Per­son­al­ized can­cer vac­cines stake their claim to the next fron­tier in im­muno-on­col­o­gy

Ugur Sahin, BioN­tech

Two small hu­man stud­ies us­ing per­son­al­ized can­cer vac­cines en­gi­neered with mu­tant pro­teins that col­lec­tive­ly cre­ate a unique thumb print which can be used to iden­ti­fy and tar­get can­cer cells for a pre­ci­sion at­tack by the im­mune sys­tem have demon­strat­ed strong po­ten­tial in a se­lect num­ber of cas­es. And their ear­ly suc­cess­es — out­lined in Na­ture to­day — are out­lin­ing a path for­ward that many aca­d­e­m­ic and in­dus­try re­searchers be­lieve rep­re­sents one of the next big steps for­ward for com­bi­na­tions us­ing the lead­ing PD-(L)1 ther­a­pies now on the mar­ket.

These first ear­ly for­ays in sin­gle arm stud­ies in­volve tech­nolo­gies now in de­vel­op­ment at Neon Ther­a­peu­tics and BioN­Tech, two biotechs on op­po­site sides of the At­lantic which share some com­mon goals. And they both fo­cused on high-risk pa­tients who had un­der­gone surgery to have their tu­mors re­moved.

The work done by Ugur Sahin, the CEO and co-founder of Ger­many’s BioN­Tech, in­volved 13 melanoma pa­tients treat­ed with a mes­sen­ger RNA ther­a­py con­tain­ing up to ten mu­tat­ed pro­teins iden­ti­fied through ge­net­ic se­quenc­ing. Of eight pa­tients in re­mis­sion at the time of ther­a­py, all eight re­mained in re­mis­sion af­ter a year. Of the five who had seen their can­cer spread ahead of ther­a­py with a per­son­al­ized can­cer vac­cine, two saw their tu­mors shrink. One lat­er saw the can­cer resurge while a third went in­to re­mis­sion af­ter the use of a PD-1 check­point.

BioN­Tech is al­ready close­ly part­nered with Genen­tech in a $310 mil­lion deal that lays the foun­da­tion for com­bi­na­tion stud­ies us­ing the phar­ma gi­ant’s PD-L1 drug Tecen­triq. Neon, mean­while, is push­ing ahead with com­bi­na­tions us­ing Bris­tol-My­ers Squibb’s Op­di­vo.

The oth­er study from Neon Ther­a­peu­tics in­volved a small­er group of six melanoma pa­tients treat­ed with a per­son­al­ized neoanti­gen vac­cine, where the neoanti­gens se­lect­ed could bind well with MHC pro­teins and stood a good chance of kick­ing up an im­mune re­sponse that would tar­get the can­cer cells and leave healthy tis­sue alone. This ap­proach al­so has demon­strat­ed po­ten­tial in re­cruit­ing CD4 and CD8 T cells that can fight the can­cer while al­so cre­at­ing dura­bil­i­ty, so the vac­cines can con­tin­ue to do their work and hold can­cer at bay.

Af­ter two years, four were with­out re­cur­rence of the can­cer and the two oth­ers ex­pe­ri­enced a com­plete re­sponse af­ter a PD-1 was added.

“Al­though the num­bers of peo­ple who were treat­ed in these stud­ies were small, both stud­ies in­di­cat­ed po­ten­tial ben­e­fits,” ob­served Lei­den Uni­ver­si­ty’s Cor­nelis Melief in an ac­com­pa­ny­ing ed­i­to­r­i­al. One not­ed ben­e­fit was a re­duc­tion in metas­ta­sis.

Cather­ine Wu, Dana-Far­ber Can­cer In­sti­tute

“This re­search shows that it is fea­si­ble to pro­duce pep­tide-based per­son­al­ized neoanti­gen vac­cines, and these vac­cines can gen­er­ate im­mune re­spons­es with re­li­a­bil­i­ty and po­ten­cy,” said Cather­ine Wu, a Dana-Far­ber in­ves­ti­ga­tor and Neon co-founder. “In this study, over 70% of all pep­tides suc­cess­ful­ly gen­er­at­ed mea­sur­able CD4 and/or CD8 T cell re­spons­es. In ad­di­tion, while pa­tient num­bers are lim­it­ed, the ini­tial clin­i­cal da­ta is in­trigu­ing and wor­thy of ex­plo­ration be­yond the ad­ju­vant set­ting in­to pa­tients with ac­tive dis­ease with im­muno-on­col­o­gy com­bi­na­tions.”

Some big hur­dles re­main. The re­sults have to be repli­cates in much larg­er stud­ies in­volv­ing many more pa­tients. Re­searchers will have to iden­ti­fy which can­cers are most like­ly to re­spond to this kind of ther­a­py. And a man­u­fac­tur­ing process that cur­rent­ly takes months will need to be cut down to a mat­ter of weeks, notes the ar­ti­cle in Na­ture. In ad­di­tion, the check­points alone cost $150,000 a year, and a com­pli­cat­ed per­son­al­ized can­cer vac­cine won’t be cheap.

BioN­Tech and Neon are al­so work­ing in a field with a num­ber of ri­vals, in­clud­ing Grit­stone and Mod­er­na, which will like­ly see these new stud­ies as fur­ther val­i­da­tion for their own work.

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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Deborah Dunsire. Lundbeck

Deb­o­rah Dun­sire is pay­ing $2B for a chance to leap di­rect­ly in­to a block­buster show­down with a few of the world's biggest phar­ma gi­ants

A year after taking the reins as CEO of Lundbeck, Deborah Dunsire is making a bold bid to beef up the Danish biotech’s portfolio of drugs in what will likely be a direct leap into an intense rivalry with a group of giants now carving up a growing market for new migraine drugs.

Bright and early European time the company announced that it will pay up to about $2 billion to buy Alder, a little biotech that is far along the path in developing a quarterly IV formulation for a CGRP drug aimed at cutting back the number of crippling migraines patients experience each month.

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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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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.