Sang­amo team rush­es to de­fend first hu­man gene edit­ing da­ta as MPS II ther­a­py of­fers a hit — and a miss

Sang­amo $SG­MO rolled out its first glimpse at the clin­i­cal ef­fi­ca­cy of their gene edit­ing ther­a­py for Hunter syn­drome (MPS II). And while re­searchers were able to point to some clear ev­i­dence that their ap­proach had an im­pact on a key bio­mark­er for the dis­ease for 2 pa­tients, there was a crit­i­cal lack of proof that it was do­ing specif­i­cal­ly what it was de­signed for.

Un­der­stand­ably, Sang­amo con­cen­trat­ed on uri­nary gly­cosamino­gly­cans (GAGs), high­light­ing big drops for both pa­tients in the sec­ond co­hort of the tiny ex­plorato­ry study. 

Ed Con­ner

The gene edit­ing ap­proach they’ve de­vel­oped with zinc fin­ger tech is in­tend­ed to cut in­to the er­rant gene and “in­sert a new copy of the IDS gene in­to a pre­cise lo­ca­tion in the DNA of liv­er cells to en­able a pa­tient’s liv­er to pro­duce a con­tin­u­ous and sta­ble sup­ply of the miss­ing hu­man IDS en­zyme.”

The iduronate-2-sul­fa­tase (IDS) en­zyme is need­ed to break down or re­cy­cle gly­cosamino­gly­cans (GAGs) der­matan sul­fate and he­paran sul­fate. 

The en­zyme gene ther­a­py, if it works, would end the need for reg­u­lar en­zyme re­place­ment in­fu­sions. And the two pa­tients in co­hort two demon­strat­ed mean re­duc­tions in GAG, der­matan sul­fate and he­paran sul­fate of 51%, 32%, and 61%.

That’s good.

How­ev­er, there was al­so this:

At base­line and for the first 16 weeks post-dos­ing of SB-913, plas­ma IDS ac­tiv­i­ty (mea­sure­ments ob­tained at trough of week­ly ERT dos­ing) was be­low the lev­el of quan­tifi­ca­tion of the cur­rent as­say.

That’s what Twit­ter be­gan buzzing about, trig­ger­ing a rapid drop in Sang­amo’s shares.  

Sandy Macrae

In a call with an­a­lysts, Sang­amo ex­ecs rushed to fight back against the back­lash.

That lack of ev­i­dence that the ther­a­py cre­ates the en­zyme need­ed, “doesn’t mean IDS isn’t be­ing pro­duced,” said Sang­amo CMO Ed Con­ner. “Cells of pa­tients with MSP II are starv­ing for IDS.” And “low lev­els may be suf­fi­cient to sup­press GAG.”

Sang­amo CEO Sandy Macrae al­so fierce­ly de­fend­ed the re­sults, say­ing you can’t get that hit on ef­fi­ca­cy un­less the gene edit­ing was tak­ing ef­fect.

In ad­di­tion, they added that the third co­hort in the study is get­ting a much stronger dose that could have a big­ger ef­fect. And ex­ecs added that they need to de­vel­op a bet­ter as­say for their clin­i­cal work to de­tect IDS. 

That wasn’t enough to over­come the first re­ac­tion by in­vestors. Their stock was down 22% in mid-morn­ing trad­ing.

This tri­al is cru­cial for Sang­amo, which is look­ing for clear ev­i­dence that it can beat its ri­vals in the fast-grow­ing field of gene edit­ing. That ri­val­ry, which in­cludes a va­ri­ety of ap­proach­es to edit­ing genes, is just get­ting start­ed.

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.

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.

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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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.

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.

With dust set­tled on ac­tivist at­tack, Lau­rence Coop­er leaves Zio­pharm to a new board

Laurence Cooper has done his part.

In the five years since he left a tenured position at Houston’s MD Anderson Cancer Center to become CEO of Boston-based Ziopharm, he’s steered the small-cap immunotherapy player through patient deaths in trials, clinical holds, short attacks and, most recently, an activist attack on the board.

So when the company has “fantastic news” like an IND clearance for a TCR T cell therapy program, he’s ready to pass on the baton.

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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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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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