One more gig: Steven Paul de­cides to ex­tend a 35-year track record with one last shot at a big de­vel­op­ment pro­gram

Steven Paul was ready to hang up the lab coat when he stepped down near the be­gin­ning of the year as CEO of the gene ther­a­py start­up Voy­ager. Af­ter 35 years spent do­ing stints as a promi­nent top in­ves­ti­ga­tor at the Na­tion­al In­sti­tute of Men­tal Health, lead­ing the ear­ly-stage neu­ro­sciences group at Eli Lil­ly and as a co-founder at Sage and Voy­ager, see­ing out his ca­reer on some high-pro­file biotech boards like Al­ny­lam seemed just right.

And then Karuna came call­ing, and yanked him right back in­to the day-to-day game of drug de­vel­op­ment.

This morn­ing Paul is step­ping out as the new chief ex­ec­u­tive of a start­up which wants to show that one of the drugs he once cham­pi­oned at Lil­ly can now be read­ied for prime time as a sig­nif­i­cant new an­ti-psy­chot­ic for schiz­o­phre­nia — and then some.

An­drew Miller

Un­til to­day, Paul was the chair­man at Karuna. But just af­ter com­plet­ing a $42 mil­lion round — with a new crossover raise in the off­ing — Paul is back as the main man in charge. He’s tak­ing the place of founder An­drew Miller, who is trans­fer­ring to a new post as chief op­er­at­ing of­fi­cer.

What brought him back to the helm? Xanome­line. 

New­ly ar­rived at Lil­ly in the ear­ly ’90s, xanome­line was one of the lead drugs Paul in­her­it­ed in the neu­ro­sciences pipeline. There was rea­son to be­lieve that the drug would im­prove symp­toms of Alzheimer’s in pa­tients, with a test­ed abil­i­ty to hit the M1 and M4 mus­carinic re­cep­tors, with some ac­tiv­i­ty on M2 and M3.

“We did see an ef­fect on mem­o­ry,” Paul told me in a pre­view of to­day’s an­nounce­ment, “sim­i­lar to Ari­cept. What was quite sur­pris­ing, we mea­sured psy­chot­ic symp­toms in a de­ment­ed el­der­ly sub­group that had psy­chosis. And what we saw was a nice dose-de­pen­dent re­duc­tion in para­noia, vo­cal out­bursts and so on, com­pared to place­bo.”

What they al­so saw was a not-so-nice set of an­ti­cholin­er­gic ad­verse ef­fects, about what you would ex­pect now in a mus­carinic re­cep­tor ag­o­nist. Lil­ly, mean­while, was off to es­tab­lish the mega-block­buster Zyprexa, and an­oth­er drug tied to se­vere weight gain and more was not in the cards.

There it would have end­ed, ex­cept for re­search sug­gest­ing that a com­bi­na­tion ap­proach adding tro­spi­um chlo­ride to the mix for a new drug they’ve dubbed KarXT could block the side ef­fects and leave the an­ti-psy­chot­ic ef­fect in place. And there’s ad­di­tion­al re­search to un­der­score its po­ten­tial in pain as a non-opi­oid. 

It’s not a big crew. Paul counts about 6 key staffers at Karuna, with plen­ty of out­sourced help. But it’s grow­ing as they plot a big Phase II to nail down ev­i­dence of ef­fi­ca­cy and safe­ty among schiz­o­phrenic pa­tients. That tri­al will get un­der­way in a cou­ple of months now, as Karuna raised more cash and lays the foun­da­tion for what could be one big piv­otal tri­al to put them­selves over the top — or join the heap of neu­ro­sciences fail­ures that have ac­cu­mu­lat­ed over the past decade.

“I worked close­ly with Steve at Sage Ther­a­peu­tics and his ex­pe­ri­ence and cre­ativ­i­ty in the field is rare,” said Bob Nelsen, man­ag­ing di­rec­tor of ARCH Ven­ture Part­ners and a board mem­ber at Karuna. “KarXT’s po­ten­tial to meet un­met pa­tient need is ex­cit­ing and Steve’s ex­pe­ri­ence is per­fect­ly aligned to sup­port Karuna’s goal of de­liv­er­ing first-in-class drugs for treat­ing psy­chosis, cog­ni­tive im­pair­ment, and pain.”

Paul has been think­ing about this for years. Now he has the chance of prov­ing this the­o­ry. And he couldn’t be more ea­ger about the op­por­tu­ni­ty.

Im­age: Steven Paul. KARUNA

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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It's not per­fect, but it's a good start: FDA pan­elists large­ly en­dorse Aim­mune's peanut al­ler­gy ther­a­py

Two days after a fairly benign review from FDA staff, an independent panel of experts largely endorsed the efficacy and safety of Aimmune’s peanut allergy therapy, laying the groundwork for approval with a risk evaluation and mitigation strategy (REMS).

Traditionally, peanut allergies are managed by avoidance, but the threat of accidental exposure cannot be nullified. Some allergists have devised a way to dose patients off-label with peanut protein derived from supermarket products to wean them off their allergies. But the idea behind Aimmune’s product was to standardize the peanut protein, and track the process of desensitization — so when accidental exposure in the real world invariably occurs, patients are less likely to experience a life-threatening allergic reaction.

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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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Rit­ter bombs fi­nal PhI­II for sole lac­tose in­tol­er­ance drug — shares plum­met

More than two years ago Ritter Pharmaceuticals managed to find enough silver lining in its Phase IIb/III study — after missing the top-line mark — to propel its lactose intolerance toward a confirmatory trial. But as it turned out, the enthusiasm only set the biotech and its investors up to be sorely disappointed.

This time around there’s little left to salvage. Not only did RP-G28 fail to beat placebo in reducing lactose intolerance symptoms, patients in the treatment group actually averaged a smaller improvement. On a composite score measuring symptoms like abdominal pain, cramping, bloating and gas, patients given the drug had a mean reduction of 3.159 while the placebo cohort saw a 3.420 drop on average (one-sided p-value = 0.0106).

Ear­ly snap­shot of Ad­verum's eye gene ther­a­py sparks con­cern about vi­sion loss

An early-stage update on Adverum Biotechnologies’ intravitreal gene therapy has triggered investor concern, after patients with wet age-related macular degeneration (AMD) saw their vision deteriorate, despite signs that the treatment is improving retinal anatomy.

Adverum, on Wednesday, unveiled 24-week data from the OPTIC trial of its experimental therapy, ADVM-022, in six patients who have been administered with one dose of the therapy. On average, patients in the trial had severe disease with an average of 6.2 anti-VEGF injections in the eight months prior to screening and an average annualized injection frequency of 9.3 injections.

Alex Ar­faei trades his an­a­lyst's post for a new role as biotech VC; Sanofi vet heads to Vi­for

Too often, Alex Arfaei arrived too late. 

An analyst at BMO Capital Markets, he’d meet with biotech or pharmaceutical heads for their IPO or secondary funding and his brain, trained on a biology degree and six years at Merck and Endo, would spring with questions: Why this biomarker? Why this design? Why not this endpoint? Not that he could do anything about it. These execs were coming for clinical money; their decisions had been made and finalized long ago.

Arde­lyx bags its first FDA OK for IBS, set­ting up a show­down with Al­ler­gan, Iron­wood

In the first of what it hopes will be a couple of major regulatory milestones for its new drug, Ardelyx has bagged an FDA approval to market Ibsrela (tenapanor) for irritable bowel syndrome.

The drug’s first application will be for IBS with constipation (IBS-C), inhibiting sodium-hydrogen exchanger NHE3 in the GI tract in such a way as to increase bowel movements and decrease abdominal pain. This comes on the heels of two successful Phase III trials.