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.

Deborah Dunsire. Lundbeck

UP­DAT­ED: Deb­o­rah Dun­sire is pay­ing $2B for a chance to leap di­rect­ly in­to a block­buster show­down with a few of the world's biggest phar­ma gi­ants

A year after taking the reins as CEO of Lundbeck, Deborah Dunsire is making a bold bid to beef up the Danish biotech’s portfolio of drugs in what will likely be a direct leap into an intense rivalry with a group of giants now carving up a growing market for new migraine drugs.

Bright and early European time Monday morning the company announced that it will pay up to about $2 billion to buy Alder, a little biotech that is far along the path in developing a quarterly IV formulation of a CGRP drug aimed at cutting back the number of crippling migraines patients experience each month. In a followup call, Dunsire also noted that the company will likely need 200 to 250 reps for this marketing task on both sides of the Atlantic. And analysts were quick to note that the dealmaking at Lundbeck isn’t done, with another $2 billion to $3 billion available for more deals to beef up the pipeline.

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Scott Gottlieb, AP Images

Scott Got­tlieb has a new board po­si­tion to add to the re­sume — and this one is fo­cused on a fa­vorite sub­ject

Scott Gottlieb has another position to add to his lengthy roster of boards and advisory roles in the wake of his departure from the helm of the FDA.

He’ll be joining the advisory board of FasterCures, a think tank which former junk bond king Michael Milken set up to help drive more drugs to the market, looking to accelerate drug R&D. That’s a subject close to the heart of Gottlieb, who blazed a trail at the FDA focused on hustling up the process. That helped endear him to the industry, making him one of the most popular commissioners in FDA history.

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Karyopharm lines up $150 mil­lion cash in­jec­tion to back con­tro­ver­sial drug launch

Karyopharm has entered into a royalty agreement worth up to $150 million to back the launch of their multiple myeloma drug — recently approved by the FDA over the objections of a majority of the agency’s outside experts.

The deal with HealthCare Royalty Partners, worth $75 million now and $75 million once certain regulatory and commercial milestones have been reached, will fund the commercialization of Karyopharm’s oral SINE compound Xpovio (selinexor) for patients with multiple myeloma who have already had at least four prior therapies. The money will help Karyopharm as it markets its newly approved drug and pushes through clinical trials testing the drug on refractory multiple myeloma patients with one to three therapies and patients with treatment-resistant diffuse large B-cell lymphoma. It will give Karyopharm a cushion through mid-2021.

Af­ter a run of CT­LA-4 com­bo fail­ures, sci­en­tists spot­light a way to make it work — in se­lect pa­tients

CTLA-4/PD-(L)1 combinations have been one of the El Dorados of oncology, its promise forever behind that next hill but apparently unattainable after a series of pivotal clinical failures. But researchers at New York’s Memorial Sloan Kettering Cancer Center and the Technical University of Munich think they may know how to fix what’s wrong and boost the drive to next-gen cancer combos.

In a preclinical animal research program, researchers found that within a cell, checkpoints rely on a specific molecule — RNA-sensing molecule RIG-I — to work. If that sounds familiar, it’s because it has already been identified as a target for boosting immune responses and was subject to at least one Phase I/II trial. Pfizer in December allied itself with Kineta with $15 million upfront and $505 million in potential milestones to develop RIG-I immunotherapies, and three years ago Merck purchased German upstart Rigontec for $137 million upfront and over $400 million in potential milestones for the same purpose.

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

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Pur­due Phar­ma files for bank­rupt­cy as first step in $10B opi­oid set­tle­ment

It’s settled. Purdue Pharma has filed for bankruptcy as part of a deal that would see the OxyContin maker hand over $10 billion in cash and other contributions to mitigate the opioid crisis — without acknowledging any wrongdoing in the protracted epidemic that’s resulted in hundreds of thousands of deaths.

The announcement came two weeks after news of a proposed settlement surfaced and largely confirm what’s already been reported.

Lisa M. DeAngelis, MSKCC

MSK picks brain can­cer ex­pert Lisa DeAn­ge­lis as its next CMO — fol­low­ing José Basel­ga’s con­tro­ver­sial ex­it

It’s official. Memorial Sloan Kettering has picked a brain cancer expert as its new physician-in-chief and CMO, replacing José Baselga, who left under a cloud after being singled out by The New York Times and ProPublica for failing to properly air his lucrative industry ties.

His replacement, who now will be in charge of MSK’s cutting-edge research work as well as the cancer care delivered by hundreds of practitioners, is Lisa M. DeAngelis. DeAngelis had been chair of the neurology department and co-founder of MSK’s brain tumor center and was moved in to the acting CMO role in the wake of Baselga’s departure.

Penn team adapts CAR-T tech, reengi­neer­ing mouse cells to treat car­diac fi­bro­sis

After establishing itself as one of the pioneer research centers in the world for CAR-T cancer therapies, creating new attack vehicles to eradicate cancer cells, a team at Penn Medicine has begun the tricky transition of using the basic technology for heart repair work.

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Tal Zaks. Moderna

The mR­NA uni­corn Mod­er­na has more ear­ly-stage hu­man da­ta it wants to show off — reach­ing new peaks in prov­ing the po­ten­tial

The whole messenger RNA field has attracted billions of dollars in public and private investor cash gambled on the prospect of getting in on the ground floor. And this morning Boston-based Moderna, one of the leaders in the field, wants to show off a few more of the cards it has to play to prove to you that they’re really in the game.

The whole hand, of course, has yet to be dealt. And there’s no telling who gets to walk with a share of the pot. But any cards on display at this point — especially after being accused of keeping its deck under lock and key — will attract plenty of attention from some very wary, and wired, observers.

“In terms of the complexity and unmet need,” says Tal Zaks, the chief medical officer, “this is peak for what we’ve accomplished.”

Moderna has two Phase I studies it wants to talk about now.

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