Geoff MacKay, Avrobio

Avro­bio is us­ing 'pod­s' to cre­ate gene ther­a­pies, and it be­lieves the ap­proach could change the game al­to­geth­er

Ge­off MacK­ay

Where oth­er com­pa­nies have gone big, Avro­bio is go­ing small. Its man­u­fac­tur­ing op­er­a­tion is no dif­fer­ent.

In­stead of try­ing to keep up with the val­i­da­tion of new fa­cil­i­ties — and spend­ing mon­ey and pre­cious time in the process — the com­pa­ny has opt­ed for a dif­fer­ent ap­proach: small, au­to­mat­ed pods that can be in­stalled in rent­ed clean rooms any­where. Though pro­duc­tion out­put isn’t as high as oth­er com­pa­nies, Avro­bio avoids brick-and-mor­tar and is able to stay flex­i­ble and nim­ble to re­spond to fluc­tu­a­tions.

“We be­lieve it’s the on­ly way to glob­al­ize,” said Ge­off MacK­ay, Avro’s founder and CEO. “We had no ap­petite to build big fa­cil­i­ties every­where in the world.”

The com­pa­ny based in Cam­bridge, MA is fo­cused on sin­gle-dose per­son­al­ized gene ther­a­py to cure Fab­ry dis­ease, Gauch­er dis­ease type 1 and cysti­nosis through the plat­form its dubbed pla­to. Un­like oth­er gene ther­a­pies that are de­liv­ered straight in­to pa­tients, Avro­Bio’s lentivi­ral-based ther­a­pies are de­liv­ered ex vi­vo in­to pa­tients’ stem cells be­fore pro­lif­er­a­tion and then in­fu­sion back in­to pa­tients.

The pods — typ­i­cal­ly used in hos­pi­tals for bone mar­row trans­plants — come from Mil­tenyi Biotec, and MacK­ay and his team re­pur­pose the tech for use in mod­i­fy­ing the pa­tients’ stem cells. The pods are housed in CMO clean rooms all over the world, from Hous­ton to Mel­bourne, San Jose and Maas­tricht, but the biotech even­tu­al­ly plans to scale up ca­pac­i­ty for its own in-house ver­sion of the tech­nol­o­gy.

MacK­ay be­lieves a lo­cal­ized man­u­fac­tur­ing chain is cru­cial be­cause it al­lows for each pa­tients’ stem cells to be stored in rel­a­tive prox­im­i­ty to the pa­tient.  The mod­el al­so al­lows a greater de­gree of flex­i­bil­i­ty — each dis­crete pod can be used for a wide va­ri­ety of ther­a­pies — and easy scal­a­bil­i­ty.

“The beau­ty here is that you val­i­date the pod, but reg­u­la­tors are ag­nos­tic about where you house the pod, be­cause the en­vi­ron­ment doesn’t change,” MacK­ay said. “It’s the ex­act same steps, the ex­act same en­vi­ron­ment, so you kind of just side­step all of the com­plex­i­ties of get­ting new man­u­fac­tur­ing fa­cil­i­ties on­line.”

It’s al­so a boon for Avro­Bio, which at the clin­i­cal stage is ap­proach­ing the point at which most gene ther­a­py com­pa­nies start think­ing of in­vest­ing heavy cap­i­tal in their own plants. With­out the need for a huge foot­print, that could Avro­Bio cap­i­tal flex­i­ble as it moves in­to the next stage of tri­als.

“When you’re a biotech com­pa­ny in ear­ly de­vel­op­ment, the cost of cap­i­tal is ob­vi­ous­ly pre­cious, and if you don’t have to spend hun­dreds of mil­lions of dol­lars with a VC type cost of cap­i­tal, that’s great … Nor­mal­ly, you don’t have that type of lux­u­ry,” MacK­ay said.

Avro­bio cur­rent­ly has 3 prod­ucts in clin­i­cal tri­als. Its gene ther­a­py for Fab­ry dis­ease is cur­rent­ly be­ing stud­ied in two clin­i­cal tri­als: 1 Phase I tri­al in Cana­da, and a Phase II tri­al in Aus­tralia, the US and Cana­da. It al­so has a ther­a­py for Gauch­er dis­ease type 1 that is in Phase I in Cana­da and Aus­tralia, and a cysti­nosis study in a Phase I/II tri­al at the Uni­ver­si­ty of Cal­i­for­nia, San Diego.

To­ward the end of 2018, the gene ther­a­py com­pa­ny saw its stock plum­met, drop­ping down 52% af­ter its da­ta sur­round­ing Fab­ry dis­ease treat­ment showed that vec­tor copy num­bers dropped in pe­riph­er­al blood in all of its pa­tients be­tween 1 and 18 months.

Re­cent­ly, the com­pa­ny an­nounced new da­ta that showed at least in a few pa­tients, the ther­a­py saw 100% re­duc­tion in kid­ney sub­strate, the end­point the FDA us­es for ap­proval. There has been strong safe­ty and ef­fi­ca­cy da­ta in all 14 pa­tients in the tri­al, and so far, a year from dos­ing, 10 pa­tients in clin­i­cal tri­als show no wan­ing ef­fi­ca­cy.

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; and more

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I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

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BAR­DA slows its $9B en­gine for new Covid-19 ther­a­peu­tics

The Biomedical Advanced Research and Development Authority is cooling its jets in looking for new, potential Covid-19 treatments, at least in the near term.

An HHS spokesperson told Endpoints News via email, “to date, BARDA has obligated more than $9 billion for the development and/or purchase of 13 therapeutics, beginning in February 2020 with support to develop Regeneron’s monoclonal antibody therapeutic. Therapeutics are an important element of the COVID-19 response, and we are focused on the programs currently underway and/or in negotiation using the funds available to us.”

Bris­tol My­ers backs up its case for heart drug mava­camten as FDA weighs app in car­diomy­opa­thy

When Bristol Myers Squibb signed off on its $13 billion acquisition of MyoKardia back in October, it was making a big bet that lead drug mavacamten could prove a game changer in cardiac myopathy. Now, with the drug up for FDA review, Bristol Myers is backing up its case with new quality of life data.

Patients dosed with myosin inhibitor mavacamten posted a clinically significant increase in scores on the Kansas City Cardiomyopathy Questionnaire, a catch-all summary of symptoms and quality of life markers, over placebo at 30 weeks, according to data from the Phase III EXPLORER-HCM study presented Saturday at the virtual American College of Cardiology meeting.

Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.

Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

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Marshall Fordyce, Vera CEO

Gene ther­a­py play­er turned kid­ney spe­cial­ist Ve­ra drops a dud in lead­up to Nas­daq, pric­ing well be­low range

Vera Therapeutics took a big risk at the start of the year, pivoting away from its gene editing mission statement to chase a lead kidney drug instead — and they doubled down with an IPO just months later. But investors don’t seem impressed with Vera’s promise, and now the biotech is looking at a far more scaled-back offering.

On Friday, Vera priced its 4.35-million-share IPO at $11 per share, well below its targeted range of $14 to $16 and good for $47.58 million in proceeds. The biotech will start trading Monday under the ticker $VERA.

Darren Ji, Elpiscience CEO (Lilly Asia Ventures)

Kept an ocean away from its sci­en­tif­ic ad­vi­sors, Shang­hai's Elpi­science keeps up the clin­i­cal progress, re­fu­els for its I/O pipeline

When Elpiscience pooled $100 million for its Series B in late 2019, CEO Darren Ji promised to move what he described as one of the broadest immuno-oncology pipelines swiftly through the clinic in both the US and China.

Then a pandemic got in the way — but not by much. The Shanghai-based biotech managed to keep testing its 4-1BB/PD-L1 drug, get an OX40 agonist cleared for clinical trials (nabbing a collaboration with Junshi in the process), while in-licensing a Phase I bispecific from California’s TRIGR Therapeutics.

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