Trillium gets a buyout while it's down

 In hindsight, the clues were there: Pfizer’s $25m equity investment in Trillium Therapeutics last year left the big pharma as the only real suitor for the CD47 specialist. And, with Pfizer rolling in Covid-19 vaccine cash and with a need for deals, it made sense to pull the trigger now.

Another reason behind the timing of today’s takeover could be Trillium’s valuation, which is not what it was in late 2020. Even with a 200% premium over Trillium’s closing share price on Friday, at $2.26bn Pfizer is getting the group for less than it was worth last November – and notably it is paying a lot less than the $4.9bn Gilead shelled out for Trillium's competitor Forty Seven last year.  

With several anti-CD47 targets now in the hands of big players, investors are no doubt asking themselves who might be next on the auction block. A look at the table below shows plenty of contenders out there.

Best in class?

Trillium has two shots at CD47 with TTI-621 and TTI-622. Both are anti-SIRPα-Fc fusion proteins, the former an IgG1 and the latter IgG4. Trillium argues that these are the only molecules targeting the SIRPα-CD47 axis that have so far shown clinically meaningful monotherapy responses.

Today, Pfizer and Trillium disclosed a 30% overall response rate among 30 patients in a phase 1 trial of TTI-622, including two complete responses, at a cut-off date of July 26.

However, the recent pivot to combination trials had dented investor confidence about the projects’ monotherapy promise, Evercore ISI’s Josh Schimmer noted. These worries have obviously not put off Pfizer, however, which acknowledged during a call today that Trillium’s projects might not be first in class, but that they have the potential to be best in class.

Executives highlighted data pointing to lower anaemia risk and possibly the potential for the Trillium assets to be dosed lower; both projects also promote a pro-phagocytic signal – or the “eat me” signal – by engaging the activating receptor FcγR on macrophages. Pfizer is targeting regulatory approvals from 2025, they added.

First in class

Gilead’s magrolimab, gained through the Forty Seven purchase, is some way ahead. In myelodysplastic syndrome the group hopes to file for accelerated approval on a phase 1b combo trial with azacitidine, results from which are due later this year.

In front-line acute myeloid leukaemia, meanwhile, Gilead recently started a phase 3 trial of magrolimab plus azacitidine, called Enhance-2.

Another late-stage contender is ALX Oncology’s evorpacept, whose shares climbed 20% today, perhaps on hopes that it could also be a takeout target.

The group will soon start a phase 2/3 trial of the asset in combo with Herceptin in Her2-positive gastric or gastroesophageal junction cancer, Aspen-06. Data in the same setting, from the phase 1 Aspen-01 trial, are set to be presented at next month’s Esmo meeting, which could give clues on this project’s future here.

ALX is also testing evorpacept in combination with Keytruda in head and neck cancer.

Pfizer itself has another CD47-targeting asset in development: a bispecific antibody that also hits PD-L1. However, this is very early in development, with a phase 1 study yet to start recruiting. Whether Pfizer will have to divest this asset to satisfy antitrust regulators is an open question.

Whether other big names now also decide to buy into CD47 or not, Pfizer’s purchase of Trillium is validation of a strategy that looked dead and buried after Celgene discontinued CC-90002 and Surface Oncology quietly shelved SRF231 (Trillium punishes its investors, February 22, 2019). What a difference two years can make in biopharma.

Anti-CD47s in the clinic
Project	Company (originator)	Description	Trial ID
Phase 3
Magrolimab	Gilead Sciences (Forty Seven)	Anti-CD47 antibody	Enhance (NCT04313881) in MSD; Enhance-2 (NCT04778397) in AML
Phase 2/3
ALX148	ALX Oncology	Anti-CD47/SIRPα fusion protein	Ph2/3 Aspen-06 in gastric (NCT05002127); ph2/3 Aspen-03 (NCT04675294) & Aspen-04 in H&N (NCT04675333)
Phase 1/2
AO-176	Arch Oncology	Anti-CD47 antibody	Ph1/2 in solid tumours (NCT03834948) & multiple myeloma (NCT04445701)
Lemzoparlimab (TJC4)	Abbvie (I-Mab)	Anti-CD47 antibody	Ph1/2 in AML/MDS (NCT04202003) & ph1 solid tumours/lymphoma (NCT03934814)
DSP107	Kahr Medical	CD47x41BB fusion protein	Ph1/2 in solid tumours (NCT04440735) & AML/MDS/CML (NCT04937166)
IBI188	Innovent Biologics	Anti-CD47 antibody	Ph1/2 China study in AML (NCT04485052)
TTI-621	Trillium Therapeutics	Anti-CD47/SIRPα fusion protein	Ph1/2 in leiomyosarcoma (NCT04996004); ph1 in haem malignancies/soild tumours (NCT02663518)
Phase 1
TTI-622	Trillium Therapeutics	Anti-CD47/SIRPα fusion protein	Ph1 in haem malignancies (NCT03530683)
TG-1801	TG Therapeutics (Light Chain Bioscience)	Anti-CD19-CD47 bispecific	Ph1 in B-cell lymphoma (NCT03804996) & B-cell lymphoma/CLL (NCT04806035)
IMC-002	Sorrento Therapeutics (Immuneoncia Therapeutics)	Anti-CD47 antibody	Ph1 in solid tumours/lymphoma (NCT04306224)
STI -6643	Sorrento Therapeutics	Anti-CD47 antibody	Ph1 in solid tumours (NCT04900519)
GS-0189 (FSI-189)	Gilead Sciences (Forty Seven)	Anti-SIRPα antibody	Ph1 in NHL (NCT04502706)
SL-172154	Shattuck Labs	Bi-functional fusion protein targeting CD47 and CD40	Ph1 in ovarian cancer (NCT04406623) & skin/H&N cancers (NCT04502888)
CC-95251	Bristol-Myers Squibb (Celgene)	Anti-SIRPα Mab	Ph1 in haem cancers/solid tumours (NCT03783403)
Effi-dem (BI 765063/OSE-172)	Boehringer Ingelheim/OSE Immunotherapeutics (Effimune)	Monoclonal antibody SIRPα antagonist	Ph1 in solid tumours in Europe (NCT03990233) & Japan (NCT04653142)
IBI322	Innovent Biologics	Anti-CD47/PD-L1 bispecific antibody	Ph1 in solid tumours (NCT04328831) & haem cancers (NCT04795128, both China only)
ZL-1201	Zai Lab	Anti-CD47 antibody	Ph1 in advanced cancers (NCT04257617)
PF-07257876	Pfizer	CD47xPD-L1 bispecific	Ph1 in solid tumours (NCT04881045)
IMM0306	Immuneonco Biopharmaceuticals	CD47xCD20 bispecific	Ph1 in B-NHL (NCT04746131)
IMM01	Immuneonco Biopharmaceuticals	Anti-CD47 antibody	Ph1 China trial in lymphoma (ChiCTR1900024904)
Source: Evaluate Pharma & clinicaltrials.gov. https://www.evaluate.com/vantage/articles/news/deals/trillium-gets-buyout-while-its-down