Antibody research and development change?

In just one week, the field of macromolecular biomedicine has continued:

On June 29, Kangfang Bio's PD-1/CTLA-4 bispecific antibody kadunilimumab (AK104) was approved for marketi.

On June 28, Kelun Pharmaceutical announced that its holding subsidiary Kelun Botai received a payment of US$30 million from Mer.

On June 28, Henlius and Palleon signed a "Cooperation and Licensing Agreemen.

On June 28, Innovent's IBI333 clinical application was accept.

On June 23, China Biopharmaceuticals issued an announcement announcing the acquisition of all outstanding ordinary shares of F-star Therapeutics, Inc, a NASDAQ-listed company, at a total consideration of US$161 milli.

It is not difficult to feel that a large number of pharmaceutical innovation companies that have risen rapidly in the past ten years have completed the pipeline layout and market segmentation in the pure monoclonal antibody fie.

Especially when the DS-8201 of Daiichi Sankyo/AstraZeneca was very successful in the recently concluded ASCO, and Merck announced the acquisition of Seagen, the leading ADC company, it seems to indicate that the era of antibody research and development that was purely based on the target point in the past is comi.

In the face of a new round of opportunities for innovation and iteration in the field of macromolecular biomedicine, can new local Biotech head companies be born? Can traditional large pharmaceutical companies seize this wave and achieve technological leaps?

Multinational pharmaceutical companies officially entered the market

Breakthrough innovation risks emerging?

With the 2022 ASCO held, DS-8201 and ADC, as the hottest industry topics, have attracted countless traffic and attenti.

Judging from the current research and development progress, DS-8201 can stand out among a large number of pipeline products such as DS-1062 and U3-140 The HER-2 target itself is a classic target, and its innovative drug development is very likely to further expand the targ.

In fact, ADC consists of three parts: antibody, linker and payload, and for DS-8201, trastuzumab (Herceptin) is coupled to a topoisomerase-I inhibitor Camptothecin derivatives, antibodies and cytotoxic drugs themselves are traditional drugs but have shown amazing efficacy, which not only opens up a new path for clinical drug use, but also completely refreshes the previous research and development of macromolecular dru.

For a long time, the research and development ideas around the target have attracted the tyrants from all walks of life, especially in popular fields such as PD-1/L1, VEGF, CD47, TIGIT, and LAG-3, the situation of Me-too drugs getting together is very serio.

Experts said that if the target itself has good drugability, especially the classic target, the development of monoclonal antibodies under the follow strategy, and the macromolecular drugs to solve the problems of the technology itself, the performance of the product can often be expected in terms of efficacy; For new targets, the main reason why innovative drugs are at risk is that the "scientific" exploration of unknown or cutting-edge targets is inherently uncertain, and the understanding of targets and mechanisms is still not deep enou.

Obviously, ADC drug research and development emphasizes bioengineering technology rather than target druggability or macromolecule antibody research, which undoubtedly leads to the pursuit of innovative technology platforms by enterpris.

In March 2019, AstraZeneca spent US$9 billion to reach a cooperation with Daiichi Sankyo to jointly develop and commercialize the blockbuster HER2 ADC drug Enhertu (DS-8201) on a global scale; in July 2020, AstraZeneca once again Spend 6 billion US dollars to develop TROP2-ADC DS-1062 in cooperation with Daiichi Sank.

In September 2020, Gilead announced the acquisition of Immunomedics for US$21 billion, and obtained the new and first-of-its-kind ADC drug Trodelvy targeting Trop-2; the Chinese name of the drug is Goxatuzumab, and the commercialization rights in China belong to Genting Xinyao has just been approved for listing in early Ju.

In September 2020, Merck and Seagen reached a cooperation agreement to jointly develop the LIV-1 ADC drug ladiratuzumab vedotin, and conduct clinical research on the combination of the drug and Merck K dr.

Based on the partnership, Merck will pay Seagen a $600 million down payment and up to $6 billion in milestone payments, and make a $1 billion equity investment in Seag.

In the era of monoclonal antibody in tumor immunotherapy, "K drug" has driven Merck to achieve huge performance growth and is expected to become the "Drug King"; however, in the face of increasingly fierce market competition, looking for the next blockbuster potential The broad market prospect of DS-8201 obviously aggravates Merck's favor for ADC technology, and Seagen is undoubtedly the most likely high-quality targ.

The data shows that Seagen ranks second in the world in the number of ADC pipelines, second only to ImmunoG.

Seagen's first ADC is Adcetris (targeting CD30), which was approved by the FDA in 2011 for the treatment of classic Hodgkin's lymphoma and CD30-positive NHL; the second is Padcev (targeting TF), in 2019 FDA-approved in December for the treatment of locally advanced or metastatic urothelial carcino.

It is understood that, as of now, Seagen has 4 ADC drugs approved for marketing, and a number of new ADC drugs are under developme.

It was Gilead who took the first step to snap up the ADC platfo.

In 2020, Gilead bought Trop2 ADC drug Trodelvy for $21 billi.

Focusing on Trodelvy, Gilead is eager to expand its product offerings and has set a goal of oncology making up a third of the company's total revenue by 203

However, any choice comes with risks, and Gilead's aggressive layout has not achieved the expected commercial succe.

Judging from the market performance of Trodelvy, Gilead's total revenue in 2021 is US$2305 billion, an increase of 11% year-on-ye.

Among them, the sales of Trodelvy are not high, and the first full annual performance is only US$380 milli.

Previously, according to.


analysts’ estimates, if Trodelvy wanted to make a return, peak sales would have to reach at least $4 billi.

Market analysis believes that in the HR+/HER2- field, Trodelvy's clinical performance in key indications HR+/HER2- breast cancer is not as good as expected; on the other hand, Daiichi Sankyo's DS-8201 is in full swing, which is bound to squeeze some of Trodelvy's market share ; What is more worrying is that DS-1062, the Trop2 ADC drug of Daiichi Sankyo, is already on the road of research and developme.

Big Molecule Popular Tracks

Platform differentiation stimulates potential

Whether it is from the technical iteration path of overseas pharmaceutical companies or the development process of domestic macromolecular drugs in China, the most common summary of antibody drug research and development is undoubtedly "monoantibodies look at the target, non-mabone look at the platform", which is also highly summarized The important value of the innovative technology platform in the upgrading of antibody R&D technolo.

In the face of competition brought about by the excessive concentration of targets in the "Red Sea", new technologies and new drug forms have become the most realistic technological upgrade angle for leading pharmaceutical companies and start-up pharmaceutical compani.

In recent years, the research and development of new macromolecular drugs in China has been rapidly heating up, and differentiation has become an inevitable choice for latecome.

On June 9, 2021, the State Food and Drug Administration passed the priority review and approval process and conditionally approved the listing of Rongchang Bio's ADC drug vedicetumab (RC48), officially kicking off the localization of ADC dru.

The industry generally believes that since the targets in the fields of double antibody and ADC involve a wider range, various drug combination schemes based on drug targets will surely create more sufficient conditions for differentiated competiti.

In the last round of China's pharmaceutical innovation opportunity period, a large number of enterprises such as Betta Pharmaceuticals, Innovent Bio, Junshi Bio, BeiGene, Rongchang Bio, Kangfang Bio, and CStone stood out; The climb has also made biotech companies such as Genting Xinyao, Anmai Bio, Immune Onco, Duoxi Bio, Pufang Bio, and Ying En Bio become a new focus:

In July 2021, Pufang Bio and biotechnology company Synaffix reached a $246 million cooperati.

Synaffix will be eligible to receive a collaborative upfront payment and potential milestone payments totaling up to $246 million, as well as tiered royalties based on net sales on future commercialization of the ADC produ.

In June 2022, Docent Bio announced that it has reached a cooperation and licensing agreement with Janssen Pharmaceutical Biotech, a subsidiary of Johnson & Johns.

Doxi Bio will apply its unique ADC innovation platform and the unique antibody provided by Janssen, and the two parties will agree on up to 5 development of novel ADC dru.

With the maturity of technology and the launch of products, it is an inevitable industry trend for large pharmaceutical companies to participate in competiti.

At present, large domestic pharmaceutical companies including Hengrui Pharmaceutical, Qilu Pharmaceutical, Simcere Pharmaceutical, Huadong Medicine, and CSPC are also looking for a new round of technological breakthrough opportunities and market growth potential areas:

In February 2021, Hangzhou Zhongmei Huadong Pharmaceutical .

, L.

, a wholly-owned subsidiary of Huadong Medicine, signed a strategic cooperation agreement with Provention Bio to introduce bispecific antibody PRV-3279 for the treatment of systemic lupus erythematosus and the prevention or reduction of immunogens for gene therapy Exclusive clinical development and commercialization rights for these two indications in Greater Chi.

PRV-3279 is a humanized dual antibody against B cell surface proteins CD32B and CD7

In August 2021, Corning Jereh and Jinmante Bio, a wholly-owned subsidiary of CSPC, signed a development and commercialization license agreement in mainland China for the anti-HER2 bispecific antibody KN026 independently developed by Corning Jer.

The total transaction amount It is RMB 1 billion and a double-digit tiered sales commissi.

From the perspective of the industry, new drugs such as double antibodies and ADCs, as a forward-looking alternative drug, have higher technical barriers in R&D, production, clinical and other aspects compared with monoclonal antibodies, accelerating the development of next-generation macromolecular drugs The process will be a new opportunity for China's pharmaceutical innovation and upgradi.

At least, judging from the US$4 billion authorization of Merck's anti-tumor drug from Kelun Pharmaceuticals, the industry generally speculates that the product is TROP2 A.

It can be seen that even if it is Me-too, multinational pharmaceutical companies still buy high-quality products with potenti.

The "post-PD-1 era" is by no means a competition for a certain target or antibody, but a competition for clinical value brought about by breakthrough technologi.

The players in the double-antibody and ADC tracks are already in place, and the competition for many entrants has just beg.

Domestic pharmaceutical companies are investing more resources in new fiel.

Traditional Pharma and emerging Biotech are expected to achieve more breakthroughs in this field in the futu.