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.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

UP­DAT­ED: Boehringer nabs FDA's first in­ter­change­abil­i­ty des­ig­na­tion for its Hu­mi­ra com­peti­tor — but will it mat­ter?

The FDA late Friday awarded Boehringer Ingelheim the first interchangeability designation for its Humira biosimilar Cyltezo, meaning that when it launches in July 2023, pharmacists will be able to automatically substitute the Boehringer’s version for AbbVie’s mega-blockbuster without a doctor’s input.

The designation will likely give Boehringer, which first won approval for Cyltezo in 2017, the leg up on a crowded field of Humira competitors.

Bio­gen hit by ALS set­back with PhI­II fail­ure for tofersen — but fol­lows a fa­mil­iar strat­e­gy high­light­ing the pos­i­tive

Patients and analysts waiting to hear Sunday how Biogen’s SOD1-ALS drug tofersen fared in Phase III didn’t have to wait long for the top-line result they were all waiting for. The drug failed the primary endpoint on significantly improving the functional and neurologic decline of patients over 28 weeks as well as the extension period for continued observation.

In fact, there was very little difference in response.

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Reshma Kewalramani, Vertex CEO (YouTube)

Ver­tex gets much-need­ed win with ‘ex­tra­or­di­nary’ first pa­tient re­sults on po­ten­tial di­a­betes cure

Vertex said Monday that the first patient dosed with its cell therapy for type 1 diabetes saw their need for insulin injections vanish almost entirely, a key early step in the decades-long effort to develop a curative treatment for the chronic disease.

The patient, who had suffered five potentially life-threatening hypoglycemic — or low blood sugar — episodes in the year before the therapy, was injected with synthetic insulin-producing cells. After 90 days, the patient’s new cells produced insulin steadily and ramped up their insulin production after a meal like normal cells do, as measured by a standard biomarker for insulin production.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'


Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

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Jeffrey Nau, Oyster Point Pharma CEO

FDA OKs an in­haled ver­sion of smok­ing ces­sa­tion drug Chan­tix — for a com­mon eye dis­ease

Oyster Point Pharma now has its first FDA-approved product — Tyrvaya. And the biotech has taken a unique route to get there by using an old drug with a storied past.

The New Jersey biotech announced this morning that the FDA has approved their nasal spray product for dry eye disease on Friday — the first nasal spray to be approved for the disease. The product’s active ingredient is 0.03 mg of varenicline, also known as smoking cessation aid Chantix.

Sheldon Koenig, Esperion CEO

Es­pe­ri­on gets out the bud­get ax, chop­ping 170 staffers as its big drug launch sput­ters

Esperion’s executive team spent years insisting that they had found the sweet spot in the market for their cholesterol drug. But that strategy has soured badly, and after struggling to sell its heart disease pill for more than a year, the biotech says it will cut about 40% of its staff over the next few weeks.

The layoffs will take place across the board, from sales and marketing to R&D, CEO Sheldon Koenig told Endpoints News on Monday. While the chief executive declined to elaborate on how many employees will be affected, an SEC filing stated that approximately 170 staffers are on the chopping block.

Two drug­mak­ers hit with PDU­FA date de­lays from FDA amid back­log of in­spec­tions

As the FDA is weighed down with more and more pandemic responsibilities, the agency is beginning to miss PDUFA dates with more frequency too. Two different companies on Monday said they received notices that the FDA has not completed their drug reviews on time.

The review of an NDA for Avadel Pharmaceuticals’ candidate treatment for narcolepsy is not coming this month, the company said, and the review of UCB’s BLA for bimekizumab, used to treat moderate to severe plaque psoriasis, will miss its target date as well.

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