Check­point in­hibitors have done won­ders for im­muno-on­col­o­gy, but the po­tent class of drugs doesn’t work across all can­cers. To rem­e­dy this, UK-based biotech up­start Grey Wolf Ther­a­peu­tics is work­ing on a fresh ap­proach that does not di­rect­ly tar­get the im­mune sys­tem, but in­stead al­ters tu­mor cells by il­lu­mi­nat­ing and prim­ing them for im­mune sys­tem an­ni­hi­la­tion — a strat­e­gy that could work in con­junc­tion with ex­ist­ing im­munother­a­pies.

An­dera Part­ners and Canaan have shown their faith in the con­cept by lead­ing an ap­prox­i­mate­ly $14 mil­lion se­ries A round for the com­pa­ny.

Pe­ter Joyce

Found­ed by for­mer Ver­tex ex­ec­u­tive Pe­ter Joyce and ex-chief of Spinifex Phar­ma­ceu­ti­cals Tom Mc­Carthy, Grey Wolf is de­vel­op­ing small mol­e­cule mod­u­la­tors of en­do­plas­mic retic­u­lum aminopep­ti­das­es (ER­APs) pro­teins, an ap­proach de­signed to shore up the quan­ti­ty and range of neoanti­gens pre­sent­ed on tu­mor cells.

“The en­zyme tar­gets we’re go­ing af­ter are ER­AP1 and ER­AP2 — they work in the anti­gen pre­sen­ta­tion path­way and es­sen­tial­ly by mod­u­lat­ing their ac­tiv­i­ty, we can mod­u­late what is pre­sent­ed on the sur­face of a can­cer cell, so we ac­tu­al­ly change the neoanti­gens and mod­u­late their vis­i­bil­i­ty,” Joyce told End­points News, adding that pre­clin­i­cal da­ta sug­gests that a monother­a­py ap­proach is fea­si­ble, as is a com­bi­na­tion with ex­ist­ing PD-1s.

Grey Wolf is work­ing with the Uni­ver­si­ty of Ox­ford, Uni­ver­si­ty of Southamp­ton, and has a strate­gic part­ner­ship with Syg­na­ture Dis­cov­ery, a Not­ting­ham-based provider of drug dis­cov­ery and pre­clin­i­cal ser­vices. Syg­na­ture and Mc­Carthy to­geth­er put in £420,000 in seed fund­ing for Grey Wolf, Joyce said.

Back in 2015, Mc­Carthy was in charge of Spinifex when it was sold to Swiss drug­mak­er No­var­tis $NVS in a $700 mil­lion deal af­ter the pub­li­ca­tion of pos­i­tive Phase II da­ta on its non-opi­oid painkiller. Not­ed VC Canaan was an in­vestor in Spinifex.

Canaan has made its first-ever in­vest­ment in UK biotech with its Grey Wolf in­vest­ment, thanks in part to Mc­Carthy’s re­la­tion­ship with the firm, and due to the sci­en­tif­ic po­ten­tial of the ER­AP ap­proach, Joyce said. “(The) fact that we’re do­ing some­thing very nov­el re­al­ly piqued their in­ter­est.”

Ac­cord­ing to Joyce, out­side of aca­d­e­m­ic in­sti­tu­tions, there aren’t any oth­er com­mer­cial en­ti­ties look­ing at mod­u­lat­ing ER­AP pro­teins for im­muno-on­col­o­gy to his knowl­edge and Grey Wolf is “aim­ing to be first-in-class.”

The com­pa­ny, which has a core team of 6, is cur­rent­ly in the drug dis­cov­ery phase, and this round of fund­ing will be used to take the com­pa­ny to pre-IND en­abling stud­ies in the next 2-3 years. “We ei­ther ex­it at that point — which we would be open to — or get a part­ner. Or we might do a Se­ries B and take it to Phase I/II. I think be­yond…the com­plex­i­ty of im­muno-on­col­o­gy clin­i­cal de­vel­op­ment re­al­ly then does need one of the big­ger part­ners,” Joyce said.

“I’m a fly fish­er­man by back­ground and Grey Wolf is a type of mayfly and it’s a bit of lucky fly for me…so I’m hop­ing it will be a sort of a good luck omen.”

89bio said its drug was better than placebo at lessening fibrosis without worsening nonalcoholic steatohepatitis, or NASH, in two of three dose groups.

The San Francisco biotech said it thinks the Phase IIb data pave the way for a potential Phase III, following in the footsteps of another biotech in its drug class, Akero Therapeutics. To fund a late-stage study, CEO Rohan Palekar told Endpoints News 89bio “would need to raise additional capital,” with the company having about $188 million at the end of last year.