Poised to launch its first mar­ket­ing ef­fort, Al­ny­lam makes a big leap in­to CNS dis­eases and Alzheimer's

With its lead RNAi drug poised for an his­toric ap­proval, Al­ny­lam $AL­NY is now lay­ing plans to cre­ate a pipeline of CNS drugs that will tar­get some of the tough­est dis­eases that face re­searchers to­day — in­clud­ing Alzheimer’s, the Night King of dis­eases.

Kevin Fitzger­ald

Al­ny­lam re­searchers are fol­low­ing up on a ro­dent study where they say they were able to de­liv­er a small in­ter­fer­ing RNA drug — or siR­NA —in­to the brain and spinal cord area. Us­ing in­trathe­cal in­jec­tion — cir­cum­vent­ing the blood-brain bar­ri­er — the biotech says that they were able to durably si­lence a dis­ease tar­get gene tran­script, of­fer­ing proof of prin­ci­ple ev­i­dence that they could suc­ceed where a long queue of con­tenders have failed.

Us­ing new tech­nol­o­gy, Al­ny­lam says the plan now is to se­lect its first CNS can­di­date lat­er this year, with a grow­ing ef­fort to go af­ter a string of tough-to-beat dis­eases, in­clud­ing Alzheimer’s, Hunt­ing­ton’s, and Parkin­son’s.

“We have now ap­plied our learn­ings, in­clud­ing ad­di­tion­al chem­istry ad­vances, to en­able de­liv­ery of siR­NAs be­yond the liv­er to the CNS, where there are a large num­ber of un­met needs well suit­ed for RNAi ther­a­peu­tics. As we be­gin to ad­vance our CNS pipeline, ini­tial ef­forts are fo­cused on ge­net­i­cal­ly val­i­dat­ed CNS tar­gets, use of bio­mark­ers for ini­tial proof-of-con­cept, and dis­ease set­tings with high un­met need and a de­fin­able path to reg­u­la­to­ry ap­proval and pa­tient ac­cess,” said Kevin Fitzger­ald, the se­nior VP of re­search at Al­ny­lam. 

Alzheimer’s in par­tic­u­lar has proven to be the tough­est tar­get in bio­phar­ma. Mer­ck’s re­cent fail­ure with a BACE1 in­hibitor led the phar­ma gi­ant to con­clude that that ap­proach — elim­i­nat­ing the flow of amy­loid be­ta in­to the brain — will like­ly not work in symp­to­matic pa­tients. Their re­searchers al­so con­ced­ed that the whole amy­loid be­ta the­o­ry could be noth­ing but a fic­tion that drove bil­lions of dol­lars of mis­spent re­search in­vest­ments.

The fo­cus now has shift­ed more to­ward pre-symp­to­matic pa­tients as well as com­bi­na­tion ther­a­pies go­ing af­ter more than one tar­get at once. And the FDA has in­di­cat­ed its will­ing­ness to pro­vide new guide­lines that fo­cus more on bio­mark­ers of the dis­ease to prove a drug’s abil­i­ty to dri­ve im­proved cog­ni­tion for pa­tients.

While a host of ma­jor play­ers like Pfiz­er and As­traZeneca and GSK have re­treat­ed from the field in the wake of mul­ti­ple fail­ures, leav­ing few or no projects in their wake, new play­ers like Cel­gene and the start­up De­nali have been get­ting in­to the Alzheimer’s are­na. You can now in­clude one more big play­er which plans to make a dif­fer­ence.

Grow­ing ac­cep­tance of ac­cel­er­at­ed path­ways for nov­el treat­ments: but does reg­u­la­to­ry ap­proval lead to com­mer­cial suc­cess?

By Mwango Kashoki, MD, MPH, Vice President-Technical, and Richard Macaulay, Senior Director, of Parexel Regulatory & Access

In recent years, we’ve seen a significant uptake in the use of regulatory options by companies looking to accelerate the journey of life-saving drugs to market. In 2018, 73% of the novel drugs approved by the U.S. Federal Drug Administration (FDA) were designated under one or more expedited development program categories (Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval).ᶦ

Sanofi out­lines big API plans as coro­n­avirus out­break re­port­ed­ly threat­ens short­age of 150 drugs

As the world becomes increasingly dependant on Asia for the ingredients of its medicines, Sanofi sees business to be done in Europe.

The French drugmaker said it’s creating the world’s second largest active pharmaceutical ingredients (API) manufacturer by spinning out its six current sites into a standalone company: Brindisi (Italy), Frankfurt Chemistry (Germany), Haverhill (UK), St Aubin les Elbeuf (France), Újpest (Hungary) and Vertolaye (France). They have mapped out €1 billion in expected sales by 2022 and 3,100 employees for the new operations headquartered in France.

UP­DAT­ED: NGM Bio takes leap for­ward in crowd­ed NASH field

South San Francisco-based NGM Bio may have underwhelmed with its interim analysis of a key cohort from a mid-stage NASH study last fall — but stellar topline data unveiled on Monday showed the compound induced significant signs of antifibrotic activity, NASH resolution and liver fat reduction, sending the company’s stock soaring.

There are an estimated 50+ companies focused on developing drugs for non-alcoholic steatohepatitis, or NASH, a common liver disease that has long flummoxed researchers. The first wave of NASH drug developers struggled with efficacy as well as safety — and companies big and small have crashed and burned.

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Mickey Kertesz, KidsandArtOrg via YouTube

Soft­Bank's newest, $165M biotech in­vest­ment looks for in­fec­tious traces in the blood

SoftBank has found its newest biotech investment.

The Japanese bank has invested $165 million into Karius, a company that uses blood tests to diagnose infectious diseases, as part of its new Vision Fund 2. The full scope of the new fund has yet to be announced, but the first and newly-beleaguered Vision Fund poured $100 billion into technology companies, including the biotechs Vir Biotechnology and Roivant and the sequencing company 10x Genomics.

Methicillin-resistant Staph aureus (Shutterstock)

FDA grants ‘break­through’ sta­tus to an­tibi­ot­ic al­ter­na­tive as Con­tra­Fect rush­es to join fight against su­per­bug

An experimental drug that promises to be the first anti-infective agent to prove superior to vancomycin — an antibiotic approved in 1958 — has notched the FDA’s “breakthrough” status.

ContraFect said the designation was based on Phase II data in which exebacase was tested against a superbug known as methicillin-resistant Staph aureus, or MRSA. In a subgroup analysis, the clinical responder rate at day 14 was 42.8% higher than that among those treated with standard of care, the company said (p=0.010).

Zhong Nanshan, CGTN via YouTube

Har­vard joins coro­n­avirus fight with $115 mil­lion and a high-pro­file Chi­nese part­ner

For two months, as the novel coronavirus swelled from a few early cases tied to a Wuhan market to a global epidemic, most of the world’s focus and dollars have flowed toward emergency initiatives: building vaccines at a record pace, plucking experimental antivirals out of freezers to see what sticks and immunizing mice for new antibodies.

Now a new and well-funded collaboration between Harvard and a top Chinese research institute will play the long game. In a 5-year, $115 million initiative backed by China Evergrande Group, researchers from the Harvard Medical School, Harvard T.H. Chan School of Public Health and Guangzhou Institute for Respiratory Health will study the virus in an effort to develop therapies against infections by the novel coronavirus, known as SARS–CoV-2, and to prevent new ones.

No­var­tis gets a boost in block­buster mul­ti­ple scle­ro­sis race with Roche

In the first step of what’s likely to be a long and uphill battle for the drugmaker, the FDA has accepted Novartis’s BLA submission for a new multiple sclerosis drug and given it priority review. The PDUFA date for the potential blockbuster drug is in June.

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Juergen Horn

An­i­mal health vet Juer­gen Horn makes new an­ti­body play for pets, rak­ing $15M in Se­ries A haul

Zoetis forked over $85 million in 2017 to acquire Nexvet Biopharma and its pipeline of monoclonal antibodies. Juergen Horn, Nexvet’s former chief product development officer, has now secured $15 million for his own biologic company for animals: Invetx.

Buoyed by emerging advances in gene therapies for humans, scientists have started looking at harnessing the technology for animals setting up companies such as Penn-partnered Scout Bio and George Church-founded Rejuvenate Bio. But akin to Nexvet, Invetx is working on leveraging the time-tested science of monoclonal antibodies to treat chronic diseases that afflict man’s best friend.

As coro­n­avirus out­break reach­es 'tip­ping point,' GSK lends ad­ju­vant tech to Chi­nese part­ner armed with pre­clin­i­cal vac­cine

As the coronavirus originating out of Wuhan spreads to South Korea, Italy and Iran, stoking already intense fears of a pandemic, GlaxoSmithKline has found another pair of trusted hands to place its adjuvant system. China’s Clover Biopharmaceuticals will add the adjuvant to its preclinical, protein-based vaccine candidate against SARS-CoV-2.

Clover, which is based in the inland city of Chengdu, boasts of a platform dubbed Trimer-Tag that produces covalently-trimerized fusion proteins. Its candidate, COVID-19 S-Trimer, resembles the viral spike (S)-protein found in the virus.