France's NASH con­tender Gen­fit leaps on­to Nas­daq with $135M IPO

As it gears up for the late-stage read­out of its lead ex­per­i­men­tal NASH drug, France’s Gen­fit is vault­ing on­to the Nas­daq on Wednes­day with a $135 mil­lion IPO un­der the sym­bol $GN­FT.

The Lille-based com­pa­ny, which is al­ready list­ed on Eu­ronext Paris al­so as $GN­FT, spelled out the terms of the of­fer­ing on Tues­day.

The com­pa­ny de­cid­ed it want­ed a US list­ing to ex­pand its base in Boston, ac­cess the US tal­ent pool — con­sid­er­ing the ge­og­ra­phy is go­ing to be a large mar­ket for the drug (elafi­bra­nor) — as well a forge a clos­er con­nec­tion with US in­vestors, Gen­fit COO Dean Hum told End­points News.

NASH, which is typ­i­cal­ly as­so­ci­at­ed with obe­si­ty and di­a­betes, is set to eclipse he­pati­tis C as the lead­ing rea­son for liv­er trans­plants by 2020.

Gen­fit is of­fer­ing 6.15 mil­lion Amer­i­can De­posi­tary Shares priced $20.32 per ADS, and has con­cur­rent­ly se­cured a pri­vate place­ment of 500,000 or­di­nary shares in Eu­rope at €18.00 per share. In to­tal, the to­tal of­fer­ing is val­ued at rough­ly $135.1 mil­lion, be­fore com­mis­sions and ex­pens­es.

Gen­fit’s fu­ture hinges on the reg­u­la­to­ry fate of elafi­bra­nor for two main liv­er dis­or­ders: NASH and pri­ma­ry bil­iary cholan­gi­tis (PBC).

The big­ger, more lu­cra­tive in­di­ca­tion is NASH, an un­treat­ed fat­ty liv­er dis­ease that has rav­aged the de­vel­oped world and sparked a flur­ry of drug de­vel­op­ment from bio­phar­ma firms big and small. It is char­ac­ter­ized by a buildup of ex­cess fat in the liv­er that in­duces chron­ic in­flam­ma­tion and even­tu­al­ly cul­mi­nates in scar­ring that can lead to cir­rho­sis, liv­er fail­ure, can­cer and death.

While oth­er ma­jor NASH con­tenders — Gilead $GILD (fail in Phase III) and In­ter­cept $ICPT (mixed win in Phase III) — have dis­closed the top line num­bers of their late-stage tri­als, Gen­fit is ex­pect­ed to come out with its Phase III in­ter­im re­sults by the end of 2019.

When com­pared to its main ri­val, In­ter­cept, Hum as­sert­ed that elafi­bra­nor’s po­ten­tial in NASH res­o­lu­tion and re­duc­ing CV risk along with a be­nign safe­ty and tol­er­a­bil­i­ty pro­file set it apart.

Late-stage da­ta on In­ter­cept’s drug — obeti­cholic acid (OCA) — showed it in­duced a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in fi­bro­sis, but not NASH res­o­lu­tion, and a high­er-than-ex­pect­ed num­ber of pa­tients dropped out due to the pesky side-ef­fect of itch­ing.

“If you think about an­oth­er liv­er dis­ease, like say vi­ral he­pati­tis. The virus…dri­ves the fi­bro­sis for­ward in the liv­er. The way to treat vi­ral he­pati­tis is you get rid of the virus, and the fi­bro­sis gets bet­ter by it­self. So NASH is not any dif­fer­ent, what you want to is to treat the un­der­ly­ing cause of the on­set of pro­gres­sion of fi­bro­sis and that’s what elafi­bra­nor was able to demon­strate (in the phase IIb),” Hum said.

Up­on the read­out of OCA’s piv­otal study last month, In­ter­cept said it would ap­ply for mar­ket­ing ap­proval based on the dataset. Al­though Gen­fit’s piv­otal read­out comes at the end of the year, which will mean that its mar­ket­ing ap­pli­ca­tion (as­sum­ing the tri­al is pos­i­tive) will cer­tain­ly come af­ter In­ter­cept. But Hum is not wor­ried.

“The drug is well po­si­tioned to be­come stan­dard-of care,” he said, em­pha­siz­ing that elafi­bra­nor has the abil­i­ty to low­er CV risk (the lead­ing cause of mor­tal­i­ty in NASH pa­tients are CV events) and that its mech­a­nism of ac­tion is such that it could treat the widest NASH pa­tient pop­u­la­tion — from ad­vanced late-stage pa­tients to ear­ly-stage pa­tients with less fi­bro­sis.

Dubbed the silent dis­ease, it is hard to di­ag­nose in the ear­ly stages, mak­ing it dif­fi­cult to es­ti­mate its preva­lence, but stud­ies show that it af­flicts up to 12% of the adult pop­u­la­tion in de­vel­oped coun­tries. Al­though there are no ap­proved drugs for the dis­ease, the size of the NASH mar­ket is ex­pect­ed to cross $20 bil­lion by 2025.

“NASH by and large is the liv­er man­i­fes­ta­tion of liv­er dis­ease — it is a mul­ti­fac­to­r­i­al dis­ease with dif­fer­ent facets to it…like oth­er meta­bol­ic dis­eases — type II di­a­betes for ex­am­ple…NASH is very sim­i­lar, I think NASH will prob­a­bly be op­ti­mal­ly man­aged clin­i­cal­ly by com­bi­na­tion ther­a­py,” Hum said, adding that if ap­proved, elafi­bra­nor could eas­i­ly serve as the back­bone ther­a­py in fu­ture NASH com­bi­na­tion reg­i­mens.

Gen­fit is cur­rent­ly work­ing on get­ting its com­mer­cial op­er­a­tions ready in an­tic­i­pa­tion of the ap­proval. The com­pa­ny plans to re­tain the com­mer­cial rights to elafi­bra­nor in the key Eu­ro­pean coun­tries, and will like­ly pur­sue part­ner­ships with a glob­al phar­ma play­er in larg­er mar­kets like North and South Amer­i­ca, Hum said, adding that the com­pa­ny is in dis­cus­sions with dif­fer­ent groups about pric­ing.

“You’ve heard num­bers of $10,000 per year, here in the Unit­ed States — I think those num­bers are rea­son­able,” he said.

Mean­while, elafi­bra­nor is be­ing test­ed for use in oth­er liv­er in­di­ca­tions. In the com­ing weeks, the com­pa­ny is re­cruit­ing pa­tients for a study eval­u­at­ing the drug in pe­di­atric NASH pa­tients. Pos­i­tive mid-stage da­ta on the use of the drug in PBC — a rare and pro­gres­sive liv­er dis­ease — were an­nounced last De­cem­ber.

An­oth­er NASH hope­ful, the Mer­ck-part­nered NGM Bio­phar­ma, on Mon­day broke out the terms of its IPO. The com­pa­ny, which plans to list on the Nas­daq un­der the sym­bol $NGM, is of­fer­ing about 6.7 mil­lion shares priced be­tween $14 to $16, ac­cord­ing to the fil­ing.

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In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

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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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