Another ADC new drug clinical failure!

On December 6, Bolt Therapeutics announced the latest clinical data of the new HER2-TLR7/8 immunostimulatory ADC drug BDC-1001 at the ESMO IO meeting.
Among them, the ORR was only 2.
5% and the DCR was 32.
5%
.
Affected by this news, Bolt shares fell 56%
.
It is understood that in August this year, Innovent announced that it has reached a new drug research and development agreement with Bolt, and will jointly develop three antibody-immunostimulatory conjugate (ISAC) drug candidates for the treatment of tumors
.
According to the terms of the agreement, Bolt will receive a cash advance of US$5 million from Cinda Biotech at the time of the contract, and an equity investment of up to US$10 million in the future
.
In addition, in terms of immunostimulating ADC, BeiGene introduced Ambrx's site-specific coupling technology, while tracking the development of immunostimulatory ADC-antibody coupled TLR7/8 agonists
.
According to "Nature" forecasts, the total sales of 10 ADC products listed before 2020 will exceed 16.
4 billion U.
S.
dollars by 2026
.
The domestic ADC market will be launched in 2020 and is expected to reach 7.
4 billion yuan and 29.
2 billion yuan in 2024 and 2030, respectively, with a compound annual growth rate of 25.
8% from 2024 to 2030
.
In the post-PD-1/L1 era, ADC has become a new hot drug, attracting pharmaceutical companies to invest in it
.
ADC drug development is not all smooth sailing As of now, a total of 14 ADC drugs have been approved for marketing worldwide
.
The wave of ADC drug research and development has been repeated.
Multinational pharmaceutical giants such as AstraZeneca, Merck, Gilead, etc.
have invested heavily in deployment through cooperation and mergers and acquisitions
.
Domestic pharmaceutical companies are also vying to enter the ADC drug field, increasing their self-research efforts, and license in/out blockbuster transactions occur frequently
.
However, ADC drug development has not been smooth sailing
.
In September of this year, Silverback Therapeutics disclosed the Phase I clinical data of the new immunostimulatory ADC drug SBT6050 at the ESMO meeting.
Among the 14 evaluable patients, the overall response rate ORR was only 7%
.
Previously, due to the failure of phase III clinical trials, the failure of second-line therapy, maintenance therapy, combined chemotherapy and combined immunotherapy, AbbVie announced in 2019 that it had terminated the first targeted DLL-3 antibody-conjugated drug ovalpituzumab tesirine (Rova-T).
) For the research and development plan for SCLC patients, the project lost nearly 10 billion U.
S.
dollars
.
In China, in February and March of this year, Biotech successively issued announcements stating that due to high clinical development and market risks, it announced the termination of Phase III clinical trials of the HER2 ADC drug BAT8001 and BAT8003 (recombinant humanized anti-injection drugs).
Clinical development of Trop2 monoclonal antibody-maytansine conjugate)
.
The ADC new drug presses the pause button, and the basic loss of R&D investment alone exceeds 300 million yuan
.
Kelun and Hengrui are researching more than ten models.
However, these failures did not stop the enthusiasm of enterprises to enter the game
.
From the perspective of R&D pipelines of domestic and foreign companies, ADC drugs have become a key layout direction, and more than 100 drugs under development are undergoing clinical trials
.
It is expected that the next 5 years will usher in a new round of peaks.
From the point of view of targets, HER2 is a popular target
.
It is worth noting that ADC drugs not only attract many innovative pharmaceutical companies, but some large pharmaceutical companies have more than ten ADCs under research, such as Kelun Pharmaceuticals and Hengrui Pharmaceuticals
.
In August of this year, KLUS PHARMA INC, a subsidiary of Kelun Pharmaceutical Holdings, received a written notice issued by the FDA, allowing its "SKB264 for injection" antibody conjugate (ADC) to carry out clinical trials in the United States
.
As early as April 2020, the official website of CDE showed that SKB264, a new class 1 drug for injection of Sichuan Kelun Botai Bio-Pharmaceutical Co.
, Ltd.
, obtained clinical tacit approval and was intended to be used for the treatment of solid tumors.

.
Kelun Pharmaceutical's ADC drug also targets HER2 A166, which has submitted a key phase II clinical application to CDE
.
In addition to A166 and SKB264, Kelun Pharmaceutical also has 11 preclinical ADC products
.
In recent years, Hengrui has also continued to deploy ADC drugs and developed new ADC technologies such as antibody-conjugated TLR7/8 agonist-conjugate, antibody-conjugated Eribulin and other new ADC technologies
.
The company has more than 22 models of new drugs in development ADC, which has been declared clinically paragraph 7, including second-generation HER2 ADC, Trop2 ADC, Claudin 18.
2 ADC and so on
.
In addition, many large pharmaceutical companies choose to invest in this field
.
In June 2021, Zhenbaodao Pharmaceutical announced that it would invest 400 million yuan in Terris to enter the field of biopharmaceuticals
.
In addition to Teruisi, Treasure Island has successively invested in a number of ADC R&D companies such as Duoxi Biology and Ecoresis in 2021, and invested 1.
7 billion yuan to build a Hangzhou biopharmaceutical project focusing on the development of anti-tumor ADC drugs.

.
Breakthrough in medical insurance access has only been successfully negotiated for domestic products.
In recent years, Cinda Bio has continued to expand its product line through self-research and BD cooperation.
In the ADC drug field, in addition to the introduction of Bolt-related platforms, it announced at the end of June this year Signed a license agreement with Synaffix on antibody-conjugated drug technology.
The latter will provide the necessary proprietary ADC technologies, including GlycoConnect, HydraSpace, and a certain linker-toxin under its toxSYN platform, enabling Inda Bio to quickly build on its own The antibody develops ADC candidate molecules with best-in-class potential
.
In terms of ADC drug layout, Cinda not only has traditional ADC cytotoxic drugs, but also develops immunostimulatory conjugate drugs
.
At the same time, ADC products based on bispecific/biparatopic antibodies will also be developed
.
In addition to Cinda, innovative pharmaceutical companies such as Rongchang Bio and Duoxi Bio also have a deeper layout
.
Rongchang Biotechnology has a fully integrated ADC platform, and 4 ADC products have entered clinical studies or have been approved for marketing
.
Among them, the first domestic ADC, vedicitumumab, was approved by the National Medical Products Administration on June 9, and is suitable for HER2 overexpression locally advanced or metastatic gastric cancer (including gastroesophageal For the treatment of patients with junctional adenocarcinoma, the indications for urothelial carcinoma have been submitted for marketing and have been included in the priority review
.
In addition, RC88 targeting mesothelin, RC108 targeting c-Met, and RC118 targeting Claudin 18.
2 have all entered the clinical development stage
.
In August of this year, Rongchang Biotech reached an exclusive global license agreement with Seagen, a well-known international biopharmaceutical company, to develop and commercialize its new ADC drug vedicitumumab.
The total potential income from this transaction is as high as US$2.
6 billion has refreshed the transaction record of overseas authorized single-variety Chinese pharmaceutical companies
.
As a hot track, ADC drugs also ushered in a breakthrough in medical insurance access this year
.
A total of two imported and one domestic ADC drugs have been approved in China, namely Roche's enmetrastuzumab for injection, Takeda's vebutuximab, and Rongchang Biologics's vedicutuzumab for injection
.
In this year's medical insurance negotiations, only domestic ADC drugs were successfully negotiated
.
As one of the domestic companies with the largest ADC product layout, Duoxi Biologics is a company focusing on the development of antibody-conjugated drugs.
It currently has 24 ADC R&D pipelines, of which 3 drugs have entered the clinical trial stage
.
In April of this year, the company's application for a clinical trial of the company's MUC1 ADC drug was accepted by the NMPA, which is the first domestically-made MUC1 ADC drug
.
Some people believe that ADC drugs may become the next "PD-1" due to the large number of companies deployed.
Only by selecting the right target can we better seize market opportunities
.
In the end, who can stand out from the encirclement, let us wait and see
.