Zai Lab has introduced over US$300 million, is it not too late to establish a KRAS inhibitor?

On November 1, 2021, the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China announced that the clinical trial application of the new class 1 drug MRTX849 (adagrasib) tablets jointly submitted by Mirati Therapeutics and Zai Lab has been accepted

Why KRAS detonated the world

As a well-known "drug-free" target, the KRAS (Kirsten rat sarcoma viral oncogene homolog) gene is one of the most common mutated oncogenes in human cancers.

A study analyzed the KRAS mutations in 64217 tumor specimens from 97 different cancer types

Since the data disclosure of Amgen's inhibitor AMG 510 (Sotorasib) targeting KRAS G12C gene mutations in 2019, it has broken the situation where there is no medicine available for the KRAS target

KRAS R&D competition landscape

From the perspective of global patents on KRAS inhibitors, the number of new KRAS patents in the United States began to rise significantly from 2014, and there was a sharp increase in 2016, but it was not until 2019 that Amgen’s AMG510 detonated the discussion of KRAS targets.

Figure 1 Regional development trends of new patents (country of ownership)

Data source: The opening report of the 6th China Pharmaceutical Innovation and Investment Conference for Listed Companies by Hu Yuanjia, "Excavating Patent Data to Help New Drug Research and Development"

From the perspective of domestic KRAS patents, the first company to apply for KRAS related patents is Chia Tai Tianqing.

The total number of KRAS patents in China is still small, and in the future there is still a possibility that new drug companies with strong R&D capabilities like Jacos overtaking halfway through the car will appear in the future

Figure 2 China's leading institutions for KRAS related patents

Data source: The opening report of the 6th China Pharmaceutical Innovation and Investment Conference for Listed Companies by Hu Yuanjia, "Excavating Patent Data to Help New Drug Research and Development"

At present, there are 11 KRAS inhibitors that have reached the clinical stage, of which 7 have been in clinical trials.

And BI1701963 tablets are also the only pan-KRAS inhibitors among these 11 varieties.

Fast follow is better to be First in class

From the above data, it can be seen that the domestic research and development of KRAS inhibitors is already relatively high.

From a global perspective, KRAS G12C has the highest research and development enthusiasm.

Figure 3 KRAS mutation types and corresponding index ratio

Data source: The opening report of the 6th China Pharmaceutical Innovation and Investment Conference for Listed Companies by Hu Yuanjia, "Excavating Patent Data to Help New Drug Research and Development"

However, the overall proportion of KRAS G12C mutations is not the highest, and for the different subtypes of KRAS mutations, the distribution of various cancer types is not uniform

In addition to the G12C mutation in KRAS-mutated non-small cell lung cancer, which has the highest proportion of 48%, KRAS-mutated colorectal cancer and pancreatic cancer have the highest proportion of G12D mutations, reaching 44% and 47%, respectively, and in non-small cell lung cancer The proportion of China has reached 17%

Looking at KRAS inhibitor patents from different mutation types, it can be seen that the number of new patents for KRAS G12D worldwide has increased significantly since 2016, but China currently has only 4 patents for KRAS G12D, which is in its infancy.

Figure 4 The trend of new patents for each subtype of KRAS mutation

Data source: The opening report of the 6th China Pharmaceutical Innovation and Investment Conference for Listed Companies by Hu Yuanjia, "Excavating Patent Data to Help New Drug Research and Development"

The differentiated competitive landscape is the solid foundation for a strong pharmaceutical country

On the whole, for KRAS inhibitors, although the current highest research and development status of KRAS G12C mutations is still in the early clinical stage, there are already more varieties under research in the clinical and pre-clinical stages, and only BigPharma companies with strong new drug research and development capabilities can have it.

But for other types such as KRAS G12D mutations, although there is no international R&D experience that can be used for reference, competition in this blank field is more advantageous for Biotech companies, because regardless of the size of the company, the strength of the company is Start from the same starting line

Only by directly facing the clinical blank areas where R&D is more difficult can these Biotech companies have the opportunity to rapidly grow into BioPharma or even BigPharma
.
At the same time, China's overall R&D can form a differentiated competitive landscape, and only the clinical resources that are currently overcrowded can be reasonably allocated, and China's pharmaceutical industry can go global and become a true pharmaceutical power
.