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.

MedTech clinical trials require a unique regulatory and study design approach and so engaging a highly experienced CRO to ensure compliance and accurate data across all stages is critical to development milestones.

In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

Avance Clinical is the Australian CRO for international biotechs providing world-class clinical research services with FDA-accepted data across all phases. With Avance Clinical, biotech companies can leverage Australia’s supportive clinical trials environment which includes no IND requirement plus a 43.5% Government incentive rebate on clinical spend. The CRO has been delivering clinical drug development services for international biotechs for FDA and EMA regulatory approval for the past 24 years. The company has been recognized for the past two consecutive years with the prestigious Frost & Sullivan CRO Best Practices Award and a finalist in Informa Pharma’s Best CRO award for 2022.

Ted Love, Global Blood Therapeutics CEO

Up­dat­ed: Pfiz­er scoops up Glob­al Blood Ther­a­peu­tics and its sick­le cell ther­a­pies for $5.4B

Pfizer is dropping $5.4 billion to acquire Global Blood Therapeutics.

Just ahead of the weekend, word got out that Pfizer was close to clinching a $5 billion buyout — albeit with other potential buyers still at the table. The pharma giant, flush with cash from Covid-19 vaccine sales, apparently got out on top.

The deal immediately swells Pfizer’s previously tiny sickle cell disease portfolio from just a Phase I program to one with an approved drug, Oxbryta, plus a whole pipeline that, if all approved, the company believes could make for a $3 billion franchise at peak.

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BREAK­ING: Math­ai Mam­men makes an abrupt ex­it as head of the big R&D group at J&J

In an after-the-bell shocker, J&J announced Monday evening that Mathai Mammen has abruptly exited J&J as head of its top-10 R&D group.

Recruited from Merck 5 years ago, where the soft spoken Mammen was being groomed as the successor to Roger Perlmutter, he had been one of the top-paid R&D chiefs in biopharma. His group spent $12 billion last year on drug development, putting it in the top 5 in the industry.

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No­vavax shares shred­ded as Covid vac­cine sales fall more than 90% in Q2

Months after Novavax celebrated its first profitable quarter as a commercial company, the Gaithersburg, MD-based company is back in the red.

Sales for Novavax’s Covid-19 vaccine slipped to $55 million last quarter, down from $586 million in Q1, CEO Stanley Erck revealed on Monday after market close. The company’s stock $NVAX plummeted more than 32% in after-hours trading.

Upon kicking off the call with analysts and investors, Erck addressed the elephant in the room:

Uğur Şahin, BioNTech CEO (Kay Nietfeld/picture-alliance/dpa/AP Images)

De­spite falling Covid-19 sales, BioN­Tech main­tains '22 sales guid­ance

While Pfizer raked in almost $28 billion last quarter, its Covid-19 vaccine partner BioNTech reported a rise in total dose orders but a drop in sales.

The German biotech reported over $3.2 billion in revenue in Q2 on Monday, down from more than $6.7 billion in Q1, in part due to falling Covid sales. While management said last quarter that they anticipated a Covid sales drop — CEO Uğur Şahin said at the time that “the pandemic situation is still very much uncertain” — Q2 sales still missed consensus by 14%.

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FDA commissioner Rob Califf (Tom Williams/CQ Roll Call via AP Images)

With drug pric­ing al­most done, Con­gress looks to wrap up FDA user fee leg­is­la­tion

The Senate won’t return from its summer recess until Sept. 6, but when it does, it officially has 18 business days to finalize the reauthorization of the FDA user fee programs for the next 5 years, or else thousands of drug and biologics reviewers will be laid off and PDUFA dates will vanish in the interim.

FDA commissioner Rob Califf recently sent agency staff a memo explaining how, “Our latest estimates are that we have carryover for PDUFA [Prescription Drug User Fee Act], the user fee funding program that will run out of funding first, to cover only about 5 weeks into the next fiscal year.”

Pascal Soriot, AstraZeneca CEO (David Zorrakino/Europa Press via AP Images)

As­traZeneca and Dai­ichi Sankyo sprint to mar­ket af­ter FDA clears En­her­tu in just two weeks

Regulators didn’t keep AstraZeneca and Daiichi Sankyo waiting long at all for their latest Enhertu approval.

The partners pulled a win on Friday in HER2-low breast cancer patients who’ve already failed on chemotherapy, less than two weeks after its supplemental BLA was accepted. While this isn’t the FDA’s fastest approval — Bristol Myers Squibb won an OK for its blockbuster checkpoint inhibitor Opdivo in just five days back in March — it comes well ahead of Enhertu’s original Q4 PDUFA date.

Bernhardt Zeiher, outgoing Astellas CMO (Astellas)

Q&A: Astel­las' re­tir­ing head of de­vel­op­ment re­flects on gene ther­a­py deaths

For anyone who’s been following discussions about the safety alarms surrounding the adeno-associated viruses (AAV) commonly used to deliver gene therapy, Astellas should be a familiar name.

The Japanese pharma — which bought out Audentes Therapeutics near the end of 2019 and later built a gene therapy unit around the acquisition — rocked the field when it reported three patient deaths in a trial testing AT132, the lead program from Audentes designed to treat a rare muscle disease called X-linked myotubular myopathy (XLMTM).

When the company restarted the trial, it adjusted the dose and instituted a battery of other measures to try to prevent the same thing from happening again. But tragically, the first patient to receive the new regimen died just weeks after administration. The therapy remains under clinical hold, and just weeks ago, Astellas flagged another safety-related hold for a separate gene therapy candidate. In the process of investigating the deaths, the company has also taken flak about the way it disclosed information.

Big questions remain — questions that can have big implications about the future of AAV gene therapies.

Bernhardt Zeiher did not imagine any of it when he first joined Astellas as the therapeutic area leader in inflammation, immunology and infectious diseases. But his ascent to chief medical officer and head of development coincided almost exactly with Astellas’ big move into gene therapy, putting him often in the driver’s seat to grapple with the setbacks.

As Zeiher prepares to retire next month after a 12-year tenure — leaving the unfinished tasks to his successor, a seasoned cancer drug developer — he chatted with Endpoints News, in part, to discuss the effort to understand what happened, lessons learned and the criticism along the way.

The transcript has been lightly edited for length and clarity.

Endpoints: I want to also ask you a bit about the gene therapy efforts you’ve been working on. Astellas has really been at the forefront of discovering the safety concerns associated with AAV gene therapy. What’s that been like for you?

Zeiher: Well, I have to admit, it’s been a bit of a roller coaster. We acquired Audentes. Huge amount of enthusiasm. What we saw with AT132 — that was the lead program in XLMTM — was just remarkable efficacy. I mean, kids who went from being on ventilators, not able to eat for themselves, sit up, do things like that, to off ventilators, walking, you know, really — one investigator called it this Lazarus-like effect. It was just really dramatic efficacy. And then to have the safety events that occurred. So they actually occurred within that first year of the acquisition. So we had the three patient deaths. Me and my organization became very, very much involved. In fact, Ed Conner, who had been the chief medical officer, he left after some of the deaths, but I stepped in as the kind of acting chief medical officer, we had another chief medical officer who was involved, and then we had a fourth death, and I became acting again for a period of time.

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Steve Paul, Karuna Therapeutics CEO (Third Rock)

Karuna's schiz­o­phre­nia drug pass­es a close­ly-watched PhI­II test, will head to FDA in mid-2023

An investigational pill that combines a former Eli Lilly CNS compound with an overactive bladder drug was better than placebo at reducing a scale of symptoms experienced by patients with schizophrenia in a Phase III trial.

Karuna Therapeutics’ drug passed the primary goal in EMERGENT-2, the Boston biotech said early Monday morning, alongside quarterly earnings. The study is the first of Karuna’s four Phase III clinical trials to read out in schizophrenia and will provide the backbone to the biotech’s first drug approval application, slated for mid-2023.

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