Graybug Could File GB-102 IND Next Year

Jeffrey Cleland, president and CEO, Graybug Vision, delivered an update on its two treatments for wet age-related macular degeneration (Wet AMD) and glaucoma. The company is working with an approved cancer treatment, Sutent, which has demonstrated the ability to restore vision in patients who also suffer from Wet AMD. An animal study of the company’s compound, GB-102, suggested it could perform better than FDA-approved Eyelea (aflibercept) and might only need to be delivered twice a year. The company also is working on an annual injection. Animal studies showed no evidence of inflammation or toxicity. The company must complete one more animal study before filing for an IND. Graybug’s GB-102 also performed better when compared against aflibercept in the animal studies. The company is on track to file an IND in 2017. Graybug’s glaucoma product is roughly one year behind its candidate for Wet AMD.



Jeffrey Cleland, PhD

Jeff has 20 years of industry experience in research and development, including more than a decade at Genentech, Inc. His experience in startups includes major roles in obtaining more than $450 million in capital at stages from Series A through D and exit via IPO including over $300 million in capital raised as CEO.

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Jeffrey Cleland, PhD: We’re developing transforming therapies for the treatment of wet AMD and glaucoma. We think we have a potential transformative therapy where we can dose potentially twice per year with a drug that targets both the VEGF receptor and the PDGF receptor. We think this could have a significant advantage over the current therapies that are in the clinic, not only around reducing the treatment burden, but also targeting two different mechanisms that are somewhat validated. We’re using a novel platform technology which we’re trying to develop into multiple different products. This technology allows you to inject into the eye, as I’ll share with you today, in a way that is pretty much similar to how the biologics are already injected today without any additional inflammation or any type of tissue damage into the eye. And it’s a tunable approach. We’re working on actually a once a year product that’s early stage at this point. The twice a year product’s the one I’ll be talking about today. In addition, we have a glaucoma program where we actually have new chemical entities that target both IOP lowering and also have neuroprotection all in a single compound that, once it’s degraded in vivo, it actually releases two active agents. The drug that we selected going forward is actually sunitinib. It’s an RTKI. Interestingly enough, when you give Sutent, which is the approved form of sunitinib, orally to cancer patients, it gets into the ocular tissues and into the uveal tract in the eye at higher levels than we can treat already with patients with our drug. So it’s already well characterized for ocular safety. In addition, it’s been used in animals to show that if you give it orally, it inhibits CNV formation in mice. And our Chief Medical Officer found a recent case study where he showed that there was a patient that was treated with renal cell carcinoma that had wet AMD that was refractory to anti-VEGF, and that patient actually responded to Sutent therapy and had an improvement in visual acuity. Of course, we can inject Sutent into the eye because of the short half-life as was mentioned in the previous presentation. So we’re focused on using our novel platform to actually dose it twice per year or less into the vitreous and get both the VEGF and PDGF effects. We think the advantage of this approach is that by targeting at the receptor level, which I’ll show you today, is a significant advantage over targeting the ligands. So how the technology works is we actually encapsulate the drug into PLJ microparticles. It’s released into the vitreous after injection, and it forms an actual implant in situ in the eye. So you don’t have free-floating particles, and there’s no inflammation. The hydrophilic coating that we use on the polymer actually prevents any kind of contact toxicity, so you don’t see any local tissue toxicity on the retina. It’s very safe and well tolerated without any side effects. And then basically you can see on the next screen where we have in this photo, you look into the vitreous directly, you don’t see it. You look down in the bottom of the eye, you can see it, and it forms a size, since the presentation of Iluvien was today, it’s also about the same size as the Iluvien implant once it’s injected into the eye. In terms of the toxicokinetic profile, this is a demonstration on the top curve is in orange is the RPE choroid. You can see very, very high levels of sunitinib out to beyond 6 months. We actually have 7-month data and it still hasn’t come back down. So this product could be at least 6 months, maybe 9-months release over the time course. We didn’t know it was going to be this long, so we actually have a product that could potentially be once a year right behind it. And in the blue is the retina, and in the black is the vitreous. So again, very high levels out too much beyond 6 months, above what’s necessary to inhibit those receptors, and almost undetectable plasma levels. Only a couple points detected in the red there. From a safety perspective, no inflammation, no toxicity out to 6 months. And because the molecule is already in human eyes at very high levels, and the platform that we’re using, the PLJ and the coating have all been used in humans before, the FDA had agreed that all we had to do is repeat this study to go into the clinic for an IND and potentially for commercial approval. So the safety from the FDA’s perspective is also very good for this compound and this formulation. Now in terms of efficacy, obviously great half-life. What does it do in vivo in terms of efficacy? And this is a rabbit CNV model. And here what we show is that we give a single injection and we wait 10 weeks. So we give very low doses. Twenty-fold lower is the top dose of what I showed you in the TK slide. We waited then after that dose for ten weeks. We did the laser in the rabbits, and then we looked for CNV area formation three weeks later. As all of you probably know, the biologics work best when you give then 24 hours within the laser, so that’s what we did afilbercept. And you can see on the panel on the bottom left corner that in each case, our drug performed significantly better than aflibercept, even though it was given ten weeks before the laser treatment. So we’re clearly having an advantage. There’s no does response, so again, I think we believe that targeting the receptor is a significant advantage over targeting ligand because once you’ve saturated all the receptors, you don’t need to add more drug. So we’re actually doing some additional studies that are ongoing, going even later in time, and longer out to 6 months, and also at lower doses to see if we see additional dose response. And this data will all be presented in a poster at AAO. So in conclusion, we believe we have potentially one of the best in class opportunities here to treat twice a year dosing in patients with wet AMD, and our glaucoma program is about one year behind that, so we hope to be able to share an update around that time. So thank you very much for your attention, and I’ll take questions off line.