I was going to post this on the upcoming weekend, who am I kidding? I can't wait that long....I've already been waiting 8 months or so for this IND!
hhhhhhh Pardigmers, indeed what a day!
Two additional facts for today:
1) Record breaking volume, 8.135 Million changed hands 2) Record share price increase in absolute terms, $0.47.
I for one, have been waiting many days for this one.... Not at all an easy feat even with on boarding some real experts along the way in this terribly long FDA IND submission process, crossing lots of t's and dotting i's...never thought it would be so arduous and just so drawn out, the victory is all the more sweeter.
Yeah I can admit it was a little scary at times, specially that last round when I at least thought we were good to go only to be frustrated once more....Sure I'm a long term holder and all but I do have a little leverage at play too. Now all of that trepidation is a distant memory...It was a joy to read your posts throughout the day,
Ok RIGHT, down to work...no stopping here....so let's start to concentrate slowly on the future eh' ? I think it is a bright one *wink*.
A number of people that read today's announcement are new to us so this post is predominately for them, some of us older folk to PAR have more of an idea of what we can expect....let's tackle it tonight.
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Well I have wanted to post this one for months...it's just been sitting in the archives....what does this all mean? What can we expect? What is the future..a little crystal ball gazing for sure, aimed squarely at the newer investor to Bio Pharmas...and to PAR.
WHO ARE WE?
It's not a secret that:
"Obtaining a “may proceed” decision from the FDA to conduct clinical trials is a milestone of particular importance for novel compound pharmaceuticals and biologics". 1
Well like a newly married couple introducing each other for the first time as this is my wife or my husband... I just gotta try this out...*clears throat*
Today we are a Third Phase Clinical Trial company.
Sure we were kinda that with Europe but getting USA is a fairly big chunk of the globe. (49% of the Pharma market to be precise)
I love the ring to that, and you know who else will? The new instos to us...the larger investors that are interested in bio pharmas and all of those guys that havent heard of many new efficacious drugs in the OA space.Sure we had the GO for Europe and that's not to be sneezed at...but mate, getting USA FDA IND opened up is as lucrative as it is sweet.
Perhaps it is sweeter for us as we have had to patiently wait for so much longer? Anyway, we are there, that's what matters, our company takes on a position on the global stage from today...we are a contender thats now allowed to be tested!
Who are we indeed?
Mate, the little Aussie battler of a company with how many staff? 20 full time staff? Maybe 25 now? We just got accepted by the SINGLE biggest pharmaceutical drug gatekeepers on the globe? We are so much more REAL as of now. We can sit the test of our lives.
Please let us keep this in Aussie hands for as long as possible yeah? Distribution tie up sure...but it fundamentally would be totally awesome as an Aussie company, I don't mind if the HQ eventually moves, if we get dual listed, but origins need to stay here for as long as possible, if not forever.
WHERE ARE WE?
Well as you have read we have had our IND opened. It was always going to be a hurdle and we did go through a few iterations of the FDA loop as a good pal keeps reminding me.Not many companies sail through without being asked ANY questions...
Strictly the granting of the open of IND means two things:
The drug manufacturer (that's Bene in Germany) can now legally ship to the investigators the new drug named in the application. In fact the drug cannot be administered to any human subjects unless and until the IND application goes into effect.2 Those of you who are a bit technical, it actually is a vehicle to allow an exemption from the New Drug Application (NDA) which allows the drug to cross state lines. This is particularly relevant for us as we have multiple clinical sites across various states in the USA in our P3.
It allows the sponsor (that's us) to begin clinical trials on humans usually at scale. It is the 3rd phase along the path:
Where are we in the scheme of things in terms of OA? 4
GOALS?
Now the good news here for us is that passing a Phase 2B was a big hurdle, some say its prob the biggest. After that its getting an IND....and then of course passing the Third Phase.To assist us with the chances of passing a P3 I note the following:
Our Trial design is very similar to P2. The Primary Endpoint and most of the Secondaries are pretty much the same. It's a big sigh of relief for us.
We have run our trial design past the FDA not only in terms of the submission but also before that in terms of the PRE IND and Type C. This took time, but well worth it and it's highly recommended to do that if you want to increase your chances of overall success.
We didn't have to have a third arm, ie go up against a competitor in P3. Yes you could argue what competitors are there? But it still will help us not to have another headache to have to worry about potentially.
A fair amount of important groundwork has been done, think PK studies. PAR have had the foresight to think about what is potentially involved in broadening the label. Yes I'm talking extension studies and insightful studies like 008 and 010 (Hip OA). It's this forward thinking that has me on board, that puts us in a different class. Now I know it's not for everyone, for shorter termers it's frustrating, this one is geared for the more coneseure of a longer vintage...liken it to a fine bottle of red...yes it costs $60 now...but let him mature over a few precious years and all of a sudden it's matured and achieves greatness in terms of not only palette but in terms of shelf price. I like it.
GMP - The single next BIG hurdle that usually companies in our situation have to think about is manufacturing. Sure it's a big issue enough just focusing on manufacturing for the trials and once we are allowed to sell, but imagine scaling this to not just one massive market, but several. Taking on USA and Europe together is no easy feat.
Now if thats not difficult enough, imagine getting batch consistency, it needs to be perfect each and every time.A lot like the multiple layers found on an onion, the next tough layer is GMP. Good Manufacturing Practice. It had to be to a certain FDA standard and this doesn't just mean all of the above, it means random audits...yes that's plural.
Thankfully this important stage is covered, in full....Thanks to our mates Bene in Germany. With some 70 years plus behind them, all of the above is simply another day in the office. It is this component that can get a lot of newly submitting big pharmas stuck...another reason to be a happy shareholder into the future.
THE GOALS OF THE NEXT STAGE
What then are the goals of our P3 OA Clinical Trial Program?
Confirm the minimally effective dose
Achieve Primary Endpoint and Secondary Endpoints
What are these?
PRIMARY: Change from baseline at Day 56 in knee pain as assessed by the average pain sub-scale score of the WOMAC® NRS 3.1 Index. [ Time Frame: Baseline, Day 56 ]
SECONDARY: Change from baseline in terms of function Change from baseline in terms of pain (varying other day markers) Percentage of patients meeting (OMERACT-OARSI) Responder Index Change from baseline in knee pain of of >=25% and >=50% (WOMAC scale) Change from baseline in knee function of >=25% and >=50% (WOMAC scale) Change from baseline in knee stiffness (WOMAC scale)PGIC scores Change from baseline in Quality of Life assessment Change from baseline in Work Productivity and Activity Impairment (WPAI) questionnaire score Number of days of rescue medication used from Day 1 to Day 168
Conduct Confirmatory phase III trial (003)
Improve and expand the label for simultaneous registration.
IT'S A LIVING DOCUMENT
The IND is a "living application" 3 This means that every year (within 60 days of the date the IND went into effect) the sponsor must submit an annual report documenting things like progress, clinical and non clinical data, any new protocols, safety reporting and any major changes to the manufacturing process as some examples.
YES BUT WHAT'S NEXT FOR US?
Right, well immediately on the agenda is the dosing study....what is this?
Well it's basically to find out what is the minimum effective dosing we can do. It's in ours and the patient's interest...how? Well for the patients, the less the pr*cks the better. err...hmmm... maybe that came out wrong. I mean the less SubQ injections the better!
Benefits or us? That's an easy one., we will still cost out the overall program to the eventual patient. This means if we are on a lower dosing schedule then we consume less raw material for the same revenue gain. ie if the eventual price is say $3000 per initial course, then we may be able to get away with just 6 injections instead of 12.
Mozz, there isn't much difference in juice (drug quantity then) between 6 and 12 injections. Yeah you are right, but where you are wrong is that you multiply this out by the x number of millions of eventual injections, (and that's per year), then you can see how much economic sense this adds up to! For PAR's bottom line, for our shareholder pockets. Get me?
So what are the proposed dosing levels? Well let's turn to the trial details itself:
There are 468 patients to be recruited for the dosing study, here are the groups:
2 mg/kg calculated for ideal body weight (IBW) PPS twice weekly
2 mg/kg IBW PPS once weekly + placebo once weekly
100/150 mg PPS ≤65/>65 kg IBW once weekly + placebo once weekly
Placebo twice weekly
Now the good news is that 002 doesn't wait for dosing study to be finished before it starts. 002 is what they call in the industry an adaptive design. So in Mozz speak this means that we start the Dosing study AND the recruitment of 002 at the same time, after a number of months when the dosing study comes to the conclusion and a minimum effective dose is determined, 002 and subsequent trial (eg 003, 007 etc) will then utilise this determined dose exclusively.
Now the little bits and pieces that are sometimes easy to miss is that the fine people at PAR are not LAZY. They CONTINUALLY look to the future. It is these clues I look for to bolster what investment I have. Example please Mr Mozz....
PAR know they are behind in terms of time. They want to make it up. Today we got this little snippet:
Yes there are a lot of sites involved in the main trials, some 65 in total in just USA.. Err Mozz ....who is going to run around to that many different areas to administer our drug? Nah, there are CRO's that do it for us. These guys have vast experience in the particular field of pain and inflammation type drugs. They have been heavily briefed as to how to conduct the protocol, what to look out for and how to be mindful of the placebo effect.
These guys are experts in execution of the trial and passing back feedback and the result set back to the trial coordinator. I'm hoping that it will be relatively smooth process.
AT THE SAME TIME
PAR will no doubt now be in the exciting position to be able to spread the word. They will need to be mindful of placebo effect so they don't want to probably go too heavy in the promoting just yet. They will do it more on the hush hush and more to the professional investor set, more to the future cornerstone investors. This means many meetings with the big boys and girls... The fatter cats, the ones with sway and the ones we like to call instos.
Don't forget it is after an IND is successfully opened that a lot more of these can see us on their radars...many new larger style investors will be curious as to what we are all about, just how does our drug work, what are the results so far and are we real? Oh you bet we are real...just read some of the testimonials and have a sticky beak at the consistent results...I can just see them all quickly searching for serious AE's and comparing this newly founded iPPS drug to Tramadol, Ibuprofen, Oxycodene, Corticosteroids and even Tanezumab. Yes fellow Hot Copper Paradigmers, we have done this work already, we are already seated at the table...bring on the main meal.
It's also slowly from this point that the probability of a deal starts to materially increase. Yes exciting negotiations. In days gone by I thought that we'd have to get 008 to a point of read out for us to really add some good value to our deal size. Not true, the Bigger pharmas that are out there already know what is a DMOAD, how many DMOAD products are already out there (err...NONE) and what our chances are of obtaining this amazing title.
Yes you could say our drug's efficacy proceeds us. There is enough literature, research and evidence for them to know and they can just take a look at our P2 data set to get a sense of it. I'm not taking anything away from what I think will be one of the single most amazing studies to come, 008 (my views) ...it could just be a glorious day when it happens perhaps sometime late next year...there are clues out there already, just read the results and effects of RRV and CHIKV peer review. Just read the MOA from P2B specifically the actions on NGF and the effect on BML's.
While all the above is going, everything else continues, MPS programs keep happening on the background, did you guys know we are now nearly up to an entire year on patient one in MPS 1? We should be getting some peer review material back soon (OA P2B) maybe a few months away?There are also the exciting new kids on the block...think Heart (Pre clinical) as an example.
THE POTENTIAL PIVOT
Yes but Mozz, why mate are you getting excited? Doesn't this just mean we have literally YEARS to wait? Aren't you getting ahead of yourself? Aren't we going to be bored now as we wait for the results of this P3?
Well yes and no.
Yes we have some way to go...but no, it's not necessarily sleep time... WHY?
Well it's from this pivotal point that a few pings start to go off....I mean the three letter Ticker Wonder 'PAR' from Down Under starts to ping on Bloomberg terminals across the USA and other countries....those Bio Pharmacist industry specialist analysts have a new candidate on the block that just got successfully vetted by the FDA!
We now will appear on a terminal somewhere stating that we have Zilosul as a contender in a space that hasn't had a lot of newness for sometime; OA. I don't know about many of the others but I can tell you at least J&J will have their ears primed....they already know of our molecule in a somewhat different format, yes PILL format called Elmiron. They no doubt have been following our story for some time now like a few others....but its from here on in that they know just what potential we have and how serious a contender we all of a sudden are.
If you are an exec from J&J....start chatting to us...don't leave your run too long, there are others that are going to be mightily interested in what we have, what we can achieve and exactly how long (durability) we last and how safe we are.
I GOT YOUR BACK
It takes time to do a lot of research. In truth it is just too much for one person to do it properly. But I have friends, I have a large network....yeah, its YOU! I have a team that helps me ...some work on charts, some verify the science, some bring us media , some tell us about competitors.
There are a few that keep me anchored and make me check facts, check research. This isn't the end of Mozz type research, just like the PAR staff, this isn't a chance to slow down...it's MORE WORK...but beautiful FUN work....REWARDING work.... so much more to come from me, more topics, more facts, more science and a couple of little surprises along the way..... I already have a guy working on the top 20 things to watch out for from here on in.
It's THIS type of research that is prudent for any decent investiture. Give me the bad with the good and I can speculate on the future.I love hearing positive stories of what iPPS is...what it can do, how does it work, why it is good and who gets what merits out of it...but I want the negatives too....I want to hear them, I want to understand why you think this, I want to research the heck out of these potential negatives and see if it stands up.
IN CONCLUDING
Lots to come...the exciting times are just dawning. I feel a shift...we as of today, are a very different company. Paradigmers, YOUR investment has changed as of today. Yes P2 was a big hurdle, I think P3 IND is up there. But, you think this is big, wait for a whiff of a deal....wait for multiple trials commencing, and of course exciting and telling data coming back.
Then there is read out and registration.... The sellers are going to thin out and the buyers are going to swell (my thoughts). Sure it won't be a straight path upwards...but its shifting from what we have experienced in the last year or so..
Excited? You bet...This is just a real start of things that are to come. Stay motivated PAR staff and investors (it's so much easier now) and take us all the way to registration and eventual sales.
hhhhhhh Pardigmers, indeed what a day!
Our Trial design is very similar to P2. The Primary Endpoint and most of the Secondaries are pretty much the same. It's a big sigh of relief for us.
We have run our trial design past the FDA not only in terms of the submission but also before that in terms of the PRE IND and Type C. This took time, but well worth it and it's highly recommended to do that if you want to increase your chances of overall success.
We didn't have to have a third arm, ie go up against a competitor in P3. Yes you could argue what competitors are there? But it still will help us not to have another headache to have to worry about potentially.
A fair amount of important groundwork has been done, think PK studies. PAR have had the foresight to think about what is potentially involved in broadening the label. Yes I'm talking extension studies and insightful studies like 008 and 010 (Hip OA). It's this forward thinking that has me on board, that puts us in a different class. Now I know it's not for everyone, for shorter termers it's frustrating, this one is geared for the more coneseure of a longer vintage...liken it to a fine bottle of red...yes it costs $60 now...but let him mature over a few precious years and all of a sudden it's matured and achieves greatness in terms of not only palette but in terms of shelf price. I like it.
GMP - The single next BIG hurdle that usually companies in our situation have to think about is manufacturing. Sure it's a big issue enough just focusing on manufacturing for the trials and once we are allowed to sell, but imagine scaling this to not just one massive market, but several. Taking on USA and Europe together is no easy feat.
Confirm the minimally effective dose
Achieve Primary Endpoint and Secondary Endpoints
Conduct Confirmatory phase III trial (003)
Improve and expand the label for simultaneous registration.
(20min delay)