People were indeed curious when they saw the two line charts with adequate separation of the active and placebo. But in reality, they would need more time to digest this and realise that n was actually so low...not in hundreds, but measured in low double digits...ie 15 (2x2) in 008 and 54 (active) in 005 ! If we could've STOPPED MID WAY and highlighted this, it would've impressed them even more! Of course I can well imagine what a presso like this would be like if it were spread over twenty mins and one day we will include an n that's much higher...eg after our P3?
Very clearly separated data...One more point about the theatre session, Par did a really good job not to release everything in this theatre session, I imagined it was like a big dangling carrot for that packed but silent room inferred by stating that the data release would occur in the main theatre session tomorrow, Saturday afternoon. I'm fairly sure most of this theatre crowd would have attended the main theatre session as a direct result. This was brilliant, I think it was quite deliberate, but we need more from PAR like this...what do I mean?
I mean SURPRISE!! I mean anticipation creation...I mean a little Pizzazz.Look we aren't a company selling the latest transistor radio (oops that was decades ago...let me try that again), we aren't a company selling the latest hydrogen fuelled ghetto blaster....
We ain't selling this......but a little magic is going to go a long way and I do think PAR are doing better in this dept. We have come along way in graphics and shown off a consistent message and exploring new ways to present the data in an attractive manner. Yes of course our drug will one day sell itself, but giving it a slight push through enthusiasm, through new media and thru a little well razzle dazzle can only help! When we sell into the American market, I believe the right Big P will bring a lot of salesperson-ship...a lot of media talent...something catchy, something that boosts appeal on top of a drug that fundamentally works well, is 'patient convenience' but isn't burdensome in the constant having to dose throughout an entire year, perpetually.
I can't tell you how enjoyable it was for me to speak to a number of researchers (both big and small!) and tell them of our science. I said it with enthusiasm and genuinity and they could look me in the eyes...they could see my MRI's...they knew I wasn't BS'ing.
The other (second) barometer was how many and when (for which slides) did the audience take the most pics of.
Definitely it was the DMOAD slide and the other three comparator slides where the crowd reacted the most. That was when the most pics were taken.
My camera didn't capture them too well; I was more interested not in the material because I could view them later for myself when PAR publishes them, my focus was on the crowd, how they were reacting. It was pin drop silence, everyone in that room was so focused on what Dr Ahuja was saying but with an even greater focus on the slides.
The room was totally silent despite it being packed to the brim and listening to every word. It was very interesting to see which slides were the most revered. How could I get a sense of that? Well that was easy, by the number of cameras that went up to take a pic!
So which were the biggest hits in terms of slides? Let's take a look:
This slide caused a bit of a stir and I suspect it was the DM title, it took a few seconds for the crowd to react as they read the title. Then the cameras went up...
It's a busy slide but look at those 6 charts, if one analyses and thinks about it, it's showing us such a broad sweep in terms of positive actions...
(Single left click on the above to view larger version).
Just look at those pertinent peach bars representing our drug and comparing it to the poor pastel blue placebo bars.
Chalk and Cheese..it's one thing to get a better effect (as a percentage for example), it's another when they go in OPPOSITE WAYS!
Yes it is a canine study, but we already have seen how well it translates into human patientents...show this in a P3 and we have made it.
In practical terms, there is no way the crowd could've digested and read through all of those measures in the short time they were on display, no wonder the cameras were out in force.
The three subsequent slides on comparators were also a big hit.
Here they are:
SLIDE A
Very insightful, function has always been a strong measure for us.
SLIDE B
This one blew me away...Over one year the effect of iPPS aced it. Even more compelling when you realise the above is derived from just the one course of initial SubQ injections. No boosters here.
SLIDE C
Even after a full year there is no comparison...but look at the second best drug, namely Sprifermin....now go back to the previous slide (Labelled Slide B above), the same drug was one of the worst performers (2nd from the bottom!) in terms of pain improvement. This gross inconsistency with the competition only adds to our charm.
This is my point, there were NO competitors that had efficiencies spanning multiple areas. Par are preparing the comparator manuscript
3, this will be quite a read, I hope we all get to read it one day, sure we may already have a fairly good idea of where we stand...but always nice to see it in print.
This comparator analysis in the form of a manuscript will be indeed a nice read...
In the FDA legislation
2 it states:
The ultimate goal of treatments related to inhibition of structural damage or
targeting the underlying pathophysiology associated with OA is to avoid or significantly
delay the complications of joint failure and the need for joint replacement, and also to
reduce the deterioration of function and worsening of pain.The FDA make it quite clear that they want to see the reduction and addressing of Symptomatic observables along with Structural. They themselves suggest that there isn't a lot of scope for a drug that ONLY has some structural benefit, we need pain and function to be addressed coupled with a decent safety profile.
Speaking of what else is out there, I've covered the competition a little in the prior OARSI Part 2 post but I will add to it in the next section.
There is no way PAR could cover too much material in the 15 mins odd they had in the theatre session, despite that, they did a really good job in the little time they had!
Mini disclaimer - the below are potential competition. It's only my personal views in regards to the below, it's totally conceivable that I have missed something and these drugs may actually end up being quite good?! Certainly they may have a place for a certain subsegment of the market. Always best to do your own research and form your own view. The below is by no means a comprehensive analysis of the competition!
LNA043
Novartis are developing this one and are in the middle of a long trial, lasting till 2027. There indeed have been some structural mods here but they didn't really mention much in this specific area. At the end of a particular session that didn't just focus on this one drug, I overheard someone say to another member of the audience that they haven't seen much data so far.
I think this is an area where we as early investors have the fortune of having the SAS and EAP programs particularly while our P2B was ongoing...with 008 and where n is just so low, to garner SS and be able to get a taste of some real data...and even access some patients to hear their testimonials, well this is such a boon for us. Yep, I do get that we now need to have the funding in place to actually be able to execute on the P3...but as I have said, in my humblest, whoever funds us here...they really potentially do have a huge potential upside. Get our P3 going and it won't be long (certainly a lot quicker than an LNA043 readout) before we could start garnering real revenue.
CANAKINUMAB
Known as an interleukin antagonist, this class of drug is also showing some symptomatic benefits however, in at least my mind there are real risks of infections. Tread with caution.
LORECIVIVINT
To me this has been hit and miss, there were some early signs of DM but I believe it's scant at best.
They showed a slide with an update on their trials, in summary:
OA-4 Phase 2 demonstrated some pain and function improvements against Placebo
OA 10/11 trials did not meet their primary endpoints in the Phase 3
They showed a couple of charts referring to Medial JSW but there was complete cross over of error bands. Womac pain also showed some (though lesser) crossover. Seems a bit hit and miss?
Not on my potential watch-out-Mozz competitor list.
Dr Ahuja did such a super job, he presented the fabulous data and material all within ten mins...on time, good delivery, wowed the crowd, full stop. He was well dressed, spoke well and was confident in the data and in what he was saying.
Only a couple of questions were asked (time was constrained)
1) Why do you think you got such a good dose response?
He answered that there were good responses over the course of a number of studies and mentioned the multi modal action.
2) Were the BMLs that appeared to reduce, closer to the cartilage or deeper in the bone?
He answered, "Nearer to the cartilage". This essentially means or refers to the subchondral bone marrow lesions.
Dr Mukesh Ahuja did a great job representing our company and giving a great overview of what our super molecule is capable of!After the presso a number of people approached PAR wanting to know more. Again, time limited how much could be discussed before the next presentation commenced.
Mozz Take:
I got the feeling that the crowd was kinda stunned with our data BUT these are top researchers, they know the next step....it's good for a P2B to show good data...now you gotta prove it in the ultimate test, a P3.
I have a feeling there will be some jumping up and down once we progress through that. I wonder about the timing of OARSI 2025...we should be a good way through our P3 by then...maybe it will be too early for a top line read out....that's why I suspect it might be more like the OARSI after that...by that time I would like to think we have sales. That will be the ultimate proof we need to really step up and really make some waves out there.
I suspect a few of them are patiently also waiting for us to get our P3 started and a readout to occur, then they will be more on the 'converted' side. What is true is that after all the rounds I made and new people I chatted to, none of them could really offer any evidence as to why iPPS isn't a good thing or wouldn't work or has gaping holes. This in itself was reassuring. Add that to the many other possible solutions and drugs they are trying but are not showing efficacies in BOTH symptomatic and structural relief and I know at least scientifically, we are on to a winner.
OARSI - A science fest and all in the OA sphere...There were so many companies and researcher teams that presented one after another, in the general format of:
INTRO
METHODS
STUDY
DESIGN
RESULTS
CONCLUSION
...and most if not all, said there was no effect, or their primary wasn't met...or placebo was as good as active...They would say in their conclusions that while the study results were futile, they did learn this...or that....a few showed some slight efficacies in some basic areas or were very early animal studies...
This is what we are mainly comparing ourselves to.
Certainly there was no one in that room that had results like ours, none that could
simultaneously address SYMPTOMATIC AND STRUCTURAL observations in the OA realm AND had the immaculate safety profile, no one.
All great Mozz...sure you had a good time, but what's in it for me...the ordinary shareholder? What does OARSI do for me? Why should I care? Why does PAR bother?
Well they are good questions, let's break it down into manageable piece meals!
The way I think about the overall meal PAR served up at OARSI 2024 is kinda like how the award winning restaurants do it...
It's about smaller portions, but exotic presentations, superb tastes...and great mixes.
They don't just lump you with copious amounts of food...nahhh...you want a certain tease element in there!
Quality, not quantity...presentation, immacule presentation of the finest data food! Even the humble broccoli is a killer explosion of taste when matched with the right sauce.Make a dish that's before the entree...it could be just the lovely touch to whet your taste buds even before the entree.
Then the entree...wait, is that just a salad...nah...the salad is sooo yum, You nearly, just nearly, think that that could be the mains! Not because it's a large portion, because it tastes so nice and has the perfect texture/crunchiness and presentation...The main is superb and again not too much...it shouldn't be overkill..finally a desert that excites the taste buds and while it leaves you wanting more....you know you have to indulge!
Hahah Par need to do this....and I learnt a little into how they are...they are covering their bases...nah it's not just about meeting the FDA's needs...it's the thoroughness, the extreme attention to details...and the striving to not meet but BEAT the FDA's expectations!
When a top restaurant presents the food it's the little stuff that adds to the experience, white cloth covering the table, the quality of the glasses...the cold sterilised cutlery and the warm plates...it all adds to the charm, this is the stuff we see...but a lot goes into the planning and execution, how often they must train their staff...and how warm and friendly the staff are and how well they know what has gone into the dish! Can they make small talk easily? Is it an effort, do they really want to be here serving you? Do they love their job?
I want wait staff that are smiley...that are warm...that are friendly...this adds taste to my meal, this adds stars to my experience. I dont think its all that different with PAR's data...I want crisp..I want clean...and I want warm (efficacious). If I as a shareholder have to pay a little more for this (time....money)...well it's critical to success. We aren't at Phase 1 people, we are at 3.
One such insight for us is the clinical trial...we think that once we are given the GO we just go ahead and screen....recruit...enrol and we are done?
Clinical Trial requirements?Oh no no no that's just the beginning. What about the careful monitoring of the patient. It's not at all set and forget and it doesn't matter that some CRO is leading it, it's Par that must also be on top of it. Par is not some non caring boss that has no clue what her employees are doing underneath. Par is in touch and on board. We may not always see this...let's take one simple example:
We aren't a drug that uses a once a month dosing cycle...(we thank goodness aren't intra-articular like 99.8% of the others that are, hellloooo SubQ) nah...we dose twice a week AND there can be sometimes a third appointment in the week for extra monitoring or to draw bloods etc.
A single patient can't slip....imagine a patient has a dosing cycle of Tues and Fri...if Fri slips it might be Sat....hopefully it isn't Monday, because what happens to the efficacy profile then?
Yeah Mozz, but it's one patient, for one given week?
Yeah but what if n isn't in the thousands, it's in the hundreds? What if two patients slip, or more? All of a sudden the drug efficacy graph might change, we need to maintain the sanctity of the trial....we want max efficacy...and we aren't dealing with a study of thousands....a smaller n mean a greater impact.It's all fine and dandy to say PAR are burning thru the cash and taking their time. Guys, it is NOW that we have to be the
most careful. They say good things come to those who patiently wait.
You have been enduring a falling SP...you have been enduring months and months and what at times seem like endless delays or quieter times, is anything tangible happening? I also have been waiting...not months...YEARS
I got in at IPO. IPO wasn't two years ago....it was 2015.
Paradigm's 2015 ProspectusI'm not saying PAR should take forever...I'm saying there is a lot involved...there is a lot of granularity, there is a lot to think about design, to take into consideration...we are at a very critical stage now...
How many Aussie companies have made it this far?
How many Aussie Bio companies have tackled the last remaining disease frontier of OA and inflammation?
How many Aussie companies have a Fast Track designation?
Indeed how many companies have a drug that checks as many boxes and attacks this inflammatory state in more than one way?
Paradigm Biopharmaceuticals have to get this last bit right, it's not just important, it's critical.
Our time is drawing near.
Be patient...
Mozz at OARSI 2025? I reckon so. It will take me a year or so to digest all the science I learnt at 2024...*whew*.Next OARSI I want more exposure. I think it will happen naturally as more will hear about us as we cross over into a P3 and as a read-out looms.
I am acutely aware of our dwindling cash...but I do also feel that once we have the FDA certainty and we know what we are dealing with and we can actually see the light at the end of this tunnel, it will be easier to get a genuine funding package. The market at some point will start to understand that we are indeed on the right track AND, importantly, we have better prospects of actually being able to proceed with the last stage before we can sell iPPS!
No doubt once we are actually selling into a market, the OARSI conference will also help to spread the word...and guess where 2026 is planned to be?Palm Beach, Florida! Perfect! That one will be in America at that time...that's a big place to have a foray in terms of early revenue and have a conference to also get the indirect word out there!
PAR did a good job with OARSI 2024, they genuinely are parring all costs back, they didn't even have a quarter of last year's team here...it was bare bones but despite that, they did a fabulous job in delivering the data, doing the rounds and generating interest. I won't forget how quiet that room was when they delivered the good data and showed those slides.
There were no sticky doubt filled questions at question time...No one could bring up ANY arguments on any negatives or risks from a scientific point of view. I do admit there seems to be a sense of let's just wait and see for the P3...but Im picking up a lot of vibes that the mood will change indeed (at least from the investment community) once we genuinely start that last stage.
They updated their slides, they gave the crowds what they wanted...they delivered such great data but not just in one corner of the room..they filled that room to the brim and this is the start. They have done this without too much advertising....wait till we start selling and the lag of the SP
catches up....this thing can REALLY turn on a dime...
(20min delay)
