Pavan Cheruvu, Sio Gene Therapies CEO

Sio Gene Ther­a­pies posts pos­i­tive PhI/II da­ta in rare pe­di­atric dis­ease, the first read­out since its name change

A lit­tle over a month af­ter a full com­pa­ny re­brand, the Biotech For­mer­ly Known as Ax­o­vant has its first da­ta read­out un­der its new moniker.

Tues­day’s in­ter­im look comes from Sio Gene Ther­a­pies’ GM1 gan­gliosi­do­sis pro­gram, where the ex-Vant says it saw pos­i­tive safe­ty and ef­fi­ca­cy out­comes in a small Phase I/II tri­al. The re­sults mark what CEO Pa­van Cheru­vu hopes can pro­vide a new foun­da­tion in rare pe­di­atric dis­eases as Sio seeks to move past an epic Alzheimer’s fail just a few years ago.

“This is tru­ly a cor­ner­stone of the ap­proach we hope to take go­ing for­ward as we con­sid­er pipeline de­vel­op­ment and ex­pan­sion,” Cheru­vu told End­points News, “and is re­al­ly the first in­stance where we see promis­ing new da­ta com­ing out at, ad­mit­ted­ly, an ear­ly time point, but that we think builds up­on the strong sci­en­tif­ic foun­da­tion that we’ve put in place at Sio.”

In­vestors took the news in stride, with Sio $SIOX shares shoot­ing up about 45% af­ter the clos­ing bell Tues­day.

There are two types of GM1 gan­gliosi­do­sis, an in­her­it­ed ge­net­ic dis­ease that falls un­der the lyso­so­mal stor­age dis­or­der um­brel­la. If left un­treat­ed, the lack of a key en­zyme al­lows for waste ma­te­r­i­al to build up in cells and cause their ear­ly de­struc­tion.

The pro­gram, called AXO-AAV-GM1, is an AAV9-based gene ther­a­py Sio ac­quired back in De­cem­ber 2018 from the Uni­ver­si­ty of Mass­a­chu­setts Med­ical School as it was un­der­go­ing its shift in strat­e­gy. De­signed to in­tro­duce func­tion­al copies of the mu­tat­ed GLB1 gene, the can­di­date aims to re­verse the en­zyme de­fi­cien­cy, pre­vent­ing the pro­gres­sive death of cells over time.

Sio’s re­sults come from the six-month fol­low-up pe­ri­od for the low-dose co­hort of the tri­al, which en­rolled five pa­tients be­tween 32 and 68 months old. Cheru­vu was main­ly look­ing for good safe­ty re­sults as, giv­en the rare na­ture of the dis­ease, these were the first pa­tients dosed with a gene ther­a­py of any kind, he said. Sio found no se­ri­ous treat­ment-re­lat­ed side ef­fects and the ther­a­py was well-tol­er­at­ed.

In terms of ef­fi­ca­cy, Sio looked at the change in serum en­zyme ac­tiv­i­ty from base­line, or how con­cen­trat­ed an en­zyme is with­in a pa­tient’s cells, af­ter six months. The five pa­tients saw an av­er­age in­crease of 110%, which amount­ed to a restora­tion of 38% of nor­mal en­zyme ac­tiv­i­ty. Cheru­vu said that in oth­er sim­i­lar stor­age dis­eases, like Tay-Sachs and Sand­hoff dis­eases, restor­ing any­where from 10% to 20% typ­i­cal­ly cor­re­lates with long-term ben­e­fits.

“[These dis­eases] act as prox­ies for GM1 gan­gliosi­do­sis; they’re linked by an un­der­ly­ing bio­chem­i­cal and cel­lu­lar path­way,” Cheru­vu said.

With its first da­ta as Sio, the biotech will con­tin­ue to push AXO-AAV-GM1 through the dose es­ca­la­tion pe­ri­od and ul­ti­mate­ly in­to a larg­er tri­al. Sio has al­ready dosed the first two pa­tients in the high­er dose co­hort and is hop­ing to see safe­ty and ef­fi­ca­cy lev­els main­tained in the low-dose through the next read­out at the 12-month mark.

The re­sults al­so mark some­thing of a win for Cheru­vu, who took on the re­spon­si­bil­i­ty of clean­ing up the Alzheimer’s mess de­spite join­ing the com­pa­ny af­ter the fall­out. When Sio an­nounced its re­brand­ing last month, the CEO pro­claimed, “We’re not a vant any longer,” em­pha­siz­ing that Vivek Ra­maswamy’s Roivant biotech smor­gas­bord was no longer a ma­jor­i­ty stake­hold­er (it still owns a rough­ly 30% stake in the com­pa­ny and holds two board seats).

Sio’s pe­di­atrics pro­grams are part of a two-pronged fo­cus — Cheru­vu al­so not­ed the com­pa­ny is look­ing at some high-risk, high-re­ward can­di­dates in Parkin­son’s. And though AXO-AAV-GM1 is still in its ear­ly stages, Cheru­vu is con­fi­dent in the ther­a­py’s po­ten­tial.

“As we build the pro­gram, we hope to have a more ex­pe­dit­ed ap­proval process around this prod­uct,” Cheru­vu said. “We know there’s a pre­dictable nat­ur­al his­to­ry of de­cline in these kids, and if we can main­tain sta­bil­i­ty, main­tain mile­stones that have al­ready been gained, that could be a ba­sis for a sig­nif­i­cant dis­cus­sion with reg­u­la­tors.”

UP­DAT­ED: Mer­ck pulls Keytru­da in SCLC af­ter ac­cel­er­at­ed nod. Is the FDA get­ting tough on drug­mak­ers that don't hit their marks?

In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders?

Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday.

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The 2021 top 100 bio­phar­ma in­vestors: As the pan­dem­ic hit and IPOs boomed, VCs swung in­to ac­tion like nev­er be­fore

The global pandemic may have roiled economies, killed hundreds of thousands and throttled entire industries, but the only effect it had on biopharma venture investing was to help turbocharge the field to giddy new heights.

Below you’ll find the new top 100 venture investors in the industry, ranked by the number of deals they were publicly involved in, as tracked by DealForma chief Chris Dokomajilar. The numbers master then calculated the estimated amount of money they put into each deal — divvying up the cash by the number of players — to indicate how they managed their syndicates.

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Hal Barron, Endpoints UKBIO19

GSK, Vir's hopes for a Covid-19 an­ti­body fall flat in NIH 'mas­ter pro­to­col' with no ben­e­fit in hos­pi­tal­ized pa­tients

GlaxoSmithKline and Vir Biotechnology were hopeful that one of their partnered antibodies would carve out a win after getting the invite to a major NIH study in hospitalized Covid-19 patients. But just like Eli Lilly, the pair’s drug couldn’t hit the mark, and now they’ll be left to take a hard look at the game plan.

The NIH has shut down enrollment for GSK and Vir’s antibody VIR-7831 in its late-stage ACTIV-3 trial after the drug showed negligible effect in achieving sustained recovery in hospitalized Covid-19 patients, the partners said Wednesday.

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As Brain­Storm con­tin­ues to tout ‘clear sig­nal’ on ALS drug, the FDA of­fers a rare pub­lic slap­down on the da­ta

A little more than a week after BrainStorm acknowledged that regulators at the FDA had informed them that the biotech needed more data before it could expect to gain an approval for its ALS treatment NurOwn — while still touting a “clear signal” of efficacy and not ruling out an application — the agency has decided to clarify the record in a most unusual statement.

The FDA statement amounts to a straight slap own, offering a different set of efficacy numbers from the company’s public presentation last November and ruling out any chance of statistical significance.

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Eli Lil­ly claims suc­cess in a new JAK in­di­ca­tion: hair loss

Over the last decade, drugmakers have proven JAK inhibitors can treat a smattering of immune-related diseases ranging from rheumatoid arthritis to Covid-19. Now Eli Lilly has pulled out a new one.

Lilly and its biotech partner Incyte announced Wednesday that their JAK inhibitor baricitinib effectively regrew patients’ hair in a Phase III trial for alopecia areata, an autoimmune condition that can cause sudden, severe and patchy hair loss. Lilly didn’t break down the results from the 546-patient trial, but the primary endpoint was improvement on a standard score for alopecia symptoms.

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In­tro­duc­ing End­points FDA+, our new pre­mi­um week­ly reg­u­la­to­ry news re­port led by Zachary Bren­nan

CRLs. 483s. CBER, CDER and RWE. For biopharma professionals, these acronyms command attention because of the fundamental role FDA plays in drug development. Now Endpoints is doubling down on regulatory coverage, and launching a weekly report focusing on developments out of White Oak, with analysis and insight into what it all means.

Coverage will be led by our new senior editor, Zachary Brennan. He joins Endpoints from POLITICO, where he covered pharma. Prior to that he was the managing editor for Regulatory Focus, a news publication from the Regulatory Affairs Professionals Society.

Thank you, next: Take­da hands Ovid $196M cash to rein back in Phase III-ready seizure drug, re­viv­ing bat­tered stock

Soticlestat made it.

Takeda is bringing the drug back into its fold more than four years after first entrusting the team at Ovid with the mid-stage clinical work. For all that — generating what they saw as positive Phase II data in Dravet syndrome and Lennox-Gastaut syndrome — the biotech has been rewarded with $196 million in upfront cash, with another $660 million reserved for regulatory and commercial milestones.

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Michael Shpigelmacher

Khosla joins bet on un­con­ven­tion­al start­up look­ing to send drug de­liv­er­ing ro­bots in­to the brain

When Michael Shpigelmacher started the project, he knew he’d have to fund it himself. Every other effort of its kind was academic, rejected as too risky by investors.

Shpigelmacher, a robotics geek and entrepreneur who had drifted into consulting for pharma, wanted to build the real-life equivalent of technology from the 1960s film “Fantastic Voyage,” the one where a submarine crew is shrunk to “about the size of a microbe” and sent on a mission to repair a scientist’s brain. He scanned the literature, found the lab that was working on the most advanced project — at the Max Planck Institute in Germany, it turned out — and started funding them with money from his and his co-founders’ own accounts, along with some seed cash from friends and family.

Antoine Papiernik, Sofinnova managing director (Business Wire)

Sofinno­va Part­ners stays fo­cused on late-stage deals with a new, $540M crossover fund

One of Europe’s most high-profile biopharma investors is getting $540 million to invest in new crossover deals for late-stage companies.

The Paris-based VC says the fresh Sofinnova Crossover Fund raise positions them as the “largest crossover investor in Europe dedicated to late-stage biopharma and medtech investments.”

They got a leg up in France after winning a special “Tibi” designation from the French government, giving them access to a pool of €6 billion that helped them gain an edge with institutional investors. Since they were founded close to 50 years ago, the venture group has backed more than 500 companies and currently has more than €2 billion under management.