ndeed to be successful in this game it's not enough to have a supreme product, as you well know we need a lot of other things to come together and apart from a large potential runway, we need there to be less competition or better still, virtually NO competition.
Tonight, the latest news and how it might affect us positively.
As always, do enjoy.
BACKGROUND
The OA landscape is littered with failures over the years. The big spectacular falls of Tanezumab, to the lesser knows ones like Fanisamab and the likes of GLP1972.
Let me just say, these pharmas are working hard, PAR included. Tanezumab underwent:
"41 clinical studies, 38 interventional trials and three observational studies, with approximately 13,000 exposed patients".1
Many have shown promise initially, but when thoroughly tested haven't been up to scratch or have resulted in too many unwanted effects. Meanwhile, the patient populations increases year on year with some predicting a steady 9% CAGAR. There is a huge pent up demand for a decent product that can stave off totally or at least partially delay the inevitable surgery and avoid a string of terrible side effects via analgesics along the way.
Just take a look at the numbers only in Australia - Helllooooo TGA?!
To have a successful drug you need three distinct 'S' components:
Symptomatic Structural Safety
3 outta 3 required for a blockbuster?
SECOND PLACE
I keep one eye on PAR but my other eye is on the competition. If I found something that's really a serious contender I don't actually, at this point, think I would do anything different. Why? Cos the market is enormous, and yeah, I'm not just talking OA. For us, OA is merely the start...it's that supremely layered future revenue that excites me.
So what competition have I had on me radar? Plenty, but a few pertinent ones....
What's been on Mozz's radar?
So for a number of years I have been following one particular drug and to me, it's the closest drug to us. Granted it is still quite a way off in terms of comparable efficacy ...it certainty did cause me to do more research into them.
The drug I had an eye on was none other than Lorecivient. They had some earlier stumbles in the Phase 2 which made me think that all is not well with their drug despite it having some efficacy in certain aspects 2:
Why did they fail? It was due to the fact that they didn't get statistical significance symptomatically, ie pain. These trials I thought initially were Phase 2, they weren't, they were Phase 3.
So what did they do? They changed gears and went for another Phase 3 trial, this time focusing on OA patients with mild pain.
But after that, they were allowed to proceed with their P3 and late last year they posted these wordings and this graphic (see further below)3 :
Now to me, that seems like they had a raging successful result!
Then I see this....
It looks quite compelling....the crossover results in a lift for the placebo group....sure it's 3 years, sure it's intra-articular and yes, the tech revolves around WNT pathways which can result in higher side effects and there is quite a bit of study to do in my mind in regards to knock on effects...but this result isn't too bad.
Hello PAR?
Do we have competition I was starting to ask?
Do I need to make some phone calls and start a thread on HC....what would I title it?
"errr guys?"
"Houston we have a problem"
"We are not alone"
I knew I'd have to do a heck of a lot more research before I start to panic.
I didn't remember hearing anything either overly exciting in regards to Lor. at Oarsi Hmmmm
So I dug a little deeper.
UNDER THE SURFACE
Well it turns out that their P3 actually wasn't as good as they made out? Potentially. In fact it appears they failed their primary endpoint!
I came across this article just recently 4 .
Biosplice actually had two phase three studies that were recently completed , OA-07 long-term structure, pain and function study, and OA-21 short-term pain study. It was the OA-21 that didn't meet the primary endpoint.
Now it's not totally game over for them, in fact I believe they are trying to resolve it and perhaps will need a further study to be constructed to show more evidence of any good data. The very best result for them is that the FDA somehow agree to a concentrated focused area for them?
"This isn’t the first time that lorecivivint has failed a clinical trial. In late 2022, the drug didn’t show statistically meaningful pain reduction among patients with more advanced osteoarthritis in a pair of placebo-controlled trials".2
As mentioned previously, the FDA really want to see OA being addressed as a whole. Remember those three 'S' bullet points?
Symptomatic, Structure and Safety. One component won't be enough. OA we know is broad, just some of the broad categories include 7:
mechanical overload
inflammatory component
cell senescence (cells that stop dividing, eg the growing old process)
metabolic alterations
cell signaling
The other side to clinical trials is managing the placebo effect, in fact Biosplice witnessed higher placebo levels in their trial and are investigating. Par are very conscientious of the placebo effect and have worked hard to not only contain it but to improve it. It's another aspect that I credit Dr D. Skerrett and team for.
Finally we know Loreciviviant is administered intra articular but within that, there is this statement from a peer review:
"There are challenges for the use of lorecivivint in the treatment of symptomatic knee OA. It is administered by intraarticular injection which might limit the number of providers who will be able to use it. Also, to verify that the drug is administered in the joint space, and to exclude the possibility of drug leak, lorecivivint is administered under ultrasound guidance" 8
We still need to keep an eye on Biosplice's OA contender but I'm not worried about them even half as much as I used to.
OTHER LEARNINGS
The other insights we can learn from a potential competitor is deal evidence.
Take a look 9:
CHINA : $140 Million KOREA : $70 Million FUNDING PARTNERS: $120 million. New investors include Eventide, aMoon, SymBiosis II, Sands Capital and Verition - Proceeds to support Biosplice’s clinical development of lorecivivint, its Phase 3 Osteoarthritis therapy, as well as its Oncology and Neurology programs
One Regional handshake is good, multiple? Great!
Paul talks about potential partners, in the event that the FDA (and possibly the TGA) come to the party, the next step for us should be some sorta of regional deal. Yes it still might take some time for these to eventuate...but if one does, the exciting prospect for us as holders is that there could be others. Sure maybe they are small but certainly they will be accreditive adding to the excitement and of course, the validation.
MULTIPERSPECTIVITY?
Depending on who you listen to, there are two distinct perspectives. Biosplice claim to have a great drug that is showing signs of structural improvements and some focused elements displaying some pain relief. I don't doubt that there is some subset of the OA population that may derive some benefit but comparing iPPS to Loreciviviant, well there is a vast systemic difference from what I can see.
As we patiently wait for the next step, it makes sense to keep abreast of what the competition is also up to and hopefully look forward to a brighter future with our own iPPS!
ndeed to be successful in this game it's not enough to have a supreme product, as you well know we need a lot of other things to come together and apart from a large potential runway, we need there to be less competition or better still, virtually NO competition.
Symptomatic
Structural
Safety
(20min delay)