Its getting hot in the IMU kitchen, as Vaxinia meets pembroluzimab
Professor Yuman Fong realised early on the ability of his 33rd virus to turn tumours from cold to hot, hence noting that was the ideal time to introduce an anti PD1 or an immune checkpoint inhibitor such as pembroluzimab. He has since done so in the current Vaxinia (MAST) trial being conducted both here and in the US. “Hot” tumors provide fertile ground for immunotherapy through high levels of T‐cell infiltration, and Immune Checkpoint Inhibitors (ICIs) can block the PD‐1/PD‐L1 pathway or CTLA‐4, normalising the immune system and inhibiting tumor growth. The “hot tumor” treatment focuses on strengthening the immune system against the tumor and increasing the activity of the immune cells. PD‐1 is abundantly expressed in various cancers, resulting in the immune escape of tumor cells and promoting malignant tumor progression. Anti PD1 checkpoint inhibitors such as pembroluzimab block the interaction of PD1 and PDL1, and abolish the inhibition of CD8+ T cell thus enhancing the anti-tumour activity.
Its a powerful combination occurring after the patient’s tumour is infected and infiltrated, a process often causing the tumour to swell and grow in size. Hence whilst initial patient scans may hint at tumour progression, due to the increased circumference of the cancerous growth, ultimately the tumour may regress or shrink over time. In the ideal situation the combination of Professor Fongs oncolytic virus and the Anti PD1 Checkpoint Inhibitor pembroluzimab combine to suppress the malignancy and stimulate the patients immune system. Therefore for those following Imugene’s current Vaxinia Trial, if in fact Professor Fongs drug is working, we may see evidence of tumour regression in patients who were initially perceived to have progressed, if not stabilised in early November 2023.
I am going out on a limb to suggest Imugene may have already been in discussions with the FDA with a view to adding another cancer indication to their fast track designation pathway, alongside the bile duct indication they have an exiting fast track approval for. Perhaps they may have put forward another indication from the gastrointestinal category of cancers, i.e., colorectal cancer. For a long time now the founder Yuman Fong has been insinuating that when his virus infects a solid tumour, it works. Based upon initial scans and subsequent IMU announcements we are aware of the fact Vaxinia has stabilised the tumour burden in trial participants, with positive signals being identified by trial supervisors. If indeed this is the situation, that may well go some of the way to explaining the exuberance exhibited by Imugene CEO and Managing Director Leslie Chong. Let’s wait and see. Its pure speculation on my part, and I could be totally wrong on all fronts, though with Vaxinia currently being dosed at the higher level of ten parts to the 8, in combination with pembroluzimab, the coast is looking somewhat clearer for IMU holders than it did this time 12 months ago.
Keep in mind that if the aforementioned combination is successful pembroluzimab, or Keytruda, as it is marketed, has displayed efficacy in a broad range of cancer indications. These include but are not limited to Non‐small cell lung cancer; melanoma; head and neck squamous cell cancer; classical Hodgkin lymphoma; primary mediastinal large B‐cell lymphoma; urothelial carcinoma; microsatellite instability‐high or mismatch repair deficient cancer; gastric cancer; esophageal cancer; cervical cancer; hepatocellular carcinoma; Merkel cell carcinoma; renal cell carcinoma; endometrial carcinoma; tumor mutational burden‐high cancer; cutaneous squamous cell carcinoma; triple‐negative breast cancer. This extensive list opens the door for Vaxinia to engage with Keytruda in combatting these cancer indications, albeit in a safer, less toxic environment. Such an outcome would undoubtedly encourage participation from Keytruda’s owners Merck, who are scrambling for answers when it comes to what to do when Keytruda’s patent expires later this decade.
DYOR Seek investment advice as and when required Opinions only
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