t's often easy to focus on the short term...on the things right in front of us...the beleaguered share price, the relatively less expected news in the immediate term....
To help pass the time, I research and I try and imagine the future. Yeah its hard to get a sense sometimes of just how bright it could be. I understand its not just about the science, we need the commercial side to come and play as well.
Science...Commercial and A Big Pharma all three playing together....this will make for a fun future story!
Tonight, lets just try and get a sense of what could be at least part of our future with PAR.
THE LYSOSOME
What is a lysosome?
Think of it as a encompassing membrane within a cell...
Here's a pic:
What are 3 things lysosomes do?
A lysosome has three main functions: the breakdown/digestion of macromolecules (carbohydrates, lipids, proteins, and nucleic acids), cell membrane repairs, and responses against foreign substances such as bacteria, viruses and other antigens.1
Lysosomes are involved with various cell processes. They break down excess or worn-out cell parts. They may be used to destroy invading viruses and bacteria. If the cell is damaged beyond repair, lysosomes can help it to self-destruct in a process called programmed cell death, or apoptosis.2
Certainly there is a link between lysosomal functioning and excess cell death, this was also evidenced by the paper written by Dr Simonaro3:
"These results demonstrate that MPS VI articular chondrocytes undergo cell death at a higher rate than normal cells, because of either increased levels of dermatan sulfate and/or the presence of inflammatory cytokines in the MPS joints. In turn, this leads to abnormal cartilage matrix homeostasis in the MPS individuals, which further exacerbates the joint deformities characteristic of these disorders".
Other studies conducted invitro (outside the body) have also found a link with the usage of Pentosan and the reduction symptomatically of such disease as Gaucher and Fabry's diseases:
"The objective of this work is to analyze the in vitro effect of PPS on inflammatory cytokines in cellular models of Gaucher and Fabry diseases, and to study its effect in Gaucher disease associated in vitro bone alterations. Cultures of peripheral blood mononuclear cells from Fabry and Gaucher patients were exposed to PPS. The secretion of proinflammatory cytokines was significantly reduced".
...and further:
"Conditioned media from this cell cultures exposed to PPS produced lower numbers of osteoclasts. We could demonstrate PPS is an effective molecule to reduce the production of proinflammatory cytokines in in vitro models of Fabry and Gaucher diseases. Moreover, it was effective at ameliorating bone alterations of in vitro models of Gaucher disease. These results serve as preclinical supportive data to start clinical trials in human patients to analyze the effect of PPS as a potential adjunctive therapy for Fabry and Gaucher diseases".
The researchers went on to show us these amazing results on inflammatory cytokines and the wonderful action of the drug that YOU own 4:
(*'s indicate significant findings)
Let me just say, I'm a bit loving the above trending of PPS's influence on these inflammatory cytokines!
Lysosomal disease represent a group of over 40 distinct genetic diseases and are caused by abnormalities of enzymes present in lysosomes.5
HOW IS THIS RELEVANT TO US?
PPS inhibits leukocyte recruitment and interferes with some functions of chemokines, cytokines, and growth factors, thereby reducing inflammation and reactive oxygen species (ROS).
We are currently running not one, but two distinct trials in this space. It has been said that the lysosomal indication is a company maker in its own right. What does this mean? It mean that one day revenue from MPS , a rare disease will be lucrative enough. We have now got the hint that there will could be some markets that don't even need a Phase 3. PAR were smart, they didn't just RANDOMLY chose a couple of the lysosomal diseases (MPS 1 and VI)....they chose two distinct diseases that have two separate current standard of cares, namely Enzyme Replacement Therapies as well as Bone Marrow Replacement therapy). iPPS will show efficacy in terms of pain reduction and function improvement to be able to work in harmonisation in BOTH of thee areas...double the revenue.
What does this mean for us?? How is it relevant?
1) Quicker time to revenue.
Yeah but Mozz, the patient numbers can be measured in the low thousands. True...I can't deny that, but what you are forgetting is that PAR won't just be charging a mere $2500 per patient course. Its once a week yearly Sub Q dosing....its more expensive...and it will be covered by insurance. Watch this space. MPS VI will most likely have a read out by the end of the year or so....its next year where things could really start to get quite interesting.
2) Higher growth trajectory....
You can't just say that the year on year trajectory is going to follow another normal drug....WHY? Because the MPS patient community is CONNECTED. Connected like you wouldn't understand...they have specialised doctors, they patients generally live very close to the hospitals, they network if there is any chance of a drug showing first time decent pain relief that's safe and efficacious... News of this is going to spread...and spread FAST. Its this area where I'm not so conservative in terms of lag of sales...it will, in my opinion occur at a decent clip.
Mate, I love flying....get me anywhere even near an airport and something goes off in my brain, MPS is one indication that isn't going to have a slow uptake- yeah, we will get a steep flight glide path upwards...
I've always assumed that the total MPS patient population in the USA is circa 13,000 odd...there are indications that this might actually be a bit more6:
So let's try and go even further beyond this. I came across a paper that has found a fairly strong link between lysosomal damage and you guessed it...a big one....Alzheimer's.
"Many neurodegenerative disorders have lysosomal impediments, and the list of proposed treatments targeting lysosomes is growing".1
But Mozz, that's all good in theory, is there any evidence to date about how iPPS might work in the brain?
I give you at least two articles I've written in the past to explore this at a higher level.
iPPS reduced inflammation of the gums for instance. But iPPS may address Alzheimer's directly? Yes it's a bit of a jump, no its not impossible. We already know of the more direct effect via the reduction of iL8 in the brain. Not by a small amount, the Mt Sinai study in canines showed a HUGE 90% reduction.
Did someone say Canines? Watch out for our Canine study results in about a month or so...giving us data on the 3 year effective term....what is a more longitudinal effect of iPPS? Yes Dog's pathologies or similar to humans in terms of natural OA.
Interested in the possible connection with iPPS and Alzheimer's ? May I suggest these two articles, single left click on the below hyperlinks:
The following is an exact quote I referring to, again I ask you, do you really know what you are holding?
"Amyloid plaques were surrounded by swollen organelles positive for the lysosome-associated membrane protein 1 (LAMP1) in the APP/PS1 cortex and hippocampus, regions with robust synaptic deterioration".1
Also this quote:
"The health and survival of neurons in the brain is dependent on a recycling pathway carried out by lysosomes, cellular organelles that help degrade and recycle proteins. Defects in the function of lysosomes are increasingly thought to be involved in the development of Alzheimer’s disease (AD)".2
"Increasing evidence suggest that dysfunction of lysosomes, a critical component within cells, plays a key role in the development of Alzheimer’s disease (AD)".7
"Compromised clearing events by lysosomes are implicated in protein accumulation disorders including Alzheimer’s disease (AD), Parkinson’s disease, and Huntington’s disease, as well as in metabolic lysosomal storage disorders [1,2,3,4]. In addition, with regard to risk factors for the age-related neurodegenerative disorders, lysosomal instability is a feature of brain aging that influences the balance between protein synthesis and protein clearance [3,5,6,7], thus producing an impact on neuronal vulnerability in aged individuals".1
FUTURE INDICATIONS
We know there is some evidence in Mad Cow's disease in humans...we understand from the canine study performed under the guidance of Dr Simonaro and PPS's positive influence on the reduction of IL8....(what percentage? 15%? Maybe as much as 30%...how about 90% (see appendix A)....but how about these future indications again I'm taking 10 years from now...hey, I can easily 40% of my current shares (called my core) for these in say 15 years from now..
Guys, seriously... I'm learning from my past miustakes...as long as our story continues, as long as our current management are intact...as long as competition doesn't start nipping at our heals...call it 40% of my current holding (I call it the core)...I will never sell this component there is simply just too much exciting potential for me to make this mistake. Yes personal thoughts here. Seek professional advice. I see a very very bright future. ..
CONCLUSION
Lysosomes play an integral part in a number of cellular functions. Yes the emphasis here is on MPOS. Don't be under the FALSE impression that a rare disease is worth a pittance. Its lucrative AND its a focal point of the authorities. There are a number of incentives afforded to Bio Pharmas companies that pursuit such indications, PAR are a lot smarter than the mass market are currently attributing to them. As a very good friend of mine recently stated we are a bathtub water flow vortex...we are getting closer.
I can't wrap it up as well as these independent researchers, have a read:
"The current study indicates that lysosomes are intimately involved in multiple types of age-related disorders. In addition to AD pathogenesis, our finding also link aspects of Parkinson’s disease and MCI to lysosomal disturbances. Furthermore, enhancing a component of the lysosomal pathway reduced several indications of protein accumulation pathology, again pointing to the vital role lysosomes play in maintaining cellular homeostasis".
t's often easy to focus on the short term...on the things right in front of us...the beleaguered share price, the relatively less expected news in the immediate term....
(20min delay)