Re­searchers at City of Hope com­bine on­colyt­ic virus with a CAR-T to erad­i­cate sol­id tu­mors in mice

A new com­bi­na­tion of ex­ist­ing can­cer treat­ments is show­ing ear­ly signs of po­ten­tial­ly crack­ing open a new ap­proach to treat­ing sol­id tu­mors.

In pre­clin­i­cal re­search pub­lished by City of Hope, a Cal­i­for­nia-based non-prof­it, sci­en­tists ef­fec­tive­ly blend­ed CAR-T ther­a­py with an on­colyt­ic virus to erad­i­cate sol­id tu­mors in mice. The virus is ge­net­i­cal­ly en­gi­neered to en­ter the tu­mors and force them to ex­press the CD19 pro­tein, al­low­ing the CAR-T cells to at­tack.

Saul Price­man

“We came up with the idea based on the com­pat­i­ble ex­per­tise and es­sen­tial­ly with sev­er­al in­ves­ti­ga­tors at City of Hope,” Saul Price­man, se­nior au­thor of the pa­per, told End­points News. “It was al­most an idea to over­come the chal­lenges as­so­ci­at­ed with treat­ing sol­id tu­mors with CAR-T cell ther­a­py … the chal­lenge be­ing what tu­mor anti­gen to go af­ter in sol­id tu­mors and al­so what we call the im­muno­sup­pres­sive mi­croen­vi­ron­ment.”

The re­searchers are ex­pect­ing to move in­to hu­man tri­als with­in the next year and a half. Price­man added he likes to de­scribe the method as “mark and kill,” where the virus marks the tu­mor with a rec­og­niz­able tar­get for the CAR-T cells that then go in for the kill.

Nor­mal­ly used to treat blood can­cers like B cell lym­phomas and acute lym­phoblas­tic leukemia, CAR-T ther­a­py has made sig­nif­i­cant head­way since net­ting its first FDA ap­proval back in late 2017. The suc­cess seen in these can­cers hasn’t trans­lat­ed in­to sol­id tu­mors as of yet giv­en that find­ing re­cep­tors on the sur­faces of those cells is much more chal­leng­ing and can lead to un­want­ed tox­i­c­i­ties.

By com­bin­ing CAR-T with a virus that es­sen­tial­ly com­pels the tu­mors in­to ex­press­ing a re­cep­tor like CD19, how­ev­er, Price­man hopes this con­cept can be a game-chang­er. Specif­i­cal­ly in the mouse tri­als, Price­man and his team showed the virus was able to ex­press CD19 in triple-neg­a­tive breast can­cer, as well as in pan­cre­at­ic, prostate, ovar­i­an, and head and neck can­cer, as well as brain tu­mor cells.

On­colyt­ic virus­es have had marked­ly less suc­cess when used on their own to treat can­cers, ac­cord­ing to pa­per co-au­thor An­tho­ny Park, large­ly be­cause the im­mune sys­tem can de­vel­op a re­sis­tance. They’ve al­so nev­er been test­ed clin­i­cal­ly, but with CAR-T’s safe­ty pro­file al­ready well-known, the team is ex­pect­ing pos­i­tive re­sults.

When used alone, the on­colyt­ic virus “will in­duce an en­doge­nous im­mune re­sponse, which could be ben­e­fi­cial for tar­get­ing tu­mors, but it can al­so be detri­men­tal to the virus ac­tiv­i­ty be­cause the im­mune sys­tem can rec­og­nize the virus to not on­ly show the tu­mor cells but al­so get rid of the virus,” Park said.

Ezra Co­hen

City of Hope’s re­sults have al­ready im­pressed some out­side ex­perts, name­ly Ezra Co­hen, the chief of UC San Diego’s hema­tol­ogy-on­col­o­gy di­vi­sion. Co­hen, who him­self is re­search­ing a sim­i­lar com­bi­na­tion us­ing ROR1-tar­get­ing CAR-T cells, said City of Hope used a “clever ap­proach” and found an added bonus in the study when the virus prop­a­gat­ed in­to oth­er tu­mor cells af­ter the orig­i­nal­ly-in­fect­ed cells died off.

That could sug­gest wide­spread ef­fi­ca­cy even if the on­colyt­ic virus doesn’t man­age to in­fect every sin­gle tu­mor cell.

“You’ve got this ham­mer, which has been suc­cess­ful in hema­to­log­i­cal dis­eases, but you can’t use it for all the pa­tients with sol­id tu­mors be­cause you can’t see the nail,” Co­hen said. “But what City of Hope did is they put the nail in­to cells that they want­ed, and now all of a sud­den you can use that ham­mer and it be­comes ef­fec­tive.”

The biggest chal­lenge mov­ing for­ward will be how well the ex­per­i­ments in mice can trans­late in­to hu­mans. Some ex­per­i­men­tal CAR-T ther­a­pies have failed at this stage be­fore, Co­hen said, as get­ting the treat­ment to hone in on the tu­mor when it’s not di­rect­ly in­ject­ed in­to its cells — some­thing that’s not al­ways pos­si­ble in hu­mans with metasta­t­ic can­cers — is im­mense­ly dif­fi­cult.

But Price­man is con­fi­dent in the ex­per­tise of the City of Hope team, not­ing that the in­sti­tu­tion has 30 ac­tive Phase I clin­i­cal tri­als with CAR-T cells in a range of dis­eases.

“One of the beau­ties of City of Hope is we’ve done this a num­ber of times,” Price­man said. “Clin­i­cal trans­la­tion of a CAR-T cell is some­thing we have a wide ex­per­tise in, and we’ve al­so grow­ing ex­per­tise in on­colyt­ic virus­es.”

So­cial: Michael Dominguez, Shut­ter­stock

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Roivant par­lays a $450M chunk of eq­ui­ty in biotech buy­out, grab­bing a com­pu­ta­tion­al group to dri­ve dis­cov­ery work

New Roivant CEO Matt Gline has crafted an all-equity upfront deal to buy out a Boston-based biotech that has been toiling for several years now at building a supercomputing-based computational platform to design new drugs. And he’s adding it to the Erector set of science operations that are being built up to support their network of biotech subsidiaries with an eye to growing the pipeline in a play to create a new kind of pharma company.

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Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

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CEO Fred Aslan (Artiva)

NK cell ther­a­py play­er Arti­va makes some more noise, pulling in $120M Se­ries B less than a month af­ter Mer­ck deal

Not even one month after Big Pharma took notice of Artiva when Merck signed a collaboration worth nearly $2 billion in milestones, the off-the-shelf NK cell biotech already has its next big fundraise.

Artiva returns from the venture well Friday with a $120 million Series B round, money they will use to get their first program into the clinic and to file INDs for another two candidates. The raise marks the latest development in a rapidly expanding footprint for Artiva, which, in addition to the Merck deal last month, has now raised almost $200 million since its Series A last June.

With dust set­tled on ac­tivist at­tack, Lau­rence Coop­er leaves Zio­pharm to a new board

Laurence Cooper has done his part.

In the five years since he left a tenured position at Houston’s MD Anderson Cancer Center to become CEO of Boston-based Ziopharm, he’s steered the small-cap immunotherapy player through patient deaths in trials, clinical holds, short attacks and, most recently, an activist attack on the board.

So when the company has “fantastic news” like an IND clearance for a TCR T cell therapy program, he’s ready to pass on the baton.

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Doug Ingram (file photo)

Why not? Sarep­ta’s third Duchenne MD drug sails to ac­cel­er­at­ed ap­proval

Sarepta may be running into some trouble with its next-gen gene therapy approach to Duchenne muscular dystrophy. But when it comes to antisense oligonucleotides, the well-trodden regulatory path is still leading straight to an accelerated approval for casimersen, now christened Amondys 45.

We just have to wait until 2024 to find out if it works.

Amondys 45’s approval was unceremonious, compared to its two older siblings. There was no controversy within the FDA over approving a drug based on a biomarker rather than clinical benefit, setting up a powerful precedent that still haunts acting FDA commissioner Janet Woodcock as biotech insiders weighed her potential permanent appointment; no drama like the FDA issuing a stunning rejection only to reverse its decision and hand out an OK four months later, which got more complicated after the scathing complete response letter was published; no anxious tea leaf reading or heated arguments from drug developers and patient advocates who were tired of having corticosteroids as their loved ones’ only (sometimes expensive) option.

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Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

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J&J ad­comm live blog: Com­mit­tee votes 22-0 to rec­om­mend an FDA OK for the J&J vac­cine, set­ting up 3rd US Covid-19 jab

The US could have a third authorized Covid-19 vaccine within hours.

The FDA’s advisory committee voted unanimously — 22-0 — to recommend the agency issue an emergency use authorization for J&J’s vaccine. If they follow the precedent of the Pfizer and Moderna vaccine,  the FDA will likely authorize the vaccine by Saturday, immediately adding a few million doses to the US supply and adding a 100 million by June. An authorization would give the world its first single-dose vaccine, a major weapon in the effort to vaccinate the world and bring the virus to heel, particularly in rural and developing areas.