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

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

David Baker working with a student on their protein design (Jason Mast)

Sci­en­tists are fi­nal­ly learn­ing how to de­sign pro­teins from scratch. Drug de­vel­op­ment may nev­er be the same

SEATTLE — It’s a cloudy Thursday afternoon in mid-July and David Baker is reclining into the futon in his corner office at the University of Washington, arms splayed out like a daytime talk show host as he coaches another one of his postdocs through the slings and arrows of scientific celebrity.

“Be jealous of your time,” he says, before plotting ways of sneaking her out of Zooms. “It’s this horrible cost to science that you’re tied up in some stupid meeting.”

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Pre­sent­ing a live End­points News event: Man­ag­ing a biotech in tur­bu­lent times

Biotech is one of the smartest, best educated industries on the planet. PhDs abound. We’ve had a long enough track record to see a new generation of savvy, experienced execs coming together to run startups.

And in these times, they are being tested as never before.

Biotech is going through quite a rough patch right now. For 2 years, practically anyone with a decent resume and some half-baked ideas on biotech could start a company and get it funded. The pandemic made it easy in many ways to pull off an IPO, with traditional road shows shut down in exchange for a series of quick Zoom meetings. Generalist investors flocked as the numbers raised soared into the stratosphere.

Patty Murray, D-WA (Graeme Sloan/Sipa USA)(Sipa via AP Images)

Sen­ate user fee reau­tho­riza­tion bill omits ac­cel­er­at­ed ap­proval re­forms, shows wide gaps with House ver­sion

The Senate health committee on Tuesday released its first version of the bill to reauthorize all the different FDA user fees. But unlike the House version, there are only a few controversial items in the Senate’s version, which does not address either accelerated approval reforms or clinical trial diversity (as the House did).

While it’s still relatively early in the process of finalizing this legislation (the ultimate statutory deadline is the end of September), the House and Senate, at least initially, appear to be starting off in different corners on what should be included.

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Warren Buffett, Berkshire Hathaway CEO

Berk­shire Hath­away pulls out of Ab­b­Vie, Bris­tol My­ers Squibb in­vest­ments

It looks like Warren Buffett is sticking to ice cream and railroads for the moment.

The billionaire CEO of Berkshire Hathaway backed out of two major holdings in the pharma industry, Forexlive first reported, including a $410 million investment in AbbVie and a $324.4 million stake in Bristol Myers Squibb.

The move comes after Berkshire abandoned its Teva shares just last quarter, Bloomberg reported.

Long-ex­pect­ed UK lay­offs im­mi­nent for No­var­tis fol­low­ing sale

Nearly a year ago, more than 200 workers at Novartis’ Grimsby, UK, facility were able to hang on to their jobs after the pharma closed a Switzerland site as a part of its workforce restructuring plan. Now, it looks like those employees’ time is up, as the site has been sold, Grimsby Telegraph reported today.

The manufacturing site has been sold to Humber Industrials, a subsidiary of International Process Plants. None of the current staff members will be working with the new owners, however.

FDA lob­bies Con­gress over rare dis­ease court rul­ing with wide im­pli­ca­tions

Usually reserved for making decisions on drug applications or enforcing what Congress stipulates, the FDA is now dipping its toe into the wild world of congressional politics as it attempts to fix a major court decision that could have a chilling effect on rare disease R&D.

The case in question from last October saw a US appeals court overturn a prior FDA court win, saying that the agency never should’ve approved a rare disease drug because a previously approved but more expensive drug with the same active ingredient has orphan drug exclusivity barring such an approval.

Peter Marks (Greg Nash/Pool via AP)

Even FDA's Pe­ter Marks is wor­ried about the com­mer­cial vi­a­bil­i­ty of gene and cell ther­a­pies

When bluebird bio’s gene therapy to treat beta thalassemia won European approval in 2019, the nearly $2 million per patient price tag for the potential cure seemed like a surmountable hurdle.

Fast forward two years later, and bluebird has withdrawn Zynteglo, the beta thal drug, along with the rest of its gene therapy portfolio from Europe, which the company said is generally unwilling to pay a fair price for the treatment.

Pri­cy in­halers re­main ex­pen­sive due to de­vice tweaks that keep com­peti­tors at bay, re­searchers find

New research published in Health Affairs today highlights the way in which the FDA’s inhaler regulations have rewarded incremental adjustments to older products, thereby enabling companies to skirt around cheaper competition.

A DC appeals court clerk and researchers from Harvard and the University of Calgary dug through all the patents and regulatory exclusivities granted to inhalers approved by the FDA between 1986 and 2020, finding that of the 62 inhalers approved, 53 (or 85%) were brand-name products, with a median of 16 years of protection from generic competition.