TanamiRod - Sorry to butt in, here is a post that gives a few potentials...at least in ERT space. Its an old post, maybe needs a freshen up - take that into account:
Posted 12/09/2020
his original post was going to be a whole lot shorter...a few lines for you...a few lines for me....and that would be the end of our role play, simple. But like a lot of times with my research as far as iPPS is concerned, one thing leads to another and I find myself somehow in a happier but further place from where I intended on ending up!
It's for this reason I thought way back mid year last year that I would soon run out of topics to write about...quite the contrary...I have heaps of material and a lot of my older posts are in need of updating as new and additional info comes to hand! I reckon we are all the winners when it comes to finding some good facts and info on iPPS and what it can do and what it might just turn out to be one day!
Ok let's first view the Table of topics for tonight....I feel like I'm publishing my own PAR Mag...Hmmm now there is an idea...
Settle in for an interesting read if I can say so myself...I'm on the James Boag's tonight, yum! Do grab a coffee...a red wine...or an aperitif and of course, do enjoy!
TABLE OF CONTENTS
ROLEPLAY
Role Play has a few advantages 1, It makes you put yourself in someone else's shoes...to see things from their prospective. We often have our own bias and I am certainly not infallible to this. What are some of the benefits of Role Play?
- You can immediately apply content in a relevant and real world context.
- Diverge from the confines of your normal self limiting boundaries and thinking.
- Engage in a higher order of thinking and learn content in a deeper way.
- Create useful and possible scenarios.
Lot's of merit and learning to be had by this form of communication.So, let's try this out tonight...
Yes yes ok - I will be playing the role of Biomarin as an example ...YOU guys are PAR(I want to be PAR as well but I sacrifice this opportunity in this post and YOU can be the hero).
Yes yes YOU be the hero...don't worry, we will all be heroes when this thing takes off...you...me...PAR...Partner of PAR that combines us with ERT...all of us.
A BIT ABOUT MYSELF - WHAT DO I DO?
Headquarters - I am based in San Rafael, California. Yes I am listed on the NASDAQ, you can buy me for some $72.05 USD per share. I have a number of subsidiaries and I was founded in 1997.What do I do?
Well a few things but my core?
Well it's something related to YOU guys...it's ERT. How is this related to PAR? l'll get to that in a sec.
I was the first company to provide therapeutics for MPS Type I which has a brand name of Aldurzyme.
WHAT IS ERT?
Ok this is a heavy one but I'll try and keep it high level...In Mozz speak (I do a lot of Mozz speaking at the pub...after a few drinks...all simple words and basic numbers....). Our cells produce waste...this waste needs to be removed and there are enzymes that break this waste down and it gets removed from the cells...MPS patients lack this enzyme or don't have enough of it...waste builds up and problems occur...not just a few symptoms, there is a list as long as Absent Friend's Gif library....extensive, but not in a good way (err the symptoms, not AF's images, they are all comedy-gold).So the ERT attempts to inject these enzymes which alleviate the symptoms. All good, but it does nothing for pain relief....this is the bit where YOU (well, PAR) steps in.Reference 4 in the reference section will give you more on this and how ERT works but I barely made it through sentence number 2 out of like 5 paragraphs from reference 4...heavy stuff.
NUMBERS?
How big is the ERT market? Yeah it's big! They estimate OUR market size to be some $1.4 B USD....it could be a separate company in it's own right.
HOW AM I RELATED TO YOU?
How is Biomarin, as an example, at all related to PAR? Well not directly but possibly indirectly, we both will have varying solutions for the MPS patient. But there is no direct overlap... we one day may be complementary to each other.
WHO IS IN COMPETITION WITH ME?
Well there are a few, I've also included market cap below to give you an idea of whether any of these guys are big enough to actually make a deal with us and if there are serious players in the space. Also note that there are up to some 50 Lysosomal diseases, not all will necessarily be relevant to us in terms of joint pain being a symptom but a lot are, I'm just listing possible ERT candidates as a rough guide/indication:
Some examples of ERT providers, I think this is most of them but there could be a few other players....will we soon partner up with one of them?
THE CASE FOR iPPS - A FACT SESSION
Ok PAR folk, what about a little comparison now...sure ERT is a different treatment compared to iPPS...but let's do a comparative with this in mind:
FACT 1
Did you know that Vimizim, a product of Biomarin, had their results trialled over 24 weeks?
FACT 2
Did you know Vimizim is charged out at some $400,000 USD per annum?
FACT 3
Did you know that Vimizim comes with warnings, there have been side effects as well as adverse effects.
FACT 4
What was the % reduction for 6 MWT ? (sounds like power generation...sorta is...it means 6 minute walk test) 23.9% mean improvement.
FACT 5
Hmmm dosage for Vimizim? Did you know it's 2mg/kg?
FACT 6
Vimizim started showing good results over placebo after as early 12 weeks...it is also prescribed on a weekly basis.
Mozz, all very good but how do these facts help ME? I'm very happy for your so called Vimizim but can't see the connection?
Ahh my Dear Paradigmer, yes as POOL_King has stated, it is cuddle time. What?I mean it's show me the money time.....
I am drawing comparisons here...from what Vimizim is...what it went through....compared to what WE might go through..there are parallels to be learnt from. I am trying to draw clues as to how long it might take us to get MPS read out from IND?...I am trying to compare how iPPS holds up against a drug like Vimizim, will we be sought after? I am asking the question - Will it be compelling for a company like Biomarin to form a partnership (yes yes and cuddles too) with us?!
Mate...we are perfectly suited....Read on!
Let's tackle each one with the Mozz - PAR magnifying glass on....let's tackle those facts from above...
FACT 1
I think this will be something very similar to what iPPS for MPS undergoes as well...at least in terms of observations of endpoints by patient batch.
FACT 2
Mozz, mate I know you like big figs..but who cares really how much Vim. sells for? Ah but look at the relevance Dear reader...if they can sell their drug for some amazing $400 K, though perhaps the ingredients and manufacturing warrant it, it helps our case of some estimated charge ranging from $50 K to around $100 K for iPPS for MPS...My calcs use the conservative 50K...But I think 75K may not be out of the questions depending on P3 results. Look at the benefit the patient will get from our drug.....THERE IS NO DRUG ON EARTH THAT IS CURRENTLY PRESCRIBED FOR SAFE MANAGEMENT OF ON GOING PAIN. Quite simply, there is no alternative...apart from "human care"...a few Panadol...that's it. There is no standard of care...the only way is up for these poor suffering individuals.
FACTS 3
AE's? What's that, we don't have a single one to date. We are getting the benefits without the downside...just imagine.
FACT 4
Ok here is where we really get to see the power of efficacy...they got 23.9% improvement in their walk test, we haven't had a large sample size so this is subject to P3...but so far we achieved:
* A massive 60% reduction in average pain reduction for MPS
* 3 out of 4 patients received an improvement of range of motion
* GAG concentrations fell from an average of 6.71 down to 2.65 mg/mol, a 60.5% reduction.
One word, incredible.Fitting partner?....I reckon we will pull our weight in this relationship! What do you think?
FACT 5
I did a double take when I read that...interesting...that's exactly our suggested dosage (subject to dosing study?)
FACT 6
I don't know when we start showing good signs, I assume it would be a little later than the standard week 4 or so that we saw in the bulk of OA patients, my guess is it will take a bit longer, eg maybe week 8 or 10...why? Well because the dosage is set to once a week...OA was twice a week...
BONUS TIME
Ok I saved the best fact till last...
SURPRISE FACT 7
Ready?
Mate...Biomarin submitted THEIR IND back on March 29, 2013. Ok Mr Mozz, so how long did it take them for the GO AHEAD by FDA?
Wouldn't it be interesting to know that? I mean was it super quick? Was it super slow with lots of delays? I would want to know this fact...Well remember, Biomarin's Vimizim's typical dosing was over 24 weeks, that's not too dissimilar from ours...now to compare us to them requires many caveats, I could do a whole separate post on them but I will just summarise and say that take this with a pinch of salt as there can and will be many differences between them and us, between their drug and ours and the processes at FDA level that will be involved, they might have had lots of hurdles, clock stops, we may not, OR the other way around!!!
They got their BLA approved on the 14th of Feb 2014...just shy of a year later.Again I reiterate, just because that's what they went through, it doesn't mean we will follow...but it sure is an insight....
WHO WANTS MORE?
Who here would be interested to SEE what a typical letter back from the FDA might look like?
Yeah I can see by all the raised hands...At the end of this post check out the appendix A...it's an insight and I'm surprised it's publically available...I guess it is old news but to me this is a rare doc...a doc I personally hope to one day see about PAR, not sure if we would ever be privy to it but it would be nice to see it one day...I might frame it alongside my Doctorate hey Edski1?
HOW COULD THIS GO DOWN?
Right, the fun stuff..imagine in this role play it works out like this:
1) Biomarin, for example, wants market share. The market is finite, it's not like there are many new patients every year and the incidence is on a markedly massive increase every year. How can I grow market share in a relatively mature market? By adding an advantage to my line of product that no one else can have!
Think of this like a new car...some manufacturer has a new idea and they come to me and say look at this new technology for sound for instance...we can reproduce sound like no other...in one tenth of the space and our dynamic range is at least twice as good as the next player....We will give you exclusive rights if you form a partnership with us. Now my cars have this additional selling point that no one else can claim, it's patented and supply is exclusive...See where I am going with this? (Special shout out to my friend M1 here, he will know this hypothetical story well).
The latest car manufacturers need to constantly out class and out-gun the competition, how do they do this? By driving added exclusive features and lifting the standard....giving the consumer the very best, the very latest in features and benefits. When it comes to health and pain, this becomes a whole new...well...Paradigm!
Now IF Biomarin as an example can form a deal with us they can claim they have a solution that will not only do what ERT does..but it will halt...or heavily reduce the acute levels of pain in the MPS patients, a feat that no one has ever been able to do....could we one day see a poster like this?? :
A future Biomarin poster/flyer?
2) Yes all very good, but what's in it for YOU? (PAR). Well that's easy...instead of spending 5 years plus building up:
Relationship with Docs
Relationships with hospitals
Relationships with patients and their families
A massive required distribution network
A massive and required marketing campaign
And visiting all these seminars and conferences.....
We get all of the above, set up automatically, overnight, with a new founded partner. Very little or reduced effort on our part saving us not months...but literally YEARS of time in building these networks and pathways to revenue.It's great for our partner as well, as I mentioned, it is a feature they do not currently have and no competitor will have...it will set them apart from the rest and it will garner them increased market share...over night.
Now this is what I call a relationship of titans...and you now what? This may not be all that long from happening!
CHART ME UP
Ok let's hypothesise graphically...again, all my rough thinking, we don't know if any of this will play out quite like this...but it's fun to imagine what a possibility might be. Note: if the following graphic is a little on the small side, simply left click once on the pic below to enlarge.
Completely my quick stab at a possible trajectory under two possible pathways, don't read too much into the actual numbers, very rough numbers but serves merely as a guide of what might be possible?
SUMMARYThis was supposed to be a simple piece but I had to give you some background on ERT, kinda like finding out about a potential business partner how do they work, what do they have, is it a complimentary business to us?I'm not saying we will go with Biomarin, it could be any of the ones mentioned or even some other? I am saying that the CHANCES of a real deal increase markedly as the IND approaches, and even more so after the IND...we become a serious contender from that point and potential partners have to act before anyone else does to secure a deal. It's a trade off...waiting for data before committing.
Don't forget, they too have to be sure what they are partnering up with is legit, has potential and isn't just going to be throwing away millions for no reason. At the same time if they are too slow to act they may miss out and their competition will get a deal!
Finally I want to see our name in the features list of our newly founded partner...I want to be the latest BMW with these sparkling new speakers that NO ONE HAS...the competition cannot come close to us...we have it all locked up...and we get an overnight BOOM...
Paradigmers I want to hear of the Lysosome conferences held all over the world and
we are the feature...
we are the latest trump card and it is being shown that
we are treating the patient's pain for the very first time...I want to be the poster boy...ok let me rephrase...I want YOU to be the hero...the poster girl...the poster boy. I want our name in lights and the key note speaker to mention us as a draw card.
Maybe I am a dreamer...but I tell you, it might happen. There is a chance.A worldwide immediate distribution channel for our drug is possible and I want to see those sales roar...then we talk about the share price.
This is like a house sale and no one really knows how many buyers there are and what offers are being made, the ball is in the vendor's court if the house is in demand. Exciting times are approaching, yes the lacklustre share price in NO way currently reflects the underlying action and the sheer potential...one day it will...and it's on that day there just won't be enough shares to fulfil demand.
DISCLAIMERSAlways best not to rely on one source, best to do your own research and don't forget things can go awry...in my mind I have waited so long already, another few months and the party will begin...another few years and I hope we will be a household name...now
that's a (role) play you don't want to miss.
APPENDIX AA rare glimpse into what WE may achieve perhaps next year!
https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2014/125460Orig1s000ltr.pdfREFERENCES1]
https://serc.carleton.edu/introgeo/interactive/roleplay.html2]
https://www.ncbi.nlm.nih.gov/books/NBK117223/3]
https://www.asx.com.au/asxpdf/20190214/pdf/442m1cq399kbcr.pdf4]
https://www.ncbi.nlm.nih.gov/books/NBK11588/
(20min delay)