Michael Ehlers (Replicate)

'Like a kid in a can­dy shop': Michael Ehlers gets be­hind RNA 'copy ma­chine' tech

Nathaniel Wang

Nathaniel Wang and An­drew Geall spent years work­ing on self-repli­cat­ing RNAs at Syn­thet­ic Ge­nomics and No­var­tis Vac­cines, re­spec­tive­ly, be­fore they re­al­ized they were com­ing at it the wrong way.

“For years and years, we thought that the tech­nol­o­gy was es­sen­tial­ly plug and play,” Wang said. “It turns out … the vec­tor it­self, the pro­tein that you’re putting in­to that vec­tor, and the fat droplet you use to for­mu­late it be­fore you in­ject it in­to a per­son are all in­de­pen­dent vari­ables.”

They de­cid­ed to start from scratch, along with Duke Uni­ver­si­ty pro­fes­sors Her­bert Kim Ly­er­ly and Zachary Hart­man — and right away, their work piqued the in­ter­est of ex-Bio­gen R&D chief and cur­rent ATP CSO Michael Ehlers. On Wednes­day, ATP un­veiled a $40 mil­lion Se­ries A round for the com­pa­ny they launched to­geth­er, dubbed Repli­cate Bio­science.

“I think one of the things, from my per­spec­tive, that’s re­al­ly nice about this tech­nol­o­gy is, it was re­al­ly in a good sit­u­a­tion where it was ripe with a lot of low hang­ing fruit,” Ehlers told End­points News.

The com­pa­ny cur­rent­ly has four dis­closed pro­grams — re­lat­ed to some­thing they call “syn­thet­ic im­mune lethal­i­ty” in breast in lung can­cers, im­munother­a­py re­sis­tance in sol­id tu­mors and au­toim­mune and in­flam­ma­to­ry dis­eases, said Wang, who’s helm­ing the com­pa­ny as CEO.

If RNA is an in­struc­tion man­u­al that teach­es a cell how to cre­ate a giv­en pro­tein, sr­RNA is the copy ma­chine. The prob­lem with RNA is that it tends to de­grade af­ter a cou­ple days.

“Imag­ine hav­ing a lit­tle tod­dler at home … con­stant­ly spilling every­thing on any doc­u­ment you have ly­ing around the house,” Wang said.

With sr­RNA, you’re es­sen­tial­ly de­liv­er­ing a copy ma­chine along with the in­struc­tion man­u­al, giv­ing you more pro­tein pro­duced over a longer pe­ri­od of time. Repli­cate thinks this ap­proach will al­low it to re­duce dos­ing lev­els by “sev­er­al or­ders of mag­ni­tude” com­pared to oth­er RNA ther­a­peu­tics.

They’re cur­rent­ly test­ing an idea fleshed out at Duke for sr­RNA tech that can pre­vent or re­move drug-re­sis­tant can­cer mu­ta­tions. With tar­get­ed ther­a­pies, like a small mol­e­cule or an an­ti­body, you run the risk of a pa­tients’ can­cer cells de­vel­op­ing a re­sis­tance mu­ta­tion.

“What we’re do­ing is for the pa­tients who are on some­thing like that hor­mone ther­a­py. We’re ed­u­cat­ing the im­mune sys­tem to rec­og­nize those mu­ta­tions that con­fer re­sis­tance to it. And so in the process, you cre­ate a force­ful link­age be­tween the two,” Wang said.

“What we’re not talk­ing about here is a run-of-the-mill neoanti­gen or some sort of pri­vate mu­ta­tion or just any old neoanti­gen,” Ehlers said. “We know that those have run in­to prob­lems … and that’s all be­cause they can’t do what Nathaniel just showed. They can all es­cape the im­mune sys­tem.”

Repli­cate is putting to­geth­er tech­nol­o­gy they be­lieve can be used to tar­get many of those mu­ta­tions and dri­vers all at the same time, he added. The team ex­pects to be in the clin­ic in the sec­ond half of next year.

“It’s like a kid in a can­dy shop with the kind of things you can do and the pa­tient im­pact that you can have,” Ehlers 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.

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.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

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 rather narrow 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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,700+ biopharma pros reading Endpoints daily — and it's free.

Rafaèle Tordjman (Jeito Capital)

Con­ti­nu­ity and di­ver­si­ty: Rafaèle Tord­j­man's women-led VC firm tops out first fund at $630M

For a first-time fund, Jeito Capital talks a lot about continuity.

Rafaèle Tordjman had spotlighted that concept ever since she started building the firm in 2018, promising to go the extra mile(s) with biotech entrepreneurs while pushing them to reach patients faster.

Coincidentally, the lack of continuity was one of the sore spots listed in a report about the European healthcare sector published that same year by the European Investment Bank — whose fund is one of the LPs, alongside the American pension fund Teacher Retirement System of Texas and Singapore’s Temasek, to help Jeito close its first fund at $630 million (€534 million). As previously reported, Sanofi had chimed in €50 million, marking its first investment in a French life sciences fund.

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.

Dave Lennon, former president of Novartis Gene Therapies

Zol­gens­ma patent spat brews be­tween No­var­tis and Re­genxbio as top No­var­tis gene ther­a­py ex­ec de­parts

Regenxbio, a small licensor of gene therapy viral vectors spun out from the University of Pennsylvania, is now finding itself in the middle of some major league patent fights.

In addition to a patent suit with Sarepta Therapeutics from last September, Novartis, is now trying to push its smaller partner out of the way. The Swiss biopharma licensed Regenxbio’s AAV9 vector for its $2.1 million spinal muscular atrophy therapy Zolgensma.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,700+ biopharma pros reading Endpoints daily — and it's free.

Time for round 2: Il­lu­mi­na-backed VC snags $325M for its next fund

Illumina Ventures closed off its second investment fund with a total commitment of $325 million, offering fresh fuel to back a slate of startups that have already included a smorgasbord of companies, covering everything from diagnostics to biotech drug development and genomics.

Fund II brings the total investment under Illumina Ventures’ oversight to $560 million, which has been focused on early-stage companies. And it has a transatlantic portfolio that includes SQZ, Twist and Encoded Therapeutics.

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,700+ biopharma pros reading Endpoints daily — and it's free.