Can we stop can­cer cells from evolv­ing and de­vel­op­ing drug re­sis­tance? British sci­en­tists take a leaf out of the HIV play­book

British sci­en­tists want to counter can­cer by us­ing an ap­proach that worked for HIV and tu­ber­cu­lo­sis: by cre­at­ing treat­ments to pre­clude can­cer’s abil­i­ty to be­come re­sis­tant to ex­ist­ing drugs and re­cur.

The drug dis­cov­ery pro­gram, or­ches­trat­ed by the In­sti­tute of Can­cer Re­search (ICR) in Lon­don, will be launched at a fa­cil­i­ty in the British cap­i­tal with an ini­tial £75 mil­lion (rough­ly $85 mil­lion) in­jec­tion.

De­spite the ad­vent of im­munother­a­pies in the can­cer ther­a­peu­tic ar­se­nal, the is­sue of re­sis­tance to can­cer drugs — in­clud­ing chemother­a­pies and mol­e­c­u­lar-tar­get­ed ther­a­pies — is ram­pant. For ex­am­ple, the clas­sic ap­proach of em­ploy­ing ag­gres­sive ‘shock and awe’ chemother­a­py can fal­ter be­cause too of­ten it helps fu­el an ‘sur­vival of the nas­ti­est’ evo­lu­tion among can­cer cells, ICR sci­en­tists con­tend.

ICR in­tends to ad­dress the chal­lenge on two fronts. First, is an ap­proach called ‘evo­lu­tion­ary herd­ing’. Us­ing ar­ti­fi­cial in­tel­li­gence, re­searchers at ICR can fore­cast how can­cer cells tend to re­act when treat­ed with a par­tic­u­lar drug. There­fore by se­lect­ing an ini­tial drug treat­ment — can­cer cells can be com­pelled to adapt in a fash­ion that makes them sus­cep­ti­ble to a sec­ondary treat­ment, or thrusts them in­to an “evo­lu­tion­ary dead end”.

The sec­ond strat­e­gy is to de­vel­op a fam­i­ly of drugs that thwart the abil­i­ty of can­cer cells to evolve and re­sist treat­ment. This fresh class of drugs are be­ing con­struct­ed to tar­get a pro­tein called APOBEC in a bid to di­min­ish the rate of mu­ta­tion in can­cer cells, slow down evo­lu­tion and de­lay re­sis­tance. Al­though the en­zyme is cru­cial for the im­mune sys­tem to adapt to dif­fer­ent in­fec­tious dis­eases, it has been im­pli­cat­ed in can­cer mu­ta­tions re­cent­ly, af­ter be­ing the fo­cus of vi­rol­o­gy re­search for over a decade.

Olivia Rossanese

Once de­vel­oped, these APOBEC in­hibitors could be ad­min­is­tered in tan­dem with ex­ist­ing tar­get­ed on­col­o­gy ther­a­pies to keep the can­cer at bay for longer pe­ri­ods, or in­deed el­e­vate it to the po­si­tion of a chron­ic dis­ease from an of­ten in­cur­able di­ag­no­sis.

“We be­lieve this will be the first treat­ment in the world that rather than deal­ing with the con­se­quences of can­cer’s evo­lu­tion and re­sis­tance, aims to di­rect­ly con­front the dis­ease’s abil­i­ty to adapt and evolve in the first place,” said Olivia Rossanese, who will serve as head of bi­ol­o­gy at the new ICR fa­cil­i­ty, in a state­ment.

An­oth­er ap­proach tout­ed by ICR is com­bin­ing can­cer drugs to com­bat drug re­sis­tance. In the lab, ICR re­searchers have ob­served that bow­el can­cer cells evolved to re­sist two tar­get­ed treat­ments, but suc­cumbed to the third, they said on Wednes­day.

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

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It's not per­fect, but it's a good start: FDA pan­elists large­ly en­dorse Aim­mune's peanut al­ler­gy ther­a­py

Two days after a fairly benign review from FDA staff, an independent panel of experts largely endorsed the efficacy and safety of Aimmune’s peanut allergy therapy, laying the groundwork for approval with a risk evaluation and mitigation strategy (REMS).

Traditionally, peanut allergies are managed by avoidance, but the threat of accidental exposure cannot be nullified. Some allergists have devised a way to dose patients off-label with peanut protein derived from supermarket products to wean them off their allergies. But the idea behind Aimmune’s product was to standardize the peanut protein, and track the process of desensitization — so when accidental exposure in the real world invariably occurs, patients are less likely to experience a life-threatening allergic reaction.

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Rit­ter bombs fi­nal PhI­II for sole lac­tose in­tol­er­ance drug — shares plum­met

More than two years ago Ritter Pharmaceuticals managed to find enough silver lining in its Phase IIb/III study — after missing the top-line mark — to propel its lactose intolerance toward a confirmatory trial. But as it turned out, the enthusiasm only set the biotech and its investors up to be sorely disappointed.

This time around there’s little left to salvage. Not only did RP-G28 fail to beat placebo in reducing lactose intolerance symptoms, patients in the treatment group actually averaged a smaller improvement. On a composite score measuring symptoms like abdominal pain, cramping, bloating and gas, patients given the drug had a mean reduction of 3.159 while the placebo cohort saw a 3.420 drop on average (one-sided p-value = 0.0106).

Ear­ly snap­shot of Ad­verum's eye gene ther­a­py sparks con­cern about vi­sion loss

An early-stage update on Adverum Biotechnologies’ intravitreal gene therapy has triggered investor concern, after patients with wet age-related macular degeneration (AMD) saw their vision deteriorate, despite signs that the treatment is improving retinal anatomy.

Adverum, on Wednesday, unveiled 24-week data from the OPTIC trial of its experimental therapy, ADVM-022, in six patients who have been administered with one dose of the therapy. On average, patients in the trial had severe disease with an average of 6.2 anti-VEGF injections in the eight months prior to screening and an average annualized injection frequency of 9.3 injections.

Alex Ar­faei trades his an­a­lyst's post for a new role as biotech VC; Sanofi vet heads to Vi­for

Too often, Alex Arfaei arrived too late. 

An analyst at BMO Capital Markets, he’d meet with biotech or pharmaceutical heads for their IPO or secondary funding and his brain, trained on a biology degree and six years at Merck and Endo, would spring with questions: Why this biomarker? Why this design? Why not this endpoint? Not that he could do anything about it. These execs were coming for clinical money; their decisions had been made and finalized long ago.

Lisa M. DeAngelis, MSKCC

MSK picks brain can­cer ex­pert Lisa DeAn­ge­lis as its next CMO — fol­low­ing José Basel­ga’s con­tro­ver­sial ex­it

It’s official. Memorial Sloan Kettering has picked a brain cancer expert as its new physician-in-chief and CMO, replacing José Baselga, who left under a cloud after being singled out by The New York Times and ProPublica for failing to properly air his lucrative industry ties.

His replacement, who now will be in charge of MSK’s cutting-edge research work as well as the cancer care delivered by hundreds of practitioners, is Lisa M. DeAngelis. DeAngelis had been chair of the neurology department and co-founder of MSK’s brain tumor center and was moved in to the acting CMO role in the wake of Baselga’s departure.

Penn team adapts CAR-T tech, reengi­neer­ing mouse cells to treat car­diac fi­bro­sis

After establishing itself as one of the pioneer research centers in the world for CAR-T cancer therapies, creating new attack vehicles to eradicate cancer cells, a team at Penn Medicine has begun the tricky transition of using the basic technology for heart repair work.

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Tal Zaks. Moderna

The mR­NA uni­corn Mod­er­na has more ear­ly-stage hu­man da­ta it wants to show off — reach­ing new peaks in prov­ing the po­ten­tial

The whole messenger RNA field has attracted billions of dollars in public and private investor cash gambled on the prospect of getting in on the ground floor. And this morning Boston-based Moderna, one of the leaders in the field, wants to show off a few more of the cards it has to play to prove to you that they’re really in the game.

The whole hand, of course, has yet to be dealt. And there’s no telling who gets to walk with a share of the pot. But any cards on display at this point — especially after being accused of keeping its deck under lock and key — will attract plenty of attention from some very wary, and wired, observers.

“In terms of the complexity and unmet need,” says Tal Zaks, the chief medical officer, “this is peak for what we’ve accomplished.”

Moderna has two Phase I studies it wants to talk about now.

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Sanofi takes a $260M hit to ex­tri­cate it­self from a dis­as­trous al­liance with Lex­i­con

Sanofi spent $300 million in cash to get into a $1.7 billion alliance with Lexicon on their SGLT1/2 diabetes drug sotagliflozin. And now that the drug has been spurned by the FDA after burning through a program that provided mixed late-stage data and a late shot at a last-place finish, the French pharma giant is forking over another $260 million to get out of the deal.

Sanofi’s unhappiness was already apparent when the company — now under new CEO Paul Hudson — posted a statement back in July that they were dropping the deal. But it wasn’t that simple. 

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