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.”

Steve Altschuler

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.

Digital therapeutics company Better Therapeutics announced on Thursday that it’s cutting 35% of its staff as it awaits FDA clearance for its first product.

The company, which launched eight years ago, is one of a growing group of companies seeking a digital alternative to traditional medicine. The space saw a record $7.5 billion in investments in 2021, according to Chris Dokomajilar at DealForma, with uses spanning ADHD, PTSD and other indications. However, private insurers have been slow to hop on board.

The FDA’s Oncology Center of Excellence has been a bright spot within the agency in terms of speeding new treatments to patients. That flexibility was on full display this morning as FDA released new draft guidance spelling out exactly how oncology drug developers can fulfill both the accelerated and full approval’s requirements with just a single randomized controlled trial.

While Congress recently passed legislation that will allow FDA to require confirmatory trials to be recruiting and ongoing prior to granting an accelerated approval, the agency is now making clear that the initial trial used to win the AA, if designed appropriately, can also serve as the trial for converting the accelerated approval into a full approval.