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.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

Covid-19 vac­cine boost­ers earn big thumbs up, but Mod­er­na draws ire over world sup­ply; What's next for Mer­ck’s Covid pill?; The C-suite view on biotech; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

You may remember that at the beginning of this year, Endpoints News set a goal to go broader and deeper. We are still working towards that, and are excited to share that Beth Snyder Bulik will be joining us on Monday to cover all things pharma marketing. You can sign up for her weekly Endpoints MarketingRx newsletter in your reader profile.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'


Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

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Susan Galbraith speaking at Endpoints News' virtual EUBIO21 summit

Imfinzi/treme­li­mum­ab com­bo scores As­traZeneca an­oth­er OS win — this time in liv­er can­cer

Is the tide turning on AstraZeneca’s battered PD-L1/CTLA4 combo?

A single priming dose of the experimental tremelimumab, followed by Imfinzi every four weeks, beat Nexavar (sorafenib) in helping a group of liver cancer patients live longer in a Phase III study, the company reported, meeting the primary endpoint.

Specifically, the two drugs extended overall survival for patients with unresectable hepatocellular carcinoma who had not received prior systemic therapy and were not eligible for localized treatment.

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Roche's Tecen­triq cross­es the fin­ish line first in ad­ju­vant lung can­cer, po­ten­tial­ly kick­ing off gold rush

While falling behind the biggest PD-(L)1 drugs in terms of sales, Roche has looked to carve out a space for its Tecentriq with a growing expertise in lung cancer. The drug will now take an early lead in the sought-after adjuvant setting — but competitors are on the way.

The FDA on Friday approved Tecentriq as an adjuvant therapy for patients with Stage II-IIIA non small cell lung cancer with PD-(L)1 scores greater than or equal to 1, making it the first drug of its kind approved in an early setting that covers around 40% of all NSCLC patients.

Amit Etkin, Alto Neuroscience CEO (Alto via Vimeo)

A star Stan­ford pro­fes­sor leaves his lab for a start­up out to re­make psy­chi­a­try

About five years ago, Amit Etkin had a breakthrough.

The Stanford neurologist, a soft-spoken demi-prodigy who became a professor while still a resident, had been obsessed for a decade with how to better define psychiatric disorders. Drugs for depression or bipolar disorder didn’t work for many patients with the conditions, and he suspected the reason was how traditional diagnoses didn’t actually get at the heart of what was going on in a patient’s brain.

Rahul Singhvi, Resilience CEO

A Bob Nelsen start­up turns to Har­vard to help sharp­en its tech, in­spir­ing first spin­out

One of Bob Nelsen’s latest projects is headed to Harvard.

Resilience, a company started with the goal of establishing itself as a “one-stop-shop” for companies looking to scale manufacturing, including for hard-to-develop cell and gene therapies, is less than a year old. Friday, it announced a five-year R&D deal with Harvard University that includes $30 million to develop biologics, including vaccines, nucleic acids and cell and gene therapies.

Stéphane Bancel, AP Images

As Mod­er­na's search for African man­u­fac­tur­ing site ramps up, Ban­cel an­swers crit­i­cism about do­na­tions

Years before the pandemic, Moderna’s CEO Stéphane Bancel had thoughts of using mRNA to fight neglected tropical diseases.

Now, while under the magnifying glass of the US government and public health organizations alike, his company will try to slide into the often-neglected area to help with Covid-19 vaccines too.

A week ago, Moderna announced that it would invest $500 million in an African manufacturing plant, though it didn’t say exactly where that would be. Bancel said Thursday in a call with Endpoints News that his team has narrowed the search down to a final list “between three and five countries,” that the company is currently assessing.

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