Alex Trebek appeared well en route to surviving pancreatic cancer this past summer when his doctors followed up his initial successful chemotherapy with an undisclosed immunotherapy. That move backfired.

“I was doing so well. And my numbers went down to the equivalent of a normal human being who does not have pancreatic cancer. So we were all very optimistic. And they said, ‘Good, we’re gonna stop chemo, we’ll start you on immunotherapy,” Trebek said September 17 on ABC’s Good Morning America. “I lost about 12 pounds in a week. And my numbers went sky-high, much higher than they were when I was first diagnosed.”

Trebek’s up-and-down results illustrated the precision nature of immuno-oncology treatments: What may work for one person will not necessarily work for another. So too did several more positive news stories that have emerged in recent weeks.

On November 7, researchers at Penn Medicine’s Abramson Cancer Center published early data from the first U.S. clinical trial of CRISPR-edited immune cells (NCT03399448), showing that genetically editing the T cells of human cancer patients and infusing the cells back into the patients appeared safe and feasible. Investigators reported infusing three participants—two with multiple myeloma and one with sarcoma. The edited T cells were observed to expand and bind to their tumor target with no serious side effects. Abramson Cancer Center is conducting the trial with the Parker Institute for Cancer Immunotherapy and Tmunity Therapeutics.

In September, AstraZeneca trumpeted results from the Phase III CASPIAN trial (NCT03043872) showing a median overall survival (OS) of 13.0 months for previously-untreated extensive-stage small cell lung cancer patients treated with Imfinzi® (durvalumab) plus chemotherapy, vs. 10.3 months for standard-of-care, consisting of up to six cycles of chemo and optional prophylactic cranial irradiation. An estimated 33.9% of patients were alive 18 months after treatment with Imfinzi plus chemotherapy, vs. 24.7% for standard-of-care.

A month later, AstraZeneca announced positive results for Imfinzi in non-small cell lung cancer (NSCLC), accounting for approximately 85% of lung cancers—as did Bristol-Myers Squibb (BMS), which also said it achieved positive Phase III results from a regimen of its two marketed cancer immunotherapies, Opdivo® (nivolumab) plus Yervoy® (ipolilumab) plus chemo. However, neither company revealed detailed data pending their presentation at upcoming medical conferences.

BMS and AstraZeneca are pursuing additional indications for their cancer immunotherapies, in hopes of competing better with Merck & Co.’s top-selling Keytruda® (pembrolizumab), which during the first nine months of 2019 generated $7.973 billion in sales, up 59% from $5.02 billion a year ago and already 11% above the $7.171 billion it racked up for all of 2018.

Keytruda thus accounted for nearly 10% of the total $84 billion cancer immunotherapy market as calculated last year by Reports and Data, which projects that market to more than triple by 2026, to $242.86 billion. That’s the highest of three recent estimates for the cancer immunotherapy market in 2026. At the low end, Kenneth Research projected $86.679 billion, while Grand View Research has forecasted $126.9 billion.

Below 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, where applicable, collaboration revenue and 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 a summary of recent news.

The top 10 startups listed this year have raised a collective $5.596 billion, 18.5% above the $4.722 billion garnered by the mostly same 10 companies ranked in last year’s GEN A-List—a sure sign that investors continue to be dazzled by the prospect of rapid, short-term cancer immunotherapy growth.

 
10. Fate Therapeutics
San Diego
 

$368.1M

Fate Therapeutics raised $173.1M in a common stock offering in September, the same month it opened a cGMP manufacturing facility in San Diego for clinical production of its off-the-shelf natural killer (NK) cell and chimeric antigen receptor (CAR) T-cell candidates using clonal master induced pluripotent stem cell (iPSC) lines. The company also generated $7.878 million in collaboration revenue between January–September 2019. Also this year, Fate treated its first patients with FT516, designed to treat acute myeloid leukemia and B-cell lymphoma. The FDA also cleared Fate’s IND for FT596, engineered to express three active anti-tumor modalities, for the treatment of B-cell lymphoma and chronic lymphocytic leukemia.

9. I-Mab Biopharma
Shanghai, China
 

$379.8M

I-Mab filed for an IPO of $100 million on October 29; the actual amount to be raised has yet to be set. The company generated licensing and collaboration revenue of 9.8 million between 2018 and June 2019. In October, China’s National Medical Products Administration (NMPA) gave IND clearances to I-Mab to launch in China clinical trials of TJD5, a novel CD73 antibody for advanced solid tumors. I-Mab and MorphoSys also received IND clearances to expand into China ongoing Phase II and III clinical trials of TJ202/MOR202, MorphoSys’ human monoclonal anti-CD38 antibody for multiple myeloma.

8. Forty Seven
Menlo Park, CA
 

$381.7M

In July, Forty Seven raised approximately $80.5M net proceeds from a follow-on financing, plus $15.7M in upfront cash from an up-to-$120M collaboration with Ono Pharmaceutical. Also this year, the company won grants of $15.2 million from the California Institute for Regenerative Medicine, and $4 million from the Leukemia and Lymphoma Society. In September, the FDA granted its Fast Track designation to magrolimab (formerly 5F9) for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

7. Arcus Biosciences
Hayward, CA
 

$383.9M

Arcus Biosciences has financed its operations primarily through net proceeds of $226.2 million from private placements of convertible preferred stock, and net proceeds of $124.7 million from its IPO in March 2018. The company has also collected $33 million from a collaboration with Taiho Pharmaceutical launched in 2017. Arcus has reported early signs of clinical activity in four Phase I dose-escalation combination studies for its lead candidate AB928, a selective adenosine receptor antagonist in development for several types of cancer in combination with the company’s lead antibody product candidate, the anti-PD-1 antibody AB122, or chemotherapy. Arcus expects to report efficacy data from multiple Phase Ib expansion studies starting in mid-2020.

6. Gritstone Oncology
Emeryville, CA
 

$388.9M

Gritstone Oncology raised approximately $74.8 million from a public stock offering in April, and about $2.5 million in collaboration revenue between January–June 2019. In August, Gritstone dosed its first patient with SLATE, a Phase I immunotherapy directed at shared tumor-specific neoantigens (TSNA) derived from driver mutations. Gritsone’s lead candidate is GRANITE, a personalized neoantigen-based immunotherapy being assessed in a Phase I/II trial in combination with checkpoint inhibitors for patients with common solid tumors, including metastatic non-small cell lung cancer, microsatellite stable colorectal cancer, gastroesophageal cancer, and bladder cancer.

5. Autolus Therapeutics
London
 

$449 million

Autolus raised approximately $109 million in aggregate net proceeds from a public offering in April. On November 5, Autolus received the FDA’s orphan drug designation for AUTO1, a treatment for acute lymphoblastic leukemia (ALL) being studied in two Phase I trials, one in pediatric ALL and one in adult ALL. Autolus plans to launch a pivotal program of AUTO1 in adult ALL with the dosing of the first patients in the first half of 2020.

4. Rakuten Medical
San Mateo, CA
 

Approximately $472M

Rakuten Medical—which changed its name from Rakuten Aspyrian in March—raised approximately $100 million on July 31 in a Series C-1 Preferred Stock financing from Japanese ecommerce giant Rakuten, which raised its stake in Rakuten Medical to 22.6%. On November 9 at the Society for Immunotherapy of Cancer (SITC) 34th annual meeting in National Harbor, MD, the company announced new preclinical data suggesting its CD25 photoimmunotherapy treatment, plus an anti-PD1 therapy, may stimulate the immune system, and lead to a synergistic, anti-cancer activity in targeted tumors.

3. Rubius Therapeutics
Cambridge, MA
 

$499.3M

Rubius presented preclinical data November 8 supporting its lead artificial antigen presenting cell program, RTX-321, a potential treatment for HPV 16-positive tumors, at the Society for Immunotherapy of Cancer (SITC) 34th Annual Meeting, held in National Harbor, MD. In October, at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer, Rubius presented data showing that its Red Cell Therapeutics™ can be engineered to create a loadable system for personal neoantigens, unlocking a potential new use of its RED PLATFORM®.

2. Allogene Therapeutics
South San Francisco, CA
 

$792.8M

Allogene Therapeutics and Notch Therapeutics said November 5 they will partner to research and develop induced pluripotent stem cell (iPSC) AlloCAR™ therapies for initial blood cancer indications that include non-Hodgkin lymphoma, leukemia, and multiple myeloma, through a collaboration that could generate more than $300M for Notch. Allogene has launched the Phase I UNIVERSAL Trial assessing ALLO-715 in relapsed/refractory multiple myeloma, and is accruing patients for the Phase I ALPHA Trial assessing ALLO-501 in relapsed/refractory non-Hodgkin lymphoma, with data expected in 1H 2020.

1. BioNTech
Mainz, Germany
 

$1.48B

BioNTech went public October 10, raising $149 million in net proceeds—and capping a transformative year that included raising $325 million in an upsized Series B financing in July, and winning an €80M ($88.4M) equity investment from Sanofi on January 4, concurrent with agreeing to co-develop the Phase I intratumoral immunotherapy SAR441000 (BNT131) for multiple solid tumors—the first candidate from a collaboration launched in 2015.

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