Global anti-tumor trade trend in 2018

Transactions in the field of anti-tumor have always been extremely hot According to the transaction data over the past year, the hot degree of transactions in this field has not abated at all: the total amount of transactions reached in 2018 is more than 50% higher than that in 2017 (Figure 1) At the beginning of 2019, two leading tumor drug companies in the world, BMS and celgene, announced a merger with a transaction volume of up to $74 billion Figure 1 The number and volume of licensing, joint venture, joint development and other transactions in the field of anti-tumor in 2014-2018 For more information about datasets, see box 1 On the whole, there are three characteristics of transactions in 2018: first, the total amount of transactions has increased significantly, but the number of transactions is relatively stable; second, most of these transactions have long-term conditional payment milestones; third, the actual down payment amount of these transactions has little change (Figure 1) Of course, there are exceptions to everything In 2017, Merck and AstraZeneca entered into a heavyweight deal on the joint development and commercialization of PARP inhibitor lynparza The former paid the latter up to $1.6 billion in down payment, which also set a new record of down payment in the past five years Last year's article was entitled biopharma dealmakers B3 – B6, March According to the analysis report of 2018, licensing transactions around tumor immunity have been dominant in the past five years, and this trend has been inherited in 2018 The total volume of transactions in the field of tumor immunity is more than US $1 billion (Table 1): only two of these transactions are based on the listed projects (Merck and Weicai, BMS and nektar, all around the new combination of PD-1), and other high-value ones Most of the trading projects are in the early stage of drug discovery and preclinical research In addition to the dominant position of tumor immunity, there are two major trends of cooperation and trade in the field of tumor: 1 More and more transactions are introduced into the East Asian market, especially in China 2 There are more and more transactions around new technology platforms In the past few years, driven by a series of policy and regulatory reforms, China's biomedical R & D environment and innovative drug market have undergone significant changes A key feature of the Chinese market is the lack of the latest generation of anti-tumor drugs, especially the biological drugs represented by PD-1 drugs Based on this, from the perspective of transactions in the field of cancer, more and more Chinese local companies are actively acquiring the development rights and sales rights of innovative drugs from foreign enterprises in the East Asian market (Figure 2) Although the number and amount of these transactions are relatively small, the rapid development of China's pharmaceutical industry will greatly promote the growth of such transactions Figure 2 Licensing transaction of Chinese companies in the field of anti-tumor as the buyer For details of data set, please refer to box 1 Among these transactions, the more famous cases are: in November 2018, Baiji Shenzhou cooperated with Canadian zymeworks company, and Baiji Shenzhou won the zymeworks Exclusive authorization for the development and commercialization of zw25, a clinical candidate for bispecific antibodies, and zw49, a preclinical antibody drug conjugate (ADC), in Asia (except Japan), Australia and New Zealand Zymeworks will receive $40 million in advance and $390 million in development and commercial mileage In June 2018, cornerstone pharmaceutical, headquartered in Suzhou, announced to reach an exclusive cooperation and licensing agreement with U.S blueprint medicines to promote the development and commercialization of kinase inhibitors avapritinib, blu-554 and blu-667 in Greater China Blueprint medicines will receive $40 million in advance and $346 million in mileage In the same month, cornerstone pharmaceutical signed an exclusive license agreement with Agios company to obtain the development and commercialization rights of ivosidenib in mainland China, Hong Kong, Macao and Taiwan (ivosidenib, a drug for the treatment of acute myeloid leukemia and cholangiocarcinoma, has now been listed in the United States under the trade name of tibsovo) As part of the agreement, Agios will receive $12 million in advance and $412 million in mileage Zaiding pharmaceutical has attracted special attention due to a number of agreements signed with American companies in recent years In November 2018, the company reached a strategic cooperation agreement with macro genetics on three products under research (including margeuximab, a monoclonal antibody targeting HER2, and the bispecific molecule blocking PD-1 and LAG-3), and obtained the exclusive authorization for the development and commercialization of the above products in mainland China, Hong Kong, Macao and Taiwan Bay On the one hand, the cooperation between Chinese companies and Western companies has accelerated the entry of overseas innovative drugs into China On the other hand, it also accelerates the development of Chinese original new drugs For example, at the end of 2018, Dabusu (cindilimab injection), a PD-1 drug jointly developed by Cinda biology and Lilly company, was approved by nmpa for the treatment of Hodgkin's lymphoma and became the second domestic PD-1 drug in the Chinese market In addition to China, pharmaceutical companies in other East Asian countries are also participants in the trading game In November 2018, LG Chemical of South Korea signed an agreement with cue biopharma, a US company, to obtain the power to develop and commercialize cue-101, the core product of the latter, and "T cell targeted tumor immunotherapy" in Asia Under the agreement, cue biopharma will receive a $400 million R & D milestone, in addition to an undisclosed advance and a $5 million equity investment At the same time, the investment capital in the Asia Pacific region is gradually maturing Hillhouse capital, the top investor of China's technology companies, completed an investment worth US $10.6 billion in September 2018, involving healthcare, consumer, technology and service industries The investment amount has set a new record for private equity financing in the region More and more new technology platform transactions last year's trend shows that, in addition to China's growth, there are more and more transactions around new technology platform, especially T-cell therapy, bispecific or multivalent antibodies Table 1 shows that although large pharmaceutical companies are usually buyers of new technologies But small innovative companies are also forces that can not be ignored, and the most noteworthy one is the allogene deal After Gilead's acquisition of kit in 2017, former executives of kit pharmaceuticals, Arie belldegarun and David Chang, founded allogene, which focuses on building a new generation of car-t therapy for "allogeneic" In April 2018, allogene received a huge amount of US $300 million through round a financing (Pfizer holds 25% of the company) In the same month, allogene reached cooperation with many famous biomedical companies such as cellectis, aiming to jointly create a "universal" car-t therapy From the perspective of technology driven, the technologies involved in licensing exchanges in recent years show that: clinical value, registration supervision and commercial success are highly collaborative According to the data, the main driving factors of the transaction in 2018 are cell therapy, oligonucleotide, other antigens as immune stimulants, etc On the contrary, although the number of transactions around antibodies accounts for one-third of all transactions, the contribution of their trading volume has declined significantly (Figure 3) Figure 3 Technical categories of licensing transactions in the field of cancer; a, number of transactions; B, amount of transactions For more information on datasets, see box 1, the new alternative technology for oligonucleotides is also a key driver of large M & A deals in 2018 (Table 2) Among them, three acquisitions of oncolytic virus platform reflect the urgent need of pharmaceutical companies to explore new treatment methods in order to achieve accurate treatment Several transactions with the highest amount in 2018 are mainly concentrated in the field of car-t cell therapy: Juno, as the leader in this field, has carried out a series of mergers and acquisitions in the past few years, consolidating its technical advantages in the field of car-t cell therapy But at the beginning of 2018, celgene included it with us $9 billion, which is second only to Gilead's acquisition of kite in 2017 (US $11.9 billion) In the field of traditional tumors, GlaxoSmithKline acquired tesaro for just over $5 billion, becoming the only multi billion dollar acquisition in the field of traditional tumors Tesaro's product portfolio includes the recently approved PARP inhibitor zejula (niraparib), as well as a number of tumor immunodrugs in the early clinical stage, including PD-1 In 2018, Eli Lilly purchased ARMA bioscience for us $1.6 billion to include the latter's PEGylated interleukin-10 candidate in phase III clinical pancreatic cancer In early 2019, the company launched a larger acquisition to acquire Loxo oncology for $8 billion (the company focuses on the development of cancer treatment drugs based on specific genetic defects) In May 2017, Merkel's PD-1 drug keytruda was approved by FDA only based on the presence of gene biomarkers (highly microsatellite unstable tumor) This event has drawn a strong mark in the history of human regulatory history In November 2018, based on a "tumor agnostic" development plan, vitrakvi (larotrecinib) of Loxo was successfully approved for the treatment of locally advanced or metastatic solid tumors in adults and children carrying ntrk gene fusion, becoming the first FDA approved broad-spectrum anti-cancer targeting drug that does not differentiate cancer species but only looks at mutations Prior to that, in November 2017, Bayer reached a license agreement with the company, with a down payment of up to $400 million Table 2 prospect of M & A transactions with a value of more than US $1 billion in 2018 In early 2019, the 12th largest BMS in the world announced the acquisition of celgene, the 21st largest in the world This transaction with a value of US $74 billion will greatly expand the therapeutic field of BMS listed drugs, especially in the field of blood tumor and inflammation In addition, the acquisition will provide BMS with a large number of pipeline drugs in advanced clinical: luspatercept (for myelodysplastic syndrome), ozanimod (for inflammatory diseases), bb2121 (for multiple myeloma) and lisocel (for lymphoma) Celgene's valuation is 54% higher than the day before the deal was announced If celgene's ozanimod, lisocel and bb2121 are approved by FDA, the capital market will bring a one-off return of $9 per share to celgene's shareholders M & A of similar scale improves the industry's M & a expectation for 2019 According to biopharma dealmakers B3 – B6, March 2018, BMS and Merck were at the top of the cancer deal list in 2017 However, in 2018, BMS made only one transaction in the field of tumor treatment: reached a US $3.6 billion cooperation agreement with nektar on the modified IL-2 candidate drug nkt214 (Table 1) In terms of the number of transactions, Merck continues to maintain its leading position in the field of anti-tumor Gilead has conducted five transactions in the field of cancer, three of which are worth more than US $1 billion, which reflects the strategic layout of Gilead's expansion from antiviral business to the field of cancer (Figure 4) Figure 4 Transactions of the top 30 * companies in the field of cancer 1 Transaction time: from January 2018 to December 2018; 2 Transaction type: M & A, licensing, joint venture, cooperative development, asset transfer; 3 *: ranking by 2017 operating revenue 4 Valeant, the top 30 pharmaceutical company, was excluded because it did not execute any buyer transactions For more information about datasets, see box 1 In 2018, most large pharmaceutical companies took the lead in anti-tumor