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.

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Justin Klee (L) and Joshua Cohen, Amylyx co-CEOs (Cody O'Loughlin/The New York Times; courtesy Amylyx)

Ad­vo­cates, ex­perts cry foul over Amy­lyx's new ALS drug, cit­ing is­sues with price, PhI­II com­mit­ment

Not 24 hours after earning the first ALS drug approval in five years, Amylyx Pharmaceuticals’ Relyvrio is already drawing scrutiny. And it’s coming from multiple fronts.

In an investor call Friday morning, Amylyx revealed that it would charge about $158,000 per year, a price point that immediately drew backlash from ALS advocates and some outside observers. The cost reveal had been highly anticipated in the immediate hours after Thursday evening’s approval, though Amylyx only teased Relyvrio would cost less than previously approved drugs.

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Land­mark Amy­lyx OK spurs de­bate; Some... pos­i­tive? Alzheimer's da­ta; Can­cer tri­al bot­tle­neck; Sanofi's CRISPR bet; 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.

After brief stops in Paris and Boston, John Carroll and the Endpoints crew are staying on the road in October with their return for a live/streaming EUBIO22 in London. The hybrid event fireside chats and panels on mRNA, oncology and the crazy public market. We hope you can join him there.

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Joshua Cohen (L) and Justin Klee, Amylyx co-CEOs

Up­dat­ed: Af­ter long and wind­ing road, FDA ap­proves Amy­lyx's ALS drug in vic­to­ry for pa­tients and ad­vo­ca­cy groups

For just the third time in its 116-year history, the FDA has approved a new treatment for Lou Gehrig’s disease, or ALS.

US regulators gave the thumbs-up to the drug, known as Relyvrio, in a massive win for patients and their families. The approval, given to Boston-area biotech Amylyx Pharmaceuticals, comes after two years of long and contentious debates over the drug’s effectiveness between advocacy groups and FDA scientists, following the readout of a mid-stage clinical trial in September 2020.

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Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

#AAO22: J&J’s first look at com­mon eye dis­ease port­fo­lio pads the case for PhII of gene ther­a­py

CHICAGO — While the later-stage drug developers in the geographic atrophy field are near the finish line, Johnson & Johnson’s Janssen is taking a more deliberate route, with a treatment that it hopes to be a one-time fix.

The Big Pharma will take its Hemera Biosciences-acquired gene therapy into a Phase II study later this year in patients with GA, a common form of age-related macular degeneration that impacts about five million people worldwide. To get there, Janssen touted early-stage safety data at the American Academy of Ophthalmology annual conference Saturday morning, half a day after competitors Apellis and Iveric Bio revealed their own more-detailed Phase III analyses.

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George Church (courtesy EnPlusOne BioSciences)

George Church, Wyss sci­en­tists and North­pond chal­lenge con­ven­tion­al RNA man­u­fac­tur­ing with new biotech

RNA medicine has been at the forefront for the past few years, with the first RNA silencing therapy approved in 2018, and mRNA Covid vaccines following after. But flying under the radar has been the process of actually making RNA for these treatments.

That’s what Daniel Wiegand and Jonathan Rittichier have been working on in George Church’s lab for the past six years.

Friday morning, they unveiled EnPlusOne Biosciences, a biotech built on their RNA synthesis platform. Wiegand will serve as the Watertown, MA-based biotech’s CEO, and Rittichier will be CSO. And no different from his other startups, Church will be acting as scientific advisor. Its fourth co-founder, Dan Ahlstedt, joined through a Harvard Business School program, and will be COO.

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Up­dat­ed: Al­ny­lam re­in­forces APOL­LO-B patisir­an da­ta be­fore head­ing to the FDA

Weeks after uncorking some mostly positive data for patisiran in transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy, Alnylam is bolstering its package with new exploratory and subgroup data before shipping it off to regulators.

The RNAi drug maintained “generally consistent” benefits in efficacy and quality of life across several prespecified subgroups at month 12, Alnylam announced on Friday afternoon, including age, baseline tafamidis use, ATTR amyloidosis type, baseline six-minute walk test score and others.

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Jerome Durso, Intercept Pharmaceuticals CEO

In­ter­cep­t's OCA fails a PhI­II NASH tri­al, rais­ing fresh doubts about its years­long quest for an OK

Intercept Pharmaceuticals has run into another big setback in its yearslong quest to win an approval for OCA in NASH. The biotech put out word Friday morning that its Phase III REVERSE study failed the primary endpoint for the liver disease, sending its share price into a tailspin.

There was no significant improvement in fibrosis among the patients suffering from cirrhosis who were treated with obeticholic acid, with investigators hunting for a minimum 1-stage histological improvement in the disease after 18 months of therapy.

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