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.

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Pfiz­er's big block­buster Xel­janz flunks its post-mar­ket­ing safe­ty study, re­new­ing harsh ques­tions for JAK class

When the FDA approved Pfizer’s JAK inhibitor Xeljanz for rheumatoid arthritis in 2012, they slapped on a black box warning for a laundry list of adverse events and required the New York drugmaker to run a long-term safety study.

That study has since become a consistent headache for Pfizer and their blockbuster molecule. Last year, Pfizer dropped the entire high dose cohort after an independent monitoring board found more patients died in that group than in the low dose arm or a control arm of patients who received one of two TNF inhibitors, Enbrel or Humira.

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Top gene ther­a­py deals, M&A pacts in 2020 high­light an­oth­er big year in one of the hottest fields in bio­phar­ma

Chris Dokomajilar at DealForma has been crunching the numbers on gene therapy deals over the last 2 years and came away with a few key observations.

Both the upfront cash and deal totals last year backed off a bit from the record high hit in 2019, but the totals are still running well ahead of anything we’ve seen in the years prior to 2019/2020.
2020 R&D partnerships came in at 23 deals, with $1.1 billion in disclosed upfront cash and equity and more than $8.5 billion in total deal value. Looking at 2019-2020 M&A, Dokomajilar found: 9 Acquisitions, with over $11.1 billion in disclosed upfront cash and equity and more than $13.4 billion in total M&A value.

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Janet Woodcock (AP Images)

Ad­vo­ca­cy groups don't want Janet Wood­cock to head the FDA, blast­ing ‘reg­u­la­to­ry fail­ures’ in opi­oid cri­sis

It turns out the controversies around Janet Woodcock’s regulatory legacy weren’t limited to Sarepta’s eteplirsen.

A coalition of advocacy groups dedicated to the opioid crisis urged Norris Cochran and Xavier Becerra — the acting and designated HHS secretary, respectively — to keep her reign as interim FDA chief a “very short transition.” During her lengthy tenure as CDER, they add, Woodcock presided over “one of the worst regulatory agency failures in U.S. history.”

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Dean Li kicks off Mer­ck­'s post-Roger Perl­mut­ter era by team­ing with Arti­va and its off-the-shelf CAR-NK tech

Even though Dean Li has now officially taken over for Roger Perlmutter as R&D chief, Merck’s appetite for dealmaking continues to be ravenous.

Li struck his first big deal at the helm Thursday morning, hammering out a collaboration with Artiva Biotherapeutics that could earn the biotech nearly $1.9 billion when all is said and done. It’s a quick rise and validation for Artiva, which just last June launched with a $78 million Series A.

Take­da earns win for its TKI in­hibitor in tiny lung can­cer group — but GI side ef­fects could be an ear­ly red flag

Japanese drugmaker Takeda has made a big push in recent years to build a hand in oncology, particularly in the next-gen cancer space. One of those candidates, tyrosine kinase inhibitor (TKI) mobocertinib, recently earned the FDA’s interest in a small section of untreated lung cancer patients, but will severe GI side effects be a roadblock?

Takeda’s oral mobocertinib posted clinically significant objective response rates in a Phase I/II adaptive trial drugging metastatic non-small cell lung cancer patients with EGFR exon 20 gene mutations who had previously undergone platinum-based chemotherapy, according to data presented Thursday at the virtual World Conference on Lung Cancer.

Covid-19 roundup: EU and As­traZeneca trade blows over slow­downs; Un­usu­al unions pop up to test an­ti­bod­ies, vac­cines

After coming under fire for manufacturing delays last week, AstraZeneca’s feud with the European Union has spilled into the open.

The bloc accused the pharma giant on Wednesday of pulling out of a meeting to discuss cuts to its vaccine supplies, the AP reported. AstraZeneca denied the reports, saying it still planned on attending the discussion.

Early Wednesday, an EU Commission spokeswoman said that “the representative of AstraZeneca had announced this morning, had informed us this morning that their participation is not confirmed, is not happening.” But an AstraZeneca spokesperson later called the reports “not accurate.”

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Covid-19 roundup: Con­tro­ver­sy around colchicine per­co­lates af­ter study fail­ure; As­traZeneca's meet­ing with EU was 'con­struc­tive,' but did­n't solve much

A group of researchers at the Montreal Heart Institute has spelled out what they had called positive results suggesting that colchicine, an inexpensive oral anti-inflammatory drug commonly used to treat gout, could prevent Covid-19 complications in newly diagnosed patients.

The study failed its primary endpoint. But the latest scientific debate around treatments for the coronavirus is just beginning to brew.

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'Bank of BAR­DA': In­ves­ti­ga­tion finds HHS raid­ed pan­dem­ic pre­pared­ness funds for decade be­fore Covid-19

Before 2020, few Americans had ever heard of the Biomedical Advanced Research and Development Authority, BARDA, or its far-flung mission to stave off future pandemics and bio-threats. Allegedly, that made it a pretty good target for others in HHS who needed to scavenge some extra cash.

Over the last decade, other HHS officials raided BARDA’s coffers and misappropriated millions of dollars that Congress had earmarked to fund vaccine research and prepare for public health emergencies like Covid-19, according to a new report from the US Office of Special Counsel, which investigated a whistleblower report.