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.

Spe­cial re­port: Meet 20 ex­tra­or­di­nary women who are su­per­charg­ing bio­phar­ma R&D

Even though many biopharma leaders have come together in recent years to address its gender gap, the consensus is clear: We still have a long way to go.

Companies this year were 2.5 times more likely than last year to have a diversity and inclusion program in place, according to a recent BIO survey, but women are still largely absent from executive roles. Getting women to enter the industry isn’t the problem — studies show that they represent just under half of all biotech employees around the world. But climbing through the ranks can be challenging, as women still report facing stereotypes, and, unfortunately, harassment.

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Op­ti­miz­ing Oral Drug De­liv­ery us­ing Zy­dis® Oral­ly Dis­in­te­grat­ing Tablet Tech­nol­o­gy to Ad­dress Pa­tient Chal­lenges


Patients prefer oral dosing, but swallowing tablets can be a challenge for many patients.
The Zydis® orally disintegrating tablet (ODT) platform addresses challenges associated with oral dosing, expanding benefits for patients and options for healthcare providers.
A strong growth trajectory is expected for ODTs given therapeutic innovation and continued technology development.

Many patients prefer conventional tablets for the administration of medications, but some geriatric and pediatric patients and those with altered mental status and physical impairments find swallowing tablets to be difficult. Orally disintegrating tablets (ODTs), which dissolve completely without chewing or sucking, offer a patient-friendly dosage form for the administration of small-molecule drugs, peptides and proteins. With the potential for multiple sites of drug absorption, often faster onset action for the active pharmaceutical ingredient (API), and potentially greater bioavailability, ODTs are an attractive option for drug developers considering first-to-market formulations or product line extensions of existing drugs with compatible API. In this report, we look at how innovation in the industry-leading Zydis ODT platform is expanding oral formulation options and bringing benefits to patients.

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Geoffrey Porges (SVB Leerink)

The 2022 wave com­ing? Top an­a­lyst says Big Phar­ma will have more than $1T avail­able to sat­is­fy its grow­ing ap­petite for biotech M&A

All through this year you could practically feel the frustration of the biotech investor class as M&A activity continued to drag behind expectations — or desires. Buyouts of public companies provide the essential juice for keeping stocks lively, and there’s been a notable lack of juice in 2021.

So is all that about to change, big time?

SVB Leerink’s Geoffrey Porges, a longtime student of biotech M&A, thinks so. In a lengthy analysis he put out last week, Porges totted up the cash flow of the major pharmas and determined that there was a good long list of industry buyers who would have around a half trillion dollars of cash to play with in 2022. Leverage that up with added debt and you could get that deal cache to $1.6 trillion.

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Mer­ck pumps the brakes on two more PhI­II tri­als for its lead an­ti-HIV drug

After trial investigators flagged a drop in immune cell counts that an external committee determined was related to treatment last month, Merck has been pausing HIV-related Phase II and III trials ever since.

On Monday, the biopharma company announced it’s pausing enrollment in two of its Phase III trials evaluating its leading anti-HIV drug candidate, which is the once-monthly, oral islatravir.

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James Sabry

'We're in': Roche and Genen­tech join forces on a multi­bil­lion-dol­lar dis­cov­ery pact with a brash AI up­start

Over the past couple of years, the top execs at Roche and Genentech have inked a flurry of deals aligning the global pair with several of the new players that have emerged in the booming AI and machine learning world. That strategy was supercharged in the spring of 2020 by their decision to recruit Aviv Regev out of the computational world she occupied at the Broad. And today they’re taking that computational approach in R&D to a whole new level.

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Chen Schor, Adicet CEO

Adicet un­veils ear­ly re­spons­es for off-the-shelf drug lever­ag­ing rare T cells. Will dura­bil­i­ty hold up?

On the hunt for the next generation of “off-the-shelf” cell therapies, biotech players like Adicet Bio have looked to leverage some of the less-obvious members of the immune system as potent cancer fighters. In Adicet’s case, scarce gamma delta T cells are on the menu, and an early cut of data is showing some promise.

Adicet’s AD-001, an off-the-shelf cell therapy developed by engineering a CD20-targeting chimeric antigen receptor (CAR) onto a donor’s gamma delta T cells, posted two complete responses across four patients in an early Phase I study testing the drug in patients with heavily pretreated B cell non-Hodgkin’s lymphoma, the biotech said Monday.

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Bolt Bio CEO Randy Schatzman

Bolt Bio goes bust as in­vestors boo sin­gle re­sponse in ear­ly test against HER2-ex­press­ing tu­mors

Bolt Bio’s BDC-1001, an antibody conjugate drug designed to amp up the body’s innate immune system response to tumors, posted a single partial response in a Phase I/II study in patients with HER2-expressing solid tumors after a year of dosing. Just 13 of 40 evaluable patients showed any signs of “clinical activity,” the biotech said Monday.

BDC-1001 links a HER2-targeting biosimilar of Herceptin with a TLR7/8 agonist, which is designed to activate myeloid cells in the innate immune system and drive tumor cytotoxicity, Bolt said. But the early results paint the picture of a drug with little effect on HER2 tumors, one of the most highly validated tumor targets in drug development.

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Biohaven CEO Vlad Coric (Photo Credit_ Andrew Venditti)

Bio­haven shakes up lead­er­ship team as it feels the heat from mi­graine com­peti­tors

As Biohaven Pharma comes off a rollercoaster pipeline year, its CEO will take on more responsibility in a full C-suite makeover.

Vlad Coric was unanimously elected to the role of chairman of the board of directors, after Declan Doogan’s retirement. Matthew Buten will take over the role of CFO after James Engelhart’s retirement, and director Michael Heffernan has been appointed lead independent director. All of the appointments are effective immediately, a company press release said.

Mar­ket­ingRx Matchup: How Ab­b­Vie and Bio­haven ads rank in head-to-head mi­graine chal­lenge

Are you ready to rumble? DTC brands that is. MarketingRx is launching a new monthly feature today called MarketingRx Matchup. We’re pitting two pharma brands’ DTC advertising in the same therapeutic category against each other to find out what consumers and patients really think.

Market research company Leger is handling the polling and analysis each month, and I’ll be writing up the results — along with my own take — inside MRx on the first Tuesday of the month.

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