PPY988 / Novartis - LARVOL DELTA

Gene Therapy in Age-related Macular Degeneration. (PubMed, Int Ophthalmol Clin) - "Current trials in wet AMD include ADVM-022 and RGX-314. Current trials in dry AMD include GT-005 and JNJ-1887."

Journal • Review • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

HORIZON: A Phase 2 Study to Evaluate the Safety and Efficacy of Two Doses of GT005/PPY988 in Patients With Geographic Atrophy (AAO 2024) - "Incidence of ocular serious adverse events was 2.3%, 5.8% and 0%, respectively. Conclusions Based on the interim results (Week 48), the benefit-risk profile of PPY988 was not favorable for further development in GA."

Clinical • P2 data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Ophthalmology

HORIZON: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005 (clinicaltrials.gov) - P2 | N=255 | Terminated | Sponsor: Gyroscope Therapeutics Limited | Active, not recruiting ➔ Terminated; The study was terminated due to the interim analysis demonstrating lack of treatment efficacy.

Trial termination • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

FOCUS: A Phase I/II First in Human Study to Evaluate the Safety and Efficacy of GT005 Administered in Subjects With Dry AMD (clinicaltrials.gov) - P1/2 | N=56 | Terminated | Sponsor: Gyroscope Therapeutics Limited | Active, not recruiting ➔ Terminated; The study was terminated due to the interim analysis demonstrating lack of treatment efficacy

Trial termination • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

EXPLORE: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005 (clinicaltrials.gov) - P2 | N=98 | Terminated | Sponsor: Gyroscope Therapeutics Limited | Active, not recruiting ➔ Terminated; The study was terminated due to the interim analysis demonstrating lack of treatment efficacy.

Trial termination • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

EXPLORE: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005 (clinicaltrials.gov) - P2 | N=98 | Active, not recruiting | Sponsor: Gyroscope Therapeutics Limited | Terminated ➔ Active, not recruiting | Trial completion date: Aug 2023 ➔ Mar 2024 | Trial primary completion date: Aug 2023 ➔ Mar 2024

Enrollment closed • Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

FOCUS: A Phase I/II First in Human Study to Evaluate the Safety and Efficacy of GT005 Administered in Subjects With Dry AMD (clinicaltrials.gov) - P1/2 | N=56 | Active, not recruiting | Sponsor: Gyroscope Therapeutics Limited | Terminated ➔ Active, not recruiting | Trial completion date: Aug 2023 ➔ Jun 2024 | Trial primary completion date: May 2023 ➔ Jun 2024

Enrollment closed • Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

HORIZON: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005 (clinicaltrials.gov) - P2 | N=255 | Active, not recruiting | Sponsor: Gyroscope Therapeutics Limited | Terminated ➔ Active, not recruiting | Trial completion date: Aug 2023 ➔ Jun 2024 | Trial primary completion date: Aug 2023 ➔ Jun 2024

Enrollment closed • Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

ORACLE: A Long-term Follow-up Study to Evaluate the Safety of GT005 in Participants With Geographic Atrophy Secondary to Age-related Macular Degeneration Treated in a Gyroscope-sponsored Antecedent Study (clinicaltrials.gov) - P2 | N=225 | Enrolling by invitation | Sponsor: Gyroscope Therapeutics Limited | Phase classification: P=N/A ➔ P2 | Trial completion date: Sep 2028 ➔ Jun 2028

Phase classification • Trial completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

EXPLORE: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005 (clinicaltrials.gov) - P2 | N=98 | Terminated | Sponsor: Gyroscope Therapeutics Limited | N=75 ➔ 98 | Trial completion date: Nov 2025 ➔ Aug 2023 | Recruiting ➔ Terminated | Trial primary completion date: Nov 2024 ➔ Aug 2023; Terminated for interim analysis demonstrating futility (trial highly unlikely to meet efficacy outcome). The trial is not ending early because of medical problems or concerns.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

HORIZON: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005 (clinicaltrials.gov) - P2 | N=255 | Terminated | Sponsor: Gyroscope Therapeutics Limited | Trial completion date: Sep 2025 ➔ Aug 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Sep 2024 ➔ Aug 2023; Terminated for interim analysis demonstrating futility (trial highly unlikely to meet efficacy outcome). The trial is not ending early because of medical problems or concerns.

Trial completion date • Trial primary completion date • Trial termination • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

FOCUS: A Phase I/II First in Human Study to Evaluate the Safety and Efficacy of GT005 Administered in Subjects With Dry AMD (clinicaltrials.gov) - P1/2 | N=56 | Terminated | Sponsor: Gyroscope Therapeutics Limited | Trial completion date: Jan 2027 ➔ Aug 2023 | Active, not recruiting ➔ Terminated; Terminated for interim analysis demonstrating futility (trial highly unlikely to meet efficacy outcome). The trial is not ending early because of medical problems or concerns.

Trial completion date • Trial termination • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Complement factor I: Regulatory nexus, driver of immunopathology, and therapeutic. (PubMed, Immunobiology) - "Supplementation of FI using plasma purified or recombinant protein has long been postulated, however, technical difficulties prevented progression into clinical trials. It is only using gene therapy that CFI supplementation has reached the clinic with GT005 in phase I/II clinical trials for geographic atrophy."

Journal • Age-related Macular Degeneration • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Dry Age-related Macular Degeneration • Gene Therapies • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Lupus • Macular Degeneration • Ophthalmology • Retinal Disorders

HORIZON: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005 (clinicaltrials.gov) - P2 | N=255 | Active, not recruiting | Sponsor: Gyroscope Therapeutics Limited | Recruiting ➔ Active, not recruiting

Enrollment closed • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

EXPLORE: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005 (clinicaltrials.gov) - P2 | N=75 | Recruiting | Sponsor: Gyroscope Therapeutics Limited | Trial completion date: Feb 2024 ➔ Nov 2025 | Trial primary completion date: Feb 2023 ➔ Nov 2024

Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Gene targeting as a therapeutic avenue in diseases mediated by the complement alternative pathway. (PubMed, Immunol Rev) - "This review explains key concepts of RNA and DNA targeting and discusses assets in clinical development for the treatment of diseases driven by the alternative pathway, including the RNA-targeting therapeutics ALN-CC5, ARO-C3, and IONIS-FB-LRX, and the gene therapies GT005 and HMR59. These therapies are but the spearhead of potential drug candidates that might revolutionize the field in coming years."

Journal • Review • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Gene Therapies • Hematological Disorders • Inflammation • Macular Degeneration • Ophthalmology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Retinal Disorders

FOCUS: First in Human Study to Evaluate the Safety and Efficacy of GT005 Administered in Subjects With Dry AMD (clinicaltrials.gov) - P1/2 | N=56 | Active, not recruiting | Sponsor: Gyroscope Therapeutics Limited | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2026 ➔ Jan 2027 | Trial primary completion date: Oct 2022 ➔ May 2023

Enrollment closed • Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

ORACLE: A Long-term Follow-up Study to Evaluate the Safety and Durability of GT005 in a Gyroscope-sponsored Antecedent Study (clinicaltrials.gov) - P=N/A | N=200 | Enrolling by invitation | Sponsor: Gyroscope Therapeutics Limited

New trial • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Preliminary Results from a Phase I/II Gene Therapy (FOCUS) of Subretinally Delivered GT005 in Patients With Geographic Atrophy Secondary to Age-Related Macular Degeneration (ASRS 2022) - No abstract available

Clinical • P1/2 data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders

Nonclinical Safety and Pharmacology of an Investigational Gene Therapy Targeting the Complement Pathway for the Treatment of Geographic Atrophy Secondary to Age-Related Macular Degeneration (GT005) (ASGCT 2022) - "GT005 was well tolerated with no safety findings outside the eye. GT005 led to local hCFI expression and wide-spread secretion of hCFI protein. Ocular dose-dependent inflammation-induced changes were observed, and correlated strongly with anti-hCFI antibody generation."

Clinical • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Gene Therapies • Immunology • Inflammation • Macular Degeneration • Ophthalmology • Retinal Disorders

GT005, an AAV Gene Therapy Targeting the Alternative Pathway of the Complement System for the Treatment of Geographic Atrophy (ASGCT 2022) - "Collectively, the non-clinical data provided here demonstrate the therapeutic potential of rAAV2-mediated expression of hCFI in slowing disease progression of GA by limiting complement-mediated inflammation in the posterior segment of the eye. More importantly, these data presented have paved the way for the evaluation of GT005 in Phase I and II clinical studies for GA secondary to AMD."

Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Gene Therapies • Immunology • Inflammation • Macular Degeneration • Ophthalmology • Retinal Disorders

In vivo expression and efficacy following subretinal delivery of GT005, an investigational gene therapy for the treatment of geographic atrophy (GA) (ARVO 2022) - "GT005 leads to expression of functional CFI protein in vitro and in vivo in mice, localizing to the target tissues that are affected in dry age-related macular degeneration (AMD). GT005 shows therapeutic efficacy in the mouse CNV model, a model of wet AMD in which complement activation plays a key pathophysiological role. These data support the therapeutic potential of GT005 for the treatment of GA by complement system modulation."

Preclinical • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Preliminary Results from a First-in-human Phase I/II Gene Therapy Study (FOCUS) of Subretinally Delivered GT005, an Investigational AAV2 Vector, in Patients with Geographic Atrophy Secondary to Age-related Macular Degeneration (ARVO 2022) - P1/2 | "GT005 had a positive safety profile at 2E10 to 2E11vg with no signs of GT005-related inflammation."

Clinical • P1/2 data • Age-related Macular Degeneration • Cataract • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Preclinical pharmacology and safety of GT005, an investigational gene therapy targeting the complement pathway for the treatment of Geographic Atrophy (ARVO 2022) - "GT005 was well tolerated with no safety findings outside the eye. GT005 led to local hCFI expression. Ocular dose-dependent inflammation-induced changes were observed, and correlated strongly with anti-hCFI antibody generation."

Preclinical • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Ophthalmology

HORIZON: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005 (clinicaltrials.gov) - P2 | N=250 | Recruiting | Sponsor: Gyroscope Therapeutics Limited | N=180 ➔ 250 | Trial completion date: Oct 2023 ➔ Oct 2025 | Trial primary completion date: Oct 2022 ➔ Oct 2024

Enrollment change • Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders