Rruming, some good questions here.I'll put your questions in...

Rruming, some good questions here.

I'll put your questions in Burgundy, my answers in the usual stone grey!
Any that I can't answer fully, maybe are ones for the webinar which you can email in advance?

• What do we know about those who did not complete phase 2/1?

Well to be honest, not a whole heap. We suspect drop out rates were actually not too bad, take the 2x2 Active arm in 008, I believe they started with 19 and 15 completed it. I don't know the reasons for each, I do know enough went through and don't forget it was a full 12 months...you will always get handful that cant commit or need to drop out for personal reasons etc.

PAR achieved sterling results and Statistical Significance (SS) or borderline approaching SS on a number of key measures. Evidence that not a lot were expecting in such a short time. To get structural positive ramifications in 6 months was definitely not expected and to achieve SS in such a small group ....well that was something else.

The other indicator is recruitment rates, these have always been very good for Paradigm in the past. If they struggle to fill recruitment, thats a red flag.

• How many? Who were they?

Not a lot and no idea would be my short answers.
If it helps, I have a good pal who went on the SAS program and got absolutely NO relief. He only had the initial course and never had boosters, he had it a number of years ago and since then I have heard a handful of people that also got no benefit tried a full repeat of the initial course a year after their first and got some pain relief.

• What do we know about side effects, toxicity of the treatment?

Ahh now here is a question I can answer. Pentosan has been used for 70 years plus. In all that time there has been zero fatalities. (Humira, one of the most popular drugs and used for RA have had more than 30,000 fatalities so far and counting and yet still is one of the most popular drugs out there). Of course I'm talking about the Real McCoy (hello bene!) (That's our supplier, the only one with a registered compound/molecule in the USA DMF). They have even dosed up rats by a factor of 20 times and even they didn't die.


"Humira’s safety profile may also be questionable. Since 2003, the FDA received 374,513 adverse event reports for Humira. Of those, 10,884 were deaths".

Ref: https://www.drugwatch.com/news/2018/06/12/humira-deaths-put-abbvie-on-fdas-radar/


Pentosan is darmed safe, but like any drug, follow the guidelines and don't over use it. Yes there has been some potential Macular (I was going to use the word sightings) observations but thats in people that have used Kilos of the stuff over 25 years plus. That's not normal. I cant ever see Paradigm recommending or needing such dosings, like, ever.

For the patients that take it and get NO effect/benefit, I have not heard of any AE's and even the Side effects were very mild. I have had some rumblings of site bruising, some mild sulphur reactions in some that may be allergic for an hour or so and sometimes slight pain at the delivery site again for a transitory amount of time. Nausea and headaches have also been some mild symptoms but have not lasted long in a few patients. These are nothing (in my view) compared to the positive and the sheer amount of pain drop and function improvement to say nothing of the longer term positives.

The brilliant Researcher, Peter Ghosh wrote a paper titled "Effects of pentosan polysulfate in osteoarthritis of the knee: A randomized, double-blind, placebo-controlled pilot study". In this paper he stated:



"Mild bruising at the injection site occurred in <1% of patients in both treatment groups".
He has never stated that extreme caution must be used with this drug or that the drug doesn't work well in a number of patients or has nasty unwanted effects. There have been many other papers that profess the safety profile of Pentosan.

Remember, the Pentosan molecule is inherently a blood thinner though a VERY mild one (one fifteenth Heparin)....BUT for this reason Doc's need to be cautious and watchful when administering. There are inclusion and exclusion criteria for a reason.

Of course DOYR here, you need to also search and be mindful of negatives. This is the entire reason we are doing a focused P3.

• Has anyone found patients from p1/p2 giving interviews / posting on social media?

I've found plenty of positive stories, not so many negatives ones, If I have come across negatives ones its more like it just didn't work or didn't have an effect. Again, I'm more talking about SubQ format. There are some fairly amazing stories of its efficacy right here in HC and a lot in the Sports world. I'll post a couple of athlete experiences at the bottom of this post in an Appendix A and lets go one better and have a read of two Prescribing Docs from Australia. These guys have had a plethora of experience and would state any negatives or if the drug wasn't great in their view. The other thing I will do for you and any newbies to us is I will post an old post with some quick one liners from previous posts from HC (See Appendix C).

• P3 aside, when do you expect the next cap raise to be? Have yet to try to work out what the rough expected cash requirement is vs. the costs and timing, seems like next cap raise likely to be announced within calendar q1 next year?

Hmm good question, I hope NEVER more! But maybe I need to be realistic and say there is always a chance they may have to top up funds as we get closer to running out? If they cant source additional funds then they will have to do that. But I personally suspect they will get funding from a better source rather than just plain sledge hammer on market...if nothing else our new friends Obsidian might continue to like our story and dig deeper? There will be competition to them too that start to understand how ridiculously skewed we are....low risk, potential massive returns.




Usual caveats, don't rely on one poster, I will have biases inherent. Definitely do you own research and if you find negatives, specially in SubQ, let us know, we want to hear about them and check em' out.





APPENDIX A

Michael Boileau – Is a former ice hockey professional representing Australia in 1973-79. Michael is 74 years of age.
Michael sated, ‘’PPS has been the greatest thing I have ever had’’, Don Angus (Michaels doctor) stated, “Michael was walking better than anyone
he has ever seen with the product given the severity of his scans prior to PPS treatment’’. Michael had his right knee replaced, and 18 months ago
learned he required the same for his left knee. Michael opted for PPS treatment, having no pain since, he can ride his bike again and plays golf twice
a week. ‘The product is sensational’, Michael had two injections every six weeks (12 injections), and stated ‘’I have no pain in the left leg at all to
this day, I just can’t believe it, walking freely considering the knee was bone on bone. The pain before was like a bad tooth ache, I would get up
during the middle of the night, I haven’t had that since’’. Michael stated ‘’he wants another dosage so the pain doesn’t come back, doesn’t want
another knee replacement’’. Michael no longer needs a knee replacement for his left knee.



Mark Riccuito - is a former Australian rules footballer who played for the Adelaide Football Club in the AFL. Mark was consistently considered one
of the best midfielders in the competition during the early 2000s (decade), Ricciuto shared the 2003 Brownlow Medal with Nathan
Buckley and Adam Goodes, and was selected in the All-Australian team for four consecutive seasons between 2002 and 2005,
captaining the side in both 2004 and 2005
Mark is 45 years of age and has had two PPS treatments. Mark stated he ‘’doesn’t run much anymore, and doesn’t want to get sore
again, having no pain at all doing general day to day stuff’’. Marks condition prior was stiffness and swollen joints, at times with significant
inflammation based on the intensity of exercise. Mark was told he would need a knee replacement, as there was nothing further doctors could do
for him, having had several arthroscopies over the course of his career. The past three years, Mark has been able to perform all his requirements
of daily living pain free. Mark stated he had his second round of PPS treatment six months ago for a top up, ‘’didn’t get sore again, just didn’t want
the pain to get back to what it was in the old days. Quick jab in the arm, takes five minutes, around the corner from work’’. Mark no longer needs
a knee replacement.


APPENDIX B

Doctor Roger Patterson - Is the co-founder of Sportsmed SA, a leading healthcare provider. Roger is a specialist in the field of anterior cruciate
ligament biomechanics and reconstruction, patella- femoral pain and instability, meniscal and chondral injuries and repair, knee
replacement, and ankle ligament injuries and sequelae.
Doctor Patterson stated ‘’we were all very skeptical at the start, nothing can work like that! There was a limited take-up to
begin with, but as word of mouth reports started coming through prior to official results, everyone started getting on board, we
were hearing up to, and possibly more than six months pain relief for two thirds or more of patients, clearly this was no placebo. We had no idea at
the time as to reasons why, but started looking further to understand. There is large cohort of patients who are past the treatment of arthroscopy,
but are not ready for a knee replacement, it’s this group of sufferers which is huge, and stand to benefit from PPS. I will be very surprised if the
product doesn’t hit the market with a bang, given what we have seen in phase 2 studies. PPS is a unique product, what it does in the joint is like
nothing we have seen before, it alters the biochemistry for the good, we are starting to believe that PPS improves the joint, which nothing has ever
done before. PPS can potentially fill a massive black hole, and overall I am very excited to see what it can do. As a shareholder I am excited of
course, but as a doctor equally as excited, as it gives us a more reliable product than anything we currently have at our disposal. There is a crying
need for an acceptable alternative, which is evident in the opioid crisis. Sufferers are in desperate need of an alternative, if it’s shown to work, and
is cost effective, there will be huge demand for it. Alternate products we use currently are A$475 for a single injection, which patients can have
every eight months, however these treatments have very limited efficacy. PPS needs to be cost effective, sufferers will take opioids because they
are cheaper.



Doctor Donald Angus – Founder of Health on Grange (1978)
Doctor Angus stated ‘’I have been very impressed with the efficacy of PPS. I had a patient come in with two walking sticks, shortly after treatment
he was playing golf without a buggy, an incredibly dramatic recovery. I had another patient who benefited from PPS in the finger joints, rather than
for the knee. All patients I have seen there has not been one person who has not benefited and believed the treatment to be worthwhile. PPS
appears to allow regrowth of cartilage, which normally if you lose it, it’s gone forever’’. Dr Angus assists with knee replacement procedures, being
witness to many knees devoid of remaining cartilage, he states ‘’that if this can be avoided then it is a great outcome for the patient, and all
concerned’’. Doctor Angus had nothing negative to say, having been administering PPS injections for the past 18 months. Dr Angus was clearly very
impressed by the efficacy of PPS. ‘’PPS is not much different from a flu injection from pain perspective, and it takes about 4-5 injections before
patients begin reporting an improvement, it would be great to treat the cause of pain rather than masking it with Panadeine Forte, I shudder every
time I need to write a script, there is nothing worse than hiding the symptoms’’.


APPENDIX C

Originally Posted 18th July 2020:




HEYITSJAY
25^thNovember 2019
"The most important thing though is that THERE IS NO PAIN TO SPEAK OF. A few weeks ago, every step hurt. I was saying 'Ow' inwardly to myself upwards of 2,000 times a day."



HAPPELL
1^stMay 2020
"After about 8 of these injections the pain in my leg had completely disappeared and about a month later I was scaling rocks and mountains in Sri Lanka."



GARYRIC
14^thof November 2019
"My pain has gone from a 8-10 to 0-1, No more pain killers and no more anti-inflammatories, this stuff is amazing."



SOOLY
1^stJuly 2020
"...gone is the "pain in his eyes" he just looks a million bucks, I've got my mate back, this drug is truly the MAGIC JUICE"



HEYITSJAY
29^thof April 2020
"... the difference is staggering "


CPHIL1970
27^thMarch 2019
"It was miraculous seeing my wife disabled with pain, some days using a walking stick, within weeks having no pain."



JTL
18^thOctober 2019
"It worked well with no side affects, it changed my life."




PAUL RENNIE - CEO
7^thNovember 2019 - AGM
"We have not seen anything yet."

.DYOR