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

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

FDA chief Stephen Hahn on Capitol Hill earlier this week (Getty Images)

As FDA’s work­load buck­les un­der the strain, Trump again ac­cus­es the agency of a po­lit­i­cal hit job

Peter Marks appeared before a virtual SVB Leerink audience yesterday and said that his staff at FDA’s CBER is on the verge of working around the clock. Manufacturing inspections, policy work and sponsor communications have all been pushed down the to-do list so that they can be responsive to Covid-related interactions. And the agency’s objective right now? “To save as many lives as we can,” Marks said, likening the mortality on the current outbreak as equivalent to “a nuclear bomb on a small city.”

David Berry (Flagship)

Flag­ship's next big tech­no­log­i­cal bet? The cloud

Earlier this month, Flagship announced their big bet on the software half the industry is talking about, launching the AI and machine learning startup. Now, they and a couple other investors are gambling $100 million on a software that much of the public generally thinks of as a cool, IT afterthought: cloud computing.

The idea, says founder and Flagship partner David Berry, is one of scale: The sheer magnitude of biological data that you can store on cloud technology is unprecedented. And that size, when leveraged properly, can allow you to ask questions and form insights that are similarly unprecedented.

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Patrick Enright, Longitude co-founder (Longitude)

As its biotechs hit the pan­dem­ic ex­it, Lon­gi­tude rais­es $585M for new neu­ro, can­cer, ag­ing and or­phan-fo­cused fund

The years have been kind to Longitude Capital. This year, too.

A 2006 spinout of Pequot Capital, its founders started their new firm just four years before the parent company would go under amid insider trading allegations. Their first life sciences fund raised $325 million amid the financial crisis, they added a second for $385 million and then in, 2016, a third for $525 million. In the last few months, the pandemic biotech IPO boom netted several high-value exits from those funds, as Checkmate, Vaxcyte, Inozyme and Poseida all went public.

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The win­dow is wide open as four more biotechs join the go-go IPO class of 2020

It’s another day of hauling cash in the biopharma world as four more IPOs priced Friday and a fifth filed its initial paperwork.

The biggest offering comes from PMV Pharma, an oncology biotech focusing on p53 mutations, which raised $211.8 million after pricing shares at $18 apiece. Prelude Therapeutics, developing PRMT5 inhibitors for rare cancers, was next with a $158 million raise, pricing shares at $19 each. Graybug Vision raised $90 million after pricing at $16 per share for its wet AMD candidates, and breast cancer biotech Greenwich Lifesciences brought up the rear with a small, $7 million raise after pricing shares at $5.75.

J&J of­fers PhI/IIa da­ta show­ing its sin­gle-dose vac­cine can stir up suf­fi­cient im­mune re­sponse

Days after J&J dosed the first participants of its Phase III ENSEMBLE trial, the pharma giant has detailed the early-stage data that gave them confidence in a single-dose regimen.

Testing two dose levels either as a single dose or in a two-dose schedule spaced by 56 days in, the scientists from Janssen, the J&J subsidiary developing its vaccine, reported that the low dose induced a similar immune response as the high dose. The interim Phase I/IIa results were posted in a preprint on medRxiv.

Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

Play-by-play of Gilead­'s $21B Im­munomedics buy­out de­tails a fren­zied push — and mints a new biotech bil­lion­aire

Immunomedics had not really been looking for a buyout when the year began. Excited by its BLA for Trodelvy, submitted to the FDA in late 2019, executive chairman Behzad Aghazadeh started off looking for potential licensing deals and zeroed in on four potential partners, including Gilead, following January’s JP Morgan Healthcare Conference in San Francisco. Such talks advanced throughout the year, with discussions advancing to the second round in mid-August.

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President Donald Trump reacts after signing an executive order following his remarks on his healthcare policies yesterday in Charlotte, North Carolina (Getty Images)

Op-ed: Will phar­ma re­al­ly pay for Trump’s lat­est law­less promise to 33 mil­lion Medicare ben­e­fi­cia­ries? Not like­ly

Sitting atop the executive branch, President Donald Trump is the ultimate authority at the FDA. He can fast track any vaccine to approval himself. If it came to that, of course.

What he can’t do is unilaterally order the legislative branch to loosen the Treasury’s coffers for $6.6 billion. Nor can he command pharmaceutical companies to pay for $200 vouchers sent to 33 million Medicare beneficiaries for prescription drugs before the election.

Pal­la­dio bags $20 mil­lion Se­ries B to top­ple a prob­lem­at­ic kid­ney dis­ease drug

Palladio Biosciences just took one step further in its quest to topple Otsuka’s Samsca with its own — it hopes safer — autosomal dominant polycystic kidney disease (ADPKD) drug.

The Pennsylvania-based biotech announced a $20 million Series B on Friday, which will fund a 10-person Phase III trial of its vasopressin V2 receptor agonist, lixivaptan. CEO Alex Martin expects to read out data in the first half of next year, then launch straight into a larger pivotal Phase III study with about 1,200 participants.