Royalty Report: Drugs, Disease, Therapeutic – Collection: 258420

License Grant

The parties entered into a collaboration to develop and commercialize gene therapy treatments for Inherited Retinal diseases (IRDs).  The Licensee will receive worldwide exclusive rights to commercialize product candidates for achromatopsia (ACHM) caused by mutations in either CNGB3 or CNGA3, X-linked retinitis pigmentosa (XLRP) and options to additional IRD programs.

License Property

Under the agreement, the two companies will collaborate in the clinical development of Licensors leading IRD pipeline, including product candidates for achromatopsia (ACHM) caused by mutations in either CNGB3 or CNGA3 and X-linked retinitis pigmentosa (XLRP). In addition, the parties are entering into a research collaboration covering Licensor’s pipeline of pre-clinical programs for IRDs. The two companies are also entering into a research collaboration to further develop AAV manufacturing technology as well as clinical and commercial manufacturing supply agreements for the clinical and research programs.

X-linked retinitis pigmentosa (XLRP) is and inherited condition caused by mutations in the RPGR gene. XLRP causes progressive vision loss in boys and young men. The condition begins with night blindness and is followed by progressive constriction of the field of vision. XLRP often results in total blindness and there is no specific treatment for this condition.

Field of Use

Achromatopsia (ACHM) is an inherited retinal disease that prevents cone photoreceptors from functioning. Patients are legally blind from birth and usually suffer from severely reduced visual acuity of 20/200 or worse; a disabling sensitivity to light, or photophobia; total color blindness; and involuntary back and forth eye movements, or nystagmus. There are currently no approved treatments for achromatopsia.

AAV-CNGB3 and AAV-CNGA3, gene therapy candidates designed to restore cone function, are delivered via subretinal injection to the area of the eye where most of the cones in the retina are located. AAV-CNGB3 was granted orphan drug designation (ODD), rare pediatric disease and Fast Track designations by the U.S. Food and Drug Administration (FDA), and orphan medicinal product and PRIME designations by the European Medicines Agency (EMA) for the treatment of achromatopsia caused by mutations in the CNGB3 gene. A Phase 1/2 clinical trial of AAV-CNGB3 in both adult and pediatric patients is underway.

X-linked retinitis pigmentosa (XLRP) represent some of the most severe forms of RP, resulting in early onset in childhood and rapid progression to blindness by the time patients reach 20 to 30 years old. In XLRP, both rods and cones function poorly, leading to degeneration of the retina and total blindness. There are currently no approved treatments for XLRP.

AAV-RGPR is designed to treat the most common form of XLRP caused by mutations in the RPGR gene. Both rod and cone photoreceptors require RPGR to function. AAV-RPGR has received Fast Track designation and ODD from the FDA and orphan medicinal product designation from the EMA. A Phase 1/2 clinical trial of AAV-RPGR in adult and pediatric patients is underway.

This strategic collaboration agreement is related to development and commercialization of gene therapies for the treatment of inherited retinal diseases (IRDs).  IRDs are a group of rare eye conditions caused by an inherited gene mutation that are often characterized by progressive retinal degeneration which leads to severe vision impairment, loss or blindness.

License Grant

Under the terms of the agreement, Licensee was granted an exclusive worldwide license to QR-1123 and relevant patents. Licensee 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 U.S. Food and Drug Administration (FDA).

License Property

QR-1123 (formerly “IONIS-RHO-2.5Rx”), an RNA medicine for autosomal dominant retinitis pigmentosa (adRP) caused by the P23H mutation in the rhodopsin (RHO) gene.

Field of Use

QR-1123 (formerly “IONIS-RHO-2.5Rx”) is an RNA medicine for autosomal dominant retinitis pigmentosa (adRP) caused by the P23H mutation in the rhodopsin (RHO) gene.  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.

License Grant

The Licensee was grantred a License from the Licensor for intellectual property relating to AAV-mediated gene therapy for X-linked retinal degeneration associated with mutations in the RPGR gene. The patent application was filed in 2013 and upon issue is expected to expire in 2033.  The license is sublicenseable. This license continues until the expiration of all the patents subject to the licenses or if later, a specified number of years following the first sale of the first product covered by the in-licensed intellectual property.

License Property

The Licensor granted  use of intellectual property relating to AAV-mediated gene therapy for X-linked retinal degeneration associated with mutations in the RPGR gene.

Field of Use

The Licensee is a clinical-stage biotechnology company developing gene therapy products designed to transform the lives of patients with severe inherited orphan diseases in ophthalmology.

License Grant

The parties amend certain terms of the original License Agreement in light of the sublicensee agreements.

The First Amendment has been amended to include but not limited to License Product, Regulatory Exclusivity, Sublicensee Royalty Term, Sublicensee Product and Royalty payments.

License Property

Patent applications relates to a novel synthetic microdystrophin gene to make, sell and distribute products for use in the treatment of Duchene and related disease indications resulting from a lack of functional dystrophin.

Licensed Product) is amended by adding (a) Any product, apparatus, kit, composition, or component thereof (i) whose use, sale, offer for sale, or importation of which is covered, in whole or in part, by any valid claim contained in the Patent Rights or (ii) which is made by any method, procedure, process, or step which is covered, in whole or in part, by any valid claim contained in the Patent Rights; or (b) An isolated synthetic nucleic acid molecule comprising a synthetic mini-dystrophin or micro-dystrophin gene encoding a synthetic, non-full-length, dystrophin protein that is able to restore nNOS to the sarcolemma, wherein the non-full-length dystrophin protein comprises, from the N terminus to the C terminus 1. the N-terminal domain of the dystrophin protein or a modified N-terminal domain of the dystrophin protein, 11. at least two repeats of the mid-rod domain of the dystrophin protein, wherein said at least two repeats comprise R16 and Rl 7, 111. at least 2 hinge regions of the dystrophin protein, whereas said at least two hinge regions comprise HI and H4, and 1v. the cysteine-rich domain of the dystrophin protein; wherein the mini- or micro-dystrophin gene is between 5 kb to about 8 kb in length or less than 5 kb in length, respectively.

Duchenne is caused by mutations in the dystrophin gene, which result in the absence or near-absence of dystrophin protein. Dystrophin protein works to strengthen muscle fibers and protect them from daily wear and tear. Without functioning dystrophin and certain associated proteins, muscles suffer excessive damage from normal daily activities and are unable to regenerate, leading to the build-up of fibrotic, or scar, and fat tissue. Efforts are focused on our lead product candidate, SGT-001, a gene transfer candidate under investigation for its ability to drive functional dystrophin protein expression in patients’ muscles and improve the course of the disease. Based on our preclinical program that included multiple animal species of different phenotypes and genetic variations, as well as preliminary clinical trial biomarker results, we believe that SGT-001, has the potential to slow or even halt the progression of Duchenne, regardless of the type of genetic mutation or stage of the disease.

Sublicensee Product means any Licensed Product commercialized by Sublicensee, its affiliates or permitted sublicensees pursuant to the Collaboration and License Agreement, dated October 22, 2020, by and between Sublicensee and Licensee.

SGT-001 is a novel adeno-associated viral (AAV) vector-mediated gene transfer therapy designed to address the underlying genetic cause of Duchenne muscular dystrophy (Duchenne). Duchenne is caused by mutations in the dystrophin gene that result in the absence or near absence of dystrophin protein. SGT-001 is a systemically administered candidate that delivers a synthetic dystrophin gene, called microdystrophin, to the body. This microdystrophin encodes for a functional protein surrogate that is expressed in muscles and stabilizes essential associated proteins, including neuronal nitric oxide synthase (nNOS). Data from Solid’s preclinical program suggests that SGT-001 has the potential to slow or stop the progression of Duchenne, regardless of genetic mutation or disease stage.

Field of Use

Field of use is for the cure Duchenne muscular dystrophy (“Duchenne”), a genetic muscle-wasting disease predominantly affecting boys, with symptoms that usually manifest between three and five years of age. Duchenne is a progressive, irreversible and ultimately fatal disease that affects approximately one in every 3,500 to 5,000 live male births.  SGT-001 is our lead gene transfer candidate and the focus of our research and development efforts. Gene transfer, a type of gene therapy, is designed to address diseases caused by mutated genes through the delivery of functional versions of those genes, called transgenes. The transgenes are then utilized by the body to produce proteins that are absent or not functional prior to treatment, potentially offering long-lasting beneficial clinical effects.

License Grant

The Company entered into a services and collaboration agreement with an undisclosed service provider for the treatment of Crigler-Najjar Syndrome related to the Company’s AT342 development program.

License Property

The program is focused on developing and commercializing gene therapy products for patients suffering from serious, life-threatening rare diseases caused by single gene defects.  The gene therapy has powerful potential to treat these diseases through delivery of a functional copy of the affected gene to cells, resulting in production of the normal protein. We have built a compelling portfolio of product candidates, including AT132 for the treatment of X-Linked Myotubular Myopathy, or XLMTM, AT342 for the treatment of Crigler-Najjar Syndrome, or Crigler-Najjar, AT982 for the treatment of Pompe disease and AT307 for the treatment of the CASQ2 subtype of Catecholaminergic Polymorphic Ventricular Tachycardia, or CASQ2-CPVT.

Field of Use

This agreement pertains to the drug industry relating to the treatment of Crigler-Najjar Syndrome.

Crigler–Najjar syndrome or CNS is a rare inherited disorder affecting the metabolism of bilirubin, a chemical formed from the breakdown of the heme in red blood cells.

Pompe disease is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. The accumulation of glycogen in certain organs and tissues, especially muscles, impairs their ability to function normally.

License Grant

License grants the Licensee  exclusive, worldwide rights to AXO-AAV-OPMD utilizing proprietary Silence-and-Replace technology, which suppresses mutant protein production while restoring expression of functional protein.   License also grants rights to five additional investigational gene therapy products for neurological conditions.

License Property

An investigational Silence-and-Replace gene therapy program for the treatment of oculopharyngeal muscular dystrophy.  The Silence-and-Replace gene therapy technology is designed to deliver a combination of DNA-directed RNA interference (silence) along with a functional copy of the gene (replace) in a single vector construct.

Field of Use

The AXO-AAV-OPMD Program is an investigational gene therapy being developed as a one-time treatment for oculopharyngeal muscular dystrophy.

Oculopharyngeal muscular dystrophy (OPMD) is a rare genetic muscle disorder with onset during adulthood most often between 40 and 60 years of age. OPMD is characterized by slowly progressive muscle disease (myopathy) affecting the muscles of the upper eyelids and the throat.