A gene ther­a­py mys­tery? Gen­Sight blast­ed as 1st PhI­II eye study ends in an in­trigu­ing fail­ure

Gen­Sight has a gene ther­a­py mys­tery on its hands, which is about the last thing it want­ed at the end of Phase III.

As­sess­ing the 48-week da­ta from its first piv­otal test of a treat­ment for Leber Hered­i­tary Op­tic Neu­ropa­thy — or LHON, a rare ge­net­ic dis­ease that caus­es blind­ness — in­ves­ti­ga­tors pulled out a mean­ing­ful im­prove­ment in sight in their one treat­ed eye.  

Bernard Gilly

The mys­tery: The oth­er eyes that re­ceived a sham ther­a­py did just as well with their eye­sight. Ex­act­ly as well.

That makes the Phase III study of GS010 a fail­ure, and rather than stay to try and solve the mys­tery, in­vestors bailed, dri­ving down the Eu­roNext stock $SIGHT down by 34%.

One of the rea­sons why the ear­ly gene ther­a­py pi­o­neers like Gen­Sight picked hered­i­tary eye dis­eases to go af­ter first is that the eye is a con­tained unit, lim­it­ing off-tar­get ef­fects. But Gen­Sight’s Paris-based CEO Bernard Gilly says that as on­ly a frac­tion of pa­tients his­tor­i­cal­ly see a spon­ta­neous im­prove­ment in eye­sight, he’s won­der­ing if the ther­a­py in­ject­ed in­to one eye de­liv­ers an un­ex­pect­ed ben­e­fit to the oth­er.

At the same time, Gen­Sight tout­ed a hit on a reti­nal bio­mark­er for the dis­ease, which they claimed as ev­i­dence that the ther­a­py had an im­pact sep­a­rate from the sham.

“The fact that struc­tur­al mea­sures of the reti­na showed such a large sta­tis­ti­cal dif­fer­ence with treat­ment is com­pelling and ob­jec­tive ev­i­dence that this gene ther­a­py pro­tects the in­tegri­ty of many reti­nal gan­glion cells from the dam­age of LHON,” com­ment­ed com­pa­ny co-founder José-Alain Sa­hel.

That’s a messy ar­gu­ment, with the com­pa­ny ar­gu­ing that it ap­peared the ther­a­py im­proved sight for both eyes, but on­ly hit the sec­ondary bio­mark­er in the treat­ed eye. 

The com­pa­ny — which tried and failed to make it on­to Nas­daq — will be left look­ing for more da­ta to an­a­lyze from its next two Phase III stud­ies, which are up­com­ing. But easy ex­pla­na­tions will be hard to come by.

Roivant par­lays a $450M chunk of eq­ui­ty in biotech buy­out, grab­bing a com­pu­ta­tion­al group to dri­ve dis­cov­ery work

New Roivant CEO Matt Gline has crafted an all-equity upfront deal to buy out a Boston-based biotech that has been toiling for several years now at building a supercomputing-based computational platform to design new drugs. And he’s adding it to the Erector set of science operations that are being built up to support their network of biotech subsidiaries with an eye to growing the pipeline in a play to create a new kind of pharma company.

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Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

CEO Fred Aslan (Artiva)

NK cell ther­a­py play­er Arti­va makes some more noise, pulling in $120M Se­ries B less than a month af­ter Mer­ck deal

Not even one month after Big Pharma took notice of Artiva when Merck signed a collaboration worth nearly $2 billion in milestones, the off-the-shelf NK cell biotech already has its next big fundraise.

Artiva returns from the venture well Friday with a $120 million Series B round, money they will use to get their first program into the clinic and to file INDs for another two candidates. The raise marks the latest development in a rapidly expanding footprint for Artiva, which, in addition to the Merck deal last month, has now raised almost $200 million since its Series A last June.

Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Covid-19 roundup: Mer­ck­'s $356M sup­ply deal on hold as FDA asks for more da­ta; FDA ap­proves Pfiz­er/BioN­Tech vac­cine stor­age at stan­dard freez­er temps

Merck is pushing back plans to supply the US government with a Covid-19 drug after the FDA asked for more data to support an emergency use authorization.

The antibody, MK-7110, had looked promising in a Phase III study conducted by OncoImmune before Merck came along and bought the biotech for $425 million. At the interim analysis, investigators looked at data from 203 patients and concluded that a single dose of the drug cut the risk of death or respiratory failure by more than 50% among severe patients. And those taking the drug had a 60% higher chance of improvement in clinical status compared to placebo.

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Fatty liver conceptual image, 3D illustration showing fatty liver silhouette made from micrograph of liver steatosis (Shutterstock)

The path to NASH: un­der­stand­ing the role of se­vere obe­si­ty in a com­plex, mul­ti-sys­tem dis­ease

Biotech Voices is a collection of exclusive opinion editorials from some of the leading voices in biopharma on the biggest industry questions today. Think you have a voice that should be heard? Reach out to senior editors Kyle Blankenship and Amber Tong.

We often think a person’s transition from a healthy to a diseased state is binary. But that’s often not the case. In reality, the onset of a disease is not something that occurs overnight, and the majority lie on a continuum that is impacted by a multitude of factors. Some of these factors are in a patient’s control. Others are not.

This is the case in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), two of the most complex diseases that “live” on this proverbial continuum. The clinical onset of NAFLD — and ultimately NASH — is a complex process that is closely related to obesity, insulin resistance and impaired adipose tissue metabolism.

Doug Ingram (file photo)

Why not? Sarep­ta’s third Duchenne MD drug sails to ac­cel­er­at­ed ap­proval

Sarepta may be running into some trouble with its next-gen gene therapy approach to Duchenne muscular dystrophy. But when it comes to antisense oligonucleotides, the well-trodden regulatory path is still leading straight to an accelerated approval for casimersen, now christened Amondys 45.

We just have to wait until 2024 to find out if it works.

Amondys 45’s approval was unceremonious, compared to its two older siblings. There was no controversy within the FDA over approving a drug based on a biomarker rather than clinical benefit, setting up a powerful precedent that still haunts acting FDA commissioner Janet Woodcock as biotech insiders weighed her potential permanent appointment; no drama like the FDA issuing a stunning rejection only to reverse its decision and hand out an OK four months later, which got more complicated after the scathing complete response letter was published; no anxious tea leaf reading or heated arguments from drug developers and patient advocates who were tired of having corticosteroids as their loved ones’ only (sometimes expensive) option.

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Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

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Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

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