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

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