Allegro Ophthalmics is developing Luminate, a first-in-class anti-integrin peptide with a novel mechanism of action for both anti-angiogenesis and vitreolysis. The company is in late-stage development with multiple programs in Phase IIb or later.
According to Vicken Karageozian, MD, president of Allegro, about 400 human eyes have been treated with about 1,000 intravitreal injections to date, with a clean safety profile. Key non-clinical aspects of the Luminate program have been significantly de-risked, including composition of matter IP, solid pharmacokinetics and toxicology, and CMC (chemistry, manufacturing, and controls) packages.
As an anti-angiogenesis agent, Luminate could address DME and wet AMD via inhibition or regression of neovascularization, as well as inhibition of leakage, with increased durability. In diabetic macular edema (DME), the Phase IIb DEL MAR study is evaluating Luminate in multiple applications, including monotherapy, combination therapy with Avastin, and adjunctive therapy, in 223 subjects over a period of five to six months. Final data readout for these studies is expected by first-quarter 2017.
As a vitreolysis agent, Luminate is being investigated for induction of posterior vitreous detachment (PVD) and release of vitreomacular traction (VMT). In VMT, top-line Phase II data were reported last year showing that Luminate met its primary endpoint related to release of traction and adhesions, with a high level of safety. Luminate is Phase III-ready in the VMT application. The 100-patient Phase IIb PACIFIC study is evaluating PVD induction in patients with early, non-proliferative diabetic retinopathy (NPDR). Study completion is targeted for late first-quarter 2017.
Vicken Karageozian, MD
Vicken Karageozian, MD, is president and chief medical officer of Allegro Ophthalmics. Dr. Karageozian has more than 22 years’ experience building and leading companies in the ophthalmic pharmaceutical space.
Vicken Karageozian, MD: I also want to take the opportunity to say thank you to everyone in the OIS community, especially Emmett, for inviting us here to present an update on Allegro Ophthalmics. What does Allegro offer with its Luminate program? This is a first in class anti-integrin drug, the first time an integrin peptide is coming into ophthalmology and into the back of the eye. It has unique mechanisms of action for both anti-angiogenesis as well as vitreolysis. We are now about 6 years in the development of this program, and are late stage development with multiple programs in DME, looking at both monotherapy, combo therapy and adjunctive therapy. These are an ongoing phase 2 Del Mar study. We also have phase 2 studies in PVD in non-proliferative diabetic retinopathies, looking at the vitreolysis aspects of the drug. You may also remember about 9 months ago we had top line data on vitreomacular traction in phase 2. It also read as a successful primary endpoint. At this point in time, we have about 400 human eyes treated with about a thousand human intravitreal injections, with a very clean safety profile. What’s also nice about this is the non-clinical aspects of the program have been significantly de-risked with composition and matter IP already issued, solid PK, solid tox, and our CMC packages are very solid as well. Looking at the dual mechanisms of action for Luminate, again, it has a unique anti-angiogenic aspect, where you both can cause regression of neovascularization, inhibition of neovascularization as well as inhibition of vascular leakage. We’ve already shown in earlier presentations our human proof of concept data in DME and wet AMD, and we’ve shown in those studies in both human patients in wet AMD and DME that you get increased durability for 12 to 16 weeks, better safety, and then you have with a new mechanism of action many new treatment options. As I said, we’re looking at monotherapy, combo therapy, and adjunctive therapy now. On the vitreolysis side, this is green fields. We’ve been looking posterior vitreous detachment as well as a VMT. We’ve been getting in our human patients very safe PVD in vitreolysis induction, excellent safety, and with this unique mechanism of action, again, there are many different ways you can use this. Currently we are looking in phase 2 at PVD induction in non-proliferative diabetics. Getting into our multiple phase 2 programs that are underway currently, our Del Mar study has two parts to it. Stage 1 is looking at again dose ranging and safety first, with monotherapy and durability. Again, the primary efficacy endpoints are central retinal thickness and visual acuity at weeks 16 and 20. The final readout will be between the end of the year and first quarter. The same Del Mar study also has arms that look at combo therapy and adjunctive therapy. Also should read out by around first quarter. Concurrently, we have the Pacific study, which is vitreolysis focused, looking at PVD. This is basically looking at PVD induction in non-proliferative diabetic retinopathy population. This study is moving along very nicely as well, and should read out by probably late first quarter. Again, what do we have here? We have a first in class anti-integrin peptide for retinal vascular diseases, with anti-angiogenesis and vitreolysis that work independently of each other. We have multiple phase 2 programs underway in the US now in DME, looking at combo therapy, monotherapy and adjunctive therapy. We have shown robust vitreolysis in the past, and again, we hope to show that in our PVD study in non-proliferative diabetics we can also induce PVD as well. All of these studies should read out in the next 6 to 9 months, depending on the study. Thank you.