The race to de­vel­op Covid-19 drugs and vac­cines is on — here’s what’s hap­pen­ing in the UK

Weeks away from the re­sults of on­go­ing US and Chi­na tri­als test­ing its ex­per­i­men­tal an­tivi­ral remde­sivir, Gilead is go­ing to tri­al the failed Ebo­la drug in a small group of coro­n­avirus pa­tients in Eng­land and Scot­land. The Unit­ed King­dom is al­so home to a range of oth­er ther­a­peu­tic ef­forts, as the pan­dem­ic rages on across the globe.

On Tues­day, Southamp­ton, UK-based start­up Synair­gen kicked off a mid-stage place­bo-con­trolled study test­ing its ex­per­i­men­tal drug, SNG001 — an in­haled for­mu­la­tion of in­ter­fer­on-be­ta-1a — that has pre­vi­ous­ly shown to be safe and ef­fec­tive in im­prov­ing lung func­tion in asth­ma pa­tients with a res­pi­ra­to­ry vi­ral in­fec­tion in a pair of Phase II tri­als.

In­ter­fer­ons, a fam­i­ly of nat­u­ral­ly oc­cur­ring pro­teins se­cret­ed by the im­mune sys­tem, typ­i­cal­ly boost the body’s im­mune re­sponse to un­in­vit­ed guests such as virus­es, bac­te­ria and can­cer.

Richard Mars­den Synair­gen

“When we’ve col­lect­ed cells from pa­tients with COPD and asth­ma and old­er peo­ple…we find that their lung cells don’t re­spond very well to virus­es,” CEO Richard Mars­den said in an in­ter­view. “We have al­so along the way al­ways rec­og­nized that with an emerg­ing virus, the drug could be used.”

As Covid-19 start­ed to gath­er steam in Chi­na, Synair­gen tried to get things start­ed, but to no avail. Italy was the next plan. “We had some re­al­ly good in­ter­ac­tion there,” said Mars­den. “But they went from, you know, just busy to very busy to ex­treme­ly busy to un­able-to-com­mu­ni­cate busy.”

Even­tu­al­ly, they de­cid­ed their home ground — the UK, where they have an on­go­ing COPD tri­al — would be the best place to kick off a Covid-19 study. Ini­tial­ly, the pi­lot phase of the tri­al will have 100 pa­tients (50 will get a place­bo, and 50 will get SNG001). If all goes well, a piv­otal study will be con­duct­ed.

This ap­proach is one of many, as com­pa­nies race to de­sign and de­vel­op di­ag­nos­tics, drugs and vac­cines to stem the tide of the pan­dem­ic. “(W)e need high qual­i­ty clin­i­cal re­search to work out what is work­ing, what isn’t work­ing; we be­lieve place­bo-con­trolled tri­als are the way to do that,” Mars­den said.

Last week, the UK gov­ern­ment is­sued a state­ment con­firm­ing that the two decades-old malar­ia drugs: chloro­quine and hy­drox­y­chloro­quine, which have been tout­ed as po­ten­tial treat­ments for pa­tients in­fect­ed with the coro­n­avirus, have not been sanc­tioned for use against the virus in the UK.

Al­though clin­i­cal tri­als are on­go­ing, no con­clu­sions have been reached on the safe­ty and ef­fec­tive­ness of these med­i­cines, not­ed the Med­i­cines and Health­care prod­ucts Reg­u­la­to­ry Agency. In stark con­trast, in the Unit­ed States, the FDA on Sun­day is­sued emer­gency au­tho­riza­tion for the pair of drugs that Pres­i­dent Don­ald Trump has re­peat­ed­ly backed, on the ba­sis of anec­do­tal re­ports.

Mar­tin Lan­dray Ox­ford

In the UK, sci­en­tists at Ox­ford Uni­ver­si­ty are al­so look­ing at re­pur­pos­ing oth­er drugs for use against Covid-19. Last week, re­searchers an­nounced they would be test­ing lopinavir-ri­ton­avir, ap­proved used to treat HIV, and the steroid dex­am­etha­sone, in con­sent­ing adults that have test­ed pos­i­tive for Covid-19 in NHS hos­pi­tals. The project, in which pa­tients will ei­ther get one of the two drugs, or place­bo in ad­di­tion to stan­dard-of-care treat­ment, has won £10.5 mil­lion in gov­ern­ment fund­ing.

“The stream­lined de­sign of this clin­i­cal tri­al al­lows con­sent­ing pa­tients to be en­rolled in large num­bers eas­i­ly and with­out com­pro­mis­ing pa­tient safe­ty or adding sig­nif­i­cant­ly to the work­load of busy hos­pi­tals and their staff,” said the tri­al’s deputy chief in­ves­ti­ga­tor Mar­tin Lan­dray, who al­so serves as a pro­fes­sor of med­i­cine and epi­demi­ol­o­gy Uni­ver­si­ty of Ox­ford, in a state­ment.

Vac­cines in the works

Ox­ford re­searchers al­so have a vac­cine can­di­date in place.

On Jan­u­ary 10 — long be­fore the coro­n­avirus in­fec­tion was named Covid-19 or as­sumed pan­dem­ic pro­por­tions — a team of Ox­ford re­searchers led by Pro­fes­sors Sarah Gilbert, An­drew Pol­lard, Adri­an Hill and Dr. Sandy Dou­glas had be­gun their search for a vac­cine. On March 18, they honed in on a can­di­date: a chim­panzee ade­n­ovirus vac­cine vec­tor (ChA­dOx1).

Chim­panzee ade­n­ovi­ral vec­tors are well stud­ied, hav­ing been used in vac­cines tar­get­ing over 10 dif­fer­ent dis­eases. The Ox­ford vac­cine con­tains the ge­net­ic se­quence of the sur­face spike pro­tein found on SARS-CoV-2 — the virus be­hind Covid-19 — in­side the ChA­dOx1 con­struct. If the project is suc­cess­ful, vac­ci­na­tion with this prod­uct will pro­duce the sur­face spike pro­tein of the coro­n­avirus, prim­ing the im­mune sys­tem to at­tack the coro­n­avirus if it lat­er in­fects the body.

The re­searchers — who have pre­vi­ous­ly de­vel­oped a vac­cine for MERS that showed promise in ear­ly clin­i­cal tri­al — said last week they would start screen­ing peo­ple for a clin­i­cal tri­al, al­though the vac­cine is still weeks away from be­ing ready for hu­man test­ing. The en­roll­ment goal is to hit 510 vol­un­teers, and work is be­ing done to scale up man­u­fac­tur­ing in haste.

About a two-hour dri­ve away, re­searchers at the Uni­ver­si­ty of Cam­bridge al­so have a Covid-19 vac­cine in the works.

Pro­fes­sor Jonathan Heeney, head of the lab­o­ra­to­ry of vi­ral zoonotics and chief of spin­off com­pa­ny DIOSyn­Vax, has spear­head­ed re­search, aid­ed by com­put­er mod­el­ing of the virus’ struc­ture.

By putting the ge­net­ics of the virus un­der a mi­cro­scope, the com­pa­ny has iden­ti­fied a key part of the ge­net­ic code that the virus us­es to pro­duce the es­sen­tial part of its coat: the spikes, which is what the vac­cine is en­gi­neered to tar­get.

“A vac­cine strat­e­gy needs to be laser spe­cif­ic, tar­get­ing those do­mains of the virus’ struc­ture that are ab­solute­ly crit­i­cal for dock­ing with a cell, while avoid­ing the parts that could make things worse,” he said in a state­ment. “Our tech­nol­o­gy does just that.”

Pre­clin­i­cal tri­als are yet to be con­duct­ed, but he ex­pects the vac­cine can­di­date could be ready for hu­man tri­als by June. Fund­ing, how­ev­er, is re­quired.

“We need a ‘Big Phar­ma’ part­ner to help us scale up our ac­tiv­i­ties,” he said.

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

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,300+ biopharma pros reading Endpoints daily — and it's free.

FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,300+ biopharma pros reading Endpoints daily — and it's free.

Troy Wilson, Kura CEO

FDA lifts par­tial hold on Ku­ra's Phase Ib AML pro­gram as biotech re­dou­bles mit­i­ga­tion ef­forts

Kura Oncology is clear to resume studies for its early-stage leukemia program after the FDA lifted a clinical hold Thursday afternoon.

Regulators had placed the hold on a Phase Ib study of KO-539, an experimental oral treatment for some genetic subsets of acute myeloid leukemia last November after a patient died while taking the drug. Kura expects to begin enrolling patients again imminently, CEO Troy Wilson told Endpoints News.

A Sen­ate bill wants to even an 'un­lev­el play­ing field' for do­mes­tic, for­eign in­spec­tion drop-ins amid back­log

Amid geopolitical tensions between the US and China, two Republican senators are calling for a bill that would aim to strike a balance on domestic and foreign inspection requirements from the FDA.

Sens. Mike Braun (R-IN) and Joni Ernst (R-IA) have penned a bill called the Creating Efficiency in Foreign Inspections Act. It contains a bit of rhetoric, highlighting “communist China” not once, but twice in the release, but states that the goal is to even the playing field between foreign and American manufacturers.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,300+ biopharma pros reading Endpoints daily — and it's free.