CEO Dipal Doshi (Entrada)

Piv­ot­ing to­ward neu­ro­mus­cu­lar dis­eases and Duchenne, En­tra­da locks down $116M crossover round

A lit­tle over two years since its last $59 mil­lion round, En­tra­da Ther­a­peu­tics is mak­ing some more noise Wednes­day with a nine-fig­ure crossover. And they’ve got a new fo­cus on neu­ro­mus­cu­lar dis­eases, led by Duchenne mus­cu­lar dy­s­tro­phy, as their re­search has broad­ened over the years.

En­tra­da pulled in a $116 mil­lion Se­ries B, with the funds pri­mar­i­ly slat­ed for get­ting its first Duchenne pro­gram in­to the clin­ic. The Boston-based biotech hopes to get past the IND ac­cep­tance phase for the lead can­di­date and then ex­pand in­to oth­er neu­ro­mus­cu­lar ar­eas.

The plat­form here, orig­i­nal­ly based on De­hua Pei’s lab re­search from Ohio State Uni­ver­si­ty, cen­ters around what En­tra­da calls en­do­so­mal es­cape ve­hi­cles, or EEVs. At their core, EEVs are cyclic pep­tides that trig­ger a process en­abling cell mem­branes to take in bi­o­log­ic con­ju­gates, CEO Di­pal Doshi told End­points News.

Back in 2018 dur­ing the Se­ries A fundraise, En­tra­da’s main ef­forts dealt with ap­ply­ing the EEVs to en­zyme re­place­ment ther­a­pies, with a pri­ma­ry tar­get of the mi­to­chon­dr­i­al dis­ease known as MNGIE. But last year, Doshi said, the com­pa­ny saw a “re­mark­able op­por­tu­ni­ty” in its oligonu­cleotide re­search and de­cid­ed to piv­ot to­ward this area in earnest.

Doshi now de­scribes En­tra­da as be­ing bro­ken in­to three parts: en­zyme re­place­ment, oligonu­cleotides and pro­tein degra­da­tion. As their sights have turned to­ward neu­ro­mus­cu­lar dis­eases with the oligonu­cleotides re­search, En­tra­da is now look­ing to part­ner out the MNGIE pro­gram.

“We’ve been very ex­plic­it to say, look, we’re not go­ing to be cute here, we want to find a home for this pro­gram,” Doshi told End­points. “We want to put it in­to a com­pa­ny that has the abil­i­ty to re­cruit an ul­tra-rare clin­i­cal study in the im­me­di­ate time frame.”

En­tra­da doesn’t nec­es­sar­i­ly have a spe­cif­ic part­ner­ship mod­el in mind, Doshi added, but they’re hop­ing to find a rare dis­ease-fo­cused phar­ma that can run the tri­al while team­ing up on man­u­fac­tur­ing.

When it comes to ap­ply­ing the EEVs to oligonu­cleotides for Duchenne and its oth­er neu­ro­mus­cu­lar pro­grams, En­tra­da does so by tar­get­ing the RNA. In such dis­eases, pa­tients have mu­ta­tions that pre­vent the trans­la­tion of RNA in­to pro­teins — in Duchenne’s case, the pro­tein in ques­tion is dy­s­trophin.

The oligonu­cleotides con­nect­ed to the EEVs force the cells to skip these mu­ta­tions in their ge­net­ic code, Doshi says, al­low­ing for the cre­ation of dy­s­trophin. And through this method, the dy­s­trophin can then get in­to the ap­pro­pri­ate mus­cles.

In ear­ly re­search, En­tra­da be­lieves it can dif­fer­en­ti­ate it­self from oth­er Duchenne play­ers due to the dy­s­trophin up­take they’ve seen in an­i­mal mod­els. Specif­i­cal­ly, re­searchers have record­ed sig­nif­i­cant up­take in the heart, which could val­i­date the EEV tech­nol­o­gy for use in oth­er neu­ro­mus­cu­lar dis­eases with sim­i­lar patholo­gies, Doshi said.

En­tra­da isn’t dis­clos­ing yet which ex­on it’s skip­ping in the lead pro­gram, but Doshi not­ed that they see a “bas­ket op­por­tu­ni­ty” in go­ing af­ter ex­ons 44, 45, 51 and 53 at around the same time. That would com­prise about 40% of all DMD pa­tients.

With Wednes­day’s fi­nanc­ing now in hand, En­tra­da is look­ing to get the lead Duchenne can­di­date in­to the clin­ic some­time next year.

Duchenne is an area that’s seen heavy in­vest­ment but few suc­cess­es in re­cent years. Last Au­gust, the FDA ap­proved the third Duchenne drug on the mar­ket, but reg­u­la­tors con­tin­ued to ex­press con­cerns about the ef­fi­ca­cy of the drug from NS Phar­ma. The oth­er two drugs come from Sarep­ta, where in one case the FDA in­fa­mous­ly flip-flopped from CRL to ac­cel­er­at­ed ap­proval af­ter just four months.

The round was led by Welling­ton Man­age­ment Com­pa­ny and joined by Red­mile Group, TCG Crossover, Green­spring As­so­ci­ates, Point72, Qatar In­vest­ment Au­thor­i­ty (“QIA”), Moore Strate­gic Ven­tures, Gold­man Sachs, Cure­Duchenne Ven­tures and one undis­closed glob­al in­vest­ment firm.

Ex­ist­ing in­vestors 5AM Ven­tures, MPM Cap­i­tal, Roche Ven­ture Fund, MRL Ven­tures Fund and Agent Cap­i­tal al­so par­tic­i­pat­ed in the Se­ries B.

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Chris Gibson (Photo By Vaughn Ridley/Sportsfile for Web Summit via Getty Images)

Re­cur­sion founders gin for­tunes as IPO back­ers show­er $436M on one of the biggest boasts in AI -- based on some very small deals

In the AI drug development world, boasting often comes with the territory. Yet few can rival Recursion when it comes to claiming the lead role in what company execs like to call the industrialization of drug development, with promises of continued exponential growth in the number of drugs it has in the pipeline.

On Friday, the Salt Lake City-based biotech translated its unicorn-sized boasts into a killer IPO, pricing more than 24 million shares at the high end of its range and bringing in $436 million — with a large chunk of that promised by some deep-pocket backers.

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Covid-19 vac­cine halt drags on, an FDA ap­point­ment at long last, the great CRO con­sol­i­da­tion, and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Conference season is upon us, and while we’d much prefer to be wandering down the hallways and presentation rooms in person, the team is ready to cover the most consequential data coming out of these scientific meetings. Get in touch early if you have news to share.

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Image: Shutterstock

Eli Lil­ly asks FDA to re­voke EUA for Covid-19 treat­ment

Eli Lilly on Friday requested that the FDA revoke the emergency authorization for its Covid-19 drug bamlanivimab, which is no longer as effective as a combo therapy because of a rise in coronavirus variants across the US.

“With the growing prevalence of variants in the U.S. that bamlanivimab alone may not fully neutralize, and with sufficient supply of etesevimab, we believe now is the right time to complete our planned transition and focus on the administration of these two neutralizing antibodies together,” Daniel Skovronsky, Lilly’s CSO, said in a statement.

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Osman Kibar (Samumed, now Biosplice)

Os­man Kibar lays down his hand at Sa­mumed, step­ping away from CEO role as his once-her­ald­ed an­ti-ag­ing biotech re­brands

Samumed made quite the entrance back in 2016, when it launched with some anti-aging programs and a whopping $12 billion valuation. That level of fanfare was nowhere to be found on Thursday, when the company added another $120 million to its coffers and quietly changed its name to Biosplice Therapeutics.

Why the sudden rebrand?

“We did that for obvious reasons,” CFO and CBO Erich Horsley told Endpoints News. “The name Biosplice echoes our science much more than Samumed does.”

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Ex­clu­sive in­ter­view: Pe­ter Marks on why full Covid-19 vac­cine ap­provals could be just months away

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, took time out of his busy schedule last Friday to discuss with Endpoints News all things related to his work regulating vaccines and the pandemic.

Marks, who quietly coined the name “Operation Warp Speed” before deciding to stick with his work regulating vaccines at the FDA rather than join the Trump-era program, has been the face of vaccine regulation for the FDA throughout the pandemic, and is usually spotted in Zoom meetings seated in front of his wife’s paintings.

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Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

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J&J faces CDC ad­vi­so­ry com­mit­tee again next week to weigh Covid-19 vac­cine risks

The CDC’s Advisory Committee on Immunization Practices punted earlier this week on deciding whether or not to recommend lifting a pause on the administration of J&J’s Covid-19 vaccine, but the committee will meet again in an emergency session next Friday to discuss the safety issues further.

The timing of the meeting likely means that the J&J vaccine will not return to the US market before the end of next week as the FDA looks to work hand-in-hand with the CDC to ensure the benefits of the vaccine still outweigh the risks for all age groups.

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Pascal Soriot (AstraZeneca via YouTube)

Af­ter be­ing goad­ed to sell the com­pa­ny, Alex­ion's CEO set some am­bi­tious new goals for in­vestors. Then Pas­cal So­ri­ot came call­ing

Back in the spring of 2020, Alexion $ALXN CEO Ludwig Hantson was under considerable pressure to perform and had been for months. Elliott Advisers had been applying some high public heat on the biotech’s numbers. And in reaching out to some major stockholders, one thread of advice came through loud and clear: Sell the company or do something dramatic to change the narrative.

In the words of the rather dry SEC filing that offers a detailed backgrounder on the buyout deal, Alexion stated: ‘During the summer and fall of 2020, Alexion also continued to engage with its stockholders, and in these interactions, several stockholders encouraged the company to explore strategic alternatives.’

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