ProQR In-licenses Worldwide Rights to Ophthalmology Drug Candidate From Ionis Pharmaceuticals

ProQR Therapeutics N.V. recently announced the signing of an agreement with Ionis Pharmaceuticals to license QR-1123 (formerly IONIS-RHO-2.5_Rx), an RNA medicine for autosomal dominant retinitis pigmentosa (adRP) caused by the P23H mutation in the rhodopsin (RHO) gene.

“Building on the recent proof-of-concept with QR-110 in LCA10 patients, we have confidence in the potential of single stranded RNA-targeted therapies to treat patients with genetic eye diseases,” said Daniel A. de Boer, Chief Executive Officer of ProQR. “By acquiring the rights to QR-1123, we have strategically expanded our pipeline in retinal diseases. Ionis has a wealth of experience in discovery and development of antisense drugs, and we look forward to working with them on this important program. Unlike other molecules we are developing, QR-1123 is a gapmer with a mutant allele-specific knockdown mechanism of action. If validated, it would further broaden the potential of RNA-targeted therapies in retinal diseases. We are excited to start clinical development to explore QR-1123’s potential in helping patients with P23H adRP.”

Under the terms of the agreement, ProQR was granted an exclusive worldwide license to QR-1123 and relevant patents. ProQR made an upfront payment in ordinary shares in the aggregate amount of $2.5 million, at $22.23 per share, which represents a 20% premium (based on the volume weighted average price of the previous 20 trading days) to its common stock, to Ionis upon signing the agreement. ProQR will also make future milestone payments, certain of which will be made in equity and others in cash or equity at ProQR’s discretion, and royalties on net sales of 20% through the royalty term.

Preclinical activities have been completed by Ionis and were presented at the 2015 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) and published in a peer-reviewed article, Murray et al 2015, IOVS. A natural history study in patients with P23H adRP has been conducted. The results of this study provide valuable information on disease progression in these patients, which is important data for designing the clinical development plan. ProQR expects to start a Phase 1/2 clinical trial in patients with adRP in 2019, pending submission and clearance of the IND application by the US FDA.

Brett P. Monia, PhD, Chief Operating Officer and Senior Vice President of Translational Medicine at Ionis, added “IONIS-RHO-2.5_Rx, now QR-1123, is an antisense oligonucleotide we designed to specifically target only the mRNA from the disease-causing rhodopsin gene, which has a single nucleotide P23H mutation, while preserving expression of the mRNA from the normal rhodopsin gene, which is important for the eye to function properly. IONIS-RHO-2.5_Rx was developed by Ionis scientists dedicated to discovering innovative therapeutics to fight diseases where no other treatments have proven effective or even existed. We believe that ProQR has the ophthalmology expertise and experience in developing oligonucleotide drugs for the eye to rapidly bring this program through clinical development and ultimately to patients.”

Autosomal dominant retinitis pigmentosa, or adRP, is a severe and rare genetic disease that causes progressive reduction in night and peripheral vision during childhood and frequently leads to blindness in mid adulthood. In the United States, the most prevalent mutation associated with adRP is the P23H point mutation (also known as the c.68C>A mutation) in the rhodopsin (RHO) gene and affects approximately 2,500 people. This gain of function mutation causes misfolding of the rhodopsin protein that becomes toxic to the photoreceptor cells in the retina. Over time the cells die and vision is progressively lost. There are currently no therapies approved or in clinical development for P23H adRP. A natural history study in patients with P23H adRP has been conducted.

QR-1123 is a first-in-class investigational oligonucleotide (gapmer) that was developed by Ionis Pharmaceuticals using Ionis’ proprietary antisense technology for the treatment of adRP due to the P23H mutation in the RHO gene. The therapy aims to inhibit the formation of the mutated toxic version of the rhodopsin protein by specifically binding the mutated RHO mRNA. Binding of QR-1123 causes allele specific knockdown of the mutated mRNA by a mechanism called RNase H mediated cleavage without affecting the normal RHO mRNA. QR-1123 is intended to be administered through intravitreal injections in the eye.

ProQR Therapeutics is dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe genetic rare diseases such as Leber’s congenital amaurosis 10, dystrophic epidermolysis bullosa and cystic fibrosis. Based on our unique proprietary RNA repair platform technologies we are growing our pipeline with patients and loved ones in mind.