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: Mer­ck pulls Keytru­da in SCLC af­ter ac­cel­er­at­ed nod. Is the FDA get­ting tough on drug­mak­ers that don't hit their marks?

In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders?

Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday.

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Paul Sekhri

The next big biotech su­per­star? Paul Sekhri has some thoughts on that

It occasionally occurs to Paul Sekhri that if they pull this off, his company will be on the front page of the New York Times and a lead story in just about every major news outlet on the planet. He tries not to dwell on it, though.

“I just want to be laser-focused on getting to that point,” Sekhri says, before acknowledging, “Yes, it absolutely crossed my mind.”

Sekhri, a longtime biopharma executive with tenures at Sanofi and Novartis, is now entering year three as CEO of eGenesis, the biotech that George Church protégé Luhan Yang founded to genetically alter pigs so that they can be used for organ transplants. He led them through one megaround and has just closed another, raising $125 million from 17 different investors to push the first-ever (humanized) pig to human transplants into the clinic.

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Bob Nelsen (Photo by Michael Kovac/Getty Images)

With stars aligned and cash in re­serve, Bob Nelsen's Re­silience plans a makeover at 2 new fa­cil­i­ty ad­di­tions to its drug man­u­fac­tur­ing up­start

Bob Nelsen’s new, state-of-the-art drug manufacturing initiative is taking shape.

Just 3 months after gathering $800 million of launch money, a dream team board and a plan to shake up a field where he found too many bottlenecks and inefficiencies for the era of Covid-19, Resilience has snapped up a pair of facilities now in line for a retooling.

The company has acquired a 310,000-square-foot plant in Boston from Sanofi along with a 136,000-square-foot plant in Ontario to add to a network which CEO Rahul Singhvi says is just getting started on building his company’s operations up. The Sanofi deal comes with a contract to continue manufacturing one of its drugs.

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Or­biMed, bio­phar­ma's biggest in­vestor, clos­es $3.5B in three new pri­vate funds

One of the world’s leading biopharma investors has pulled in its next rounds of cash, with the funds planned to go to dozens of companies around the world.

OrbiMed raised $3.5 billion across three private investment funds, it announced Monday, as it continues building on its long track record in healthcare and biopharma. All in all, the firm expects to invest in at least 60 companies across the US, Asia and Europe.

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Af­ter bail­ing on Covid-19 vac­cines, Mer­ck will team up with J&J to pro­duce its shot as part of un­usu­al Big Phar­ma pact

Merck took a big gamble when it opted to jump into the Covid-19 vaccine race late, and made an equally momentous decision to back out in late January. Now, looking to chip in on the effort, Merck reportedly agreed to team up with one of the companies that has already crossed the finish line.

President Joe Biden on Tuesday is expected to announce a partnership between drugmakers Merck and Johnson & Johnson to jointly produce J&J’s recombinant protein Covid-19 vaccine that received the FDA’s emergency use authorization Saturday, the Washington Post reported.

Ab­b­Vie tees up a biotech buy­out af­ter siz­ing up their Parkin­son's drug spun out of Ke­van Shokat's lab

AbbVie has teed up a small but intriguing biotech buyout after looking over the preclinical work it’s been doing in Parkinson’s disease.

The company is called Mitokinin, a Bay Area biotech spun out of the lab of UCSF’s Kevan Shokat, whose scientific explorations have formed the academic basis of a slew of startups in the biotech hub. One of Shokat’s PhD students in the lab, Nicholas Hertz, co-founded Mitokinin using their lab work on PINK1 suggesting that amping up its activity could play an important role in regulating the mitochondrial dysfunction contributing to Parkinson’s disease pathogenesis and progression.

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Fi­bro­Gen shares skid low­er as a sur­prise ad­comm rais­es risks on roxa OK

FibroGen will likely have to delay its US rollout for roxadustat once again.

In an unexpected move, the FDA is convening its Cardiovascular and Renal Drugs Advisory Committee to review the NDA in an advisory committee meeting. The date is yet to be confirmed.

Just a few weeks ago, SVB Leerink analyst Geoffrey Porges predicted that the roxa approval could come ahead of the PDUFA date on March 20 — effusive despite already being let down once by the FDA’s extension of its review back in December. AstraZeneca, which is partnered with FibroGen on the chronic kidney disease-related anemia drug, disclosed regulators had requested further clarifying analyses of clinical data.

In­tro­duc­ing End­pointsF­DA+, our new pre­mi­um week­ly reg­u­la­to­ry news re­port led by Zachary Bren­nan

CRLs. 483s. CBER, CDER and RWE. For biopharma professionals, these acronyms command attention because of the fundamental role FDA plays in drug development. Now Endpoints is doubling down on regulatory coverage, and launching a weekly report focusing on developments out of White Oak, with analysis and insight into what it all means.

Coverage will be led by our new senior editor, Zachary Brennan. He joins Endpoints from POLITICO, where he covered pharma. Prior to that he was the managing editor for Regulatory Focus, a news publication from the Regulatory Affairs Professionals Society.

UP­DAT­ED: Feds clear the road for J&J to start de­liv­er­ing mil­lions of dos­es of their Covid-19 vac­cine — but frets linger about run­ner-up sta­tus

All the pieces needed to trigger a third wave of Covid-19 vaccine supply to start washing over the US fell neatly into place over the weekend.

After providing for a brief mime of regulatory judiciousness, the FDA stamped their emergency approval on J&J’s Covid-19 vaccine Saturday, adding to the Biden administration’s plan aimed at ending the pandemic in the near term — at least in the US. The CDC came through on Sunday with its stamp of approval and J&J is reportedly expected to start delivering vaccine sometime in the next few days.

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