The numbers keep rising for immuno-oncology, starting with the size of the market.

Last time GEN visited the topic in September, the most generous forecast for the future size of the cancer immunotherapy market was $34 billion in 2024 (GlobalData). Six months later, the rosiest of market growth projections has nearly quadrupled to $119.39 billion by 2021 (MarketsandMarkets), or merely more-than-doubled to $75.8 billion by 2022 (GBI Research).

Behind the climbing numbers is the expectation of rising sales as new immuno-oncology drugs win approvals, and as established treatments gain new indications. Already, the top three best-selling cancer immunotherapies have all generated billion-dollar-plus “blockbuster” sales, and generated a combined $6.388 billion last year, more than double the $2.634 billion made in 2015.

The top cancer immunotherapy accounted for more than half the total—Bristol-Myers Squibb (BMS)’s marketed Opdivo® (nivolumab) racked up $3.774 billion in 2016. Next came Merck & Co.’s Keytruda® (pembrolizumab) at $1.402 billion, followed by BMS’ Yervoy® (ipilimumab) at $1.053 billion.

Below is GEN’s updated list of the top 10 immuno-oncology collaborations, 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.

The total value of all 10 ranked collaborations is approximately $26.233 billion, up 6% from $24.687 billion six months ago, thanks to a significant expansion of last year’s No. 10 ranked collaboration (announced March 20) which zoomed as a result to No. 2 on this year’s list. Another reflection of the rising value of partnerships: While last year’s No. 10 collaboration was worth up to $1.242 billion, this year’s No. 10 partnership was worth potentially 21% more, up to $1.5 billion. This year’s list also shows a shift in immuno-oncology from the creation and announcement of billion-dollar partnerships, to more clinical activity within those alliances.

Not included on this list are collaborations that combine immuno-oncology and other areas; that would include Amgen and Xencor’s up-to-$1.7 billion alliance disclosed in 2015 to develop six candidates in cancer immunotherapy and inflammation, since the companies’ announcement did not break down how many programs were in each area.

Also not included are collaborations whose full total potential value was not disclosed. For example, on November 16, 2016, BMS agreed to pay $30 million upfront in a partnership with Enterome to discover and develop microbiome-derived biomarkers, drug targets, and bioactive molecules; no other financial terms were disclosed. And on September 21, 2016, BioNTech said it was launching a collaboration with Roche subsidiary Genentech to develop individualized messenger RNA (mRNA)-based, individualized cancer vaccines, through a collaboration whose value includes $310 million in upfront and near-term payments tied to achieving unspecified milestones.

#10. Shire (Baxalta) and Symphogen

Value: Up to €1.4 billion ($1.5 billion) for Symphogen

Date announced: January 4, 2016

Summary: Companies agreed to develop Symphogen’s portfolio of early-stage immuno-oncology programs. Companies agreed to advance new treatments against six undisclosed checkpoint targets, with the first program to enter clinical studies in 2017.

Updates: On June 3, Baxalta became an indirect wholly-owned subsidiary of Shire following completion of the companies’ $32 billion merger. In its Form 10-K Annual Report for 2016, filed February 22, Shire disclosed that it has options under the collaboration to obtain exclusive licensing rights for four specified proteins in development for the treatment of immuno-oncology diseases, as well as two additional unspecified proteins that may be selected at a later date. Each option is exercisable for a period of 90 days when each protein is ready for Phase II clinical trials. Symphogen is responsible for development costs for each protein until option exercise, at which point Shire would become responsible for development costs.

#9. Shire (Baxalta) and Precision BioSciences

Value: Up to $1.7 billion for Precision, including $105 million upfront

Date announced: February 25, 2016

Summary: Companies agreed to develop allogeneic chimeric antigen receptor T cell (CAR-T) therapies, by bringing together immuno-oncology candidates of Baxalta (since acquired by Shire) with Precision’s ARCUS genome-editing platform technology.

Baxalta and Precision agreed to develop CAR-T therapies for up to six undisclosed targets addressing areas of major unmet need in multiple unspecified cancers. Precision agreed to oversee early-stage research activities up to Phase II, after which Baxalta has the exclusive right to opt in for late-stage development and commercialization. However, Precision also has the right to participate in the development and commercialization of any licensed products resulting from the collaboration through a 50/50 co-development and co-promotion option in the U.S.

Updates: Baxalta became an indirect wholly-owned subsidiary of Shire on June 3 following completion of the companies’ $32 billion merger. In its Form 10-K Annual Report for 2016, filed February 22, Shire restated that the first development program created through the collaboration is expected to enter clinical studies in late 2017.

#8. Bristol-Myers Squibb (BMS) and Five Prime Therapeutics

Value: Up to $1.74 billion for Five Prime, including $350 million upfront

Date announced: October 15, 2015

Summary: BMS agreed to co-develop and co-commercialize Five Prime’s colony stimulating factor 1 receptor (CSF1R) antibody program, led by the Phase I cancer/immunology compound cabiralizumab (FPA008). BMS agreed to oversee development and manufacturing of cabiralizumab for all indications, subject to an option by Five Prime to conduct and pay for future studies to support approval of cabiralizumab in pigmented villonodular synovitis (PVNS), and cabiralizumab in combination with Five Prime’s internal pipeline assets in immuno-oncology.

Updates: On February 23, Five Prime said it expects to complete enrollment of the Phase II trial of cabiralizumab in PVNS in the first half of 2017. Five Prime is evaluating response rate, pain, and range of motion in approximately 30 PVNS patients. Five Prime plans to disclose clinical data from the trial at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting.

In October 2016, Five Prime launched the Phase Ib portion of a trial evaluating the combination of cabiralizumab with BMS’ Opdivo® (nivolumab). Five Prime and BMS are evaluating the safety, tolerability, and preliminary efficacy of the combination in advanced solid tumors, including non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck, pancreatic cancer, glioblastoma, renal cell carcinoma, and ovarian cancer. Five Prime expects to complete enrollment in the current Phase Ib trial cohorts in the second half of 2017.

#7. Servier and Pieris Pharmaceuticals

Value: Up to €1.7 billion ($1.8 billion) for Pieris, including €30 million ($32 million) upfront

Date announced: January 5, 2017

Summary: Servier will partner with Pieris to co-develop Pieris’ PRS-332 and up to seven other immuno-oncology bispecific drug candidates. Companies agreed to initially pursue five bispecific therapeutic programs. These are led by the preclinical bispecific checkpoint inhibitor PRS-332, a programmed cell death protein 1 (PD-1)-targeting therapy, and include four immuno-oncology bispecific drug candidates that may combine antibodies from the Servier portfolio with one or more of Pieris’ Anticalin® proteins. Pieris retains all U.S. commercial rights, with Servier having commercial rights elsewhere in the world. Servier and Pieris also agreed to allow for expansion of their collaboration by up to three additional therapeutic programs.

Updates: In reporting fourth-quarter and full-year 2016 results on March 22, Pieris said it expected this year to advance preclinical evaluation of PRS-332 with Servier, “with IND-enabling activities planned for later in 2017.”

#6. Sanofi and Regeneron

Value: Up to $2.17 billion for Regeneron, including $640 million upfront

Date announced: July 28, 2015

Summary: Sanofi and Regeneron agreed to jointly develop REGN2810, a programmed cell death protein 1 (PD-1) inhibitor then in Phase I, and launch clinical trials in 2016 with new therapeutic candidates based on ongoing preclinical programs. The partners committed to spend $325 million each toward developing REGN2810.

Updates: In releasing fourth-quarter 2016 results on February 9, Regeneron said REGN2810 was the subject of a Phase II “potentially pivotal” study for the treatment of advanced cutaneous squamous cell carcinoma that was launched in the second quarter of 2016, as well as various Phase I studies, all of which continue to enroll patients. REGN2810 is also being studied in combination with other antibodies and treatments, the company said in its Form 10-K Annual Report for 2016. In 2017, Regeneron said that Phase II studies of REGN2810 will be initiated in non-small cell lung cancer (NSCLC) and in basal cell carcinoma.

#5. Celgene and Jounce Therapeutics

Value: Up to $2.6 billion-plus for Jounce, including $225 million upfront, and a $36 million equity investment by Celgene

Date announced: July 19, 2016

Summary: Celgene received options to develop and commercialize jointly cancer immunotherapies that include Jounce’s lead candidate JTX-2011, a monoclonal antibody (mAb) expected to enter clinical trials by year’s end, and other cancer immunotherapies. Celgene gained options from Jounce for up to four of its early-stage programs to be selected from a defined pool of B cell-, regulatory T cell-, and tumor-associated macrophage targets emerging from the Jounce Translational Science Platform; and an additional option to share JTX-4014, Jounce’s PD-1 product candidate, equally with Jounce. The collaboration agreement has an initial term of four years, which may be extended up to three additional years.

Update: On March 10, Jounce said it expects to report data this year from the Phase I/II ICONIC study of JTX-2011. Data includes safety and PK/PD data from the Phase I portion of the study, expected in the first half of 2017, followed in the second half by preliminary efficacy data in both a monotherapy setting and combination therapy setting with Bristol-Myers Squibb’s anti-PD-1 antibody Opdivo® (nivolumab). The combination will be assessed “in patients with NSCLC, HNSCC, triple negative breast cancer (TNBC), melanoma, stomach cancer, and additional niche indications identified through our Translational Science Platform,” Jounce said in its Form 10-K Annual Report for 2016.

#4. Merck KGaA and Pfizer

Value: Up to $2.85 billion for Merck KGaA, including $895 million upfront

Date announced: November 17, 2014

Summary: Merck KGaA agreed to jointly develop and commercialize its PD-L1 checkpoint inhibitor MSB0010718C [since renamed Bavencio® (avelumab) and also known as PF-06834635] with Pfizer, both as a single agent and in various combinations with the companies’ oncology therapies.

Update: On March 23, Merck KGaA entity EMD Serono and Pfizer announced FDA approval for Bavencio Injection 20 mg/mL, for intravenous use, for adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC)—the first treatment approved for the rare, aggressive form of skin cancer. Bavencio’s Biologics License Application (BLA) was accepted for review in November under the FDA’s Priority Review status, which shortened the agency’s expected review time from 10 months. Also in November, Pfizer said it will collaborate with the National Cancer Institute’s Center for Cancer Research to assess Bavencio and two other immunotherapy candidates by arranging and conducting clinical and preclinical trials.

#3. Pfizer, Cellectis, and Servier

Value: Up to $2.885 billion for Cellectis, including $80 million upfront

Date announced: June 18, 2014

Summary: Pfizer and Cellectis agreed to develop Chimeric Antigen Receptor T-cell (CAR-T) cancer immunotherapies directed at select targets using the French biotech’s CAR-T platform technology. Pfizer has exclusive rights to develop and commercialize CAR-T cancer therapies directed at a total of 15 targets of its choosing. Both companies agreed to work together on preclinical research for four of 12 additional targets to be selected by Cellectis, with Pfizer having the right of first refusal to the four. In return, Pfizer agreed to fund R&D costs for the 15 targets, and a portion of R&D costs associated with four other Cellectis-selected targets. Cellectis is eligible for payments tied to achieving development, regulatory, and commercial milestone payments of up to $185 million per product resulting from the Pfizer-selected targets, and tiered royalties on net sales of any products commercialized by Pfizer.

In November 2015, Servier acquired exclusive rights from Cellectis for UCART19, for up to $338 million-plus. Servier then granted exclusive rights to Pfizer to develop and commercialize UCART19 in the U.S.—in a deal whose value has not been disclosed—while retaining rights elsewhere in the world.

Updates: On March 9, Servier and Pfizer announced that the FDA granted Servier an IND clearance to proceed in the U.S. with clinical development of UCART19 for relapsed/refractory acute lymphoblastic leukemia. UCART19 is an allogeneic CAR-T cell candidate for CD19-expressing blood malignancies, gene-edited with Thermo Fisher Scientific’s TALEN® technology and co-developed by Servier and Pfizer. Servier is sponsoring the CALM Phase I study on UCART19, which was launched in the U.K. in August 2016. The study is assessing UCART19 in patients with CD19-positive B-cell relapsed/refractory acute lymphoblastic leukemia.

Pfizer owned approximately 8% of Cellectis’ outstanding shares as of November 30, 2016.

#2. Bristol-Myers Squibb (BMS) and CytomX Therapeutics

Value: Up to $2.888 billion for CytomX, including $200 million upfront (1)

Date announced: March 20, 2017

Summary: In expansion of up-to-$1.242 billion, up-to-four-target cancer immunotherapy collaboration announced May 27, 2014, BMS and CytomX agreed to discover up to eight additional targets—six oncology targets, two non-oncology—using CytomX’s Probody™ drug discovery platform. CytomX granted BMS exclusive worldwide rights to develop and commercialize the eight targets. In return, BMS agreed to pay CytomX $200 million upfront, plus research funding, and up to $448 million per candidate tied to achieving development, regulatory and sales milestones, plus tiered royalties from the mid-single digits to low-double digits on net sales of each product commercialized by BMS.

Update: In announcing the expanded collaboration March 20, BMS and CytomX said the four oncology targets called for under the original agreement had been selected by BMS, with a CTLA-4 Probody therapeutic progressing to IND-enabling studies, and the three other programs remaining in the lead discovery and optimization phase.

#1. Merck & Co. and Ablynx

Value: €5.78 billion ($6.4 billion)

Date announced: July 22, 2015

Summary: In an up-to-€4.08 billion (about $4.5 billion) expansion of an up-to-€1.7 billion ($2.3 billion) immuno-oncology collaboration to address additional checkpoint modulator targets, announced February 3, 2014, the companies agreed to discover and develop up to 12 additional cancer drugs based on single-domain antibody fragments, or Nanobodies®, through preclinical proof-of-concept. After that, Merck & Co. will have the option to advance specific lead candidates. Merck will also oversee clinical development, manufacturing, and commercialization of any products resulting from the collaboration, which grew to 17 Nanobodies programs.

Updates: On February 23, Ablynx included among its “significant clinical and regulatory catalysts anticipated for 2017” the initiation of the first clinical trial of a Nanobody developed through the collaboration. On October 12, Ablynx announced a second extension of the collaboration, which it said entailed developing and commercializing Nanobody candidates toward an undisclosed voltage gated ion channel. Ablynx said the extension resulted in a payment to the company by Merck & Co. of €1 million (about $1.1 million), and a commitment by Merck & Co. to extend funding of the research collaboration to September 2018.


1. Value of deal reflects only the six oncology targets among the eight additional targets BMS and CytomX added to their collaboration; the other two will be in non-oncology indications. The value for all eight targets rises to $3.784 billion.