Oculogenex founder talks about collaboration with NASA and ISS on experiment in macular degeneration

Hema Ramkumar, an ophthalmologist and founder of Oculogenex, sat down with David Hutton of Ophthalmology Times to discuss their connection with NASA and their experiment on macular degeneration-treated mice in space.

Video Transcript

Editor's note - This transcript has been edited for clarity.

David Hutton:

I'm David Hutton of Ophthalmology Times. Today I'm joined by Dr. Hema Ramkumar, an ophthalmologist and scientist who founded Oculogenex. For more than 17 years, she has focused her research on treatments for age-related macular degeneration. Thank you so much for joining us today. First, tell us about your focus on this insidious disease, and what drove you to form Oculogenex.

Hema Ramkumar, MD:

Thank you so much for having me here today, David. So dry macular degeneration is very prevalent. And as a practicing retina specialist in Orange County, I see many patients suffering with this diagnosis. Many of whom may also have family members who are getting injections or slowly had to lose some of their ability to care for themselves or drive because of this devastating, persistent disease. I also have the opportunity to provide care for patients with wet macular degeneration, and see the improvement in vision that they get with treatment, but also understand the burden of needing monthly or bi-monthly injections on the patient, the caretaker, and the family. So there are two things that really drove me to found Oculogenex. One, I really believed to change the prognosis and the natural history of dry macular degeneration, or even of advanced disease, we need to intervene in the disease early. Before we have tissue loss before we have many of the symptoms of advanced disease. If this were possible, it might be that we don't have severe tissue loss from geographic atrophy or wet macular degeneration. And this would allow patients to preserve their vision and independence for much longer. Also, I understand that developing a therapy that only lasts a month or three months, comes with it all the burdens of chronic intravitreal injections. And so that's why Oculogenex is developing gene therapies that will allow for a much more durable and consistent response to therapy, so that patients can still have continuous treatment without needing to see their retina doctor every month or every other month. So those two are what led me to form the company. And we're really focused on helping patients with macular degeneration improve vision from all the other parts of the disease that cause vision loss, other than excitation, which we see in wet [AMD].

David Hutton:

You've developed an interesting connection with NASA. Could you tell us a little bit about that?

Hema Ramkumar, MD:

Yeah, that was an exciting connection. Oculogenex was in the 2021 mass challenge incubator. And during the course of this incubator, we were offered, actually reached out to by the International Space Station National Laboratory. And they asked us if partnership with NASA and ISSNL would help hasten our technologic development and bring us to the clinic faster. And so we looked into it. And one of the challenges that we were having and many other companies in the space are having is developing a good animal model of intermediate AMD. You know, there are many transgenic models and many models that take years to develop. And that's one of the limitations in developing a good therapy for these patients. And so I found that there was some recent work by other groups showing that there was increased retinal oxidative stress, and some loss of retinal photoreceptor function and a small amount of retinal tissue loss after a 35 day mission to the International Space Station. And also, there was an increase in AMD related gene expression. So I found based on the limited data that there was that this might be an excellent quick model for dry AMD. Since the therapy we're developing, inhibits oxidative stress induced tissue loss and enhances mitochondrial function. We believe that our therapy might be able to mitigate that oxidative stress and damage that you see in a quick spaceflight mission.

David Hutton:

Tell us a little bit about the experiment that was recently sent to the space station.

Hema Ramkumar, MD:

Sure, all the previous other missions, looking at the retinal function, were mostly observational. There was one other that involved a systemic therapy. But what our experiment is, the first mission that has ever sending any ophthalmic treated or eye treated animal to space. So the way we're doing this experiment is that we've collected mice from Jackson labs. We treated half of them with our investigational therapy and half of them with a control with the suprachoroidal injection. And then we did baseline ERG, OCT, and fundus photos. And then one month after drug levels have stabilized after the injection, they're being then flown to the space station, and that launch occurred a couple of weeks ago. And so they docked at the space station and they're exposed to normal, you know, microgravity. They're not having any treatments there and they're being cared for with usual animal husbandry by the astronauts. And when they come back, shortly after we'll be measuring their OCT thickness and their ERG. In this way, we also have a ground control. So the purpose of this experiment is twofold. One, we'll be collecting biomarkers from the RPE and retinal tissues of the mice that are going to space and coming back to further validate the use of spaceflight as an intermediate AMD marker. And second, we'll assess if our therapy is able to inhibit oxidative stress and tissue damage and function loss by using ERG and OCT. And we'll be taking the first images of mouse retinas immediately after spaceflight.

David Hutton:

How could the retinal scans of these mice ultimately help ophthalmologists provide better outcomes for patients diagnosed with AMD.

Hema Ramkumar, MD:

So the entire purpose of this mission is to help patients see better with dry AMD, not just prevent tissue loss or lose vision. And so if these scans show that we're able to mitigate the diffuse retinal thinning, that we see with spaceflight, with our therapy, this would be additional proof of concept that our epigenetic gene therapy could prevent that chronic oxidative stress related to age and genetic predisposition in patients with AMD.

David Hutton:

Then, as you mentioned, this is certainly a first amongst studies like this being the first ophthalmic treatment study on live animals in space. Could it also yield information about other eye issues?

Hema Ramkumar, MD:

Yes, that is possible. So in addition to being the first ophthalmic treatment on live animals in space, we recently found out it's also the first gene therapy in live animals to ever be in space, of any type. So two firsts, one for ophthalmology, and one for gene therapy. And so we are definitely going to be evaluating everything related to these eyes coming back, as you may know, fluid shifts associated with a globe change is also a problem with spaceflight. And with astronauts, and so we'll be doing a retinal thickness scans and evaluating if there is any impact of our therapy on that. The we will be looking at taking a global approach to all to all the gene expression and biomarkers that we see. And so there are many retinal diseases that get worse with age and even ocular diseases, including, you know, glaucoma. And so what we are going to be looking at is all all the tissues and you know, their oxidative stress plays a role in age-related diseases, but also even diabetic retinopathy. So we'll be looking at all the different biomarkers that are changed with spaceflight that we know lead to retinal degeneration. And we'll be seeing how our therapy influences that.

David Hutton:

After the mice have returned, what are your next steps in this research?

Hema Ramkumar, MD:

So we are planning and in the process of submitting a package to the FDA to start IND enabling studies and to get concurrence with them on our Phase 1/2 clinical trial plan. So this is our next step. We're planning to get an IND by next year, and hopefully, be into the clinic by the following year. And so that is our goal. And this work, and this research will help contribute to our regulatory package.

David Hutton:

And that kind of segues into my next question, ultimately, how will you measure success of this research?

Hema Ramkumar, MD:

So we'll measure success if we're able to accurately describe the retinal pigment epithelial function and retinal function on these very detailed and sensitive tests. And if we're able to see any changes in oxidative stress related pathways, and retinal function of photoreceptors, with our therapy compared to control.

David Hutton:

Lastly, are there any other areas of this research maybe that we haven't yet touched upon?

Hema Ramkumar, MD:

So I think there are a couple of things that make our investigational therapy different from others that are in development. One is that it is a gene therapy. So that will be more durable. And second is that it is the mechanism is by enhancing mitochondrial function, and in this way, attacking the disease more upstream. So this is a very exciting approach because other therapies that have improved mitochondrial function have also resulted in improved vision in patients with intermediate AMD. So we're going after an area that we know has a promise to improve vision. And I think that our therapy is unique and well positioned and targeted to address dry AMD and potentially other age related diseases relating to mitochondrial dysfunction.