Dutch CF biotech ProQR Therapeutics files for a $75 million IPO

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enniob

Administrator
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Dutch CF biotech ProQR Therapeutics files for a $75 million IPO

If their claims turn out to be true, this could very well lead to a new drug for CF that would be suitable for a large % of CFers. It would also give Vertex some "healthy" competition, which is what we need in this "Race to a cure for CF".

ProQR's aims to relieve patients from their symptoms by repairing the basic defect underlying the disease. CF is caused by mutations on the CFTR gene in the DNA, this mutation is then copied in the RNA leading to a non-functional CFTR protein that causes the severe symptoms in patients. With ProQR's very unique approach the mutation is repaired at the RNA level, leading to normal functional protein, relieving patients from their symptoms.

They are preparing a first clinical trial for its lead candidate, QR-010, an RNA-based therapy for CF. The drug is designed to correct an underlying cause of the disease by repairing defects in the CFTR gene, delivered through a handheld inhaler to improve lung function. ProQR expects to file an IND in the fourth quarter and launch a Phase Ib trial thereafter, targeting CF patients with two copies of the F508del mutation in their CFTR genes.

We will keep you posted on the progress of this exciting new development.

Something to read in the meantime.
 
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Aboveallislove

Super Moderator
Chris,
My understanding is that the other correctors/potentiators don't affect RNA. If so, is it possible this could be ADDED to the Vertex drugs to get to 100% function?? I don't understand the science enough, but that could be great!
 
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enniob

Administrator
Staff member
It is very possible (and likely) that a drug targeted to RNA would have an additive effect to the protein corrector/potentiator combos from Vertex. If this turns out to be the case it would be very exciting and may indeed result in greater restoration of organ function (lungs being the most important in most cases). 100% is actually not needed. There are studies that suggests only 10% of CFTR function is needed to regain most of the functionality. This video on CF gene therapy approaches explains CFTR function in terms of a gene therapy approach...very much worth the watch!

[video=youtube;WQ45TFATYxA]https://www.youtube.com/watch?v=WQ45TFATYxA[/video]
 
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Aboveallislove

Super Moderator
Thanks! I'd never heard the 10% before. Carriers have 90% function and I thought from various graphs on functions that the g551 has like 30-40% function but still serious problems. But that's great to know it could be additive to the Vertex drugs.
 
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enniob

Administrator
Staff member
Aboveallislove;bt777 said:
Thanks! I'd never heard the 10% before. Carriers have 90% function and I thought from various graphs on functions that the g551 has like 30-40% function but still serious problems. But that's great to know it could be additive to the Vertex drugs.
Click to expand...

There is a big difference between CFTR function and lung function. What you are refering to is lung function. I am referring to CFTR function. Lung function is an outcome of many complex factors of course....CFTR obviously has an important role to play in the function for people with CF.

I am getting into CF gene therapy and will report back with literature references when I come across them.

Basically, the take home message is that you do not need 100% CFTR function to get adequate improvements in lungs for proper lung function. Actually, it seems that relatively low CFTR relative function is needed. I remember reading a 10% CFTR function result in 80-90% lung function respiration....but thats of the top of my head and would need to look up the literature. They do say that in the video I posted above.
 
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Aboveallislove

Super Moderator
Actually Chris I am referring to cftr function. I'll see I'd I can find the slides but vertex shows what the drugs do in vitro for cftr function and the combo will only get dd508f to 35% cftr function which equates o lie what 4% improvement o lung function. I'd love to e wrong, but ave never seen anything suggesting you only need 10% cftr function for normal functioning body.
 
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enniob

Administrator
Staff member
Hi Aboveallislove, we are both correct and referencing sound studies. I am a scientist and I can tell you that we are both correct and basically comparing apples and oranges :)

What the video above of Prof. Eric Alton who explains CFTR function that "maybe" needed for sufficient lung function improvements. The piece I am referring to starts at 15:20 in the video so scroll to that part. There he explains that studies have shown that up to 10% CFTR function you get a massive improvement in lung function, and after that the improvement gains diminish significantly.

Its on ly todo list to speak with Prof. Eric Alton at some stage. Will reach out to him and ask what studies he is referencing. I was not able to find them on a quick literature scan.

Thank you for the vertex clinical trial reference!

chris
 
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Aboveallislove

Super Moderator
Thanks Chris. That is really interesting. If that is the case, what I don't get is why, for instance, with the Vertex drugs, they will get those with ddf508 to about 30% CFTR function (from about 1-3%), but that is just barely enough to get a clinical benefit for FEV. If you do talk with him, too, I'd be really interested in the rest of the impact. To me, FEV improvement is just one thing: Having the GI track work, the reproductive track (for those with vas deferens), no horrible aquagentic wrinkling, and not worrying about pseudo and other things that don't affect those with normal CFTR function. What % of function do we need for everything to function normal or "near" normal?
 
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enniob

Administrator
Staff member
It really comes down to how you quantify CFTR function... depending on the measurement and technique used very different conclusions can be drawn in most cases. And the study I refer is specific to CFTR function in the lungs. This gene therapy also has a local effect only in the lungs...so you would see no benefit from this in GI and other areas. I think your last question does not have a clear answer yet. And likely has many assumptions based on the study and conditions the study was performed in. I guess all we can do is do the research and slowly put the pieces of the puzzel together until one day it "just clicks" and a breakthrough is made.
 
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Aboveallislove

Super Moderator
Ah. That makes perfect sense now. If they are talking cftr function in lungs versus entire cftr function. I think that's why the combo had minimal in the sweat test response but had some in lungs--that the cftr function differs in different parts of the body! Thanks for insights!
 
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enniob

Administrator
Staff member
There is a piece in this article on CFTR function relating to lung disease and how pigs could help shed light on this question: http://www.sciencedaily.com/releases/2011/03/110316152947.htm

"We know that people with 50 percent CFTR function have no disease, and now we know that 6 percent of full activity is not enough to prevent disease in the pigs," Stoltz said. "We still don't know how much CFTR is enough to prevent the disease, but this model animal could give us a way to investigate."
Click to expand...

-chris
 
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