Darrell Irvine. MIT

Su­per­charg­ing CAR-T with can­cer vac­cine, MIT team spot­lights some new tech un­der­pin­ning Dar­rell Irvine's start­up

Many of the ef­forts to im­prove on the first gen­er­a­tion of CAR-T ther­a­pies such that they can reach sol­id tu­mors had fo­cused on tweaks in­her­ent to the can­cer killing agent — specif­i­cal­ly, uti­liz­ing more po­tent T cells as their base, from stem mem­o­ry T cells to vi­ral­ly as­so­ci­at­ed T cells to mar­row in­fil­trat­ing lym­pho­cytes. But what if just am­pli­fy­ing CAR-T cells can do the job? Dar­rell Irvine and his team at MIT have some in­trigu­ing mouse da­ta for one such tech.

Leyuan Ma Irvine Lab

Writ­ing in Sci­ence, Irvine — an in­ves­ti­ga­tor at the Koch In­sti­tute for In­te­gra­tive Can­cer Re­search — and his post­doc Leyuan Ma de­scribe “am­phiphile CAR-T lig­ands (amph-lig­ands) that, up­on in­jec­tion, traf­ficked to lymph nodes and dec­o­rat­ed the sur­faces of anti­gen-pre­sent­ing cells, there­by prim­ing CAR-Ts in the na­tive lymph node mi­croen­vi­ron­ment.” Among mice giv­en the boost­er shot af­ter CAR-T in­fu­sion, 60% ex­pe­ri­enced a com­plete re­sponse for a va­ri­ety of tu­mors in­clud­ing glioblas­toma, breast and melanoma. In con­trast, bare­ly any­thing hap­pened to those giv­en just the cell ther­a­py.

It rep­re­sents a twist to the once-hot — but elu­sive — can­cer vac­cine ap­proach, whose premise is to in­duce an im­mune at­tack on tu­mor cells. It al­so promis­es to solve the dura­bil­i­ty prob­lem of CAR-T that many re­searchers have high­light­ed.

“This is a strat­e­gy that can be as­signed to any CAR-T cell and po­ten­tial­ly en­hance its func­tion,” he tells me, ren­der­ing it ex­po­nen­tial­ly more po­tent. “So what­ev­er oth­er strat­e­gy they might be tak­ing en­gi­neer­ing bet­ter CARs, build­ing in oth­er ge­net­ic pay­loads in­to the T cells, this would be a way to make those cells more func­tion­al in vi­vo.”

By send­ing a vac­cine di­rect­ly to the lymph nodes to stim­u­late CAR-T cells, he ex­plains, they hit two birds with one stone: Pre­vent­ing vac­cines from get­ting de­grad­ed and CAR-T cells from re­leas­ing tox­ic cy­tokines — both of which hap­pen in blood­streams. And it com­bines the promis­es of both ther­a­pies.

“If we take the an­i­mals that ap­pear to be cured and we rechal­lenge them with tu­mor cells, they will re­ject all of them,” Irvine said in an in­ter­view with MIT News. “That is an­oth­er ex­cit­ing as­pect of this strat­e­gy. You need to have T cells at­tack­ing many dif­fer­ent anti­gens to suc­ceed, be­cause if you have a CAR-T cell that sees on­ly one anti­gen, then the tu­mor on­ly has to mu­tate that one anti­gen to es­cape im­mune at­tack. If the ther­a­py in­duces new T-cell prim­ing, this kind of es­cape mech­a­nism be­comes much more dif­fi­cult.”

To de­liv­er the amph-lig­ands, the sci­en­tists tagged on a lipid tail that binds to al­bu­min in the blood­stream and fol­lows it to the lymph nodes. Once there, the anti­gen in­side the vac­cine — ei­ther the same one the CAR-T is orig­i­nal­ly en­gi­neered to rec­og­nize or an­oth­er, they test­ed both — su­per­charges T cells and spurs their pro­lif­er­a­tion.

Irvine is hope­ful about con­duct­ing first-in-hu­man tri­als with­in one to two years through Eli­cio Ther­a­peu­tics, the sec­ond biotech he co-found­ed. In ad­di­tion to go­ing af­ter sol­id tu­mor in­di­ca­tions, he al­so sees ap­pli­ca­tion of his am­pli­fied CAR-T in the more tra­di­tion­al CD19 and BC­MA set­tings, as well as de­ploy­ing the vac­cine can­di­date alone for KRAS-mu­tant can­cers.

Eli­cio launched ear­li­er this year with $30 mil­lion in fund­ing, Robert Con­nel­ly (old timers may re­mem­ber him as found­ing CEO of Do­man­tis) as chief and Gami­da Cells’ Ju­lian Adams as ex­ec­u­tive chair­man. The com­pa­ny is in talks with part­ners that might bring their own CAR-T to the ta­ble.

“Part of the beau­ty of this is,” he adds, “in the grand scheme of things, it will add noth­ing to the cost of CAR-T cell ther­a­py be­cause [it’s] es­sen­tial­ly a de­fined mol­e­c­u­lar en­ti­ty that can be made at scale pret­ty sim­ply.”

The re­search pub­lished to­day was par­tial­ly fund­ed by J&J — along­side the NIH, the Mar­ble Cen­ter for Can­cer Nanomed­i­cine and the Na­tion­al In­sti­tute of Gen­er­al Med­ical Sci­ences. Irvine said the phar­ma gi­ant is not cur­rent­ly an in­vestor, though it has been in touch.

Here comes the oral GLP-1 drug for di­a­betes — but No­vo Nordisk is­n't dis­clos­ing Ry­bel­sus price just yet

Novo Nordisk’s priority review voucher on oral semaglutide has paid off. The FDA approval for the GLP-1 drug hit late Friday morning, around six months after the NDA filing.

Rybelsus will be the first GLP-1 pill to enter the type 2 diabetes market — a compelling offering that analysts have pegged as a blockbuster drug with sales estimates ranging from $2 billion to $5 billion.

Ozempic, the once-weekly injectable formulation of semaglutide, brought in around $552 million (DKK 3.75 billion) in the first half of 2019.

As Nas­daq en­rolls the fi­nal batch of 2019 IPOs, how have the num­bers com­pared to past years?

IGM Biosciences’ upsized IPO haul, coming after SpringWorks’ sizable public debut, has revved up some momentum for the last rush of biotech IPOs in 2019.

With 39 new listings on the books and roughly two more months to go before winding down, Nasdaq’s head of healthcare listings Jordan Saxe sees the exchange marking 50 to 60 biopharma IPOs for the year.

“December 15 is usually the last possible day that companies will price,” he said, as companies get ready for business talks at the annual JP Morgan Healthcare Conference in January.

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A fa­vorite in Alex­ion’s C-suite is leav­ing, and some mighty sur­prised an­a­lysts aren’t the least bit hap­py about it

Analysts hate to lose a biotech CFO they’ve come to trust and admire — especially if they’re being blindsided by a surprise exit.

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Oxitec biologist releases genetically modified mosquitoes in Piracicaba, Brazil in 2016 [credit: Getty Images]

In­trex­on unit push­es back against claims its GM mos­qui­toes are mak­ing dis­ease-friend­ly mu­tants

When the hysteria of Zika transmission sprang into the American zeitgeist a few years ago, UK-based Oxitec was already field-testing its male Aedes aegypti mosquito, crafted to possess a gene engineered to obliterate its progeny long before maturation.

But when a group of independent scientists evaluated the impact of the release of these genetically-modified mosquitoes in a trial conducted by Oxitec in Brazil between 2013 and 2015, they found that some of the offspring had managed to survive — prompting them to speculate what impact the survivors could have on disease transmission and/or insecticide resistance.

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Pur­due threat­ens to walk away from set­tle­ment, asks to pay em­ploy­ees mil­lions in bonus­es

There are two updates on the lawsuit against Purdue Pharma over its role in fueling the opioid epidemic, as the Sackler family threatens to walk away from their pledge to pay out $3 billion if a bankruptcy judge does not stop outstanding state lawsuits against them. At the same time, the company has asked permission to pay millions in bonuses to select employees.

Purdue filed for chapter 11 bankruptcy this week as part of its signed resolution to over 2,000 lawsuits. The deal would see the Sackler family that owns Purdue give $3 billion from their personal wealth and the company turned into a trust committed to curbing and reversing overdoses.

Aerial view of Genentech's campus in South San Francisco [Credit: Getty]

Genen­tech sub­mits a big plan to ex­pand its South San Fran­cis­co foot­print

The sign is still there, a quaint reminder of whitewashed concrete not 5 miles from Genentech’s sprawling, chrome-and-glass campus: South Francisco The Industrial City. 

The city keeps the old sign, first erected in 1923, as a tourist site and a kind of civic memento to the days it packed meat, milled lumber and burned enough steel to earn the moniker “Smokestack of the Peninsula.” But the real indication of where you are and how much has changed both in San Francisco and in the global economy since a couple researchers and investors rented out an empty warehouse 40 years ago comes in a far smaller blue sign, resembling a Rotary Club post, off the highway: South San Francisco, The Birthplace of Biotech.

While No­var­tis ban­ish­es Zol­gens­ma scan­dal scars — Bio­gen goes on a Spin­raza 'of­fen­sive'

While Novartis painstakingly works to mop up the stench of the data manipulation scandal associated with its expensive gene therapy for spinal muscular atrophy (SMA) Zolgensma— rival Biogen is attempting to expand the use of its SMA therapy, Spinraza. 

The US drugmaker $BIIB secured US approval for Spinraza for use in the often fatal genetic disease in 2016. The approval covered a broad range of patients with infantile-onset (most likely to develop Type 1) SMA. 

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Eye­ing big ther­a­peu­tic push, Gink­go bags $290M to build a cell pro­gram­ming em­pire

Ginkgo Bioworks is on a roll. Days after publicizing a plan to nurture new startups via partnerships with accelerators Y Combinator and Petri, the Boston biotech says it has raised another $290 million for its cell programming platform to reach further and wider.

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UP­DAT­ED: Speak­er Nan­cy Pelosi to un­veil bill for fed­er­al­ly ne­go­ti­at­ed drug prices

After months of buzz from both sides of the aisle, Speaker Nancy Pelosi will today introduce her plan to allow the federal government to negotiate prices for 250 prescription drugs, setting up a showdown with a pharmaceutical industry working overtime to prevent it.

The need to limit drug prices is a rare point of agreement between President Trump and Democrats, although the president has yet to comment on the proposal and will likely face pressure to back a more conservative option or no bill at all. Republican Senator Chuck Grassley is reportedly lobbying his fellow party members on a more modest proposal he negotiated with Democratic Senator Ron Wyden in July.