An­oth­er myo­statin pro­gram com­busts, but Ac­celeron has plen­ty in the pipeline

Myo­statin in­hibitors — en­gi­neered to build mus­cle and im­prove mo­bil­i­ty in pa­tients — the­o­ret­i­cal­ly make sense for use in pa­tients with mus­cle-wast­ing dis­eases. But the field is lit­tered with fail­ure — and so it was hard­ly sur­pris­ing when Ac­celeron, which years ago scrapped a myo­statin pro­gram it had part­nered with Shire, dis­closed an­oth­er flopped myo­statin drug on Mon­day.

Ac­celeron’s drug, ACE-083, was be­ing test­ed in a mid-stage study in pa­tients with Char­cot-Marie-Tooth dis­ease (CMT), a group of in­her­it­ed dis­or­ders that cause nerve dam­age and are char­ac­ter­ized by small­er, weak­er mus­cles.

In the study, ACE-083 in­duced a sta­tis­ti­cal­ly sig­nif­i­cant in­crease in mean to­tal mus­cle vol­ume — meet­ing the main goal. How­ev­er, that in­crease did not trans­late to sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ments in any of the func­tion­al or qual­i­ty of life sec­ondary end­points, ver­sus place­bo. Ac­celeron is, there­fore, dis­con­tin­u­ing the de­vel­op­ment of the ex­per­i­men­tal com­pound, it said.

Back in Sep­tem­ber, ACE-083 failed to elic­it func­tion­al ben­e­fit in a sep­a­rate study in pa­tients with fa­cioscapu­lo­humer­al mus­cu­lar dy­s­tro­phy, a ge­net­ic mus­cle-wast­ing con­di­tion that caus­es the mus­cles of the limbs, shoul­ders, and face to weak­en.

This CMT re­sult was not sur­pris­ing, giv­en the sim­i­lar lack of func­tion­al ben­e­fit from the FSHD tri­al, SVB Leerink’s Ge­of­frey Porges wrote in a note.

The Cam­bridge, Mass­a­chu­setts-based com­pa­ny’s stock $XL­RN closed down about 6.6% at $85.29 on Mon­day and was bare­ly down 0.1% in Tues­day pre­mar­ket trad­ing.

ACE-083 is the lat­est ca­su­al­ty in a list of myo­statin ef­forts that have crashed and burned. Ac­celeron and Shire halt­ed clin­i­cal work on ACE-031 as ear­ly as 2011 and scrapped the pro­gram al­to­geth­er in 2013; No­var­tis’ bima­grum­ab failed a mid-stage study in 2016; Pfiz­er dropped the Duchenne plans for do­ma­grozum­ab fol­low­ing a dis­ap­point­ing Phase II tri­al in 2018; and last No­vem­ber, Roche aban­doned its Duchenne drug (ac­quired from Bris­tol My­ers Squibb in 2017) af­ter a fu­til­i­ty analy­sis sug­gest­ed de­vel­op­ing the com­pound fur­ther was fu­tile.

Myo­statin is a pro­tein that forms part of the trans­form­ing growth fac­tor be­ta (TGFβ) su­per­fam­i­ly — a group of pro­teins that help con­trol the growth and de­vel­op­ment of tis­sues across the body. The pro­tein nor­mal­ly re­strains mus­cle growth, en­sur­ing that mus­cles do not grow too large.

Mean­while, Ac­celeron has oth­er ar­eas of fo­cus.

The com­pa­ny in No­vem­ber se­cured the ap­proval of Cel­gene-part­nered red blood cell boost­ing drug Re­blozyl — known chem­i­cal­ly as lus­pa­ter­cept — to treat ane­mia in pa­tients with be­ta-tha­lassemia who re­quire reg­u­lar trans­fu­sions. Al­though its use in myelodys­plas­tic syn­dromes — which will like­ly de­ter­mine if the drug, pegged to even­tu­al­ly gen­er­ate glob­al peak sales of more than $3 bil­lion, is a big com­mer­cial suc­cess  — is still un­der Phase III re­view.

Ear­li­er this year, fo­cus al­so turned to so­tater­cept as the com­pa­ny re­port­ed pos­i­tive mid-stage da­ta in pa­tients with pul­monary ar­te­r­i­al hy­per­ten­sion (PAH). Un­like ex­ist­ing PAH ther­a­pies that are de­signed to di­late the pul­monary ar­ter­ies and re­duce blood pres­sure, so­tater­cept is en­gi­neered to re­store BM­PR-II sig­nal­ing, a key dri­ver of the dis­ease. If all goes well in piv­otal stud­ies, and the drug wins ap­proval — Porges es­ti­mates the drug could rake in glob­al sales of about $1.2 bil­lion in 2028.

“Af­ter that (FSHD) re­sult we re­moved all of the val­ue of this pro­gram from our mod­el and fore­casts, and for this rea­son, this (CMT) dis­clo­sure has no im­pact on our val­u­a­tion,” Porges said.

“It does con­firm that Ac­celeron in­vestors and man­age­ment were in­deed for­tu­nate that their so­tater­cept phase II tri­al in PAH had a pos­i­tive out­come, and the mag­ni­tude of the ben­e­fit in that tri­al, and the fu­ture de­vel­op­ment path, time­line and cost, be­come even more im­por­tant to the stock and its val­ue now.”

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Dipal Doshi, Entrada Therapeutics CEO

Ver­tex just found the next big ‘trans­for­ma­tive’ thing for the pipeline — at a biotech just down the street

Back in the summer of 2019, when I was covering Vertex’s executive chairman Jeff Leiden’s plans for the pipeline, I picked up on a distinct focus on myotonic dystrophy Type I, or DM1 — one of what Leiden called “two diseases (with DMD) we’re interested in and we continue to look for those assets.”

Today, Leiden’s successor at the helm of Vertex, CEO Reshma Kewalramani, is plunking down $250 million in cash to go the extra mile on DM1. The lion’s share of that is for the upfront, with a small reserve for equity in a deal that lines Vertex up with a neighbor in Seaport that has been rather quietly going at both of Vertex’s early disease targets with preclinical assets.

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Rami Elghandour, Arcellx CEO

Up­dat­ed: Gilead, Ar­cel­lx team up on an­ti-BC­MA CAR-T as biotech touts a 100% re­sponse rate at #ASH22

Gilead and Kite are plunking down big cash to get into the anti-BCMA CAR-T game.

The pair will shell out $225 million in cash upfront and $100 million in equity to Arcellx, Kite announced Friday morning, to develop the biotech’s lead CAR-T program together. Kite will handle commercialization and co-development with Arcellx, and profits in the US will be split 50-50.

Concurrent with the deal, Arcellx revealed its latest cut of data for the program known as CART-ddBCMA, ahead of a full presentation at this weekend’s ASH conference — a 100% response rate among patients getting the therapy. Investors jumped at the dual announcements, sending Arcellx shares $ACLX up more than 25% in Friday’s morning session.

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Christian Itin, Autolus CEO (UKBIO19)

Au­to­lus tips its hand, bags $220M as CAR-T show­down with Gilead looms

The first batch of pivotal data on Autolus Therapeutics’ CAR-T is in, and execs are ready to plot a path to market.

With an overall remission rate of 70% at the interim analysis featuring 50 patients, the results set the stage for a BLA filing by the end of 2023, said CEO Christian Itin.

Perhaps more importantly — given that Autolus’ drug, obe-cel, is going after an indication that Gilead’s Tecartus is already approved for — the biotech highlighted “encouraging safety data” in the trial, with a low percentage of patients experiencing severe immune responses.

WIB22: Am­ber Salz­man had few op­tions when her son was di­ag­nosed with a rare ge­net­ic dis­ease. So she cre­at­ed a bet­ter one

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Amber Salzman’s life changed on a cold, damp day in Paris over tiny plastic cups of lukewarm tea.

She was meeting with Patrick Aubourg, a French neurologist studying adrenoleukodystrophy, or ALD, a rare genetic condition that causes rapid neurological decline in young boys. It’s a sinister disease that often leads to disability or death within just a few years. Salzman’s nephew was diagnosed at just 6 or 7 years old, and died at the age of 12.

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Ahead of ad­comm, FDA rais­es un­cer­tain­ties on ben­e­fit-risk pro­file of Cy­to­ki­net­ic­s' po­ten­tial heart drug

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.

Ab­b­Vie slapped with age dis­crim­i­na­tion law­suit, fol­low­ing oth­er phar­mas

Add AbbVie to the list of pharma companies currently facing age discrimination allegations.

Pennsylvania resident Thomas Hesch filed suit against AbbVie on Wednesday, accusing the company of passing him over for promotions in favor of younger candidates.

Despite 30 years of pharma experience, “Hesch has consistently seen younger, less qualified employees promoted over him,” the complaint states.

WIB22: Lead­ing NK cell re­searcher re­flects on roots in Iran, the UK and Texas

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

In a small but widely-cited 11-person study published in NEJM in 2020, seven patients saw signs of their cancer completely go away after getting a new therapy made from natural killer cells. The study was one of the earliest to provide clinical proof that the experimental treatment method had promise.

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Philip Astley-Sparke, Replimune CEO

Replimune looks to rope in $225M on the back of melanoma da­ta

The Massachusetts-based, oncolytic virus biotech Replimune is feeling bullish now that it has lifted the cover on data for its lead product.

Replimune said Thursday it looks to nab about $225 million from a public offering after giving a snapshot of some initial data from its IGNYTE clinical study earlier this week. The trial is investigating RP1 in combination with Opdivo, for patients with melanoma and who did not have a response when being treated with a PD-1.