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.

Part club, part guide, part land­lord: Arie Bellde­grun is blue­print­ing a string of be­spoke biotech com­plex­es in glob­al boom­towns — start­ing with Boston

The biotech industry is getting a landlord, unlike anything it’s ever known before.

Inspired by his recent experiences scrounging for space in Boston and the Bay Area, master biotech builder, investor, and global dealmaker Arie Belldegrun has organized a new venture to build a new, 250,000 square foot biopharma building in Boston’s Seaport district — home to Vertex and a number of up-and-coming biotech players.

Endpoints News

Basic subscription required

Unlock this story instantly and join 54,900+ biopharma pros reading Endpoints daily — and it's free.

Novotech CRO Ex­pands Chi­na Team as Biotech De­mand for Clin­i­cal Tri­als In­creas­es up to 79%

An increase in demand of up to 79% for clinical trials in China has prompted Novotech the Asia-Pacific CRO to rapidly expand the China team, appointing expert local clinical executives to their Shanghai and Hong Kong offices. The company is planning to expand their team by 30% over the next quarter.

Novotech China has seen considerable demand recently which is borne out by research from GlobalData:
A global migration of clinical research is occurring from high-income countries to low and middle-income countries with emerging economies. Over the period 2017 to 2018, for example, the number of clinical trial sites opened by biotech companies in Asia-Pacific increased by 35% compared to 8% in the rest of the world, with growth as high as 79% in China.
Novotech CEO Dr John Moller said China offers the largest population in the world, rapid economic growth, and an increasing willingness by government to invest in research and development.
Novotech’s 23 years of experience working in the region means we are the ideal CRO partner for USA biotechs wanting to tap the research expertise and opportunities that China offers.
There are over 22,000 active investigators in Greater China, with about 5,000 investigators with experience on at least 3 studies (source GlobalData).

H1 analy­sis: The high-stakes ta­ble in the biotech deals casi­no is pay­ing out some record-set­ting win­nings

For years the big trend among dealmakers at the major players has been centered on ratcheting down upfront payments in favor of bigger milestones. Better known as biobucks for some. But with the top 15 companies competing for the kind of “transformative” pacts that can whip up some excitement on Wall Street, with some big biotechs like Regeneron now weighing in as well, cash is king at the high stakes table.

We asked Chris Dokomajilar, the head of DealForma, to crunch the numbers for us, looking over the top 20 deals for the past decade and breaking it all down into the top alliances already created in 2019. Gilead has clearly tipped the scales in terms of the coin of the bio-realm, with its record-setting $5 billion upfront to tie up to Galapagos’ entire pipeline.

Dokomajilar notes:

We’re going to need a ‘three comma club’ for the deals with over $1 billion in total upfront cash and equity. The $100 million-plus club is getting crowded at 164 deals in the last decade with new deals being added towards the top of the chart. 2019 already has 14 deals with at least $100 million in upfront cash and equity for a total year-to-date of over $9 billion. That beats last year’s $8 billion and sets a record.

Add upfronts and equity payments and you get $11.5 billion for the year, just shy of last year’s record-setting $11.8 billion.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

UP­DAT­ED: With loom­ing ‘apoc­a­lypse of drug re­sis­tance,’ Mer­ck’s com­bi­na­tion an­tibi­ot­ic scores FDA ap­proval on two fronts

Merck — one of the last large biopharmaceuticals companies in the beleaguered field of antibiotic drug development — on Wednesday said the FDA had sanctioned the approval of its combination antibacterial for the treatment of complicated urinary tract and intra-abdominal infections.

To curb the rise of drug-resistant bacteria and maintain the efficacy of the therapy, Recarbrio (and other antibacterials) — the drug must be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible gram-negative bacteria, Merck $MRK said.

Endpoints News

Basic subscription required

Unlock this story instantly and join 54,900+ biopharma pros reading Endpoints daily — and it's free.

John McHutchison in 2012. Getty Images

The $1.1M good­bye: Gilead CSO John McHutchi­son is out as Daniel O’Day shakes up the se­nior team

Just a little more than a year after John McHutchison grabbed a promotion to become CSO at Gilead in the wake of Norbert Bischofberger’s exit, he’s out amid a shakeup of the senior team that is also triggering the departure of two other top execs.

Gilead stated that McHutchison “has decided to step down” from the job as of August 2nd. And their SEC filing notes that he’ll be getting a $1.1 million check to settle up on his contract.

Endpoints News

Basic subscription required

Unlock this story instantly and join 54,900+ biopharma pros reading Endpoints daily — and it's free.

Thomas Gajewski, David Steinberg. (CRI, Pyxis)

Bay­er, Long­wood back star re­searcher's deep dive in­to the tu­mor mi­croen­vi­ron­ment for new I/O tar­gets

From PD-1 targeting to the RAS pathway to the STING complex, Thomas Gajewski has spent the past two decades of his career decoding the various ways the immune system can be unleashed to defend against cancer. So when the University of Chicago professor comes around to putting all his findings into a new platform for finding new targets, VCs and pharma groups alike pay attention.

“He’s been studying T cells for 20 years, plus he’s one of the world’s leaders if not the world leader in the space,” David Steinberg, partner at Longwood Fund, said. “Furthermore, let me add he did a lot of the foundational research and also some of the seminal clinical trials in the existing set of I/O agents. He understands the space really well, he understands the current strengths, and I think he understood really well what was missing, so he knew where to look.”

Kamala Harris speaking yesterday at the Des Moines Register Iowa Presidential Candidate Forum [via Getty]

Who’s the tough­est on drug prices? A game of po­lit­i­cal one-up­man­ship is dri­ving the pol­i­cy de­bate in Wash­ing­ton

Earlier this week we got a look at Senator Kamala Harris’ position on drug prices. She’s proposing that HHS take an average price from single-payer systems like the UK, Germany and Canada — which leverage market access for lower prices — and use that to set the US price. Anything drug companies collect above that would be taxed at a rate of 100%.

And the rhetoric is scathing:
While families struggle to make it to the end of the month, pharmaceutical companies are turning record profits. They’re spending nearly as much on advertising as R&D. They’re manipulating their market power to hike prices on lifesaving generic drugs. They’re making twice the profit of the average industry in America and still increased drug prices by 10.5% over the past six months alone. Meanwhile, they are charging dramatically higher prices to American consumers.
That’s an escalation on Joe Biden’s plan, which includes drug importation from those cheaper markets as well as allowing Medicare to negotiate prices — something that virtually all Dems agree on now.

SJ Lee [File photo]

Go­ing in­side cells, Sung Joo Lee has sketched some big goals for his small — but glob­al — team of drug hunters

For a small biotech based in South Korea with a research arm in Cambridge, MA, Orum Therapeutics has sketched out some big goals aimed at developing antibodies for intracellular targets. And now they have a new $30 million round to push the work forward, aiming at a slate of currently undruggable quests.

Orum has been working on a platform tech out of Ajou University that relies on endocytosis to smuggle antibodies and their cargo inside a cell. They’ve published work in Nature that illustrates its preclinical potential in RAS mutations, and KRAS is on their list of targets. 

Endpoints News

Basic subscription required

Unlock this story instantly and join 54,900+ biopharma pros reading Endpoints daily — and it's free.

Astel­las buys in­to Fre­quen­cy's re­gen­er­a­tive med strat­e­gy with a $625M al­liance on hear­ing loss

The executive team at Frequency Therapeutics never oversold the results of their maiden Phase I/II study for a new drug to rectify hearing loss. It was, they said back in April, primarily about safety and tolerability, where their drug FX-322 performed as they had hoped. 

That early glimpse of efficacy everyone searches for in their first try on humans? 

(I)mprovements in hearing function, including audiometry and word scores, were observed in multiple FX-322 treated patients.

We don’t know exactly what that means. But whatever the details, Astellas found enough in the data to jump in with a sizable collaboration deal.

Endpoints News

Basic subscription required

Unlock this story instantly and join 54,900+ biopharma pros reading Endpoints daily — and it's free.