appy New Years to you and what a year 2023 just might end up being for a typical PAR Holder...but we will get to that in a sec.
Still on holidays and enjoying the down time, but can one really have both eyes closed when we have so much excitement going on in the background?
My point tonight, other than wishing you all a wonderful and prosperous year for 2023...
Its been exactly 6 months since last patient recruited in our pivotal 008 program:
PAR have stated that we should get results of the 6 month stage (Sorry Pool_King, it really does sound like a r*cket launch with these multiple stages that potentially can assist in firing us further into the stratosphere? Top line...6 month...12 month) some time in Q1 2023. More on timing in a sec.
THE PROGRAM
More for the new investor to us....why is 008 such a pivotal program?
Overall the program's aim sounds quite high level:
An Exploratory Phase 2, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Treatment Effect of Pentosan Polysulfate Sodium Compared with Placebo on Synovial Fluid Biomarkers in Participants with Knee Osteoarthritis Pain.
But from what I can see, there are four main components that we should get from PAR in Q1:
- More separation data from between the cohorts
- More information and data on the Bio Chemical observations
- Juicy Structural bio markers, at least at a high level and helpfully an example (eg one MRI before and after image?)
- Canine 20 week data - potentially giving us a more longitudinal clue as to the power of YOUR drug.
Packaging the above is going to be very interesting and potentially very exciting.
We already saw a glimpse of 6 key biomarkers at Top line at the end of September, lets review briefly their separate functions:
- NGF reduction - Nerve Growth Factor, think of this as the secretions from cells under inflammatory duress producing a secretion that binds to the appropriate sensory neurons to generate pain. Importantly ol' Pentosan does not block this pain/NGF. If it fully blocked, I wouldn't be here typing and researching today, we would follow the degenerative path of Tanezumab. You cant fully block pain...you cant be a total immunosuppressant, this is not the pathway to success.
- TNF
- This is an inflammatory cytokine which is produced by macrophages as an inflammatory response. lt Ieads to cell necrosis or apoptosis, you don't want this in abundance. I want a safe drug that can stave off at least some cell death, don't you?
- IL-6 - Ahh indeed the good and the bad. IL6 definitely plays a strong role in inflammatory response...but there are some positive benefits of IL-6. In other words you don't want to block it fully. IPPS has the wonderful effect of down regulating higher levels of IL-6. Its complex, the molecule of IL6 itself consists of an incredible 212 separate amino acids.
When IL-6 gets out of control there are many destructive ramifications
5. Just take a look at the disastrous list on the right hand side of the below graphic.
- COMP - Another biomarker that was reduced in 008. We have already seen the reduction of COMP in the serum in our Phase 2...the fact that we are seeing a consistent reduction within the serum and now within the synovium, bodes so well for us.
"In various studies, COMP has shown promise as a diagnostic and prognostic indicator and as a marker of the disease severity and the effect of treatment".6Wouldn't it be great to get some sorta clue as to what iPPS can do to these levels of COMP? Like we know it reduces it, but by how much? 2%? 7%? And what is the placebo group experiencing? Are their levels coming down also but by perhaps a lesser extent? We are already privy to the actual percentage drops...here was the announcement back in Aug 2019:
Guys - I can't vouch for you, but let me tell you right here tonight in the new year ....I await the 008 peer review, it could just be one heck of an incredible read!
- ARGS - According to one research group7, "The acute inflammatory arthritis group had the highest median level, 177-fold greater than that of the reference group". and further, "Levels of aggrecan ARGS fragments in human synovial fluid are increased in human arthritis, OA and after knee injury".
Its another biomarker that we have just observed at the end of September showing a reversal...a
reduction due to the amazing effects of iPPS!
Some of you will certainly remember my Graphic Equaliser analogy...we want 008 to show a real shift in not just one, but many biomarkers, but some (the majority) we want to see reduced, but there are some, like TIMP-1, (inhibitors of inflammation) that we want to see go up:
This is what we are hearing about in the top line 008 data, hopefully much more to come over the next few months!
TIMINGYes we all want this to be published and declared as soon as possible, but I reckon there is a lot involved in gleaning the data and then sifting and then presenting.
008 is a multi layers multi pronged study. Its quite complex in terms of stats, comparison and observations. For this reason it might take a number of weeks to work out what they have and then how to present it. Discussing the data with the authorities is another entire process again.
For this reason I'm personally not expecting the announcement till sometime later in Q1. A lot like Christmas taking ages and ages when you are a kid...its worth the wait in my opinion.
When can we open these gifts? When will our share price catch up? One day Christmas will come....one day our share price will boom. My views. Any Bio Pharma play is a long one, add in the complexity of our trials and it can be extra frustrating for the short term impatient holder. This prize is going to be worth the wait in my view. The sheer potential of just OA is magnificent, add in all the additional possibilities in terms of future potential and indeed it begins to boggle the mind. I cant even begin to really think about how big this COULD get one day. I increase my base so that if I want to trim as we go higher, my base is still meaningful. This isn't a play I want just 100 shares left after we truly launch. I want a meaningful core that I will potentially NEVER sell...
TRIGGERSThere are a number of parties waiting for the 6 month data. They are waiting to further de-risk before entering or taking more meaningful positions. I believe that the 6 month data will be more illustrative and indicative of what we have and this could certainly lead to increased discussion with potential partners but it will certainly lead to interesting discussions with the authorities.
Where to from here? There would potentially be a heap of different and exciting options available to PAR... a faster pathway is possible but perhaps a separate study may be required to more directly link any observations such as positive structural biomarkers and pathology to the clinical endpoints required. In any case there will be a lot involved.
MOZZ VIEWIt's not a long time till we get the 6 month 008 data even if its delayed a bit - till closer towards the end of Q1. It will spark a number of discussions, not just with the authorities, but with really large funds and potential partners. For the first time in the world's history, we have a drug that can address inflammation on MULTIPLE FRONTS....and to do that safely, effectively and the positive effects LAST a whole heap longer than NSAIDS for instance. Now add in the real chance of DMOAD...disease progression modification, there are real chances we are going to make some headlines.
Guess what? If it play out like we anticipate, well gosh, we are so early and we are in such a small group that actually know a fair amount about the science, the medicine, the biology, the chemistry and yes, the potential, already!!
To get all of the above at $1.41 AUD??
Mind blowing.
Happy New Year indeed.
Mozz
DYOR required
REFERENCES1)
https://app.sharelinktechnologies.com/announcement/asx/fa31694b6b5919adc469e18a683a3c832)
https://app.sharelinktechnologies.com/announcement/asx/ba5d2cd6dc841528f165121ded6027433)
https://medlineplus.gov/genetics/gene/ngf/4)
https://pubmed.ncbi.nlm.nih.gov/10891884/5)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176007/6)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716683/
7) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2714148/8)
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381039&isReview=true
(20min delay)