G'day Davy,Great to have you and OvF back on the threads. I...

G'day Davy,

Great to have you and OvF back on the threads.

I would agree that it's highly likely IMU have already applied for breakthrough therapy for Vaxinia following FDA reviewing initial data. The benefit (faster development timeline) of breakthrough designation will fall on the whole phase I MAST but especially the 10 patient expansion trial taking place for bile duct patients. First things first though, dose escalation has recently been extended, meaning efficacy is potentially getting better without safety issues arising. Ultimately, the expansion trials wont begin until the ideal dose is found (RP2D). Leslie mentioned that they are currently interrogating the potential dose for the expansion study. So could be looking to start that trial in the next 6 months. I'd anticipate that if the data is promising for the expansion trial/s that Accelerated Approval could likely be granted, for that indication. Given the rate at which patients are being enrolled this could happen very quickly.

Accelerate approval doesn't require the lengthy endpoints to be confirmed and instead can be approved based on surrogate or intermediate clinical endpoints. FDAs definitions of these endpoints:

A surrogate endpoint used for accelerated approval is a marker - a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit, but is not itself a measure of clinical benefit. Likewise, an intermediate clinical endpoint is a measure of a therapeutic effect that is considered reasonably likely to predict the clinical benefit of a drug, such as an effect on irreversible morbidity and mortality (IMM).

hNIS would help with the imagery. Tumour shrinkage and increase T-Cell activation all would likely fit the bill. Coupled with safety in spades I would be very surprised Vaxinia wouldn't already meet these requirements. Especially, in cancer types that have an unmet need, unresectable Bile duct cancer being one of them.



For this patient pseudoprogression was witnessed at their second (first after baseline) scan at circa 6 weeks. Two scans later, complete remission. Pretty remarkable, for a patient that had a cold tumour and progression on 3 lines of therapy, there are plenty here that would have an idea of how significant that result is clinically and also for this patient and their family. As Paul Woodard mentioned in the webinar, the most recent large phase III studies for first line therapies in Bile duct cancer have led to a median survival of "about a year" with most patients relapsing and having a very poor prognosis thereafter.

Of note, the 25 patients that have been evaluated have receive at least their first scan, so it's possible the results even at the mid dose range could get much better that was has been released thus far. Keeping in mind the CR above was confirmed after their third scan after baseline not sure how many weeks later.

Your points around Azer-Cell highlight how quickly that therapy could reach commercial outcome. It's likely these commercial outcomes will occur within the scope of blood cancers first. But its unlikely IMU will sell Azer-Cell if OnCARlytics proves to be as effective as we think it will. Following on from that if OnCARlytics is effective CF33 would also need to packaged in. So it begs the question, are IMU going to seek a partner or commercial outcomes with one suitor across the three therapeutic approaches? Arguably, Azer-Cell has much larger commercial viability in combo with OnCARlytics, than with blood cancers alone, but needs to pursue the path to commercialisation first within blood cancers to give it the nod for OnCARlytics combo.

It also means that a potential suitor doesn't need to have their own CAR-T and instead have an off the shelf therapy that has shown efficacy in multiple indications, the mind boggles at the opportunity here. The team have a lot more data to build but its looking increasingly promising on a number of fronts, and commercial outcomes could be much closer than some realise.

Cheers.