THE NEW PATENT REAL WORLD EXAMPLES - PART 2
t was in Part 1 of the patient examples specifically linked to the combination of Celebrex and Pentosan in pill format that we went over 4 examples of the efficacy and the real positive changes patients experienced.
But tonight I dial it up....not only we cover more examples of what this amazing combo can do but I want to illustrate a possible marketing idea where PAR might find themselves able to execute on in the future. We will take a deeper look at some more robust data sets to hammer home just exactly what you and I own.
Please as per usual, now do enjoy.
MEANINGLegitimely, one could ask, Mozz, why would PAR bother to invest and buy a patent for a pathway that may have some good benefits but prob doesn't really compare to the Sub Q mode of Administration?I myself have barely covered the Pill format in all these years. But yes, there have been some ace reports and peer reviews just documenting the great efficacy of the Pill format, but definitely I have focused on the SubQ version over the yeaes as it is so much more prolific.
Mind the gap? How about no gap!So what's the reason? Why would PAR bother with yet another patent? The reason is to address
Mind the Gap...it's to fill in the gap. Yes we have KL stages 2 plus covered, but it is the milder stages that we want to cover. There are a few big advantages that I can see why PAR did this:
The gap is large! That initial mild pain and preliminary diagnosis of OA is a large market in itself. Why not try and address this for comparatively less effort/expense (see point three below)
Continuity. I'm really talking marketing and patient acceptance. Panadol and Forte example (see also below).
It didn't cost a lot and it is de-risked. We don't pay till much later on and even then we can decide if the revenue profiles looks great and we stand to make a decent clip out of it, then we go for it!
The royalty payments we pay out is only on one component. Ie we don't have to pay the original owners of the patent anything for the animal component. We can even use this as a de-risked testing ground to see how it pans out and learn from it and have the human studies continue in the background.
Time to market. Animal studies are much quicker and a lot less onerous. Yes we still have to have clinical studies, but we could get to the market much before the human model.
We were highly focused on the KL grades 2 plus, we still are primarily focused on this segment of the market via iPPS....(see my orange vertical lines introduced on the slide below). BUT, now we are fixing the gap (see green arrow in the slide below). Yes of course there are analgesics that address this initial part of the market, 'First line treatment' as its known as...but the solutions such as those listed in the slide below on the right hand side all come with nasties, Side effects, Adverse effects. Indeed the market has a large unmet need for a SAFE and effective pain solution. It is THIS section of the market that PAR is proposing to sew up with their latest patent acquisition.
Orange Lines indicate iPPS treatment potential, green arrow is what the new patent gives us access to.Right, advantages out of the way, let's tackle even more examples of this exemplarily drug combo!Note: Again, my annotations in this
burgundy colour, the rest are excerpts from the patent.
EXAMPLE 5 (Continued on from Part 1)LM: A generally fit 72 year old male experienced unacceptable pain at rest from his left hip joint that was exacerbated on walking.
Radiological examination showed almost complete loss of joint articular cartilage corresponding to Kellgren and Lawrence grade 4 ОА. Following hip replacement surgery and subsequent physiotherapy the pain was resolved.
Now remember, some 20 to 30% of knee and hip surgery patients still complain of pain after the surgery. So how did "LM" go?
Well his pain was "resolved" right?
Think again:However, within 6 months of the operation he complained of pain arising from his contralateral hip joint and lumbar spine. Subsequent radiographic examination of his spine revealed loss of disc height and marginal osteophytes indicative of spinal OA. This pain was not ameliorated by oral analgesics or NSAIDs including daily consumption of Celebrex™ (200mg).
A couple of points here, often people that have OA don't just have it in one area. Yes there are a few so called up and coming drugs that are intraarticular, how many of these are you going to take, are you going to take them for all your aching joints? Are you going to take the risk that they get rejected (Stem cells) or an infection develops and that's if you don't end up having any side effects like so many of the other so called wanna be solutions.The second point here is that this particular patient had post op pain, we also have a separate patent for this condition too.LM was then treated with Pentabrex
TM composed of 250 mg NaPPS and 200 mg celecoxib (Proteobiactives Pty Ltd) taken orally thrice weekly.
The dosing regime is so conservative, just three of these super tablets a week! NASAIDS typically are twice a day...so 14 times a week! Incredible. I say incredible because take a look at the efficacy, the boost in efficacy afforded by the combo, we will investigate this soon further down in this post.
How then did LM fare?After following this regimen for 6 - 12 weeks LM reported total relief of pain emanating from both his right hip joint and lumbar spine. No adverse side effects attributable to the medications were reported by LM over this period.
EXAMPLE 6In example 6, there is not just one case, but 4.In this study, five female patients with established OA of the hands were enlisted in an open clinical trial to evaluate the efficacy and tolerability of a Pentabrex TM formulation (2 x 250 mg capsules, each capsule containing 125mg Celecoxib and 125 mg NaPPS) when taken orally 3 times a week for 6 weeks. These patients were referred to the Subiaco Rheumatology Clinic (Subiaco, Perth, WA, Australia) as their OA symptoms were not satisfactorily resolved by their current usage of analgesics or NSAIDs (including coxibs). To be included in the clinical trial, patients had to be 50 years of age or older and have an OA grade of 3-4 (Kellgren JH, Lawrence JS. Radiological assessment of osteoarthrosis. Annals Rheumatic Dis.1957; 16:494 – 502) that had been symptomatic for at least 6 months.
These patients had had symptoms for at least 6 months, that's a fair while and they would've been quite sick of the pain, function loss and discomfort.Following their consent to participate in the study, patient's details of the symptomatic hand joints affected and grade of OA were recorded and the level of hand pain and stiffness determined to provide baseline values using validated 10 cm visual analogue scale (VAS) scoring systems. The duration of their early morning hand stiffness was recorded in minutes, and the grip strength of the symptomatic hand quantified (in kgs) using a Constant electronic hand dynamometer (model number 14192-709E). The use of a dynamometer to quantify grip strength in patients with hand OA has also been validated . The patients were then provided with six week supplies of Pentabrex™ contained in labelled containers. Over the 6 week study period, patients were requested to refrain from using additional analgesics or NSAIDs unless absolutely necessary and return the container provide for the Pentabrex™ formulation to confirm compliance.
The 4 patients who completed the six week study were re-examined to determine the final values of the same medical parameters that were assessed at the commencement of the study. The net changes between the baseline values and the corresponding final values were calculated and the % change from baseline for each parameter determined. Patient's blood was also collected for routine haematological analysis plus additional assessment of Activated Partial thromboplastin time (APTT) and Prothrombin times (PT) at the time of commencement of the trial and immediately after its completion.
So what do you think the percentage drop of pain, increase in hand grip strength and decrease of duration of stiffness should be?
Well if it was iPPS, I'd say a fair bit more, but given it is just tablets and only three times a week for 6 weeks, I would've guessed a good 25% reduction would be as good as a result that we could realistically get ??
Hand Grip strength, again to really be able to squeeze a lot more....I'd guess at about a 20% increase/improvement would be a pretty good result... Joint stiffness, a reduction of about 25% would again be quite good and finally, duration of stiffness...maybe around a 20% decrease?
Guys?
Here were the results:
Pain change from baseline -58.9%
Grip strength +32.68%
Joint stiffness - 45.55%
Duration of stiffness -29.16%
To think the above stellar results are from Pill format is quite impressive. It's also NOT twice daily dosing, just three times a week and not into perpetuity. A 6 week course. As in investor, this is what I want. This is what encourages me.
Almost a 60% decrease in pain and almost a 50% reduction in joint stiffness from our tablet form?
I want to take just one of those 4 patient's results to show you how prolific the outcome was in this one individual.
The red arrows depict what I'm talking about. Granted it is just one patient's result, it was totally amazing (The other patients also achieved good results however, this above was a standout.).
Paradigmers, if we achieve even 10% of the patients getting results even approaching these figures, just tell me how wide spread our drug will be used?In my humble, the share price is still so disconnected...it absolutely reflects NOTHING in terms of the future benefit we will one day confer on a vast amount of patients, a large amount of society that are suffering daily.
I am in the midst of slowly increasing my exposure at Reddit, I have to do it in baby steps as the moderators are quite sensitive in regards to blatant self promotion.. There are already a number of sub-redit channels that are highly focused on pentosan and OA, the few stories over there on the positive effects of Pentosan only confirm what we have known for years!
Baby steps!THERE'S MORE?Mozz, all very good in terms of the patent, in terms of whatDr Ghosh and team has uncovered and indeed now Paul R. and team. When can we get some REAL evidence?
REAL evidence?
Those last 6 examples were all Real World Evidence!?
No I mean,well controlled hard evidence...
Welcome to example 7EXAMPLE 7A prospective, dose ranging, double-blind, comparator clinical trial to evaluate the tolerability and efficacy of Pentabrex
TM, (Proteobioactives Pty Ltd, Balgowlah, NSW, Australia) compared to celecoxib, for the relief of symptoms in elderly patients with OA of the hand and knee conducted at the Subiaco Rheumatology Clinic, Subiaco, Perth, WA, Australia.
Guys and gals, some 33 patients were studied with symptomatic hand or knee OA in Perth, Australia under a well controlled placebo double blinded study.To be included in the clinical trial, patients had to be 50 years of age or older and have an OA grade of 3- 4 (Kellgren JH, Lawrence JS. Radiological assessment of osteoarthrosis. Annals Rheumatic Dis.1957; 16:494 – 502) that had been symptomatic for at least 6 months prior to their inclusion. If a patient had pain in both knees or both hands, the more painful knee or hand was the joint used for assessment. If patients had both hand and knee OA each most painful joint was assessed separately.
Now before I go on I need a break out session to explain something.
In this particular study there were two dosings utilised.
This has particular commercial ramifications for us as shareholders. I'm not talking about the shareholders amongst us that just want to see this baby go to $1.00 a share and they are out. Im talking to those that are here for the longer term, those that not only want deals and want us to have meaningful revenue and divvys one day. Im talking to those that will hold some shares way beyond that, when we have this pill format in play as a precursor to iPPS treatments too, ie when we have the entire market.....CORNERED.
Take a read of this from the patent:Dosages regimens for double blind comparator clinical study Two test dosage formulations of Pentabrex™ were examined in this study as follows.
(a) Pentabrex™ (350mg) HPMC capsules containing PPS (175 mg) and celecoxib (175 mg) together with crystalline methyl cellulose and magnesium stearate as the only excipients. Patients were requested to take a single capsule with water daily for 6 weeks from the blister pack supplied.
(b) Pentabrex Forte
TM: HPMC capsules containing PPS (325 mg) and celecoxib (175 mg) together with crystalline methyl cellulose and magnesium stearate as the only excipients. Patients were requested to take a single capsule with water daily for 6 weeks. PentabrexTM (Pentacoxib
TM) and Pentabrex Forte
TM are trade mark of Proteobioactives Pty Ltd, Balgowlah, NSW, Australia.
To spell it out, THIS is the extreme commercial application I can see for us one day.
I mean there will be MULTIPLE products available for us, I can clearly see three of them so far, where are my dream clouds...
You have mild pain starting to occur, be it in your wrists, thumb, lower back, knees, heck even ankles or some slight gout. You first Try PentabrexTM
You have something a bit stronger than in Step 1, so you bypass Step 1 and you go straight onto Pentabrex ForteTM.This gives you stronger pain relief, for the 3 or 4 out of 10 pain and beyond. Try this step 2 if you are in a greater degree of pain and discomfort.
Perhaps you are later stage OA, perhaps you have done yourself some injury and STEPS 1 and 2 can be bypassed, perhaps you want something stronger now...
Welcome to iPPS ZilosulTM
Guys, I see these three offerings on shelves across the country.
I see deals with Sigma (Chemist Warehouse), Priceline maybe Amcal...the likes. I want a range of products in the USA as well.
These are just three products, couldn't we see something for the Heart (HFpEF) one day? Maybe even a topical Pentosan cream for instance? Something for the respiratory system (ARGS)?
This is the commercial slam dunks I want one day, sometime into the future yes...but one day it will be upon us, look out!
Ok Breakout session done, let's get back to the Patent examples.
Take a look at just one of the patient's results utilising the Forte formula:
Those percentage changes from baseline are just simply nutty. I have said it a few times, I will say it again...what will our p values be like when n hits 466? In summarising, the patents suggests that the most benefit was obtained in patients with Hand OA.
Indeed Hand OA is highly prevalent in society with very little other than feeble painkillers available that can be taken and these too come at a cost to one's health with known side effects specially if used over the longer term.
This again from the patent:Osteoarthritis of the hand is highly prevalent in elderly populations of developed countries. For example, in the USA more than 50% of 60-year-old individuals show radiographic evidence of hand OA (Altman RD. Pharmacological therapies for osteoarthritis of the hand: a review of the evidence. Drugs Aging. 2010;27:729-45), while in Japan the prevalence of hand OA with KL grade ≥2 has been reported to be as high as 89.9% in elderly males and 92.3% in females (Kodama R, Muraki S, Oka H, Iidaka et al. Prevalence of hand osteoarthritis and its relationship to hand pain and grip strength in Japan: The third survey of the ROAD study. Mod Rheumatol. 2016 ;26:767-73).
Hand OA has been considered to be a more erosive disease than hip and knee OA and is still treated with traditional analgesics and NSAIDs but with limited success. However, hand OA has now been shown to respond more favorably to more powerful anti-arthritic drugs such as methotrexate.
Did you read that above properly, some 89.9% of elderly males and 92.3% of elderly females in Japan have hand OA!! Is this not a massive market for us?Finally the patent discusses the notable presence of the usual suspects that we have observed to date with large joints such as the knee and hips:More recently European research groups have employed longitudinal magnetic resonance imaging (MRI) studies to investigate in more detail the underlying pathology of hand OA (Haugan IK. Hand osteoarthritis: Current Knowledge and new ideas. Scand J Rheumatology. 2016:45(sup128): 58 63, Haugen IK, Slatkowsky Christensen B, Bøyesen P, Sesseng S, van der Heijde D, Kvien TK.
Increasing synovitis and bone marrow lesions are associated with incident joint tenderness in hand osteoarthritis. Ann Rheum Dis. 2016;75:702–8, Liu R, W. Damman W, Reijnierse M, J.L. Bloem JL, Rosendaal FR, Kloppenburg M. Bone marrow lesions on magnetic resonance imaging in hand osteoarthritis are associated with pain and interact with synovitis. (Osteoarthritis and Cartilage.2017;25: 1093-1099).
These recently published reports of the high incidence of bone marrow lesions (BML) in joints of patients with symptomatic hand OA could provide a possible explanation for the favorable clinical outcomes observed in the present clinical studies since a previous report (Ghosh P. Patent CA2826166A1 - Treatment of bone marrow edema (oedema) (BME)) with polysulfated polysaccharides. Publication date August 9, 2012) had shown that PPS when administered systemically (IM or SC) resolved the bone marrow lesions (oedema) and accompanying pain in patients diagnosed with this bone marrow pathology by MRI.
Fellow investors, Paradigm have made a very strategic move in procuring this patent. It's going to fill quite a gap and it will be an introductory revenue stream for us. But it's not just additional revenue I'm excited about. No, I am loving the further concreting of our foundation. Patient convenience is an ultimate foray and prelude into the SubQ version ... once patients understand how well this works, the news of it's efficacy will spread, trust in the brand increases and people talk. It will definitely take some time to get established but word of a genuine pain reliever coupled with structural regression of BMELs and osteophytes, potential for increased cartilage volume growth with a reduced inflammation level will make some waves.
All we have to do is hold on...
- Mozz
DYOR as always, applies.REFERENCES
MAIN REFERENCE:
1] https://patentimages.storage.googleapis.com/82/dd/bd/824e58151aec70/WO2019157560A1.pdf
OTHER REFERENCES
2] https://paradigmbiopharma.com/wp-content/uploads/2025/03/Paradigm-Biopharmaceuticals-Virtual-Healthcare-Conference-Presentation.mp4
(20min delay)