Post-Bris­tol/My­ers buy­out, the IFM team lines up $31M to tack­le a troi­ka of NL­RP3 tar­gets

Af­ter years of lab work, the NL­RP3 in­flam­ma­some has emerged as a promi­nent drug tar­get in the bio­phar­ma world.

Just weeks af­ter the UK’s NodThera launched to cre­ate new in­hibitors for NL­RP3, the team at IFM has round­ed up $31 mil­lion to work on new drugs that could play a range of roles in fi­bro­sis and er­rant im­mune re­spons­es linked to a med­ley of ail­ments, in­clud­ing neu­rode­gen­er­a­tive dis­eases.

Gary Glick

Bris­tol-My­ers snapped up IFM a year ago in a $2.3 bil­lion deal, tak­ing on­col­o­gy as­sets from the deal but leav­ing CEO Gary Glick and his team free to pur­sue oth­er as­sets, with a right to ne­go­ti­ate for any­thing else they might do with NL­RP3. And the IFM team still has plen­ty of back­ing from At­las Ven­ture, Abing­worth, Bris­tol-My­ers Squibb and now IFM’s man­age­ment.

The big idea here is that if you can tack­le NL­RP3 in the right way, you can al­so pre­vent the down­stream de­vel­op­ment of pro-in­flam­ma­to­ry cy­tokines IL-1 and IL-18, which trig­ger dis­eases. And the IFM team is de­vel­op­ing drugs specif­i­cal­ly for de­liv­ery to the cen­tral ner­vous sys­tem, the gut and the brain.

Their work has been heav­i­ly in­flu­enced by two key sci­en­tists, Eicke Latz and Lui­gi Franchi, who have spent years study­ing NL­RP3.

Eicke Latz

“They have prob­a­bly for­got­ten more about NL­RP3 than the world knows,” says Glick. It’s their sci­en­tif­ic work which is be­ing mar­ried to the drug dis­cov­ery ac­tiv­i­ties at IFM in Boston.

IFM kept its staff in the wake of the Bris­tol-My­ers deal, which cen­tered on NL­RP3 ag­o­nists for can­cer. About 35 em­ploy­ees are on the pay­roll as they dive in­to this new work.

Lui­gi Franchi

This is still a trans­la­tion­al field for biotech to ex­plore, but there are some in­ter­est­ing late-stage con­nec­tions to con­sid­er re­gard­ing the IL-1 path­way. No­var­tis’ heart drug canakinum­ab is fo­cused on that IL-1 in­flam­ma­to­ry path­way, with Phase III da­ta to prove that it can help at-risk car­dio pa­tients. That drug is still in late-stage de­vel­op­ment, with re­cent pos­i­tive gout da­ta of its own.

Glick notes, though, that mov­ing up­stream of IL-1 has a num­ber of ad­van­tages, go­ing af­ter a spe­cif­ic tar­get with dif­fer­ent drugs fo­cused on dif­fer­ent points in the anato­my. And that could play well on safe­ty, avoid­ing any un­ex­pect­ed con­se­quences of IL-1 block­ades.

It is worth not­ing that NL­RP3 has been the fo­cus of some lim­it­ed amount of pre­clin­i­cal work re­gard­ing the ke­to­genic di­et. A Yale in­ves­ti­ga­tor, Vish­wa Deep Dix­it, has done mouse work to il­lus­trate a po­ten­tial con­nec­tion be­tween the ke­tone be­ta-hy­drox­y­buter­ate — which is pro­duced when you move to a high-fat, low carb di­et — and tamp­ing down on NL­RP3, see­ing how that could in­flu­ence the course of gout. And more work is un­der­way.

You can ex­pect to hear a lot more about NL­RP3 in the com­ing years.

The Avance Clinical leadership team: CEO Yvonne Lungershausen, Sandrien Louwaars - Director Business Development Operations, Gabriel Kremmidiotis - Chief Scientific Officer, Ben Edwards - Chief Strategy Officer

How Aus­tralia De­liv­ers Rapid Start-up and 43.5% Re­bate for Ear­ly Phase On­col­o­gy Tri­als

About Avance Clinical

Avance Clinical is an Australian owned Contract Research Organisation that has been providing high-quality clinical research services to the local and international drug development industry for 20 years. They specialise in working with biotech companies to execute Phase 1 and Phase 2 clinical trials to deliver high-quality outcomes fit for global regulatory standards.

As oncology sponsors look internationally to speed-up trials after unprecedented COVID-19 suspensions and delays, Australia, which has led the world in minimizing the pandemic’s impact, stands out as an attractive destination for early phase trials. This in combination with the streamlined regulatory system and the financial benefits including a very favourable exchange rate and the R & D cash rebate makes Australia the perfect location for accelerating biotech clinical programs.

As­traZeneca trum­pets the 'mo­men­tous' da­ta they found for Tagris­so in an ad­ju­vant set­ting for NSCLC — but many of the ex­perts aren’t cheer­ing along

AstraZeneca is rolling out the big guns this evening to provide a salute to their ADAURA data on Tagrisso at ASCO.

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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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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David Chang, Allogene CEO (Jeff Rumans)

Head­ed to PhII: Al­lo­gene CEO David Chang com­pletes a pos­i­tive ear­ly snap­shot of their off-the-shelf CAR-T pi­o­neer

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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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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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.

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

UP­DAT­ED: Gilead leas­es part­ner rights to TIG­IT, PD-1 in a $2B deal with Ar­cus. Now comes the hard part

Gilead CEO Dan O’Day has brokered his way to a PD-1 and lined up a front row seat in the TIGIT arena, inking a deal worth close to $2 billion to align the big biotech closely with Terry Rosen’s Arcus. And $375 million of that comes upfront, with cash for the buy-in plus equity, along with $400 million for R&D and $1.22 billion in reserve to cover opt-in payments and milestones..

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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As­traZeneca’s $7B ADC suc­ceeds where Roche failed, im­prov­ing sur­vival in gas­tric can­cer

Another day, another win for Enhertu.

The antibody-drug conjugate AstraZeneca promised up-to $7 billion to partner on has had a quite a few months, beginning with splashy results in a Phase II breast cancer trial, a rapid approval and, earlier this month, breakthrough designations in both non-small cell lung cancer and gastric cancer.

Now, at ASCO, the British pharma and their Japanese partner, Daiichi Sankyo, have shown off the data that led to the gastric cancer designation, which they’ll take back to the FDA. In a pivotal, 187-person Phase II trial, Enhertu shrunk tumors in 42.9% of third-line patients with HER2-positive stomach cancer, compared with 12.5% in a control arm where doctors prescribed their choice of therapy. Progression-free survival was 5.4 months for Enhertu compared to 3.5 months for the control.