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

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Mark Genovese (Stanford via Twitter)

Gilead woos fil­go­tinib clin­i­cal in­ves­ti­ga­tor from Stan­ford to lead the charge on NASH, in­flam­ma­to­ry dis­eases

With an FDA OK for the use of filgotinib in rheumatoid arthritis expected to drop any day now, Gilead has recruited a new leader from academia to lead its foray into inflammatory diseases.

Mark Genovese — a longtime Stanford professor and most recently the clinical chief in the division of immunology and rheumatology — was the principal investigator in FINCH 2, one of three studies that supported Gilead’s NDA filing. In his new role as SVP, inflammation, he will oversee the clinical development of the entire portfolio.

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Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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Stephen Isaacs, Aduro president and CEO (Aduro)

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After a drumbeat of failure, setbacks and reorganizations over the last few years, Aduro CEO Stephen Isaacs is handing over his largely gutted-out shell of a public company to another biotech company and putting up some questionable assets in a going-out-of-business sale.

Isaacs —who forged a string of high-profile Big Pharma deals along the way — has wrapped a 13-year run at the biotech with one program for kidney disease going to the new owners at Chinook Therapeutics. A host of once-heralded assets like their STING agonist program partnered with Novartis (which dumped their work on ADU-S100 after looking over weak clinical results), the Lilly-allied cGAS-STING inhibitor program and the anti-CD27 program out-licensed to Merck will all be posted for auction under a strategic review process.

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No­var­tis chips in $10M for IPO-bound part­ner Pli­ant; Tenax shares soar on heart drug da­ta

Novartis is coming in with $10 million to help support the looming IPO of a partner. Pliant Therapeutics posted a new filing with the SEC showing that Novartis is buying the shares at $15, the mid-point of the range. It’s adding several million shares to the offering, bringing the total to around $135 million. Biotech companies have been enjoying quite a run on virtual Wall Street, with investors boosting new offerings to some big hauls.

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In a Phase III trial, patients given a 5-day dose of remdesivir were 65% more likely to show “clinical improvement” compared to an arm given standard-of-care. The trial, though, gave little indication for whether the drug had an impact on key endpoints such as survival or time-to-recovery. And in a surprising twist, a 10-day dosing arm of remdesivir didn’t lead to a statistically significant improvement over standard of care.

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Fangliang Zhang (Imaginechina via AP Images)

The big mon­ey: Poised to make drug R&D his­to­ry, a Chi­na biotech un­veils uni­corn rac­ing am­bi­tions in a bid to raise $350M-plus on Nas­daq

Almost exactly three years after Shanghai-based Legend came out of nowhere to steal the show at ASCO with jaw-dropping data on their BCMA-targeted CAR-T for multiple myeloma, the little player with Big Pharma connections is taking a giant step toward making it big on Wall Street. And this time they want to seal the deal on a global rep after staking out a unicorn valuation in what’s turned out to be a bull market for biotech IPOs — in the middle of a pandemic.

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Bris­tol My­ers Squib­b's just-launched MS drug Zeposia makes the cut in key ul­cer­a­tive col­i­tis tri­al

In March, Zeposia became the third oral S1P modulator to secure US approval for multiple sclerosis. Now, the drug has succeeded in a key ulcerative colitis study.

The immunomodulator, akin to others in its class, controls lymphocyte trafficking by limiting the white blood cells to the lymphatic system, in the lymph nodes, and thwarting their ability to jam up lymph nodes — precluding their ability to penetrate the bloodstream and the central nervous system.

Hill­house re­casts spot­light on Chi­na's biotech scene with $160M round for Shang­hai-based an­ti­body mak­er

Almost two years after first buying into Genor Biopharma’s pipeline of cancer and autoimmune therapies, Hillhouse Capital has led a $160 million cash injection to push the late-stage assets over the finish line while continuing to fund both internal R&D and dealmaking.

The Series B has landed right around the time Genor would have listed on the Hong Kong stock exchange, according to plans reported by Bloomberg late last year. Insiders had said that the company was looking to raise about $200 million.

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