Double Anti-New Deal for comments!

On April 11, in order to further standardize the clinical research and development of bispecific antibody-based anti-tumor drugs, CDE issued the "Technical Guidelines for Clinical Research and Development of Bi-specific Antibody Anti-tumor Drugs (Draft for Comment)" to solicit opinions from the industry

In the past two years, the research and development of double-antibody drugs has entered the fast lane, becoming another outlet following popular tracks such as PD-1, CAR-T, and antibody-conjugated drugs

In the field of oncology drugs, the competitive landscape of domestic PD-1 has led many innovative companies to change their commercialization ideas

Recently, the cooperation between Harbin Pharmaceutical and AZ on the development and commercialization of the bispecific antibody (HBM7022) project has attracted widespread attention in the industry
.
And not just because it received a whopping $300 million-plus in payments, plus royalties based on its future sales
.
What is even more eye-catching is that AZ will fully take over all its preclinical research and development work, and the latter will bear all the costs
.
It is equivalent to saying that the former discovered a "rich mine" and sold it to the latter for development and benefit sharing
.

Looking at this case, the strategy chosen by Hebo Pharmaceuticals, which has only been established for 7 years, is to reduce the cost of commercialization and quickly realize the development of other pipelines
.
At the end of March, its bispecific antibody targeting both tumor antigen B7H4 and T cell costimulatory molecule 4-1BB was approved for clinical application in China, which is a typical development logic of "small but beautiful"
.
Since its establishment in 2016, all revenue has come from external authorization and cooperation
.
At the end of 2020, AbbVie bought out the development rights of its new coronavirus antibody ABBV-47D11, and Hebo Pharmaceuticals will no longer participate in the subsequent clinical development and commercialization of this product
.
From the perspective of AZ, the new Shuangkang track has strategic investment value
.

The cooperation between domestic innovative companies and multinational pharmaceutical companies has a new vision
.
In fact, combing through several typical domestic Biotech companies, it is not difficult to find that the biggest common point of companies that have been or are planning commercialization is "borrowing external forces"
.
Kangfang Bio and Corning Jereh did not put commercialization on their shoulders like Hengrui, Baiji, Xinda, etc.
Kangfang Bio chose to invest in Chia Tai Tianqing; He sold the commercialization rights to Sidi Pharmaceuticals, which then handed over the domestic commercialization rights to Simcere Pharmaceuticals
.

With the gradual formation of an ecological environment in which "small biotech companies are the driving force for innovation, and multinational companies are the boosters for the amplification of innovation value", can you make a bold guess: whether domestic "small and beautiful" companies will become multinational companies in the future The target of pharmaceutical mergers and acquisitions? Take Pfizer as an example.
Last year, it acquired a medium-sized Biotech company for $6.
7 billion, and nearly half of its 13 clinical pipelines have entered or are about to enter clinical phase III
.
Another $2.
26 billion acquisition went to a global leader in CD47
.
In fact, CSPC also invested in Biotech
.
"Looking for blockbuster drugs at low cost through early investment + later authorization purchase will be a very important way for pharmaceutical innovation
.
" According to industry insiders, Amicus in the United States is a typical representative of a "small but beautiful" biological company: not large in scale , but the research and development strength is strong
.
It employs around 150 people and has a market value of over $1 billion
.
Being needed and leading the world, when more real innovations continue to emerge, it may be a matter of time before China's "small but beautiful" companies are incorporated into the world-class pharmaceutical company system
.

See the highs and lows in innovation

As emphasized in the "Draft", the research and development of double antibody needs to further clear the barriers for innovation, and focus on the design and development ideas oriented by clinical needs
.

Kangfang Bio's candenizumab (AK104) has submitted a marketing application to NMPA in September last year for the treatment of relapsed or refractory cervical cancer; Corning Jereh's KN046 is suitable for non-small cell lung cancer and thymic cancer.
The disease is in a critical clinical stage, and domestic double-antibodies will soon be launched one after another
.
Henlius also announced not long ago that the clinical trial application for PD-L1/TIGIT dual antibody HLX301 has been accepted
.
According to incomplete statistics, at least ten domestic models are currently in Phase III clinical trials, and more than 20 are in Phase II clinical trials
.
Throughout these dual-antibody targets are very diverse, PD-L1/4-1BB, EGFR/MET, CD3/CD20, etc.
are all popular targets
.

However, innovation is still being tested
.
In 2021, Merck's Bintrafuspalfa (PD-L1/TGF-β bifunctional fusion protein) under development suffered 4 consecutive clinical trial failures, casting a shadow on the development of dual antibodies
.
At present, 4 double-antibody products have been launched in the world.
The first drug, catulumumab, was approved for cancer ascites.
However, it was delisted in 2017 due to poor sales performance after the launch
.
A year ago, the domestic Lingteng pharmaceutical industry restarted the listing process of the drug on a global scale
.
The second dual-antibody drug on the market is blinatumomab developed by Amgen
.
The sales in 2020 are 379 million yuan.
The main reason for affecting its sales is that the half-life is only 2 hours, which reduces the compliance of patients with medication
.
BeiGene has obtained the authorization for the introduction of the drug and was included in the priority review
.
The third double-antibody on the market is the Roche-developed Emicizumab, which breaks the replacement therapy for hemophilia that only relies on factor VIII
.
In 2020, global sales reached 2.
335 billion US dollars, and it was listed in China in 2018
.
In addition, emeclizumab was granted priority review by the CDE for the treatment of hemophilia A in the presence of factor VIII inhibitors
.
Due to the strong impact of biosimilars on Roche China in the oncology sector: the "old troika" bevacizumab, trastuzumab, and rituximab, the overall oncology business revenue is still declining, and double antibody Drugs have high hopes
.

Analysts believe, "At present, the domestic double-antibody drug industry chain is concentrated in the middle and upper reaches
.
Many companies reduce R&D costs through R&D outsourcing services.
The main factors affecting the upstream are the types of bioreactors and culture conditions
.
At the same time, due to the bispecific antibody It is easy to cause agglomeration, which puts forward higher requirements for the purification of antibodies
.
" But he believes that, despite this, 4 of the top 10 global best-selling drugs in 2021 are antibody drugs, which are double antibodies with differentiated competitiveness.
There is still much to be done
.