Oncolytics Biotech Inc ONCY

Pelareorep + Paclitaxel = ADC/HER2 failed breast cancer

[Noteable]

https://stockhouse.com/companies/bullboard/t.onc/oncolytics-biotech-inc?threadid=36048690

[Noteable]

Besides the ADC Enhertu being approved for multiple stages of ER+/Her2 (+/-) (posotove/negative) breast cancer,  ONCY's decision to target the HER2 failed breast cancer patient population with pelareorep + paclitaxel may have been also influenced by today's Roche/Genentech's breakthrough therapy announcement involving  ER+/Her2- (negative) breast cancer May 21, 2024

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Should read: ' ...ER+/Her2 (+/-) (positive/negative) breast cancer..."

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Regardless of whatever influenced ONCY's decision to target the HER2 failed breast cancer patient population, the HER2 failed population is a large and conclusively identifiable population since they are the same who had been previously identified as having HER2 (positive/negative) breast cancer, treated with an ADC therapy and then ultimately failing on this same therapy. These failed breast

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ONCY's Phase 2 Bracelet-1 study 2 year breast cancer patient overall survival (OS) milestone being reached at the end of this month- May 2024.

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Key one (1) year biomarker and safety findings of ONCY's Phase 2 Bracelet-1 breast cancer study:  Association between T cell expansion and efficacy measures:  A statistically significant increase in T cell fraction, a measure of T cell expansion, was observed in cohort 2 (paclitaxel + pelareorep) but not cohort 3 (paclitaxel + pelareorep + avelumab) Generally favorable and

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May 21, 2024 - - Roche Holding AG said an experimental breast-cancer treatment will get an expedited review from US regulators after showing it helped patients live longer without the disease progressing. The decision is based on research showing the medicine, called inavolisib, could offer a more effective first treatment option for women with a ER+/HER2 - (negative) breast cancer mutation

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ONCY's IND213 breast cancer study conducted by the Canadian Trials Group - found that patients with increased age, better performance status (PS), no prior paclitaxel therapy and mutations in TP53, PTEN, AKTI and KIT had longer OS, while those with PIK3CA, APC and ATM mutations had shorter OS.

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May 29, 2024 - Roche/Genentech's priority review for inavolisib, an investigational oral therapy, in combination with palbociclib (Ibrance®) and fulvestrant was evaluated in adult patients with P1K3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer,is based on the positive Phase III

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Inavolisib is currently being investigated in three company-sponsored Phase III clinical studies (INAVO120, INAVO121, INAVO122) in PIK3CA-mutated locally advanced or metastatic breast cancer in various combinations.  https://www.biospace.com/article/releases/fda-grants-priority-review-to-genentech-s-inavolisib-for-advanced-hormone-receptor-positive-her2-negative-breast-cancer-with-a

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Comparing Roche's inavolisib's + palbociclib and fulvestrant combination Phase 3 results to ONCY's pelareorep + paclitaxel Phase 2 results ... The results showed the inavolisib-based regimen more than doubled progression-free survival (PFS), reducing the risk of disease worsening or death by 57% compared to palbociclib and fulvestrant alone (15.0 months vs. 7.3 months

[canadafan]

I agree 100%, clearly an advantage utilizing Pela as a cotherapy. the numbers you indicated are substantial. check in box 

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August 12, 2024 - Oncology, rare diseases, and immunology will likely continue to be hot targets for investors, and snapping up drugs from smaller startups has advantages over in-house development.   “What we’re seeing is the elimination of riskier and longer-shot products in the R&D portfolio for the big pharma companies, basically swapping those out for acquisitions with more

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August 12, 2024 - Oncology, rare diseases, and immunology will likely continue to be hot targets for investors, and snapping up drugs from smaller startups has advantages over in-house development.   “What we’re seeing is the elimination of riskier and longer-shot products in the R&D portfolio for the big pharma companies, basically swapping those out for acquisitions with more

[Noteable]

ONCY's pelareorep, which enhances  including topoisomerase I inhibitors, + the chemotherapy paclitaxel can enhance the efficacy of CPIs providing an opportunity to combine immune CPI therapy with Dato-DXd, a Trop-2 antibody-drug conjugate (ADC).

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Should read : ONCY's pelareorep, which enhances topoisomerase I inhibitors, + the chemotherapy paclitaxel can further enhance the efficacy of CPIs, as already demonstrated, thus providing an opportunity to combine immune CPI therapy with Dato-DXd, a Trop-2 antibody-drug conjugate (ADC).

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Additionally Stewart et.al. (2019) found that "topoisomerase inhibitors are a class of drugs that enhance reovirus infectivity and cytotoxicity of triple-negative breast cancer cells."  Dato-DXd is a TROP-2-directed ADC where a humanized anti-TROP-2 IgG1 MAb is attached to a topoisomerase I inhibitor payload via tetrapeptide-based cleavable linker. 

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" Merck’s sac-TMT is an antibody-drug conjugate (ADC) targeting TROP2, a protein that’s overexpressed in many tumors and plays a part in promoting cancer. The first TROP2-directed ADC, Gilead’s Trodelvy, reached the market in 2020. And AstraZeneca and partner Daiichi Sankyo’s datopotamab deruxtecan, or Dato-DXd, looks likely to be the second in the class to enter the ring, with its two

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In a key mechanism of ADCs, once the antibody part of the drug binds to the target antigen expressed on the surface of tumor cells, the drug is absorbed into the tumor, where it releases the toxic payload to kill the cancer. Because Dato-DXd uses a very stable linker that barely breaks off and sets the payload free before entering the tumor, that internalization process becomes very important to

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  All FDA Approved ADC Therapies  Drug Lead Company Indication/s First Approval

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Daichii Sanyo's Enhertu consists of a HER2 monoclonal antibody (trastuzumab) attached to a topoisomerase I inhibitor  (DXd)  payload, 

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Berry et.al. (2020) "  ...data demonstrate that crosslinking chemotherapeutic agents to oncolytic viruses facilitates functional drug delivery to cells targeted by the virus, making it a viable approach for combination therapy against TNBC." " Reovirus oncolytic efficacy is further augmented by combination with topoisomerase inhibitors .." .. similar to the topoisomerase

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As part of the pro-inflammatory activity, certain signals, referred to as “damage-associated molecular patterns”, (DAMPs) are emitted. DAMPs are endogenous molecules that would have been concealed in normal cells but that are released upon stress, cell injury, or cell death. As a result of this signaling pattern, an interphase is established with the host immune system (particularly

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Should read : " ....  and in a basic way explain how ONCY's pelareorep is also able to remodel the TME and overcome T-cell resistance and T-cell exhaustion."

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According to an October 2023 paper in the Oncologist regarding the ' Evolving Landscape of Immune Checkpoint Inhibitors and Antibody-Drug Conjugates in the Treatment of Early Breast Cancer ' various novel modalities of immunotherapy, including CAR-T cell therapy, bispecific T-cell engagers, and other immunomodulatory receptors like LAG-3 have been evaluated in patients with breast cancer

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ONCY will have 13 years of FDA marketing exclusivity from the date of FDA approval for pelareorep in breast cancer for example. And another 13 year of market exclusivity for pancreatic cancer, as another example, ...and so on for subsequent FDA approvals for pelareorep in subsequent indications.

[Noteable]

Don't worry about Matt .... he's entirely pre-occupied in the statistical analysis of the breast cancer Bracelet-1 and Goblet-1 Phase 2 studies for Accelerated Approvals.

[CMHarring218431]

[CMHarring218431]

Lost my post. In short, judging from Note's own post, it would seem that he is very close to the situation at ONC. Matt feeling better?