GlaxoSmithKline (GSK)’s recently announced $4.2 billion partnership to co-develop and co-commercialize Merck KGaA, Darmstadt’s cancer immunotherapy candidate M7824 was a reminder of just how much biopharma giants are willing to invest in a therapeutic area that has generated sometimes-dazzling results.

How high is up for immuno-oncology? Numerous firms have ventured their best projections for the size of the market over the next few years. Transparency Market Research estimates that cancer immunotherapy will grow from $37.5 billion in 2015 to $124.88 billion by 2024, a compound annual growth rate (CAGR) of 14.5%. Other forecasts put the size of the potential future immuno-oncology market by 2024 even higher: from $128.3 billion (KBV Research), to $152.829 billion (Meticulous Research), to $173 billion (Market Research Engine).

While the size of the future market remains unknown, what is certain is that immuno-oncology is growing, and that its lead products enjoy blockbuster ($1 billion-plus/year in sales) status several times over. The biggest-selling cancer immunotherapies in 2018 were Celgene’s Revlimid (lenalidomide), which generated $9.685 billion; Opdivo® (nivolumab), which generated $7.570 billion in 2018 sales—$6.735 billion for Bristol-Myers Squibb (BMS) and ¥92.5 billion ($835 million) for Ono Pharmaceutical—and Merck & Co.’s Keytruda® (pembrolizumab) with $7.171 billion.

Celgene and Ono are two of three companies to have generated more than 40% of revenues from cancer immunotherapies in 2017, according to GBI Research; the other was Incyte. A desire to expand its cancer immunotherapy franchise helped compel BMS to pursue its planned $74 billion acquisition of Celgene, announced January 3.

Two other biopharma giants disclosed plans to expand in immuno-oncology earlier this year: Sanofi will use Biomunex Pharmaceuticals’ proprietary BiXAb® platform for generating and optimizing bi- and multi-specific antibodies, while Genentech, a member of the Roche group, is partnering with Xencor to develop and commercialize its novel IL-15 cytokine therapeutics, including its most advanced preclinical cytokine program, XmAb®24306, through a partnership that could generate more than $280 million for Xencor.

Hoping to surpass, or at least equal, the biopharma giants in immuno-oncology are hundreds of startups scrambling to develop what GBI Research calculated last year were 3863 cancer immunotherapy products in development. The firm counted the largest number of candidates in active development (526) as being for leukemia indications, followed by lymphoma (456), breast cancer (448), melanoma (415), and non-small cell lung cancer (374).

Interestingly, GBI Research offered the most conservative forecast for the immuno-oncology market, projecting growth only to $103.4 billion by 2024, but the fastest CAGR of 17.4%, having based its forecast on a market it calculated as being $33.7 billion in 2015.

The following is GEN’s list of the Top 10 Immuno-Oncology Startups, which includes developers of cancer immunotherapies that have yet to reach the market, ranked by total capital raised through a combination of private financing and, for most of the companies listed, net proceeds from initial public offerings (IPOs). Companies are listed by name, headquarters city, web address, and total capital raised, followed by a brief description of how the capital was raised and their 2019 plans.

Investors appear very warm to immuno-oncology drug developers, with seven of the companies on this list having completed their first stock sales on public markets even with the absence of any marketed treatments, and in some cases with their lead candidates only in early clinical phases.

The absence of commercialized products has also not deterred private investors, as all top-10 companies have attracted hundreds of millions in capital, much of it fueled by venture capital (VC) financing rounds. All three of the companies that narrowly missed inclusion in the top 10 this time around—Atreca, Unum Therapeutics, and Neon Therapeutics—have raised more than $200 million to date.

 

10. Forty Seven

Menlo Park, CA
www.fortyseveninc.com

$285.3 million

Forty Seven raised $150 million in private financing, $19 million in grants, and $116.3 million in net proceeds from its June 2018 IPO. Plans for 2019 include three clinical readouts for its 5F9 development program, IND-enabling studies for FSI-189, and advancement of its third development program FSI-174.

 

9. Genocea Biosciences

Cambridge, MA
www.genocea.com

$303 million

Genocea has raised approximately $303 million since 2007 inception—including $56 million when it pivoted from infectious disease to immuno-oncology last year. In January, the company dosed the first patients in its Phase I/IIa trial assessing its neoantigen cancer vaccine candidate GEN-009.

 

8. Gritstone Oncology

Emeryville, CA
gritstoneoncology.com

$311.6 million

Gritstone raised $216 million in private financing and $95.6 million in net proceeds from its IPO, completed in October 2018. The company plans a first quarter dosing of first patient in a Phase I study of its lead, personalized tumor-specific immunotherapy product candidate, GRANITE-001 for colorectal cancer, and a mid-2019 IND filing for SLATE-001, Gristone’s investigational, off-the-shelf cancer immunotherapy.

 

7. Autolus Therapeutics

London
www.autolus.com

$336.8 million

Autolus raised $160.4 million in net proceeds from its June 2018 IPO plus $176.4 million in private financing. In January, the company signed a lease with Alexandria Real Estate Equities for a manufacturing site and U.S. headquarters in Rockville, MD, at the Shady Grove Life Sciences Center, with a planned capacity to produce 5000 T-cell therapies annually.

 

6. Arcus Biosciences

Hayward, CA
www.arcusbio.com

$351.4 million

Arcus raised $124.7 million in net proceeds in its March 2018 IPO, plus $226.7 million in private financing. In December, company presented positive Phase I dose-escalation data for AB122, in-licensed from WuXi Biologics and under study in multiple combinations.

 

5. I-Mab Biopharma

Shanghai, China
www.i-mabbiopharma.com/en

$370 million

I-Mab more-than-doubled its capital in June 2018, completing a $220 million Series C round. In January, the company saw its third pipeline candidate approved for clinical trials within a month when the FDA approved an IND application for TJC4, a fully human anti-CD47 monoclonal antibody.

 

4. Rakuten Aspyrian

San Mateo, CA
rakutenaspyrian.com

Approximately $372 million

Rakuten Aspyrian completed a two-tranche, $284 million Series C round last year. Proceeds will support the company’s Phase III ASP-1929 Photoimmunotherapy for head and neck squamous cell carcinoma, and Phase I/II studies to launch this year in additional solid tumors.

 

3. Rubius Therapeutics

Cambridge, MA
www.rubiustx.com

$499.3 million

Rubius raised $254.3 million in net proceeds from its July 2018 IPO, and $245 million in private financing. The company’s 2019 goals include filing its first IND application for phenylketonuria candidate RTX-134 during the first quarter, with clinical data expected in the second half of this year.

 

2. Allogene Therapeutics

South San Francisco, CA
www.allogene.com

$792.8 million

Allogene raised $372.6 million in its October 2018 IPO, and $420.2 million in earlier private capital, starting with $300 million when the company was launched in April 2018. Allogene won FDA clearance in January 2019 of an IND for ALLO-501, an anti-CD19 allogeneic chimeric antigen receptor T cell (CAR-T) therapy for relapsed/refractory Non-Hodgkin Lymphoma being developed with Servier.

 

1. BioNTech

Mainz, Germany
biontech.de

$1.1 billion

BioNTech on January 4 won an €80 million (approximately $91 million) equity investment from Sanofi, concurrent with agreeing to co-develop the first cancer immunotherapy candidate from a collaboration launched in 2015, entering clinical testing for multiple solid tumors. The company also made news in January by acquiring the operational antibody generation unit of MAB Discovery for an undisclosed price.