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.”

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

UP­DAT­ED: White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

Covid-19 roundup: Mod­er­na read­ies to en­ter PhI­II in Ju­ly, As­traZeneca not far be­hind; EU ready to ne­go­ti­ate vac­cine ac­cess with $2.7B fund

Moderna may soon add another first to the Covid-19 vaccine race.

In March, the mRNA biotech was the first company to put a Covid-19 vaccine into humans. Next month, they may become the first company to put their vaccine into the large, late-stage trials that are needed to prove whether the vaccine is effective.

In an interview with JAMA editor Howard Bauchner, NIAID chief Anthony Fauci said that a 30,000-person, Phase III trial for Moderna’s vaccine could start in July. The news comes a week after Moderna began a Phase II study that will enroll several hundred people.

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José Basel­ga finds promise in new class of RNA-mod­i­fy­ing can­cer tar­gets, lock­ing in 3 pre­clin­i­cal pro­grams with $55M

Having dived early into some of the RNA breakthroughs of the last decades — betting on Moderna’s mRNA tech and teaming up with Silence on the siRNA front — AstraZeneca is jumping into a new arena: going after proteins that modify RNA.

Their partner of choice is Accent Therapeutics, which is receiving $55 million in upfront payment to steer a selected preclinical program through to the end of Phase I. After AstraZeneca takes over, the Lexington, MA-based startup has the option to co-develop and co-commercialize in the US — and collect up to $1.1 billion in milestones in the long run. The deal also covers two other potential drug candidates.

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Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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Joseph Kim, Inovio CEO (Andrew Harnik, AP Images)

Caught in a stand­off with its con­tract man­u­fac­tur­er over Covid-19 vac­cine, In­ovio files suit in an at­tempt to break free while ri­vals race ahead

Inovio was one of the first vaccine developers to snag attention for a jab that their execs said promised to end the Covid-19 pandemic. Using their own unique DNA tech, CEO Joseph Kim said it took just 3 hours to work it out.

But while rivals are racing to the finish line with ambitious plans to make vast quantities of their vaccines with billions of dollars of deals, Inovio is still stuck at the starting line on manufacturing.