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

John Hood [file photo]

UP­DATE: Cel­gene and the sci­en­tist who cham­pi­oned fe­dra­tinib's rise from Sanofi's R&D grave­yard win FDA OK

Six years after Sanofi gave it up for dead, the FDA has approved the myelofibrosis drug fedratinib, now owned by Celgene.

The drug will be sold as Inrebic, and will soon land in the portfolio at Bristol-Myers Squibb, which is finalizing a deal to acquire Celgene.

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UP­DAT­ED: AveX­is sci­en­tif­ic founder was axed — and No­var­tis names a new CSO in wake of an ethics scan­dal

Now at the center of a storm of controversy over its decision to keep its knowledge of manipulated data hidden from regulators during an FDA review, Novartis CEO Vas Narasimhan has found a longtime veteran in the ranks to head the scientific work underway at AveXis, where the incident occurred. And the scientific founder has hit the exit.

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Ab­b­Vie gets its FDA OK for JAK in­hibitor upadac­i­tinib, but don’t look for this one to hit ex­ecs’ lofty ex­pec­ta­tions

Another big drug approval came through on Friday afternoon as the FDA OK’d AbbVie’s upadacitinib — an oral JAK1 inhibitor that is hitting the rheumatoid arthritis market with a black box warning of serious malignancies, infections and thrombosis reflecting fears associated with the class.

It will be sold as Rinvoq — at a wholesale price of $59,000 a year — and will likely soon face competition from a drug that AbbVie once controlled, and spurned. Reuters reports that a 4-week supply of Humira, by comparison, is $5,174, adding up to about $67,000 a year.

The top 10 fran­chise drugs in bio­phar­ma his­to­ry will earn a to­tal of $1.4T (tril­lion) by 2024 — what does that tell us?

Just in case you were looking for more evidence of just how important Amgen’s patent win on Enbrel is for the company and its investors, EvaluatePharma has come up with a forward-looking consensus estimate on what the list of top 10 drugs will look like in 2024.

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UP­DAT­ED: Sci­en­tist-CEO ac­cused of im­prop­er­ly us­ing con­fi­den­tial in­fo from uni­corn Alec­tor

The executive team at Alector $ALEC has a bone to pick with scientific co-founder Asa Abeliovich. Their latest quarterly rundown has this brief note buried inside:

On June 18, 2019, we initiated a confidential arbitration proceeding against Dr. Asa Abeliovich, our former consulting co-founder, related to alleged breaches of his consulting agreement and the improper use of our confidential information that he learned during the course of rendering services to us as our consulting Chief Scientific Officer/Chief Innovation Officer. We are in the early stage of this arbitration proceeding and are unable to assess or provide any assurances regarding its possible outcome.

There’s no explicit word in the filing on what kind of confidential info was involved, but the proceeding got started 2 days ahead of Abeliovich’s IPO.

Abeliovich, formerly a tenured associate professor at Columbia, is a top scientist in the field of neurodegeneration, which is where Alector is targeted. More recently, he’s also helped start up Prevail Therapeutics as the CEO, which raised $125 million in an IPO. And there he’s planning on working on new gene therapies that target genetically defined subpopulations of Parkinson’s disease. Followup programs target Gaucher disease, frontotemporal dementia and synucleinopathies.

But this time Abeliovich is the CEO rather than a founding scientist. And some of their pipeline overlaps with Alector’s.

Abeliovich and Prevail, though, aren’t taking this one lying down.

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Chi­na has be­come a CEO-lev­el pri­or­i­ty for multi­na­tion­al phar­ma­ceu­ti­cal com­pa­nies: the trend and the im­pli­ca­tions

After a “hot” period of rapid growth between 2009 and 2012, and a relatively “cooler” period of slower growth from 2013 to 2015, China has once again become a top-of-mind priority for the CEOs of most large, multinational pharmaceutical companies.

At the International Pharma Forum, hosted in March in Beijing by the R&D Based Pharmaceutical Association Committee (RDPAC) and the Pharmaceutical Research and Manufacturers of America (PhRMA), no fewer than seven CEOs of major multinational pharmaceutical firms participated, including GSK, Eli Lilly, LEO Pharma, Merck KGaA, Pfizer, Sanofi and UCB. A few days earlier, the CEOs of several other large multinationals attended the China Development Forum, an annual business forum hosted by the research arm of China’s State Council. It’s hard to imagine any other country, except the US, having such drawing power at CEO level.

As dis­as­ter struck, Ab­b­Vie’s Rick Gon­za­lez swooped in on Al­ler­gan with an of­fer Brent Saun­ders couldn’t say no to

Early March was a no good, awful, terrible time for Allergan CEO Brent Saunders. His big lead drug had imploded in a Phase III disaster and activists were after his hide — or at least his chairman’s title — as the stock price continued a steady droop that had eviscerated share value for investors.

But it was a perfect time for AbbVie CEO Rick Gonzalez to pick up the phone and ask Saunders if he’d like to consider a “strategic” deal.

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As­traZeneca's jug­ger­naut PARP play­er Lyn­parza scoops up an­oth­er dom­i­nant win in PhI­II as the FDA adds a 'break­through' for Calquence

AstraZeneca’s oncology R&D group under José Baselga keeps churning out hits.

Wednesday morning the pharma giant and their partners at Merck parted the curtains on a successful readout for their Phase III PAOLA-1 study, demonstrating statistically significant improvement in progression-free survival for women with ovarian cancer in a first-line maintenance setting who added their PARP Lynparza to Avastin. This is their second late-stage success in ovarian cancer, which will help stave off rivals like GSK.

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ICER blasts FDA, PTC and Sarep­ta for high prices on DMD drugs Em­flaza, Ex­ondys 51

ICER has some strong words for PTC, Sarepta and the FDA as the US drug price watchdog concludes that as currently priced, their respective new treatments for Duchenne muscular dystrophy are decidedly not cost-effective.

The final report — which cements the conclusions of a draft issued in May — incorporates the opinion of a panel of 17 experts ICER convened in a public meeting last month. It also based its analysis of Emflaza (deflazacort) and Exondys 51 (eteplirsen) on updated annual costs of $81,400 and over $1 million, respectively, after citing “incorrect” lower numbers in the initial calculations.