Dave Ricks, Eli Lilly

Eli Lil­ly bets on an RNA base edit­ing out­fit lever­ag­ing the body's own en­zymes to re­verse mu­ta­tions

With its con­tro­ver­sial Alzheimer’s med do­nanemab near­ly ready for FDA scruti­ny, Eli Lil­ly has grown more em­bold­ened in its ef­forts to be­come the top dog in neu­ro­science. A new part­ner­ship with a qui­et RNA edit­ing play­er fo­cused around neu­ro­science could now add even more bite to Lil­ly’s bark.

Lil­ly will pay $50 mil­lion in up­front cash and eq­ui­ty and up to $1.25 bil­lion in down­stream mile­stones for ac­cess to five RNA edit­ing can­di­dates from Dutch biotech Pro­QR Ther­a­peu­tics, which is us­ing edit­ed oligonu­cleotides to kick off an RNA base edit­ing sys­tem ini­ti­at­ed by the body’s own en­zymes, the part­ners said Wednes­day.

Pro­QR’s oligonu­cleotide plat­form, dubbed Ax­iomer, re­cruits “en­doge­nous” en­zymes in the cell — which are known as adeno­sine deam­i­nas­es act­ing on RNA, or ADARs — to at­tach to tar­get RNA and in­duce an adeno­sine to in­o­sine base switch, what’s called A-to-I.

When that edit­ed RNA is tran­scribed, the in­o­sine is in­ter­pret­ed as guano­sine, ef­fec­tive­ly cre­at­ing an A-to-G switch. That’s im­por­tant be­cause Pro­QR thinks its plat­form could ad­dress around 20,000 known G-to-A mu­ta­tions that are as­so­ci­at­ed with hu­man dis­ease. The first tar­gets in the col­lab are liv­er and ner­vous sys­tem dis­eases, Pro­QR said, and rep­re­sent a change of pace for the biotech’s pipeline, which is cur­rent­ly fo­cused on ge­net­ic eye dis­ease with a lead can­di­date in late-stage clin­i­cal test­ing.

An­drew Adams

“RNA edit­ing is an ex­cit­ing emerg­ing tech­nol­o­gy, which al­lows tran­sient, re­versible edit­ing, which in some in­di­ca­tions may be an ex­treme­ly at­trac­tive ther­a­peu­tic ap­proach,” said An­drew Adams, Lil­ly’s VP for new ther­a­peu­tic modal­i­ties, in a state­ment. “Through this col­lab­o­ra­tion with Pro­QR, we hope to uti­lize this tech­nol­o­gy to un­lock nov­el treat­ments to im­prove the lives of pa­tients across a spec­trum of dis­eases.”

It’s an ap­proach sim­i­lar to the tech­nol­o­gy for which Roche re­cent­ly ear­marked more than $3 bil­lion in a tie-up with Shape Ther­a­peu­tics, al­so tar­get­ing ADARs. That fam­i­ly of en­zymes is par­tic­u­lar­ly at­trac­tive for brain cell RNA edit­ing, po­ten­tial­ly due to nat­u­ral­ly high lev­els of ex­pres­sion there. Roche and Shape say they’re go­ing af­ter Alzheimer’s and Parkin­son’s, among oth­er dis­eases, and it’s not a stretch to say that Lil­ly — with Alzheimer’s can­di­date do­nanemab near fil­ing — could be in­ter­est­ed in those tar­gets as well.

This part­ner­ship rep­re­sents a con­tin­ued ef­fort on Lil­ly’s part to ex­pand its next-gen RNA ther­a­peu­tics wing as well as its work in neu­ro­science, which has re­ceived a big shot in the arm from do­nanemab’s res­ur­rec­tion af­ter the con­tro­ver­sial Aduhelm ap­proval. Late last month, Lily an­nounced it would spin its um­brel­la Bio­Med­i­cines unit off in­to two new busi­ness ar­eas — neu­ro­science and im­munol­o­gy — in­di­cat­ing the com­pa­ny’s re­newed fo­cus on the cen­tral ner­vous sys­tem.

Mean­while, Lil­ly has inked deals in RNA ther­a­peu­tics and gene edit­ing, tak­ing a broad swing at next-gen meds. In April 2019, the drug­mak­er signed a deal with Avid­i­ty Bio­sciences worth $35 mil­lion up­front and $405 mil­lion per opt-in for the biotech’s plat­form that com­bines mon­o­clon­al an­ti­bod­ies and oligonu­cleotide-based ther­a­pies tar­get­ing RNA. The ini­tial fo­cus area for the part­ner­ship was im­munol­o­gy, the part­ners said at the time.

More than a year lat­er, in No­vem­ber, Lil­ly agreed to a part­ner­ship with Pre­ci­sion Bio­Sciences worth $100 mil­lion up­front for mol­e­cules out of that biotech’s in vi­vo gene edit­ing plat­form based on the I-Crel en­zyme with an ini­tial fo­cus in Duchenne mus­cu­lar dy­s­tro­phy.

Pro­QR, mean­while, has been work­ing on edit­ed oligonu­cleotides, what it calls EONs, for quite some time but pri­mar­i­ly fo­cused on ge­net­ic eye dis­ease. The biotech’s lead drug, se­po­farsen for Leber con­gen­i­tal amau­ro­sis 10, is cur­rent­ly in Phase II/III test­ing with an in­ter­im read­out sched­uled for the first half of 2022.

Daniel de Boer

Ac­cord­ing to CEO Daniel de Boer, Pro­QR’s plat­form can touch a range of ge­net­ic mu­ta­tions across or­gans, putting liv­er and brain dis­ease well with­in range. Those cer­tain­ly aren’t easy ther­a­peu­tic ar­eas and ones that re­quire a high de­gree of tis­sue speci­fici­ty, but de Boer thinks hav­ing Lil­ly on board will help in terms of re­fin­ing ar­eas of ther­a­peu­tic need.

“We said, ‘what if we can en­able oth­ers to use this tech­nol­o­gy but for oth­er ther­a­peu­tic ar­eas that are non-core to us?'” de Boer said. “That’s what led to this part­ner­ship with Lil­ly where we will help on the RNA side but they will even­tu­al­ly take the drugs in­to de­vel­op­ment. So it’s re­al­ly com­bin­ing our ex­per­tis­es where we con­tribute all our know-how on the RNA sci­ence and they bring in the ther­a­peu­tic area ex­per­tise.”

With its plat­form “ready for prime­time,” Pro­QR will like­ly de­clare its first can­di­date in this part­ner­ship with­in the next 12 months, de Boer said.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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Jay Bradner (Jeff Rumans for Endpoints News)

Div­ing deep­er in­to in­her­it­ed reti­nal dis­or­ders, No­var­tis gob­bles up an­oth­er bite-sized op­to­ge­net­ics biotech

Right about a year ago, a Novartis team led by Jay Bradner and Cynthia Grosskreutz at NIBR swooped in to scoop up a Cambridge, MA-based opthalmology gene therapy company called Vedere. Their focus was on a specific market niche: inherited retinal dystrophies that include a wide range of genetic retinal disorders marked by the loss of photoreceptor cells and progressive vision loss.

But that was just the first deal that whet their appetite.

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When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

The research comes as the FDA is at a crossroads with its expedited-review pathways. The accelerated approval pathway is under fire as the agency recently signed off on a controversial new Alzheimer’s drug, with little precedent to explain its decision. Meanwhile, top officials like Rick Pazdur have called for a major push to simplify and clarify all of the various expedited pathways, which have grown to be must-haves for sponsors of nearly every newly approved drug.

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Take­da snaps up the Japan­ese rights to an old Shire cast-off; Boehringer In­gel­heim ac­quires Abexxa Bi­o­log­ics

A week before the FDA is set to decide on Mirum Pharmaceuticals’ lead liver disease drug — an old Shire cast-off called maralixibat — Takeda is swooping in to secure the rights in Japan.

Maralixibat’s roots trace back to Lumena, which was snapped up by Shire for $260 million-plus back in 2014. While the candidate had failed mid-stage studies at Shire, Mirum believes better trial design and patient selection will deliver the wins it needs. The drug is currently in development for Alagille syndrome (a condition called ALGS in which bile builds up in the liver), progressive familial intrahepatic cholestasis (PFIC, which causes progressive liver disease) and biliary atresia (a blockage in the ducts that carry bile from the liver to the gallbladder).

FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.

Vicente Anido (University of West Virginia via YouTube)

Aerie fires CEO af­ter lead pro­gram flop, com­ments about pri­ma­ry end­points be­ing 'not re­quired'

Aerie Pharmaceuticals CEO Vicente Anido has left the company less than a week after trying to chart a Phase III study in the wake of a serious Phase IIb flop.

Anido’s last day at Aerie was Friday, the biotech announced in a news release Tuesday morning, and Benjamin McGraw is taking his place in an interim role. The now former CEO was terminated without cause, according to an SEC filing.

The board has started looking for a full-time chief to take his place.

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