On December 11, Baili Tianheng announced that its wholly-owned subsidiary, Systimmune, and Bristol-Myers Squibb have reached an exclusive license and cooperation agreement on an EGFR x HER 3 bispecific antibody ADC (BL-B01D1).
Under the terms of the agreement, Bristol-Myers Squibb will acquire exclusive development and commercialization rights to BL-B01D1 outside of Chinese mainland. To this end,BMS is required to make an upfront payment of US$800 million and up to US$500 million in immediate contingent payments to Baili Tianhengand milestone payments of up to $7.1 billion. The total potential transaction fees are as high as $8.4 billion.
800 million US dollars, setting a record for the down payment of domestic innovative drugs going overseas, and Baili Tianheng is likely to get the first milestone payment of 500 million US dollars。It has been disclosed that this bispecific antibody ADC is currently in a global multi-center Phase 1 clinical trial (BL-B01D1-LUNG101) to evaluate its safety and efficacy in patients with metastatic or unresectable non-small cell lung cancer.
On December 12th,Baili Tianheng-u 20cm daily limit, the stock price came to 131$11
BL-B01D1 is an ADC drug developed by Baili Tianheng based on its own EGFR x HER3 drug SI-B001. The indication of SI-B001 bispecific antibody for non-small cell lung cancer in China has reached phase III clinical trials. The druggability of this double target has been demonstrated.
The Health Bureau noted,BL-B01D1 is currently undergoing phase III clinical trials in China for the treatment of advanced or metastatic nasopharyngeal carcinoma
Source: wwwchinadrugtrials.org
In addition to Baili Tianheng, there are also AstraZeneca's EGFR x C-Met ADC, Biocytogen's HER2 X TROP2 and other bispecific antibody ADCs, and the HER2 bispecific antibody ADC (ZW49) that was returned by BeiGene a while ago.
At this year's ASCO conference, Baili Tianheng disclosed one of the EGFR x HER3 bispecific antibody ADCsPhase 1 clinical results: A total of 195 patients with locally advanced or metastatic solid tumors who failed the criteria** were included in the studyThe overall effective rate ORR for each tumor was 453%with a median follow-up of 41 month.
Among them,The overall ORR of 38 patients with EGFR-positive NSCLC was 632%, including 34 patients who had received three generations of EGFR inhibitors** and were resistant;The ORR for the EGFR wild-type NSCLC group was 449%；The ORR of the nasopharyngeal carcinoma group also reached 536%。In terms of clinical outcomes for lung cancer alone, BL-B01D1 has shown better efficacy than other ADC drugs such as HER3 or TROP 2.
Bristol-Myers Squibb noted in a press release that BL-B01D1 has broad potential in different solid tumors with a manageable safety profile. According to the official website of Baili Tianheng, in addition to non-small cell lung cancer, it was carried out for BL-B01D1Clinical trials include colorectal cancer, nasopharyngeal cancer, colorectal cancer, breast cancer, gastric cancer, etc., which are currently in phase 2 clinical trials
For ADCs, effectiveness is one thing, but reducing toxicity is just as important. According to Baili Tianheng, the small molecule toxin of BL-B01D1 has stronger tumor killing activity, but the payload adopts a more stable "linker" to avoid the shedding of drug molecules and make the drug have higher safety. The results published on ASCO show that:Adverse events leading to discontinuation or intolerance occurred in 3% of patients。According to the clinical results published so far, there are no cases of interstitial pneumonia caused by drugs ** in BL-B01D1.
Can BL-B01D1 overtake in corners?It's too early to tell. After all, Baili Tianheng is publicMost of the data are still only phase I clinical trials, and it is still unknown whether the dose and population can play stably after climbing
In 2023, there will be a lot of innovative drugs authorized in China, including many ADC drugs
The most well-known drug for BMS is the PD-1 drug Odivo. Drug O is the world's first marketed PD-1, which has opened the era of tumor immunity**. However, for lung cancer, which is the most common disease in the world, the results of O drug have not been satisfactory.
At the beginning of the competition, the sales of O drug have been leading, butIn August 2016, the unexpected upset of drug O in the phase III clinical trial of non-small cell lung cancer (NSCLC) deprived BMS of the opportunity to win the first-line NSCLC of single agents, ceded to Merck. After the failure of the O drug monotherapy, BMS has been working hard to strengthen the strength of the O drug combination ** in the first line of non-small cell lung cancer**. It was not until 2020 that BMS won the indication of first-line non-small cell lung cancer with the combination of "O+Y".
On the other hand, K drug, as early as 2016, won the indication of single-drug first-line non-small cell lung cancer, and took the lead all the way, and quickly completed the sales of O drug two years later. According to the data, the total sales of the global non-small cell lung cancer drug market in 2021 will be 24.1 billion US dollars, of which 60% will come from immunology** drugs led by K drugsK earned about $9.9 billion in sales for this indication, accounting for more than half of that year
In 2022, the sales of O medicine will only reach half of that of K medicine, even with Y medicine. And according to the patent layout of BMS Ono Pharmaceutical,Patents in China and the U.S. will expire in the coming years, and BMS will have to fill the vacancies sooner before then
At present, the most powerful BL-B01D1 of Baili Tianheng is non-small cell lung cancer. This is precisely the position where BMS lost in PD-1, and it makes sense to shoot heavily.
Moreover, compared with monoclonal or bispecific antibodies, the industry is currently more optimistic about ADCs. After the success of DS-8201, multinational pharmaceutical companies spared no expense to start the layout: Pfizer acquired Seagen for $43 billionIn October, Merck spent $22 billion to acquire three of Daiichi Sankyo's ADC drugsThis time Baili Tianheng'sThe potential transaction volume of 8.4 billion US dollars has set a new record for domestic ADCs to go overseas
In the ADC space, BMS is actually lagging a little behind. Since the beginning of this year, BMS has accelerated the pace of ADC deployment: in April, BMS reached a cooperation agreement from Tubulis, a German ADC R&D company, to buy ADCs with an upfront payment of $22.75 million and a milestone payment of $1 billion. In November, BMS introduced a new ADC drug, ORM-6151, from ORUM Therapeutics for an upfront payment of $100 million.
According to this agreement, Baili Tianheng will be with BMSShare the global development costs of this bispecific ADC, as well as the profits and losses in the U.S. marketand each other can get the sales share of the other party in the responsible area. If BL-B01D1 is successful, it will be a win-win situation for BMS and Baili Tianheng.
Written by Yang Xixia.
Edited by Jiang Yun Jia Ting.
Operations |Twenty-three.
Source丨Visual China.