Targeting the global pattern of CTLA-4 R&D, Chinese companies are in a favorable position

The preface "CTLA-4 kicks off: A grand gold rush feast" pointed out that CTLA-4 has ushered in the second wave of development boom.
This article will focus on the global development pattern of CTLA-4 drugs and the difference in progress between China and the United States.
From an equal angle, more intuitively expound the opportunities for CTLA-4 drugs and domestic companies in the upsurge
.

1.
Newcomers to commercialization

2.
Late clinical

3.
New wind direction

4.
Differences between China and the United States create opportunities

5 Conclusion

1 Drug Y, a new member of commercialization, has been approved for the treatment of 6 cancer types, including melanoma, renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, non-small cell lung cancer and pleural mesothelioma.
The good news about the target of CTLA-4, such as Kangfang Bio's AK104 for the treatment of 2L/3L cervical cancer NDA was accepted by the NMPA, and the interim analysis of the Y drug combined with the O drug for the treatment of untreated esophageal squamous cell carcinoma showed that OS was successful.
The benefits have statistical significance and clinical significance, making the indications about to expand from 6 cancer types to 8 cancer types
.

Figure 1 New indications for the commercialization of CTLA-4 products (source: public information, compiled by Fengshuo Ventures)

2 Late-stage clinical There are currently about 27 registered/critical clinical trials for CTLA-4 products.
In addition to the cancer types mentioned above, there are more new cancer types under trial, such as gastric cancer/esophageal adenocarcinoma , Urothelial cancer, small cell lung cancer, bladder cancer, thymic cancer, pancreatic cancer and breast cancer
.

Figure 2 Products that are active in the registration/critical clinical phase for CTLA-4 (source: public information, compiled by Fengshuo Ventures)

3 In addition to the two veteran level CTLA-4 drugs Y drug and Tremelimumab, in the past 5 years, new CTLA-4 drugs have entered the clinical stage, and there are about 19 new drug candidates
.

Figure 3 Products targeting CTLA-4 that have entered the clinical stage in the past 5 years (source: public information, compiled by Fengshuo Ventures; including some CD80 fusion proteins)

Except for the two veteran products, only Kangfang Bio (including one transferred to Merck) and Kangning Jerry's products are in the critical/registered clinical/NDA stage, and the remaining new drug candidates are in the POC proof-of-concept stage
.

Figure 4 The current stage of CTLA-4 products that have entered the clinical stage in the past 5 years (source: public information, Fengshuo Venture Capital; POC is the proof-of-concept stage; including some CD80 fusion proteins)

The combined use of CTLA-4, in addition to the currently approved combination O drug/chemotherapy, is slowly exploring and expanding in more aspects, including pan-RTKi (multi-target receptor tyrosine kinase inhibition) that affects cell survival.
Agents), HER2, EGFR and Nectin-4, VEGF that affects angiogenesis, and PARP that affects DNA damage repair
.

Figure 5 Combination methods adopted for CTLA-4 products (source: public information, Fengshuo Venture Capital; only statistics clearly indicate trials with specific indications; figures refer to the number of trials)

4 Opportunities created by differences between China and the United States The following picture shows the distribution of CTLA-4 tumor types in the United States.
Seven of the top 10 cancer types in the United States include 7 types.
The red is the tumor that is only distributed in the United States and other regions but not in China.
The types, namely bladder cancer, head and neck cancer, prostate cancer and colorectal cancer, play a role in exploring the way for domestic enterprises
.

Figure 6 The distribution of tumor types for CTLA-4 products in the United States (source: public information, Fengshuo Venture Capital; only statistics that clearly indicate specific indications; * is the top 10 cancer types in the United States)

The following figure shows the distribution of CTLA-4 tumor types in China.
Seven of the top 10 cancer types in China are included in the top 10 cancer types.
Red is the tumor types that are only distributed in China but not currently distributed in the United States.
They are breast cancer, Domestic companies have played the role of explorers for thymic cancer, pancreatic cancer and nasopharyngeal cancer
.

Figure 7 The distribution of tumor types for CTLA-4 products in China (Source: public information, Fengshuo Venture Capital; only statistics clearly indicate the specific indications; * is the top 10 cancer types in China)

The following figure shows that the development situation in the United States is in a trend of "low at both ends and high in the middle", and most of them are in the registration/critical clinical stage.
These registered/critical clinical trials are all made up of two old-level drugs.
Contributed by Tremelimumab, the new generation of CTLA-4 drugs are in the POC stage
.

Figure 8: Stage distribution of products targeting CTLA-4 in the United States (Source: public information, compiled by Fengshuo Ventures; only statistics clearly indicate trials with specific indications; * is the top 10 cancer types in the United States)

The figure below shows that the development situation in China is in a "decreasing" trend.
One indication of Y drug has been approved in China.
The NDA of Kangfang Bio's AK104 has been accepted by NMPA, and all registered/critical clinical trials have been accepted.
Contributed by two drugs, Kangfang Bio's AK104 and Kangning Jerry's KN046, and the rest of the new generation of CTLA-4 drugs are in the POC stage
.

Figure 9 China's CTLA-4 product phase distribution (source: public information, Fengshuo Ventures; only statistics clearly indicate trials with specific indications; * is the top 10 cancer types in China)

The differences in the development of CTLA-4 drugs between China and the United States have created three major opportunities for domestic companies.
The first is that there are very few domestic approvals, and most of them are on the same starting line.
The future competitive landscape of the domestic market has yet to be determined
.

Concluding remarks

Throughout the full text, CTLA-4 continues to expand from the number of cancer types and the number of combination therapies.
More and more new indications are about to enter the NDA stage.
At the same time, a large number of new generation CTLA-4 enter the clinical stage.
The CTLA-4 has entered the development boom
.