Can two old drugs — in­clud­ing an Eli Lil­ly flop — make one good treat­ment for Alzheimer’s? Karuna has $42M to find out

Back when Steven Paul was a star CNS re­searcher who had jumped to in­dus­try at Eli Lil­ly back in ’93, he boast­ed of a broad pipeline of in­trigu­ing new drugs he was work­ing on — in­clud­ing a promis­ing mus­carinic acetyl­choline re­cep­tor ag­o­nist called xanome­line. But that drug, like so many oth­ers at Lil­ly, was scut­tled — in this case by the ad­verse events trig­gered by off-tar­get ef­fects.

To­day, Paul — who re­cent­ly stepped down as CEO of Voy­ager — is in­vest­ing in a $42 mil­lion round with some high-pro­file in­vestors to back a com­pa­ny that be­lieves it has found a way to make xanome­line work the way they had seen in the clin­ic, with­out the oner­ous side ef­fects that killed the ear­li­er project.

An­drew Miller

The biotech is Boston-based Karuna Phar­ma­ceu­ti­cals, a PureTech ven­ture that has al­so at­tract­ed Bob Nelsen at Arch, along with the Well­come Trust and some oth­er un­named in­vestors. As part of the round, the com­pa­ny is con­vert­ing $22 mil­lion in debt in­to eq­ui­ty.

So what’s the big idea here? 

Karuna has been work­ing with seed mon­ey to ad­vance its no­tion that their com­bi­na­tion of xanome­line with tro­spi­um chlo­ride can al­low the ther­a­py to do its work in the brain, where they be­lieve it can have a sig­nif­i­cant ef­fect as an an­tipsy­chot­ic for schiz­o­phre­nia and Alzheimer’s dis­ease. Xanome­line tar­gets M1 re­cep­tors in the brain, for pos­si­ble cog­ni­tive and an­tipsy­chot­ic ef­fects, while the old drug tro­spi­um chlo­ride (Sanc­tura) works as a mus­carinic an­tag­o­nist to counter the side ef­fects.

They’ve dubbed the com­bi­na­tion KarXT. Karuna is helmed by MIT grad­u­ate An­drew Miller, and Paul is chair­man of the board.

Bob Nelsen

Build­ing off of Paul’s ear­li­er work at Eli Lil­ly along with the clin­i­cal work they’ve done with back­ing by the Well­come Trust, they’re shoot­ing for new hu­man da­ta to prove that the crew at Karuna could have the first vi­able new drug for Alzheimer’s in more than a decade. And that’s one very tall or­der that has now de­feat­ed a long line­up of re­searchers.

They’re not alone in the field, though. Al­ler­gan in-li­censed M1 and M4 tar­get­ed drugs from Hep­tares in the spring of 2016 in a $3.3 bil­lion deal, in­ter­est­ed in push­ing ahead here as well. And re­searchers at Van­der­bilt told me a cou­ple of years ago about their own clin­i­cal plans. There are oth­ers.

Nelsen — who’s been in­volved in a se­ries of big rounds over the past year — did the hon­ors pro­mot­ing the po­ten­tial here.

Karuna has all of the char­ac­ter­is­tics we look for in a game-chang­ing CNS com­pa­ny. Its lead drug can­di­date has a unique mech­a­nism of ac­tion for treat­ing both psy­chosis and cog­ni­tion, as well as an ex­cit­ing non-opi­ate ap­pli­ca­tion for pain. These are ther­a­peu­tic in­di­ca­tions where there is a pro­found need for new treat­ments.

Im­age: Steven Paul. TU­LANE UNI­VER­SI­TY

Brent Saunders [Getty Photos]

UP­DAT­ED: Ab­b­Vie seals $63B deal to buy a trou­bled Al­ler­gan — spelling out $1B in R&D cuts

Brent Saunders has found his way out of the current fix he’s in at Allergan $AGN. He’s selling the company to AbbVie for $63 billion in the latest example of the hot M&A market in biopharma.

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Af­ter rais­ing $158M, this up­start's founders have star back­ers and plans to break new ground in gene ther­a­py

Back in 2014, Stephanie Tagliatela opted to take an early exit out of her PhD program after working in Mark Bear’s lab at MIT, where she specialized in the synaptic connections between neuronal cells in the brain. She never finished that PhD, but she and fellow MIT student Kartik Ramamoorthi — who was on the founding team at Voyager — came away with some ideas for a gene therapy startup.

Today, fully 5 years later, she and Ramamoorthi are taking the wraps off of a $104 million mega-round designed to take the cumulative work of their preclinical formative stage for Encoded Therapeutics into human studies. They’ve now raised $158 million since starting out in Illumina’s incubator in the Bay Area, and they believe they are firmly on track to do something unique in gene therapy.

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Top an­a­lyst of­fers a rare, up­beat in­ter­pre­ta­tion of Ab­b­Vie’s $63B Al­ler­gan deal — but there’s a catch

Af­ter get­ting beat up on all sides from mar­ket ob­servers who don’t much care for the lat­est mega-deal to ar­rive in bio­phar­ma, at least one promi­nent an­a­lyst now is start­ing to like what he sees in the num­bers for Ab­b­Vie/Al­ler­gan.

But it’s go­ing to take some en­cour­age­ment if Ab­b­Vie ex­ecs want it to last.

Ab­b­Vie’s mar­ket cap de­clined $20 bil­lion on Tues­day as the stock took at 17% hit dur­ing the day. And SVB Leerink’s Ge­of­frey Porges can see a dis­tinct out­line of an up­side af­ter re­view­ing the fun­da­men­tals of the deal.

While Ako­rn works to re­vive its for­tunes, the FDA hits it with an­oth­er warn­ing let­ter

Ako­rn just can’t dig it­self out of its hole.

The spe­cial­ty gener­ic drug­mak­er has re­ceived yet an­oth­er warn­ing let­ter from the FDA this year. With­out dis­clos­ing any specifics, the Lake For­est, Illi­nois-based drug­mak­er on Wednes­day said the US reg­u­la­tor had is­sued the let­ter, cit­ing an in­spec­tion of its Som­er­set, New Jer­sey man­u­fac­tur­ing fa­cil­i­ty in Ju­ly and Au­gust of 2018. The com­pa­ny’s shares $AKRX dipped about 1.7% to $4.65 be­fore the bell.

Image: Chris Varma. Frontier

UP­DAT­ED: Chris Var­ma un­veils MP­M's lat­est start­up — eye­ing 'un­drug­gable' can­cer tar­gets and pow­ered by ma­chine learn­ing, $67M

Two years af­ter MPM Cap­i­tal en­list­ed Chris Var­ma on its busy on­col­o­gy team, the for­mer en­tre­pre­neur-in-res­i­dence is un­veil­ing his first ven­ture project out of his new stomp­ing grounds in the Bay Area: Fron­tier Med­i­cines.

For Var­ma, who’s al­so co-found­ed Blue­print Med­i­cines and built com­pa­nies at Third Rock and Flag­ship, this marks an­oth­er op­por­tu­ni­ty to ap­ply some cut­ting-edge sci­ence to “sev­er­al of the most im­por­tant and dif­fi­cult tar­gets in can­cer” — tar­gets that oth­ers have tried to tack­le with more clas­si­cal meth­ods and failed. The launch round comes in at $67 mil­lion, which should go some way in scaf­fold­ing a pre­clin­i­cal pipeline and push one or more as­sets in­to the clin­ic three years from now, he tells me.

Richard Gonzalez testifying in front of Senate Finance Committee, February 2019 [AP Images]

Ab­b­Vie's $63B buy­out spot­lights the re­turn of ma­jor M&A deals — de­spite the back­lash

Big time M&A is back. But for how long?

Over the past 18 months we’ve now seen three major buyouts announced: Takeda/Shire; Bristol-Myers/Celgene and now AbbVie/Allergan. And with this latest deal it’s increasingly clear that the sharp fall from grace suffered by high-profile players which have seen their share prices blasted has created an opening for the growth players in big pharma to up their game — in sharp contrast to the popular bolt-on deals that have been driving the growth strategy at Novartis, Merck, Roche and others.

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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.

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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The top 15 mega-deals in bio­phar­ma: Ab­b­Vie and Bris­tol-My­ers ac­qui­si­tions stir fresh de­bate over what's too big to buy

The debate over what’s too big to buy in biotech is back. A number of top analysts went right after AbbVie’s rationale for the Allergan deal today, just as Bristol-Myers Squibb stirred immediate debate over the worth and wisdom of acquiring Celgene.

To help provide some added context to this discussion, we asked DealForma chief Chris Dokomajilar to look over the past decade of major M&A in biopharma to decipher the top 15 plays.

The new numbers, unadjusted for inflation, harken back to the days of the Pfizer-Wyeth buyout and Merck’s decision to absorb Schering-Plough — both triggered in 2009. The heat over those acquisitions made the big pharma mega-deal highly unpopular for most everyone — except Pfizer — as industry leaders swore off almost all but the handy bolt-on acquisition.

Until recently.

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