Physicians, industry, investors convene for Ophthalmology Innovation Summit

CHICAGO – As has become the tradition, the Ophthalmology Innovation Summit was held on the Thursday prior to the American Academy of Ophthalmology with a goal to be a common ground to discuss the opportunities and obstacles to ophthalmic innovation. Ocular Surgery News has captured the substance and spirit of the remarks made by the speakers here during the BioPharma Company Showcase.

BioPharma Company Showcase

Henry Hsu, MD, founder and CEO of Allysta Pharmaceuticals discussed the company’s development of Aly1337, a small molecule multikinase inhibitor for the treatment of glaucoma.

Hsu: There is an unmet need in glaucoma from a mechanistic standpoint are drugs that target trabecular meshwork. Aly1337 has shown a good dose response in albino rabbits and it can effectively be combined with other IOP-lowering drugs. In monkeys, Aly1337 lowered IOP more effectively than latanoprost. Aly1337 has shown potent and long-lasting IOP-lowering in animal models. We have seen solid preclinical safety and tolerability profile with wide therapeutic indications.

And while Hsu did not show the data, he did mention a good safety profile for Aly1337.

Vicente Anido Jr., PhD, CEO of Aerie Pharmaceuticals, discussed the company’s US clinical trials for new glaucoma therapies – Rhopressa and Roclatan.

Anido: Our strategic goal is to keep the rights for Rhopressa and Roclatan in North America.  We've been very successful in the clinical and financial environment. In the last 12 months, we've been very successful in the clinic as well as the fundraising area. Rocket 1 is a 90-day non-inferiority, efficacy clinical trial that compares timolol twice daily and Rhopressa 0.02% in 200 patients. Data for Rocket 1 will be available in summer 2015. The safety study data will be available in 2015.

Roclatan Phase 2b clinical trial compares Roclatan 0.02% (n=72 patients), 0.2% Rhopressa (n=78 patients) and 0.005% latanoprost (n=73 patients).  About half the patients had a 35% reduction in IOP compared with latanoprost. In this study, we were able to show the separation we needed; and all endpoints were statistically significant. The most commonly observed adverse reactions in this study was conjunctival hyperemia. Of those, 80% were mild.

We’re very pleased with the outcome and are moving forward to phase 3. We will have efficacy results sometime next year. We will file the NDA for Rhopressa in the first part of 2016 and hopefully have approval by 2017.

John Freshley, CEO, of ONL Therapeutics, discussed ONL-101, a small injectable peptide targeting retinal detachment prior to surgery.

Freshley: We are developing first-in-class therapeutics to prevent photoreceptor cell death. Despite current therapies, photoreceptor cell death remains the root cause of vision loss and the leading cause of blindness. There are more than 50,000 retinal detachments in the US per year. It is a serious disease with unmet needs that are perhaps underappreciated.

The good news is we have excellent surgical techniques to reattach retinas. This is effective approximately 90% of the time. The mean BCVA is 20/50 and one-third of patients have vision worse than 20/60.

We’ve received orphan drug status in retinal detachment. We have identified a small peptide inhibitor of Fas receptor, Met12. We’ve highjacked and leveraged the survival attribute of this gene. We’ve demonstrated this works in well-recognized retinal detachment in rats.

Charlie McDermott, interim president and CEO of Kala Pharmaceuticals, discussed the company’s nanotechnology mucus penetrating particle platform technology.

McDermott: Kala eyecare pipeline includes products and indications in post cataract surgery, dry eye, meibomian gland disease, topical diabetic macular edema and topical wet AMD.

Kala is developing the loteprednol etabonat mucus penetrating particle (LE-MPP). In a rabbit study, LE-MPP outperformed Lotemax suspension (Bausch + Lomb) and similarly sized non-MPP nanoparticles in corneal drug levels after a single dose.

In the DME pre-clinical trial that tested retinal levels after topical dosing of 1% LE-MPP in mini-pigs demonstrated that LE-MPP did reach the back of the eye.

In a rabbit study, K0010-MPP dosed every 4 hours or once daily showed efficacy equivalent to Avastin (Genentech). K0010-MPP was dosed in three additional different dose designs, all showed efficacy equivalence to Avastin indicating it is not only getting to the back to the eye but is efficacious.

We are going to have all of our clinical data readouts by Q1 2015

We are a platform program, and are working with many companies and their partner compounds.

Jesper J. Lange, president and cofounder of MC2 Biotek Group, presents on the company’s oil-in-water dispersion technology aimed at improving comfort, compliance and effectiveness of topical medications.

Lange: We are a privately held company and are in it for the long-term. We believe the key to a successful drug is to get a label that is recognized by payers and clinicians as clinically superior.

PADciclo is a dry eye drug and phase 2 is just starting up. Why dry eye? We think David Pyott and Allergan has done a wonderful job maturing the market.

Our challenge is to find a dry eye treatment that has less stinging. Our solution was to reduce surfactant levels approximately 30-fold and the reduce concentration of CsA. We also aim to get a best in class claim for treatment.

More than 1,000 patients have been treated with PADciclo 0.06% in the UK. The company collaborated with Moorfields Pharma at Moorfields Eye Hospital. We have global rights to develop this into a licensed medical product.

In the US, we are ready to start a large phase 2 clinical trial.

Bernhard Gunther, CEO of Novaliq GMBH, discussed the company’s patented semifluorinated alkane formulations.

Gunther: Our first products were NovaTears (CE Mark in 2013) and NovaTears Omega 3 (CE Mark expected in 2015). NovaTears plus Omega-3 is a clear solution and is preservative-free.

The CyclASol (cyclosporine) phase 1 study demonstrated that the drug had no stinging, no burning and excellent tolerability. CyclASol is the first and only clear solution based eye drop formulation in clinical development for patients with dry eye disease.

The EyeSol platform technology is available to partner companies.

Novaliq gmbh offers a compelling and proven drug development opportunity to enhance the performance of topical eye drops.

Ed Timm, president and CEO of Mobius Therapeutics, discussed Mitosol and the Mobius ABX Procedure kit.

Timm: The retasking of existing molecules is preferred over drug discovery. Our first product in the marketplace is mitomycin C (Mitosol).  We launched this product 2 years ago and we have become gold standard in glaucoma filtration surgery. The next step is to take the exact same molecule into refractive surgery.

Are we a glaucoma company? Kinda, sorta. But I just mentioned PRK. The best way to look at us is a drug delivery company.

Our next step is endophthalmitis. Acute, intraocular infection. How are we going to treat them? Current standard of care is highly unstable, toxic, and there are sterility/transfer issues. The solution is Mobius ABX Procedure kit. The drug is reconstituted at the time of treatment.

Michael O’Rourke, president and CEO of GrayBug, discussed the company’s technology aimed at reducing intravitreal injections for the treatment of AMD to every 4 to 6 months.

O’Rourke: Reduction of the frequency of intravitreal injections is a major unmet medical need. The lead drug we are looking at is GB-102 for wet AMD. It is both anti-VEGF and anti-PDGF.

We project that we will file an Investigational New Drug application in 2015.

Thomas W. Chalberg, PhD, founder and CEO of Avalanche Biotechnologies, discussed the company’s Ocular BioFactory gene therapy platform.

Chalberg: We are at the intersection of the really interesting fields of gene therapy and ophthalmology and have the potential transformative treatments. Avalanche’s Ocular BioFactory enables long-term protein delivery to the eye. It is delivered through a single subretinal injection.

Our platform secretes therapeutic protein for years following a single administration and offers a functional cure of wet AMD. AVA-101 is our lead product. AVA-101 upregulates a naturally occurring VEGF-inhibitor implicated in AMD. It penetrates the retina and overcomes the barriers to delivery.

There is an initial onset of vision loss and patients typically present with vision of 20/80.

In the study, the majority of AVA-101 treated patients did not require any rescue treatment at 1 year.  Also, the majority of patients gained VA from baseline.

What is in store for Avalanche? We are also looking at AVA-101 for DME and RVO; and AVA-201 for wet AMD and XLRS in collaboration with Regeneron.

Vicken Karageozian, MD, co-founder and CTO of Allegro Ophthalmics, discussed integrin peptide therapy for vitreoretinal diseases

Karageozian: Allegro has a first-in-class drug that is anti-integrin vs. anti-VEGF.

Human clinical trial (n=350 human intravitreal injections) results for Luminate have shown excellent safety profile. The DME study that was just initiated in October is a randomized, controlled, double-masked study with 150 patients in 5 arms. Endpoints are OCT central macular thickness and increased durability.

We are leveraging strategic partnerships and financial investments to execute to commercialization.

Shelley Boyd, MD, president and CSO of Translatum Medicus, discussed a transcriptional modulator to reduce protein levels of pro-inflammatory targets.

Boyd: We have reverse engineered an animal model to test our hypothesis. Our drug is a first-in-class transcriptional modulator. Tmi-018 drug goal is the reduction of protein levels of pro-inflammatory targets.

This first-in-class transcriptional modular acts to differentially regulate gene expression in the innate immune system. We hold a suite of utility patents and are working with the company that originated this drug. The preclinical work is to determine the efficacy of Tmi-018 which is a repurposed drug with the goal to protect against the development and expansion of geographic atrophy in dry AMD.

David R. Guyer, MD, CEO of Ophthotech discussed a first-in-class anti-PDFG drug for wet AMD.

Guyer: OPHTHOTECH's Fovista is a first-in-class anti-PDFG agent for wet AMD combination therapy. Phase 3 is on track with top-line data expected in 2016.

Our philosophy is that we will remain anti-VEGF agnostic. The anti-VEGF market is now a validated multibillion dollar opportunity. With the partnership between OPHTHOTECH and Novartis, Novartis will seek co-formulation and the development prefilled syringes.

The upcoming Tuesday AAO abstract will include results from a masked, retrospective analysis by independent reading center of fundus images at baseline and 24 weeks in a subset (n=70 eyes) from the Fovista phase 2b study with >0 ETDRS letter loss. In the study, the mean change in fibrosis was 0.97 vs. 2.0 (P = .003). Of the eyes, 27% (Fovista + Lucentis) vs. 54% (Lucentis monotherapy) had greater than/equal to 2 step worsening of fibrosis (2x difference). In eyes with no fibrosis, 10% (Fovista + Lucentis) vs. 51% (Lucentis monotherapy) developed fibrosis.

In summary, Fovista is a first-in-class anti-PDGF agent for wet AMD combo therapy in a multibillion dollar market.

Franz Obermayr PhD, co-founder and CEO of Panoptes discussed autoimmune uveitis.

Obermayr: We are investigating a best-in-class DHODH inhibitor that is 100-fold more potent than Arava and Aubagio (for RA and MS, respectively). It inhibits T cells proliferation which is quite important in inflammatory disease, and is a selective nanomolar inhibitor IL-17 IFN-y and VEGF.

PP-001 is a new treatment for intravitreal and oral posterior uveitis.

In summary, we have showed proof of concept in rat model for uveitis and found it superior to cyclosporine.

Paul Rubin, MD, chief marketing officer, XOMA Corporation, discussed….

Rubin: Gevokizumab is an IL1B allosteric modulator. Its mechanism is clearly unique in this particular field.

To date, more than 1,000 patients have received gevokizumab in a completed and ongoing study with dosing up to 2 years. We, at Xoma, are committed to ophthalmology as a therapeutic area, in addition to looking at other indications where it can be important. A phase 2 study showed improvements in BCVA.

Visit Healio.com/Ophthalmology tomorrow to read the Device, Delivery and Diagnostic Company Showcase. – by Samantha Costa, David Mullin and Joan-Marie Stiglich