As­traZeneca’s $7B bet on Dai­ichi Sankyo’s an­ti­body drug con­ju­gate pays off with piv­otal da­ta to back their reg­u­la­to­ry pitch­es

Buoyed by the per­for­mance of its on­col­o­gy drugs, in March As­traZeneca chief Pas­cal So­ri­ot bet big to part­ner with Dai­ichi Sankyo on its ex­per­i­men­tal breast can­cer drug, with $1.35 bil­lion up­front in a deal worth up to rough­ly $7 bil­lion. On Wednes­day, the Japan­ese drug­mak­er said the ther­a­py had cleared a piv­otal mid-stage study, paving the way for reg­u­la­to­ry sub­mis­sions in the first half of fis­cal 2019.

The drug, trastuzum­ab derux­te­can, is an an­ti­body drug con­ju­gate (ADC) — ther­a­peu­tics in which a can­cer-killing tox­in is at­tached to a spe­cif­ic an­ti­body us­ing a biodegrad­able link­er — for can­cers that ex­press HER2, a pro­tein as­so­ci­at­ed with ag­gres­sive dis­ease that of­ten re­sides on cer­tain breast can­cer cells. About 30% of breast can­cers are HER2 pos­i­tive, ac­cord­ing to the NIH’s Na­tion­al Can­cer In­sti­tute. De­spite treat­ment with trastuzum­ab (Roche’s Her­ceptin), per­tuzum­ab (Roche’s Per­je­ta), and T-DM1 (Roche’s Kad­cy­la) — many breast can­cer pa­tients con­tin­ue to see their dis­ease progress, the com­pa­ny said.

In the phase II DES­TINY-Breast01 tri­al, trastuzum­ab derux­te­can was eval­u­at­ed in pa­tients with HER2-pos­i­tive un­re­sectable and/or metasta­t­ic breast can­cer, who dis­ease had pro­gressed de­spite Kad­cy­la ther­a­py.  The main goal of the 253-pa­tient study was ob­jec­tive re­sponse rate, while sec­ondary end­points in­clud­ed du­ra­tion of re­sponse, pro­gres­sion-free sur­vival and over­all sur­vival.

As as­sessed by an in­de­pen­dent re­view com­mit­tee, the re­sponse-rate in the heav­i­ly-pre­treat­ed glob­al pa­tient pop­u­la­tion mir­rored the “un­prece­dent­ed” clin­i­cal ac­tiv­i­ty in the re­cent­ly pub­lished phase I tri­al, in which a large pro­por­tion of pa­tients achieved dis­ease con­trol, and a long du­ra­tion of re­sponse, Dai­ichi said.

In this ear­ly-stage study, the first por­tion of the tri­al was ded­i­cat­ed to find­ing the op­ti­mal dose of the drug to use in the sec­ond tranche of the tri­al. From the evalu­able 111 pa­tients in the sec­ond phase of the tri­al — 66 achieved a con­firmed ob­jec­tive re­sponse; and 104 ex­pe­ri­enced con­firmed dis­ease con­trol, with a me­di­an fol­low-up of 9·9 months. The me­di­an du­ra­tion of re­sponse was 20·7 months, the me­di­an pro­gres­sion-free sur­vival was 22·1 months and tu­mour shrink­age was ob­served in 102 pa­tients with mea­sur­able le­sions who had at least one post­base­line scan. From a safe­ty and tol­er­a­bil­i­ty per­spec­tive, eval­u­at­ed pa­tients had one or more treat­ment-emer­gent ad­verse event of any grade.

An­toine Yver

De­tailed re­sults from the mid-stage study will be pre­sent­ed at an up­com­ing med­ical meet­ing.

“These re­sults con­firm our com­mit­ment to pur­sue ac­cel­er­at­ed reg­u­la­to­ry path­ways in HER2 pos­i­tive metasta­t­ic breast can­cer…” said An­toine Yver, glob­al head of on­col­o­gy R&D at Dai­ichi Sankyo, in a state­ment.

Trastuzum­ab derux­te­can, which has se­cured break­through ther­a­py sta­tus and fast track des­ig­na­tion from the FDA, is an HER2-tar­get­ed ADC with a topoi­so­merase I in­hibitor pay­load — a chemother­a­peu­tic agent de­signed to in­ter­rupt DNA repli­ca­tion in can­cer cells. It is be­ing de­vel­oped for oth­er HER2-ex­press­ing can­cers in­clud­ing gas­tric can­cer, with an added fo­cus on non-small cell lung and col­orec­tal can­cer.

If ap­proved, Dai­ichi will book drug sales in the Unit­ed States and cer­tain coun­tries in Eu­rope, in ad­di­tion to oth­er mar­kets where it has af­fil­i­ates — while As­traZeneca $AZN will book sales in all oth­er glob­al mar­kets, in­clud­ing Chi­na, Aus­tralia, Cana­da and Rus­sia.

So­ri­ot un­veiled the Dai­ichi tie-up months af­ter ex­e­cut­ing a re­struc­ture of its R&D by dis­man­tling the Med­Im­mune name and di­vid­ing de­vel­op­ment op­er­a­tions be­tween can­cer — un­der new ar­rival Jose Basel­ga — and every­thing else un­der Mene Pan­ga­los.

Pablo Legorreta, founder and CEO of Royalty Pharma AG, speaks at the annual Milken Institute Global Conference in Beverly Hills, California (Patrick T. Fallon/Bloomberg via Getty Images)

Cap­i­tal­iz­ing Pablo: The world’s biggest drug roy­al­ty buy­er is go­ing pub­lic. And the low-key CEO di­vulges a few se­crets along the way

Pablo Legorreta is one of the most influential players in biopharma you likely never heard of.

Over the last 24 years, Legorreta’s Royalty Pharma group has become, by its own reckoning, the biggest buyer of drug royalties in the world. The CEO and founder has bought up a stake in a lengthy list of the world’s biggest drug franchises, spending $18 billion in the process — $2.2 billion last year alone. And he’s become one of the best-paid execs in the industry, reaping $28 million from the cash flow last year while reserving 20% of the cash flow, less expenses, for himself.

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Paul Hudson, Sanofi CEO (Getty Images)

Sanofi CEO Paul Hud­son has $23B burn­ing a hole in his pock­et. And here are some hints on how he plans to spend that

Sanofi has reaped $11.1 billion after selling off a big chunk of its Regeneron stock at $515 a share. And now everyone on the M&A side of the business is focused on how CEO Paul Hudson plans to spend it.

After getting stung in France for some awkward politicking — suggesting the US was in the front of the line for Sanofi’s vaccines given American financial support for their work, versus little help from European powers — Hudson now has the much more popular task of managing a major cash cache to pull off something in the order of a big bolt-on. Or two.

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The Advance Clinical leadership team: CEO Yvonne Lungershausen, Sandrien Louwaars - Director Business Development Operations, Gabriel Kremmidiotis - Chief Scientific Officer, Ben Edwards - Chief Strategy Officer

How Aus­tralia De­liv­ers Rapid Start-up and 43.5% Re­bate for Ear­ly Phase On­col­o­gy Tri­als

About Avance Clinical

Avance Clinical is an Australian owned Contract Research Organisation that has been providing high-quality clinical research services to the local and international drug development industry for 20 years. They specialise in working with biotech companies to execute Phase 1 and Phase 2 clinical trials to deliver high-quality outcomes fit for global regulatory standards.

As oncology sponsors look internationally to speed-up trials after unprecedented COVID-19 suspensions and delays, Australia, which has led the world in minimizing the pandemic’s impact, stands out as an attractive destination for early phase trials. This in combination with the streamlined regulatory system and the financial benefits including a very favourable exchange rate and the R & D cash rebate makes Australia the perfect location for accelerating biotech clinical programs.

De­nali un­veils new way of cross­ing blood brain bar­ri­er as the big neu­ro­science bets en­ter its clin­i­cal years

Five years ago, as much of pharma began leaving neuroscience, three big-name scientists from Genentech and some A-list investors, including ARCH and Flagship, made a $217 million bet that new genetic insights and a reliance on biomarkers could bring them success. They called it Denali Therapeutics.

Still, Denali faced the problem that neuroscience developers have faced for decades: How do you get a large molecule across the blood-brain barrier, a natural defense evolved precisely to keep them out? Enzyme replacement therapy, for instance, would be a great candidate to treat several neurological disorders, but enzymes can’t cross the barrier.

Bryan Roberts, Venrock

Ven­rock sur­vey shows grow­ing recog­ni­tion of coro­n­avirus toll, wan­ing con­fi­dence in ar­rival of vac­cines and treat­ments

When Venrock partner Bryan Roberts went to check the results from their annual survey of healthcare leaders, what he found was an imprint of the pandemic’s slow arrival in America.

The venture firm had sent their form out to hundreds of insurance and health tech executives, investors, officials and academics on February 24 and gave them two weeks to fill it out. No Americans had died at that point but the coronavirus had become enough of a global crisis that they included two questions about the virus, including “Total U.S. deaths in 2020 from the novel coronavirus will be:”.

Dan O'Day, Gilead CEO (Andrew Harnik, AP Images)

UP­DAT­ED: Gilead leas­es part­ner rights to TIG­IT, PD-1 in a $2B deal with Ar­cus. Now comes the hard part

Gilead CEO Dan O’Day has brokered his way to a PD-1 and lined up a front row seat in the TIGIT arena, inking a deal worth close to $2 billion to align the big biotech closely with Terry Rosen’s Arcus. And $375 million of that comes upfront, with cash for the buy-in plus equity, along with $400 million for R&D and $1.22 billion in reserve to cover opt-in payments and milestones..

Hotly rumored for weeks, the 2 players have formalized a 10-year alliance that starts with rights to the PD-1, zimberelimab. O’Day also has first dibs on TIGIT and 2 other leading programs, agreeing to an opt-in fee ranging from $200 million to $275 million on each. There’s $500 million in potential TIGIT milestones on US regulatory events — likely capped by an approval — if Gilead partners on it and the stars align on the data. And there’s another $150 million opt-in payments for the rest of the Arcus pipeline.

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Roger Perlmutter, Merck R&D chief (YouTube)

UP­DAT­ED: Backed by BAR­DA, Mer­ck jumps in­to Covid-19: buy­ing out a vac­cine, part­ner­ing on an­oth­er and adding an­tivi­ral to the mix

Merck execs are making a triple play in a sudden leap into the R&D campaign against Covid-19. And they have more BARDA cash backing them up on the move.

Tuesday morning the pharma giant simultaneously announced plans to buy an Austrian biotech that has been working on a preclinical vaccine candidate, added a collaboration on another vaccine with the nonprofit IAVI and inked a deal with Ridgeback Biotherapeutics on an early-stage antiviral.

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Fabrice Chouraqui, Cellarity CEO-partner (LinkedIn)

Drug de­vel­op­er, Big Phar­ma com­mer­cial ex­ec, now an up­start biotech chief — Fab­rice Chouraqui is ready to try some­thing new as a ‘CEO-part­ner’ at Flag­ship

Fabrice Chouraqui’s career has taken some big twists along his life journey. He got his PharmD at Université Paris Descartes and jumped into the drug development game for a bit. Then he took a sharp turn and went back to school to get his MBA at Insead before returning to pharma on the commercial side.

Twenty years later, after steadily rising through the ranks and journeying the globe to nab a top job as president of US pharma for the Basel-based Novartis, Chouraqui exited in another career switch. And now he’s headed into a hybrid position as a CEO-partner at Flagship, where he’ll take a shot at leading Cellarity — one of the VC’s latest paradigm-changing companies of the groundbreaking model that aspires to deliver a new platform to the world of drug R&D.

Covid-19 roundup: Roche pairs Actem­ra with remde­sivir in new PhI­II; GSK makes its own 1B vac­cine man­u­fac­tur­ing plan

A month after a small study in France suggested that Roche’s IL-6 inhibitor Actemra helped Covid-19 patients do better — even as Sanofi and Regeneron found somewhat disappointing results with their rival drug — Roche is doubling down on the strategy.

The Swiss pharma giant is kicking off a second Phase III global placebo-controlled study involving Actemra. But rather than testing it as a monotherapy, they will add Gilead’s remdesivir to the regimen.

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