Mene Pangalos, AstraZeneca R&D chief (AstraZeneca via YouTube)

A day af­ter Mod­er­na vac­cine re­sults, ru­mors swirl of pend­ing As­traZeneca da­ta

A day af­ter Mod­er­na and the NIH pub­lished much-an­tic­i­pat­ed da­ta from their Phase I Covid-19 vac­cine tri­al, at­ten­tion is turn­ing to As­traZeneca which, ac­cord­ing to a UK re­port, is ex­pect­ed to pub­lish its own ear­ly da­ta to­mor­row.

ITV’s Robert Pe­ston re­port­ed that As­traZeneca will pub­lish the Phase I da­ta in The Lancet. 

As­traZeneca and Mod­er­na rep­re­sent the two most am­bi­tious Covid-19 vac­cine ef­forts, hav­ing set the quick­est time­lines for ap­proval (though they were re­cent­ly joined in that re­gard by the Pfiz­er-BioN­Tech part­ner­ship) and some of the lofti­est goals in to­tal dos­es. Yet there is even less known about As­traZeneca’s vac­cine’s ef­fect on hu­mans than there was about Mod­er­na’s be­fore yes­ter­day. Al­though, in a con­tro­ver­sial move, Mod­er­na re­leased some sta­tis­tics from its Phase I in May, As­traZeneca has yet to say any­thing about what it saw in its Phase I tri­al — a move con­sis­tent with the sci­en­tif­ic con­ven­tion to with­hold da­ta un­til it can be pub­lished in a peer-re­viewed jour­nal.

In­stead, so far what the world knows about the ef­fects of a vac­cine that the US, EU, UK and a sig­nif­i­cant por­tion of the de­vel­op­ing world have signed agree­ments for — bil­lions of dol­lars for bil­lions of dos­es — can be re­duced to a pri­ma­ry study and the com­ments so far from sci­en­tists at Ox­ford Uni­ver­si­ty, where the vac­cine was first de­vel­oped, and com­pa­ny ex­ec­u­tives.

Those sci­en­tists and ex­ec­u­tives have been lay­ing the case, most re­cent­ly in a lengthy Bloomberg fea­ture re­leased to­day, that when it comes to their vac­cine, peo­ple should fo­cus on the T cell re­sponse rather than an­ti­bod­ies. Al­though vac­cines work both by elic­it­ing both a T cell re­sponse and neu­tral­iz­ing an­ti­bod­ies from B cells, in­ves­ti­ga­tors gen­er­al­ly fo­cus on an­ti­bod­ies, in part be­cause they are eas­i­er to mea­sure. Mod­er­na called its Phase I a suc­cess in part be­cause tri­al sub­jects made more neu­tral­iz­ing an­ti­bod­ies than pa­tients who had been in­fect­ed with the virus.

Re­cent com­ments from As­traZeneca ap­pear de­signed to low­er any ex­pec­ta­tions that they would show sim­i­lar re­sults. “Neu­tral­iz­ing an­ti­bod­ies is one of the things you’ll look at,” As­traZeneca R&D chief Mene Pan­ga­los told Bloomberg, “but the T-cell re­sponse is go­ing to be im­por­tant.”

Pe­ston cit­ed an un­named source who told him, “Every­body is fo­cused on an­ti­bod­ies but there is a grow­ing body of ev­i­dence sug­gest­ing that the T cells’ re­sponse is im­por­tant in the de­fence against coro­n­avirus.”

Adri­an Hill

Talk of As­traZeneca and an­ti­bod­ies be­gan af­ter ear­ly crit­ics point­ed out that the an­i­mal da­ta sup­port­ing As­traZeneca’s Phase I didn’t find high lev­els of an­ti­bod­ies. In that pri­mate study, con­duct­ed at NI­AID’s Rocky Moun­tain Lab­o­ra­to­ries in Mon­tana, in­ves­ti­ga­tors in­oc­u­lat­ed six rhe­sus mon­keys with the ex­per­i­men­tal vac­cine and ex­posed them to high dos­es of SARS-CoV-2 28 days lat­er. The mon­keys showed no signs of pneu­mo­nia or dis­ease, a re­sult that Adri­an Hill, one of the two sci­en­tists who de­vel­oped the vac­cine, told Bloomberg “wasn’t promis­ing — it was fan­tas­tic.”

William Hasel­tine, a for­mer pro­fes­sor at Har­vard Med­ical School and HIV re­searcher, wrote in Forbes that the vac­cine like­ly wouldn’t be pro­tec­tive be­cause the mon­keys didn’t pro­duce high lev­els of an­ti­bod­ies. He raised the specter of peo­ple who were pro­tect­ed from de­vel­op­ing the dis­ease but still ca­pa­ble of spread­ing the in­fec­tion to oth­ers. As­traZeneca and Ox­ford sci­en­tists coun­tered that the vac­cine didn’t need to pro­duce high lev­els of an­ti­bod­ies if it pro­duced a T cell re­sponse, and that it wasn’t fair to com­pare mon­keys ex­posed to mas­sive dos­es of the virus to re­al world sce­nar­ios any­way.

Sarah Gilbert

“No one knows how strong the im­mune re­sponse needs to be to achieve pro­tec­tion in peo­ple of any age,” Sarah Gilbert, the prin­ci­pal Ox­ford sci­en­tist be­hind the vac­cine, told Bloomberg. “If we get a strong T-cell re­sponse, we don’t need such a high neu­tral­iz­ing an­ti­body titre to achieve pro­tec­tion.”

These ques­tions of just how pro­tec­tive vac­cines are, if they might in­oc­u­late some­one from dis­ease but still al­low them to spread the virus, and how long im­mu­ni­ty might last, will like­ly be de­bat­ed for months. But a much bet­ter test for the da­ta is com­ing. As­traZeneca has al­ready be­gun one Phase III tri­al in Brazil and will soon be­gin an­oth­er in the US. Mod­er­na will launch its Phase III on Ju­ly 27th. These stud­ies, con­duct­ed on tens of thou­sands of peo­ple, will ex­am­ine T cell re­sponse and an­ti­bod­ies but the more im­por­tant ques­tion will be sim­pler: Do peo­ple in­oc­u­lat­ed with the vac­cine be­come sick, or not?

For a look at all End­points News coro­n­avirus sto­ries, check out our spe­cial news chan­nel.

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

Biohaven CEO Vlad Coric (Photo Credit: Andrew Venditti)

Pssst: That big Bio­haven Alzheimer's study? It was a bust. Even the sub­group analy­sis ex­ecs tout­ed was a flop

You know it’s bad when a biopharma player plucks out a subgroup analysis for a positive take — even though it was way off the statistical mark for success, like everything else.

So it was for Biohaven $BHVN on MLK Monday, as the biotech reported on the holiday that their Phase II/III Alzheimer’s study for troriluzole flunked both co-primary endpoints as well as a key biomarker analysis.

The drug — a revised version of the ALS drug riluzole designed to regulate glutamate — did not “statistically differentiate” from placebo on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11 (ADAS-cog) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB).  The “hippocampal volume” assessment by MRI also failed to distinguish itself from placebo for all patients fitting the mild-to-moderate disease profile they had established for the study.

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Janet Woodcock and Joshua Sharfstein (AP, Images)

Poll: Should Joshua Sharf­stein or Janet Wood­cock lead the FDA from here?

It’s time for a new FDA commissioner to come on board, a rite of passage for Joe Biden’s administration that should help seal the new president’s rep on seeking out the experts to lead the government over the next 4 years.

As of now, the competition for the top job appears to have narrowed down to 2 people: The longtime CDER chief Janet Woodcock and Joshua Sharfstein, the former principal deputy at the FDA under Peggy Hamburg. Both were appointed by Barack Obama.

Dan Skovronsky, Eli Lilly CSO (Lilly via Facebook)

Eli Lil­ly tees up dis­cov­ery pact worth more than $1.6B with Merus for T cell-fo­cused bis­pe­cif­ic an­ti­bod­ies

Under science chief Dan Skovronsky, Eli Lilly has taken some big swings at next-gen therapies, including trying to find the next big thing in oncology. Now, after one early failure in the field, Lilly is going back to the bispecific antibody well with a new deal with a Dutch biotech.

Lilly will pay $40 million upfront with an additional $20 million equity stake in Merus NV to identify and develop three bispecific antibodies looking to engage the CD3 antigen on T cells and redirect immune cells, the Indianapolis pharma giant said Tuesday.

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Andrew Cuomo, AP

Covid-19 roundup: Con­va­les­cent plas­ma flops in UK tri­al; New York Gov. An­drew Cuo­mo seeks to pur­chase vac­cines di­rect­ly from Pfiz­er

The UK’s RECOVERY trial is no longer recruiting patients for the convalescent plasma arm after an independent data monitoring committee found no significant improvement in mortality — another nail in the coffin for President Donald Trump’s so-called “historic breakthrough” treatment.

The RECOVERY trial spans several potential Covid-19 treatments, including  Regeneron’s antibody cocktail, and the anti-inflammatories colchicine and tocilizumab. But convalescent plasma missed its primary endpoint in a preliminary analysis, and the DMC “saw no convincing evidence that further recruitment would provide conclusive proof of worthwhile mortality benefit either overall or in any pre-specified subgroup,” according to a report by the trial’s co-chairs, Peter Horby and Martin Landray.

Andrew Allen (Gritstone)

As coro­n­avirus vari­ants trig­ger new alarms, the NIH is putting an un­der-the-radar ‘next-gen’ vac­cine in­to PhI

Over the past year, the world has been transfixed by the development of new vaccines to fight SARS-CoV-2. In a frenzy of activity, the new mRNA approach has delivered pioneering emergency approvals in record time. And with some setbacks, the more traditional big players are coming along with added jabs as the most affluent nations in the world begin to vaccinate large portions of their populations.

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Janet Woodcock (AP Images)

Janet Wood­cock is in the run­ning for FDA com­mis­sion­er — what does that mean for the agen­cy's fu­ture?

Just a day after reports emerged that Janet Woodcock will serve as interim chief of the FDA, word has gotten out that she is also in the running for the permanent job.

The decision, as the initial wave of reactions suggest, could have dramatic implications for where the agency is headed in the next four years — if not beyond.

Woodcock, the longtime CDER director, is being vetted alongside former FDA principal deputy commissioner Joshua Sharfstein, Bloomberg reported. Already tapped as acting head of the agency, she’s set to take over from Stephen Hahn right after Biden’s inauguration next week.

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The IPO queue adds 5 more biotechs hop­ing to ring in 2021 by blitz­ing Nas­daq

Following a record year for IPOs — in terms of both proceeds and count — there’s already a long lineup of biotechs ready to jump onto Nasdaq in the new year. The companies are likely looking for much higher raises than they initially projected on their S-1s. Now it’s time to see if investors are still hungry for another round of biotech stocks.

Sana helped set the pace early on, as its founders look to divvy up a fortune from their IPO. And late last week 5 more biotechs crowded in, looking to pick up the pace where 2020 left off. Here they are:

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News brief­ing: Beam bags a $260M pri­vate place­ment; mi­Ra­gen re­brands to Virid­i­an Ther­a­peu­tics

Agios vet John Evans has demonstrated how to raise big money for a little biotech.

The Beam Therapeutics CEO — and ARCH partner — has pieced together a $260 million private placement from a group of backers that includes Perceptive Advisors, Farallon Capital, Casdin Capital, Redmile Group and Cormorant Asset Management. And there are 3 main goals they’ll pursue with it: clinical development, strategic partnerships and general corporate purposes.