The highlight moment of ADC drugs and the internationalization journey of domestic pharmaceutical innovation-September pharmaceutical frontier update excerpts
September’s pharmaceutical frontier innovations, the most impressive ones: one is ADC drugs are ushering in a bright moment, and another is the small explosion of new domestic pharmaceutical innovation forces on their journey to internationalization.
1). ADC Therapeutics’ ADC drug (Lonca) targeting CD19 submitted a marketing application to the FDA for the treatment of DLBCL in September. Lonca achieved 48.3% in the fourth-line treatment in the key phase 2 The objective response rate and the complete response rate of 24.1% were strong. In the same month, ADC Therapeutics also announced preclinical data of the ADC drug (Cami) targeting CD25. Cami can effectively deplete Tregs and thereby enhance the anti-tumor effect of the immune system. This product A pivotal Phase 2 trial in Hodgkin lymphoma is already underway.
2). Daiichi San's HER2-targeting ADC drug (deruxtecan) was approved in Japan as a third-line treatment for HER2-positive metastatic gastric cancer in September. The drug treated patients in the pivotal phase 2 clinical trial. The risk of death was reduced by 41% (the median survival time in the treatment group was 12.5 months vs. the median survival time in the chemotherapy group was 8.4 months); in addition, No. 13 *** announced an ADC drug targeting HER3 at the ESMO 2020 conference in Shanghai ( The latest phase I data of U3-1402) achieved an objective response rate of 25% and a disease control rate of 70% in patients with EGFR-positive non-small cell lung cancer who failed multiple tyrosine kinase inhibitor treatments, which is also the efficacy protrude.
3). Seattle Genetics and Genmab demonstrated key phase 2 data of the TF-targeting ADC drug (tisotumab vedotin) in the treatment of recurrent and metastatic cervical cancer at the ESMO 2020 Annual Meeting, achieving an objective response rate of 24% , with a median survival time of 12.1 months. Compared with the objective response rate of less than 15% and the median survival time of less than 10 months that are common with current therapies, this therapy has the potential to significantly improve the treatment situation for this indication; in the same month, Seattle Genetics and Astellas announced that the jointly developed ADC drug (Padcev) targeting Nectin4 reduced the risk of death compared with the chemotherapy control group in a phase 3 clinical trial of patients with urothelial cancer treated with chemotherapy and immunotherapy. by 30%, reaching the primary endpoint of Phase 3.
4). Immunomedics announced at the ESMO2020 annual meeting that the ADC drug (Trodelvy) targeting Trop2 was used in the late-line treatment of triple-negative breast cancer, achieving an objective response rate of 35% and a median survival time of 12.1 months. , in contrast, the control chemotherapy group only had an objective response rate of 5% and a median survival time of 6.7 months. The risk of death was reduced by 52% and the efficacy was strong. In addition, Immunomedics also announced the key benefits of Trodelvy in the treatment of metastatic urothelial cancer. Phase 2 clinical data showed an objective response rate of 31%, a progression-free survival of 5.4 months, and a median survival of 10.5 months, which is also significantly better than chemotherapy.
It can be seen that the development progress of ADC drugs has had an explosive performance in the past September. In addition to R&D progress, the layout actions of big pharmaceutical companies in the ADC field are also eye-catching. Less than 2 months after AstraZeneca reached a US$6 billion cooperation agreement with the first three companies in July, Gilead announced on September 13, 2020 Japan announced a $21 billion acquisition of Immunomedics to acquire Trodelvy and other drugs targeting Trop2.
Rongchang Biology is the leader in the ADC field in China. In August, it reported the production of the first domestic ADC drug (RC48) to treat HER2-positive gastric cancer; in September, RC48 was used to treat HER2-positive urinary tract cancer. The indication for skin cancer was granted breakthrough therapy designation by the FDA; at the same time, Rongchang Biotech also applied for a new clinical trial of an ADC drug targeting c-Met in September.
We remain positive and optimistic about the prospects of engineered antibodies, including ADCs and bis-antibodies, and have shared the logic in many previous roadshow reports: The evolution of biological sciences has multiple dimensions, one of which is It is "the continuous improvement of the degree of transformation intervention" in the same technical field.
In the field of peptide drugs, we have witnessed the evolutionary direction of biotechnology from "natural extraction" to "human recombination" to "engineering". A typical example is the essence of the first generation of pig/cow animal insulin. Natural extraction, second-generation recombinant human insulin is humanized transformation, and third-generation insulin is various engineering transformations based on recombinant human insulin;
Monoclonal antibody drugs are truly industrial because of their larger molecular weight. Chemical breakthroughs are 15 years later than peptide drugs, but they are expected to follow a similar evolutionary path: the first generation of mouse-derived monoclonal antibodies is roughly equivalent to the natural extraction stage, and the second-generation humanized monoclonal antibodies are roughly equivalent to recombinant human sources. In the stage of chemical transformation, with the maturity and popularization of humanization technology and the increasing difficulty of screening blockbuster new targets, it may be inevitable for monoclonal antibody drugs to enter the "engineering era" if they want to continue to open up a larger market space. Logically speaking, creating unprecedented molecules is an important basis for creating unprecedented therapeutic effects;
Therefore, the monoclonal antibody industry will move from the first half of "recombinant humanization" to The key to the second half of "engineering transformation" is whether engineered antibodies with "unprecedented" structures can achieve "unprecedented" clinical efficacy - this can logically be determined in advance, such as ADC drugs can use the precise targeting of monoclonal antibodies to carry highly toxic chemotherapy drugs to achieve precise targeted treatment capabilities that were previously impossible; another example is bispecific antibodies, which can bind two kinds of targeting to each other. This physical connection can also achieve double confirmation, further increase targeting and greatly improve security. Now, more and more clinical data are also confirming the logical advantages of engineered antibodies such as ADCs and bisAbs. Against this background, the monoclonal antibody industry is also entering the second half characterized by "engineered antibodies". There should be considerable industry opportunities here, and there are many companies in the Hong Kong stock biotech industry.
In addition to the explosion in the ADC field in September, the internationalization process of domestic pharmaceutical innovation companies also ushered in a small explosion in September.
1). I-Mab and AbbVie reached a strategic cooperation on September 4. I-Mab authorized the overseas rights of its CD47 monoclonal antibody lemzoparlimab to AbbVie for development. For this purpose, I-Mab Received US$180 million in down payment and US$20 million in Phase I clinical milestones, as well as up to US$1.74 billion in mileage and double-digit sales commissions.
2). CStone Pharmaceuticals (02616) reached a strategic cooperation with Pfizer on September 30. CStone Pharmaceuticals licensed the mainland market rights of its PDL1 product sugemalimab to Pfizer. CStone Pharmaceuticals For this purpose, it will receive up to US$280 million in mileage payments and additional tiered royalties; at the same time, Pfizer subscribed for US$200 million worth of CStone Pharmaceuticals' equity at a price of HK$13.37 per share.
3). Junshi Biologics (688180) announced on September 10 that toripalimab received breakthrough therapy designation from the FDA for the treatment of nasopharyngeal carcinoma. This indication was approved in May this year. Obtained orphan drug designation from the FDA.
4). Rongchang Biologics announced on September 21 that vidicetomab (RC48) has received breakthrough therapy designation from the FDA for the treatment of HER2-positive urothelial cancer. This was approved a few months ago. The product has just received Fast Track designation from the FDA.
5). Genetron’s stem cell cancer early screening liquid biopsy product received breakthrough therapy designation from the FDA on September 30, becoming the first domestic product to receive FDA breakthrough medical device designation. Genetron Health’s HCCscreen The prospective clinical data shows stronger sensitivity and specificity than the retrospective study of liver cancer early screening products published by Exact Sciences, an established early screening company.
The performance of domestic pharmaceutical innovation in September can be said to be a "blowout": in the years before September this year, domestic innovative pharmaceutical products had only received breakthrough therapy designation from the FDA twice ( BeiGene’s zanubrutinib, Legend Biotech’s LCAR-B38M cell preparation); and within just one month in September, domestic companies won two new drugs and one new drug designated as breakthrough therapy by the FDA. Breakthrough medical device designation!
In addition, in terms of international external authorization, regardless of the three external authorizations of Hengrui, BeiGene, and Kangfang, which are not listed below, projects that are truly licensed to multinational pharmaceutical giants at high prices and are substantially promoted, The legendary LCAR-B38M was licensed to Johnson & Johnson, and Innovent's sintilimab was licensed to Eli Lilly. In just one month in September, two major deals occurred, namely I-Mab's licensing to AbbVie and CStone's licensing to Pfizer. Amount transaction.
This is an exciting event, which essentially shows that the innovative capabilities of domestic pharmaceuticals are beginning to be recognized by mainstream markets in developed countries, and is a clear sign of the rise of domestic pharmaceutical innovation.
The innovation trend in the domestic pharmaceutical industry began to grow around 2011. BeiGene, Cinda, Junshi, etc. were established around 2011. Hengrui, Tianqing, etc. strengthened their determination to innovate and transform around 2011. This coincides with the time when the entire society began to strengthen its will to transform; the drug review reform and the development of the capital market that began in 2015 further accelerated the industry's awareness of innovation and transformation, and pharmaceutical innovation gradually became the industry's awareness. , more emerging start-ups began to be born around 2015, and their innovative layout gradually entered the harvest period after 2017. More and more domestic innovative products began to enter the public eye, and a number of products with international competitiveness began to Stand out and carry the international banner of domestic pharmaceutical innovation.
However, the rise of domestic pharmaceutical innovation is also accompanied by a systemic risk: such a strong awareness of innovation trends attracts too much resource investment, and the clinical acceptance of Class 1 innovative drugs Document numbers, for example, have been increasing year by year since 2017, and are expected to exceed 700 in 2020, reaching 10 times the number 10 years ago. Moreover, according to the current growth trend, the number of domestic Class 1 new drug acceptance documents is likely to exceed 1,000 in the next two years - this is an exaggerated number. Given the stage and size of the Chinese pharmaceutical market, there may be at most 10-20 new drugs every year1 Class 1 new drugs are domestically produced, which means that more than 95% of existing innovative drugs will be destined to fail. Judging from the current rapid growth rate of Class 1 new drugs, the pharmaceutical industry and the capital market have obviously not yet fully priced in the potential here. risk.
There are many specific catalytic forces behind the excessive blowout of domestic innovative supply, including the "innovation anxiety" of traditional pharmaceutical companies caused by the reconstruction of expectations for generic drugs, as well as typical emerging companies in the early stages of industrial trends. The phenomenon of "horse racing and enclosure". However, with the advancement of various products and the advancement of industry stages, a large number of so-called Class 1 new drugs have begun or are about to enter the "falsification period". It is expected that in the next few years, a number of innovative products and innovative pharmaceutical companies will Faced with life and death challenges - a large number of innovative products and innovative pharmaceutical companies have fallen, which will also be accompanied by the strong rise of a large number of new innovative drug forces. With the combined force of the two trending forces, industry innovation will also enter a period of relatively fierce competition and fierce competition. A new stage with higher requirements for innovation and comprehensive capabilities.