Hengrui lays out large indications, and Junshi is eye-catching in the sea... Where is the domestically-made PD-1 R&D internal rollout?

Recently, news of PD-1 frequently came out.

PD-1 products are undoubtedly the most competitive track in China.

For local innovative pharmaceutical companies, medical insurance fee control and drug price negotiations have become the norm.

01 Hengrui: PD-1 layout for large indications, follow-up pipelines are diversified

Hengrui's PD-1 indications are almost the most in the four families that have entered the medical insurance

At present, Carrelizumab has been approved for 6 indications, 4 of which have entered the medical insurance, including the treatment of locally advanced or metastatic esophageal squamous cell carcinoma patients who have previously received first-line chemotherapy and have disease progression or intolerance; For the treatment of patients with relapsed or refractory classic Hodgkin's lymphoma who have undergone at least second-line chemotherapy; combined with pemetrexed and carboplatin, it is suitable for epidermal growth factor receptor (EGFR) gene mutation negative and anaplastic lymphoma Kinase (ALK)-negative, non-resectable locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) as the first-line treatment and for the previous treatment with sorafenib and/or oxaliplatin-containing system chemotherapy Treatment of patients with advanced hepatocellular carcinoma

For the treatment of patients with advanced nasopharyngeal cancer who have previously received second-line or above chemotherapy, the disease has progressed or is intolerable, and the combination of cisplatin and gemcitabine for the first-line treatment of patients with locally recurring or metastatic nasopharyngeal cancer is coming soon Entered into 2021 drug price negotiations

Carrelizumab follow-up main clinical development pipeline

The new indications and combined pipelines of Karelizumab are also huge, with a total of 17 pipelines

The combination with famitinib is mainly for 6 indications of urinary system tumors, cervical cancer, renal cell carcinoma, etc.

Overseas, the pipeline of carrelizumab is also mainly used in combination.

The mid-term report "Research on the Commercialization Transformation Model of R&D Biotech Companies" issued by the China Pharmaceutical Enterprise Management Association pointed out that one of the conditions for Biotech's successful commercialization transformation is the clinical value and differentiation of its products.

This is undoubtedly true for large pharmaceutical companies in transition

From the perspective of R&D pipeline alone, the expansion of PD-1 indications is aimed at large indications such as lung cancer and liver cancer, and the pipeline layout of other innovative drugs is also diversified.

02 Junshi: There are fewer PD-1 combined pipelines and outstanding results in the sea

According to the semi-annual report recently disclosed by Junshi, there are 20 PD-1s of Junshi Biological, which is nothing compared to Hengrui

But unlike carrelizumab, teriprizumab is more often used in combination with chemotherapy and single-agent therapy.

For Junshi's PD-1, its overseas performance is very impressive

Junshi Bio's other pipelines in research also cover almost from pre-clinical to NDA

03 Cinda: The PD-1 combined pipeline is rich in drug forms

Judging from the research status of Sintilimab disclosed in Cinda's 2021 Interim Report, its pipelines cover all stages of clinical phase I to NDA, and the combined pipelines account for almost two-thirds of the nearly 30 pipelines
.

Sintilimab single-agent treatment for relapsed or refractory non-squamous classic Hodgkin’s lymphoma that has undergone at least second-line system chemotherapy is the first PD-1 to enter the medical insurance list.
In addition, combined chemotherapy for first-line treatment of EGFR or Three indications for ALK-negative advanced non-squamous NSCLC, first-line treatment of unresectable locally advanced or metastatic squamous NSCLC with chemotherapy, and first-line treatment of hepatocellular carcinoma with Dayoutong (bevacizumab biosimilar) Entered into 2021 medical insurance negotiations
.

The combination pipeline of Sintilimab is also focused on the combination with Sinda’s self-developed products.
In addition to bevacizumab biosimilar drugs, it also includes 5 lines with the research IBI-310 (CTLA-4 monoclonal antibody) It is worth noting that there is also a second-line treatment line for hepatocellular carcinoma in combination with small nucleic acid drugs in the combination pipeline.
still in phase I clinical
.
Most of the indications targeted by Cinda are gastric cancer, hepatocellular carcinoma, non-small cell lung cancer and other major indications
.

In terms of going overseas, Sintilimab currently has four clinical trial pipelines in the United States, including combined chemotherapy for the first-line treatment of non-squamous non-small cell lung cancer, combined chemotherapy for the first-line treatment of esophageal cancer, and monotherapy for solid tumors and advanced endometrial cancer.
and so on
.
The fastest-growing non-small cell lung cancer has entered the NDA stage
.

It can be seen from the research pipeline that has been disclosed in the interim report that Cinda has more than 20 innovative drug products in the research pipeline, of which 2 products have entered the NDA stage, 4 products have entered the critical clinical stage, and the remaining pipelines are also located in IND, Clinical Phase I and II
.
Moreover, these products cover many fields such as monoclonal antibodies, double antibodies, small molecules, and even cell therapy.
In terms of targets, they also include popular targets such as TIGIT, CD47, FGFR, and PCSK9.
The therapeutic field is mainly for tumors and Immunity
.

Cinda's pipeline

04 BeiGene: The global multi-center clinic covers almost every pipeline

The most notable feature of BeiGene's PD-1 is the number of global multi-center clinics.
Almost every clinical pipeline in research is a global multi-center
.

At present, tislelizumab has entered medical insurance for two indications: classic Hodgkin's lymphoma that has undergone at least second-line therapy and locally advanced or metastatic urothelial carcinoma with high PD-L1 expression
.
Combination chemotherapy for first-line treatment of squamous NSCLC, combination chemotherapy for first-line treatment of advanced non-squamous NSCLC, and single-drug treatment with at least one systemic treatment of large hepatocellular carcinoma and other three indications are about to enter the medical insurance negotiation in 2021
.

According to the BeiGene Interim Report, as of the first half of the year, tislelizumab had 8 pipelines under development, of which the more noteworthy is the combination with BeiGene's self-developed PARP inhibitor and BTK inhibitor, but it has not been disclosed yet.
Specific cancer
.

BeiGene’s other pipeline layouts demonstrate the reasons for its billions of R&D investment.
There are more than 30 innovative products under research, with indications covering leukemia, lymphoma, non-small cell lung cancer, nasopharyngeal cancer, ovarian cancer, fallopian tube cancer In terms of targets, it not only covers popular targets such as PD-1/PD-L1, BTK, PARP1, PARP2, TIGIT, etc.
, but also covers BCL-2, OX40, HPK1 Waiting for a crowded track
.

05 Two new PD-1 models: the differentiation is not obvious, and the follow-up competitiveness is doubtful

For the two new PD-1s, Kangfang’s Paimrizumab and Yuheng Biological’s Sepalizumab, the approved indications are all lymphomas.
There is no significant difference compared with the above four.
There are even three PD-1 products in the medical insurance for this indication
.

From the perspective of the pipeline of research, according to the CDE clinical registration information, the three indications of Sepalizumab in the treatment of triple-negative breast cancer, cervical cancer and gastric cancer have entered the clinical phase I.
Anti-therapeutic treatment The recurrence or metastasis that has progressed after receiving first-line or above platinum-containing standard chemotherapy, and the positive expression of PD-L1 (CPS≥1) cervical cancer is also included in the breakthrough therapy category
.
However, from the perspective of these three pipelines, the aforementioned four companies are also making significantly faster progress
.

According to the official website of Kangfang Biology, there are 8 pipelines of Peamprizumab under development, including two pipelines for the first-line treatment of non-squamous non-small cell lung cancer and liver cancer in combination with anlotinib, which have entered clinical III.
period, the rest are or in combination with chemotherapy alone, therapeutic areas including nasopharyngeal carcinoma, lung cancer, liver cancer and the like
.

In summary, the four PD-1s that have entered medical insurance have entered the competition of indications and combination drugs in the domestic PD-1 competition.
The subsequent two models are relatively slow in progress, whether they are approved indications or in research, and can compete.
Perhaps only treatment data
.

However, the environment facing innovative pharmaceutical companies is relatively severe.
The report of the China Pharmaceutical Enterprise Management Association pointed out that the current situation of the competition intensity of the domestic innovative drug market is: there are many drugs with the same target, and many innovative drugs are in a strong competitive situation; in medical insurance negotiations and the market Price wars arise in competition; competition from imported new drugs
.

From this point of view, for pharmaceutical companies, only in terms of R&D, expansion of indications and combination therapy are on the one hand, and more are still seeking differentiation in the field of products and treatments
.