Se­r­i­al start­up sci­en­tist Ronald Evans tests a new Mighty Mouse drug, mak­ing marathon run­ners with a pill

Ronald Evans

Salk In­sti­tute’s leg­endary sci­en­tist Ronald Evans has co-found­ed a string of new biotech com­pa­nies over the years, in­clud­ing Lig­and Phar­ma­ceu­ti­cals, Syn­dax and more re­cent­ly San Diego-based Metacrine. And now he’s com­plet­ed new pre­clin­i­cal re­search on a drug that he says has at­tract­ed at­ten­tion from some oth­er com­pa­nies in the bio­phar­ma world in­ter­est­ed in try­ing it on hu­mans.

And this one is a doozie.

It starts with a pair of ques­tions: “How does en­durance work?” he asked. “And if we re­al­ly un­der­stand the sci­ence, can we re­place train­ing with a drug?”

Evans and his lab crew have al­ready done work on mice that demon­strate how per­ma­nent­ly ac­ti­vat­ing the PPARδ gene could turn your av­er­age ro­dent in­to the an­i­mal world’s marathon run­ners. Then they came up with a drug — GW1516 — that ac­ti­vat­ed the tar­get gene, but found that the mice still had to ex­er­cise in or­der to build en­durance.

So they tried it again, up­ping the dose and dou­bling the treat­ment time from 4 weeks to 8.

This time the drug worked on build­ing en­durance, with mice on the con­trol arm able to run for 160 min­utes com­pared to the marathon-like 270 min­utes in the drug arm.

So what’s go­ing on here?

The sci­en­tists say that ex­haus­tion for these run­ning mice set in when blood sug­ar dropped to a cer­tain lev­el. The mech­a­nism of ac­tion im­proved ex­pres­sion in genes that are in­volved in break­ing down fat for en­er­gy but blocked a sim­i­lar ef­fect on sug­ar, pre­serv­ing glu­cose for brain ac­tiv­i­ty.

“This study sug­gests that burn­ing fat is less a dri­ver of en­durance than a com­pen­sato­ry mech­a­nism to con­serve glu­cose,” says Michael Downes, a Salk se­nior sci­en­tist and co-se­nior au­thor of the pa­per. “PPARδ is sup­press­ing all the points that are in­volved in sug­ar me­tab­o­lism in the mus­cle so glu­cose can be redi­rect­ed to the brain, there­by pre­serv­ing brain func­tion.”

Par­tial view of a mouse calf mus­cle stained for dif­fer­ent types of mus­cle fibers: ox­ida­tive slow-twitch (blue), ox­ida­tive fast-twitch (green), gly­colyt­ic fast-twitch (red). Salk In­sti­tute/Waitt Cen­ter

“Ex­er­cise ac­ti­vates PPARδ, but we’re show­ing that you can do the same thing with­out me­chan­i­cal train­ing. It means you can im­prove en­durance to the equiv­a­lent lev­el as some­one in train­ing, with­out all of the phys­i­cal ef­fort,” says Wei­wei Fan, a Salk re­search as­so­ciate and the pa­per’s first au­thor.

In a none too sub­tle pitch to drug de­vel­op­ers, the team says that their work has at­tract­ed some ac­tive in­ter­est on the part of bio­phar­ma com­pa­nies in­trigued by the no­tion that a drug like this could be a ma­jor help to the obese, di­a­bet­ics and peo­ple weak­ened by surgery.

It’s al­so worth not­ing that the more won­der­ful a drug’s ef­fect is in mice, whether it’s cur­ing can­cer or cre­at­ing Mighty Mouse with drugs, the high­er the bar on get­ting a drug like that in­to hu­mans. And that goes dou­ble for any­thing re­lat­ed to burn­ing fat.

Pablo Legorreta, founder and CEO of Royalty Pharma AG, speaks at the annual Milken Institute Global Conference in Beverly Hills, California (Patrick T. Fallon/Bloomberg via Getty Images)

Cap­i­tal­iz­ing Pablo: The world’s biggest drug roy­al­ty buy­er is go­ing pub­lic. And the low-key CEO di­vulges a few se­crets along the way

Pablo Legorreta is one of the most influential players in biopharma you likely never heard of.

Over the last 24 years, Legorreta’s Royalty Pharma group has become, by its own reckoning, the biggest buyer of drug royalties in the world. The CEO and founder has bought up a stake in a lengthy list of the world’s biggest drug franchises, spending $18 billion in the process — $2.2 billion last year alone. And he’s become one of the best-paid execs in the industry, reaping $28 million from the cash flow last year while reserving 20% of the cash flow, less expenses, for himself.

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Sanofi brings in 4 new ex­ec­u­tives in con­tin­ued shake-up, as vac­cines and con­sumer health chief head out the door

In the middle of Sanofi’s multi-pronged race to develop a Covid-19 vaccine, David Loew, the head of their sprawling vaccines unit, is leaving – part of the final flurry of moves in the French giant’ months-long corporate shuffle that will give them new-look leadership under new CEO Paul Hudson.

The company also said today that Alan Main, the head of their consumer healthcare unit, is out, and they named 4 executives to fill new or newly vacated positions, 3 of whom come from both outside both Sanofi and from Pharma.

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Ab­b­Vie wins an ap­proval in uter­ine fi­broid-as­so­ci­at­ed heavy bleed­ing. Are ri­vals My­ovant and Ob­sE­va far be­hind?

Women expel on average about 2 to 3 tablespoons of blood during their time of the month. But with uterine fibroids, heavy bleeding is typical — a third of a cup or more. Drugmakers have been working on oral therapies to try and stem the flow, and as expected, AbbVie and their partners at Neurocrine Biosciences are the first to make it across the finish line.

Known chemically as elagolix, the drug is already approved as a treatment for endometriosis under the brand name Orilissa. It targets the GnRH receptor to decrease the production of estrogen and progesterone.

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Cancer R&D chief José Baselga calls the disease-free survival data for their drug in an adjuvant setting of early stage, epidermal growth factor receptor-mutated NSCLC patients following surgery “momentous.” Roy Herbst, the principal investigator out of Yale, calls it “transformative.”

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Fabrice Chouraqui, Cellarity CEO-partner (LinkedIn)

Drug de­vel­op­er, Big Phar­ma com­mer­cial ex­ec, now an up­start biotech chief — Fab­rice Chouraqui is ready to try some­thing new as a ‘CEO-part­ner’ at Flag­ship

Fabrice Chouraqui’s career has taken some big twists along his life journey. He got his PharmD at Université Paris Descartes and jumped into the drug development game for a bit. Then he took a sharp turn and went back to school to get his MBA at Insead before returning to pharma on the commercial side.

Twenty years later, after steadily rising through the ranks and journeying the globe to nab a top job as president of US pharma for the Basel-based Novartis, Chouraqui exited in another career switch. And now he’s headed into a hybrid position as a CEO-partner at Flagship, where he’ll take a shot at leading Cellarity — one of the VC’s latest paradigm-changing companies of the groundbreaking model that aspires to deliver a new platform to the world of drug R&D.

David Chang, Allogene CEO (Jeff Rumans)

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Allogene CEO David Chang has completed the upbeat first portrait of the biotech’s off-the-shelf CAR-T contender ALLO-501 at virtual ASCO today, keeping all eyes on a drug that will now try to go on to replace the first-wave personalized pioneers he helped create.

The overall response rate outlined in Allogene’s abstract for treatment-resistant patients with non-Hodgkin lymphoma slipped a little from the leadup, but if you narrow the patient profile to treatment-naïve patients — removing the 3 who had previous CAR-T therapy who didn’t respond, leaving 16 — the ORR lands at 75% with a 44% complete response rate. And 9 of the 12 responders remained in response at the data cutoff, offering a glimpse on durability that still has a long way to go before it can be completely nailed down.

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Look­ing to move past an R&D fi­as­co, Ipsen poach­es their new CEO from Sanofi

Ipsen has turned to another Paris-based biopharma company for its next CEO.

Sanofi Pasteur chief David Loew — who’s been leading one of the most advanced efforts to develop vaccines for Covid-19 — is making the journey to Ipsen, 5 months after David Meek jumped ship to run a startup in late-stage development.

Loew arrives as Ipsen works to get back on track with their rare bone disease drug palovarotene, picked up in the $1.3 billion Clementia buyout, which was slammed with a partial hold after researchers observed cases of “early growth plate closure” in patients under the age of 14. But they are pushing ahead with the over-14 crowd after writing down slightly more than half of its initial development.

Dan O'Day, Gilead CEO (Andrew Harnik, AP Images)

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Hotly rumored for weeks, the 2 players have formalized a 10-year alliance that starts with rights to the PD-1, zimberelimab. O’Day also has first dibs on TIGIT and 2 other leading programs, agreeing to an opt-in fee ranging from $200 million to $275 million on each. There’s $500 million in potential TIGIT milestones on US regulatory events — likely capped by an approval — if Gilead partners on it and the stars align on the data. And there’s another $150 million opt-in payments for the rest of the Arcus pipeline.

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Paul Hudson, Sanofi CEO (Getty Images)

Sanofi CEO Paul Hud­son has $23B burn­ing a hole in his pock­et. And here are some hints on how he plans to spend that

Sanofi has reaped $11.1 billion after selling off a big chunk of its Regeneron stock at $515 a share. And now everyone on the M&A side of the business is focused on how CEO Paul Hudson plans to spend it.

After getting stung in France for some awkward politicking — suggesting the US was in the front of the line for Sanofi’s vaccines given American financial support for their work, versus little help from European powers — Hudson now has the much more popular task of managing a major cash cache to pull off something in the order of a big bolt-on. Or two.

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