Take­da drops $300M cash to kick off $1B RNAi al­liance with Ar­row­head, shoot­ing for first-in-class rare dis­ease drug

Twelve years ago, Take­da be­came the first ma­jor Asian phar­ma com­pa­ny to buy in­to Al­ny­lam’s pi­o­neer­ing RNAi plat­form with a land­mark $1 bil­lion al­liance. Two FDA ap­provals and a slew of new deals for the field lat­er, the Japan­ese drug­mak­er is mak­ing a new $1.04 bil­lion bet on a rare dis­ease pro­gram from a J&J-part­nered RNAi play­er.

Christo­pher An­za­lone

Ar­row­head is grab­bing $300 mil­lion of that up­front in ex­change for co-de­vel­op­ment and co-com­mer­cial­iza­tion rights of ARO-AAT, which is de­signed to knock down the pro­duc­tion of mu­tant al­pha-1 an­tit­rypsin pro­teins in pa­tients with AAT-as­so­ci­at­ed liv­er dis­ease.

Un­der the deal, the part­ners are go­ing for a 50/50 prof­it-shar­ing struc­ture in the US while Take­da will spear­head the glob­al com­mer­cial­iza­tion and re­serve 20-25% roy­al­ties for the biotech.

For Ar­row­head, this marks an op­por­tu­ni­ty to lean on a large com­pa­ny with ex­per­tise in the gas­troin­testi­nal space and AAT de­fi­cien­cy, ac­cord­ing to CEO Christo­pher An­za­lone, while it fo­cus­es on car­diometa­bol­ic and pul­monary in­di­ca­tions.

“We think there’s no part­ner in the world bet­ter suit­ed than Take­da to bring ARO-AAT for­ward,” he said in a con­fer­ence call, adding lat­er: “This was a no-brain­er for us.”

While there are ri­val RNAi ef­forts tar­get­ing the AATLD — with Al­ny­lam and Dicer­na ty­ing up a few months ago to pool their re­spec­tive drugs for a R&D pact — and oth­ers, like Ver­tex, ex­plor­ing al­ter­na­tive ap­proach­es, Asit Parikh, Take­da’s head of gas­troen­terol­o­gy, said there’s a lot that re­mains to be proven. In­ter­im Phase II re­sults from Ar­row­head, mean­while, sug­gest it has an “ex­quis­ite­ly tar­get­ed” drug on hand.

Asit Parikh

“I ac­tu­al­ly be­lieve that this is go­ing to be the first drug out there for pa­tients with this dis­ease and I ac­tu­al­ly think that it’s go­ing to be the strongest drug out there based on what we know so far,” he said.

Last month Ar­row­head re­port­ed that af­ter 24 weeks of treat­ment, four pa­tients saw their serum and to­tal in­tra-he­pat­ic Z-AAT de­crease by up to 93% and 95%, re­spec­tive­ly.

By treat­ing the un­der­ly­ing cause of AATLD, ARO-AAT has the po­ten­tial to help pa­tients avoid the need for liv­er trans­plan­ta­tion and oth­er co­mor­bidi­ties, Parikh added.

With the lat­est deal, all three of Ar­row­head’s lead drugs have now been part­nered, fu­el­ing a turn­around four years in the mak­ing. Am­gen signed on a $674 mil­lion pact to de­vel­op ARO-LPA, now AMG-890, tar­get­ing apolipopro­tein A for car­dio­vas­cu­lar dis­ease in 2016 short­ly be­fore Ar­row­head was slammed with a clin­i­cal hold due to non-hu­man pri­mate deaths in a tox study.

The com­pa­ny jet­ti­soned all pro­grams us­ing the im­pli­cat­ed EX1 de­liv­ery ve­hi­cle, which amount­ed to its en­tire clin­i­cal-stage pipeline then, and axed close to a third of its staff. But the new dis­cov­ery en­gine kept churn­ing out new com­pounds, and in 2018 J&J hand­ed over $250 mil­lion cash to kick-start a deal that can add up to $3.7 bil­lion, head­lined by a treat­ment for he­pati­tis B.

“This agree­ment al­so sup­ports our strat­e­gy of us­ing part­ner­ing se­lec­tive­ly to con­tin­ue to in­vest in our Tar­get­ed RNAi Mol­e­cule (TRiMTM) plat­form and the grow­ing pipeline of RNAi ther­a­peu­tics tar­get­ing di­verse tis­sue types, while fo­cus­ing our com­mer­cial or­ga­ni­za­tion on op­por­tu­ni­ties in two key ar­eas of car­diometa­bol­ic and pul­monary,” An­za­lone said in a state­ment.

Mani Fa­roohar, an an­a­lyst at SVB Leerink, called it “a pru­dent move.”

“While bulls may grum­ble that the prof­it split and roy­al­ty agree­ment lim­it po­ten­tial up­side in a blue-sky sce­nario, we see the terms of the deal as at­trac­tive, and ap­plaud man­age­ment’s de­ci­sion to lock in a floor val­ue for ARO-AAT (the sin­gle largest val­ue dri­ver in our mod­el), share some de­vel­op­ment costs, and mit­i­gate risk ahead of com­peti­tor da­ta from VRTX, DR­NA and oth­ers,” he wrote in a note.

In his­toric Covid-19 ad­comm, vac­cine ex­perts de­bate a sea of ques­tions — but of­fer no clear an­swers

The most widely anticipated and perhaps most widely watched meeting in the FDA’s 113-year history ended late Thursday night with a score of questions and very few answers.

For nearly 9 hours, 18 different outside experts listened to public health agencies and foundations present how the United States’ Covid-19 vaccine program developed through October, and they debated where it should go from there: Were companies testing the right metrics in their massive trials? How long should they track patients before declaring a vaccine safe or effective? Should a vaccine, once authorized, be given to the volunteers in the placebo arm of a trial?

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 92,400+ biopharma pros reading Endpoints daily — and it's free.

Ul­tragenyx in­jects $40M to grab Solid's mi­crody­s­trophin trans­gene — while side­step­ping the AAV9 vec­tor that stirred up safe­ty fears

Since before Ilan Ganot started Solid Bio to develop a gene therapy for kids like his son, who has Duchenne muscular dystrophy, Ultragenyx CEO Emil Kakkis has been watching and advising the former investment banker as he navigated the deep waters of drug development.

Just as Solid is getting back up on its feet after a yearlong clinical hold, Kakkis has decided to jump in for a formal alliance.

With a $40 million upfront, Ultragenyx is grabbing 14.45% of Solid’s shares $SLDB and the rights to its microdystrophin construct for use in combination with AAV8 vectors. Solid’s lead program, which utilizes AAV9, remains unaffected. The company also retains rights to other applications of its transgene.

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 92,400+ biopharma pros reading Endpoints daily — and it's free.

Pascal Soriot, AstraZeneca CEO (Zach Gibson/Bloomberg via Getty Images)

UP­DAT­ED: FDA gives As­traZeneca the thumbs-up to restart PhI­II Covid-19 vac­cine tri­als, and J&J is prepar­ing to re­sume its study

Several countries had restarted their portions of AstraZeneca’s global Phase III Covid-19 vaccine trial after the study was paused worldwide in early September, but the US notably stayed on the sidelines — until now. Friday afternoon the pharma giant announced the all clear from US regulators. And on top of that, J&J announced Friday evening that it’s preparing to resume its own Phase III vaccine trial.

A top drug pro­gram at Bay­er clears a high bar for CKD — open­ing the door to an FDA pitch

Over the past 4 years, Bayer has been steering a major trial through a pivotal program to see if their drug finerenone could slow down the pace of chronic kidney disease in patients suffering from both CKD as well as Type 2 diabetes.

Today, their team jumped on a virtual meeting hosted by the American Society of Nephrology to offer a solid set of pivotal data to demonstrate that the drug can delay dialysis or a kidney replacement as well as cardio disease, while also adding some worrying signs of hyperkalemia among the patients taking the drug. And they’re hustling it straight to regulators in search of an approval for kidney disease and cardio patients — one of the toughest challenges in the book, as demonstrated by repeated past failures.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 92,400+ biopharma pros reading Endpoints daily — and it's free.

Adam Koppel and Jeffrey Schwartz, Bain

Bain ex­ecs Adam Kop­pel and Jef­frey Schwartz line up $125M for their first blank check deal as Wall Street con­tin­ues to em­brace biotech

Adam Koppel and Jeffrey Schwartz have jumped into the blank check game, raising $125 million for a stock listing in search of a company.

Their SPAC, BCLS Acquisition Corp, raised $125 million this week, with a line on $25 million more as it scouts for a biotech in search of money and a place on Wall Street.

The two principals at Bain Life Sciences have been on a romp since they set up the Bain operation 4 years ago. Their S-1 spells out a track record of 22 deals totaling $650 million for the life sciences group, which led to 9 IPOs.

Covid-19 roundup: An mR­NA play­er gets a boost out of the lat­est round of an­i­mal da­ta; Phase­Bio pulls the plug on treat­ment tri­al

The big tell for CureVac $CVAC is coming up with a looming early-stage readout on their mRNA Covid-19 vaccine in the clinic. But for now they’ll make do with an upbeat assessment on the preclinical animal data they used to get into the clinic.

Researchers for the German biotech say they got the high antibody titers and T cell activation they were looking for, lining up a hamster challenge to demonstrate — in a simple model — that the vaccine could protect the furry creatures. Like the other mRNA vaccines, the drug sends instructions to spur cells to decorate themselves with the distinctive spike on the virus to elicit an immune response.

Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 92,400+ biopharma pros reading Endpoints daily — and it's free.

Retrophin beefs up the rare dis­ease drug pipeline with a $517M buy­out deal

A little more than a year after Retrophin conceded the complete failure of a drug co-invented by company founder Martin Shkreli, the biotech is beefing up its rare disease pipeline through a $517 million buyout deal — fronted with $90 million in cash.

After the bell sounded Thursday, Retrophin $RTRX put out word that it’s acquiring the low-profile biotech Orphan Technologies. The buyout gives them an enzyme replacement therapy called OT-58 for the treatment of classical homocystinuria, a rare disease that is triggered by insufficient levels of an enzyme called cystathionine beta synthase.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 92,400+ biopharma pros reading Endpoints daily — and it's free.