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.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

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Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.