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ProQR -  RNA Editing Company Focusing On Rare Diseases Like Cystic Fibrosis, Usher Syndrome

|Includes: ProQR Therapeutics (PRQR)

ProQR specializes in RNA editing and has pioneered Axiomer® platform technology and uses it to correct RNA in the cells in patients and target mutations.

Platform discovery creates extensive pipeline of candidates leading to multiple shots at goals in multiple clinical development targets.

Focuses on rare and orphan diseases like Leber’s Congenital Amaurosis - a genetic eye disorder that leads to childhood blindness; Usher syndrome – a genetic disorder.

Both Ushersyndrome and Leber’s Congenital Amaurosis don’t have any current treatments.

Brief History of the company:

The company was founded by the current CEO when he was confronted with the news that his newborn son was diagnosed with Cystic Fibrosis. ProQR was founded in 2012 in Netherlands focusing on creating new medicines to rare diseases. ProQR specializes in the development of RNA therapeutics; drugs that consist of a short piece of synthetic RNA. This method enables ProQR to make temporary corrections to “genes” and therefor restore protein expressions that are crucial to human function.

Source: ProQR Website

PRQR stock price was $7:60 on 8/24/2018 and the market cap was around $242M

Source: Nasdaq

Now, let us understand the diseases that PRQR is focusing on:

Cystic Fibrosis: Many of the readers may be aware of Cystic Fibrosis. Still I thought a brief introduction is warranted. CF is an inherited disease that affects glands such as mucus and sweat glands. CF is caused by a mutation of CF gene on Chromosome 7. The production of excessively thick and sticky mucus leads to blockages in lungs and airways creating serious lung infections and damage to the lungs in long term. Cystic Fibrosis has no approved treatment yet though there are approved treatments for some of the effects of CF.

The answer QR-010 – Also called Eluforsen is being developed by PRQR for cystic fibrosis with F508del mutation. 2 global clinical trials for Eluforsen (QR-010) for patients with cystic fibrosis (CF) have been completed. Clinical trial 1 was a Phase 1b safety and tolerability clinical trial in 70 people with CF due to two copies of the F508del mutation and Study 002, was a proof of concept clinical trial in 18 people with CF due to one or two copies of the F508del mutation. QR-010 has ODD designation from the US and EU. Also, it has received the FT from the US FDA.

On Sep 25, 2017, PRQR announced positive top line results of the Ph 1b study.

In summary,

  • the drug was safe and well tolerated across all doses by the patients with no serious adverse events related to the treatment
  • The mean improvement was 13 to 19 points compared to the established minimal clinically important difference of 4.0 points. In fact, in a pre-defined subgroup of patients with a lower lung function at baseline, the mean improvement was even better at 27.5 points compared to placebo
  • The positive results reported on QR-0101 has significantly increase the confidence that QR-010 has the potential to become an effective treatment of CF

Also, PRQR is working with the next generation of 3 more drugs in the discovery stages for other mutations.

Source:  ProQR Press Releases

Usher Syndrome Type 2A: is the leading cause of combined deafness and blindness. Anyone affected by this disease is, generally, progresses to a stage when they almost lose their central vision and have moderate to severe deafness. Usher syndrome type 2A is one of the most common forms of Usher syndrome and is caused by mutations in the USH2A gene. As of now, there are no treatments approved or products in clinical development that treat the vision loss associated with Usher syndrome type 2A.

The answer QR-421a:

QR-421a is a first-in-class investigational RNA-based oligonucleotide designed to address the underlying cause of vision loss in Usher syndrome 2A due to mutations in exon 13 of the USH2A gene. Mutations in this exon can cause loss of functional usherin protein that causes the disease. QR-421a is designed to exclude the genetic defect from the RNA in the eye, such that it leads to the expression of a shortened but functional protein, thereby modifying the underlying disease. QR-421a has received orphan drug designation in the United States and the European Union.

Leber’s Congenital Amaurosis 10:

Leber’s congenital amaurosis (LCA) is the most common cause of blindness due to genetic disease in children and consists of a group of diseases of which LCA 10 is one of the more severe forms. LCA 10 is caused by mutations in the CEP290 gene, of which the p.Cys998X mutation is the most common. LCA 10 leads to early loss of vision causing most people to lose their sight in the first few years of life. To date, there are no treatments approved or other products in clinical development that treat the underlying cause of the disease. Approximately 2,000 people in the Western world have LCA 10 because of this mutation.

The answer QR-110:

QR-110 is a first-in-class investigational RNA-based oligonucleotide designed to address the underlying cause of Leber’s congenital amaurosis 10 due to the p.Cys998X mutation in the CEP290 gene. The p.Cys998X mutation is a substitution of one nucleotide in the pre-mRNA that leads to aberrant splicing of the mRNA and non-functional CEP290 protein. QR-110 is designed to restore wild-type CEP290 mRNA leading to the production of wild-type CEP290 protein by binding to the mutated location in the pre-mRNA causing normal splicing of the pre-mRNA. QR-110 is intended to be administered through intravitreal injections in the eye and has been granted orphan drug designation in the United States and the European Union and fast track status by the FDA.

Dystrophic Epidermolysis Bullosa:

Epidermolysis Bullosa (NYSE:EB) forms the core of a group of rare genetic skin diseases causing blistering of skin and mucosal membranes lining many tracts such as the mouth and food pipe. The most severe form of DB is the Dystrophic EB (DEB). DEB causes the skin to be so fragile, it is called ‘Butterfly Skin’. People with DEB live in constant pain, low appetite, and infections. The DEB is caused by mutation in a gene called COL7A1. COL7A1 is responsible for the formation of collagen type VII (C7) protein responsible for forming fibrils to bind dermal and epidermal skin layers together. There are no approved treatments that resolves the underlying gene mutation. The only available treatments are used in the management of the disease.

The answer QR-313:

This drug targets DEB associated with COL7A1 gene mutation due exon 73. The drug uses exon skipping for exon 73 from COL7A! RNA. PRQR expects this exon 73 skipping slows C& protein to be restored allowing the anchoring fibrils and strengthening of the skin. QR-313 has received ODD from US FDA and EU.

PRQR is working with other drugs that target other forms of exon skipping.

Summary of Drugs:

QR-010/ Eluforsen targets Cystic Fibrosis (CF) patients with F508del mutation and it has FDA Fast Track designation and ODD in the U.S. and Europe.

QR-110 for children and adults with Leber’s congenital amaurosis 10 (LCA 10). QF-110 was granted FDA Fast Track designation. QR-110 has orphan drug designation (ODD) in the U.S. and Europe.

QR-421a and QR-411 for Usher syndrome targeting mutations in exon 13. QR-421a and QR-411 have received ODD from the FDA and Europe.

QR-313 was granted ODD in the U.S. and Europe.

PRQR Drug Pipeline:

Source: ProQR Website

Management Team: A strong, deep, and committed management team benefits any organization. ProQR was started with a mission. The CEO started the company when he was confronted with the news that his newborn son was diagnosed with Cystic Fibrosis. The management and the advisory board is a deep bench with former or current executives from Gilead (GILD), Vertex (VRTX), Galapagos NV (GLPG), Ovascience (OVAS), Sanofi (SNY)

Financial Details - At June 30, 2018, PRQR held cash and cash equivalents of €33.0 million, compared to €48.1 million at December 31, 2017. The company expects that the current cash and cash equivalents are enough for it to conduct business until end of 2019.

Source: ProQR Financial Statement 

Acknowledgement: ProQR Website, Press Releases, Financial Statements

Risks in Business:

As in any development stage biotech, the company may not be able to achieve the goals it is set to achieve. PRQR may need to raise more cash in order to conduct further clinical trials to prove that the drugs work on the intended target.

Disclosure: I am/we are long PRQR.

I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.