Hop­ing to chal­lenge block­buster breast can­cer fran­chis­es, a small Dutch biotech says its ADC passed a PhI­II test

For the last sev­er­al years, an un­der-the-radar chal­lenger to Big Phar­ma’s breast can­cer fran­chis­es has been work­ing on an an­ti­body drug con­ju­gate in­volv­ing Her­ceptin. On Tues­day, the Dutch biotech re­vealed the pro­gram had met its pri­ma­ry end­point in a Phase III study, and they say they’re ready to make a deal.

Byondis’ ADC, com­bin­ing Her­ceptin with the ex­per­i­men­tal drug duo­car­mazine, reached its goal of a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment of pro­gres­sion-free sur­vival over physi­cian’s choice, the biotech said ear­ly Tues­day. None of the da­ta were re­vealed in the topline re­sults, but Byondis not­ed it plans to sub­mit its pitch to the FDA by the end of the year.

The biotech stayed mum on the sec­ondary end­points as well, which in­clud­ed over­all sur­vival, ob­jec­tive re­sponse rate, in­ves­ti­ga­tor-as­sessed PFS, pa­tient re­port­ed out­comes and safe­ty and tol­er­a­bil­i­ty.

For­mer­ly known as Syn­thon Bio­phar­ma­ceu­ti­cals, a sub­sidiary of Syn­thon in the Nether­lands, Byondis re­brand­ed in April 2020 af­ter a British pri­vate eq­ui­ty firm bought out its hold­ing com­pa­ny in No­vem­ber 2019. The founder of the sub­sidiary elect­ed to spin out as its own op­er­a­tion, and com­plet­ed its re­launch soon af­ter.

Their pro­gram, of­fi­cial­ly clas­si­fied as [vic-]trastuzum­ab duo­car­mazine, works sim­i­lar­ly to tar­get­ed chemother­a­py treat­ments, Byondis said. Af­ter bind­ing to HER2 on can­cer cells, it ac­ti­vates the nec­es­sary cy­to­tox­in to po­ten­tial­ly in­duce tu­mor cell death. The com­pa­ny says if the cy­to­tox­in is ac­ci­den­tal­ly re­leased ear­ly, it “rapid­ly self-de­struc­ts” to lim­it sys­temic tox­i­c­i­ty.

That as­pect of the ADC is de­rived from the fam­i­ly of syn­thet­ic duo­carmycin, first iso­lat­ed from Strep­to­myces bac­te­ria in the 1970s.

If every­thing goes as planned, Byondis will sit along­side the ranks of oth­er Her­ceptin-based AD­Cs that have made their way in­to the mar­ket­place. As­traZeneca’s En­her­tu fol­lows a sim­i­lar mod­el as does Roche’s Kad­cy­la, which was the first ADC ap­proved to tar­get HER2-pos­i­tive metasta­t­ic breast can­cer.

And Byondis has been here be­fore, hav­ing pre­vi­ous­ly sold a Her­ceptin biosim­i­lar to Am­gen back in 2012.

Tues­day’s re­sults come from a Phase III study that en­rolled 436 breast can­cer pa­tients who had failed at least two lines of HER2-tar­get­ing ther­a­pies or pro­gressed on Kad­cy­la. Pa­tients were ran­dom­ized to the ex­per­i­men­tal drug arm at a 2-to-1 ra­tio and re­ceived treat­ments un­til dis­ease pro­gres­sion or un­ac­cept­able tox­i­c­i­ty.

Byondis is al­so test­ing the can­di­date in four oth­er clin­i­cal stud­ies, in­clud­ing a Phase II in HER2-ex­press­ing re­cur­rent, ad­vanced or metasta­t­ic en­dome­tri­al can­cer and a Phase I in com­bi­na­tion with Glax­o­SmithK­line’s Ze­ju­la in HER2-ex­press­ing lo­cal­ly ad­vanced or metasta­t­ic sol­id tu­mors.

So­cial: Mar­co Tim­mers, Byondis CEO

In­side Track: Be­hind the Scenes of a Ma­jor Biotech SPAC

Dr. David Hung and Michelle Doig are no strangers to the SPAC phenomenon. As Founder and CEO of Nuvation Bio, a biotech company tackling some of the greatest unmet needs in oncology, Dr. Hung recently took the company public in one of this year’s biggest SPAC related deals. And as Partner at Omega Funds, Doig not only led and syndicated Nuvation Bio’s Series A, but is now also President of the newly formed, Omega-sponsored, Omega Alpha SPAC (Nasdaq: OMEG; oversubscribed $138m IPO priced January 6, 2021).

Barry Greene, Sage CEO

UP­DAT­ED: Sage's sec­ond chance at de­pres­sion hits the PhI­II pri­ma­ry, but ques­tions re­main over dura­bil­i­ty, side ef­fects

Looking to make a comeback after a big Phase III flop, Sage Therapeutics revealed data they believe could change the entire depression treatment landscape, given the vast array of failures in the field. But some results are spooking investors, sending Sage $SAGE shares down early Tuesday.

First, the primary: Sage and Biogen reported Phase III data for once-daily zuranolone Tuesday morning, saying the experimental drug hit its primary endpoint by spurring a statistically significant change from baseline in the 17-item Hamilton Rating Scale for Depression total score. After 15 days, patients in the drug arm saw an average change of -14.1 points, compared to -12.3 on placebo.

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In a first, Re­gen­eron's an­ti­body cock­tail re­duces deaths for a sub­group of hos­pi­tal­ized Covid-19 pa­tients

Scientists have come up with the first evidence that Regeneron’s antibody cocktail, which has so far only been authorized for the outpatient setting, may reduce deaths of hospitalized Covid-19 patients — albeit only a subset.

The combination of casirivimab and imdevimab is the subject of the latest data cut from RECOVERY, the large-scale UK-based trial testing a variety of potential treatments. In total, 9,785 patients hospitalized with Covid-19 were enrolled in this arm of the study and were randomly assigned to receive either usual care plus the intravenous combo or usual care alone.

Janet Woodcock, acting FDA commissioner (Al Drago/Bloomberg via Getty Images)

New Alzheimer's drug ap­proval fall­out: Pub­lic Cit­i­zen seeks re­moval of FDA's Wood­cock, Cavaz­zoni and Dunn

As Capitol Hill begins to wake up to the financial and scientific mess behind the FDA’s approval of Biogen’s new controversial Alzheimer’s drug Aduhelm, nonprofit watchdog Public Citizen is now calling for the top three FDA officials who are responsible to be removed from their positions.

In a letter to HHS Secretary Xavier Becerra on Wednesday, the group highlighted the “litany of flaws” in the FDA’s approval of the new drug, including the “unprecedented, inappropriately close” collaboration between the FDA and Biogen in the analysis of key trial data, basing approval on an unvalidated surrogate endpoint, not following the advice of its expert advisory committee (3 members of which have since resigned), and the wide label that the agency granted.

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Bio­gen sig­nals a big PhI­II fail­ure as the lead gene ther­a­py in their $800M Night­star buy­out goes down in flames

That $800 million buyout of Nightstar has turned into a bust for Biogen as the lead therapy in the deal failed a pivotal study, signaling a severe setback for the biotech’s ambitions in gene therapies.

The big biotech put out the word after the market closed on Monday that the gene therapy they picked up in the deal for a degenerative blindness called choroideremia failed the Phase III study, just a month after their #2 drug in the deal also flopped in a mid-stage study.

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CEO Harith Rajagopalan (Fractyl)

Af­ter a decade in the type 2 di­a­betes game, Fractyl Lab­o­ra­to­ries recharges with a fresh $100M and a new name

Harith Rajagopalan compared the way type 2 diabetes is managed to sticking your fingers in a dam that’s leaking from a number of places.

You can take drugs to lower your blood sugar, cholesterol, or blood pressure, but you’re not addressing what he says is the core issue — the metabolic abnormality that causes the disease.

“We’re so busy plugging the holes in the dam, we don’t have time to see that the whole infrastructure is at risk,” he said. “That infrastructure is a full-body systemic metabolic abnormality called metabolic syndrome, that we’re ignoring while we’re so busy trying to treat all of the individual symptoms of the condition.”

Michel Sade­lain puts his name and new cell en­gi­neer­ing tech be­hind 'ag­nos­tic' CAR-T start­up chas­ing epi­ge­net­ic anti­gens

It felt natural for Alain Maiore and Sebastian Amigorena to bring in Michel Sadelain as a co-founder of Mnemo Therapeutics. A CAR-T pioneer, Sadelain had been involved as an advisor since the early days — enthusiastic about Amigorena’s work in a genetic knockout that could enhance T cell memory and a new class of potential targets he’s discovered — and could introduce some well-known technologies to the toolbox. So they got the initial cash from Sofinnova Partners to plant roots in Paris and New York in early 2019; within a few months, they began to see more clearly just what the antigen discovery platform might unlock.

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Geoffrey Porges, SVB Leerink

Top an­a­lyst maps a rocky road for Ver­tex — un­less they adopt a $10B M&A cam­paign to save the pipeline

After repeatedly poking Vertex $VRTX execs with pointed criticism of their R&D strategy, top SVB Leerink analyst Geoffrey Porges is now turning up the heat to a full-scale roasting.

In a note out early Monday morning, Porges spotlights the impact of Vertex’s recent follow-up failure on AATD — their treatment hit the endpoint but missed on commercial prospects — rewriting his recommended scenario for CEO Reshma Kewalramani as she grapples with the setback.

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Lynn Fitch, Mississippi Attorney General (Rogelio V. Solis/AP Images)

Mis­sis­sip­pi sues Eli Lil­ly, Sanofi and No­vo over in­sulin prices as in­ter­change­able biosim­i­lars may ar­rive soon

Mississippi Attorney General Lynn Fitch last week sued the top three insulin manufacturers, which collectively cover almost the entire US insulin market, alleging that they’ve colluded to raise their prices in lockstep, and in some cases by more than 1,000% for drugs that are decades old.

“Because of Manufacturer Defendants’ collusive price increases, nearly a century after the discovery of insulin, diabetes medications have become unaffordable for many diabetics,” the lawsuit says.

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