How does TDP-43 bog up the brains of ALS, FTLD pa­tients? AC Im­mune en­lists Penn sci­en­tists to find out

AC Im­mune, the Swiss biotech known for its tau ap­proach to Alzheimer’s, is shin­ing light on an­oth­er mis­fold­ing pro­tein be­lieved to be re­spon­si­ble for oth­er neu­rode­gen­er­a­tive dis­eases in a new re­search pact with the Uni­ver­si­ty of Penn­syl­va­nia.

Vir­ginia Lee

The trans­ac­tive re­sponse (TAR) DNA bind­ing pro­tein, or TDP-43 in short, is found in most hu­man tis­sues but its mis­fold­ed form was iden­ti­fied in 2006 as a com­mon patho­log­ic sub­stance link­ing fron­totem­po­ral lo­bar de­gen­er­a­tion (FTLD) and amy­otroph­ic lat­er­al scle­ro­sis (ALS). Re­searchers have since sug­gest­ed that when in the wrong shape, the pro­tein ac­ti­vates the “cell au­tophagy gene” ATG7, which prompts neu­rons to de­com­pose.

John Tro­janows­ki

Of­fer­ing a grant to John Tro­janows­ki and Vir­ginia Lee — co-di­rec­tors of Penn’s Cen­ter for Neu­rode­gen­er­a­tive Dis­ease Re­search and a mar­ried cou­ple — AC Im­mune now wants to de­ci­pher “the gov­ern­ing prin­ci­ples of how patho­log­i­cal forms of TDP-43 spread from neu­ron to neu­ron.” The ul­ti­mate goal is to sup­port de­vel­op­ment of both ther­a­peu­tic and di­ag­nos­tic ap­proach­es in FTLP and oth­er ail­ments.

Both renowned in the field of neu­rode­gen­er­a­tion, Tro­janows­ki and Lee are cred­it­ed for elu­ci­dat­ing the role of pro­tein cul­prits such as tau, al­pha-synu­cle­in, the Abe­ta pre­cur­sor pro­tein, and TDP-43 in neu­rode­gen­er­a­tive dis­eases.

AC Im­mune has sev­er­al an­ti­bod­ies in its ar­se­nal de­signed to bind to TDP-43 and lined up pre­clin­i­cal proof-of-con­cept stud­ies set to an­nounce re­sults lat­er this quar­ter. It’s hint­ing that TDP-43 might even be a tar­get for Alzheimer’s — an im­por­tant new av­enue to in­ves­ti­gate at a time the dom­i­nant amy­loid be­ta hy­poth­e­sis has all but crum­bled.

Sci­en­tists from the Uni­ver­sité Laval in France have gen­er­at­ed an an­ti­body can­di­date. When in­ject­ed to mice en­gi­neered to ex­hib­it symp­toms of ALS, the drug ap­peared to re­duce the num­ber of TDP-43 ag­gre­gates and de­crease in­flam­ma­tion in the brain, while im­prov­ing the mice’s cog­ni­tive and mo­tor per­for­mance.

An­drea Pfeifer

AC Im­mune al­so finds at least one oth­er spe­cial­ist play­er in the TDP-43 are­na. Aquin­nah, a biotech based out of Cam­bridge, MA, has re­ceived small but no­table in­vest­ments from Pfiz­er, Ab­b­Vie and Take­da to work on break­ing down the pro­tein buildups. It’s al­so in­ter­est­ed in ap­ply­ing these small mol­e­cule drugs to tau for Alzheimer’s.

“The field is still in­ves­ti­gat­ing the pre­cise caus­es of neu­rode­gen­er­a­tive dis­eases and how to pre­vent, treat and even cure them, in­clud­ing neu­ro-or­phan in­di­ca­tions such as FTLD,” AC Im­mune CEO An­drea Pfeifer said in a state­ment. “In­creas­ing our knowl­edge of the role of TDP-43 in dis­ease pathol­o­gy will mark valu­able progress in this ef­fort.”

2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

FDA hands off its lat­est whirl­wind drug OK as Hori­zon hus­tles would-be block­buster to the mar­ket

The FDA isn’t letting its foot off the gas pedal just because it’s January.

The agency came through with an approval for Horizon Therapeutics’ $HZNP new thyroid eye drug Tepezza (teprotumumab), close to two months ahead of the PDUFA date — which was already set early in the year due to a priority review designation. But that sort of thing is becoming routine at the agency, especially if it has a designated “breakthrough therapy” on its hands.

Endpoints News

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Hal Barron and Emma Walmsley, GSK

GSK’s ‘break­through’ BC­MA can­cer drug gets a pri­or­i­ty re­view — and a big win for the on­col­o­gy R&D team

After largely whiffing the past 2 years on the pharma R&D front, GlaxoSmithKline research chief Hal Barron has seized boasting rights to a key win that puts them back in the cancer drug development game.

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Who are the young bio­phar­ma lead­ers shap­ing the in­dus­try? Nom­i­nate them for End­points' spe­cial re­port

Two years ago, when we did our first Endpoints 20-under-40, we profiled a set of up-and-comers who promised to help reshape the industry as we know it. Now we’re back and once again looking for the top 20 biopharma professionals under the age of 40. We’ll be profiling folks who have accomplished a lot at a young age but seem on the verge of accomplishing so much more.

And we need your help.

John Oyler, Endpoints

BeiGene lines up its first shot at crack­ing the megablock­buster PD-1 mar­ket for lung can­cer. But can they over­come un­der­dog sta­tus?

BeiGene took another big step towards challenging Merck, Bristol-Myers Squibb, AstraZeneca and some other Big Pharma heavyweights for a share of the lucrative lung cancer market for the PD-(L)1s racking up billions in annual revenue.

The China-based biotech $BGNE run by CEO John Oyler posted positive top-line progression-free survival results for their pivotal Chinese study on their PD-1 antibody tislelizumab combined with chemo for squamous non-small cell lung cancer in frontline cases. Squamous NSCLC accounts for about 30% of the overall lung cancer market.

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Pascal Soriot (AP Images)

As­traZeneca plans to spend $535M-plus to ex­pand its R&D net­work and man­u­fac­tur­ing ops in France

UK-based AstraZeneca is steering a significant amount of R&D and manufacturing spending to France,

On the Monday holiday the pharma giant made a splash with its French release outlining plans by CEO Pascal Soriot — a native of France — to invest $275 million in additional R&D partnering with its growing network of French biotech and research groups. In particular, AstraZeneca execs want to amp up their work involving French researchers in their global clinical trial network.

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Rev­o­lu­tion Med shoots for $100M+ IPO — and di­vulges some se­crets about that Warp Dri­ve buy­out

Biotech investors who like to wager on the race to the front of the KRAS market now have a new team to consider.

Revolution Medicines, which extended its reach on RAS with a deal to acquire Warp Drive Bio about 18 months ago, filed their S-1 in search of $100 million-plus. And they gave up a few secrets in the process.

The main clinical claim to fame that Revolution has centered on is the SHP2 inhibitor RMC-4630, partnered with Sanofi back in the summer of 2018 — just after John Reed was named the incoming R&D chief. We already knew that the pharma giant handed over $50 million in cash plus a commitment of hundreds of millions more to align itself with Revolution as it makes a fresh foray into oncology. Now we know that Sanofi is also footing 80% of Revolution’s R&D bill on the program, while setting up a smorgasbord of $235 million in development milestones and $285 million in commercial bonuses.

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What do Mass Gen­er­al, the NCI and Mayo Clin­ic have in com­mon? They rou­tine­ly blow off an FDA rule on post­ing tri­al re­sults

Two years ago, an FDA rule went into effect requiring all clinical trials to report their results on clinicaltrials.gov within a year of completion. It was meant to guard against a publication bias that can leave negative results unpublished and skew the literature and, by extension, our understanding of how and if drugs work.

A team at Ben Goldacre’s Evidence-Based Medicines Data Lab at the University of Oxford just examined how well trial organizers are complying with those rules, and the results, at least for some organizations, are damning.

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