Olivier Morand (Azafaros)

Dutch biotech scores €25M in small mol­e­cule bet to tack­le lyso­so­mal stor­age dis­or­ders

While a host of biotech com­pa­nies work on gene and en­zyme re­place­ment ther­a­pies for cer­tain lyso­so­mal stor­age dis­or­ders, a Dutch play­er is aim­ing to slot in its small mol­e­cule ap­proach across a range of these rare in­her­it­ed meta­bol­ic dis­or­ders.

The com­pa­ny — Aza­faros — found­ed in 2018 based on sci­ence de­vel­oped from Lei­den Uni­ver­si­ty and Am­s­ter­dam Uni­ver­si­ty Med­ical Cen­ter has se­cured €25 mil­lion in Se­ries A fi­nanc­ing as it works on shep­herd­ing its lead ex­per­i­men­tal drug in­to the clin­ic.

The drug, dubbed AZ-3102, is de­signed to work via a dual mode of ac­tion — by di­min­ish­ing metabo­lite ac­cu­mu­la­tion and en­hanc­ing lyso­so­mal func­tion.

There has been a lot of at­ten­tion for gene ther­a­py in lyso­so­mal stor­age dis­or­ders — but some ef­forts have shown no ben­e­fit and there are some chal­lenges such as the risk of im­muno­genic­i­ty, not­ed Aza­faros chief Olivi­er Morand in an in­ter­view with End­points News. “But still, it ob­vi­ous­ly has a lot of po­ten­tial.”

Lyso­so­mal stor­age dis­or­ders are in­her­it­ed meta­bol­ic dis­eases char­ac­ter­ized by an ab­nor­mal build-up of var­i­ous tox­ic ma­te­ri­als in the body’s cells as a re­sult of en­zyme de­fi­cien­cies. Lyso­somes are like the stom­ach of the cell, in charge of di­gest­ing com­plex com­po­nents like pro­teins, poly­sac­cha­rides, nu­cle­ic acids, or lipids and break­ing them down in­to sim­pler units. When this process doesn’t oc­cur, a sort of a traf­fic jam en­sues — which can cul­mi­nate in a reser­voir of tox­i­c­i­ty in dif­fer­ent or­gans such as the liv­er, spleen, heart, kid­ney, skin, bones and brain.

Al­to­geth­er, there are rough­ly 50 such dis­or­ders — in­clud­ing Tay-Sachs, Fab­ry, Hunter and San­fil­lipo — each char­ac­ter­ized by dif­fer­ent symp­toms re­sult­ing from the tox­ic ac­cu­mu­la­tion of a cer­tain metabo­lite. For ex­am­ple, tox­ic ac­cu­mu­la­tion in the brain can lead to de­vel­op­men­tal de­lays, seizures, res­pi­ra­to­ry in­fec­tions, loss of vi­sion and hear­ing, and cog­ni­tive func­tion.

“I think the re­cur­rent no­tion is that these dis­eases are very com­plex and very se­vere,” Morand not­ed. “So hav­ing sev­er­al treat­ment modal­i­ties and com­bin­ing them may be the way to go for a so­lu­tion.”

In con­trast to gene or en­zyme re­place­ment ther­a­py de­vel­op­ers, Aza­faros’ small mol­e­cule ef­fort has the po­ten­tial for use across sev­er­al in­di­ca­tions, he added, with­out dis­clos­ing how long it will take AZ-3102 to be ready for clin­i­cal test­ing.

The Se­ries A round was led by For­bion, with par­tic­i­pa­tion from Bio­Med­Part­ners and found­ing in­vestor Bio­Gen­er­a­tion Ven­tures.

Months ago, Mer­ck shelled out up to $576 mil­lion to swal­low Cal­por­ta, which has been work­ing on small mol­e­cule ag­o­nists of TRPML1 — de­signed to re­store cal­ci­um ef­flux and nor­mal­ize lyso­so­mal func­tion — to treat lyso­so­mal stor­age dis­or­ders, as well as neu­rode­gen­er­a­tive dis­eases.

Mean­while, Sang­amo Ther­a­peu­tics has test­ed its gene edit­ing zinc fin­ger tech­nol­o­gy in pa­tients with two lyso­so­mal stor­age dis­eases. Lentivi­ral gene ther­a­py de­vel­op­er Avro­bio al­so is in the ear­ly stages of as­sess­ing the po­ten­tial of its tech­nol­o­gy across dif­fer­ent lyso­so­mal stor­age dis­eases.

Tesla and SpaceX founder Elon Musk gestures to the audience after being recognized by President Trump following the successful launch of a Falcon 9 rocket at the Kennedy Space Center. (via Getty Images)

Tes­la chief Elon Musk teams up with Covid-19 play­er Cure­Vac to build 'R­NA mi­cro­fac­to­ries'

Elon Musk has joined the global tech crusade now underway to revolutionize vaccine manufacturing — now aimed at delivering billions of doses of a new mRNA vaccine to fight Covid-19. And he’s cutting right to the front.

In a late-night tweet Wednesday, the Tesla chief announced:

Tesla, as a side project, is building RNA microfactories for CureVac & possibly others.

That’s not a lot to go on. But the tweet comes a year after Tesla’s German division in Grohmann and CureVac filed a patent on a “bioreactor for RNA in vitro transcription, a method for RNA in vitro transcription, a module for transcribing DNA into RNA and an automated apparatus for RNA manufacturing.” CureVac, in the meantime, has discussed a variety of plans to build microfactories that can speed up the whole process for a global supply chain.

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George Yancopoulos (Regeneron)

UP­DAT­ED: Re­gen­eron co-founder George Yan­copou­los of­fers a com­bat­ive de­fense of the po­lice at a high school com­mence­ment. It didn’t go well

Typically, the commencement speech at Yorktown Central School District in Westchester — like most high schools — is an opportunity to encourage students to face the future with confidence and hope. Regeneron president and co-founder George Yancopoulos, though, went a different route.

In a fiery speech, the outspoken billionaire defended the police against the “prejudice and bias against law enforcement” that has erupted around the country in street protests from coast to coast. And for many who attended the commencement, Yancopoulos struck the wrong note at the wrong time, especially when he combatively challenged someone for interrupting his speech with a honk for “another act of cowardness.”

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Elias Zerhouni (Photo by Vincent Isore/IP3/Getty Images)

Elias Zer­houni dis­cuss­es ‘am­a­teur hour’ in DC, the de­struc­tion of in­fec­tious dis­ease R&D and how we need to prep for the next time

Elias Zerhouni favors blunt talk, and in a recent discussion with NPR, the ex-Sanofi R&D and ex-NIH chief had some tough points to make regarding the pandemic response.

Rather than interpret them, I thought it would be best to provide snippets straight from the interview.

On the Trump administration response:

It was basically amateur hour. There is no central concept of operations for preparedness, for pandemics, period. This administration doesn’t want to or has no concept of what it takes to protect the American people and the world because it is codependent. You can’t close your borders and say, “OK, we’re going to be safe.” You’re not going to be able to do that in this world. So it’s a lack of vision, basically just a lack of understanding, of what it takes to protect the American people.

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Sec­ond death trig­gers hold on Astel­las' $3B gene ther­a­py biotech's lead pro­gram, rais­ing fresh con­cerns about AAV

Seven months after Astellas shelled out $3 billion to acquire the gene therapy player Audentes, the biotech company’s lead program has been put on hold following the death of 2 patients taking a high dose of their treatment. And there was another serious adverse event recorded in the study as well, with a total of 3 “older” patients in the study affected.

The incidents are derailing plans to file for a near-term approval, which had been expected right about now.

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Look­ing for 'ex­ter­nal in­no­va­tion,' Boehringer In­gel­heim re­serves $500M+ for new Shang­hai hub

Now that Boehringer Ingelheim’s bet on contract manufacturing in China has paid off, the German drugmaker is anteing up more to get into the research game.

Boehringer has set aside $507.9 million (€451 million) for a new External Innovation Hub to be built in Shanghai over five years. The site will become one of its “strategic pillars” as the team strives to get 71 approvals — either for new products or indications — by 2030, said Felix Gutsche, president and CEO of Boehringer Ingelheim China.

Vas Narasimhan, Novartis CEO (Patrick Straub/​EPA-EFE/​Shutterstock)

No­var­tis pays $678M for kick­back scheme as Vas Narasimhan tries to dis­tance phar­ma gi­ant from shady be­hav­ior

Novartis has reached another large settlement to resolve misconduct allegations, agreeing to pay more than $678 million to settle claims that it had spent hundreds of millions of dollars on lavish dinners, so-called speaking fees and expensive alcohol “that were nothing more than bribes” to get doctors to prescribe Novartis medications.

The top-shelf alcohol and lavish meals included a $3,250 per person night at Nobu in Dallas, a $672-per person dinner at Washington DC’s Smith & Wollensky and a $314 per person meal at Sushi Roku in Pasadena, according to the Justice Department complaint. There were at least 7 trips to Hooters and fishing trips in Alaska and off the Florida coast. Each of these events were supposed to be “speaker programs” where doctors educated other doctors on a drug, but the DOJ alleged many were “bogus” wine-and-dine events where the drug was barely mentioned, if at all.  (“Nobody presented slides on the fishing trips,” the complaint says.)

No­vavax snags Ben Machielse for CMC and pro­motes a trio of staffers; Mar­ty Du­vall lands an­oth­er CEO post at On­copep­tides

Novavax has been making waves recently by securing a $384 million commitment from CEPI to cover R&D and manufacturing for its Covid-19 vaccine while also spending $167 million on a 150,000 square-foot facility. The Maryland biotech continues to shore up its leadership team as well, bringing in Ben Machielse as their EVP of CMC just a couple weeks after nabbing AstraZeneca vet Filip Dubrovsky as their new CMO. Machielse was president and CEO of Vtesse from 2014-17, and before that, he also spent more than 11 years at MedImmune and was EVP of operations for the back half of his tenure.

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Dan Gold, MEI Pharma CEO

De­vel­op­ment part­ners at MEI, Helsinn dump a high-risk PhI­II AML study af­ter con­clud­ing it would fail sur­vival goal

Four years after Switzerland’s Helsinn put $25 million of cash on the table for an upfront and near-term milestone to take MEI Pharma’s drug pracinostat into a long-running Phase III trial for acute myeloid leukemia, the partners are walking away from a clinical pileup.

The drug — an HDAC inhibitor — failed to pass muster during a futility analysis, as researchers concluded that pracinostat combined with azacitidine wasn’t going to outperform the control group in the pivotal.

Douglas Love, Annexon CEO (Annexon)

IPO bound? A Bay Area biotech grabs a mega-round on the road to a piv­otal neu­rode­gen­er­a­tion pro­gram

South San Francisco-based Annexon has added $100 million to its cash reserves, along with a new roster of marquee investors backing their play on the classical complement pathway involved in neurodegeneration. And that may well fit the profile for an IPO — though right now everything seems to be working on that score.

Eighteen months after Bain and their syndicate partners put up $75 million to fuel clinical work, Annexon is back at the trough. And this time they’re adding Redmile Group for the lead role, with supporting investments from these new arrivals: BlackRock, Deerfield Management Company, Eventide Asset Management, Farallon Capital Management, Janus Henderson Investors and Logos Capital.

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