Ear­ly snap­shot of Ad­verum's eye gene ther­a­py sparks con­cern about vi­sion loss

An ear­ly-stage up­date on Ad­verum Biotech­nolo­gies’ in­trav­it­re­al gene ther­a­py has trig­gered in­vestor con­cern, af­ter pa­tients with wet age-re­lat­ed mac­u­lar de­gen­er­a­tion (AMD) saw their vi­sion de­te­ri­o­rate, de­spite signs that the treat­ment is im­prov­ing reti­nal anato­my.

Ad­verum, on Wednes­day, un­veiled 24-week da­ta from the OP­TIC tri­al of its ex­per­i­men­tal ther­a­py, AD­VM-022, in six pa­tients who have been ad­min­is­tered with one dose of the ther­a­py. On av­er­age, pa­tients in the tri­al had se­vere dis­ease with an av­er­age of 6.2 an­ti-VEGF in­jec­tions in the eight months pri­or to screen­ing and an av­er­age an­nu­al­ized in­jec­tion fre­quen­cy of 9.3 in­jec­tions.

Over the six month pe­ri­od, pa­tients did not re­quire any an­ti-VEGF res­cue in­jec­tions — and five of six pa­tients saw a com­plete re­sponse with a to­tal res­o­lu­tion of flu­id fol­low­ing the Ad­verum in­jec­tion. There were no se­ri­ous ad­verse events, and the ma­jor­i­ty of side-ef­fects were mild.

How­ev­er, pa­tients lost vi­su­al acu­ity by two let­ters on av­er­age, with a 90% con­fi­dence in­ter­val of -9.1 let­ters to +5.1 let­ters.

Mani Foroohar

“The range of in­di­vid­ual pa­tient da­ta were not pre­sent­ed, though the wide con­fi­dence in­ter­val sug­gests that some pa­tients may have ex­pe­ri­enced a loss of more than 10 let­ters dur­ing the course of the tri­al – lack of res­cue in­jec­tions is dif­fi­cult to square with de­clin­ing vi­sion.” SVB Leerink’s Mani Foroohar wrote in a note.

“How­ev­er, the study in­ves­ti­ga­tor in­sist­ed no loss in vi­sion was due to wet AMD pathol­o­gy and ob­served loss of vi­su­al acu­ity is due to nor­mal vari­abil­i­ty…in a small set of pa­tients – an as­ser­tion that, if proved out with ad­di­tion­al fol­low-up, would very sub­stan­tial­ly im­prove the im­plied qual­i­ty of this dataset.”

Shares of the com­pa­ny — which spec­tac­u­lar­ly failed years ago when it was chris­tened Avalanche Biotech­nolo­gies — $AD­VM were down about 6.8% to $5.56 in Fri­day pre­mar­ket trad­ing. The stock sank on Thurs­day, evap­o­rat­ing mil­lions from its mar­ket val­ue.

“This da­ta sug­gest AD­VM-022 is po­ten­tial­ly ac­tive in de­liv­er­ing an ex­press­ible gene cas­sette in wet AMD, but mixed sig­nals in this small dataset should lift some of the com­pet­i­tive over­hang on RGNX shares,” Foroohar added. Re­genexBio ex­per­i­men­tal gene ther­a­py for wet AMD, RGX-314, is cur­rent­ly in a Phase I/II tri­al.

Wet AMD, which is char­ac­ter­ized by blurred vi­sion or a blind spot in an in­di­vid­ual’s vi­su­al field, is typ­i­cal­ly caused by ab­nor­mal growth of blood ves­sels that leak flu­id or blood in­to the mac­u­la. Mac­u­lar de­gen­er­a­tion is the lead­ing cause of se­vere, ir­re­versible vi­sion loss in the el­der­ly. An­ti-VEGF in­jec­tions such as Re­gen­eron’s $REGN flag­ship Eylea, as well as Roche’s $RHB­BY Lu­cen­tis and Avastin, are com­mon­ly used to treat wet AMD.

In April, the FDA im­posed a clin­i­cal hold on an ap­pli­ca­tion to test AD­VM-022 in hu­mans, ask­ing for ad­di­tion­al da­ta on Ad­verum’s chem­istry, man­u­fac­tur­ing and con­trol process. In May, the hold was lift­ed. Late last year, the biotech aban­doned its then lead ex­per­i­men­tal drug, AD­VM-043, for the treat­ment of A1AT de­fi­cien­cy.

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.

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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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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J&J ad­comm live blog: J&J faces ques­tions on old­er adults, asymp­to­matic in­fec­tion, long-term im­mu­ni­ty

The FDA adcomm has advanced to the free-for-all question stage of the hearing and, as they did for Moderna and Pfizer, committee members are raising questions about the lingering issues surrounding the vaccine.

In J&J’s case, one of those unknowns is a group of participants who appeared to respond worse to the vaccine: those over 60 with comorbidities. In that group, the vaccine was only 42% effective at stopping disease starting 28 days after vaccination.

Genen­tech plots $53M dis­cov­ery quest aimed at spark­ing a 'Holy moly' piv­ot in neu­ro R&D

Genentech has committed $53 million to back a 10-year quest aimed at going back to the drawing board to use new technology and fresh scientific insights to generate a pipeline of drugs for neurological diseases.

Roche’s big South San Francisco hub will mix it up with the scientists drawn together for the Weill Neurohub — formed in 2019 as a joint research partnership involving UCSF, Berkeley and the University of Washington — in an exploration of the field to develop new therapies for some of the toughest diseases in drug R&D: Alzheimer’s, Parkinson’s, Huntington’s, ALS and autism.

Am­gen, As­traZeneca speed to­ward fil­ing next-gen an­ti­body for asth­ma af­ter un­cork­ing full late-stage da­ta

On the hunt for a novel competitor to Sanofi and Regeneron’s Dupixent in severe asthma, Amgen and AstraZeneca posted “exciting” results from their next-gen antibody late last year. Now, the partners are showing their hands, and the results look good enough for approval.

Amgen and AstraZeneca’s tezepelumab plus standard of care cut the rate of severe asthma attacks by 56% at the one-year mark compared with SOC alone, according to full data from the Phase III NAVIGATOR study presented Friday at the virtual American Academy of Allergy, Asthma & Immunology meeting. And those significant results were consistent regardless of patients’ baseline eosinophil counts.

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.

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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