Rene Russo (Credit: Alicia Petitti Photography)

Xilio Ther­a­peu­tics eyes the fast track to the clin­ic with $95M in in­vestor cash to test re­designed IL-2, CT­LA-4 meds

About three years af­ter join­ing the search for IL-2  and CT­LA-4 ther­a­pies with­out all those nasty side ef­fects, Xilio Ther­a­peu­tics has teed up $95 mil­lion to dri­ve its two lead can­di­dates in­to the clin­ic.

The Se­ries C round was led by Rock Springs Cap­i­tal, and should al­low the small Waltham, Mass­a­chu­setts-based biotech to file INDs for XTX101, its an­ti-CT­LA-4 an­ti­body, in Q2 and XTX202, its IL-2 ag­o­nist, in Q3.

Tim Clack­son

Xilio got its start in 2018 un­der the name Akre­via with $30 mil­lion in launch mon­ey from At­las and F-Prime. The 13-per­son shop was head­ed by sci­en­tist Tim Clack­son, whose last job was run­ning R&D at Ari­ad un­til Take­da bought it out. Clack­son is now pres­i­dent and CTO.

The big idea — based on tech­nol­o­gy in-li­censed from Thomas Jef­fer­son Uni­ver­si­ty and City of Hope — was to take a set of an­ti­bod­ies, cy­tokines and chemokines that are ei­ther too dan­ger­ous or plagued with tox­i­c­i­ty is­sues and re­design them.

Two years lat­er, with CEO Rene Rus­so at the helm, the com­pa­ny bagged a $100.5 mil­lion Se­ries B and re­brand­ed to Xilio. The name was in­spired by ex ni­hi­lo, a Latin term for cre­ation or big bang.

“We view how our mol­e­cules work as com­plete­ly off or dark when they’re cir­cu­lat­ing in the pe­riph­ery,” Rus­so told End­points News at the time, “and this cre­ation or big bang as ef­fi­ca­cy in the tu­mor specif­i­cal­ly.”

Xilio’s plat­form in­volves shield­ing the bind­ing ac­tiv­i­ty of mol­e­cules un­til they meet the pro­teas­es in the tu­mor. Then the block­ing mod­ules are re­moved, re­leas­ing the ther­a­py just where it’s need­ed.

The biotech joins sev­er­al oth­ers work­ing on a new-and-im­proved IL-2, in­clud­ing Alk­er­mes, which high­light­ed its first glimpse of ef­fi­ca­cy at vir­tu­al ES­MO 2020. Nek­tar, whose pro­gram with Bris­tol My­ers Squibb’s Op­di­vo hit a snag back in 2018, an­nounced ear­li­er this month that it’s en­ter­ing be­m­pe­galdesleukin in a Phase II/III tri­al with Keytru­da. Sanofi struck a deal with Mer­ck in Oc­to­ber to pair Keytru­da with a next-gen im­muno-on­col­o­gy can­di­date snagged in the Syn­thorx buy­out. And back in Ju­ly, Bright Peak Ther­a­peu­tics launched out of Ver­sant’s Ridge­line Ther­a­peu­tics Dis­cov­ery En­gine with its own mod­i­fied IL-2 mol­e­cule.

“In our view, agents like IL-2 and CT­LA-4 have tremen­dous ther­a­peu­tic po­ten­tial, but have been re­al­ly lim­it­ed by their tox­i­c­i­ty,” Rus­so said. “And our ap­proach re­al­ly aims to take ad­van­tage of what’s dif­fer­ent in­side the tu­mor mi­croen­vi­ron­ment, name­ly high ac­tiv­i­ty of MMPs, or ma­trix  met­al­lo­pro­teinas­es, and then uti­lize that to re­al­ly turn on the ac­tiv­i­ty and con­cen­trate it on­ly in the tu­mors.”

The team, which has since grown to 45 staffers, is al­so work­ing on IL-12 and IL-15 pro­grams. How­ev­er, it’s too soon to tell when those might be ready for IND sub­mis­sions.

When asked if an IPO is on the hori­zon, Rus­so said: “We will be think­ing care­ful­ly about that and what the right tim­ing will be for us to max­i­mize the de­vel­op­ment of these pro­grams and to fur­ther ad­vance the pipeline.”

The End­points 20 un­der 40, biotech's new nor­mal, Stéphane Bancel's one re­gret, 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.

What a week! We were proud to present a slate of special reports that showcase the breadth and depth Endpoints is striving to deliver, and it’s truly a team effort. None of this can happen without our readers — so thank you for your support.

David Meek (Photographer: Marlene Awaad/Bloomberg via Getty Images)

Scoop: Fer­ring, Black­stone’s $570M gene ther­a­py ven­ture has im­plod­ed af­ter CMC is­sues stymied a once high-pro­file quest

Back in late 2019, FerGene looked golden. It had a gene therapy for bladder cancer — spun out of Ferring — at the FDA, with a priority review and breakthrough status indicating that great things awaited on the near horizon.

Ferring backed up the venture with $170 million, with Nick Galakatos’ Blackstone Life Sciences chipping in another $400 million with great fanfare to get the company running. David Meek jumped from the CEO job at Ipsen to run it all, and a little over a year ago much of the executive team was assembled to bring it all home.

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Stéphane Bancel at the Endpoints #JPM20 breakfast panel in San Francisco, January 2020 (Photo: Jeff Rumans, Endpoints News)

The CHIC in­ter­view: Stéphane Ban­cel on Mod­er­na's overnight trans­for­ma­tion, the new time­line on vac­cine de­vel­op­ment and his one re­gret in 2020

The China Healthcare Investment Conference — better known as CHIC — took place last week in Shanghai at the Ritz-Carlton Pudong. Endpoints partnered with CHIC this year in an effort to highlight the global nature of drug development, and John Carroll conducted two virtual “fireside chats” that was broadcast to attendees. We’ll be sharing both with the Endpoints Premium audience, and first up is a one-on-one interview with Moderna’s Stéphane Bancel.

John Carroll has been covering Moderna and Bancel since the very beginning. He started their conversation by noting it was the first time he’s taken a drug from a company he’s covered from its inception. They go on to discuss how Moderna is being transformed by cash-flow earlier than expected, Bancel’s one big regret in 2020, and much more.

Their conversation is below, and we hope you enjoy.

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Paul Hudson, Sanofi CEO (Eric Piermont/AFP viaGetty Images)

Sanofi CEO Paul Hud­son dives deep­er in­to mR­NA, buy­ing out an un­der-the-radar Fred Hutch spin­out

Sanofi CEO Paul Hudson may not be fully on board with the mRNA revolution, but he evidently still believes in the technology’s potential.

On Friday afternoon, Sanofi announced that they bought out the little-known mRNA biotech Tidal Therapeutics, hoping to leverage their technology to treat cancer and immunological disorders. Spun out of the Fred Hutch institute in 2019 and seeded at Cambridge’s LabCentral, the young company will now receive $160 million in cash and $310 million in potential milestones.

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Joe Biden (Credit: Doug Mills/The New York Times/Bloomberg via Getty Images)

Biden’s bud­get wish list: Re­store the CDC, build a new NIH re­search cen­ter, pump in bil­lions to end the opi­oid and HIV epi­demics

President Joe Biden’s first budget request (Congress is the ultimate decider on budgets) for FY 2022 includes a massive influx of funds to the CDC, plans to launch a new $6.5 billion research center within the NIH, as well as almost $11 billion to end the opioid epidemic and another $670 million to aggressively reduce new HIV cases.

But details on what exactly this new $6.5 billion, DARPA-like, NIH-based center, to be known as Advanced Research Projects Agency for Health (ARPA-H), will research remain to be seen. Biden’s budget request only said the center will initially focus on a wide range of diseases that other NIH centers typically work on.

Jeff Leiden (L) and Reshma Kewalramani (Vertex)

The num­bers are in, and new Ver­tex CEO Resh­ma Ke­wal­ra­mani took home half of what pre­de­ces­sor Jeff Lei­den did in his last year on the job

Despite an up year for Vertex, which celebrated a nearly 50% increase in product revenue, the company’s new CEO Reshma Kewalramani made just half of what former chief executive Jeff Leiden did in his last full year on the job.

Kewalramani’s compensation package in her first year as CEO amounted to $9.11 million — significantly smaller than Leiden’s $16.47 million total for 2020, and about half the size of his $18.79 million package in 2019.

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Emer Cooke, Shutterstock

EMA in­ves­ti­gat­ing 4 'se­ri­ous cas­es' of blood clots fol­low­ing J&J vac­ci­na­tions

The European Medicines Agency’s safety committee said Friday that it has initiated a review of 4 “serious cases of unusual blood clots with low blood platelets,” including one death, reported after people received the J&J vaccine in the US.

The EMA said the cases point to a “safety signal” but it’s unclear if there is a causal association between the J&J vaccine and these conditions. One of the cases occurred in a clinical trial. In its emergency use authorization in the US, the FDA also previously noted deep vein thrombosis cases in six recipients of the vaccine, including 5 within the first 28 days of the vaccine’s administration.

The End­points 100 sur­vey: CEOs changed the way biotechs op­er­ate dur­ing the pan­dem­ic. Things will nev­er be the same again

With the US at the front of the line for new Covid-19 vaccines, the biotech industry is looking at the near-term end of the pandemic — or at least a more manageable easing of the rules established during the lockdown. But only a relative handful of CEOs expect things to return to the way they were in a pre-pandemic era. Most are planning to go forward with a whole new set of guidelines for staffers — and flexibility lies at the heart of what’s ahead as people are cleared to go back to the office.

We surveyed our group of Endpoints 100 executives, mostly CEOs, to take the industry’s pulse. This was the latest in close to 5 years of surveys. And several common themes were clear.

First, after a rip-roaring spin on Wall Street as a wave of new IPOs delivered fresh billions to drug hunters, there’s a  record level of excitement about asset valuations and access to capital. The vast majority are expanding this year with new hires. And a remarkable 88% of the 82 executives who took the survey say they won’t be returning to the business-as-usual style they were accustomed to in a pre-pandemic world.

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EMA finds link be­tween ‘very rare’ but some­times fa­tal blood clots and As­traZeneca vac­cine

The EMA said Wednesday that very rare but sometimes fatal blood clots should be listed as a side effect for AstraZeneca’s Covid-19 vaccine.

The EMA’s safety committee said the change to the vaccine label is part of an in-depth review of 62 cases of cerebral venous sinus thrombosis (CVST) and 24 cases of splanchnic vein thrombosis reported in the EU drug safety database as of March 22. Eighteen of the cases were fatal.