Theresa Heah, Kevin Slawin, Chris Garabedian (AsclepiX)

Bet­ter than Eylea, as durable as gene ther­a­py? Per­cep­tive, Xon­toge­ny boost oph­thalmic star­tup's shot for best of all worlds

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.

Regeneron CEO Leonard Schleifer speaks at a meeting with President Donald Trump, members of the Coronavirus Task Force, and pharmaceutical executives in the Cabinet Room of the White House (AP Photo/Andrew Harnik)

OWS shifts spot­light to drugs to fight Covid-19, hand­ing Re­gen­eron $450M to be­gin large scale man­u­fac­tur­ing in the US

The US government is on a spending spree. And after committing billions to vaccines defense operations are now doling out more of the big bucks through Operation Warp Speed to back a rapid flip of a drug into the market to stop Covid-19 from ravaging patients — possibly inside of 2 months.

The beneficiary this morning is Regeneron, the big biotech engaged in a frenzied race to develop an antibody cocktail called REGN-COV2 that just started a late-stage program to prove its worth in fighting the virus. BARDA and the Department of Defense are awarding Regeneron a $450 million contract to cover bulk delivery of the cocktail starting as early as late summer, with money added for fill/finish and storage activities.

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UP­DAT­ED: Bio­gen shares spike as ex­ecs com­plete a de­layed pitch for their con­tro­ver­sial Alzheimer's drug — the next move be­longs to the FDA

Biogen is stepping out onto the high wire today, reporting that the team working on the controversial Alzheimer’s drug aducanumab has now completed their submission to the FDA. And they want the agency to bless it with a priority review that would cut the agency’s decision-making time to a mere 6 months.

The news drove a 10% spike in Biogen’s stock $BIIB ahead of the bell.

Part of that spike can be attributed to a relief rally. Biogen execs rattled backers and a host of analysts earlier in the year when they unexpectedly delayed their filing to the third quarter. That delay provoked all manner of speculation after CEO Michel Vounatsos and R&D chief Al Sandrock failed to persuade influential observers that the pandemic and other factors had slowed the timeline for filing. Actually making the pitch at least satisfies skeptics that the FDA was not likely pushing back as Biogen was pushing in. From the start, Biogen execs claimed that they were doing everything in cooperation with the FDA, saying that regulators had signaled their interest in reviewing the submission.

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Sin­gu­lar fo­cus on ROR1 earns Velos­Bio $137M to fund PhI ADC and oth­er pro­grams

Years after selling Acerta to AstraZeneca for $7 billion, largely on the promise of its BTK inhibitor, Dave Johnson has once again gathered hefty financial support behind a new cancer target.

Matrix Capital Management and Surveyor Capital are leading a $137 million round for VelosBio, which has recently begun a Phase I study for its lead antibody-drug conjugate targeted against ROR1. Johnson took up the CEO post in October 2018.

Zai Lab inks Chi­na deal with Turn­ing Point with $25M up­front; Xen­cor, Atre­ca team up on bis­pecifics

Zai Lab is paying out a $25 million upfront for the rights to sell Turning Point Therapeutics’ lead drug repotrectinib in Greater China. The San Diego-based biotech is also in line for up to $151 million in milestones, along with mid-to-high teen royalties. Zai plans to add sites to the Phase II trial of the drug, which is designed to treat ROS1-positive advanced NSCLC in patients who were not previously treated with a TKI.

Alexander Vos, VarmX CEO

'Fun­da­men­tal­ly dif­fer­en­t' from Por­to­la, Dutch biotech lands €32M to steer an­ti-an­ti­co­ag­u­lant through the clin­ic

Portola may not have had much success proving the commercial value of an anti-anticoagulant, but that’s not stopping European investors from pouring $36.2 million (€32 million) into what they see as a superior approach put forth by a Dutch biotech.

VarmX’s blood thinner reversal agent stems from research done by founder and CSO Pieter Reitsma at Leiden University Medical Center. A modified recombinant form of factor X, VMX-C001 “has an insertion of 16 amino acids that replaces a stretch of 7 amino acids in the so-called serine protease domain” compared to the native coagulation factor, CEO Alexander Vos told Endpoints News.

FDA bars the door — for now — against Mer­ck’s star can­cer drug af­ter Roche beat them to the punch

Merck has been handed a rare setback at the FDA.

After filing for the accelerated approval of a combination of their star PD-1 drug Keytruda with Eisai’s Lenvima as a first-line treatment for unresectable hepatocellular carcinoma, the FDA nixed the move, handing out a CRL because Roche beat them to the punch on the same indication by a matter of weeks.

According to Merck:

Ahead of the Prescription Drug User Fee Act action dates of Merck’s and Eisai’s applications, another combination therapy was approved based on a randomized, controlled trial that demonstrated overall survival. Consequently, the CRL stated that Merck’s and Eisai’s applications do not provide evidence that Keytruda in combination with Lenvima represents a meaningful advantage over available therapies for the treatment of unresectable or metastatic HCC with no prior systemic therapy for advanced disease. Since the applications for KEYNOTE-524/Study 116 no longer meet the criteria for accelerated approval, both companies plan to work with the FDA to take appropriate next steps, which include conducting a well-controlled clinical trial that demonstrates substantial evidence of effectiveness and the clinical benefit of the combination.

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Roger Tung, Concert Pharmaceuticals CEO (Concert)

Con­cert gets BTD for alope­cia drug, set­ting up a late-stage show­down with gi­ant ri­val Pfiz­er

Concert Pharmaceuticals’ path to developing a drug that treats alopecia areata has been bumpy, but the pharma company scored a win Wednesday.

The FDA granted Concert a Breakthrough Therapy Designation (BTD) for its oral Janus kinase inhibitor, named CTP-543, paving the way for a Phase III study of the drug to begin in the fourth quarter of 2020. The news follows positive Phase II results from last September, which saw the drug meet its primary endpoint in both 8 mg and 12 mg twice-daily doses.

Covid-19 roundup: Mod­er­na sticks to Ju­ly for its Phase III as ru­mors swirl; Fol­low­ing US lead, EU buys up Covid-19 treat­ments

The Phase III might be delayed from its original early July goal, but Moderna says it will still kick off the pivotal study for what could ultimately be the first Covid-19 vaccine before the end of the month.

A day after Reuters reported that squabbling between the Cambridge biotech and government regulators had held up the trial by about two weeks, Moderna released a statement saying that they had completed enrollment of their 650-person Phase II trial and were on track to begin Phase III by the end of the month. The protocol for that study, which is meant to prove whether or not the vaccine can prevent people from becoming sick, has been finalized, they said.

Stephen Hahn, AP

Trump and Navar­ro press again for hy­drox­y­chloro­quine. Can the FDA stay in­de­pen­dent?

Tuesday morning, economist and Trump advisor Peter Navarro walked onto the White House driveway and promptly brought a political cloud back onto the FDA.

Speaking to a White House pool reporter, Navarro said that four Detroit doctors were, based on a single disputed study, filing for the FDA to again issue an emergency authorization for hydroxychloroquine, the anti-malarial pill that President Trump hyped for months as a Covid-19 treatment over the objections of his own scientists. Then, while avoiding directly calling for the FDA to OK the drug, blasted the agency. He said its decision to pull an earlier authorization “was based on bad science” and “had a tremendously negative effect” on doctors and patients.

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