Eli Lil­ly shut­ters the last PhI­II so­la study, cer­tain of fail­ure

David Ricks, Lil­ly

Eli Lil­ly has tak­en an­oth­er big re­verse step in its re­treat from solanezum­ab, the Alzheimer’s drug once con­sid­ered the com­pa­ny’s lot­tery tick­et in R&D.

Fol­low­ing the fail­ure of Ex­pe­di­tion 3, Lil­ly’s mas­sive­ly ex­pen­sive third at­tempt to come up with sol­id da­ta of its ef­fi­ca­cy, in­ves­ti­ga­tors have now washed their hands of Ex­pe­di­tion Pro, an­oth­er Phase III study mount­ed for pa­tients with prodomal dis­ease, when their mem­o­ry be­gins to fade but they can still func­tion well on a dai­ly ba­sis.

In a call with an­a­lysts on Tues­day, CEO David Ricks says that in light of the over­lap in Ex­pe­di­tion 3 and the Ex­pe­di­tion Pro study, there was no sci­en­tif­ic ba­sis to be­lieve they would find a “mean­ing­ful ben­e­fit to pa­tients with prodomal Alzheimer’s dis­ease.”

Lil­ly had set out to re­cruit 2,450 patents for Ex­pe­di­tion Pro, which was due to wrap in 2021.

In an­oth­er note, Lil­ly’s Q4 up­date in­clud­ed the end of a Phase I study for “A ß An­ti­body Fab PEG,” a new bi­o­log­ic en­ti­ty that had been stud­ied for Alzheimer’s dis­ease.

Ricks took over as CEO at the start of his year, and gets to start his tenure by large­ly bury­ing what re­mains of one of the biggest late-stage ef­forts in the in­dus­try, long pur­sued by John Lech­leit­er. An­a­lysts have long been re­luc­tant to give Lil­ly good odds on the drug, but in the off chance they were suc­cess­ful, many be­lieved it could have racked up $10 bil­lion in an­nu­al sales.

In­stead, the drug has be­come the lat­est vic­tim in a near com­plete clin­i­cal rout on the Alzheimer’s front, where re­searchers have been shut out of any im­por­tant ad­vances for the past decade.

Lil­ly is not quite fin­ished with so­la, though. The pre­clin­i­cal study in Alzheimer’s dis­ease (An­ti-Amy­loid Treat­ment in Asymp­to­matic Alzheimer’s “A4”), and Dom­i­nant­ly In­her­it­ed Alzheimer’s Dis­ease, known as ”DI­AN,” con­tin­ue).

Lil­ly’s most ad­vanced Alzheimer’s ef­fort now cen­ters on a BACE drug it in-li­censed from As­traZeneca (AZD3293), to re­place its own pro­gram that was scut­tled by tox­i­c­i­ty.

Dur­ing Tues­day’s Q&A with an­a­lysts, Lil­ly chief sci­en­tist Jan Lund­berg was giv­en the task of ex­plain­ing the com­pa­ny’s at­ti­tudes about the A be­ta hy­poth­e­sis, which it’s been ex­plor­ing for years. So­la was de­signed to get rid of tox­ic con­cen­tra­tions of amy­loid be­ta, which many be­lieve is a cause of the dis­ease. It’s worth quot­ing him at length.

The amy­loid-be­ta hy­poth­e­sis and the con­nec­tion to Alzheimer’s dis­ease has strong ev­i­dence from ge­net­ics, where if you have too much amy­loid in your brain, you get ear­ly Alzheimer’s dis­ease. And al­so the op­po­site, if you have less amy­loid-be­ta pro­duc­tion then by mu­ta­tions in the APP in the BACE1 cleav­age side, you al­so seem to be pro­tect­ed from de­men­tia.

The key ques­tion is so how do you trans­late then these ge­net­ics in­to re­al­i­ties of phar­ma­co­log­i­cal treat­ment in an aged pa­tient? And here there are a va­ri­ety of ap­proach­es that have been used. And it’s al­so a key one here to think about if you have an an­ti­body with ac­cess to brain, 0.1% through the blood/brain bar­ri­er, how can you com­pare that re­sult then to, for in­stance, an oral BACE in­hibitor, which some of them go 100% in­to the brain and are I think more like­ly to have a marked ef­fect than on the free amy­loid be­ta?

And the sec­ond ques­tion is clear­ly then how ear­ly do you have to treat? And I think we should rec­og­nize that even if you have mild Alzheimer’s dis­ease, your brain has been ac­cu­mu­lat­ing amy­loids for decades, and you al­most have max­i­mum amy­loid in your brain al­ready. So I think there could be two com­po­nents here, like I say. If solanezum­ab re­al­ly en­tered the brain enough to af­fect amy­loid be­ta, I think our bio­mark­ers like amy­loid PET didn’t re­al­ly change very much by solanezum­ab, nor did the ac­tu­al­ly tau then changes, which are more re­lat­ed to neu­rode­gen­er­a­tion change. So from that stand­point, we didn’t see any ob­jec­tive mea­sures I think that we changed the amy­loid con­tent in the brain, nor then neu­rode­gen­er­a­tion.

Is this against or does this prove that the amy­loid hy­poth­e­sis is wrong? My view is it’s too ear­ly to say. We need to wait for even more pow­er­ful agents. And the next in turn are the oral-based in­hibitors, which are more like­ly I think to have an even stronger ef­fect on the amy­loid be­ta in the brain. And in ad­di­tion then, we need to look at ear­li­er stages of Alzheimer’s.

Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

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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Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

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.

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.

Mer­ck wins a third FDA nod for an­tibi­ot­ic; Mereo tack­les TIG­IT with $70M raise in hand

Merck — one of the last big pharma bastions in the beleaguered field of antibiotic drug development — on Friday said the FDA had signed off on using its combination drug, Recarbrio, with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The drug could come handy for use in hospitalized patients who are afflicted with Covid-19, who carry a higher risk of contracting secondary bacterial infections. Once SARS-CoV-2, the virus behind Covid-19, infects the airways, it engages the immune system, giving other pathogens free rein to pillage and plunder as they please — the issue is particularly pertinent in patients on ventilators, which in any case are breeding grounds for infectious bacteria.