CD47, known as the “don’t eat me” molecule, is expressed on cancer cells. When CD47 binds to its receptor on macrophages (immune cells which engulf and digest cancer cells), the cancer can escape macrophage destruction. There has been a recent surge in research identifying CD47 as a target for cancer treatments. As the field becomes more crowded, companies will look to differentiate themselves by combining CD47 with other therapies targeting the innate or adaptive immune system.
In April 2018, Boehringer Ingelheim (BI) announced a partnership with OSE Therapeutics that could total more than $1.4B to develop OSE-172 for the treatment of solid cancers. By binding to SIRPα, OSE-172 blocks CD47 from binding to and activating SIRPα.
In May 2018, Forty Seven, Inc was granted fast track designation for 5F9, its anti-CD47 mAb, for the treatment of diffuse large B-cell lymphoma and follicular lymphoma.
These events represent a new school of thought in cancer immunotherapy. Traditionally, therapies that target the adaptive immune system have been more popular avenues of exploration, and while these have rightfully generated much excitement, there is a growing body of evidence to suggest that the innate immune response is likely to be important too.
Macrophages are the primary effector cells of the innate immune system, so it is natural that they should have accrued the most interest in this new wave of innate immune cell therapies. Research has focused particularly on the CD47/SIRPα axis, which has resulted in a four-fold increase in CD47-based patents (see below). CD47 is an inhibitory checkpoint molecule on the tumor cell which binds to SIRPα on the surface of macrophages. This binding causes the macrophage to ignore the cancer cell, which has led to CD47’s “don’t eat me” nickname.
Figure 1: Growth in IP for CD47 in Cancer
Table 1: CD47/SIRPɑ based therapies in clinical trials
CD47 is being developed by several big pharma companies and a slew of startups, who are all competing to bring therapies to the market. Research is still in early stages, with the most advanced therapies only reaching Phase II clinical trials, indicating that the field is still open to newcomers. With big deals such as the BI-OSE Therapeutics billion-dollar deal, and with the new FDA fast track designation, more companies will be attracted to develop CD47 programs.
Table 2: Preclinical CD47/SIRPɑ based therapies
As the field gets more crowded companies will look to differentiate themselves by combining
CD47 with other targets:
1. Combinations with adaptive immune system therapies
The efficacy of tumor-binding antibodies is linked, in part, to their ability to stimulate antibody-dependent cellular phagocytosis of cancer cells. The tumor is thus able to dampen antibody efficacy by up-regulating CD47. Administering current antibody therapies together with anti-CD47 therapies should vastly improve their efficacy. BI has already announced plans to trial the anti SIRPα antibody it licensed in April together with anti-PD1.
2. Combinations with innate immune systems therapies
Recently, a second “don’t eat me” molecule, LILRB1, was discovered at Stanford by the same team who discovered CD47. Targeting both pathways simultaneously could significantly enhance tumor clearance and might therefore prove an important future direction in macrophage-based therapies. Since the Stanford team has strong links with Forty Seven, Inc, it is probable that this company may pioneer the first LILRB1 therapies.
Macrophage therapies, especially CD47-based therapies, while still relatively nascent, hold much potential as an alternative category of cancer immunotherapies. The high number of start-ups and the early interest exhibited by Big Pharma companies such as Celgene and BI, mark it as a highly attractive new opportunity.
Written by Naomi Bassan, MSc
Healthcare Business Consultant. Naomi has been working at Signals for over 4 years and has been involved in many projects from initial data collection all the way through to data analysis and insight generation. She holds an MSc in biology from Bar-Ilan University, where her research focused on cancer drug delivery systems.