Hey @DerrickJ, let me first say that any thoughts of mine are...

Hey @DerrickJ, let me first say that any thoughts of mine are based on pure speculation on my part... and pls don't laugh or be peturbed at the length! But i do warn all readers, its long-winded. LOL... This was to be expected, I suspect (grrr), given that the full picture is unknown to, at least, yours truly. Our collaborative work with MDA involved proprietary technology doesn't help with the transparency aspect. Surely, though, SYC could provide greater context without discussing the details or specifics of their binder technology at our upcoming webinar.

"It doesn’t make sense to me that we have scrapped the collaboration unless we plan to put the AML trial on the back burner."

You could well be right. Whether the decision was directly or indirectly based upon data from the R&D and/or some external factors, who knows? There are a myriad of possible reasons for ending the collab and for potentially putting the AML trial on the back burner. Its certainly not ideal to leave the market guessing or worse, taking the negative stance. I dare say the main reason is based on ROI associated with juggling too many moving parts within one trial design. The data coming online from Car-T trials in the clinic would also be taken into account by our team on an ongoing basis in tandem with our ultimate goal.

The main problem with AML is that it can express so many different antigens that evolve differently throughout treatment from patient to patient... and the latter may be the sticking point. We know that single antigen targeting is futile (hence why OmniCAR could be the answer). However, we can't be armed with 33 binders in a trial setting (for obvious reasons) but maybe we need to pursue another dominant antigen rather than a discreet one (as Dan Shelly alludes to in his interview). The cost of accessibility to a multitude of binders at this juncture probably makes AML a tricky candidate for our trials. It could well be that MDA's particular binder targets an antigen in the "discreet" category... too discreet to justify taking into the clinic at this stage given that there is a possibility that our patients won't necessarily express that specific intracellular antigen. OmniCAR needs our trials to shine on its functionality to target antigens (which it will given applicable binders), so we have to go after the most commonly expressed ones - we are so far in having chosen CD-33 and CLL1. One more dominant one one, please!

Rather than assume the negative possibility that our R&D with MDA rendered either technology ineffective, there is the possibility that it was fruitful in determining early compatibility for future application (in the Dan's "real world" context). However, the fact remains that no one AML patient will present the same in terms of antigen expression during clinical trials. How can clinical trials be designed when a platform technology such as OmniCAR is designed for customised / personalised treatment? So, rather than carrying out further R&D on MDA's binders for blood cancer (at who knows what cost), perhaps enough data was derived to serve its purpose for the time being. If so, its been a very prudent and smart call (probably on SYC's part). It could lead to fruitful consideration when the landscape is more accommodating. By that, I mean, when more binders have been developed alongside off-the-shelf cells and amenable regulatory frameworks for clinical trials. OR maybe the collaboration had a far more distant purpose at its core from the outset... namely to appease MDA's curiousity about OmniCAR's applicability for them down the track. Without details, its probably futile guessing either way... good or bad.

"Perhaps this means we are going to pursue one of our solid tumour targets as our first in human trial. If we can make a dent in solid tumours with our CAR-T therapy that will well and truly put us on the worlds radar."

Agree totally, DJ. Even if our AML trial is now on the backburner, it may not be a bad thing, so long as the market and industry recognises that and agrees... and holders don't attempt to push the SP down in the hope of buying back later at a lower price and that coming to fruition. Certainly the data contained in our ISCT posters (optimisation lab tests specific to solid tumours) points to OmniCAR and CellPryme moving forward with immediate purpose and the supportive preclinical data backs that up. Car-T is attracting attention in the solid tumour space more than ever lately, and given Dan Shelly's picture on how AML should most effectively be approached, we may need allogeneic manufacturing to become the accepted norm for the optimal commercial environment for such diseases. Does PTX see the FDA becoming more amenable to allo in the near-term when it comes to trial approvals?

Car-T in blood cancers already has score on the board. To crack it in solid tumours would undoubtedly capture the imagination of the industry more (eventhough Car-T for AML sufferers has yet to be solved). As far as the stockmarket is concerned, PTX needs to provide definitive goals and timelines now for OmniCAR. Whilst speed is important, derisking our chance of nailing the data in the clinic should still be paramount... but to what avail in the short term price action if newsflow is minimal?

I hope you don't mind me splitting up your queries and addressing them this way, DJ. They are good questions and warrant giving some thought and perspective to them.

"How does allogenic vs autologous CAR-T cells impact whether we attack the multitude of antigens expressed form AML?

I guess the option doesn't have to impact our trials. However, maybe our scientific and business development teams are thinking welll ahead... to commercialisation of OmniCAR. If AML is better treated via off-the-shelf cells as Dan explains from a commercial perspective and as Bec states from a scientific perspective, then perhaps that is how OmniCAR should be approached in the clinic too. If the optimal way to treat AML is via the consistency of cell quality (being from healthy donors) and speed of targeting new antigens (by using allo cells and binders), then perhaps we need to consider that our in-house Car-T therapy should emulate that in our clinical trial. It would reduce one unnecessary hypothetical, wouldn't it? Although, if OmniCAR proves successful in the clinic (fullstop) regardless of donor-source method, we'll be home and hosed to a great extent. But lets do it now in indications where autologous is likely to be less of a hinderance and have impact on the market if successful... and lets "buy some time" for allo to become a viability for AML.

There'd be no point in pursuing a sub-optimal route for AML at this point if autologous cells are more congenial for solid cancers. Maybe our collab with MDA has led both PTX and MDA to considering allo for AML. If so, then our collab with Thermo Fisher may be extended to make provision for OmniCAR in the allogeneic space at commercial-scale. Big Daniel, has made reference to allo and TF in the same sentence a couple of times. Positive outcomes from trials being done by other biotechs in the lab and clinic using allo will support our advancements in this area too with regards to future FDA approval application.

Dan Shelly states in his interview that there are 33 discreet antigens for AML in a static-CAR format being evaluated globally at the moment. But he guarantees that we probably only need to consider targeting 4, 5 or 6 that would be the most dominant in an indication. For me, that raises the question as to whether MDA's particular binder is one of the most dominant intracellular antigens or not. Could be its one of those "discreet" anitigens... too discreet to be used for testing a platform like OmniCAR (at this stage) in which we need to showcase functionality and, ultimately, efficacy. I wonder how much it costs to make binders. Can PTX contract the makng of a third binder, such as CD-123 (in conjunction with CD-33 and CLL1) or are all binders proprietary?

Is AML the best choice for our maiden OmniCAR clinical trial...? As Unique stated: "Too many spinning plates." Its not too many spinning plates for OmniCAR (as binders can be swappped out for limitless sequential dosing but also administered simultaneously with up to three or four different antigen targets from the same cell administration) but it may be too many within the constraints of clinical trials and just too damn difficult to design a trial that would do OmniCAR justice. Imagine trying to convince the FDA that our trial involves targeting up to 6 antigen targets to effectively treat AML patients. Imagine trying to design a trial with so many contingencies or having one binder wasted on targeting an antigen that may never present within our trial. Maybe solid tumours would be simpler for a maiden trial. Afterall, throwing everything at a particular cancer once safety and efficacy in humans is known is one thing, but doing it in a maiden trial could be fraught with risk... and that's clear given the detail in the Qtrly about the trial designing. I had at one point (some time ago) alluded to the inherent complexity of designing the OmniCAR trials. But, I have confidence that our particular team can achieve it with success.

"Isn’t the idea of Omnicar, that we can choose multiple different binders and administer that to the patient, regardless if the CAR-T cell is auto or allo?"

Yes, but each disease and each patient is different as Dan Shelly explains precisely in the interview above. The fact that AML is an aggressive disease and the fact that autologous cells present variability in manufacture makes treatment of AML that much less challenging using allo. Speed is of the essence when it comes to treating AML, according to my reading. Whilst OmniCAR can use either cell manufacturing regime, there are advantages and disadvantages to both... and AML may be one of the cancer types best addressed with off-the-shelf cells.... and it may be better to ride on the coat tails of those biotechs carrying the torch for the allo camp to convince the FDA of its merits, as opposed to us.

The fact isclinical trials are limiting and not OmniCAR as such. The applicability of OmniCAR is broad by nature and, therefore, impossible to trial across all cancer types and all antigen targets in one swelll swoop. So its probably best to make our maiden trial the one that will make the most impact in the eyes of the industry and the investment market. As you suggest, our Her2 trial in solid tumours could be our first baby.

It looks as though AML is going to continue to be one of those blood cancers on the back burner until such time that the FDA catches up to the speed at which the biotechnology field is moving. They also need to be more accommodating as to how universal platforms can be best served and showcased in the clinical environment. In other words, allogeneic "off the shelf" cells and non-viral vector manufacturing, whilst not the favoured methods yet in terms of FDA approval rates (due to less available supportive clinical data), will likely improve evolve soon given the FDA's changing attitude.

Co-existence of auto and allo, and co-existence of viral and non-viral vectoring too, looks to be where the industry is headed in personalised imunothereapy treatment. The FDA and other regulatory bodies just need to become more amenable to the advancement of more recent innovation and advancements, so that personalised / precision medical treatment is not stymied by an outdated approvals system. Enabling biotechs to employ the most effective methods available in CGT and thus giving future practitioners the best methods for administering it in a personalised framework, is the way to go.


Apologies, I'm sure there is concise answers to your questions in there somewhere, DJ. You may have to do some sifting, though.... sowwy!

Bring on updated details on PTX-100 clinical data, CellPryme evaluations by third parties and a definitive timeline for our OmniCAR trials, and the SP should move back in the right direction. Oh, and sincere and direct responses to questions in our upcoming webinar (leaving no stones unturned within reason) won't go astray!