IL-2 with­out the tox­ic side ef­fects? Or­bimed backs the idea in Syn­thorx' $63M round

A start­up in San Diego that’s bold­ly re-writ­ing the code for life by ex­pand­ing the ge­net­ic “al­pha­bet” just got a big in­fu­sion of cash from Or­bimed. The com­pa­ny, called Syn­thorx, raised $63 mil­lion on the promise of po­ten­tial ther­a­pies built on break­throughs in syn­thet­ic bi­ol­o­gy.

Floyd Romes­berg

Syn­thorx is build­ing its tech on work pi­o­neered by Floyd Romes­berg, a pro­fes­sor at The Scripps Re­search In­sti­tute in San Diego, who found a way to ex­tend the ge­net­ic al­pha­bet. In ad­di­tion to the nat­ur­al DNA base pairs A-T and G-C, Romes­berg de­vel­oped a third, syn­thet­ic base pair coined X-Y. The ex­tra pair cre­ates a huge op­por­tu­ni­ty to tweak pro­teins, as they can be built with up to 172 amino acids in­stead of the measly 20 avail­able with nat­ur­al base pairs.

When I first en­coun­tered Syn­thorx back in 2014, its then-CEO Court Turn­er put it this way:

“If you have a ques­tion and you can on­ly an­swer it with 20 words, how good would your an­swer be?” Now imag­ine hav­ing 172 words.

Even though Syn­thorx is a tiny com­pa­ny still ear­ly in its field, this is not the first time its caught our at­ten­tion. The com­pa­ny, in­cu­bat­ed in its ear­ly days at Aval­on Ven­tures’ start­up cam­pus COI Phar­ma­ceu­ti­cals, at­tract­ed A-list tal­ent late last year when Lau­ra Shawver came on board as CEO. Shawver is best known for lead­ing Cleave Bio­sciences through two siz­able rounds of fund­ing. She left Cleave when it was well-cap­i­tal­ized and in the midst of ad­vanc­ing an ex­cit­ing pipeline to in­stead lead Syn­thorx.

Lau­ra Shawver

“It’s not very of­ten that one gets to par­tic­i­pate in some­thing that is po­ten­tial­ly game-chang­ing for ther­a­peu­tics and like­ly will — this plat­form tech­nol­o­gy will be uti­lized for years to come,” she told End­points News at the time.

With the com­pa­ny’s ge­net­ic lex­i­con, Syn­thorx is cre­at­ing a pipeline of par­tial­ly syn­thet­ic bi­o­log­ics, in­clud­ing its lead pro­gram in in­ter­leukin-2 (IL-2) for can­cer (which the com­pa­ny is call­ing Syn­thorin IL-2). Shawver tells me the ap­proved IL-2 drug is known to work in­cred­i­bly well at boost­ing an­ti-tu­mor ac­tiv­i­ty, but it comes with side ef­fects so se­vere that the treat­ments are hard­ly used any­more.

“Tra­di­tion­al­ly, you have to give IL-2 at very high dos­es, which stim­u­lates the im­mune sys­tem and you get pro­found an­ti-tu­mor ac­tiv­i­ty,” Shawver said. “But comes with very bad side ef­fects. We’re try­ing to pre­serve the ef­fi­ca­cious part, but not have the side ef­fects.”

Lots of com­pa­nies (in­clud­ing the ever-pop­u­lar Nek­tar) are try­ing to make IL-2 ther­a­pies, and of­ten they do this by PE­Gy­lat­ing their drug, there­by im­prov­ing the half-life. But the treat­ment still has side ef­fects be­cause IL-2 can both sup­press and ac­ti­vate the im­mune sys­tem.  With Syn­throx’ ex­pand­ed ge­net­ic al­pha­bet, the com­pa­ny can take a dif­fer­ent ap­proach, tweak­ing the make­up of the pro­tein it­self by care­ful­ly plac­ing syn­thet­ic amino acids and the PEG mol­e­cule to boost the mol­e­cule’s ef­fi­ca­cy and lim­it un­want­ed (and off-tar­get) side ef­fects.

Pe­ter Thomp­son

Syn­thorx has achieved this al­ready in pre­clin­i­cal stud­ies, and now it’s tak­ing it in­to the clin­ic in the first half of 2019. The re­cent Se­ries C round, led by Or­bimed and in­clud­ing new in­vestors Medicxi and Os­age Uni­ver­si­ty Part­ners (along with ex­ist­ing in­vestors), will fund the progress of the IL-2 pro­gram.

“We are im­pressed with the da­ta for Syn­thorin IL-2 and how the Syn­thorx tech­nol­o­gy plat­form can specif­i­cal­ly iden­ti­fy and se­lect pro­tein mod­i­fi­ca­tions that re­sult in the de­sired ther­a­peu­tic ef­fect and phar­ma­co­ki­net­ics,” said Or­biMed’s Pe­ter Thomp­son, who’s join­ing the Syn­thorx board. “It is easy to see how this plat­form could be ap­plied to a va­ri­ety of pro­tein ther­a­peu­tics.”

Shawver says the IL-2 drug will pri­mar­i­ly be used as a com­bo ther­a­py used in tan­dem with im­muno-on­col­o­gy agents. But op­por­tu­ni­ties ex­tend way be­yond on­col­o­gy. The com­pa­ny has plans to ap­ply the tech to the au­toim­mune space, per­haps tack­ling dis­eases like Crohn’s and rheuma­toid arthri­tis.

Im­age: Re­searchers at work in Syn­thorx’ lab. SYN­THORX

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Big week for Alzheimer’s da­ta; As­traZeneca buys cell ther­a­py start­up; Dig­i­tal ther­a­peu­tics hits a pay­er wall; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

You may start to notice more stories exclusively available to Premium subscribers. This week alone, paid subscribers can read our in-depth reporting on Alzheimer’s data, digital therapeutics and Allogene’s cell therapy for solid tumors, as well as scoops on Twitter ads and Catalent. With your support, we can keep growing our team and spend more time on quality work. We have both individual and company plans available — check them out to unlock the full Endpoints experience.

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Am­gen, years be­hind ri­vals, says PhI obe­si­ty drug shows dura­bil­i­ty signs

While NBC ran “The Biggest Loser” for 17 seasons, deemed toxic by critics for the reality show’s punishing exercise and diet upheavals, researchers in pharmaceutical labs have been attempting to create prescription drugs that induce weight loss — and one pharma betting it can require less frequent dosing is out with a new crop of data.

Amgen was relatively late to the game compared to its approved competitor Novo Nordisk and green light-approaching rival Eli Lilly. But early data suggested Amgen’s AMG 133 led to a 14.5% weight reduction in the first few months of dosing, buoying shares earlier this fall, and now the California pharma is out with its first batch of durability data showing that figure fell slightly to 11.2% about 150 days after the last dose. Amgen presented at the 20th World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease on Saturday afternoon.

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Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls



Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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Chris Kim, Liminatus Pharma CEO

A fledg­ling biotech goes SPAC route to bankroll can­cer vac­cine, CAR-T and CD47

A relatively unknown clinical-stage biotech — backed by a Korean lighting company and focused on a cancer vaccine out of a Thomas Jefferson University lab — is headed to Nasdaq via the blank check route.

Liminatus Pharma will get about $316 million in proceeds from the SPAC combination to fund its ongoing Phase IIa study of a cancer vaccine, bring a CAR-T therapy into the clinic and prep a CD47 immune checkpoint inhibitor for human trials, the company said this week.

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Bay­er starts work on $43M+ ex­pan­sion of OTC man­u­fac­tur­ing site in Penn­syl­va­nia

German pharma giant Bayer will be looking to make a significant investment into one of its US plants that produces over-the-counter drugs.

Bayer announced that it will spend $43.6 million to expand its facility in Myerstown, PA, a small town east of Harrisburg. Bayer plans to increase the site by 70,000 square feet and will have room for the installation of eight packaging lines and an area to install rooftop solar panels. The project is expected to be completed by 2025 and will add around 50 to 75 jobs.

US month­ly costs for biosim­i­lars 'sub­stan­tial­ly high­er' than Ger­many or Switzer­land, JA­MA re­search finds

As the global biologics market is expected to hit nearly the half-trillion-dollar mark this year, new JAMA research points to the importance of timely biosimilar entry, particularly as fewer biosimilars are entering the US than in Europe, and as monthly treatment costs for biosimilars were “substantially higher” in the US compared with Germany and Switzerland.

Among the three countries, biosimilar market share at launch was highest in Germany, but increased at the fastest rate in the US, the authors from the University of Zurich’s Institute of Law wrote in JAMA Network Open today.

Kirk Myers is shown in a still image from a new film series showcasing the efforts of HIV advocates funded by Gilead.

Gilead spot­lights HIV projects and the com­mu­ni­ty lead­ers dri­ving them in new mi­ni-doc­u­men­tary films

Gilead is going behind the scenes of some of the HIV initiatives it funds through grants in a new film series narrated by the people helming the projects.

The first four films and leaders come from across the US — Arianna Lint in Florida and Puerto Rico, Cleve Jones in San Francisco, June Gipson in Mississippi and Kirk Myers in Texas. Their HIV-focused efforts range from addressing unmet needs of the transgender community to delivering social services and high-quality health care in underserved communities.

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