The October 30, 2020 Eyecelerator webinar took a closer look at the future of retina care through its presentation titled, “The Retina Combine: Scouting the Next Generation of Ophthalmic Stars.”
The complimentary live stream was a two-hour program which featured many important KOLs in the field of ophthalmology. Together, they explored advanced AMD therapies and novel strategies for bringing retina innovations to market. Here are some of the highlights…
Is Vision Loss Reversible in Dry AMD?
Allegro Ophthalmics (California, USA) is at the cutting-edge of treatment for dry age-related macular degeneration (AMD) with a new class of drugs that may revolutionize how ocular diseases are treated.
According to Dr. Vicken Karageozian, president & CEO of Allegro Ophthalmics, “Risuteganib is the lead product in this novel class of peptides that regulate integrin function, resulting in mitochondrial stabilization and suspension of apoptosis.” Risuteganib is unique for targeting dry AMD because it can re-energize and reactivate sick retinal tissue and prevent further tissue death.
Data show that a majority of dry AMD patients have intermediate AMD, for which there is no approved therapy. Allegro has completed phase 2 clinical trials in the U.S. for intermediate dry AMD, with results showing that vision can be recovered in dry AMD if the right population is targeted. Risuteganib showed excellent results in reversing vision loss with no treatment related serious adverse events. The company is preparing to launch global and U.S. phase 3 trials in 2021.
Shielding the Retina to Treat Dry AMD
Reactive oxygen molecules contribute to the accelerated aging of retinal cells in patients with dry AMD. But what if there was a way to get rid of these molecules?
Dr. Natalia Perekhvatova and colleagues at Mitotech are developing a new mitochondrial-targeted antioxidant molecule, known as SKQ1, which protects the retinal scavenging reactive oxygen species, regulating inflammation, and preventing cellular apoptosis.
Perekhvatova shared: “We have very positive animal data, and we are preparing for phase 2 studies in the U.S. Safety data is available since SKQ1 has already been tested extensively in patients with dry eye disease. Our available data also shows good pharmacokinetics, which is appropriate for back-of-the-eye administration. Overall, SKQ1 is very well-positioned for entering into phase 2 studies in dry AMD.”
Into the Posterior Chamber, One Drop at A Time
For a long time, physicians and patients have dreamt of non-invasive treatments for retinal diseases. The challenge with current therapeutic options has always been poor distribution into the retinal tissues, necessitating intravitreal injections.
Now, OcuTerra Therapeutics (Massachusetts, USA) has developed the OTT166 eye drop to treat retinal diseases.
According to Dr. Kerry Brady, the company’s CEO, “OTT166 is a potent, selective integrin antagonist designed to reach the retina from topical eye application.”
“We have successfully demonstrated that OTT166 remains at required concentrations over 12 hours in retinal and choroidal tissue after topical administration of the 5% formulation in rabbits. We have also shown early data in diabetic retinopathy patients, where decreased retinal thickness was maintained up till day 56 post-treatment.
“We are therefore confident to commence phase 2 studies in 2021,” concluded Dr. Brady.
Harnessing the Power of Light
Our vision is to develop a cost-effective, safe treatment solution. We are using multiple-wavelength, non-invasive, photobiomodulation to improve visual function, stop or slow the progression of debilitating eye disease, and prevent blindness,” said Dr. Clark Tedford, CEO of Lumithera (Washington, USA).
“The mechanism of photobiomodulation at the cellular level has been ascribed to the activation of mitochondrial respiratory chain components resulting in stabilization of metabolic function and initiation of a signaling cascade, which promotes cellular proliferation and cytoprotection,” he continued.
“The Valeda Light Delivery System was developed after prototype testing of light scatter and tissue absorption parameters for three different wavelengths. We then conducted three clinical trials that led to its approval in the European market,” said Dr. Tedford.
On the learning curve and user-friendliness, Dr. Tedford explained that “it is the first approved treatment for dry AMD and photobiomodulation in a short procedure repeated over several weeks. Each treatment session lasts about 4 minutes, no pupil dilation is required, and it can be delivered by both physicians or trained non-physicians.”
New Therapies for Dry AMD in 2020: What Will it Take?
By 2040, over 20 million people in the U.S. will have dry AMD. In a panel discussion moderated by Dr. Allen Ho, experts in retinal drug development share their thoughts on the critical priorities for accelerating new molecules’ development for dry AMD treatment.
“The most promising treatments are best initiated in early AMD, before geographic atrophy sets in. We are beginning to see exciting new molecules by innovative companies. What are the most important considerations for companies wanting to bring these new treatments to patients?” began Dr. Ho.
According to Dr. Wiley Chambers from the U.S. FDA: “From the FDA’s point of view, in intermediate AMD, the goal of trials should be to demonstrate improved visual function or prevent visual function loss in trial participants. Therefore, companies should try to incorporate controlled clinical trials as early as possible in the development process. While it’s nice to have enthusiasm, the bias introduced when studies of new therapies are either uncontrolled or open-label can potentially give misleading information.
“For drugs and biologics, adequate controlled trials are needed to demonstrate safety and efficacy before approval can be given,” he continued, adding that “we strongly encourage the use of endpoints that improve patients’ daily life activities, such as visual acuity, visual field and visual function in low contrast situations.”
Dr. Emily Chew of the NIH added: “The AREDS1 trial provided the natural history of dry AMD that we are using today. In those days, we had less advanced imaging than OCT today, and I think surrogate endpoints of intermediate disease are needed. This is an area of unmet needs, and it’s exciting to see innovations like different delivery systems, but the efficacy must be demonstrated, so randomized trials are needed early. In addition, scales of structural and functional changes, such as geographic atrophy, are needed, and hopefully, we will see more of these soon.”
Dr. Peter Kaiser added: “We need more biomarkers of late-stage changes, and mitochondrial dysfunction may be an interesting marker. However, it’s up to the clinical trialists to prove that these biomarkers will provide long-term patient benefits.”
A FASter Approach to Preventing Vision Loss
FAS inhibitors represent a novel approach to treating retinal diseases. And because patients with retinal diseases lose vision from retinal cell death, there has been a lot of excitement in the industry about the potential of drugs that block retinal cell death pathways.
“ONL Therapeutics is one of those companies at the forefront of developing FAS inhibitors. Our lead compound, called ONL1204, is currently in the clinic in a phase 1 study of retinal detachment,” said Dr. David Esposito, company CEO. “Early data from our phase 1 study has demonstrated safety, tolerability, and early hints of efficacy.
“We have a clear path to regulatory approval for retinal detachment and are moving into a chronic indication of geographic atrophy, and we look forward to delivering this world-class treatment in the coming years,” concluded said Dr. Esposito.
One Intravitreal Injection Per Year? Yes, We Can!
Asclepix Therapeutics (Maryland, USA) is breaking new ground in the treatment of retinal diseases. According to Dr. Theresa Heah, chief medical officer: “Anti-VEGF monotherapies have hit the ceiling for efficacy and short duration of action. Our computational biology approach has led to the development of AXT107, which has demonstrated superior durability and long duration of action.”
How does this molecule work? “AXT107 works by disrupting integrins, leading to reduced neovascularization, blood vessel leakage, and inflammation,”said Dr. Heah. “AXT107 is a potentially best-in-class molecule with an impressive duration of action that inhibits VEGF and activates Tie2.”
“Safety has been demonstrated in animal and toxicological studies for 15 months. We have a well-defined regulatory pathway, and we aim to start phase 3 studies in 2022,” concluded Dr. Heah.
In Search of the Ultimate Drug Delivery Platform for Dry AMD
Sustained-release formulations have the potential to improve the compliance of patients with dry AMD significantly. Vinci Pharmaceuticals (Paris, France) presented data on their novel, first-in-class approach toward developing new treatments for this group of patients. Philip Gioia, the company’s co-founder & CEO, stated: “Our goal is to develop a first-in-class treatment for dry AMD that is minimally invasive and patient-friendly.”
He added: “With our proprietary episcleral sustained-release ocular implant, treatment can be guaranteed for six or more months. Therefore, we seek additional seed funding, which will be vital towards achieving our proof-of-concept studies in dry AMD and DME (diabetic macular edema) programs that will accelerate our development of this novel therapy.”
Editor’s Note: The Eyecelerator webinar “The Retina Combine: Scouting the Next Generation of Ophthalmic Stars” took place on October 30. 2020. Reporting for this story also took place during the webinar.