Oncolytics Biotech Inc T.ONC

ONCY's pelareorep activates interferon (IFN) signalling

[Noteable]

Tumor cells require an active interferon (IFN) signalling pathway for the success of many anticancer therapies.

https://www.frontiersin.org/articles/10.3389/fimmu.2022.821816/full

The AWARE-1 study results presented at SABC 2022 on December 07, 2022 demonstrated that pelareorep activated the IFN signalling pathway and "primes" the tumor in advance of immune checkpoint inhibition. (see below)

“Pelareorep primes the tumor for checkpoint inhibition therapy by activating the interferon-gamma signaling pathway and tumor inflammation signature in early breast cancer patients - results of the AWARE-1 trial”

Loghmani, Houra et al, Previously presented at the 2022 San Antonio Breast Cancer Symposium®; December 6-10, 2022

https://www.oncolyticsbiotech.com/technology/posters-publications

And by pelareorep's effect in down-regulating HIF-1a the issue of TME hypoxia is simultaneously addressed.

 

Which is an issue highlighted in the above referenced Frontiers - University of Oxford England paper ...

"In solid tumors, as the tumor grows and the disease progresses, hypoxic regions are often generated, but in contrast to most normal cells which cannot survive under these conditions, tumour cells adapt to hypoxia by HIF-driven mechanisms. Hypoxia can further promote cancer development by generating an immunosuppressive environment within the tumour mass, which allows tumour cells to escape the immune system recognition. This is achieved by recruiting immunosuppressive cells and by upregulating molecules which block immune cell activation. Hypoxia can also confer resistance to antitumor therapies by inducing the expression of membrane proteins that increase drug efflux or by inhibiting the apoptosis of treated cells. In addition, tumor cells require an active interferon (IFN) signalling pathway for the success of many anticancer therapies, such as radiotherapy or chemotherapy. Therefore, hypoxic effects on this pathway needs to be addressed for a successful treatment."

https://www.frontiersin.org/articles/10.3389/fimmu.2022.821816/full

[Noteable]

Hypoxia-inducible factor-1α (HIF-1a) is a direct transcriptional suppressor of interferon regulatory factors, the transcriptional activators of type I IFN. These findings may aid in understanding and control of impaired IFN production by severe acute respiratory syndrome coronavirus 2 infection .... and why Big Pharma companies like Pfizer, Moderna, BMS, Roche, MerckKGaA and others are be

[Noteable]

Big Biotech/Pharma companies involved in COVID-19 R&D who are increasingly interBig Biotech/Pharma companies involved in COVID-19 R&D who are increasingly interested in ONCY's pelarorep's activation of the IFN signalling pathway and in pelareorp's synergistic capacity as an anti-cancer agent which enhances muliple currently marketed and in development I/O agents, such as immune

[Noteable]

Should read: - Big Biotech/Pharma companies involved in COVID-19 R&D are increasingly interested in ONCY's pelarorep's activation of the IFN signalling pathway and in pelareorp's synergistic capacity as an anti-cancer agent which enhances muliple currently marketed and in development I/O agents, such as immune checkpoint inhibitors, CAR-T therapy, proteosome, PARP and CDK4,6

[Noteable]

Interesting 2014 paper - which supports ONCY's pelareorep clinical development as a immune molecule platform technology and its mechanism of action (MOA) in "priming" the TME in advance of the addition of PD_(L)1 immune checkpoint inhibitors.Skip Nav Destination Brief Definitive Report|April 28 2014 PD-L1 is

[Noteable]

And now you should be able to understand why ONCY's acquisition value is worth somehwhere starting in the middle of Big Pharma's US$5 to $15 Billion "sweet-spot" range.

[fox7mf]

....I'd like to think that valuation will be closer to $15b usd when one considers a psoriasis treatment just received $6b usd in a buyout. Merry Christmas/happy holidays to all the patient longs, cancer patients everywhere & even the desperate bashers. Health & happiness. 

[Noteable]

  In the recent past, high patent expiration exposures have triggered merger activity: BMS’s Celgene Corporation buy in 2019 ahead of its Eliquis patent loss, for example, and AbbVie Inc.’s acquisition of Allergan, Inc. in 2020, several years ahead of its 2023 Humira exclusivity loss. Most of the companies facing the highest cliffs, such as BMS, Pfizer Inc. and Merck & Co., Inc

[Noteable]

HIF-1α is a master hypoxia transcription factor mediating expression of a defined set of genes with different physiological and pathological functions, such as epithelial–mesenchymal transition (EMT), angiogenesis and metastasis (i.e. termed hypoxic responses). Thus, targeting the inflammatory interferon-driven and hypoxia-induced pathological TME and corresponding signaling pathways present an

[Noteable]

ONCY's pelareorep activation of IFN-α signaling /pathways while simultaneously inducing the down regulation of HIF-1α expression resuls in particular "cross-talk" involved in the remodeling of a hypoxic TME while "priming" the TME for the addition of immune checkpoint inhibitors, and is leading to a rationale strategy in the development of new therapeutic interventions

[Noteable]

Besides ONCY's pelareorep ability to directly lyse the cancer cell, pelareorep's ability to also activate the IFN-α signaling /pathways along with the down regulation of HIF-1α expression that results in "cross-talk" which remodels the hypoxic TME, pelareorep's down-regulation of HIFs can be viewed as an important step in the elimination of a tumor cancer cell. Because

[Noteable]

https://www.nature.com/articles/cgt200984

[Noteable]

As studies in Multiple Myeloma have demonstrated "Reolysin (pelareorep) followed by anti-PD-L1 therapy demonstrated superior efficacy compared to simultaneous co-administration. The pre-treatment with Reolysin is required in order to allow sufficient time for oncolytic reovirus to replicate inside MM cells and subsequently increase PD-L1 expression." The following study also showed that

[jimsenior]

@ Noteable. This is getting heady for us lay folk. Is it possible that the cross-talk explains the efficacy of the pelareorep boost in the pre-clinical CAR T work. Never did quite understand that. TIA

[jimsenior]

Put my idea to a small search, and I may be right. Would be nice to get an official confirmation. We may be heading into unknown territory.

[westcoast1000]

JIm, I would say all this work on the tumor environment and the sequential administration of pela before other agents is all nearly unknown territory, barely explored. But the article that came out last summer about the effects on the TME is extremely powerful and in one of the world's top science journals. Other biotechs addressing cancer would be rocketing on such news. Because we are ONCY

[Buckhenry]

unnoteable getting in some last minute stroking of his ego. 

[Noteable]

CARs initiate robust T cell activation and subsequent cytolytic killing of the target cell through an intracelluar signaling domain.. Utilizing T cells expressing chimeric antigen receptors (CARs) to identify and attack solid tumors has proven challenging, in large part because of the lack of tumor-specific targets to direct CAR binding. Tumor selectivity is crucial because on-target

[jimsenior]

Not sure if this is germane. Search  -  CAR T cell killing requires the IFNyR pathway in solid but not liquid tumors.

[Noteable]

HIF is a direct transcriptional suppressor of interferon regulatory factors. As already discussed pelareorep is able to down-regulate the expression of the HIF genes and in so doing facilitates interferon (IFN) activation, as the AWARE-1 study reported on during SABCS 2022 earlier this month. https://www.nature.com/articles/s41586-022-04585-5

[jimsenior]

CAR T - I have been giving this some thought and question why we have not been updated on this subject. While we wait. I did find  the following. CAR T cells in solid tumors: challenges and opportunities. Very complex, but read down to at least the section entitled - Trafficking and infiltration into tumor tissue. Is ONCY scheduled to give a poster on CAR T in 2023. This is such a

[jimsenior]

CAR T   - Fifth European CAR T Cell Meeting. Feb  9-11, 2023 Another board stated ONCY have a poster due. Not sure if this is the place. I am tempted to add, but shall wait til 2023. An update would not go amiss.

[fasttrack5]

My opinion a great  buy opportunity. wishIng all a happy healthy & prosperous 2023.

[jimsenior]

CAR T  - Next Generation CAR & T Cell Therapies Feb 27 - March 2, 2023. This event is in San Diego, and a more likely venue. It would simplify matters if the company would issue an update. Que sera sera.

[Buckhenry]

we would all like to think that... but then reality sets in and no one here jas a clue if or when anything will happen. 

[Noteable]

In an earlier post I explained how ONCY's oncolytic virus pelareorep down-regulates HIF-1a by an activated IFN-gamma, which in turn down-regulates adenosine, a downstream chemokine-like catalyst in the TME hypoxia pathway, that acts as a potent TME immunosuppressive agent. As further background, in 2019 the Nobel Prize in Physiology or Medicine was awarded to William G. Kaelin Jr., Sir Peter

[Noteable]

Should read : " In an earlier post I explained how ONCY's oncolytic virus pelareorep down-regulates HIF-1a by an activated IFN-gamma pathway,..."

[Noteable]

Reovirus Induces Downregulation of HIF-1α Target Genes in Tumor Cells - Hotani et al. (2019) The results of this paper indicated that reovirus downregulated the expression levels of not only HIF-1α but also its target genes in the tumors following systemic administration.

[Noteable]

ONCY's pelareorep (reovirus) is capable of remodeling an immunosuppressive / hypoxic tumor microenvironment (TME) through the downregulation of HIF-1α target genes in tumor cells. The result is that ONCY's pelareorep is able to "prime" the innate immune system in advance of the addition of PD-(L)1 immune checkpoint inhibitors to produce a synergistic outcome seen by adding

[Noteable]

Cancer immunotherapy is based on using the immune system components to fight tumors, without destroying normal cells.  Many tumors can resist immunotherapy due to the absence or insufficient infiltration of tumors with CD8+ T cells and hence, are called “cold” or non-inflammatory tumors. Cold tumors are characterized by a lack of infiltrating CD8+ T cells, the presence of anti-inflammatory

[Noteable]

Should read: "... results in the ability of turning "cold" tumors into "hot" tumors through innate and adaptive immune responses to treat a variety of cancers,"

[Noteable]

Repost : Hypoxia-inducible factor-1α (HIF-1a) is a direct transcriptional suppressor of interferon regulatory factors, the transcriptional activators of type I IFN. These findings may aid in understanding and control of impaired IFN production by severe acute respiratory syndrome coronavirus 2 infection .... and why Big Pharma companies like Pfizer, Moderna, BMS, Roche, MerckKGaA and others are

[Noteable]

https://stockhouse.com/companies/bullboard/t.onc/oncolytics-biotech-inc?postid=35191733

[Noteable]

So when everyone was asking what the AWARE-1 results were on December 7th 2022, I provided the larger answer under the above subject header.