By slightly popular request…maybe 3 people were interested I’ve created a low brow guide to the science. I thought it might help new or old investors who don’t have a background in this stuff.
Please feel free to correct mistakes or add anything I’ve missed.I thought it might spark some discussion.I promise not to be offended.
There are 2 major components.
The first is the cell penetrating peptide.
A major challenge for RNA therapeutics is they have to get into the cell.Cells have developed mechanisms to stop things penetrating them.With RNA therapeutics you can be caught between needing to give too much drug and causing toxicity or not delivering enough and not being effective.
Peptides are fragments of proteins.They are made of short chains of amino acids which are the building blocks of proteins.Despite only being fragments they can retain the function that the fragment of the protein had when it was part of the whole protein (sometimes).
What PYC did is created a library of a bunch of peptides that they got from viruses, bacteria and Archaea (ancient bacteria like things).These organisms have spent a lot of evolutionary time trying to get into cells. Hence they are likely to have some peptides that might be good at entering cells.
They found some that could enter.In the case of the retina cells the CPP they found was 100 times more likely.This effectively eliminates the risk of toxicity although we are still waiting the final trials to prove it.
In my opinion this science has value on its own. And can be applied to multiple other applications.
The second part is the actual therapy itself.
PYC is choosing single strand mutation diseases.What this means is in general genes have 2 copies of DNA one from Mum and one from Dad.
In these people one of the genes is faulty but both copies are required to make enough protein for that particular cell type to function properly 50 percent made by each.Importantly it is only just not quite enough.They don’t need 100 percent maybe 55 percent might be enough (just a number I plucked out of thin air)So with the disease people aren’t born blind or with massive cyst filled kidneys, instead the disease progresses as the cells become unable to cope with the low levels of protein over the persons lifetime.
To make a protein DNA makes a temporary copy called RNA.The RNA then moves elsewhere in the cell and joins with a little protein manufacturing plant inside the cell that reads the code from the RNA converting that code into individual amino acids and joining them together in the right sequence to make the protein.
There are various alterations that can be made to RNA once you can get in the cell using our CPP but in our case so far PYC have chosen to make a change that enhances protein production.This means the single copy now makes about 80 percent of what would be made by two copies. In theory more than enough.As these people have only slightly less than they need.This has been confirmed in the preliminary trials.
The molecule that increases the protein production by altering the RNA is called a PMO.If you can join the CPP to the PMO while keeping the function of both then you have a potentially pretty powerful drug.CPP-PMO.It can get into the cell and increase protein production of the relevant gene.Treating the underlying protein deficit and stopping the disease process for a time. Once the time is up you can administer the drug again.
Like all biotechs we do have the issue of the trials that seem never ending.Unfortunately they are essential.Historically medicine is littered with treatments people were convinced would work but were actually harmful.Perhaps the most famous is leaches, thalidomide is also a good example but there are too many embarrassing and sometimes tragic mistakes to count.Due to this the level of evidence required to allow a drug to be freely used in humans is extremely high.Even after a drug is released to market there is continued monitoring for adverse events.
In this setting there can never be an assumption that because the science is good the drug will be efficacious and safe.It has to be proved.
Therefore in my opinion it feels like the share price lags the science.I hope that at some point the market will catch up with the science if the proof keeps coming and/or if there is proof of commercialisation.We are starting to get to the pointy end of the trials.From my point of view the fact that we now have enough cash to prove the science takes away a lot of the risk.
(20min delay)