Benzinga | Nov 13, 2020 08:07AM EST

NGM Biopharma Reports Presentation Of Phase 1 Safety, Pharmacokinetics Data For NGM621 In Patients With Geographic Atrophy At American Academy Of Ophthalmology Virtual

NGM Biopharmaceuticals, Inc. (NASDAQ:NGM), a biotechnology company focused on discovering and developing transformative therapeutics for patients, announced that findings from its Phase 1 clinical study of NGM621, an anti-complement C3 antibody, in patients with geographic atrophy (GA) were presented today at the American Academy of Ophthalmology 2020 Virtual. The poster presentation titled, "Inhibition of Complement Component 3 in GA With NGM621: Phase 1 Dose-Escalation Study Results," was given by the study's lead investigator Charles C. Wykoff, M.D., Ph.D., Director of Research at Retina Consultants Houston and the Greater Houston Retina Research Foundation. The presentation is available on the NGM Bio website here.

The primary objective of the Phase 1 trial was to assess the safety and tolerability of single and multiple intravitreal (IVT) injections of NGM621 in patients with GA. Secondary objectives were to characterize the serum PK of single or multiple doses of NGM621. The study enrolled 15 patients across three single-ascending dose cohorts of NGM621, 2 mg, 7.5 mg and 15 mg, the maximum planned dose in the study, and a multiple dose cohort that received two 15 mg doses separated by four weeks. Patients were dosed sequentially and followed closely over 12 weeks.

In the study, NGM621 was well tolerated, with no patients experiencing serious adverse events (SAEs), drug-related adverse events (AEs), intraocular inflammation, endophthalmitis or choroidal neovascularization (CNV). No dose-related safety patterns or concerns were reported. Ocular AEs observed were mild in severity and representative of those commonly associated with IVT injections. No vision-related safety signals were detected. On average, patients maintained their visual acuity over the 12-week follow-up study duration.

The serum PK of NGM621 was linear and dose-proportional. Based on ocular PK/PD modeling, NGM621 is predicted to achieve >90% reduction in free C3 in the eye for 7 weeks following a single IVT dose of 15 mg. Taken together, the PK profile of NGM621 demonstrated in the Phase 1 study and subsequent PK/PD modeling support up to an every eight-week (or every other month) dosing regimen of NGM621 at the 15 mg dose level. NGM621 serum exposure was below concentrations expected to produce systemic complement inhibition after IVT injection of the 15 mg dose. No anti-drug antibodies were detected in any patient at any timepoint.

"The findings from this first-in-human study of NGM621 in patients with geographic atrophy give us important insights regarding the potential of this therapeutic to address this progressive and devastating disease," said Dr. Wykoff. "The favorable safety and tolerability profile seen in this study, combined with the potential for every other month dosing suggest NGM621 may be valuable as a complement C3 inhibitor to treat geographic atrophy. I look forward to continuing to advance our clinical understanding of NGM621 in the ongoing, double-masked Phase 2 CATALINA study."

GA, an advanced form of age-related macular degeneration, is a progressive retinal degenerative disease associated with irreversible loss of vision, diminished quality of life and eventual blindness. Dysregulated activation of the complement system, a key component of the immune system, has been implicated in the onset and progression of GA. NGM621 is a humanized IgG1 monoclonal antibody engineered to potently inhibit activity of complement C3. It is being tested in the Phase 2 CATALINA trial to evaluate its effects on disease progression when given every four weeks or every eight-weeks.

"We are very pleased to see NGM621's exciting preclinical data now translating in the clinic as expected. These results support our belief that NGM621 may have a highly differentiated therapeutic profile in the complement inhibition space, and we look forward to building on this body of data with our ongoing Phase 3-enabling CATALINA study," said Hsiao D. Lieu, M.D., Chief Medical Officer at NGM Bio. "We recognize the difficult and far-reaching impact geographic atrophy can have on patients' quality of life, and we are committed to advancing this promising therapeutic candidate for these patients."

More details on the Phase 2 CATALINA study can be found at this link on clinicaltrials.gov.