Apellis Eyeing 2017 Release of Phase II Results

Cedric Francois, CEO, Apellis Pharmaceuticals, hopes to deliver positive results to the company’s Phase II clinical trials of APL-2, a peptide targeting the C3 inhibitor in the complement cascade as a treatment for geographic atrophy (GA). The company has fully enrolled the Filly trial of APL-2. (APL-1 is targeting COPD.) The 240 patients in the trial have been divided into three groups – those who receive the treatment once a month, those receiving it every other month, and those in the sham arm of the study. By inhibiting complement, Apellis hopes to disrupt the formation of GA. Patients in the Filly trial will be tested to see if the pace of GA is slowing. Apellis will also test for telltale blood markers that would measure success. The primary endpoint is the change in square root GA lesion size from baseline at month 12 as measured by fundus autofluorescence (FAF). Francois says the company anticipates reading out the results in September 2017 and hopes to report at next year’s American Academy of Ophthalmology (AAO) meeting.


Cedric Francois

Dr. Francois is a co-founder of Apellis and has served as a member of our board of directors and as our President and Chief Executive Officer since September 2009.

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Cedric Francoiss: Apellis is a company that was born really out of another company that you might have heard of in the past called Potenza Pharmaceuticals. And we are a company focused on complement factor C3 as an inhibitory mechanism. We currently have 2 compounds in development, APL1 and APL2. We are not focused only on ophthalmology, but we are focused generally on immunology and the potential that C3 inhibition has to correct adaptive immunity. The two compounds that we currently have in development are APL 1 and APL2. APL1 does not apply to ophthalmology. It used to. Some of you might remember POT4. This is a drug that we applied to chronic obstructive pulmonary disease in an effort to modify that disease. APL2 was developed as a PEGylated version of APL1, and is given either once a day subcutaneously or intravitreally once a month or every other month in a clinical trial that I’m going to speak about today. So I won’t bore you with this, but the brief science behind what we do is something that we refer to as complement immunotherapy. And what that really means is that in the different diseases that we study, which seemingly we all think of as being very different, we see very similar underlying immunology taking place. And specifically in the local tissue of these conditions, you can find an interplay between antigen presenting cells and T-cells that regular immuno-modulatory therapies have a very hard time breaking out of, including, for example, steroids. And by inhibiting complement and specifically targeting what we call the fluid phase of complement, we see an opportunity to break that cycle. And that is something that we apply to 3 therapeutic areas at this point in time. One, are rare conditions with paroxysmal nocturnal hemoglobinuria, which some of you might know as the lead indication for Solaris, as our primary indication. And in that particular disease, what we are currently doing is clinically both in treatment-naïve patients with PNH as well as in patients with PNH who are treated with Solaris, but continue to be transfusion dependent, to find out if that has an effect on improving the conditions of these patients. We expect to have more data on that by the end of this year. Then in geographic atrophy, I want to talk a little bit more about a clinical trial that is now fully enrolled in geographic atrophy. I don’t think I need to explain to this audience what geographic atrophy is, but it’s the advanced stage of the dry form of the disease, where the atrophic lesions in the back of the eye continue to grow, and as most of you probably know, including in patients with wet AMD who have been on anti-VEGF agents for a long time, GA can start to occur. So something very important and which currently we don’t have any proved therapies, and where we hope to make a difference. What is unique about the target that we use, complement factor C3, is that it sits centrally in this famous/notorious complement cascade. And by inhibiting C3 as mentioned earlier today, you can inhibit all of the downstream effects of complement, regardless of the pathway that actually activates it. And many of you are probably familiar with the very exciting program that Genentech currently has in phase 3 with lampalizumab, where the alternative pathway of complement is inhibited for the purpose of reducing the growth of geographic atrophy. We saw very promising data, I think it was at the same conference, two years ago or three years ago now in Toronto. And it is a pathway that we think is very interesting, on one hand, from the disease modifying potential angle, and on the other hand, from the other advantages that potentially C3 could convey to this disease. So this is something that many of you probably have seen before. What we know from lampalizumab is that in patients who have a mutation in complement factor I, we see reduction of the atrophic growth by approximately 50%. The drug had to be injected every month, and one of the things that we would like to evaluate with APL2 is whether every other month injections work as well, because our health lives are very promising in that regard; and secondly, whether there is the potential to also have an effect on these patients that are not just predisposed, or as it appears to be from that phase 2 study, by their CFI mutation. So this is the trial that we currently have ongoing. We call it Filly because we are based in Kentucky, so we love horses. But it’s a human study. Two hundred and forty patients, randomized in two groups. Well, three groups I should say: sham, every month, and every other month injections with APL2. This is the design. That trial is currently fully enrolled, so we have 246 patients that we are following right now. We are going to read out that study in September of next year, and hopefully present it at AAO next year around, well, in a couple of months in October. The endpoints are very similar to what we saw in the Mahalo study, where we look at reducing the growth of geographic atrophy in the back of the eye, where we also have certain things that we look at with blood biomarkers in terms of the disease modifying potential of C3. And again, I wish I had more data to show to you, but that will be for next year. Thank you so much.