Syn­thekine nabs megaround in bid to edge out Mer­ck, Sanofi in IL-2 sprint

Nine months af­ter launch­ing out of Stan­ford with $82 mil­lion and a port­fo­lio of en­gi­neered cy­tokines, Syn­thekine has land­ed a $107.5 mil­lion Se­ries B from Deer­field Man­age­ment and oth­ers to push their two lead can­cer pro­grams in­to the clin­ic.

Like a smat­ter­ing of ri­vals, Syn­thekine is try­ing to reimag­ine one of the most no­to­ri­ous can­cer drugs in his­to­ry: IL-2, a syn­thet­ic ver­sion of an im­mune mes­sen­ger mol­e­cule that proved too po­tent for most pa­tients to tol­er­ate, even though it could be high­ly ef­fec­tive at amp­ing the im­mune sys­tem to at­tack tu­mors. The in­dus­try-wide hope is that new ap­proach­es to pro­tein en­gi­neer­ing, along with some cre­ative think­ing, could al­low de­vel­op­ers to dis­till the tu­mor-shrink­ing pow­er, with­out all the tox­i­c­i­ties.

IL-2 is tox­ic in part be­cause it has a three-pronged re­cep­tor that binds to and ac­ti­vates all types of T cells; the goal is to build one that on­ly ac­ti­vates tu­mor-killing T cells. Most com­pa­nies, in­clud­ing Sanofi and Mer­ck, have tried to get at the prob­lem by build­ing ar­ti­fi­cial pro­teins that don’t have the prong, called al­pha, that ac­ti­vates so-called reg­u­la­to­ry T cells. That leaves on­ly the two prongs, called be­ta and gam­ma, that ac­ti­vate the killers.

Syn­thekine will use their new pot of gold to get an al­ter­na­tive path. They ar­gue that al­pha is abun­dant on the best T cells: T cells that are al­ready pro­grammed to at­tack the tu­mor, AKA anti­gen-spe­cif­ic killer T cells. So they’ve ac­quired an IL-2 that, with a mix­ture of spe­cial­ly mod­i­fied al­pha and be­ta prongs, bonds vir­tu­al­ly on­ly to those cells.

De­ban­jan Ray

CEO De­ban­jan Ray claims their mouse da­ta show it can shrink tu­mors bet­ter than the ri­val ap­proach — which, so far, has yield­ed rather mixed re­sults.

“We had a dif­fer­ent bi­o­log­i­cal the­sis,” he told End­points News. “In these ex­per­i­ments, our mol­e­cule has looked uni­ver­sal­ly bet­ter.”

Syn­thekine will look to file an IND for their IL-2 to­ward the end of this year. A few months lat­er, they al­so plan to file an IND on their sec­ond pro­gram, where they’ll look to use a dif­fer­ent cus­tom-built IL-2 as an on/off switch for CAR-T. Us­ing a form of the pro­tein that on­ly binds to a spe­cif­ic pock­et they’ve en­gi­neered on­to their CAR-T cells, they hope to use the IL-2 to help the cells pro­lif­er­ate when­ev­er need­ed.

Ide­al­ly, Ray said, that will al­low doc­tors to give low­er dos­es of cells ear­ly on and then mod­u­late the amount of IL-2 over the en­su­ing months and years to en­sure that a pa­tient’s re­sponse lasts as long as pos­si­ble.

The round, co-led by Janus Hen­der­son In­vest­ments, will al­so al­low the Cal­i­for­nia biotech to con­tin­ue their ear­ly-stage dis­cov­ery work on a hand­ful of fol­low-up mol­e­cules, both for can­cer and au­toim­mune dis­eases. They’ve al­ready li­censed three in April from the lab of their founder, Chris Gar­cia: IL-10, IL-12 and IL-22.

But Ray is par­tic­u­lar­ly ex­cit­ed about their name­sake, what they call the “syn­thekine plat­form.” The com­pa­ny, he said, is work­ing on a class of mol­e­cules that are de­signed en­tire­ly syn­thet­i­cal­ly, rather than by re­ly­ing on the nat­ur­al pro­tein. That could open up the po­ten­tial for new types of ther­a­pies, un­teth­ered by the struc­ture mil­lions of years of evo­lu­tion have ham­mered in.

“We think that could be tru­ly rev­o­lu­tion­ary to the field,” he said.

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).

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.”

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.

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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.

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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.

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Hal Barron, GSK R&D chief (Endpoints News)

Hal Bar­ron gam­bles $625M cash on high-wire TIG­IT act, throw­ing Glax­o­SmithK­line in­to heat­ed race and com­plet­ing next-gen I/O trin­i­ty

Count Hal Barron and GlaxoSmithKline in for the TIGIT fight.

The stakes are as high as the risks: While a growing pack of Big Pharma rivals is lending credence to the hypothesis that TIGIT will be the next big immune checkpoint and cancer drug target, the first clinical trials have shown response rates that can be described as modest at best. But Barron’s bet is on the whole “axis” that the receptor sits on, with an eye on testing its new anti-TIGIT antibody not just in combo with PD-1 but also in triplets.

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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.

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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.