Eye­ing clin­i­cal proof-of-con­cept for HER3 drug, Am­gen-part­nered biotech scores $125M for pre­ci­sion an­ti­bod­ies

When it comes to re­draw­ing the bound­aries of what pro­teins are drug­gable, small mol­e­cules have soaked up the spot­light. Hordes of new en­trants — in­hibitors, al­losteric mod­u­la­tors, de­graders — promise to make a big dif­fer­ence by hit­ting dis­ease-caus­ing pro­teins at the right spot.

Over the last five years a biotech out of Sin­ga­pore has been try­ing to show that the same ap­proach can be ap­plied to an­ti­bod­ies. Now No­vo Hold­ings is lead­ing a $125 mil­lion Se­ries C de­signed to push them to­ward clin­i­cal proof-of-con­cept.

It all start­ed, Hum­ming­bird CEO Piers In­gram said, with a tar­get that’s puz­zled him since his PhD years: HER3.

Jerome Boyd-Kirkup

De­spite am­ple ev­i­dence that it should be a great drug tar­get, none of the an­ti­bod­ies pre­vi­ous re­searchers have gen­er­at­ed had the ex­pect­ed bi­o­log­i­cal ac­tiv­i­ty. When he and co-founder/CSO Jerome Boyd-Kirkup dug in­to it, they found that these HER3 in­hibit­ing an­ti­bod­ies all shared very sim­i­lar mech­a­nisms of ac­tion. And it wasn’t op­ti­mal — they of­ten al­ways stopped one route of ac­ti­va­tion, leav­ing a “huge gap­ing hole” for the pro­tein to be ac­tive.

Their hy­poth­e­sis was sim­ple: You prob­a­bly need to shut down the whole thing. Ex­e­cut­ing it was the big­ger chal­lenge, as the B cells that see the anti­gen first usu­al­ly are the ones that spawn the ma­jor­i­ty of an­ti­bod­ies, all tar­get­ing the iden­ti­cal, most im­muno­genic — a phe­nom­e­non known as im­mun­odom­i­nance. Of­ten, these epi­topes are not the spots that are most func­tion­al­ly use­ful as a drug.

Rather than feed­ing anti­gens to B cells, Hum­ming­bird takes a guid­ed ap­proach, first lever­ag­ing com­pu­ta­tion­al mod­el­ing to pre­dict the re­gions of in­ter­est on the pro­tein then en­gi­neer­ing an­ti­bod­ies that are dri­ven to bind to those spe­cif­ic epi­topes.

Hum­ming­bird has gen­er­at­ed four in-house an­ti­bod­ies on this plat­form, with a lead can­di­date tar­get­ing HER3 and oth­ers hit­ting VISTA, BC­MA-TACI and an undis­closed pro­tein as­so­ci­at­ed with lu­pus.

Am­gen has al­so signed on for a dis­cov­ery pact, re­serv­ing $100 mil­lion each for up to 12 projects.

Piers In­gram

“If you are lucky and na­ture gives you good an­ti­bod­ies the first time around, then you don’t have to wor­ry about any of these cool tech­nolo­gies,” In­gram said. But if you’re not, “it’s re­al­ly a huge op­por­tu­ni­ty to take ad­van­tage of all of the struc­tur­al and func­tion­al in­sights that we have around pro­tein tar­gets these days and then use the pow­er of an­ti­bod­ies on these as well as small mol­e­cules.”

The com­pa­ny now has 65 staffers, with the re­search team based in Sin­ga­pore and a de­vel­op­ment group in the US.

The Se­ries C comes two years af­ter the last round, which In­gram said un­locked the team’s cre­ative po­ten­tial around the tech­nol­o­gy. In ad­di­tion to No­vo, the Se­ries C syn­di­cate fea­tures Fra­zier Health­care Part­ners, Oc­ta­gon Cap­i­tal, ED­BI, AM­GEN Ven­tures, DROIA Ven­tures, Morn­ing­side Ven­tures, Pure­os Bioven­tures, Po­laris Part­ners, Affin­i­ty As­set Ad­vi­sors, Al­ly Bridge Group and Al­tri­um Cap­i­tal Man­age­ment. Ex­ist­ing in­vestors in­clud­ing SK, Her­i­tas Cap­i­tal, and Mi­rae As­set Ven­ture Cap­i­tal al­so joined the round.

In­side Track: Be­hind the Scenes of a Ma­jor Biotech SPAC

Dr. David Hung and Michelle Doig are no strangers to the SPAC phenomenon. As Founder and CEO of Nuvation Bio, a biotech company tackling some of the greatest unmet needs in oncology, Dr. Hung recently took the company public in one of this year’s biggest SPAC related deals. And as Partner at Omega Funds, Doig not only led and syndicated Nuvation Bio’s Series A, but is now also President of the newly formed, Omega-sponsored, Omega Alpha SPAC (Nasdaq: OMEG; oversubscribed $138m IPO priced January 6, 2021).

Barry Greene, Sage CEO

UP­DAT­ED: Sage's sec­ond chance at de­pres­sion hits the PhI­II pri­ma­ry, but ques­tions re­main over dura­bil­i­ty, side ef­fects

Looking to make a comeback after a big Phase III flop, Sage Therapeutics revealed data they believe could change the entire depression treatment landscape, given the vast array of failures in the field. But some results are spooking investors, sending Sage $SAGE shares down early Tuesday.

First, the primary: Sage and Biogen reported Phase III data for once-daily zuranolone Tuesday morning, saying the experimental drug hit its primary endpoint by spurring a statistically significant change from baseline in the 17-item Hamilton Rating Scale for Depression total score. After 15 days, patients in the drug arm saw an average change of -14.1 points, compared to -12.3 on placebo.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,500+ biopharma pros reading Endpoints daily — and it's free.

CEO Harith Rajagopalan (Fractyl)

Af­ter a decade in the type 2 di­a­betes game, Fractyl Lab­o­ra­to­ries recharges with a fresh $100M and a new name

Harith Rajagopalan compared the way type 2 diabetes is managed to sticking your fingers in a dam that’s leaking from a number of places.

You can take drugs to lower your blood sugar, cholesterol, or blood pressure, but you’re not addressing what he says is the core issue — the metabolic abnormality that causes the disease.

“We’re so busy plugging the holes in the dam, we don’t have time to see that the whole infrastructure is at risk,” he said. “That infrastructure is a full-body systemic metabolic abnormality called metabolic syndrome, that we’re ignoring while we’re so busy trying to treat all of the individual symptoms of the condition.”

Michel Sade­lain puts his name and new cell en­gi­neer­ing tech be­hind 'ag­nos­tic' CAR-T start­up chas­ing epi­ge­net­ic anti­gens

It felt natural for Alain Maiore and Sebastian Amigorena to bring in Michel Sadelain as a co-founder of Mnemo Therapeutics. A CAR-T pioneer, Sadelain had been involved as an advisor since the early days — enthusiastic about Amigorena’s work in a genetic knockout that could enhance T cell memory and a new class of potential targets he’s discovered — and could introduce some well-known technologies to the toolbox. So they got the initial cash from Sofinnova Partners to plant roots in Paris and New York in early 2019; within a few months, they began to see more clearly just what the antigen discovery platform might unlock.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,500+ biopharma pros reading Endpoints daily — and it's free.

Bio­gen sig­nals a big PhI­II fail­ure as the lead gene ther­a­py in their $800M Night­star buy­out goes down in flames

That $800 million buyout of Nightstar has turned into a bust for Biogen as the lead therapy in the deal failed a pivotal study, signaling a severe setback for the biotech’s ambitions in gene therapies.

The big biotech put out the word after the market closed on Monday that the gene therapy they picked up in the deal for a degenerative blindness called choroideremia failed the Phase III study, just a month after their #2 drug in the deal also flopped in a mid-stage study.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,500+ biopharma pros reading Endpoints daily — and it's free.

As Covid-19 shifts the world's at­ten­tion to biotech, Noubar Afeyan's Flag­ship builds $3.4B fund to fu­el new in­ven­tions. Here's the plan

A little more than a year ago, Flagship Pioneering rolled out a monster fund with $1.1 billion in it to bankroll the platform companies they were creating inside their own labs. But it turns out, that was just the prelude to a much, much larger raise, as both current investors — who’ve been reaping the rewards of some booming biotech stocks — join in with new investors betting on more in the years to come.

Endpoints Premium

Premium subscription required

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

An­oth­er busy week for IPOs be­gins with an off-the shelf cell ther­a­py play­er sniff­ing around uni­corn sta­tus

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

A flurry of biotechs are expected to hit Nasdaq this week, with two companies, Ambrx Biopharma and Century Therapeutics, setting the terms for their public debuts, with expected raises at $126 million and $200 million, respectively. Alzamend Neuro is also joining in with a $12.5 million raise and two preclinical Alzheimer’s treatments in tow.

Alexander Vos, VectorY CEO

Start­ing fresh in man­u­fac­tur­ing, For­bion start­up re­fu­els to steer next-gen gene ther­a­py ap­proach for ALS, Alzheimer's in­to clin­ic

Forbion laid out its case for a next-generation gene therapy approach when it took the wraps off VectorY Therapeutics and its vectorized antibody tech in February. Now, the Dutch VC has tapped an experienced hand at cell and gene therapy manufacturing to steer the ship — and pulled a marquee syndicate for a €31 million ($37.6 million) seed round.

Alexander Vos, the new CEO, is a venture partner at BioGeneration Ventures and jumps immediately from VarmX, a BGV portfolio company developing an anticoagulant. But before that, he had led Dutch CDMO PharmaCell for eight years until it was bought out by Lonza.

Lynn Fitch, Mississippi Attorney General (Rogelio V. Solis/AP Images)

Mis­sis­sip­pi sues Eli Lil­ly, Sanofi and No­vo over in­sulin prices as in­ter­change­able biosim­i­lars may ar­rive soon

Mississippi Attorney General Lynn Fitch last week sued the top three insulin manufacturers, which collectively cover almost the entire US insulin market, alleging that they’ve colluded to raise their prices in lockstep, and in some cases by more than 1,000% for drugs that are decades old.

“Because of Manufacturer Defendants’ collusive price increases, nearly a century after the discovery of insulin, diabetes medications have become unaffordable for many diabetics,” the lawsuit says.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,500+ biopharma pros reading Endpoints daily — and it's free.