A Randomized, Controlled, Masked, Multi-center Study Evaluating the Efficacy, Safety, and Tolerability of Two Doses of AGTC-501 Compared to an Untreated Control Group in Male Participants With X-linked Retinitis Pigmentosa

This study will evaluate and compare the safety, efficacy, and tolerability of 2 doses of a recombinant adeno-associated virus vector (AGTC-501) to an untreated control group in male participants with X-linked retinitis pigmentosa caused by RPGR mutations.

Start Date14 Mar 2024

Sponsor / Collaborator-

NCT06275620 / Enrolling by invitationPhase 2

A Phase 1/2 Open-Label Dose Escalation Study to Evaluate the Safety and Efficacy of AGTC-501 (rAAV2tYF-GRK1-RPGR) and a Phase 2 Randomized, Controlled, Masked, Multi-center Study Comparing Two Doses of AGTC-501 in Male Participants With X-linked Retinitis Pigmentosa

This Phase 2 study is a non-randomized, open-label, study of the safety of AGTC-501 in participants with XLRP who have previously been treated with a full-length AAV vector-based gene therapy targeting RPGR protein.

Start Date14 Nov 2023

Sponsor / Collaborator-

NCT06333249 / Active, not recruitingPhase 2

This study will evaluate the safety and efficacy of a recombinant adeno-associated virus vector (rAAV2tYF-GRK1-RPGR) in patients with X-linked retinitis pigmentosa caused by RPGR mutations.

Start Date13 Apr 2021

Sponsor / Collaborator

Beacon Therapeutics (USA), Inc.

100 Clinical Results associated with Laruparetigene zosaparvovec

100 Translational Medicine associated with Laruparetigene zosaparvovec

100 Patents (Medical) associated with Laruparetigene zosaparvovec

Literatures (Medical) associated with Laruparetigene zosaparvovec

01 Feb 2020·Human gene therapyQ2 · MEDICINE

Toxicity and Efficacy Evaluation of an Adeno-Associated Virus Vector Expressing Codon-Optimized RPGR Delivered by Subretinal Injection in a Canine Model of X-linked Retinitis Pigmentosa

Q2 · MEDICINE

Article

Author: Dufour, Valérie L. ; Weinstein, Nicole M. ; Swider, Malgorzata ; Cideciyan, Artur V. ; Beltran, William A. ; Habecker, Perry L. ; Ying, Gui-Shuang ; Pan, Wei ; Timmers, Adrian ; Robinson, Paulette M. ; Shearman, Mark S. ; Jacobson, Samuel G. ; Ye, Guo-jie ; Knop, David R. ; Durham, Amy C. ; Song, Chunjuan ; Chulay, Jeffrey D. ; Aguirre, Gustavo D.

Applied Genetic Technologies Corporation (AGTC) is developing a recombinant adeno-associated virus (rAAV) vector AGTC-501, also designated rAAV2tYF-GRK1-hRPGRco, to treat X-linked retinitis pigmentosa (XLRP) in patients with mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. The vector contains a codon-optimized human RPGR cDNA (hRPGRco) driven by a photoreceptor-specific promoter (G protein-coupled receptor kinase 1 [GRK1]), and is packaged in an AAV2 capsid variant with three surface tyrosine residues changed to phenylalanine (AAV2tYF). We conducted a toxicity and efficacy study of this vector administered by subretinal injection in the naturally occurring RPGR mutant (X-linked progressive retinal atrophy 2 [XLPRA2]) dog model. Sixteen RPGR mutant dogs divided into four groups of three to five animals each received either a subretinal injection of 0.07 mL of AGTC-501 at low (1.2 × 10¹¹ vector genome [vg]/mL), mid (6 × 10¹¹ vg/mL), or high dose (3 × 10¹² vg/mL), or of vehicle control in the right eye at early-stage disease. The left eye remained untreated. Subretinal injections were well tolerated and were not associated with systemic toxicity. Electroretinography, in vivo retinal imaging, and histological analysis showed rescue of photoreceptor function and structure in the absence of ocular toxicity in the low- and mid-dose treatment groups when compared with the vehicle-treated group. The high-dose group showed evidence of both photoreceptor rescue and posterior segment toxicity. These results support the use of AGTC-501 in clinical studies with patients affected with XLRP caused by RPGR mutations and define the no-observed-adverse-effect level at 6 × 10¹¹ vg/mL.

01 Dec 2018·Human gene therapy. Clinical development

Toxicology and Pharmacology of an AAV Vector Expressing Codon-Optimized RPGR in RPGR-Deficient Rd9 Mice

Article

Author: Plummer, Cayrn ; Hauswirth, William W. ; Zhu, Ping ; Ye, Guo-jie ; Sharma, Alok K. ; Timmers, Adrian ; Robinson, Paulette M. ; Sonnentag, Peter ; Shearman, Mark S. ; Knop, David R. ; Van Hoosear, Mailin ; Chulay, Jeffrey D. ; Coleman, Kirsten E. ; Conlon, Thomas J ; Song, Chunjuan ; Green, Kari B. ; Mandapati, Savitri ; Deng, Wen-Tao

Applied Genetic Technologies Corporation (AGTC) is developing a recombinant adeno-associated virus (rAAV) vector AGTC-501, also designated AAV2tYF-GRK1-RPGRco, to treat retinitis pigmentosa (RP) in patients with mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. The vector contains a codon-optimized human RPGR cDNA (RPGRco) driven by a photoreceptor-specific promoter (G protein-coupled receptor kinase 1, GRK1) and is packaged in an AAV2 capsid with three surface tyrosine residues changed to phenylalanine (AAV2tYF). We conducted a safety and potency study of this vector administered by subretinal a injection in the naturally occurring RPGR-deficient Rd9 mouse model. Sixty Rd9 mice (20 per group) received a subretinal injection in the right eye of vehicle (control) or AAV2tYF-GRK1-RPGRco at one of two dose levels (4 × 10⁸ or 4 × 10⁹ vg/eye) and were followed for 12 weeks after injection. Vector injections were well tolerated, with no systemic toxicity. There was a trend towards reduced electroretinography b-wave amplitudes in the high vector dose group that was not statistically significant. There were no clinically important changes in hematology or clinical chemistry parameters and no vector-related ocular changes in life or by histological examination. Dose-dependent RPGR protein expression, mainly in the inner segment of photoreceptors and the adjacent connecting cilium region, was observed in all vector-treated eyes examined. Sequence integrity of the codon-optimized RPGR was confirmed by sequencing of PCR-amplified DNA, or cDNA reverse transcribed from total RNA extracted from vector-treated retinal tissues, and by sequencing of RPGR protein obtained from transfected HEK 293 cells. These results support the use of rAAV2tYF-GRK1-RPGRco in clinical studies in patients with XLRP caused by RPGR mutations.

News (Medical) associated with Laruparetigene zosaparvovec

15 Oct 2024

·pipelinereview.com

Beacon Therapeutics Announces Positive 24-Month Data from Phase 2 SKYLINE Trial of AGTC-501 in Patients with X-Linked Retinitis Pigmentosa

LONDON, UK and CAMBRIDGE, MA, USA I October 15, 2024 I Beacon Therapeutics Holdings Limited (‘Beacon Therapeutics’ or ‘the Company’), a leading ophthalmic gene therapy company with a purpose to save and restore the vision of patients with blinding retinal diseases, today announced the presentation of 24-month interim safety and efficacy results of the Phase 2 SKYLINE trial in patients with XLRP at the American Academy of Ophthalmology’s Annual Meeting in Chicago, Illinois. The 24-month data showed a response rate of 57% (4/7) in study eyes treated with a high dose (6.8 E+11 vg/eye) of AGTC-501, defined as a patient who has an improvement in retinal sensitivity as assessed by microperimetry of at least 7 decibels (dB) in at least 5 loci. Patients in the high-dose cohort also showed a robust improvement in mean retinal sensitivity. Study eyes treated with a low dose (7.5 E+10 vg/eye) of AGTC-501 showed a response rate of 25% (1/4). There were no clinically significant safety events associated with AGTC-501 treatment in this trial, and any treatment-emergent adverse events were mostly non-serious and mild to moderate in severity. XLRP is a severe, aggressive, inherited retinal disease that often leads to blindness by middle age, with no treatment options available. XLRP primarily affects an estimated 3.4 – 4.4 per 100,000 young males with RPGR mutations in US, Europe and Australia. AGTC-501 expresses the full length RPGR protein and is therefore expected to address the entirety of photoreceptor damage caused by XLRP, including both rod and cone loss, making it uniquely well-suited to improve the lives of patients with XLRP as a potential treatment. Lance Baldo, MD, Chief Executive Officer of Beacon Therapeutics, stated, “Our Phase 2 SKYLINE 24-month data reinforces AGTC-501’s favorable safety profile and robust improvements in mean retinal sensitivity. We will continue to assess the long-term safety and durability of AGTC-501 but are encouraged by the results we’ve seen in the SKYLINE trial to date.” Beacon Therapeutics is also enrolling its pivotal Phase 2/3 VISTA and open-label Phase 2 DAWN trials as the Company progresses toward the development of a treatment for XLRP. Poster – Subretinal AGTC-501 Gene Therapy for XLRP: 24-Month Interim Results of the Phase 2 SKYLINE Trial. Presenting Author – Robert Sisk, MD, FACS, FASRS, Associate Professor of Ophthalmology at the University of Cincinnati; Vitreoretinal Surgeon and partner at Cincinnati Eye Institute; Director of Pediatric Retinal Surgery and Director of Ophthalmic Genetics at Cincinnati Children’s Hospital. Contact: info@beacontx.com Media: beacontherapeutics@edelman.com About Beacon Therapeutics Beacon Therapeutics is an ophthalmic gene therapy company founded in 2023 to save and restore the vision of patients with a range of prevalent and rare retinal diseases that result in blindness. The Company has an established scientific foundation that combines a late-stage development candidate to treat X-linked retinitis pigmentosa (XLRP), as well as two preclinical programs, one targeting dry age-related macular degeneration (AMD) and another targeting an inherited cone-rod dystrophy (CRD). Beacon Therapeutics also has access to a target generation technology platform that will identify, screen, and search secreted proteins in the ophthalmology space. Lead development candidate AGTC-501, is a gene therapy program currently being investigated for the treatment of XLRP, an inherited monogenic recessive disorder that causes progressive vision loss, primarily in boys and young men. XLRP is predominantly caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. AGTC-501 expresses the full length RPGR protein, thereby addressing the full complement of photoreceptor damage caused by XLRP, including both rod and cone loss. Beacon is supported by funds from Syncona Limited, Forbion, Oxford Science Enterprises, TCGX, Advent Life Sciences and additional investors. Find out more about Beacon Therapeutics at beacontx.com. SOURCE: Beacon Therapeutics Holdings

Phase 2Clinical ResultGene Therapy

23 Sep 2024

·www.fiercepharma.com

Rejuveron Life Sciences rejuvenates as Centenara Labs

Swiss anti-aging biotech Rejuveron's most advanced med is the early clinical stage EA-2353 program, in trials for retinitis pigmentosa, which can cause vision loss. Swiss anti-aging biotech Rejuveron is seeking its rejuvenation as it morphs into Centenara Labs.The biotech, as Rejuveron Life Sciences AG, raised $75 million in dual tranche series B and convertible loan financing one year ago this month and is focused on a small-molecule approach to regenerate endogenous stem cells.Its most advanced med is the early clinical stage EA-2353 program, in trials for retinitis pigmentosa (RP), which can cause vision loss. This month, new data for the med have also been released, which shows “encouraging preliminary results,” predominately in safety.While the startup is still at the beginning of its journey, the name change comes amid a “wider rebranding initiative” set up for “differentiation in the marketplace,” as well as boosting awareness of the company, it said in a statement.Several companies are in clinical trials are seeking to treat RP, including gene therapy biotech Beacon Therapeutics, which is working on AGTC-501, a phase 2/3 therapy for the treatment of X-linked RP.Nanoscope Therapeutics is also using a gene therapy approach with MCO-010, which saw positive data presented earlier this year.“Our transition to Centenara is a bold and forward-thinking step that aligns with our strategic vision and represents more than just a new name; it underscores a renewed focus on working together to build a business that can successfully develop therapies for regenerative medicine and age-related disorders,” said Aksana Labokha, CEO of Centenara.“Our updated visual identity demonstrates our evolution and sets us apart within the biotechnology sector putting a focus on the drivers of an extended quality of life.”Biotechs focusing on aging have reveled in the hype over the years, though some struggled as that initial hype failed to live up to expectations. This includes anti-aging biotech Unity Biotechnology, which was forced to ditch its leading knee pain program in 2020 after it failed a key midstage test.Another anti-aging biotech, AgeX Therapeutics, also saw trouble and appeared locked in limbo for years as it consistently warned that its cash was about to run out while its preclinical pipeline stalled. It had a reprieve last year when Serina Therapeutics decided to act on the opportunity to leverage AgeX’s public listing and merge with the company.

Gene TherapyAcquisition

19 Sep 2024

·www.prnewswire.com

Beacon Therapeutics Presents 36-Month Interim Results from Phase I/2 HORIZON Trial of AGTC-501 in Patients with XLRP

LONDON and CAMBRIDGE, Mass., Sept. 19, 2024 /PRNewswire/ -- Beacon Therapeutics Holdings Limited ('Beacon' or 'the Company'), a leading ophthalmic gene therapy company with a purpose to save and restore the vision of patients with blinding retinal diseases, today presented 36-month interim results from its Phase I/2 HORIZON trial of its lead asset, AGTC-501, in patients with X-linked retinitis pigmentosa (XLRP) at the 24th EURETINA Congress held in Barcelona, Spain. Key presentation highlights included: AGTC-501 was reported to be generally safe and well-tolerated in the 29 patients enrolled with no clinically significant safety events related to the therapy. Data also demonstrated that a difference in visual function between the treated and untreated eyes was still observed at month 36. The benefit-risk profile of AGTC-501 supports ongoing clinical development for the treatment of patients with XLRP caused by RPGR mutations. Lance Baldo, MD, Chief Executive Officer of Beacon, stated, "This emerging longer-term data is another clinical validation of the safety of AGTC-501 for the treatment of XLRP. We look forward to achieving several upcoming clinical milestones, including 24-month data from the Phase 2 SKYLINE trial in XLRP later this year, and continued enrollment into our open-label Phase 2 DAWN trial and Phase 2/3 VISTA trial." HORIZON is a Phase 1/2, open-label, dose-escalation study of patients with XLRP treated with subretinal AGTC-501, which has completed enrollment of 29 male participants and all participants are in long-term follow-up. Presentation – Subretinal Gene Therapy Drug AGTC-501 for X-Linked Retinitis Pigmentosa (XLRP) Phase 1/2 Multicenter Study (HORIZON): 36-Month Interim Results Presenter – Paul Yang, MD, PhD, Chief, Paul H. Casey Ophthalmic Genetics Division, Casey Eye Institute, OHSU The presentation took place on Thursday, September 19th at 15:30 CEST. About Beacon Therapeutics Beacon Therapeutics is an ophthalmic gene therapy company founded in 2023 to save and restore the vision of patients with a range of prevalent and rare retinal diseases that result in blindness. The Company has an established scientific foundation that combines a late-stage development candidate to treat X-linked retinitis pigmentosa (XLRP), as well as two preclinical programs, one targeting dry age-related macular degeneration (AMD) and another targeting cone-rod dystrophy (CRD). Beacon Therapeutics also has access to a target generation technology platform that will identify, screen, and search secreted proteins in the ophthalmology space. Lead development candidate AGTC-501, is a gene therapy program currently being investigated for the treatment of XLRP, an inherited monogenic recessive disorder that causes progressive vision loss, primarily in boys and young men. XLRP is predominantly caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. AGTC-501 expresses the full length RPGR protein, thereby addressing the full complement of photoreceptor damage caused by XLRP, including both rod and cone loss. Beacon is supported by funds from Syncona Limited, Forbion, Oxford Science Enterprises, TCGX, Advent Life Sciences and additional investors. Find out more about Beacon Therapeutics at beacontx.com. Contact: [email protected] Media: [email protected] SOURCE Beacon Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultGene TherapyPhase 2

100 Deals associated with Laruparetigene zosaparvovec

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Indication	Highest Phase	Country/Location	Organization	Date
X-linked retinitis pigmentosa	Phase 3	US	-	14 Mar 2024
X-linked retinitis pigmentosa	Phase 3	AU	-	14 Mar 2024
X-linked retinitis pigmentosa	Phase 3	GB	-	14 Mar 2024
Retinitis Pigmentosa	Phase 3	-	Beacon Therapeutics (USA), Inc.	05 Apr 2021

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06333249 (SKYLINE, Company_Website) Manual	Phase 2	X-linked retinitis pigmentosa	-	AGTC-501	odljsgyiox(pjvbsqyqtl) = nnbjmewnbn hswarhfamz (emybpgiljo )	Positive	15 Oct 2024
EURETINA2024	Not Applicable	X-linked retinitis pigmentosa	-	AGTC-501	trwfnxyend(vcwhzciybg) = No SUSARs or endophthalmitis were reported out to Month 36, and no participants early terminated due to a TEAE. Seven ocular SAEs were reported in 7 participants (retinal detachment [4], subcapsular cataract [1], glaucoma [1] and reduced visual acuity [1]). None of these were thought to be related to the investigational material. Of note, 3 of the retinal detachments occurred in periperally dosed patients. The TEAEs deemed related to AGTC-501 were all non-serious (mostly Grade 1-2 in severity), except one Grade 3 retinal depigmentation in the highest dose group which was not associated with any visual sequelae. Temporally, 73% of ocular TEAEs occurred within 3 months of AGTC-501 administration, 52% of which resolved within 1 month of onset. irikdgtkyw (hguaerbign )	-	19 Sep 2024
Horizon (EURETINA2023)	Phase 1/2	X-linked retinitis pigmentosa	29	AGTC-501	boeyoxwgby(xoupvlwahd) = All non-serious (mostly Grade 1-2 in severity), except one Grade 3 retinal depigmentation rfadieweek (arobkqxzbk ) View more	Positive	05 Oct 2023

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