Pfizer Inc.'s $1.85 billion purchase of Trillium Therapeutics Inc. demonstrated the potential market value of early-stage cancer treatments called CD47 inhibitors, with several biopharmaceutical players poised to release their own study results in the next few years.

CD47 inhibitors trigger a response from the immune system to "eat" cancer cells by suppressing signals on a tumor's surface that normally stop them from doing so.

The Trillium acquisition — particularly from a pharmaceutical giant like Pfizer — indicates that the space is heating up even as most research remains in the earliest clinical stage, RBC Capital Markets analyst Brian Abrahams said in an interview.

"Pfizer's entry into CD47 shows that interest in this class is growing, certainly," Abrahams said. "And when we look at the promise from Gilead's magrolimab, this introduces competition but also validates the CD47 opportunity."

Trillium's two CD47 programs, called TTI-621 and TTI-622, have returned initial phase 1 results that show promise in a broad range of blood cancers, with early-stage clinical trials for acute myeloid leukemia and multiple myeloma ongoing.

General Manager of Pfizer Oncology Andy Schmeltz acknowledged on an Aug. 23 call with analysts that entering the space through the Trillium acquisition at an early stage means the company will have to differentiate itself from the competition.

"TTI-622 and TTI-621 ... have the potential to be foundational immunotherapy of hematologic malignancies, analogous to the role PD-1 and PD-L1 play in solid tumors," Schmeltz said. "Additionally, TTI-622 and 621 seem particularly well suited for combination use with other agents, including our own CD3/BCMA bispecific elranatamab, now in development for multiple myeloma."

RBC's Abrahams said he is looking to Gilead Sciences Inc. to showcase the potential of the CD47 market and what it might mean for earlier-stage companies.

The drugmaker acquired an interest in the CD47 class when it purchased immunotherapy company Forty Seven Inc. in 2020, including its CD47 antibody magrolimab. Gilead has since brought the therapy to phase 3 trials for two types of blood cancer called myelodysplastic syndrome and acute myeloid leukemia, but remains in phase 1b/2 trial in diffuse large B cell lymphoma.

Gilead is likely one to two years ahead of its closest competitors, including Pfizer, with potential commercialization by late 2022 and total revenue from magrolimab of more than $2 billion, Abrahams said in an Aug. 23 note.

Some companies are taking the combination route with the CD47 class. For instance, Californian biotech ALX Oncology Holdings Inc. has teamed up with pharmaceutical giants Merck & Co. Inc. and Eli Lilly and Co. to bring early-stage CD47 antibodies to the cancer market in combination with blockbuster immunotherapies that could help the newer drugs collect better results.

Other competitors have not been as successful, such as Cambridge, Mass.-based Surface Oncology Inc., which pulled back from its own early-stage CD47 program in 2018 because of toxicity issues.

Ketamine for gambling addiction

Away from cancer, psychedelic drugs have attracted increasing attention in recent years due to early-stage clinical research for conditions as varied as neurological disorders, anorexia and headaches. Among these therapies is ketamine, which Awakn Life Sciences Corp. is trialing in a phase 1 study for gambling addiction.

The Canadian biotech is investigating the drug as a means to curb the urge to gamble as well as "superstitious thinking" that comes with the territory, the company said in a release. There are no pharmacological treatments available for the condition, which affects about 10 million people in the U.S. alone, Awakn added.

"This study is an exciting first step toward a new treatment for gambling disorder, and one which will give new insights into the neurobiology of this damaging and often overlooked addiction," said Celia Morgan, professor of psychopharmacology at the U.K.'s University of Exeter who is leading the research.

Awakn has already completed a mid-stage study of ketamine-assisted psychotherapy to treat alcohol use disorder, with a late-stage study planned for MDMA to treat the same disorder.

If the Canadian company's latest bet pays off, it could result in the second U.S. approval for a ketamine-based treatment after Johnson & Johnson's Spravato received the green light in 2019 to treat depression.