Pfizer Joins Gilead and AbbVie in CD47 Race with $25M Investment in Trillium Therapeutics Ahead of IPO

Compilation/Newborn

——Following Gilead, AbbVie, Boehringer Ingelheim, and a host of emerging biotech companies, another pharmaceutical giant has entered the CD47 field.

Last Tuesday, Pfizer made a $25 million equity investment, purchasing approximately 2.3 million ordinary shares of Trillium Therapeutics at $10.88 per share, representing a 15% premium over the closing price from the previous Friday. Following the announcement of the transaction, Trillium Therapeutics attracted strong investor interest, with its stock price surging 43% on Wednesday.

This transaction allows Trillium Therapeutics to retain full rights to its assets while leveraging Pfizer’s expertise and resources. Jeff Settleman, Chief Scientific Officer of Pfizer Oncology Research and Development, will become one of the inaugural members of Trillium Therapeutics’ Scientific Advisory Board.

Trillium Therapeutics is a Canada-based immuno-oncology company dedicated to developing innovative immunotherapies for the treatment of cancer. The company’s clinical programs, TTI-621 and TTI-622, are two unique SIRPα-Fc fusion proteins that function as decoy receptors to target and bind CD47, thereby blocking its activity.

CD47 is a glycoprotein widely expressed on the surface of various cells. It prevents macrophages from phagocytosing healthy cells by binding to SIRPα on the surface of phagocytes and releasing a "don't eat me" signal. However, cancer cells cunningly exploit this mechanism to induce immune suppression and evade phagocytosis by macrophages.

In recent years, CD47 has gradually emerged as a star target in the field of immuno-oncology, with investment in this area showing significant growth:

In 2018, Boehringer Ingelheim paid only $37 million to reach a CD47 antibody collaboration with Surface Oncology;

In March this year, Gilead acquired Forty Seven, a company specializing in CD47 antibodies, for $4.9 billion;

Recently, AbbVie and I-Mab entered into a transaction worth a total of $1.94 billion to collaborate on the global development and commercialization of lemzoparlimab (TJC4), a highly differentiated innovative CD47 monoclonal antibody independently developed by I-Mab.

Previously, analysts had predicted that Trillium Therapeutics would be the next CD47-focused company to be acquired. Pfizer’s recent equity investment may represent preparatory groundwork for such a move. However, during an investor conference call on Tuesday afternoon, Jan Skvarka, CEO of Trillium Therapeutics, stated that Pfizer’s investment is not associated with any right of first refusal regarding partnerships or acquisitions, and that these options remain fully open.

So, what kind of assets are attracting Pfizer? Just prior to this conference call, Trillium Therapeutics provided early human data for its two lead programs, TTI-621 and TTI-622, which is an update to the data presented at the ASCO Annual Meeting three months ago.

TTI-622

TTI-622 is a SIRPα-IgG4-Fc fusion protein. Similar to I-Mab’s candidate drug, it exhibits very weak binding to normal red blood cells and does not induce hemagglutination. Current data show that in patients with relapsed/refractory lymphoma who had previously received multiple therapies, monotherapy with TTI-622 achieved an overall response rate (ORR) of 33% (6/18) at dose levels of 0.8–9 mg/kg. Notably, at the 8 mg/kg dose level, 3 out of 6 patients achieved objective responses, yielding an ORR of 50%. Safety assessment at higher doses has been completed, and researchers are now proceeding to evaluate 12 mg/kg as the next step in the dose-escalation study.

In comparison, among patients with relapsed/refractory DLBCL, Gilead’s magrolimab in combination with rituximab at a full dose of 30 mg/kg achieved an ORR of 36%; ALX Oncology’s ALX148 in combination with rituximab at a full dose of 50 mg/kg achieved an ORR of 55%. Although this is not a head-to-head comparison, TTI-622 has shown encouraging signs, as it has already achieved “comparable” results to those of competing products at their highest doses in combination studies across the dose levels tested to date. Meanwhile, study results also indicate that “not all IgG4s are equal,” given that Celgene terminated its Phase I trial of the IgG4-CD47 molecule CC-90002 two years ago, while data for TTI-622 have clearly outperformed analysts’ expectations.

Cowen analyst Boris Peaker noted, “This represents the most robust monotherapy data demonstrated by a CD47-targeted candidate therapy to date, with an impressive safety profile. We believe that even if the higher dose of 12 mg/kg proves intolerable, the 50% overall response rate (ORR) achieved at the 8 mg/kg level is sufficient to warrant further advancement of this drug.”

However, Trillium Therapeutics is not necessarily required to compete solely with monotherapy. Bob Uger, the company’s Chief Scientific Officer, has identified anti-PD-(L)1 agents, the proteasome inhibitor Darzalex, Erbitux, and Folotyn as potential combination partners for different indications. Nevertheless, establishing robust monotherapy data as a foundation will give regulators greater confidence that the drug will perform more effectively in combination regimens.

Regarding safety, Trillium Therapeutics disclosed one case of a Grade 4 adverse event. However, Yaping Shou, Chief Business Officer, explained that this classification was primarily due to researchers’ heightened caution and the administration of prophylactic platelet transfusions during the COVID-19 pandemic, rather than any symptoms (the patient was asymptomatic). The patient has discontinued the 8 mg/kg dose but continues to receive TTI-622 treatment.

TTI-621

TTI-621 is a SIRPα-IgG1-Fc fusion protein characterized by its ability to achieve significant efficacy at very low doses. Among the six evaluable patients in the 1 mg/kg cohort, one patient achieved partial response, and one patient with cutaneous T-cell lymphoma achieved complete clearance of skin lesions. Two patients successfully underwent allogeneic transplantation. The 1.4 mg/kg dose has now been deemed well-tolerated in patients with advanced relapsed/refractory hematologic malignancies, and the next step is to test the 2.0 mg/kg dose.

Trillium Therapeutics plans to continue evaluating these two projects to determine which one will emerge as the lead candidate; however, if the two projects target different indications, the company may advance both simultaneously. Ultimately, the company intends to expand into the solid tumor space, with CEO Jan Skvarka noting that Pfizer has a strong interest in this area.

Analyst Boris Peaker pointed out that before Pfizer's investment, Trillium Therapeutics had a total of $130.8 million in cash and investments in the second quarter, which was considered sufficient to last until 2022.

After Celgene terminated CC-90002 in 2018, the CD47 mechanism seemed to be on the brink. However, with the resurgence of interest in CD47 within the pharmaceutical industry, more deals may be forthcoming, and buyers have a wide array of assets to choose from.

An analytical article by New Kangjie points out that, after resolving hematologic adverse reactions, innovative therapies targeting the CD47-SIRPα pathway are poised to become another fertile frontier in cancer immunotherapy, following PD-(L)1 inhibitors. In 2019, the global market for PD-(L)1 drugs saw cumulative sales of $22.432 billion for just four PD-(L)1 monoclonal antibodies marketed by Merck & Co., Bristol Myers Squibb, Roche, and AstraZeneca. This suggests that, given their similar broad-spectrum antitumor efficacy to PD-1 inhibitors, CD47-targeted drugs could also tap into a potential market worth $20 billion.

Reference Source:

1、Abbvie looks east for CD47

2、Trillium Therapeutics: Corporate Overview(2020.09.08)

3、Dabbling in CD47, Pfizer infuses $25M into a biotech player touting positive monotherapy data

4. New Kangjie: What Exactly Is I-Mab’s CD47 That Attracted AbbVie’s Bet?