Art Levin (Avidity Biosciences)

#JPM21: Avid­i­ty CSO Art Levin runs full speed to the clin­ic with 'dream' an­ti­body oligonu­cleotide con­ju­gate ther­a­py

Art Levin is liv­ing his “sci­en­tist’s dream come true.”

The Avid­i­ty Bio­sciences CSO set out years ago to build a new class of oligonu­cleotide-based ther­a­pies for se­vere mus­cle dis­eases, like Duchenne mus­cu­lar dy­s­tro­phy (DMD) and my­oton­ic dy­s­tro­phy (DM1) — rare, ge­net­ic dis­or­ders that caus­es pro­gres­sive mus­cle weak­ness.

“As you might imag­ine, in the 15 or 16 years I’ve been work­ing on this, I’ve seen boys go from be­ing tod­dlers, to be­ing wheel­chair-bound, or even ven­ti­la­tor-bound,” he said, re­fer­ring to DMD. “It would be re­al­ly … a sci­en­tif­ic dream of mine to ac­tu­al­ly make a dif­fer­ence for this pa­tient pop­u­la­tion.”

At JP Mor­gan, Avid­i­ty is up­dat­ing in­vestors that their DM1 can­di­date is of­fi­cial­ly off to the races — head­ed for a Phase I/II tri­al in the sec­ond half of this year. The team is al­so div­ing in­to a part­ner­ship with Bris­tol My­ers Squibb sub­sidiary MyoKar­dia to ex­plore their ap­proach in car­diac tis­sue.

“It’s re­al­ly grat­i­fy­ing that this tech­nol­o­gy that we built and en­gi­neered in-house our­selves is com­ing to fruition,” Levin said.

DM1 is caused by hun­dreds of thou­sands of nu­cleotide re­peats at the end of a gene called DMPK. When the DMPK gene is tran­scribed in­to RNA, the RNA al­so car­ries the nu­cleotide re­peats, which form a hair­pin loop struc­ture, mak­ing the RNA tox­ic to the cell.

“Us­ing the tech­nol­o­gy that we’re talk­ing about, you can re­verse that and re­place these mis­placed pro­teins or mis­s­pliced RNA with prop­er­ly spliced RNA,” Levin told End­points back in 2019. “In the ac­tu­al treat­ment of pa­tients, we should ac­tu­al­ly be able to re­verse some of the na­ture of this dis­ease.”

The idea that you can use oligonu­cleotides to mod­i­fy hu­man RNA isn’t new. The prob­lem has al­ways been de­liv­ery, Levin said.

“Cells have evolved over eons to try and keep out RNA and keep out for­eign DNA,” he said. “So you re­al­ly have to trick the cell in­to want­i­ng to take up our oligonu­cleotide ther­a­peu­tic.”

The team is work­ing on An­ti­body Oligonu­cleotide Con­ju­gates (AOCs) — oligonu­cleotides com­bined with mon­o­clon­al an­ti­bod­ies in­to a sin­gle con­ju­gate that can be more eas­i­ly di­rect­ed to pre­cise tis­sues.

Avid­i­ty al­so has AOC pro­grams for fa­cioscapu­lo­humer­al mus­cu­lar dy­s­tro­phy (FSHD), Duchenne mus­cu­lar dy­s­tro­phy (DMD), and mus­cle at­ro­phy (MA). The FSHD pro­gram is head­ed for IND en­abling stud­ies this year, and the biotech ex­pects to file for a clin­i­cal tri­al in 2022. There are three pro­grams with­in DMD, the leader of which tar­gets Ex­on 44. The com­pa­ny plans on sub­mit­ting for per­mis­sion to en­ter the clin­ic in 2022.

In June, the biotech land­ed a near­ly $300 mil­lion IPO to make it all hap­pen. They tagged $65 mil­lion for their DM1 can­di­date, $35 mil­lion for DMD, and $25 mil­lion for MA, ac­cord­ing to an S-1/A. 

“We al­so in­tend to pur­sue the de­vel­op­ment of AOCs in cell types in ad­di­tion to mus­cle. In pre­clin­i­cal mod­els, we ob­served the abil­i­ty of AOCs not on­ly to de­liv­er to the liv­er, skele­tal and car­diac mus­cle, but al­so to oth­er tis­sue and cell types, in­clud­ing im­mune cells,” the doc­u­ment states.

Eli Lil­ly holds 6.6% of Avid­i­ty’s stock, ac­cord­ing to the S-1/A. Back in 2019, Avid­i­ty inked a li­cens­ing and re­search deal with Lil­ly, snag­ging $20 mil­lion up­front and an in­vest­ment of $15 mil­lion. Lil­ly is of­fer­ing up to $405 mil­lion more in mile­stones, plus roy­al­ties.

Levin kept mum about what the com­pa­ny is work­ing on with MyoKar­dia, on­ly re­veal­ing that they’re de­vel­op­ing a “sin­gle ther­a­peu­tic en­ti­ty.” The com­pa­nies are keep­ing the fi­nan­cial terms of the deal un­der wraps for now.

“We’re now re­al­ly now see­ing the fruits of all those labors come true,” Levin said. “We can build on peo­ple’s new ap­pre­ci­a­tion for what is a fun­da­men­tal build­ing block of life: RNA. Peo­ple are fi­nal­ly be­gin­ning to re­al­ize that this is a re­al way to cre­ate ther­a­peu­tic en­ti­ties.”

A cor­rec­tion has been made to clar­i­fy that Levin was re­fer­ring to DMD, not DM1, in his quote in the third para­graph.

Paul Hudson, Sanofi CEO (Cyril Marcilhacy/Bloomberg via Getty Images)

FDA side­lines Paul Hud­son's $3.7B MS drug af­ter es­tab­lish­ing link to liv­er dam­age

One of Sanofi CEO Paul Hudson’s top picks in the pipeline — picked up in a $3.7 billion buyout 2 years ago — has just been sidelined in the US by a safety issue.

The pharma giant put out word early Thursday that the FDA has put their Phase III studies of tolebrutinib in multiple sclerosis and myasthenia gravis on partial clinical hold, halting enrollment and suspending dosing for patients who have been on the drug for less than 60 days. Patients who have completed at least 60 days of treatment can continue therapy as researchers explore a “limited” — but unspecified in Sanofi’s statement — number of cases of liver injury.

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Phar­ma re­acts to post-Roe; Drug­mak­ers beef up cy­ber de­fense; Boehringer, Roche qui­et­ly axe drugs; 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 a reminder, we are off on Monday for the Fourth of July. I hope this recap will kick off your (long) weekend well and that the rest of it will be just what you need. See you next week for a shortened edition!

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Eric Hughes, incoming Teva EVP of global R&D and CMO

Te­va chief raids Ver­tex for his new glob­al head of re­search and de­vel­op­ment

Teva CEO Kåre Schultz has found his new R&D chief and CMO in Vertex’s ranks.

The global generics giant, which has some 3,500 staffers in the R&D group, has named Eric Hughes to the top research spot in the company. He’ll be replacing Hafrun Fridriksdottir, who held the role for close to five years, on Aug. 1.

Hughes hasn’t been at Vertex for long, though. He jumped from Novartis less than a year ago, after heading the immunology, hepatology & dermatology global development unit. Before that, he completed a five-year stint as head of early clinical research for the specialty discovery medicine department in the exploratory clinical & translational research group at Bristol Myers Squibb, according to his LinkedIn profile.

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#BIO22: Man­ag­ing a biotech in tur­bu­lent times. 'There's a per­fect shit­show out there'

On Tuesday, June 14, Endpoints News EIC John Carroll sat down with a group of biotech execs to discuss the bear market for industry stocks and how they were dealing with it. Here’s the conversation, which has been lightly edited for brevity.

Martin Meeson, sponsor opening:

Thank you, John. Hello everyone. My name’s Martin Meeson, I’m the CEO of Fujifilm Diosynth. For those of you who don’t know Fujifilm Diosynth, we operate in the development of clinical and commercial product scale up, we have facilities in Europe and the US, and around about 4,000 employees. We run on average about 150 programs, so when it comes to managing in turbulent times over the last two years, we’ve had quite a lot of experience of that. Not just keeping the clinical pipelines and the commercial pipelines open, but also our response to the pandemic and the molecules that we’ve had within there. One of the phrases that I coined probably about a year ago when we were talking at JP Morgan, was I talked about managing through turbulent times. Well, it’s become the fact that we are not managing and leading through these times, we are managing in them, which is why that’s really the purpose of and the topic that we’ve got today.

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Susan Galbraith, AstraZeneca EVP, oncology R&D

Catch­ing up with Bris­tol My­ers and Mer­ck, As­traZeneca de­clares neoad­ju­vant win for PD-L1/chemo com­bo

When AstraZeneca started the Phase III AEGEAN trial for Imfinzi in 2018, it was, alongside several Big Pharma brethren, hoping to push the use of PD-(L)1 therapies into earlier lines of treatment. Three and a half years later, the British drugmaker has nabbed promising data in a type of lung cancer.

Topline results from an interim analysis showed that adding Imfinzi to chemotherapy before surgery spurred a “statistically significant and meaningful” improvement in pathologic complete response for patients with resectable non-small cell lung cancer compared to chemotherapy alone.

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Nassim Usman, Catalyst Biosciences CEO

Fac­ing set­backs for months and an ac­tivist at­tack, Cat­a­lyst Bio­sciences pre­pares to call it quits

After downsizing for several months, Catalyst Biosciences is getting ready to tap out.

The San Francisco biotech announced Wednesday that it would be liquidating and distributing cash back to shareholders, with total proceeds expected to reach $65 million. Catalyst intends to return the money “as soon as practicable,” the company said, as it has ceased all R&D activities, CEO Nassim Usman said in a statement.

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Amgen's taking social media followers around the globe as it introduces the many different

From Tam­pa to Mu­nich, Am­gen’s ‘Places’ cam­paign in­tro­duces its lo­ca­tions around the world

Amgen is taking social media followers around the world with its latest corporate campaign. Called “Places of Amgen,” the twice monthly posts highlight the biopharma’s different offices and sites – and the people who work there.

Each post runs on LinkedIn, Facebook and Instagram with details about the work Amgen does in that location, when it was established, comments from people who work there and other interesting facts. The most recent one about Paris, France, for example, notes that Amgen France last year signed a French association charter committed to the inclusion of LBGT+ people in the workplace.

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On Friday, Lonza announced plans to construct a large-scale commercial drug product fill and finish facility in the town of Stein, Switzerland.

Lon­za to in­vest $500M+ on fill-fin­ish fa­cil­i­ty on its home turf

Lonza has been expanding its reach across the globe, bringing sites in China and the US online this year, but now they are looking closer to home for their next major investment.

The Swiss manufacturer on Friday announced plans to construct a large-scale commercial drug fill and finish facility in the town of Stein, Switzerland. The new facility will be delivered through an investment of approximately CHF 500 million, or $519 million, and is expected to be completed in 2026. The facility will also be constructed on the same campus as Lonza’s current clinical drug product facility.

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Bio­haven takes mi­graine cam­paign to pa­tients' Twit­ter feeds, months ahead of Pfiz­er takeover

Two weeks ago, Biohaven hit an all-time high in weekly Nurtec prescriptions. CEO Vlad Coric attributes at least some of that success to a new interactive Twitter campaign that encourages patients to free their feed of potential migraine triggers.

Earlier this month, Biohaven in partnership with Twitter launched the #RelieveYourFeed campaign that allows users to customize their app settings based on their migraine triggers.