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.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data is messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data is exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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David Lockhart, ReCode Therapeutics CEO

Pfiz­er throws its weight be­hind LNP play­er eye­ing mR­NA treat­ments for CF, PCD

David Lockhart did not see the meteoric rise of messenger RNA and lipid nanoparticles coming.

Thanks to the worldwide fight against Covid-19, mRNA — the genetic code that can be engineered to turn the body into a mini protein factory — and LNPs, those tiny bubbles of fat carrying those instructions, have found their way into hundreds of millions of people. Within the biotech world, pioneers like Alnylam and Intellia have demonstrated just how versatile LNPs can be as a delivery vehicle for anything from siRNA to CRISPR/Cas9.

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David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

Leen Kawas (L) has resigned as CEO of Athira and will be replaced by COO Mark Litton

Ex­clu­sive: Athi­ra CEO Leen Kawas re­signs af­ter in­ves­ti­ga­tion finds she ma­nip­u­lat­ed da­ta

Leen Kawas, CEO and founder of the Alzheimer’s upstart Athira Pharma, has resigned after an internal investigation found she altered images in her doctoral thesis and four other papers that were foundational to establishing the company.

Mark Litton, the company’s COO since June 2019 and a longtime biotech executive, has been named full-time CEO. Kawas, meanwhile, will no longer have ties to the company except for owning a few hundred thousand shares.

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Sen. Richard Durbin (D-IL, foreground) and Sen. Richard Blumenthal (D-CT) (Patrick Semansky/AP Images)

Sen­a­tors back FDA's plan to re­quire manda­to­ry pre­scriber ed­u­ca­tion for opi­oids

Three Senate Democrats are backing an FDA plan to require mandatory prescriber education for opioids as overdose deaths have risen sharply over the past decade, with almost 97,000 American opioid-related overdose deaths in the past year alone.

While acknowledging a decline in overall opioid analgesic dispensing in recent years, the FDA said it’s reconsidering the need for mandatory prescriber training through a REMS given the current situation with overdoses, and is seeking input on the aspects of the opioid crisis that mandatory training could potentially mitigate.

Suresh Katta, Saama CEO (via YouTube)

As AI con­tin­ues to en­tice Big Phar­ma, a Car­lyle-led drug­mak­er syn­di­cate shells out $430M for cloud com­put­ing play­er

The AI revolution permeating Big Pharma took a big financial step forward Wednesday, with VCs and major drugmakers coming together to acquire a cloud-focused company.

Led by the Carlyle Group, the investors will put up $430 million for a majority stake in Saama, a company that collects patient data to help speed along the drug development process. The investment arms of Pfizer, Merck, Amgen and McKesson all participated in the financing, in addition to other prominent life sciences VCs like Northpond.

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Raju Mohan, Ventyx Biosciences CEO

Ven­tyx sprints to Wall Street less than a year af­ter emerg­ing from stealth

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

It took seven months from exiting “quiet mode” for Ventyx Biosciences to land its very own stock ticker, raising $165 million in venture funds along the way.

Now, after pricing a massive $151.5 million IPO, the Encinitas, CA-based biotech is gunning for Phase II.

Ventyx priced close to 9.5 million shares at $16 apiece on Wednesday, the midpoint of its $15 to $17 range. CEO Raju Mohan filed the S-1 papers at the end of September, just over a week after unveiling a $114 million Series B round. He penciled in the standard figure of $100 million at first, likely knowing that in the last year, it’s been common for biotechs to raise much more than those initial estimates.

Bris­tol My­ers pledges to sell its Ac­celeron shares as ac­tivist in­vestors cir­cle Mer­ck­'s $11.5B buy­out — re­port

Just as Avoro Capital’s campaign to derail Merck’s proposed $11.5 billion buyout of Acceleron gains steam, Bristol Myers Squibb is leaning in with some hefty counterweight.

The pharma giant is planning to tender its Acceleron shares, Bloomberg reported, which add up to a sizable 11.5% stake. Based on the offer price, the sale would net Bristol Myers around $1.3 billion.

To complete its deal, Merck needs a majority of shareholders to agree to sell their shares.