Jay Bradner (Jeff Rumans for Endpoints News)

No­var­tis part­ners with the Gates Foun­da­tion on one of the Holy Grails in gene ther­a­py: a sim­ple, in vi­vo ap­proach to cur­ing sick­le cell dis­ease

Hav­ing helped ush­er in a “new era” of sick­le cell dis­ease treat­ment with Adakveo, No­var­tis has set its sights on an even high­er goal: a cu­ra­tive, rel­a­tive­ly low cost, once-and-done in vi­vo gene ther­a­py that can work in de­vel­op­ing coun­tries.

Tap­ping in­to the cof­fers of the Bill & Melin­da Gates Foun­da­tion, the phar­ma gi­ant says it will de­ploy its drug dis­cov­ery and gene ther­a­py ex­perts in search of a prod­uct that can cater to re­gions with less re­sources. And they’re us­ing to­day’s an­nounce­ment to open its doors to any oth­er groups that would like to pitch in.

Jay Brad­ner, who heads up the No­var­tis In­sti­tutes for Bio­Med­ical Re­search, tells End­points News that this col­lab­o­ra­tion dates back 5 years, when the phar­ma gi­ant mapped out a sick­le cell strat­e­gy run­ning the gamut from ac­cess to cur­rent­ly avail­able meds to an ex vi­vo gene edit­ed stem cell ap­proach to cur­ing sick­le cell dis­ease, now in the clin­ic.

“It’s our job to look around the cor­ner and imag­ine what the next wave of tech­nol­o­gy might be,” he says, “and this part­ner­ship with the Gates Foun­da­tion re­flects one piece of that for­ward-think­ing strat­e­gy — to imag­ine a sin­gu­lar ther­a­peu­tic in­fu­sion of vi­ral gene ther­a­py to cure this dis­ease.” They’ve learned a lot about CRISPRed ap­proach­es, which are tough to pull off in the most so­phis­ti­cat­ed med­ical cen­ters. Now they want to de­vel­op tech that could be used prac­ti­cal­ly any­where, in­clud­ing the poor­est coun­tries in Africa, Asia and Latin Amer­i­ca, which have lit­tle in terms of ba­sic hos­pi­tal in­fra­struc­ture.

Sue Steven­son

“Gene ther­a­py is al­ways about de­liv­ery,” notes Sue Steven­son, the ex­ec­u­tive di­rec­tor of hema­tol­ogy at NI­BR, as in­ves­ti­ga­tors look to cor­rect or re­pair a mu­tant gene, or in­sert a new one to do the job that was in­tend­ed. “The first step is go­ing to be fig­ur­ing out the best way to de­liv­er vi­ral vec­tors to the stem cells in vi­vo with a sin­gle ad­min­is­tra­tion.”

NI­BR will now have em­bed­ded labs ded­i­cat­ed to the task.

That’s a big, lengthy task, and it’s play­ing out as the lead­ers in the ex vi­vo side of R&D have ex­pe­ri­enced a line­up of com­plex chal­lenges and safe­ty threats that have de­layed the ar­rival of the pi­o­neers, in some cas­es rais­ing doubts as to whether they can ever make it to the mar­ket in af­flu­ent coun­tries.

The new part­ners are un­veil­ing their col­lab­o­ra­tion just a day af­ter blue­bird bio, which has one of the lead­ing gene ther­a­pies in the space, re­vealed it had halt­ed sick­le cell tri­als for Lenti­Glo­bin — in­clud­ing a Phase III — in or­der to in­ves­ti­gate two new se­ri­ous side ef­fects among pa­tients in the pro­gram.

Blue­bird’s ap­proach, like the CRISPR pro­grams un­der de­vel­op­ment at Ed­i­tas and Ver­tex/CRISPR Ther­a­peu­tics, in­volves tak­ing stem cells from pa­tients and en­gi­neer­ing them ex vi­vo be­fore in­fus­ing the gene edit­ed cells back in­to pa­tients.

Bio­phar­ma com­pa­nies, doc­tors and pa­tients placed high hopes on these drugs be­cause those cur­rent­ly on the mar­ket — in­clud­ing No­var­tis’ P-se­lectin-bind­ing Adakveo and Glob­al Blood Ther­a­peu­tics’ sick­le he­mo­glo­bin poly­mer­iza­tion in­hibitor Oxbry­ta — on­ly re­duce the fre­quen­cy of painful va­so-oc­clu­sive crises but can’t ful­ly pro­tect pa­tients from them, or the cu­mu­la­tive or­gan dam­age they can cause.

The fo­cus re­search team with­in NI­BR will now put all its ef­forts to com­ing up with an idea for a gene ther­a­py that can “be ad­min­is­tered once, di­rect­ly to the pa­tient, with­out the need to mod­i­fy the cells in a lab.”

“Gene ther­a­pies might help end the threat of dis­eases like sick­le cell, but on­ly if we can make them far more af­ford­able and prac­ti­cal for low-re­source set­tings,” Trevor Mundel, pres­i­dent of glob­al health at the Gates Foun­da­tion, added. “What’s ex­cit­ing about this project is that it brings am­bi­tious sci­ence to bear on that chal­lenge. It’s about treat­ing the needs of peo­ple in low­er-in­come coun­tries as a dri­ver of sci­en­tif­ic and med­ical progress, not an af­ter­thought.”

It’s the same phi­los­o­phy un­der­ly­ing the grant it gave In­tel­lia Ther­a­peu­tics, which is di­vert­ing from its CRISPR peers to re­search an in vi­vo way to ed­it stem cells.

The group didn’t dis­close just how much re­search fund­ing it’s hand­ing to No­var­tis, but says it will lend its “long his­to­ry and ex­pe­ri­ence in glob­al health to this col­lab­o­ra­tion.”

No­tably, No­var­tis — whose first gene ther­a­py, spinal mus­cu­lar at­ro­phy treat­ment Zol­gens­ma, holds the du­bi­ous ti­tle of the world’s most ex­pen­sive drug — says it will be bound by spe­cif­ic pro­vi­sions to sup­port glob­al ac­cess to any re­sult­ing med­i­cines.

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

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Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Tom Barnes (Orna)

The mR­NA era is here. MPM be­lieves the fu­ture be­longs to oR­NA — and Big Phar­ma wants a seat at the ta­ble

If the ultra-fast clinical development of Covid-19 vaccines opened the world’s eyes to the promises of messenger RNA, the subsequent delays in supply offered a crash course on the ultra-complex process of producing them. Even before the formulation and fill-finish steps, mRNA is the precious end product from an arduous journey involving enzyme-aided transcription, modification and purification.

For Bristol Myers Squibb, Novartis Institutes for Biomedical Research, Gilead’s Kite and Astellas, it’s time to rethink the way therapeutic RNA is engineered.

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Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

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S&P ex­pects steady ero­sion in Big Phar­ma's cred­it pro­file in 2021 as new M&A deals roll in — but don't un­der­es­ti­mate their un­der­ly­ing strength

S&P Global has taken a look at the dominant forces shaping the pharma market and come to the conclusion that there will be more downgrades than upgrades in 2021 — the 8th straight year of steady decline.

But it’s not all bad news. Some things are looking up, and there’s still plenty of money to be made in an industry that enjoys a 30% to 40% profit margin, once you factor in steep R&D expenses.

Tal Zaks, Moderna CMO (AP Photo/Rodrique Ngowi, via still image from video)

CMO Tal Zaks bids Mod­er­na a sur­prise adieu as biotech projects $18.4B in rev­enue, plots post-Covid ex­pan­sion

How do you exit a company after six years in style? Developing one of the most lucrative and life-saving products in pharma history is probably not the worst way to go.

Tal Zaks, Moderna’s CMO since 2015, will leave the mRNA biotech in September, the biotech disclosed in their annual report this morning. The company has already retained the recruitment firm Russell Reynolds to find a replacement.

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Glax­o­SmithK­line re­thinks strat­e­gy for Covid-19 an­ti­body — not the Vir ones — af­ter tri­al flop. Is there hope in high-risk pa­tients?

In the search for a better Covid-19 therapeutic, GlaxoSmithKline and Vir have partnered up on two antibodies they hope have a chance. GSK is also testing its own in-house antibody, and early results may have shut the door on its widespread use.

A combination of GSK’s monoclonal antibody otilimab plus standard of care couldn’t best standard of care alone in preventing death and respiratory failure in hospitalized Covid-19 patients after 28 days, according to data from the Phase IIa OSCAR study unveiled Thursday.

Photo: Shutterstock

Bio­phar­ma's suc­cess rate in bring­ing drugs to mar­ket has long been abysmal. Can new tools help rewrite that trou­bled past?

In 2011, a team of researchers at British drugmaker AstraZeneca had a problem they were looking to solve.

For years, drug discovery and development were a wasteland for innovation. Novel drugs largely fell into one of two categories — monoclonal antibodies and small molecules — and new therapeutic modalities were hard to come by. After a rush of promising approvals in the late 1990s — including then-Biogen’s CD20 targeting antibody breakthrough Rituxan — the field stagnated and attrition rates stayed sky-high. What exactly is the industry doing wrong? AstraZeneca asked itself.

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