Cal­i­for­nia up­start Xyphos wants to tack­le CAR-T's big prob­lems

A San Fran­cis­co biotech that’s been de­vel­op­ing an­tibi­otics for the past decade has spun out a new on­col­o­gy start­up that bor­rows ideas from ex­ist­ing CAR-T and an­ti­body ther­a­pies — and com­bines them.

That’s ac­cord­ing to the start­up’s founder and CEO Jim Knighton. The new spin­out, called Xyphos, con­sid­ers its tech “sec­ond gen­er­a­tion CAR-T” as it ad­dress­es many of the field’s no­to­ri­ous chal­lenges (in an­i­mal mod­els, at least).

“We’ve tak­en all the work that Kite, Juno, and No­var­tis have done in CAR and come up with a new set of ideas that builds on what they start­ed to ad­dress some if not all of (CAR-T’s) short­com­ings,” Knighton said.

CAR-T’s chal­lenges

Jim Knighton

Al­though these ex­per­i­men­tal im­munother­a­pies show im­mense up­side, CAR-T ther­a­pies are not per­fect. For one, they can trig­ger tox­i­c­i­ty and po­ten­tial­ly fa­tal im­mune re­ac­tions in can­cer pa­tients.

“In a sense, the prod­uct is too ef­fec­tive and caus­es such a large re­ac­tion that pa­tients ex­pe­ri­ence tox­i­c­i­ty,” said Ezra Co­hen, an on­col­o­gist and can­cer re­searcher at UC San Diego. “Some have even died.”

Knighton said the tech be­ing de­vel­oped at Xyphos might hur­dle these chal­lenges by us­ing its new­ly en­gi­neered CAR in com­bi­na­tion with a mod­i­fied an­ti­body ther­a­py. In short, the com­pa­ny’s CAR has been en­gi­neered to be in­ert when it en­ters the pa­tient’s body. The CAR will not bind to (or at­tack) any­thing. It’s on­ly ac­ti­vat­ed when the pa­tient is dosed with Xyh­pos’ spe­cial­ly en­gi­neered an­ti­body, which the com­pa­ny calls a “Mi­ca­body.” Once the two are bound, the CAR is ac­ti­vat­ed and does its killer work.

If, how­ev­er, the can­cer pa­tient be­gins ex­pe­ri­enc­ing tox­i­c­i­ty, the doc­tor could stop the an­ti­body ther­a­py. The an­ti­body then cy­cles out of the pa­tient, and the CARs re­vert to harm­less, in­ac­tive T cells. Its sort of like switch­ing T cells on and off when need­ed.

Knighton said the idea works in mice, and now he needs mon­ey to move the re­search fur­ther along.

Co­hen, an in­ter­na­tion­al­ly rec­og­nized ex­pert on nov­el can­cer ther­a­pies and the di­rec­tor of Moore’s Can­cer Cen­ter in San Diego, said in­no­va­tion in CAR-T is cer­tain­ly due.

“The ap­proved prod­ucts in CAR-T are quite sim­ple in de­sign,” Co­hen said. “A lot of us are think­ing about sec­ond, third, and fourth gen­er­a­tion CAR-T. How do we mod­i­fy it? Make it stronger? Con­trol it? The next wave of CARs will be tremen­dous­ly bet­ter.”

The spin­out’s ori­gin

The tech be­hind Xyphos has been qui­et­ly stud­ied in the labs of an an­tibi­otics com­pa­ny called Avid­Bi­otics since about 2012. Why is an an­tibi­otics com­pa­ny dab­bling in can­cer drugs? Knight said there’s no shared tech­nol­o­gy be­tween Avid­Bi­otics and Xyphos. In­stead, the re­search was the re­sult of “cor­po­rate ADD.”

David Mar­tin

“We had an idea. Rather than go­ing out and start­ing a new com­pa­ny, we just hired a cou­ple of peo­ple in­ter­nal­ly to work on the prob­lem in­de­pen­dent­ly,” Knighton said.

Now the tech is de­vel­oped enough to split from Avid­Bi­otics. In fact, the com­pa­ny is split­ting in­to two new parts: one on­col­o­gy com­pa­ny (Xyphos) and a new­ly formed an­tibi­otics com­pa­ny called Py­lum Bio­sciences, which will car­ry on Avid­Bi­otics’ re­search pro­grams.

Knighton is serv­ing as CEO of Xyphos, while Avid­Bi­otics’ for­mer chief ex­ec­u­tive David Mar­tin will lead Py­lum as CEO. As of now, there are no ex­ec­u­tives with on­col­o­gy back­grounds work­ing at Xyphos.

The mon­ey

Knighton said both new en­ti­ties will need to raise $20 mil­lion to $30 mil­lion right away be­fore beef­ing up the C-suite with ex­pe­ri­enced folks.

Avid­Bi­otics has raised $38 mil­lion since its 2006 in­cep­tion, pri­mar­i­ly from cor­po­rate col­lab­o­ra­tions with DuPont (now DowDuPont) and Cu­bist (be­fore Mer­ck’s ac­qui­si­tion). That cap­i­tal al­so in­cludes NIH grants, and con­tri­bu­tions from friends, fam­i­ly and the founders.

Brent Saunders [Getty Photos]

UP­DAT­ED: Ab­b­Vie seals $63B deal to buy a trou­bled Al­ler­gan — spelling out $1B in R&D cuts

Brent Saunders has found his way out of the current fix he’s in at Allergan $AGN. He’s selling the company to AbbVie for $63 billion in the latest example of the hot M&A market in biopharma.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,600+ biopharma pros reading Endpoints daily — and it's free.

Af­ter rais­ing $158M, this up­start's founders have star back­ers and plans to break new ground in gene ther­a­py

Back in 2014, Stephanie Tagliatela opted to take an early exit out of her PhD program after working in Mark Bear’s lab at MIT, where she specialized in the synaptic connections between neuronal cells in the brain. She never finished that PhD, but she and fellow MIT student Kartik Ramamoorthi — who was on the founding team at Voyager — came away with some ideas for a gene therapy startup.

Today, fully 5 years later, she and Ramamoorthi are taking the wraps off of a $104 million mega-round designed to take the cumulative work of their preclinical formative stage for Encoded Therapeutics into human studies. They’ve now raised $158 million since starting out in Illumina’s incubator in the Bay Area, and they believe they are firmly on track to do something unique in gene therapy.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,600+ biopharma pros reading Endpoints daily — and it's free.

Novotech CEO Dr. John Moller

Novotech CRO Award­ed Frost & Sul­li­van Best Biotech CRO Asia-Pa­cif­ic 2019

Known in the in­dus­try as the Asia-Pa­cif­ic CRO, Novotech is now lead CRO ser­vices provider for the grow­ing num­ber of in­ter­na­tion­al biotechs se­lect­ing the re­gion for their stud­ies.

Re­flect­ing this Asia-Pa­cif­ic growth, Novotech staff num­bers are up 20% since De­cem­ber 2018 to 600 in-house clin­i­cal re­search peo­ple across a full range of ser­vices, across the re­gion.

Novotech’s ca­pa­bil­i­ties have been rec­og­nized by an­a­lysts like Frost & Sul­li­van, most re­cent­ly with the pres­ti­gious Asia-Pa­cif­ic CRO Biotech of the year award for best prac­tices in clin­i­cal re­search for biotechs for the fifth year. See oth­er awards here.

Sanofi/Re­gen­eron mus­cle ahead of a ri­val No­var­tis/Roche team, win first ap­proval in key rhi­nos­i­nusi­tis field

Re­gen­eron and their part­ners at Sanofi have beat the No­var­tis/Roche team to the punch on an­oth­er key in­di­ca­tion for their block­buster an­ti-in­flam­ma­to­ry drug Dupix­ent. The drug team scored an ac­cel­er­at­ed FDA ap­proval for chron­ic rhi­nos­i­nusi­tis with nasal polyps, mak­ing this the first such NDA for the field.

An­a­lysts have been watch­ing this race for awhile now, as Sanofi/Re­gen­eron won a snap pri­or­i­ty re­view for what is now their third dis­ease in­di­ca­tion for this treat­ment. And they’re not near­ly done, build­ing up hopes for a ma­jor fran­chise.

Image: Chris Varma. Frontier

UP­DAT­ED: Chris Var­ma un­veils MP­M's lat­est start­up — eye­ing 'un­drug­gable' can­cer tar­gets and pow­ered by ma­chine learn­ing, $67M

Two years af­ter MPM Cap­i­tal en­list­ed Chris Var­ma on its busy on­col­o­gy team, the for­mer en­tre­pre­neur-in-res­i­dence is un­veil­ing his first ven­ture project out of his new stomp­ing grounds in the Bay Area: Fron­tier Med­i­cines.

For Var­ma, who’s al­so co-found­ed Blue­print Med­i­cines and built com­pa­nies at Third Rock and Flag­ship, this marks an­oth­er op­por­tu­ni­ty to ap­ply some cut­ting-edge sci­ence to “sev­er­al of the most im­por­tant and dif­fi­cult tar­gets in can­cer” — tar­gets that oth­ers have tried to tack­le with more clas­si­cal meth­ods and failed. The launch round comes in at $67 mil­lion, which should go some way in scaf­fold­ing a pre­clin­i­cal pipeline and push one or more as­sets in­to the clin­ic three years from now, he tells me.

Richard Gonzalez testifying in front of Senate Finance Committee, February 2019 [AP Images]

Ab­b­Vie's $63B buy­out spot­lights the re­turn of ma­jor M&A deals — de­spite the back­lash

Big time M&A is back. But for how long?

Over the past 18 months we’ve now seen three major buyouts announced: Takeda/Shire; Bristol-Myers/Celgene and now AbbVie/Allergan. And with this latest deal it’s increasingly clear that the sharp fall from grace suffered by high-profile players which have seen their share prices blasted has created an opening for the growth players in big pharma to up their game — in sharp contrast to the popular bolt-on deals that have been driving the growth strategy at Novartis, Merck, Roche and others.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,600+ biopharma pros reading Endpoints daily — and it's free.

Two biotech uni­corns swell pro­posed IPOs, eye­ing a $600M-plus wind­fall

We’ve been wait­ing for the ar­rival of Bridge­Bio’s IPO to top off the wave of new biotech of­fer­ings sweep­ing through Nas­daq at the end of H1. And now we learn that it’s been sub­stan­tial­ly up­sized.

Ini­tial­ly pen­ciled in at a uni­corn-sized $225 mil­lion, the KKR-backed biotech has spiked that to the neigh­bor­hood of $300 mil­lion, look­ing to sell 20 mil­lion shares at $14 to $16 each. That’s an added 5 mil­lion shares, re­ports Re­nais­sance Cap­i­tal, which fig­ures the pro­posed mar­ket val­u­a­tion for Neil Ku­mar’s com­pa­ny at $1.8 bil­lion.

No­var­tis holds back the copy­cat brigade's at­tack on its top drug fran­chise — for now

A fed­er­al judge has put a gener­ic chal­lenge to No­var­tis’ block­buster mul­ti­ple scle­ro­sis drug Gilenya on hold while a patent fight plays out in court.

Judge Leonard P. Stark is­sued a tem­po­rary in­junc­tion ear­li­er this week, forc­ing My­lan, Dr. Red­dy’s Lab­o­ra­to­ries and Au­robindo Phar­ma to shelve their launch plans to al­low the patent fight to pro­ceed. He ruled that al­low­ing the gener­ics in­to the mar­ket now would per­ma­nent­ly slash the price for No­var­tis, even if it pre­vails. 

Top an­a­lyst finds a sil­ver lin­ing in Ab­b­Vie’s $63B Al­ler­gan buy­out — but there’s a catch

Af­ter get­ting beat up on all sides from mar­ket ob­servers who don’t much care for the lat­est mega-deal to ar­rive in bio­phar­ma, at least one promi­nent an­a­lyst now is start­ing to like what he sees in the num­bers for Ab­b­Vie/Al­ler­gan.

But it’s go­ing to take some en­cour­age­ment if Ab­b­Vie ex­ecs want it to last.

Ab­b­Vie’s mar­ket cap de­clined $20 bil­lion on Tues­day as the stock took a 17% hit dur­ing the day. And SVB Leerink’s Ge­of­frey Porges can see a dis­tinct out­line of an up­side af­ter re­view­ing the fun­da­men­tals of the deal.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,600+ biopharma pros reading Endpoints daily — and it's free.