Alex­ion doles out $22M up­front for two pre­clin­i­cal RNAi drugs from Dicer­na

For­mer biotech ace Alex­ion Phar­ma­ceu­ti­cals is still shop­ping to fat­ten its pipeline as it con­tin­ues to shake off a sales prac­tices scan­dal linked to its ex­pen­sive rare dis­ease drug Soliris that cul­mi­nat­ed in an ex­ec­u­tive ex­o­dus and top-to-bot­tom re­or­ga­ni­za­tion. On Wednes­day, the Boston, MA-based com­pa­ny said it would fork out $22 mil­lion up­front to co-de­vel­op two pre­clin­i­cal RNAi ther­a­pies owned by Dicer­na Phar­ma­ceu­ti­cals $DR­NA.

The agree­ment fol­lows a Sep­tem­ber deal to buy pri­vate­ly held Syn­tim­mune for up to $1.2 bil­lion, and the ac­qui­si­tion of Swe­den’s Wil­son Ther­a­peu­tics for $855 mil­lion in April.

RNAi ther­a­pies of­fer the po­ten­tial to over­come key lim­i­ta­tions of tra­di­tion­al ap­proach­es to treat­ment, and has long in­ter­est­ed drug de­vel­op­ers, but has fre­quent­ly been met with clin­i­cal fail­ure. RNA in­ter­fer­ence (RNAi) is a process in which cer­tain dou­ble-strand­ed RNA mol­e­cules in­hib­it the ex­pres­sion of dis­ease-caus­ing genes by de­stroy­ing the mes­sen­ger RNAs (mR­NAs) of those genes. Rather than tar­get­ing and bind­ing to pro­teins to in­hib­it their ac­tiv­i­ty like mon­o­clon­al an­ti­bod­ies, RNAi ex­erts its ef­fects one step ear­li­er in the gene si­lenc­ing process by tar­get­ing the mR­NA, the in­struc­tion set that di­rects the build­ing of dis­ease-caus­ing pro­teins. Ear­li­er this year, the FDA ap­proved the first-ever RNAi drug, On­pat­tro, for the treat­ment of the hered­i­tary transthyretin-me­di­at­ed (hAT­TR) amy­loi­do­sis, which is a rare, pro­gres­sive life-threat­en­ing dis­ease.

Dou­glas Fam­brough

Dicer­na is fo­cus­ing on liv­er-tar­get­ed dis­eases that have not been amenable to con­ven­tion­al ther­a­pies, and says its GalXC RNAi plat­form has fu­eled a pipeline of ther­a­pies de­signed to con­quer chal­lenges posed by pri­or gen­er­a­tions of RNAi ther­a­peu­tics — the tech­nol­o­gy is de­signed to si­lence the ex­pres­sion of dis­ease-dri­ving genes in a way that is “high­ly spe­cif­ic, gen­er­al­ly well tol­er­at­ed, and al­lows for con­ve­nient, in­fre­quent sub­cu­ta­neous ad­min­is­tra­tion,” ac­cord­ing to CEO Dou­glas Fam­brough.

“These ther­a­pies mi­grate to the liv­er where com­ple­ment pro­teins are pro­duced and de­grade the mes­sen­ger RNA be­fore the com­ple­ment pro­tein can be trans­lat­ed. As such, these treat­ments would op­er­ate more up­stream than Alex­ion’s cur­rent com­ple­ment an­ti­bod­ies that block the com­ple­ment pro­teins af­ter they have been cre­at­ed, and the mech­a­nism should al­so pro­vide a longer du­ra­tion of ef­fect than an­ti­bod­ies,” not­ed Leerink’s Ge­of­frey Porges in a note.

As part of the deal, Dicer­na is el­i­gi­ble to re­ceive po­ten­tial de­vel­op­ment and reg­u­la­to­ry mile­stone pay­ments of up to $105 mil­lion per tar­get, in ad­di­tion to ag­gre­gate sales mile­stones of up to $160 mil­lion and roy­al­ties on fu­ture prod­uct sales. In ad­di­tion, Alex­ion is mak­ing a con­cur­rent $15 mil­lion eq­ui­ty in­vest­ment in Dicer­na at a price of 17.95 per share, a pre­mi­um of near­ly 47% to its Tues­day close. Alex­ion, which al­so re­port­ed high­er-than-ex­pect­ed Q3 earn­ings and rev­enue that just missed an­a­lyst es­ti­mates on Wednes­day, has the right to ex­er­cise op­tions on two ad­di­tion­al GalXC RNAi mol­e­cules from Dicer­na un­der the agree­ment.

Ri­val RNAi drug de­vel­op­er — and mak­er of On­pat­tro — Al­ny­lam Phar­ma­ceu­ti­cals $AL­NY an­nounced this April that Dicer­na had agreed to fork out $25 mil­lion in cash and stock to set­tle a law­suit filed in 2015 claim­ing it stole in­tel­lec­tu­al prop­er­ty re­lat­ed to Al­ny­lam’s gene-si­lenc­ing tech­nol­o­gy to de­vel­op ther­a­pies, open­ing the door for Dicer­na to forge new al­liances.

Oth­er play­ers in the RNAi field in­clude Ar­row­head Phar­ma­ceu­ti­cals $AR­WR, RXi Phar­ma­ceu­ti­cals $RXII, Si­lence Ther­a­peu­tics (LSE: $SLN) and iTher­a­peu­tics.

UP­DAT­ED: In sur­prise switch, Bris­tol-My­ers is sell­ing off block­buster Ote­zla, promis­ing to com­plete Cel­gene ac­qui­si­tion — just lat­er

Apart from revealing its checkpoint inhibitor Opdivo blew a big liver cancer study on Monday, Bristol-Myers Squibb said its plans to swallow Celgene will require the sale of blockbuster psoriasis treatment Otezla to keep the Federal Trade Commission (FTC) at bay.

The announcement — which has potentially delayed the completion of the takeover to early 2020 — irked investors, triggering the New York-based drugmaker’s shares to tumble Monday morning in premarket trading.

Celgene’s Otezla, approved in 2014 for psoriasis and psoriatic arthritis, is a rising star. It generated global sales of $1.6 billion last year, up from the nearly $1.3 billion in 2017. Apart from the partial overlap of Bristol-Myers injectable Orencia, the company’s rival oral TYK2 psoriasis drug is in late-stage development, after the firm posted encouraging mid-stage data on the drug, BMS-986165, last fall. With Monday’s decision, it appears Bristol-Myers is favoring its experimental drug, and discounting Otezla’s future.

The move blindsided some analysts. Credit Suisse’s Vamil Divan noted just days ago:

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Novotech CEO Dr. John Moller

Novotech CRO Award­ed Frost & Sul­li­van Best Biotech CRO Asia-Pa­cif­ic 2019

Known in the in­dus­try as the Asia-Pa­cif­ic CRO, Novotech is now lead CRO ser­vices provider for the grow­ing num­ber of in­ter­na­tion­al biotechs se­lect­ing the re­gion for their stud­ies.

Re­flect­ing this Asia-Pa­cif­ic growth, Novotech staff num­bers are up 20% since De­cem­ber 2018 to 600 in-house clin­i­cal re­search peo­ple across a full range of ser­vices, across the re­gion.

Novotech’s ca­pa­bil­i­ties have been rec­og­nized by an­a­lysts like Frost & Sul­li­van, most re­cent­ly with the pres­ti­gious Asia-Pa­cif­ic CRO Biotech of the year award for best prac­tices in clin­i­cal re­search for biotechs for the fifth year. See oth­er awards here.

Bris­tol-My­ers star Op­di­vo fails sur­vival test in a matchup with Nex­avar aimed at shak­ing up the big HCC mar­ket

Bris­tol-My­ers Squibb has suf­fered an­oth­er painful set­back in its years-long quest to ex­pand the reach of Op­di­vo. The phar­ma gi­ant this morn­ing not­ed that their Check­mate-459 study com­par­ing Op­di­vo with Bay­er’s Nex­avar in front­line cas­es of he­pa­to­cel­lu­lar car­ci­no­ma — the most com­mon form of liv­er can­cer — failed to hit the pri­ma­ry end­point on over­all sur­vival.

This was a sig­nif­i­cant mile­stone in Bris­tol-My­ers’ tal­ly of PD-1 cat­a­lysts this year. Nex­avar (so­rafenib) has been the stan­dard of care in front­line HCC for the past decade, though Op­di­vo has been mak­ing head­way in sec­ond-line HCC cas­es, where it’s go­ing toe-to-toe with Bay­er’s Sti­var­ga (re­go­rafenib) af­ter re­cent ap­provals shook up the mar­ket.

Fol­low­ing news of job cuts in Eu­ro­pean R&D ops, Sanofi con­firms it’s of­fer­ing US work­ers an 'ear­ly ex­it'

Ear­li­er in the week we learned that Sanofi was bring­ing out the bud­get ax to trim 466 R&D jobs in Eu­rope, re­tool­ing its ap­proach to car­dio as re­search chief John Reed beefed up their work in can­cer and gene ther­a­pies. And we’re end­ing the week with news that the phar­ma gi­ant has al­so been qui­et­ly re­duc­ing staff in the US, tar­get­ing hun­dreds of jobs as the com­pa­ny push­es vol­un­tary buy­outs with a fo­cus on R&D sup­port ser­vices.

Suf­fer­ing No­var­tis part­ner Cona­tus is pack­ing it in on NASH af­ter a se­ries of un­for­tu­nate tri­al events

The NASH par­ty is over at No­var­tis-backed Cona­tus. And this time they’re turn­ing off the lights.

More than 2 years af­ter No­var­tis sur­prised the biotech in­vest­ment com­mu­ni­ty with its $50 mil­lion up­front and promise of R&D sup­port to part­ner with the lit­tle biotech on NASH — ig­nit­ing a light­ning strike for the share price — Cona­tus $CNAT is back with the lat­est bit­ter tale to tell about em­ri­c­as­an, which once in­spired con­fi­dence at the phar­ma gi­ant.

Dean Hum. Nasdaq via YouTube

Gen­fit goes to Chi­na with a deal worth up to $228M for NASH drug

Fresh off the high of its Nas­daq IPO de­but, and the low of com­par­isons to Cymabay — whose NASH drug re­cent­ly stum­bled — Gen­fit on Mon­day un­veiled an up to $228 mil­lion deal with transpa­cif­ic biotech Terns Phar­ma­ceu­ti­cals to de­vel­op its flag­ship ex­per­i­men­tal liv­er drug — elafi­bra­nor — in Greater Chi­na.

The deal comes weeks af­ter Gen­fit $GN­FT is­sued a fiery de­fense of its dual PPAR ag­o­nist elafi­bra­nor, when com­peti­tor Cymabay’s PPARδ ag­o­nist, se­ladel­par, fiz­zled in a snap­shot of da­ta from an on­go­ing mid-stage tri­al. The main goal at the end of 12 weeks was for se­ladel­par to in­duce a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in liv­er fat con­tent, but da­ta showed that pa­tients on the place­bo ac­tu­al­ly per­formed bet­ter.

Alex­ion wins pri­or­i­ty re­view for Ul­tomiris' aHUS in­di­ca­tion; FDA ex­pands ap­proval of Ver­tex's Symdeko

→ Alex­ion $ALXN has scored a speedy re­view for Ul­tomiris for pa­tients with atyp­i­cal he­molyt­ic ure­mic syn­drome (aHUS) af­ter post­ing pos­i­tive da­ta from a piv­otal study in Jan­u­ary. The drug is the rare dis­ease com­pa­ny’s shot at pro­tect­ing its block­buster blood dis­or­der fran­chise that is cur­rent­ly cen­tered around its flag­ship drug, Soliris, which is a com­ple­ment in­hibitor typ­i­cal­ly ad­min­is­tered every two weeks. Ul­tomiris has a sim­i­lar mech­a­nism of ac­tion but re­quires less-fre­quent dos­ing — every eight weeks. The de­ci­sion date has been set to Oc­to­ber 19. Late last year, Ul­tomiris se­cured ap­proval for noc­tur­nal he­mo­glo­bin­uria (PNH) pa­tients.

Bet­ter than Am­bi­en? Min­er­va soars on PhI­Ib up­date on sel­torex­ant for in­som­nia

A month af­ter roil­ing in­vestors with what skep­tics dis­missed as cher­ry pick­ing of its de­pres­sion da­ta, Min­er­va is back with a clean slate of da­ta from its Phase IIb in­som­nia tri­al.

In a de­tailed up­date, the Waltham, MA-based biotech said sel­torex­ant (MIN-202) hit both the pri­ma­ry and sev­er­al sec­ondary end­points, ef­fec­tive­ly im­prov­ing sleep in­duc­tion and pro­long­ing sleep du­ra­tion. In­ves­ti­ga­tors made a point to note that the ef­fects were con­sis­tent across the adult and el­der­ly pop­u­la­tions, with the lat­ter more prone to the sleep dis­or­der.

Gene ther­a­py biotech sees its stock rock­et high­er on promis­ing re­sults for rare cas­es of but­ter­fly dis­ease

Shares of Krys­tal Biotech took off this morn­ing $KRYS af­ter the lit­tle biotech re­port­ed promis­ing re­sults from its gene ther­a­py to treat a rare skin dis­ease called epi­der­mol­y­sis bul­losa.

Fo­cus­ing on an up­date with 4 new pa­tients, re­searchers spot­light­ed the suc­cess of KB103 in clos­ing some stub­born wounds. Krys­tal says that of 4 re­cur­ring and 2 chron­ic skin wounds treat­ed with the gene ther­a­py, the KB103 group saw the clo­sure of 5. The 6th — a chron­ic wound, de­fined as a wound that had re­mained open for more than 12 weeks — was par­tial­ly closed. That brings the to­tal so far to 8 treat­ed wounds, with 7 clo­sures.