Enrollment completed in Phase 1 SAD study in patients with high-risk genetic variants for dry AMD.
Phase 1 topline results demonstrate promising safety profile, with no treatment-related adverse events as well as PK and biomarker changes in genetically defined dry AMD.
CAMBRIDGE, Mass. —(BUSINESS WIRE)— Gemini Therapeutics, a clinical stage precision medicine company developing innovative treatments for genetically defined Age-related Macular Degeneration (AMD) and linked ocular disorders, today announced the initiation of enrollment in its Phase 2a “ReGAtta” study. ReGAtta will evaluate GEM103, a recombinant, human Complement Factor H (CFH) for the treatment of patients with geographic atrophy (GA) secondary to dry AMD. Additionally, the Company announced that the Phase 1 study has completed enrollment. Topline results indicate the study met all its endpoints. AMD is the leading cause of irreversible blindness in the western world, affecting millions of people in the U.S. alone. At least 90% of AMD patients have dry AMD, for which there are no approved therapies. Loss of function variants at the factor H gene result in hyperactive (intra-ocular) complement activation and an overall failure to assist the retinal cells in maintaining activities in promoting the health of these cells. Administration of a factor H therapeutic in the ocular compartment at levels necessary for correct function can restore complement regulation and achieve retinal homeostasis.
“The ability to treat with no dose-limiting toxicity, and without inflammation is a critical benchmark of successful dry AMD therapy, and we look forward to the results of this clinical trial.”
“The results from this Phase 1 study underscore the potential of GEM103 as a directed treatment, combining genetic insights with a targeted, novel therapy that may potentially address the unmet need for a treatment for dry AMD,” said Arshad M. Khanani, MD, MA, Director of Clinical Research at Sierra Eye Associates, Reno, Nevada, and invesitgator in the Phase 1 trial. “The safety, pharmacokinetics, and pharmacodynamics data from the Phase 1 study supports the advancement of GEM103 to a Phase 2a study.”
“The Phase 2a ReGAtta clinical trial will provide important scientific insights about GEM103, and may ultimately provide physicians with a simultaneously well tolerated and genetically targeted therapeutic option for alleviating the burden of dry AMD,” said Marc Uknis, MD, Chief Medical Officer of Gemini Therapeutics. “The ability to treat with no dose-limiting toxicity, and without inflammation is a critical benchmark of successful dry AMD therapy, and we look forward to the results of this clinical trial.”
The Phase 2a, multi-center, open-label, multiple dose study in patients with GA secondary to dry AMD is designed to investigate the safety, pharmacokinetics and clinical effect of intravitreal (IVT) injections of GEM103 dosed either monthly or every other month in genetically defined subjects. As in the preceding Phase 1 study, the study will evaluate aqueous humor samples for pharmacokinetics and markers of inflammation. The study will enroll up to 80 patients and will include both patients who participated in the Phase 1 study, as well as a treatment-naïve, genetically enriched population.
Topline Phase 1 Results
The Phase 1 study was a single ascending dose (SAD) clinical study designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of intravitreal injections of GEM103 dosed either monthly or every other month. The Phase 1 portion of the study enrolled 12 patients in a genetically screened population with dry AMD and central GA.
In the four ascending doses tested, no dose limiting toxicities were observed. Additionally, there were no cases of inflammation, no anti-drug antibody, and no treatment-related adverse events. A single intra-vitreal injection of GEM103 resulted in prolonged suprahysiologic CFH that had an effect on biomarkers of complement hyperactivity as measured by aqueous humor taps.
About Dry AMD
AMD is a progressive retinal disease affecting older adults, and the leading cause of irreversible blindness in the western world, affecting millions. Symptoms, including blurry vision, loss of night vision and loss of central vision, make activities of daily living such as reading, driving and even recognizing faces more difficult over time. Dry AMD results from an interaction of both environmental and genetic risk factors. Aging and smoking confer the strongest non-genetic risk, but genetic risk is significant, with approximately 70% attributable risk of advanced disease to heritability. With CFH risk variants reported to occur in approximately 40% of patients with dry AMD, these patients are strongly associated with the risk of developing the disease and progression from intermediate AMD to GA. The complement system, of which CFH is a modulator, is dysregulated in patients with these risk variants, and results in amplification of aberrant inflammatory responses in the eye. Over time, this dysregulation leads to damage to the macular region of the retina. Research over the last decade has uncovered multiple genetic variants which can increase risk of developing advanced AMD by up to 20-fold. Gemini Therapeutics is examining many of these genetic variants through CLARITY, its natural history study in people with dry AMD.
About Gemini Therapeutics
Gemini Therapeutics is a clinical stage precision medicine company developing innovative treatments for age-related macular degeneration (AMD) and linked ocular disorders by developing drugging strategies that are matched to specific genetic mutations found in patients
with high clinical unmet need. Gemini’s lead clinical stage candidate, GEM103, is a recombinant form of the naturally occurring complement factor H protein currently in a Phase 2a trial. The company has generated a rich pipeline including recombinant proteins, gene therapies, and monoclonal antibodies. Gemini’s CLARITY natural history study is designed to provide unprecedented insight into the role of genetic risk in common retinal diseases and began in December 2018. Gemini was launched with funding from leading life science investors and powered by academic partnerships globally.
For more information, visit www.geminitherapeutics.com.