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.

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

No­vo Nordisk re­mains un­der UK scruti­ny as MHRA con­ducts its own re­view in 'in­cred­i­bly rare' case

The UK’s Medicines and Healthcare products Regulatory Agency is now reviewing Novo Nordisk’s marketing violation that resulted in its loss of UK trade group membership last week. Novo Nordisk was suspended on Thursday from the Association of the British Pharmaceutical Industry (ABPI) for two years after an investigation by its regulatory arm found the pharma broke its conduct rules.

MHRA said on Tuesday that its review of the Prescription Medicines Code of Practice Authority (PMCPA) investigation is standard practice. An MHRA spokesperson emphasized in an email to Endpoints News that the situation with Novo Nordisk is “incredibly rare” while also noting ABPI took “swift and proportionate action.”

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Andy Plump, Takeda R&D chief (Jeff Rumans for Endpoints News)

What kind of PhI­Ib da­ta is worth $4B cash? Take­da’s Andy Plump has some thoughts on that

A few months back, when Takeda caused jaws to drop with its eye-watering $4 billion cash upfront for a mid-stage TYK2 drug from Nimbus, it had already taken a deep dive on the solid Phase IIb data Nimbus had assembled from its dose-ranging study in psoriasis.

Now, it’s rolling that data out, eager to demonstrate what inspired the global biopharma to go long in a neighboring, but new, disease arena for the pipeline. And the most avid students of the numbers will likely be at Bristol Myers Squibb, who will have a multi-year head start on pioneering the TYK2 space with Sotyktu (deucravacitinib) as Takeda makes its lunge for best-in-class status.

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FDA in­di­cates will­ing­ness to ap­prove Bio­gen ALS drug de­spite failed PhI­II study

Ahead of Wednesday’s advisory committee hearing to discuss Biogen’s ALS drug tofersen, the FDA appeared open to approving the drug, newly released briefing documents show.

Citing the need for flexibility in a devastating disease like ALS, regulators signaled a willingness to consider greenlighting tofersen based on its effect on a certain protein associated with ALS despite a failed pivotal trial. The documents come after regulatory flexibility was part of the same rationale the agency expressed when approving an ALS drug last September from Amylyx Pharmaceuticals, indicating the FDA’s openness to approving new treatments for the disease.

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FDA warns Proc­ter & Gam­ble over NyQuil la­bel's in­gre­di­ent list­ings

The FDA on Tuesday released a warning letter sent earlier this month to the Mason, OH-based site of Procter & Gamble Manufactura, raising questions about the list of ingredients on the label and in the electronic filing.

The warning says that for P&G’s over-the-counter Vicks Nyquil Severe Hot Remedy Cold and Flu Plus Congestion, there’s a “mismatched” list of active ingredients between the labeling and the electronic listing file. The listing file for the active ingredients did not match the active ingredients in the electronic file.

FTC says patent bat­tle over Parkin­son's drug could have 'sig­nif­i­cant im­pli­ca­tion­s' for pa­tients

The Federal Trade Commission has gotten involved in a patent feud over Supernus’ Parkinson’s drug Apokyn, a case the agency said may have ‘‘significant implications” for patients who rely on the drug.

Sage Chemical won the first generic approval for its Apokyn formulation (also known as apomorphine hydrochloride injection) back in 2022. The non-ergoline dopamine agonist is approved to treat Parkinson’s symptoms during “off episodes,” such as difficulty moving, tremors and intense cramping. However, regulators specified that the approval pertained to the generic drug cartridges only, not the injector pen required for administration.

Growth hor­mone from No­vo Nordisk is in short­age over man­u­fac­tur­ing de­lays

Novo Nordisk’s growth hormone Norditropin is in shortage because of manufacturing delays, according to an FDA site that tracks drug shortages as well as the American Society of Health-System Pharmacists’ shortages list.

The FDA has shortages of the drug listed for its 5, 10, 15 and 30 mg doses, while the pharmacists’ group, also known as ASHP, reported shortages of the same doses, except for the 15 mg version.

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PhRMA calls for more di­verse in­fra­struc­ture up­grades to US emer­gency tri­als frame­work

The White House’s Office of Science and Technology Policy (OSTP) last year sought to find ways to better coordinate large-scale clinical trials in the US — as the UK lead by example during the pandemic — especially for these emergency clinical trials.

The lobbying group PhRMA Tuesday called for more clinical trial diversity in underserved areas, including by making participation less of a burden, and expanding eligibility criteria when appropriate.

Mar­ket­ingRx roundup: What could a US Tik­Tok ban mean for phar­ma? Pfiz­er, Lil­ly lead phar­ma March Mad­ness ad­ver­tis­ers

Just as pharma marketers finally make moves into TikTok, the threat of a US ban on the social media channel is now looming. Already banned on federal employee phones by an initial Congressional act, more bills and maybe bans are on the way. With rare bipartisan agreement, lawmakers have introduced legislation that would give the US president the power to ban TikTok (although not mentioned by name) and other foreign-owned technology platforms that represent a security threat to the US.

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