What’s the biggest breakthrough in the ophthalmology space since Lucentis and Eylea?
Novartis’ Beovu, launched last November for wet age-related macular degeneration, has been hampered by safety issues. Kodiak Sciences sports $2.74 billion on the promise of an antibody biopolymer conjugate that can be dosed every 16 weeks — reducing the treatment burden. Then there’s the line of gene therapy players from regenxbio to Adverum, following in the footsteps of Spark Therapeutics.
But AsclepiX believes it has an even better answer.
Johns Hopkins professors Aleksander Popel and Jordan Green founded the startup after designing and running an artificial intelligence algorithm to mine the human proteome for any sequences that seem anti-angiogenic. They got a hit in the non-coding sequences for collagen 4: a 20mer peptide they named AXT107, which exhibited anti-VEGF properties like the common eye drugs.
It stood out for two other reasons. It also activated the angiopoietin receptor Tie2, and when injected into the vitreous, it turns into a slow-release gel with a half life of 5 to 7 months.
That could mean once-a-year or even less frequent dosing. Since then, the small and scattered team at AsclepiX has confirmed the drug’s effect in turning off angiogenesis through integrins in 10 animal models and found no side effects.
“This was one of the most robust preclinical datasets we saw across therapeutic areas and they were well done, and they were referenceable, meaning that others use similar models to access the efficacy and safety of their compounds,” said Chris Garabedian, whose Perceptive Xontogeny Fund is leading a $35 million Series A.
AXT107 owes much of its desirable properties to the fact that it’s a naturally occurring peptide that’s “evolved over millions of years” as part of the homeostasis mechanism, added Kevin Slawin, an early investor and interim CEO.
“This is not a drug where 10 pharmaceutical employees went into a lab and had orders to drug a certain target, and went ahead and tried and then came up with something that often had side effects like inflammation,” he said.
AsclepiX is working with a contract manufacturer in Italy — one of three in the world equipped with the peptide production and filtration capacity through commercial stage — to finalize the batch of drug for the upcoming trio of Phase I/IIa studies. The process is straightforward enough that Slawin doesn’t envision any CMC issues.
The first-in-human trials will begin later this year, simultaneously testing in three patient populations: diabetic macular edema (DME), wet age-related macular degeneration (wet AMD) and macular edema secondary to retinal vein occlusion (RVO).
“So next year we will have proof of concept, or at least a signal on the three indications,” CMO Theresa Heah said. “These are 3 very large indications from a global market size perspective. We are talking 10 billion dollar-plus-plus-plus right now. If we are able to demonstrate once-a-year injection, we will be entering another larger indication that’s not been touched by anybody else, which is diabetic retinopathy.”
Positive data there could open up countless doors — strategic partnerships, a bigger financing, IPO, you name it. Especially with Perceptive’s main funds on the syndicate alongside Slawin’s Rapha Capital Management and Celgene co-founder Sol Barer’s Barer & Son Capital.
“We have a very safe product,” Slawin added. “It’s still intravitreal, we don’t need subretinal injections or anything like that, yet we have the longevity to match any kind of gene therapy.”
Heah, an ophthalmologist by training and biopharma vet who helped Bayer launch Eylea outside the US, brought both her own subject expertise and a group of seasoned drug developers to AsclepiX. From her perch in New Jersey, she manages two other staffers in the area, two in Baltimore and another two in California. Covid-19 has changed little.
“I’m used to running teams in Japan, Australia, Europe, US East Coast, West Coast,” she said. “In fact we realized we got more done without the travels.”
Slawin, who spoke to Endpoints News just before a flight from Houston to Florida, might be the exception. Depending on how the CEO search goes, he might continue leading the company or retreat back to a board now led by Spark co-founder Steve Altschuler, alongside Garabedian and Ben Askew, an R&D partner at Xontogeny.
