Ear­ly da­ta snap­shots of Ax­o­van­t's gene ther­a­pies for Parkin­son's, Tay Sachs ap­pear promis­ing

Fol­low­ing the col­lapse of its neu­ro-fo­cused strat­e­gy, Ax­o­vant’s for­ay in­to gene ther­a­pies — with their po­ten­tial for one-shot, long-term cures — has gen­er­at­ed con­sid­er­able in­ter­est. On Mon­day, the biotech pro­vid­ed an ear­ly pos­i­tive snap­shot of two of its pro­grams: in Parkin­son’s and in­fan­tile Tay-Sachs dis­ease.

Two pa­tients were giv­en the low­est dose of Ax­o­vant’s Parkin­son’s gene ther­a­py — AXO-Lenti-PD — as part of a mid-stage study called SUN­RISE-PD. Pa­tients were as­sessed three months af­ter their dose, hav­ing been washed out of their oral lev­odopa ther­a­py — the gold stan­dard treat­ment for Parkin­son’s. On a physi­cian-rat­ed scale (UP­DRS) as­sess­ing mo­tor func­tion (the Part III score), both pa­tients ex­pe­ri­enced an im­prove­ment. The scale mea­sures scores rang­ing from 0 to 108, with low­er scores in­di­cat­ing im­prove­ment. At three months, one pa­tient saw an im­prove­ment of 14 points, the oth­er 36 points — trans­lat­ing to an av­er­age im­prove­ment of 25 points or a mean 42% from base­line, Ax­o­vant said.

Gavin Cor­co­ran

Progress was al­so ob­served on oth­er parts of the UP­DRS scale. In ac­tiv­i­ties of dai­ly liv­ing (UP­DRS Part II), pa­tients ex­pe­ri­enced an av­er­age im­prove­ment of 22 points from base­line, while for com­pli­ca­tions of ther­a­py (UP­DRS Part IV), they saw a mean im­prove­ment of 7 points from base­line.

Ax­o­vant li­censed the in­ves­ti­ga­tion­al gene ther­a­py, as well as the pre­de­ces­sor prod­uct ProSavin, from Ox­ford Bio­Med­ica last year for $30 mil­lion up­front. AXO-Lenti-PD is de­signed to de­liv­er three genes — ty­ro­sine hy­drox­y­lase, cy­clo­hy­dro­lase 1, and aro­mat­ic L-amino acid de­car­boxy­lase — via a lentivi­ral vec­tor to en­code a set of crit­i­cal en­zymes re­quired for dopamine syn­the­sis to re­store steady lev­els of dopamine in the brain in one shot.

These re­sults sug­gest that the low­est dose of AXO-Lenti-PD at three months may have greater ef­fi­ca­cy com­pared to the high­est dose of ProSavin pre­vi­ous­ly test­ed, Ax­o­vant said.

Roger Bark­er

“The mech­a­nism of ac­tion of AXO-Lenti-PD…as well as our pri­or clin­i­cal ex­pe­ri­ence with ProSavin, led us to ex­pect that the ma­jor ben­e­fit would be in im­prov­ing the OFF state – and the re­sults so far are very en­cour­ag­ing in this re­gard,” said Roger Bark­er, one of the prin­ci­pal in­ves­ti­ga­tors on the SUN­RISE-PD study.

Based on feed­back from the da­ta mon­i­tor­ing com­mit­tee, Ax­o­vant is go­ing to test a sec­ond dose of the ther­a­py, and the first ad­min­is­tra­tion of that new dose is ex­pect­ed in the sec­ond quar­ter, the com­pa­ny said.

Ax­o­vant al­so pro­vid­ed an ear­ly look in­to the three-month da­ta for its gene ther­a­py for ad­vanced in­fan­tile Tay-Sachs dis­ease, a rare and fa­tal pe­di­atric neu­rode­gen­er­a­tive ge­net­ic dis­or­der with no ap­proved ther­a­pies.

The ther­a­py — AXO-AAV-GM2 — is de­signed to re­store β-Hex­osaminidase A en­zyme ac­tiv­i­ty in the cen­tral ner­vous sys­tem (im­paired ac­tiv­i­ty of this en­zyme caus­es Tay-Sachs) and was giv­en to an ad­vanced 30-month old pa­tient.

It was gen­er­al­ly well tol­er­at­ed and the pa­tient’s clin­i­cal con­di­tion was deemed sta­ble three months fol­low­ing ad­min­is­tra­tion.

β-Hex­osaminidase A ac­tiv­i­ty was de­ter­mined us­ing a stan­dard as­say. At base­line, the pa­tient’s en­zyme ac­tiv­i­ty in the cere­brospinal flu­id was 0.46% of nor­mal, but af­ter three months there was an ap­par­ent in­crease in en­zyme ac­tiv­i­ty to 1.44% of nor­mal, eclips­ing the 0.5% thresh­old that could rep­re­sent a clin­i­cal­ly rel­e­vant ef­fect, Ax­o­vant un­der­scored.

“This is the first time a gene ther­a­py has been ad­min­is­tered to a child with Tay-Sachs dis­ease, and it is re­mark­able that we have not on­ly seen good safe­ty and tol­er­a­bil­i­ty to date, but al­so ev­i­dence of func­tion­al β-Hex­osaminidase A en­zyme ac­tiv­i­ty,” said Gavin Cor­co­ran, Ax­o­vant’s ex­ec­u­tive VP of R&D.

Ini­tial da­ta for both gene ther­a­pies are promis­ing, but on­ly time will tell how ef­fec­tive, durable and safe their use is.

“AXGT should be con­sid­ered amongst the oth­er gene ther­a­py play­ers in the space (e.g., MGTX, VY­GR, SG­MO, etc. which all trade at 2-5x high­er mar­ket caps. (1) For their Parkin­son’s dis­ease gene ther­a­py, new da­ta to­day demon­strat­ing an av­er­age +42% im­prove­ment in UP­DRS PART III and im­prove­ment in dysk­i­ne­sia is sol­id and beat ex­pec­ta­tions and looks at least as good al­ready or bet­ter than oth­er pro­grams and the com­pa­ny plans to dose pa­tients at a high­er dose in Q2, set­ting the pro­gram up to be a ri­val to VY­GR’s (Voy­ager’s) re­cent­ly part­nered AAV-based gene ther­a­py. (2) We think the da­ta for Tay Sachs dis­ease are al­so com­pelling and sug­gest the po­ten­tial for dis­ease mod­i­fi­ca­tion,” Jef­feries’ Michael Yee wrote in a note.

Shares of the New York-based com­pa­ny $AXGT jumped more than 28% to $1.90 in pre­mar­ket trad­ing. Ax­o­vant is one of the var­i­ous drug de­vel­op­ers cre­at­ed and cham­pi­oned by for­mer hedge fund play­er Vivek Ra­maswamy un­der his um­brel­la Switzer­land-based com­pa­ny Roivant.

Aerial view of Genentech's campus in South San Francisco [Credit: Getty]

Genen­tech sub­mits a big plan to ex­pand its South San Fran­cis­co foot­print

The sign is still there, a quaint reminder of whitewashed concrete not 5 miles from Genentech’s sprawling, chrome-and-glass campus: South Francisco The Industrial City. 

The city keeps the old sign, first erected in 1923, as a tourist site and a kind of civic memento to the days it packed meat, milled lumber and burned enough steel to earn the moniker “Smokestack of the Peninsula.” But the real indication of where you are and how much has changed both in San Francisco and in the global economy since a couple researchers and investors rented out an empty warehouse 40 years ago comes in a far smaller blue sign, resembling a Rotary Club post, off the highway: South San Francisco, The Birthplace of Biotech.

Here comes the oral GLP-1 drug for di­a­betes — but No­vo Nordisk is­n't dis­clos­ing Ry­bel­sus price just yet

Novo Nordisk’s priority review voucher on oral semaglutide has paid off. The FDA approval for the GLP-1 drug hit late Friday morning, around six months after the NDA filing.

Rybelsus will be the first GLP-1 pill to enter the type 2 diabetes market — a compelling offering that analysts have pegged as a blockbuster drug with sales estimates ranging from $2 billion to $5 billion.

Ozempic, the once-weekly injectable formulation of semaglutide, brought in around $552 million (DKK 3.75 billion) in the first half of 2019.

As Nas­daq en­rolls the fi­nal batch of 2019 IPOs, how have the num­bers com­pared to past years?

IGM Biosciences’ upsized IPO haul, coming after SpringWorks’ sizable public debut, has revved up some momentum for the last rush of biotech IPOs in 2019.

With 39 new listings on the books and roughly two more months to go before winding down, Nasdaq’s head of healthcare listings Jordan Saxe sees the exchange marking 50 to 60 biopharma IPOs for the year.

“December 15 is usually the last possible day that companies will price,” he said, as companies get ready for business talks at the annual JP Morgan Healthcare Conference in January.

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Oxitec biologist releases genetically modified mosquitoes in Piracicaba, Brazil in 2016 [credit: Getty Images]

In­trex­on unit push­es back against claims its GM mos­qui­toes are mak­ing dis­ease-friend­ly mu­tants

When the hysteria of Zika transmission sprang into the American zeitgeist a few years ago, UK-based Oxitec was already field-testing its male Aedes aegypti mosquito, crafted to possess a gene engineered to obliterate its progeny long before maturation.

But when a group of independent scientists evaluated the impact of the release of these genetically-modified mosquitoes in a trial conducted by Oxitec in Brazil between 2013 and 2015, they found that some of the offspring had managed to survive — prompting them to speculate what impact the survivors could have on disease transmission and/or insecticide resistance.

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[via AP Images]

Pur­due threat­ens to walk away from set­tle­ment, asks to pay em­ploy­ees mil­lions in bonus­es

There are two updates on the lawsuit against Purdue Pharma over its role in fueling the opioid epidemic, as the Sackler family threatens to walk away from their pledge to pay out $3 billion if a bankruptcy judge does not stop outstanding state lawsuits against them. At the same time, the company has asked permission to pay millions in bonuses to select employees.

Purdue filed for chapter 11 bankruptcy this week as part of its signed resolution to over 2,000 lawsuits. The deal would see the Sackler family that owns Purdue give $3 billion from their personal wealth and the company turned into a trust committed to curbing and reversing overdoses.

David Grainger [file photo]

'Dis­con­nect the bas­tard­s' — one biotech's plan to break can­cer cell­s' uni­fied de­fens­es

Chemotherapy and radiotherapy are the current gladiators of cancer treatment, but they come with well-known limitations and side-effects. The emergence of immunotherapy — a ferocious new titan in oncologist’s toolbox — takes the brakes off the immune system to kill cancer cells with remarkable success in some cases, but the approach is not always effective. What makes certain forms of cancer so resilient? Scientists may have finally pieced together a tantalizing piece of the puzzle, and a new biotech is banking on a new approach to fill the gap.

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A fa­vorite in Alex­ion’s C-suite is leav­ing, and some mighty sur­prised an­a­lysts aren’t the least bit hap­py about it

Analysts hate to lose a biotech CFO they’ve come to trust and admire — especially if they’re being blindsided by a surprise exit.

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Scott Gottlieb, AP Images

Scott Got­tlieb is once again join­ing a team that en­joyed good times at the FDA un­der his high-en­er­gy stint at the helm

Right after jumping on Michael Milken’s FasterCures board on Monday, the newly departed FDA commissioner is back today with news about another life sciences board post that gives him a ringside chair to cheer on a lead player in the real-world evidence movement — one with very close ties to the FDA.

Aetion is reporting this morning that Gottlieb is joining their board, a group that includes Mohamad Makhzoumi, a general partner at New Enterprise Associates, where Gottlieb returned after stepping out of his role at the FDA 2 years after he started.

Gottlieb — one of the best connected execs in biopharma — knows this company well. As head of FDA he championed the use of real-world evidence to help guide drug developers and the agency in gaining greater efficiencies, which helped set up Aetion as a high-profile player in the game.

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While No­var­tis ban­ish­es Zol­gens­ma scan­dal scars — Bio­gen goes on a Spin­raza 'of­fen­sive'

While Novartis painstakingly works to mop up the stench of the data manipulation scandal associated with its expensive gene therapy for spinal muscular atrophy (SMA) Zolgensma— rival Biogen is attempting to expand the use of its SMA therapy, Spinraza. 

The US drugmaker $BIIB secured US approval for Spinraza for use in the often fatal genetic disease in 2016. The approval covered a broad range of patients with infantile-onset (most likely to develop Type 1) SMA.