Oncolytics Biotech Inc ONCY

Pfizer acquires Canadian Trillium for US$2.3 Billion

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Aug 23 (Reuters) - Pfizer Inc (PFE.N) said on Monday it would buy Canadian drug developer Trillium Therapeutics Inc (TRIL.TO) in a $2.26 billion deal to strengthen its arsenal of blood cancer therapies.

Pfizer, which acquired a $25 million stake in Trillium last year, will buy the remaining outstanding shares for $18.50 apiece, representing a 203.8% premium on the stock's last closing price.

Pfizer expects to benefit from Canada-based Trillium's blood-cancer therapies that target a "don't eat me" signal used by cancer cells to evade the immune system.

Forty Seven Inc, which is also developing drugs that target the same antibodies, was bought by Gilead Sciences Inc (GILD.O) for $4.9 billion last year.

https://www.reuters.com/business/pfizer-buy-trillium-therapeutics-226-bln-deal-2021-08-23/

The relationship between the CD47 "don't eat me" signal / CD47 antibodies / and oncolytic virus is interesting as OVs like pelareorep work to neutralize CD47 on tumor cells and promotes phagocytosis.

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Oncolytic virus, like ONCY's pelareorep, has a neutralizing effect on CD47 which is a transmembrane protein that is over expressed on certain tumor cells. CD47 acts as a 'don't eat me' signal in innate immune and adaptive signaling by binding with SIRP-α to inhibit immune elimination, which is the cellular process in how tumor cells escape detection by the immune system. On this

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CD47 deals about T cells being able to infiltrate the tumor. Infiltration of two types of immune cells, CD8 T-cells and macrophages has been demonstrated to happen with CD47 antibody therapy,which ONCY has also been able to demonstrate with pelareorep. Furthermore, since pelareorep is able to convert an immunosuppressive TME into a more conducice environment that results in the  "priming

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As a point of clarification, macrophages have emerged as a new potential target of immunotherapy. Tumor-associated macrophages (TAMs) can eliminate tumor cells through phagocytosis, maintaining a suppressive tumor microenvironment (TME).  Cluster of differentiation 47 (CD47) is a transmembrane glycoprotein ubiquitously expressed in normal cells and serves as a cellular receptor

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Pfizer acquired Trillium in the midst of over 30 companies involved in the development of drugs against CD47 antibodies or its ligand SIRPα, including monoclonal antibodies, bispecific antibodies, fusion proteins, and small molecules. More than 20 of them have entered the clinical research stage. From the perspective of the geographical distribution of CD47 projects, China has become the most

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 According to Fiercebiotech - "The New York-based giant [Pfizer] also has a relatively weak pipeline for such a major pharma. Pfizer's late-stage pipeline is gene therapy heavy and the last year has shown how manufacturing and safety concerns can make these bets a risky proposition. In short, Pfizer has a lot of extra cash that was likely unexpected 18 months ago and a pipeline to

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Jefferies analysts see the current drawdown in biotech stocks , with the XBI is down 25% from a peak in February, as setting the stage for some serious M&A, exemplified by Pfizer's acquisition of the pre-clinical / early stage immuno-oncology company Trillium Therapeutics this week.

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Relationship between ONCY's OV pelareorep - Pfizer/Trillium's CD47 inhibitor - immune checkpoint inhibitors (ICIs) - and CAR-T therapy Enhancing the patient's adaptive immunity, or turning “cold tumor” into “hot tumor,” has become the primary goal for glioblastoma research. [ ONCY has demonstrated that pelareorep is able to 'prime' the adaptive immune system, increase T-cell

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Over past decades, remarkable progress in cancer immunotherapies has been made, such as developing ICIs, BiTE, and CAR-T cells. Although developing mAbs against immune checkpoints axes has improved anti-tumoral immune responses, their applications have been associated with a remarkable risk for autoimmunity development. Since macrophages can cleave these mAbs, targeting immune checkpoints via mAbs

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OVs in combination with ICIs can be a strategy to address the inefficacy of ICI against cold tumors, as these viruses can inflame the TME into a more immunologically favorable environment for cancer immunotherapeutics. Other immunotherapeutics (like CAR-T and ICI) in combination with ICIs are well known to compound adverse events, whereas OV such as ONCY's pelareorep do not, and this superior

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Preconditioning of the tumor microenvironment with oncolytic reovirus converts CD3-bispecific antibody treatment into effective immunotherapy Replication-competent reovirus induced an early interferon signature, followed by a strong influx of natural killer cells and CD8+ T cells, at the cost of FoxP3+ Tregs. Reovirus as a preconditioning regimen performed significantly better than

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August 17, 2022 - "AbbVie is stopping another early-phase clinical trial of anti-CD47 antibody lemzoparlimab. Weeks after pulling the plug on a multiple myeloma trial, the Big Pharma is halting a phase 1b trial that is testing the prospect in combination with azacitidine and venetoclax. AbbVie’s termination of early-phase studies follows a tough period for the broader CD47 race

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Targeted Blockade of Immunosuppressive Pathways following Reovirus Oncolytic Virotherapy Can Induce Synergistic Anti-tumor Responses The ability of OVs to sensitize immunologically cold tumors to ICB is due to their potent ability to inflame tumor microenvironments with both innate and adaptive immune cells. The following linked study demonstrated that reovirus infection of TRAMP-C2 tumors

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"Trillium’s portfolio includes biologics that are designed to enhance the ability of patients’ innate immune system to detect and destroy cancer cells. Its two lead molecules, TTI-622 and TTI-621, block the signal-regulatory protein α (SIRPα)–CD47 axis, which is emerging as a key immune checkpoint in hematological malignancies. TTI-622 and TTI-621 are novel, potentially best-in-class SIRPα-Fc

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"Trillium, like peers such as Forty Seven and Arch Oncology, has identified CD47 blockade as a way to unleash the power of the innate immune system against tumors. The two candidates are designed to block CD47 while simultaneously delivering an “eat me” signal to macrophages and, in the case of TTI-621, activating natural killer (NK) cells." Trillium is enrolling blood cancer patients

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Pfizer's acquisition of Trillium now has stock market speculators looking to 'double down' on oncology companies that are currently running clinical trials. https://www.thestreet.com/jim-cramer/jim-cramer-pfizer-trillium-oncology-speculation

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Trillium had undergone a significant change. Originally headquartered in Canada, the company has now moved its home base to Cambridge. The new CEO joined in 2019 when the stock had tumbled from $30 apiece to just 30 cents after some difficult data readouts failed to impress investors. Despite the plummet, the new CEO Jan Skvarka saw promise in the CD47 drug class and the science underpinning

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Trillium Therapeutics secured funding from Pfizer's Breakthrough Growth Initiative (PBGI) in January 2021, receiving a $25 million investment to support clinical development of Trillium's CD47 program. The investment put Pfizer in a strong position to pick up rights to assets in a field targeted by AbbVie and Gilead if Trillium gathered the data needed to land a deal.

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 Correction:  Trillium Therapeutics secured funding from Pfizer's Breakthrough Growth Initiative (PBGI) during the second half of 2020

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Gilead's "don't eat me" monoclonal antibody CD47, designed to interfere with the recognition of CD47 by the SIRPα receptor on macrophages, to int-turn block the “don’t eat me” signal used by cancer cells, presently in clinical trials in combination with a macrophage checkpoint inhibitor, had studies put on partial hold by FDA  due to concerns of unexpected serious

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February 02. 2022 -  Gilead revealed that a partial clinical hold for its CD47 targeted cancer hopeful is larger than originally thought. Magrolimab is an anti-CD47 antibody that Gilead acquired through the $4.9 billion takeover of Forty Seven. https://www.fiercebiotech.com/biotech/gilead-s-cd47-clinical-hold-expands-as-ceo-expresses-sense-urgency-getting-trials-back