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.”

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

US paus­es J&J vac­ci­na­tions amid new re­ports of rare, se­ri­ous blood clots

The FDA and CDC have jointly decided to stop administering J&J’s Covid-19 vaccine after reviewing data involving six reported US cases of a rare and severe type of blood clot in individuals after receiving the vaccine.

CDC will convene a meeting of its Advisory Committee on Immunization Practices on Wednesday to further review these cases and assess their potential significance. “FDA will review that analysis as it also investigates these cases. Until that process is complete, we are recommending a pause in the use of this vaccine out of an abundance of caution,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research and Anne Schuchat, Principal Deputy Director of the CDC, said in a joint statement Tuesday morning.

Toad ven­om to treat de­pres­sion? RA Cap­i­tal wa­gers $125M on lat­est psy­che­del­ic biotech

Can an inhaled version of the psychedelic known as ‘toad venom’ be used to treat tough-to-crack depression? For GH Research, that’s the $125 million question.

The Dublin-based biotech announced Monday it closed a Series B round to help advance its lead program, an inhalant called GH001, for psychiatric and neurological disorders. GH is beginning with treatment-resistant depression and has two as-yet-undisclosed indications on tap.

Rami Elghandour, Arcellx

Ar­cel­lx rais­es mega-round to put con­trol­lable CAR-T in­to the clin­ic

Arcellx claims to have the first controllable CAR-T ready for the clinic. Now they’ll have cash — a boatload of cash — to get it through.

The Gaithersburg, MD-based biotech announced Tuesday a $115 million Series C led by Samsara BioCapital and CAM Capital. Arcellx will use their first round, their first since an $85 million launch in 2019, to begin two Phase I trials for their reprogrammable CAR-Ts, while pushing a more traditional CAR-T for multiple myeloma into a pivotal study.

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Iain Dukes, Theseus interim CEO

Or­biMed-backed The­seus de­buts with $100M round in hero­ic quest for 'pan-vari­ant' ki­nase in­hibitors

Despite the promise of kinase inhibitors in treating rare tumors, narrow therapeutic targets for most candidates can halt efficacy the moment a patient’s tumor cells mutate. Now, an OrbiMed-backed startup will take a nine-figure fundraising round to advance its purposefully broad candidates against treatment-resistant tumors.

Boston-based Theseus Pharmaceuticals has bagged a $100 million Series B round it will use to advance a suite of “pan-variant” tyrosine kinase inhibitors (TKI), including a lead compound targeting KIT-mutant gastrointestinal stromal tumors, the company said Tuesday.

Patrizia Cavazzoni, new CDER director

Pa­trizia Cavaz­zoni named per­ma­nent di­rec­tor of CDER, adding to ques­tions around where Wood­cock will end up

Patrizia Cavazzoni on Monday became the permanent director of the FDA’s Center for Drug Evaluation and Research, which puts to rest the idea that Janet Woodcock, Cavazzoni’s predecessor, might return to lead CDER if she isn’t made permanent commissioner.

Woodcock, who’s currently serving as acting commissioner and principal medical advisor to the commissioner, a position she was detailed to last year, may not make the move to permanent commissioner because of lingering questions from Senate Democrats. She previously served as director of CDER since 1994. Cavazzoni took over as acting director of CDER when Woodcock moved over to Operation Warp Speed to run the therapeutics side of the Trump-era program.

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John Thero (Christopher Goodney/Bloomberg via Getty Images)

Amarin CEO John Thero pass­es ba­ton to Eu­rope com­mer­cial chief as M&A hopes con­tin­ue to de­flate

As Amarin breaks into the European market, John Thero is heading out.

After steering the ship for 7 years, Thero is handing the CEO job to Karim Mikhail, who came on board earlier this year to head the commercialization of Amarin’s fish oil pill in Europe. Mikhail’s appointment is effective August 1, when Thero will officially retire and transition to an advisor role until the end of 2021.

Since joining Amarin in 2009, Thero has been credited for a slate of achievements that gave investors lots to be excited about. Under his watch, Vascepa — the pharmaceutical grade omega-3 fatty acid product first approved in 2012 — was cruised to a positive Phase III data readout despite some controversy, spurring an impressive reduction in risk of cardiovascular events that led to a quick FDA add-on approval.

John Cox (file photo)

In­vestors throw $189M at Flag­ship star­tup's mis­sion to 'de­code' in­ter­ac­tions be­tween T cells and anti­gens

Two is often better than one in the world of biopharma investment. If you need proof, look no further than Repertoire Immune Medicines.

Repertoire launched last March out of a merger between Flagship startups Cogen Immune Medicines and Torque Therapeutics. And early Monday morning, the team uncloaked a massive $189 million Series B round to fund its mission to decode the interactions between T cells and antigens.

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Re­gen­eron’s Covid mAb as a pro­phy­lac­tic in­jec­tion: Re­duced risk of symp­to­matic in­fec­tion by 81%

Regeneron’s monoclonal antibody cocktail for Covid-19 continues to impress, this time in a joint trial with NIH that found the normally infused treatment works as a preventive subcutaneous injection.

The trial showed that REGEN-COV (casirivimab with imdevimab) reduced the risk of symptomatic infections by 81% in those who did not have Covid before the trial within 29 days. There were 11 cases in the 753-person mAb arm, versus 59 cases in the 752-person placebo arm.