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.

The DCT-OS: A Tech­nol­o­gy-first Op­er­at­ing Sys­tem - En­abling Clin­i­cal Tri­als

As technology-enabled clinical research becomes the new normal, an integrated decentralized clinical trial operating system can ensure quality, deliver consistency and improve the patient experience.

The increasing availability of COVID-19 vaccines has many of us looking forward to a time when everyday things return to a state of normal. Schools and teachers are returning to classrooms, offices and small businesses are reopening, and there’s a palpable sense of optimism that the often-awkward adjustments we’ve all made personally and professionally in the last year are behind us, never to return. In the world of clinical research, however, some pandemic-necessitated adjustments are proving to be more than emergency stopgap measures to ensure trial continuity — and numerous decentralized clinical trial (DCT) tools and methodologies employed within the last year are likely here to stay as part of biopharma’s new normal.

Onno van de Stolpe, Galapagos CEO (Thierry Roge/Belga Mag/AFP via Getty Images)

Gala­pa­gos chops in­to their pipeline, drop­ping core fields and re­or­ga­niz­ing R&D as the BD team hunts for some­thing 'trans­for­ma­tive'

Just 5 months after Gilead gutted its rich partnership with Galapagos following a bitter setback at the FDA, the Belgian biotech is hunkering down and chopping the pipeline in an effort to conserve cash while their BD team pursues a mission to find a “transformative” deal for the company.

The filgotinib disaster didn’t warrant a mention as Galapagos laid out its Darwinian restructuring plans. Forced to make choices, the company is ditching its IPF molecule ’1205, while moving ahead with a Phase II IPF study for its chitinase inhibitor ’4617.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 104,800+ biopharma pros reading Endpoints daily — and it's free.

Ron DePinho (file photo)

A 'fly­over' biotech launch­es in Texas with four Ron De­Pin­ho-found­ed com­pa­nies un­der its belt

In his 13 years at Genzyme, Michael Wyzga noticed something about East Coast drugmakers. Execs would often jet from Boston or New York to San Francisco to find more assets, and completely miss the work being done in flyover states, like Texas or Wisconsin.

“If it doesn’t come out of MGH or MIT or Harvard, probably not that interesting,” he said of the mindset.

Now, he and some well-known industry players are looking to change that, and they’ve reeled in just over $38 million to do it.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 104,800+ biopharma pros reading Endpoints daily — and it's free.

Stéphane Bancel, Getty

Mod­er­na CEO brush­es off US sup­port for IP waiv­er, eyes more than $19B in Covid-19 vac­cine sales in 2021

Moderna is definitively more concerned with keeping pace with Pfizer in the race to vaccinate the world against Covid-19 than it is with Wednesday’s decision from the Biden administration to back an intellectual property waiver that aims to increase vaccine supplies worldwide.

In its first quarter earnings call on Thursday, Moderna CEO Stéphane Bancel shrugged off any suggestion that the newly US-backed intellectual property waiver would impact his company’s vaccine or bottom line. Still, the company’s stock price fell by about 9% in early morning trading.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 104,800+ biopharma pros reading Endpoints daily — and it's free.

Ad­comm splits slight­ly in fa­vor of FDA ap­prov­ing Chemo­Cen­tryx’s rare dis­ease drug

The FDA’s Arthritis Advisory Committee on Thursday voted 10 for and 8 against the approval of ChemoCentryx’s $CCXI investigational drug avacopan as a treatment for adults with a rare and serious disease known as anti-neutrophil cytoplasmic autoantibody (ANCA)-vasculitis.

The vote on whether the FDA should approve the drug was preceded by a split vote of 9 to 9 on whether the efficacy data support approval, and 10 to 8 that the safety profile of avacopan is adequate enough to support approval.

Drug pric­ing watch­dog joins the cho­rus of crit­ics on Bio­gen's ad­u­canum­ab: What about charg­ing $2,560 per year?

As if Biogen’s aducanumab isn’t controversial enough, the researchers at drug pricing watchdog ICER have drawn up the contours of a new debate: If the therapy does get approved for Alzheimer’s by June, what price should it command?

Their answer: At most $8,290 per year — and perhaps as little as $2,560.

Even at the top of the range, the proposed price is a fraction of the $50,000 that Wall Street has reportedly come to expect (although RBC analyst Brian Abrahams puts the consensus figure at $11.5K). With critics, including experts on the FDA’s advisory committee, making their fierce opposition to aducanumab’s approval loud and clear, the pricing pressure adds one extra wrinkle Biogen CEO Michel Vounatsos doesn’t need as he orders full-steam preparation for a launch.

Biden ad­min­is­tra­tion backs a po­lar­iz­ing pro­pos­al to waive IP for all Covid-19 vac­cines

In a surprise U-turn, the Biden administration said Wednesday that it will support a proposal at the World Trade Organization to temporarily waive intellectual property protections on Covid-19 vaccines.

The proposal, backed by South Africa and India at the WTO, seeks to help developing countries with limited vaccine supplies. The US and Europe historically opposed the proposal, saying IP should be protected because it incentivizes new drug and vaccine development.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 104,800+ biopharma pros reading Endpoints daily — and it's free.

FDA ex­tends re­search agree­ment with MIT-li­censed or­gan-on-chip sys­tems

The FDA on Wednesday extended its four-year agreement with CN Bio, a developer of single- and multi-organ-on-chip systems used for drug discovery, for another three years.

CN Bio said the scope of the research performed by the FDA’s Center for Drug Evaluation and Research has expanded to include the exploration of the company’s lung-on-a-chip system to help with the agency’s evaluation of inhaled drugs, in addition to the agency’s work on its liver model.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

In quest to meet user fee goals, FDA’s per­for­mance con­tin­ues down­ward trend

A recent update to the FDA’s running tally of how it’s meeting its user fee-related performance goals during the pandemic shows an agency that is not out of the woods yet.

The latest numbers reveal that for a second straight quarter in 2021, the FDA has met its user fee goal dates for 93% of original new drug applications, which compares with 94% and 98% for the previous two quarters in 2020, respectively.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.