Beacon Therapeutics (USA) Profile
Applied Genetic Technologies Corporation operates as a clinical-stage biotechnology company that uses its proprietary gene therapy platform technology to develop transformational genetic therapies for people suffering from rare and debilitating diseases. The company’s initial focus is in the field of ophthalmology, where it has wholly owned clinical-stage programs in X-linked retinitis pigmentosa (XLRP) and achromatopsia (ACHM), and an optogenetics program through its collaboration with Bionic Sight, Inc. (Bionic Sight). The company’s preclinical pipeline includes a program in dry age-related macular degeneration (dAMD), two programs targeting central nervous system (CNS) disorders, including frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), and a program in otology through its collaboration with Otonomy, Inc. (Otonomy).
In May 2022, the company released interim, masked, clinical data from the Skyline trial in its XLRP program and it has 24-month data from the XLRP Phase 1/2 trial (Horizon). In addition to its product pipeline, the company developed broad technological and manufacturing capabilities, utilizing its internal scientific resources and collaborating with others.
Strategy
The key elements of the company’s strategy are to advance its pipeline of gene therapies to treat inherited retinal diseases (IRDs) with an initial focus on ophthalmology; further develop our manufacturing capabilities; and selectively invest in its platform and its clinical and preclinical product candidates.
Product Candidate Pipeline
AGTC-501 for the treatment of XLRP
AGTC-501 (laruparetigene zosaparvovec), the company’s lead gene therapy development program for the treatment of XLRP, is designed to use an engineered AAV vector to insert a stabilized and functional copy of the RPGR gene into the patient’s photoreceptor cells. AGTC-501 is consisted of a stabilized RPGR gene and a promoter that was specifically selected to drive efficient gene expression in primate rods and cones, maintain photoreceptor function and delay disease progression in preclinical models of disease.
The company is conducting multiple clinical trials of AGTC-501 that are intended to support the potential submission of a Biologics License Application (BLA), including a Phase 1/2 trial, or Horizon, which incorporates an expansion portion that it refers to as the Skyline trial.
AGTC-401 and AGTC-402 for the treatment of ACHM
The company is developing two gene therapy product candidates for the treatment of ACHM. The product candidates are designed to use the same engineered AAV vector to insert a stabilized and functional copy of the Cyclic Nucleotide Gated Channel Subunit Beta 3 (CNGB3) gene in the case of AGTC-401 and a stabilized and functional copy of the Cyclic Nucleotide Gated Channel Subunit Alpha 3 (CNGA3) gene in the case of AGTC-402. The company choses the promoter based on data from preclinical studies that showed the promoter drove efficient gene expression in all three types of primate cone photoreceptors and restored cone photoreceptor function in dog, mouse and sheep models of ACHM.
The company is conducting a Phase 1/2 clinical trial of AGTC-401 in ACHM patients with mutations of the CNGB3 gene (ACHMB3) and a separate Phase 1/2 clinical trial of AGTC-402 in ACHM patients with mutations of the CNGA3 gene (ACHMA3). Each Phase 1/2 clinical trial is being conducted at multiple clinical sites that specialize in inherited retinal diseases.
The company defines two pediatric patients (17 and 7 years old) in the 1.1E+12 vg/mL dose group as responders based on improvements in visual sensitivity as measured by the Octopus static perimeter. The company also reported updated interim 3-month pediatric data and adult and pediatric safety data for the 24 patients enrolled in the Phase 1/2 study of AGTC-402 targeting CNGA3 mutations in patients with ACHMA3. The company intends to continue to follow the ACHMA3 patients for long-term safety observations.
The company had a collaborative and productive End of Phase 2 (EOP2) meeting with the FDA to discuss the potential future development of AGTC-401 and received constructive feedback from the FDA on its proposed primary and secondary endpoints for a Phase 2/3 clinical trial.
Product Candidate to Treat Advanced Retinal Disease
In partnership with Bionic Sight, Inc. (Bionic Sight), the company provided preclinical and IND application support in Bionic Sight’s development of an optogenetic candidate treatment for individuals with retinitis pigmentosa (RP) who have lost light sensitivity. RP is a large group of inherited retinal disorders in which progressive degeneration of photoreceptors or retinal pigment epithelium (RPE) leads to vision loss that is independent of a patients’ genetic mutation. In Europe and the United States, about 200,000 patients suffer from RP and every year between 15,000 and 20,000 patients with RP suffer vision loss.
Preclinical Pipeline Programs
The company’s advanced gene therapy platform will enable it to develop and test new adeno-associated virus (AAV) vectors that carry gene sequences both for other inherited diseases in ophthalmology (it is estimated that approximately 290 genes causing inherited retinal disease have been identified), as well as larger ocular indications for which intervention at a specific target gene or pathway has been clearly identified.
The company is seeking to the augment Progranulin (PGRN) levels in order to restore its physiological balance, and this approach is supported by several studies in PGRN-deficient mouse models, where both the pathological and behavioral changes that occur as a result of PGRN loss have been rescued.
Strategic collaborations
The company has formed strategic alliances in which both parties contribute expertise to enable the discovery and development of potential gene therapy product candidates.
On October 1, 2019, the company entered a strategic collaboration with Otonomy, Inc. (Otonomy), a San Diego based biopharmaceutical company focused on neurotology.
On February 2, 2017, the company entered into a strategic research and development collaboration agreement with Bionic Sight to develop therapies for patients with visual deficits and blindness due to retinal disease. Through the AGTC-Bionic Sight collaboration, the companies are seeking to develop a new optogenetic therapy that leverages its deep experience in gene therapy and ophthalmology and Bionic Sight’s innovative neuro-prosthetic device and algorithm for retinal coding.
Bionic Sight is responsible for conducting the Phase 1/2 clinical trial, which enrolled its first patient in March 2020.
In April 2021, the company announced a licensing agreement with TeamedOn International, Inc., a biotechnology company dedicated to advancing gene therapies for rare diseases, including ophthalmic indications, to advance gene therapy to treat X-linked retinoschisis, or XLRS, an inherited disease that causes loss of vision due to degeneration of the retina in males. Under the terms of the agreement, the company will provide TeamedOn with the clinical trial material, preclinical and clinical data generated for the development of its investigational intravitreal gene therapy candidate, rAAV2tYF-CB-hRS1.
In April 2021, the company announced a licensing agreement to provide its proprietary cone specific promoter technology to SparingVision SAS, a genomic medicine company developing vision saving treatments for ocular diseases.
Relationship with the University of Florida (UF)
As of July 31, 2022, the company had four agreements wherein it licensed seven U.S. patents and multiple pending applications covering inventions made at UF.
Intellectual property
As of July 31, 2022, the company’s patent portfolio included 119 patents and patent applications that it owned and 69 patents and patent applications that it had exclusively licensed. More specifically, as of such date, the company owned 3 U.S. patents, 12 pending U.S. patent applications, 49 foreign patents and 55 foreign patent applications. As of July 31, 2022, the company in-licensed 7 U.S. patents, 2 pending U.S. patent applications, 58 foreign patents and 2 pending foreign patent applications. Of the patents and patent applications that the company owned or in-licensed, 37 covered methods to manufacture AAV vectors, the longest lived and most significant of which is expected to expire in 2029. In October 2017, the company was awarded U.S. Patent Number 9,783,826 directed to methods of producing recombinant AAV viral particles using suspension BHK cells. This patent extends the protection on the company’s AAV manufacturing platform from 2025 to 2029.
The company’s owned and in-licensed patent portfolio includes, but is not limited to, patents and patent applications directed to its XLRP and ACHM programs, as well as its foundational AAV production platform. The issued patents that are material to the company’s business are expected to expire on various dates from 2022 to 2029.
License Agreements
The University of Florida
As of July 31, 2022, the company had four agreements with the University of Florida Research Foundation, or UFRF, an affiliate of the University of Florida, or UF, of which the principal licenses are as follows:
A joint license from UFRF and Johns Hopkins University, or JHU, signed in October 2003 related to a particular herpes simplex virus (HSV) construct and various compositions thereof. The company had an exclusive license in all fields of use. The longest-lived patent covered by this license expired on September 23, 2022, and this license is terminated.
Two licenses from UFRF, signed in September and November 2012, respectively, relate to the use of engineered AAV capsids. The company has an exclusive license to the patents covered by the November 2012 license in the fields of ACHM, XLRS and XLRP and a semi-exclusive license in all other fields of orphan ophthalmology. The company has a non-exclusive license in all fields of use with respect to the patents covered by the September 2012 license.
On April 20, 2020, the company amended the capsid license to add further rights to these licenses in exchange for a non-exclusive grant-back of the intellectual property for use by UF investigators to enable research on four gene targets that are not of strategic interest to it. The longest-lived patent covered by these licenses is expected to expire in 2029. There are also patent applications pending under these licenses.
Research and Development
The company’s research and development expenses were $49.5 million for the year ended June 30, 2022.
Government Regulations
Within the FDA, the Center for Biologics Evaluation and Research, or CBER, regulates gene therapy products, and the company’s communication is specifically with the Office of Tissues and Advanced Therapeutics within CBER. Before clinical testing of biological products may begin, the company must submit an investigational new drug (IND) which must go into effect, and each clinical trial protocol for a gene therapy product candidate is reviewed by the United States Food and Drug Administration (the FDA).
History
Applied Genetic Technologies Corporation was founded in 1999. The company was incorporated in Florida in 1999 and reincorporated in Delaware in 2003.
