Over 20 billion U.S. dollars!

Article source: Medical Rubik's Cube Info

Author: Old Rain

According to incomplete statistics, there were a total of 86 global pharmaceutical transactions in July 2021, of which a total of 24 transactions related to Chinese companies (domestic transactions and cross-border transactions)

Note: The transaction amount comes from the information disclosed in public data; each transaction can include multiple transaction modes; the statistical scope does not include transactions such as medical equipment, production, and CDMO services (data source: NextPharma®)

In July, the types of global transaction projects were dominated by innovative drugs and technologies, accounting for about 85%

Note: histogram statistics include project cooperation on technology platforms (data source: NextPharma®)

In July, the disease fields of the global transactional innovative drug projects were mainly distributed in the tumor field, neurological field and infection field

Note: The indications of drugs can include multiple disease areas; early products without specific projects are considered pre-clinical in the research and development stage; the rare diseases listed in the chart are TTR amyloidosis and maple syrupuria (data source: medical Rubik's Cube NextPharma®)

Key domestic/cross-border transactions

1.

On July 12, 2021, Nuocheng Jianhua announced that it will authorize the exclusive global rights of abutinib in multiple sclerosis (MS) to Bojian, and it retains its global rights in the field of oncology and certain autoimmune properties.

Obutinib is the third BTK inhibitor marketed in China

Data source: NextPharma®

The MS drug market is currently mainly concentrated in the European and American international markets, and has been divided by several MNC companies.

2.

On July 14, 2021, Cinda Biosciences and Yasheng Pharmaceutical launched a multi-level strategic cooperation, including: joint commercialization of the third-generation BCR-ABL inhibitor HQP1351; anti-CD20 monoclonal antibody Dabohua® (rituximab) Injection), anti-CD47 monoclonal antibody IBI188 (letaplimab), and Bcl-2 inhibitor APG-2575 in joint clinical development for certain indications; Innovent has made equity investment in Yasheng Pharmaceutical

Joint commercialization

Joint clinical development

Image source: NextPharma®

Equity investment

The joint commercialization-joint clinical development-equity investment model is a pioneering attempt among domestic innovative pharmaceutical companies.

3.

Established in 2019, Jiachen Xihai is an innovative pharmaceutical company dedicated to the development of an mRNA platform

On July 9, 2021, Tianjing Bio announced that it will use Jiachen Xihai's world-leading self-replicating mRNA technology to develop in vivo synthetic (in vivo) anti-tumor antibody drugs

Affected by the new crown epidemic, mRNA technology with unique advantages in vaccine development has attracted more attention
.
In addition to Jiachen Xihai, it has also driven a wave of companies on the mRNA track, including Smicrobiology, Livanda Biology, Aibo Biology, Bendao Gene, and Blue Magpie Biology.
Many of them were established around 2019.
Among them, Aibo With the late-stage clinical new crown vaccine ARCoVaX, Biology completed a financing of 750 million yuan within half a year, and Microbiology also completed a financing of nearly 200 million yuan
.

Image source: InvestNewsTM

Not only mRNA drugs, but as a branch of nucleic acid drugs, it has also driven the rapid development of the entire field
.
In the field of nucleic acid, small nucleic acid drugs are actually more mature.
At present, 14 drugs have been approved for marketing in the world, including Ionis’ antisense therapy, Alnylam’s RNAi therapy, etc.
, while most of China’s small nucleic acid drugs are in clinical practice.
Early and late stage products also depend on introduction
.

From the perspective of product development, China is still in the follow-up stage.
It is relatively conservative in product project establishment and relatively weak in independent innovation capabilities.
At the same time, it is difficult to achieve true differentiation in technology
.
From the perspective of the product itself, the challenges we face mainly come from two aspects, immunogenicity and delivery issues
.
Immunogenicity is unavoidable, and this falls to the delivery problem.
Future development still needs to further optimize the delivery problem in order to usher in a real breakthrough
.

4.
China Resources Double-Crane introduced the world's first small molecule inhibitor that acts on Fascin protein, and its clinical efficacy is beginning to show.

On July 21, 2021, China Resources Double Crane announced that it has obtained the development, production and commercialization of the new target Fascin protein inhibitor NP-G2-044 from Novita in the Greater China Region (Mainland China, Hong Kong, Macau and Taiwan) The exclusive authorization, the down payment reached 115 million U.
S.
dollars
.

A recent study showed that elevated Fascin protein levels were found in metastatic tumors, and were associated with clinically aggressive phenotypes, poor prognosis, and shorter survival
.
Based on its animal-level experiments, fascin inhibitors can enhance the anti-tumor immune response, and the combination with immune checkpoint inhibitors (ICI) has a positive effect on the survival of tumor-bearing mice
.
From the mechanism of further excavation, it can be found that NP-G2-044 can promote the accumulation and activation of dendritic cells (DC) in the tumor space
.

Image source: NextPharma®

At the ASCO meeting in 2021, Novita Company also announced the phase I clinical results of NP-G2-044.
Although no objective remission was observed, preliminary signals of anti-tumor and anti-metastatic activity can be seen, and the drug safety is good.
In the future, the efficacy of single drugs and combination with PD-(L)1 inhibitors will be further evaluated in breast cancer
.

China Resources Pharmaceutical has invested heavily in the introduction of this anti-tumor metastasis drug, mainly to accelerate innovation transformation and quality development, and to further supplement its own tumor pipeline.
However, the development of NP-G2-044 is still in the early stage, and there is still a long way to go in the future.
Go
.
With more and more domestic license in products, this trend has led to higher and higher prices of imported products.
In the future, how to no longer rely solely on the introduction of products and realize true independent innovation is a question worthy of our consideration
.
At present, Chinese companies are also gradually changing.
Not only are some innovative pharmaceutical companies starting to focus on the early stage of product R&D based on technology platforms, but also some of the license in models represented by Zai Lab Biotech have also begun to change.
I believe that the future will be in the big environment.
Driven by national policies, China can develop more FIC drugs
.

Key overseas transactions

1.
Pfizer has invested heavily in PROTAC and is expected to achieve the world's first PROTAC molecule to be listed

On July 22, 2021, Pfizer and Arvinas, founded by PROTAC pioneer Professor Craig Crews, reached an agreement on the development and commercialization of ARV-471, with a total amount of US$2.
4 billion and a down payment of US$650 million
.

ARV-471 is one of the fastest PROTAC molecules developed by Arvinas, which acts on the more mature target-ER
.
The previously disclosed interim analysis of the Phase I clinical study of patients with ER-positive and HER2-negative breast cancer who have received an average of 5 pre-therapies shows that ARV-471 can significantly reduce the ER expression level in the patient’s tumor tissue, and on average the ER level A reduction of 62%, and a maximum reduction of nearly 90%
.
Moreover, ARV-471 showed degrading effects on both wild-type ER and ESR1 mutants
.
The research and development progress of ARV-471 and the expected clinical efficacy, as well as the founder's strong influence in this field, have contributed to the cooperation between Pfizer and Arvinas, and also demonstrates Pfizer's determination to be the first in this field
.

There are currently 130 PROTAC products under research worldwide, of which only 9 have entered the early clinical stage, and 2 are in the IND stage
.
Not only are major international pharmaceutical companies deploying PROTAC one after another.
Looking at the country, in addition to universities, such as Haisco, Kaixing Pharmaceutical, and Yasheng Pharmaceutical all have their own PROTAC pipelines, and self-research and external cooperation go hand in hand
.

Domestic competitive landscape

Data source: NextPharma®

It is worth noting that most of PROTAC's products under development target validated targets, such as BET, BTK, AR, etc.
, and there are very few products under development that are traditionally regarded as non-drugable targets
.
Although in theory PROTAC has good performance in tissue distribution, penetration, oral availability, etc.
, more cases and clinical trials are needed to prove its advantages in non-prepared drug targets
.
At the same time, because PROTAC is an emerging technology, future drug efficacy evaluation and molecular design also need to be further modified and optimized
.

2.
Regeneron reveals GPR75, a new obesity target, and AstraZeneca makes another bet in the field of obesity and related metabolism

On July 27, 2021, AstraZeneca and Regeneron announced the cooperation to develop small molecule compounds targeted by GPR75 to treat obesity and related comorbidities, including type 2 diabetes and heart disease
.
If Regeneron succeeds in bringing an anti-obesity drug to the market, it will improve its position in metabolic diseases
.

This collaboration is based on the fact that Regeneron published an article in "Science" on July 2 about their discovery that a mutation in the GPR75 gene can prevent obesity
.
This new target was discovered by sequencing nearly 650,000 people and identifying individuals with rare protective mutations
.
Compared with people without genetic mutations, people with at least one inactive copy of GPR75 have a lower BMI, tend to be about 12 pounds lighter on average, and have a 54% lower risk of obesity
.
Based on the above results, the GPR75 target has potential for future development
.

At the same time, the improvement of diabetes parameters (including lower blood sugar) is also closely related to GPR75
.
AstraZeneca has extensive experience in the field of diabetes.
Its flagship product, SGLT2 inhibitor Farxiga/Forxiga (dapagliflozin), has sales of nearly 2 billion U.
S.
dollars in 2020, and AstraZeneca also has several weight-loss drugs under development.
This cooperation has further enriched its R&D pipeline
.

It has to be said that people have never stopped studying drugs for the treatment of obesity.
For example, on June 6, 2021, Novo Nordisk’s Wegovy (semaglutide) 2.
4 mg subcutaneous injection was approved by the FDA for weight management.
It is the first and only weekly GLP-1 receptor agonist approved for weight management of obese patients
.
And Eli Lilly’s LY3298176 (tirzepatide), which has achieved impressive weight loss data in the treatment of diabetes.
On March 4, 2021, Eli Lilly announced the phase 3 trial SURPASS-2 (NCT03987919) of tirzepatide.
Line data for the treatment of type 2 diabetes
.
The results of the study showed that 15mg tirzepatide vs.
1mg semaglutide A1c decreased by 2.
46% vs.
1.
86%, and weight loss was 12.
4kg vs.
6.
2kg after 40 weeks of treatment
.
The study is currently in the third phase of the treatment of obesity .

Obesity and related comorbidities still have huge unmet clinical needs around the world.
Whether it is finding new targets or optimizing the administration of existing drugs, it is necessary to further improve patient compliance while ensuring efficacy.
This is our unchanging direction
.

3.
PeptiDream, a peptide coupling technology company, reached two blockbuster deals to further promote the concept of PDC

On July 27, 2021, Alnylam Pharmaceuticals, an RNAi therapy pioneering company, announced that it has partnered with PeptiDream to develop peptide-siRNA conjugates to promote the delivery of RNAi therapy in extrahepatic tissues, with a total amount of US$2.
2 billion
.
On the 29th of the same month, PeptiDream and Takeda further expanded their cooperation to develop peptide-conjugated drugs (PDC) around central nervous system targets, with a total amount of US$3.
5 billion
.

PeptiDream's PDC technology platform combines various forms of payload, including antibodies, nucleic acids, small molecules, etc.
, making peptide drugs more diversified
.

Image source: PeptiDream

In addition to the above two companies, PeptiDream has also reached cooperation with a number of MNC companies
.
Why is PeptiDream favored by many companies?

First of all, peptide drugs are relatively mature and are no longer a completely new concept.
By coupling active molecules to peptide drugs, it can solve a series of pharmaceutical problems, such as peptide-siRNA conjugates.
Peptides can promote the development of siRNA.
Transcytosis, to solve the problem of drug delivery due to other physiological factors such as the blood-brain barrier
.
Secondly, PeptiDream has established a solid foundation, and its drugs are in various forms.
At present, it has stocked hundreds of pipelines and obtained preliminary efficacy verification
.
Although the concept of PDC was put forward very early, and peptide-conjugated drugs have been approved for marketing, it is worthwhile to continue to cultivate peptide-conjugated drugs based on its future market size to treat more diseases
.

Company acquisition/M&A

Data source: NextPharma®

Concluding remarks

In July, the proportion of cooperation based on technology platforms increased significantly.
It can also be seen that companies are more and more inclined to early drug research and development cooperation instead of simply introducing a product.
AI technology and drug research and development are also increasing.
Tightly
.

At present, the transaction of pharmaceutical projects has become an important business activity of Chinese enterprises under the new situation.
The NextPharma data medical transaction module of the medical cube "tracks transaction dynamics and grasps the trend of innovation"
.
You only need to pay attention to Medicine Cube plus, subscribe to "Medicine Transaction", and you can also watch Medicine Cube's monthly global new drug monthly live broadcast and other themed live broadcasts, and you will not miss important industry trends
.

appendix:

TOP10 list of total global pharmaceutical transaction value in July 2021