Biopharma giants have proven willing to shell out billions in collaborations with smaller biotechs aimed at developing new immunotherapies for cancer. [Paul Bradbury/Getty]
Nowhere in biopharma does the adage, “Follow the money” better apply, perhaps, than immuno-oncology, whose market size is expected to balloon to $19 billion in 2019 and $34 billion in 2024 (GlobalData).
With a combined roughly $2.5 billion in sales last year, drugs that harness the body’s immune system as a weapon against cancer have already begun to generate billions. Bristol-Myers Squibb (BMS) immuno-oncology treatment Yervoy® (ipilimumab) surpassed $1 billion in worldwide revenues last year, with BMS’ Opdivo® (nivolumab) close behind at $942 million. Opdivo has already surpassed that total this year, zooming in January–June to $1.544 billion. And while Yervoy slid 19% to $504 million this year due to competition from Opdivo and Merck & Co.’s Keytruda® (pembrolizumab), the two BMS drugs are expected to generate a combined $7.5 billion in sales by 2022, according to Trefis.
Speaking of Keytruda, its $563 million in the first half of 2016 is just $3 million shy of what the drug made all of last year. And Keytruda is expected to leap to $7 billion in sales by 2024 (Research and Markets).
With the potential for billions in new revenues, biopharma giants have proven willing to shell out billions in collaborations with smaller biotechs aimed at developing new immunotherapies for cancer. Earlier this year, the Tufts Center for the Study of Drug Development reported that more than 130 biotechs and 20 pharmaceutical companies were working on immuno-oncology therapies, with the number of collaborations rising to 58 last year from six in 2013.
The largest of these—and several others that were launched this year—can be found in GEN’s list of top 15 immuno-oncology collaborations below. The alliances are ranked by dollar value as disclosed by the companies in regulatory filings, press announcements, and other public statements. Each collaboration is listed by partner names, value, and date announced, followed by a summary, and updates provided by the companies since their launch announcements.
Interestingly, the total value of all 15 ranked collaborations is approximately $30 billion. It’s also fair to say, for now, that the pace of billion-dollar-plus partnership activity is rising, as 2016 has already seen five such collaborations, compared to six last year and four in 2014. However, the list does not include collaborations where details were not disclosed. For example, Novartis and Xencor only revealed the $150 million upfront portion of their partnership to develop bispecific antibodies, announced June 28.
#15. Celgene and Juno Therapeutics
Value: Approximately $1 billion for Juno, including approximately $150 million upfront
Date announced: June 29, 2015
Summary: 10-year global collaboration to develop and commercialize cancer and autoimmune diseases immunotherapies, with an initial focus on chimeric antigen receptor (CAR) technology and T-cell receptor (TCR) technologies. Celgene has the option to serve as commercialization partner for Juno's oncology and cell therapy autoimmune product candidates, including Juno's CD19- and CD22-directed CAR T-cell product candidates.
Updates: On April 28 in announcing first-quarter results, Celgene disclosed that during that month, it exercised its option to develop and commercialize Juno’s CD19 program outside North America and China. The companies agreed to share global development expenses for products in the CD19 program. Celgene agreed to pay Juno a royalty at a percentage in the mid-teens on any future net sales of therapeutic products developed through the CD19 program in Celgene's territories. Celgene entered into a prenegotiated license agreement, with Juno by paying $50 million for the license, Celgene disclosed recently.
#14. Celgene and Agios Pharmaceuticals
Value: About $1 billion-plus for Agios, including $200 million upfront
Updates: In a July report, Celgene said the collaboration’s initial 4-year term will expire in May 2020, adding: “We may extend the term for up to two additional 1-year terms or in specified cases, up to 4 additional years.” At the end of the research term, Agios said “Celgene may designate for continued development up to three research programs for which development candidates have yet to be nominated, which are referred to as continuation programs.” Agios said it may conduct further research and preclinical and clinical development activities on any continuation program, at its expense, “through completion of an initial Phase I dose-escalation study.”
#13. Eli Lilly and Innovent Biologics
Value: More than $1 billion, including $56 million upfront
Date announced: October 11, 2015
Summary: In expansion of up-to-$456 million cancer therapy strategic alliance announced March 20, 2015, companies agreed to support development and potential commercialization of up to three anti-programmed cell death-1 (PD-1)-based bispecific antibodies for cancer treatments over the next decade, both inside and outside of China. Lilly agreed to exercise rights from the earlier agreement to develop, manufacture, and commercialize these potential cancer treatments outside of China, while Innovent won rights to develop, manufacture, and commercialize the treatments for China, subject to a Lilly opt-in right for co-development and commercialization.
Updates: No subsequent announcements.
#12. Celgene and Sutro Biopharma
Value: More than $1 billion-plus for Sutro, including $95 million upfront (a sum that includes an unspecified equity investment)
Date announced: October 23, 2014
Summary: Companies agreed to advance into immuno-oncology, in expansion of a nearly 2-year-old cancer collaboration originally intended to discover and develop multispecific antibodies and antibody–drug conjugates (ADCs). Expansion doubled the value of the partnership, which was refocused on established immuno-oncology targets such as programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), as well as new undisclosed targets, using Sutro’s Xpress CF™ and Xpress CF+™ cell-free biologics development platforms. After the initial period, Celgene was given exclusive option to acquire Sutro.
Updates: No subsequent announcements.
#11. Roche and Blueprint Medicines
Value: Up to $1.01 billion for Blueprint, including $45 million upfront
Date announced: March 15, 2016
Summary: Companies agreed to discover, develop, and commercialize up to five small-molecule therapeutics targeting kinases deemed important in cancer immunotherapy. The five could be either single products or products to be combined with Roche therapeutics. Roche will hold options triggered upon achievement of Phase I proof-of-concept for an exclusive license to each drug candidate developed under the collaboration.
Updates: In August, Blueprint disclosed that the partners “have identified targets for three of the collaboration programs, two of which began in the first half of 2016 and the third of which is expected to begin in 2016, and the parties have agreed to work together to use the company’s novel target discovery engine and proprietary compound library to select targets for up to two additional collaboration programs.”
#10. Bristol-Myers Squibb (BMS) and CytomX Therapeutics
Value: Up to $1.242 billion for CytomX, including $50 million upfront
Date announced: May 27, 2014
Summary: Companies agreed to discover, develop, and commercialize new immunotherapies against multiple cancer immunotherapy targets, using CytomX’s Probody™ drug discovery platform. CytomX agreed to grant BMS exclusive worldwide rights to develop and commercialize Probody therapeutics designed to bind selectively to tumors for up to four oncology targets, including the immune inhibitory checkpoint receptor cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). BMS will have additional rights to substitute up to two collaboration targets.
Updates: On January 20, CytomX disclosed its receipt of a $10 million milestone payment from BMS following its selection of a third target in the companies’ strategic oncology collaboration.
#9. Sanofi and BioNTech
Value: Up to $1.5 billion-plus for BioNTech, including $60 million upfront
Date announced: November 3, 2015
Summary: Companies agreed to discover and develop up to five cancer immunotherapies, each consisting of a mixture of synthetic messenger RNAs (mRNAs), using BioNTech’s mRNA formulation technology. BioNTech will also supply part of the mRNA material needed for development activities from its in-house GMP manufacturing unit. BioNTech has the option to co-develop and co-commercialize two of the five mRNA therapeutics products with Sanofi in the EU and the U.S.
(20min delay)