As Ac­thar trou­bles per­sist, Mallinck­rodt in­vests in RNAi and Si­lence Ther­a­peu­tics

A day af­ter it was forced to ax an amy­otroph­ic lat­er­al scle­ro­sis study test­ing its con­tro­ver­sial Ac­thar gel, Mallinck­rodt is in­vest­ing in RNA tech­nol­o­gy to tar­get rare dis­eases by en­list­ing Si­lence Ther­a­peu­tics as a part­ner.

Si­lence Ther­a­peu­tics, akin to oth­ers in its field such as Al­ny­lam who pi­o­neered the first RNA in­ter­fer­ence ther­a­py last Au­gust, is bet­ting on the promise of si­lenc­ing the ex­pres­sion of dis­ease-caus­ing pro­teins. The land­mark dis­cov­ery of RNA in­ter­fer­ence was re­ward­ed with a No­bel prize in 2006. Though found­ed in 1994, the Lon­don biotech changed course to cham­pi­on RNA ther­a­peu­tics in 2012 — and is still in the pre­clin­i­cal phas­es with its slate of ex­per­i­men­tal drugs.

The com­pa­nies are set to co-de­vel­op RNAi ther­a­peu­tics en­gi­neered to in­hib­it the com­ple­ment cas­cade — a group of pro­teins that are in­volved in the im­mune sys­tem and that play a role in the de­vel­op­ment of in­flam­ma­tion.

As part of the agree­ment, Mallinck­rodt is get­ting an ex­clu­sive glob­al li­cense to Si­lence’s C33 com­ple­ment as­set, SLN500, as well as op­tions to li­cense up to two ad­di­tion­al com­ple­ment-tar­get­ed as­sets. The pre­clin­i­cal ther­a­py, SLN500, al­lows the com­pa­nies to tar­get a range of rare dis­eases as well as con­di­tions of im­mune dys­reg­u­la­tion.

Si­lence is in charge of pre­clin­i­cal ac­tiv­i­ties, as well as Phase I stud­ies — and Mallinck­rodt $MNK will be re­spon­si­ble for fur­ther clin­i­cal de­vel­op­ment as well as com­mer­cial­iza­tion.

Un­der the deal, Si­lence se­cures an up­front pay­ment of $20 mil­lion and is el­i­gi­ble to re­ceive up to $10 mil­lion in re­search mile­stones for SLN500 and for each op­tioned as­set, in ad­di­tion to fund­ing for Phase I clin­i­cal de­vel­op­ment in­clud­ing GMP man­u­fac­tur­ing. The SLN500 col­lab­o­ra­tion al­so pro­vides for po­ten­tial added clin­i­cal and reg­u­la­to­ry mile­stone pay­ments of up to $100 mil­lion, com­mer­cial mile­stone pay­ments of up to $563 mil­lion, in ad­di­tion to roy­al­ties.  Should Mallinck­rodt de­cide to li­cense any oth­er as­sets, Si­lence could re­ceive up to $703 mil­lion in sim­i­lar mile­stone pay­ments per as­set, in ad­di­tion to roy­al­ties.

Sep­a­rate­ly, Staines-up­on-Thames-based Mallinck­rodt al­so in­ject­ed $5 mil­lion in­to Si­lence Ther­a­peu­tics, in ex­change for about 5.1 mil­lion shares from its part­ner.

The more than 150-year-old com­pa­ny has a suite of spe­cial­ty med­i­cines and gener­ic treat­ments in its ar­se­nal of drugs, but its Ac­thar gel — which it ac­quired in 2014 with the takeover of Quest­cor — ac­count­ed for a lit­tle over a third of Mallinck­rodt’s rough­ly $3.2 bil­lion in net sales last year.

The prod­ucts list price has been hiked from $40 per vial in 2001 to a whop­ping $38,892 cur­rent­ly. Ex­tract­ed from the pi­tu­itary glands of slaugh­tered pigs, it’s man­u­fac­tured es­sen­tial­ly the same way as it was in the 1950s, and is cleared for use in 19 in­di­ca­tions. The drug­mak­er has there­fore long elicit­ed the ire of reg­u­la­to­ry agen­cies for its mar­ket­ing prac­tices in re­la­tion to Ac­thar.

In May, Mallinck­rodt was dealt a heavy blow when the Cen­ters for Medicare & Med­ic­aid Ser­vices de­cid­ed to re­vert to the base date av­er­age man­u­fac­tur­er price on Ac­thar from the rate used since 2013, which was pri­or to the com­pa­ny’s ac­qui­si­tion of Quest­cor. “(T)he shift will sub­stan­tial­ly raise the cal­cu­lat­ed re­bate such that the net re­al­ized price on Ac­thar sales to Med­ic­aid ben­e­fi­cia­ries will fall from the cur­rent ~$30k+ per vial to ‘dol­lars’ per vial. With Med­ic­aid rep­re­sent­ing ~10% of Ac­thar sales, the shift if put in­to ef­fect would im­pact an­nu­al sales by ~$100 mil­lion per year. In re­sponse, MNK has filed for in­junc­tive re­lief un­der the Ad­min­is­tra­tive Pro­ce­dure Act (APA) where the time­line is ex­pect­ed to be ex­pe­dit­ed; hence a fi­nal rul­ing should at some point in the 2Q-3Q time­frame,” Jef­feries an­a­lysts wrote in a note.

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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George Yancopoulos (Regeneron)

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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Pfiz­er shares surge on pos­i­tive im­pact of their mR­NA Covid-19 vac­cine — part­nered with BioN­Tech — in an ear­ly-stage study

Pfizer and their partners at the mRNA specialist BioNTech have published the first glimpse of biomarker data from an early-stage study spotlighting the “robust immunogenicity” triggered by their Covid-19 vaccine, which is one of the leaders in the race to vanquish the global pandemic.

Researchers selected 45 healthy volunteers 18-55 years of age for the study. They were randomized to receive 2 doses, separated by 21 days, of 10 µg, 30 µg, or 100 µg of BNT162b1, “a lipid nanoparticle-formulated, nucleoside-modified, mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein RBD.” Their responses were compared against the effect of a natural, presumably protective defense offered by a regular infection.

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An ex­pe­ri­enced biotech is stitched to­geth­er from transpa­cif­ic parts, with 265 staffers and a fo­cus on ‘new bi­ol­o­gy’

Over the past few years, different teams at a pair of US-based biotechs and in labs in Japan have labored to piece together a group of cancer drug programs, sharing a single corporate umbrella with research colleagues in Japan. But now their far-flung operations have been knit together into a single unit, creating a pipeline with 10 cancer drug development programs — going from early-stage right into Phase III — and a host of discovery projects managed by a collective staff of some 265 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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Joseph Kim, Inovio CEO (Andrew Harnik, AP Images)

Pos­i­tive Covid-19 vac­cine da­ta? New mouse study? OWS in­clu­sion? Yep, but some­how, the usu­al tid­bits from In­ovio back­fire

You don’t go more than 40 years in biotech without ever getting a product to market unless you can learn the art of writing a promotional press release. And Inovio captures the prize in baiting the hook.

Tuesday morning Inovio, which has been struggling to get its Covid-19 vaccine lined up for mass manufacturing, put out a release that touched on virtually every hot button in pandemic PR.

There was, first and foremost, an interim snapshot of efficacy from their Phase I program for INO-4800.

Jan van de Winkel, Genmab CEO

Seat­tle Ge­net­ics, Gen­mab turn on TV for a high­light reel in cer­vi­cal can­cer — but a ri­val biotech promis­es a bet­ter show

Seattle Genetics $SGEN and their partners at Genmab $GMAB polished up some positive Phase II numbers for their antibody drug conjugate tisotumab vedotin — you can call it TV — for recurrent cervical cancer. And while they mapped out a shortcut to a potential quick approval, the big challenge for this team is being presented by a rival biotech which muscled its way into the spotlight for the same indication a year ago.

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Randy Schatzman, Bolt CEO (Bolt Biotherapeutics)

Bolt Bio­ther­a­peu­tics nabs $93.5M to push Provenge in­ven­tor's new idea deep­er in the clin­ic

A cancer-fighting concept from the inventor of the first cancer vaccine is nearing prime time, and its biotech developer has received a significant new infusion of cash to get it there.

Bolt Biotherapeutics announced a $93.5 million Series C round led by Sofinnova Investments and joined by more than 9 others, including Pfizer Ventures and RA Capital Management. That money will go toward pushing the San Francisco biotech’s platform of innate immune-boosting warheads through its first trial on metastatic solid tumors and into several more.

Days af­ter In­ter­cept re­jec­tion, Akero surges on ‘un­prece­dent­ed‘ NASH da­ta

A year and a half after scoring a $70 million Series B and a top Gilead executive as CEO, Akero Therapeutics has announced new data on their NASH drug. And with the field still reeling from a surprise FDA rejection this week, the news was enough to send their stock surging.

Akero had already said in March that its lead drug had beaten placebo in its Phase II trial, reducing liver fat by 14% in the highest dose group compared to 0.3% in placebo, according to MRI scans. But although NASH is an obesity-related condition and results from fatty buildup in the liver, the real immediate question for any therapy is whether it can resolve the fibrosis and inflammation that results from that buildup. Those data require biopsying the patients, a longer and more invasive process that was further complicated by a pandemic.