

[8] Hebo Pharma will announce the research results of a new generation of anti-CTLA-4 antibody phase I clinical trials at the 2021 ESMO annual meeting.
Retrieved Jul 26, 2021, from https:// shtml

[9] The PD-1/VEGF double antibody (AK112) has initiated multiple clinical studies.
Retrieved May 12, 2021, from https://mp.
weixin.
qq.
com/s/jbVRhmhXBzHTo5tcwYb2Lw

[10] The clinical trial application of Qilu's new bispecific antibody anti-tumor drug QLF31907 targeting PD-L1 and 4-1BB was accepted by China CDE.
Retrieved Jul 8, 2021, from https://mp.
weixin.
qq.
com/s /-hHwfZJ8PU9pL458ZXC3vA

[11] Leading Portfolio | Jiayue Pharmaceutical completed more than 300 million yuan in Series B financing.
SDIC Ventures and Sequoia Capital China Fund jointly led the investment.
Retrieved July 28, 2021, from https://mp.
weixin.
qq.
com /s/tSUgVkUhVUbWb__wV1mYmQ