AACR: Bay Area biotech bets on an­ti­bod­ies armed with im­muno-stim­u­lant to fight check­point-re­sis­tant can­cers

The sci­en­tist be­hind the first prostate can­cer vac­cine Provenge — once cel­e­brat­ed as a his­toric break­through, but now a fad­ing star — has de­vised a type of armed an­ti­body — loaded with an im­muno-stim­u­lant rather than a cy­to­tox­ic pay­load — to fight can­cers re­sis­tant to the army of ex­ist­ing check­point in­hibitors.

Ed En­gle­man

The re­searcher, Stan­ford’s Ed En­gle­man, has built on his re­search in­to den­drit­ic cells — which are con­sid­ered ‘sen­tinels’ of the im­mune sys­tem as they are re­spon­si­ble for in­duc­ing im­mune T-cell re­spons­es — to de­vel­op this Im­mune-Stim­u­lat­ing An­ti­body Con­ju­gate (ISAC) tech­nol­o­gy, which was un­veiled by ex­clu­sive li­censee Bolt Bio­ther­a­peu­tics at the Amer­i­can As­so­ci­a­tion for Can­cer Re­search (AACR) Con­fer­ence on Mon­day.

“What Bolt has come up with is to wake up den­drit­ic cells with­in the (tu­mor) mi­croen­vi­ron­ment, and we were able to do this in a tar­get­ed way,” said David Dor­nan, se­nior VP of re­search, in an in­ter­view with End­points News ahead of the con­fer­ence.

Many pa­tients are re­frac­to­ry to check­point in­hibitors be­cause there are a num­ber of im­muno­sup­pres­sive fac­tors present in their tu­mor mi­croen­vi­ron­ment, and so re­searchers have been try­ing to har­ness dif­fer­ent mol­e­cules to stim­u­late the im­mune sys­tem, one of which are toll-like re­cep­tor (TLR) ag­o­nists — spe­cial­ized pro­teins that ini­ti­ate an im­mune re­sponse to for­eign pathogens or, in this case, can­cer cells.

David Dor­nan

But the chal­lenge of de­liv­er­ing these ad­ju­vants is that they must be de­liv­ered in­tra­tu­moral­ly, be­cause if they were ad­min­is­tered sys­tem­i­cal­ly — say oral­ly or in­tra­venous­ly — they can be­come tox­ic as im­mune cells across the body are ac­ti­vat­ed and the im­pact is not tar­get­ed, Dor­nan em­pha­sized.

Bolt’s ISAC tech­nol­o­gy is there­fore tar­get­ed — it con­ju­gates an ad­ju­vant on to a tu­mor tar­get­ing an­ti­body in or­der to de­liv­er this im­mune ag­o­nist di­rect­ly to the tu­mor.

Grant Yone­hi­ro

This is a log­i­cal evo­lu­tion — orig­i­nal­ly, re­searchers were tar­get­ing the tu­mor with chemother­a­peu­tics or an­ti­body drug con­ju­gates, then came the check­point in­hibitors that were de­signed to prime the im­mune sys­tem to at­tack the tu­mor, Bolt’s chief op­er­at­ing of­fi­cer Grant Yone­hi­ro said. “We do both, we’re tar­get­ing the tu­mor with our an­ti­body, but we’re al­so turn­ing on the im­mune sys­tem in the tu­mor.”

But it’s still ear­ly days. Bolt has so far con­duct­ed pre­clin­i­cal stud­ies.

The da­ta sug­gest that the tech can “rein­vig­o­rate the im­mune sys­tem to an ex­tent that if the can­cer came back you have a reper­toire of T-cells that can find, start pro­lif­er­at­ing and then start to kill the can­cer cells,” Dor­nan said.

“We see pro­found tu­mor shrink­age in pre­clin­i­cal mod­els, we see im­muno­log­i­cal mem­o­ry — the abil­i­ty for once when you clear a tu­mor, that if the can­cer comes back — if we give the mouse the can­cer cells, we don’t have re-ad­min­is­ter any ther­a­py — the mouse’s T-cells rec­og­nize the tu­mor and erad­i­cate it. We’ve done these mod­els in can­cers that are large­ly re­frac­to­ry to stan­dard-of-care ther­a­pies.”

With the ad­di­tion of a cy­to­tox­ic pay­load, the du­ra­tion of re­sponse is the main hur­dle — but adding on an im­muno-stim­u­lant can cir­cum­vent that, the ex­ec­u­tives un­der­scored. Bolt’s pre­clin­i­cal da­ta has shown that the ISAC ap­proach is arm­ing the body with a reper­toire of T-cells that even if the can­cer tries to mu­tate around it, the pa­tient has a fight­ing chance.

Bolt has sev­er­al pro­grams in its ar­se­nal, and its lead pro­gram is like­ly go­ing to be de­vel­oped for use in breast can­cer, gas­tric can­cer and blad­der can­cer, Dor­nan said.

The 30-em­ploy­ee Bay Area com­pa­ny has raised $72 mil­lion so far, and hopes to be in the clin­ic by 2020. An IPO is al­so on the cards. “We’re still a lit­tle ear­ly for that, but we think there’s a lot of po­ten­tial for an IPO down the line,” Yone­hi­ro said.

Why it Works: Man­u­fac­tur­ing a Vac­cine in a Mul­ti-Prod­uct Fa­cil­i­ty.

COVID-19 launched the pharmaceutical industry to the frontline in the battle against the fast-spreading global pandemic. The goal: distribute a safe, effective vaccine as quickly as possible. Major players in the vaccine market needed to partner with contract development and manufacturing organizations (CDMOs) to achieve the goal of mass vaccine quantities under expedited timelines. With CDMOs stepping up to play a critical role in the vaccine manufacturing process, multi-product CDMO facilities took the spotlight. Partnerships quickly formed as the race to save lives and fight a pandemic was on.

Habib Dable, Acceleron CEO

Days of heat­ed ru­mors cul­mi­nate in a re­port that Ac­celeron is in ad­vanced buy­out talks

Days of frothy rumors about possible M&A discussions at Acceleron were capped late Friday with a Bloomberg report asserting that the biotech company is in advanced talks for an $11 billion buyout deal.

Bloomberg was unable to identify any bidders in the deal, but speculation has been running rampant that the surging value of Acceleron stock had to be the result of leaks around the auction of the company. As of early Monday morning, we’re still awaiting the final word.

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Merck CEO Rob Davis

Mer­ck emerges as lead bid­der in po­ten­tial Ac­celeron buy­out with deal pos­si­ble this week — re­port

With rumors swirling about a potential buyout of biotech Acceleron and its lead PAH drug sotatercept, market watchers have been keeping close tabs on industry movers and shakers due up for an expensive bolt-on. According to a new report, it appears Merck may be the one.

Merck is in “advanced talks” on a deal to acquire Cambridge, MA-based Acceleron in what previous reports pegged as a potential $11 billion buyout, the Wall Street Journal reported Monday. A deal could come as early as this week, according to the Journal.

Alexander Lefterov/Endpoints News

The coro­n­avirus vac­cine that the world for­got could still help save it

Back at the beginning of the pandemic — back when we still called the virus “novel” and a single case in Washington state could make headlines — there emerged the story of the coronavirus vaccine that the world forgot.

It was an allegory for our pandemic ill-preparedness. At a time when the world had been caught so flat-footed, there were a pair of scientists who had seen the crisis coming, lab-coated Cassandras with an antidote if only the world had listened sooner.

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Anthony Fauci, NIAID director (AP Images)

NIH spot­lights trio of aca­d­e­m­ic teams chas­ing af­ter 'pan-coro­n­avirus' vac­cines

Having made loud and clear its call for new research on vaccines that can tackle future pandemics, the NIH is shedding light on some of the projects it’s funding.

The National Institute of Allergy and Infectious Diseases (NIAID) has awarded around $36.3 million to three academic groups that are working on developing “pan-coronavirus vaccines” — inoculations that can protect against a diverse family of coronaviruses, especially the voracious ones like SARS-CoV-2.

Safe­ty fears force Pfiz­er to change piv­otal DMD gene ther­a­py tri­al pro­to­col

As one of the biggest players in an increasingly packed gene therapy space, Pfizer has taken an early lead over specialists like Sarepta in taking a Duchenne muscular dystrophy (DMD) candidate into late-stage testing. But new safety fears have led Pfizer to scale back that trial, cutting out patients with certain genetic mutations.

Pfizer has amended its enrollment protocol for a Phase III test for gene therapy fordadistrogene movaparvovec in DMD after investigators flagged severe side effects tied to specific mutations, according to a letter the drugmaker sent to Parent Project Muscular Dystrophy, a patient advocacy group.

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Albert Bourla, Pfizer CEO (John Thys, Pool via AP Images)

Covid-19 roundup: Pfiz­er/BioN­Tech sub­mit vac­cine da­ta to FDA for younger chil­dren; Doc­tors kept pre­scrib­ing hy­drox­y­chloro­quine

Pfizer and BioNTech said Tuesday they submitted to FDA positive data from a Phase II/III trial of their Covid-19 vaccine in children aged 5 to less than 12 years old.

A formal EUA submission for the vaccine in these children is expected to follow “in the coming weeks,” the companies said in a statement.

The trial of 2,268 healthy participants aged 5 to less than 12 years old showed the vaccine was safe and elicited robust neutralizing antibody responses using a two-dose regimen of 10 μg doses, which is one-third the dose that’s administered to adults.

From left to right: Mark Springel, Kristina Wang, Lin Ao, Soufiane Aboulhouda

George Church, his stu­dents, and top VCs go na­tion­wide with a biotech train­ing camp

One night last fall, Floris Engelhardt sat down in her Boston apartment and logged onto a Zoom call, armed with a comic and a vague idea about starting a biotech.

Engelhardt was joining a student-run “match night.” A postdoc at MIT’s Bathe BioNanoLab, where researchers use DNA and RNA like Lego blocks for nanometer-sized structures, Engelhardt wanted to find real-world applications for her work. She sketched out — literally — a plan to use DNA origami, a decade-old technique for precisely folding DNA, to make therapies.

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Paul Hudson, Sanofi CEO (Cyril Marcilhacy/Bloomberg via Getty Images)

Sanofi calls it quits on mR­NA Covid-19 shots, scrap­ping vac­cine from $3.2B Trans­late Bio buy­out

Sanofi is throwing in the towel on mRNA-based Covid-19 vaccines.

The French drugmaker will halt development on its unmodified mRNA Covid-19 shot despite what it said were positive Phase I/II results, a spokesperson told Endpoints News on Tuesday morning. Sanofi said the reason it’s stopping the Covid-19 mRNA program, developed in partnership with its new $3.2 billion acquisition Translate Bio, is because the market is too crowded.