David Hutton of Ophthalmology Times talks with Jeffrey Cleland, PhD, President and CEO of Ashvattha Therapeutics, about the company's D-4517.2, a unique nanomedicine technology for the treatment of wet AMD and DME.
David Hutton of Ophthalmology Times talks with Jeffrey Cleland, PhD, President and CEO of Ashvattha Therapeutic, about the company's D-4517.2, a unique nanomedicine technology for the treatment of wet AMD and DME.
Editor's note - This transcript has been edited for clarity.
I'm David Hutton of Ophthalmology Times. Joining me today is Jeff Cleland, CEO of Ashvattha Therapeutics. Thanks for joining us, Jeff. First off, the company had a great year in 2023. Tell us a little bit about D-4517.2 for wet AMD and DME.
Yeah, thanks, David, I appreciate the opportunity to speak with you again. Really, what we're focused on is trying to remove the need to have intravitreal injections, and have an at home administered product. Which is very unusual for treating retinal disease, because as you know, right now, everyone has to have an injection directly in the eye. And so what we're working on is the unique nanomedicine technology that was developed by our founders at Johns Hopkins University in the Wilmer Eye Institute. What they've done is taken what we call a hydroxyl dendrimer, and what it does is very uniquely targets inflammation, specifically in the back of the eye.
And is taken up after systemic administration, by those activated cells in the back of the eye that are causing the retinal disease. And so what we've been able to show is that in animal studies, by putting on a drug that actually blocks VEGF signaling and blocks, the VEGF expression by those cells on this nanomedicine, we're actually able to shut down that neovascularization, that happens in the back of the eye that cause wet AMD, and DME. And so what we've been able to show in patients so far, is that it's very safe, very well tolerated, no systemic adverse events, which is very unusual for a lot of these drugs that, as you know, block VEGF, who often have systemic side effects. We've seen no systemic side effects, we're now on repeat dosing studies. Again, no systemic side effects have been noted so far. And in animals also, we've only seen a localized effect on the kidney when we give very, very high doses, because that's [inaudible] for this molecule. So now what we've done is a study where we're comparing directly in the same patients, and intravitrial dose of aflibercept. So giving them intravitrial aflibercept, then waiting to see how long it is before the fluid comes back by OCT.
And when fluid comes back, we gave a single subcutaneous dose of our drug primarily at either one or two milligrams per kilogram, in wet AMD and DME patients. So 7, wet AMD and 5 DME patients. And those data were pretty encouraging to us, saying that even just a single administration, we were able to stabilize fluid in 11 out of 12 patients for at least 2 weeks, and then in 9 out of 12 patients for 4 weeks, and actually 4 patients remain stable with no change in fluid or BCVA out to 12 weeks from just a single administration, subcutaneous administration, so not intravitreal. So now the question is, can we prolong that and do a treat and extend and really treat the maintenance phase of this disease, these diseases. And really, what we're doing now is exactly that.
So again, we want to see how long they would normally respond to an aflibercept injection. So we do that first, they get that in the trial, inravitrial in the eye. And then when they see fluid come back, we give both aflibercept and our drug at the same time. Aflibercept - IVT, our drug - subcutaneous. And then we can continue to treat with our drugs subcutaneously, either once or twice a month, out to 9 months. So we'll actually be able to see how long can we keep these patients rescue free without having to have an injection of aflibercept in the eye. And hopefully, we'll keep them dry for a very long period of time, and not have to have them come back and get an intravitrial dose of aflibercept. So right now we've enrolled 15 of the subjects.
So far, 7 of them have been dosed with our drug and are in that continuous dosing phase that I described to you. And we hope to have the initial data around the time of ARVO, and they will have a significant amount of 6 month data, hopefully keeping them dry out to 6 months by ASRS in July.
Excellent. And you've kind of alluded to it, but what are the next steps as you move forward with this candidate.
Assuming we see very compelling positive data that I just described here over the next few months, then we would plan to go into a randomized masked and placebo controlled study head to head against aflibercept and hopefully show you know non-inferiority of this approach and you know, keeping patients rescue free for very long periods of time. Such that we can give an at home administered product.
And we're also advancing this year, a way to make the same product instead of sub-q once or twice a month, it would be oral once or twice a month. And we have some pretty exciting preclinical data. And if it continues to play out as we hope we could be in healthy volunteers this summer showing equivlaent and exposure to what we give sub-q and then eventually in 2025 looking at giving an oral dosage form in these patients as well.
Tell us a little bit about the company's outlook for 2024, including any new candidates in the pipeline that you can discuss.
Yes, absolutely. So we're pretty excited about this platform, I think the unique thing about a nanomedicine technology is that it can be applied across multiple products. And so one of the other challenges, as you know, besides getting across the blood retinal barrier, when you give a drug systemically, is getting across the blood brain barrier. And so we actually have a program which is really unique is that we can put [inaudible], which is a radioisotope on the nanomedicine. And then we can actually scan the person's body by PET, and see exactly where the nanomedicine goes. And so we've done that now in healthy volunteers. And it does, if no one's seen it in the video, on our website, it's exactly like the video, except that an actual person watching the nanomedicine move around and it actually stays in the in the plasma compartment. And a healthy person goes straight to their kidneys into their bladder is excreted. So there's no inflammation doesn't escape the vasculature.
And so now we're doing Alzheimer's, Parkinson's, multiple sclerosis, and ALS patients. And hopefully, we'll be able to see it cross the blood brain barrier and just go into that region in their brain where they have the neuro inflammation. And so that data will be coming out over the next few months. And we're pretty excited about that program. And then we have another program that's been in the clinic, and showed that we actually doubled survival in severe COVID patients. But of course, there's not really a market for that any longer fortunately for the world. And so now we're pivoting that molecule into looking at other indications, we may go into progressive multiple sclerosis, that's one indication we're considering for that program, which would start later this year. And then we have another program that's got very compelling preclinical data, that's CSF-1, our tyrosine kinase inhibitor, this covalently, linked to the same nanomedicine that we've shown positive proof of concept in preclinical models of multiple sclerosis and Alzheimer's. So that molecule can be pretty exciting to move forward and 2025 into the clinic as well.
And lastly, from your perspective, what's your outlook for ophthalmology in 2024?
I think you know, based on a lot of the recent data that you've seen as well, that people are starting to recognize that our approach similar to other people's approaches with tyrosine kinase inhibitors are really being able to either implant them directly in the eye and keep the eye dry for a long period of time, or give them systemically like we are. That I think is going to be exciting data coming out, that's really going to help alleviate the treatment burden from patients having to go back and get repeated intravitreal injections. And physicians also feel the same way. We've talked to 51 US retinal ophthalmologists. And they all see the need to get out of the clinic and not have to be constantly injecting people all day long. So So
I think that's going to be exciting to see our data, other people's data, really helping patients not need to have so many needles in the eye, as we like to call it, which no one likes. In 30 years of doing drug development. I've never seen a drug go through 6 clinical trials with 3 different products with no systemic adverse events. So even placebo, you see, so we haven't seen anything. So I think I'm pretty excited if we can get some positive readouts here in the next few few months.