CEO Harith Rajagopalan (Fractyl)

Af­ter a decade in the type 2 di­a­betes game, Fractyl Lab­o­ra­to­ries recharges with a fresh $100M and a new name

Harith Ra­jagopalan com­pared the way type 2 di­a­betes is man­aged to stick­ing your fin­gers in a dam that’s leak­ing from a num­ber of places.

You can take drugs to low­er your blood sug­ar, cho­les­terol, or blood pres­sure, but you’re not ad­dress­ing what he says is the core is­sue — the meta­bol­ic ab­nor­mal­i­ty that caus­es the dis­ease.

“We’re so busy plug­ging the holes in the dam, we don’t have time to see that the whole in­fra­struc­ture is at risk,” he said. “That in­fra­struc­ture is a full-body sys­temic meta­bol­ic ab­nor­mal­i­ty called meta­bol­ic syn­drome, that we’re ig­nor­ing while we’re so busy try­ing to treat all of the in­di­vid­ual symp­toms of the con­di­tion.”

Fol­low­ing ev­i­dence that the gut is a key dri­ver of meta­bol­ic con­trol, Ra­jagopalan launched Fractyl Lab­o­ra­to­ries with a $5.5 mil­lion Se­ries A round back in 2011. Al­most ex­act­ly a decade lat­er, the com­pa­ny’s back with a $100 mil­lion Se­ries F round and a shiny new name to con­tin­ue the hunt for ther­a­pies to re­verse meta­bol­ic dis­ease.

Fractyl Health will use the Se­ries F funds to ad­vance its en­do­scop­ic ther­a­py, Re­vi­ta DMR, in late-stage stud­ies across the spec­trum of type 2 di­a­betes. The tech­nol­o­gy re­cent­ly re­ceived break­through de­vice des­ig­na­tion, and is ex­pect­ed to com­plete a reg­is­tra­tional tri­al in in­sulin-treat­ed pa­tients in the US in 2023.

Why the sub­tle name change? “We want to stand re­al­ly firm­ly on the side of im­prov­ing health for pa­tients and for so­ci­ety, rather than man­ag­ing dis­ease,” Ra­jagopalan told End­points News. 

The com­pa­ny has raised about $280 mil­lion so far. But when asked whether he has plans to go pub­lic, Ra­jagopalan re­spond­ed: “We don’t have any news to share on that as of now.”

Re­vi­ta DMR makes use of a bal­loon catheter to in­ject saline in­to the walls of the duo­de­num, the first part of the small in­tes­tine im­me­di­ate­ly be­yond the stom­ach. Duo­de­nal lin­ing thick­ens over time due to mod­ern di­ets high in fat in sug­ar. This “cush­ion of saline” thick­ens the lin­ing, in or­der to sep­a­rate it from deep­er struc­tures. The bal­loon then heats up to about 90 de­grees Cel­sius (194 de­grees Fahren­heit), es­sen­tial­ly strip­ping away that ex­ces­sive lay­er. Then the body heals it­self, re­gen­er­at­ing a new, healthy lin­ing which Fractyl be­lieves could re­store in­sulin sen­si­tiv­i­ty.

“The rea­son we tar­get the duo­de­num is be­cause there’s a lot of ev­i­dence that, in peo­ple with type 2 di­a­betes and obe­si­ty, there’s a dys­func­tion­al duo­de­nal sig­nal that’s trig­ger­ing in­sulin re­sis­tance in the liv­er, and that we be­lieve to be one of the very first events in the meta­bol­ic syn­drome,” Ra­jagopalan ex­plained.

Fractyl be­gan en­rolling in the reg­is­tra­tional tri­al, dubbed RE­VI­TA-T2Di, in the first half of this year. The pri­ma­ry end­point in that study is the per­cent­age of pa­tients who achieve glycemic con­trol (de­fined as HbA1c lev­els less than or equal to 7%) with­out the need for in­sulin af­ter 24 weeks.

In a tri­al con­duct­ed in Eu­rope and Brazil, Re­vi­ta DMR didn’t reach sta­tis­ti­cal sig­nif­i­cance in re­duc­tion of HbA1c lev­els in the com­bined pop­u­la­tions, though Ra­jagopalan said the Brazil group was un­der­pow­ered. In just the Eu­ro­pean pop­u­la­tion, me­di­an HbA1c change from base­line was –6.6mmol/mol (17.5mmol/mol) in the Re­vi­ta group, ver­sus –3.3mmol/mol (10.9mmol/mol) in a sham group, with a p-val­ue of 0.033, ac­cord­ing to da­ta pub­lished in the BMJ. 

While Ra­jagopalan be­lieves the pro­ce­dure can ben­e­fit pa­tients for “a very long time,” he’s still un­sure ex­act­ly how of­ten pa­tients might need to re­peat it.

“We’re look­ing for­ward to do­ing some stud­ies in which we can show the re­peata­bil­i­ty af­ter sev­er­al years,” he said.

Adap­tive De­sign Meth­ods Of­fer Rapid, Seam­less Tran­si­tion Be­tween Study Phas­es in Rare Can­cer Tri­als

Rare cancers account for 22 percent of cancer diagnoses worldwide, yet there is no universally accepted definition for a “rare” cancer. Moreover, with the evolution of genomics and associated changes in categorizing tumors, some common cancers are now characterized into groups of rare cancers, each with a unique implication for patient management and therapy.

Adaptive designs, which allow for prospectively planned modifications to study design based on accumulating data from subjects in the trial, can be used to optimize rare oncology trials (see Figure 1). Adaptive design studies may include multiple cohorts and multiple tumor types. In addition, numerous adaptation methods may be used in a single trial and may facilitate a more rapid, seamless transition between study phases.

Matt Gline (L) and Pete Salzmann

UP­DAT­ED: Roivant bumps stake in Im­muno­vant with a $200M deal. But with M&A off the ta­ble, shares crater

Roivant has worked out a deal to pick up a chunk of stock in its majority-owned sub Immunovant $IMVT, but the stock buy falls far short of its much-discussed thoughts about buying out all of the 43% of shares it doesn’t already own.

Roivant, which recently inked a SPAC move to the market at a $7 billion-plus valuation, has forged a deal to boost its ownership in Immunovant by 6.3 points, ending with 63.8% of the biotech’s stock following a $200 million injection. That cash will bolster Immunovant’s cash reserves, giving it a $600 million war chest to fund a slate of late-stage studies for its big drug: the anti-FcRn antibody IMVT-1401.

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Sanofi preps a multi­bil­lion-dol­lar buy­out of an mR­NA pi­o­neer af­ter falling be­hind in the race for a Covid-19 jab — re­port

It looks like Sanofi CEO Paul Hudson is dead serious about his intention to vault directly into contention for the future of mRNA vaccines.

A year after paying Translate Bio a whopping $425 million in an upfront and equity payment to help guide the pharma giant to the promised land of mRNA vaccines for Covid-19, Sanofi is reportedly ready to close the deal with a buyout.

Translate’s stock $TBIO soared 78% after the market closed Monday. A spokesperson for Sanofi declined to comment on the report, telling Endpoints News that the company doesn’t comment on market rumors.

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Anthony Sun, Zentalis and Zentera CEO (Zentalis)

With clin­i­cal tri­als lined up for Zen­tal­is drugs, Chi­na's Zen­tera sets its sights on more deal­mak­ing and an IPO

As Zentalis geared up for an AACR presentation of early data on its WEE1 inhibitor earlier this year, its Chinese joint venture Zentera wasn’t idle, either.

Zentera, which has headquarters in Shanghai, had already nabbed clearance to start clinical trials in China for three of the parent company’s drugs. In May — just a month after Zentalis touted three “exceptional responses” out of 55 patients for their shared lead drug, ZN-c3 — it got a fourth CTA approval.

Thomas Soloway, T-knife CEO

What hap­pens when you give a mouse a hu­man self-anti­gen? In­vestors bet $110M to find out

T-knife Therapeutics launched last August on a mission to isolate T cell receptors not from human donors, but from mice. Now, with a new CEO and a candidate bound for the clinic, the Versant-backed company is reloading with a fresh $110 million.

“What we are trying to do for the field of TCR therapy and solid tumor therapy is very analogous to what the murine platforms have done in antibody development,” CEO Thomas Soloway told Endpoints News. 

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UP­DAT­ED: Watch out Glax­o­SmithK­line: As­traZeneca's once-failed lu­pus drug is now ap­proved

Capping a roller coaster journey, AstraZeneca has steered its lupus drug anifrolumab across the finish line.

Saphnelo, as the antibody will be marketed, is the only treatment that’s been approved for systemic lupus erythematosus since GlaxoSmithKline’s Benlysta clinched an OK in 2011. The British drugmaker notes it’s also the first to target the type I interferon receptor.

Mirroring the population that the drug was tested on in late-stage trials, regulators sanctioned it for patients with moderate to severe cases who are already receiving standard therapy — setting up a launch planned for the end of August, according to Ruud Dobber, who’s in charge of AstraZeneca’s biopharmaceuticals business unit.

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Not all mR­NA vac­cines are cre­at­ed equal. Does it mat­ter?; Neu­ro is back; Pri­vate M&A af­fair; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

As part of our broader and deeper drive, Endpoints has been pairing webinars with our special reports to cover more angles on a given topic. In conjunction with Max Gelman’s neuroscience feature, Kyle Blankenship moderated an insightful panel to discuss where the field is headed. You can register to watch it on demand here.

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Bris­tol My­ers pulls lym­phoma in­di­ca­tion for Is­to­dax af­ter con­fir­ma­to­ry tri­al falls flat

Amid an industrywide review of cancer drugs with accelerated approval, Bristol Myers Squibb had to make the tough call last month to yank an approval for leading I/O drug Opdivo after flopping a confirmatory study. Now, a second Bristol Myers drug is on the chopping block.

Bristol Myers has pulled aging HDAC inhibitor Istodax’s indication in peripheral T cell lymphoma after a Phase III confirmatory study for the drug flopped on its progression-free survival endpoint, the drugmaker said Monday.

Rick Pazdur (via AACR)

FDA's on­col­o­gy head Rick Paz­dur de­fends the ac­cel­er­at­ed ap­proval path­way, claim­ing it is 'un­der at­tack'

The FDA is sounding the alarm over its accelerated approval pathway as backlash continues over the recent nod in favor of Biogen’s Alzheimer’s drug Aduhelm, and an ODAC meeting on six such approvals that could potentially be pulled from the market — two of which already have.

“Do you think accelerated approval is under attack? I do,” Rick Pazdur, head of FDA’s Oncology Center of Excellence, said at a Friends of Cancer Research webinar on Thursday.

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