Ali Tehrani, Zymeworks CEO

Zymeworks squares up with Her­ceptin af­ter HER2 bis­pe­cif­ic aces mid-stage test in esophageal can­cer

Roche’s Her­ceptin has long stood as stan­dard of care across mul­ti­ple ad­vanced can­cers, but a suite of next-gen play­ers are look­ing to beat the ag­ing gi­ant at its own game. In HER2-ex­press­ing esophageal can­cer, BeiGene part­ner Zymeworks thinks its bis­pe­cif­ic an­ti­body could have the juice to get it done.

Zymeworks’ bis­pe­cif­ic an­ti­body zanidatam­ab, com­bined with one of two chemother­a­py reg­i­mens, post­ed an over­all re­sponse rate of 75% in pa­tients with ad­vanced gas­troe­sophageal ade­no­car­ci­no­ma (GEA) who had not pre­vi­ous­ly re­ceived a HER2-tar­get­ed can­cer ther­a­py, the Van­cou­ver-based biotech said Thurs­day.

The re­sults from the Phase II study are set to be pre­sent­ed at this week­end’s #ES­MO21 and look to set the bat­tle lines be­tween Zymeworks and part­ner BeiGene and Her­ceptin, the long­time stan­dard of care in first-line ad­vanced esophageal can­cer.

Zymeworks in­tends to pur­sue a Phase III study based on these re­sults look­ing in par­tic­u­lar at the com­bi­na­tion of zanidatam­ab and the chemo reg­i­men known as CAPOX/FP. That com­bo post­ed a re­sponse rate of 93% in the Phase II study, which the part­ners see as a po­ten­tial strong con­tender against Her­ceptin in this set­ting for the first time in years.

Mean­while, the me­di­an du­ra­tion of re­sponse was 16.4 months with a me­di­an pro­gres­sion-free sur­vival of one year across all pa­tients, Zymeworks said. At the cut­off, 61% of pa­tients were still in the study.

Zymeworks thinks those ef­fi­ca­cy and dura­bil­i­ty da­ta stack up well against what Her­ceptin has shown in its own tri­als. In the Phase III TO­GA tri­al, Her­ceptin plus chemo post­ed a 47.3% re­sponse rate in gas­tric or gas­troe­sophageal junc­tion can­cers with a me­di­an PFS of around 7 months. Those re­sults would ap­pear to give zanidatam­ab the clear lead, but it’s im­por­tant to note the da­ta in Zymeworks’ open-la­bel study were not pow­ered for ef­fi­ca­cy and the pool was fair­ly small — 36 pa­tients to­tal and 28 evalu­able. A Phase III test, how­ev­er, will put those re­sults to the test.

That planned study, dubbed HER­I­ZON-GEA-01, is set to open in the fourth quar­ter, and will test the zanidatam­ab-CAPOX com­bo with or with­out No­var­tis and BeiGene’s PD-1 in­hibitor tislelizum­ab in a head-to-head matchup with the Her­ceptin-chemo stan­dard of care in first-line ad­vanced GEA.

Mean­while, Zymeworks is al­so keep­ing an eye on evolv­ing stan­dard of care in this set­ting, with Mer­ck and Roche’s col­lab­o­ra­tion on Keytru­da plus Her­ceptin plus chemo in first-line esophageal can­cer in the KEYNOTE-811 study cur­rent­ly on­go­ing. Zymeworks has its own Phase II study look­ing at zanidatam­ab plus chemo and PD-1 to keep up, but thinks its da­ta with or with­out PD-1 can stack up well.

The rise of bis­pe­cif­ic an­ti­bod­ies, an old-school drug con­cept that has on­ly re­cent­ly caught on with the FDA, has raised the prospect of chal­leng­ing long-stand­ing stan­dards of care in ad­vanced can­cers, and zanidatam­ab’s case is no dif­fer­ent. The drug, known as a “HER2xHER2” bis­pe­cif­ic, works by si­mul­ta­ne­ous­ly bind­ing two non-over­lap­ping HER2 epi­topes — ECD2 and ECD4 — ef­fec­tive­ly of­fer­ing a dou­ble down ap­proach to tar­get­ing that well-known tu­mor tar­get.

Zymeworks thinks zanidatam­ab could have a par­tic­u­lar­ly strong ef­fect in HER2 over­ex­pressers, which make up just 20% of ad­vanced GAE pa­tients.

Back in No­vem­ber, the FDA of­fered a break­through des­ig­na­tion for the drug in pre­vi­ous­ly-treat­ed HER2 gene-am­pli­fied bil­iary tract can­cer based on the strength of its Phase I da­ta.

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.

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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Covid-19 vac­cine boost­ers earn big thumbs up, but Mod­er­na draws ire over world sup­ply; What's next for Mer­ck’s Covid pill?; The C-suite view on biotech; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

You may remember that at the beginning of this year, Endpoints News set a goal to go broader and deeper. We are still working towards that, and are excited to share that Beth Snyder Bulik will be joining us on Monday to cover all things pharma marketing. You can sign up for her weekly Endpoints MarketingRx newsletter in your reader profile.

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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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Amit Etkin, Alto Neuroscience CEO (Alto via Vimeo)

A star Stan­ford pro­fes­sor leaves his lab for a start­up out to re­make psy­chi­a­try

About five years ago, Amit Etkin had a breakthrough.

The Stanford neurologist, a soft-spoken demi-prodigy who became a professor while still a resident, had been obsessed for a decade with how to better define psychiatric disorders. Drugs for depression or bipolar disorder didn’t work for many patients with the conditions, and he suspected the reason was how traditional diagnoses didn’t actually get at the heart of what was going on in a patient’s brain.

Roche's Tecen­triq cross­es the fin­ish line first in ad­ju­vant lung can­cer, po­ten­tial­ly kick­ing off gold rush

While falling behind the biggest PD-(L)1 drugs in terms of sales, Roche has looked to carve out a space for its Tecentriq with a growing expertise in lung cancer. The drug will now take an early lead in the sought-after adjuvant setting — but competitors are on the way.

The FDA on Friday approved Tecentriq as an adjuvant therapy for patients with Stage II-IIIA non small cell lung cancer with PD-(L)1 scores greater than or equal to 1, making it the first drug of its kind approved in an early setting that covers around 40% of all NSCLC patients.

Rahul Singhvi, Resilience CEO

A Bob Nelsen start­up turns to Har­vard to help sharp­en its tech, in­spir­ing first spin­out

One of Bob Nelsen’s latest projects is headed to Harvard.

Resilience, a company started with the goal of establishing itself as a “one-stop-shop” for companies looking to scale manufacturing, including for hard-to-develop cell and gene therapies, is less than a year old. Friday, it announced a five-year R&D deal with Harvard University that includes $30 million to develop biologics, including vaccines, nucleic acids and cell and gene therapies.

Susan Galbraith speaking at Endpoints News' virtual EUBIO21 summit

Imfinzi/treme­li­mum­ab com­bo scores As­traZeneca an­oth­er OS win — this time in liv­er can­cer

Is the tide turning on AstraZeneca’s battered PD-L1/CTLA4 combo?

A single priming dose of the experimental tremelimumab, followed by Imfinzi every four weeks, beat Nexavar (sorafenib) in helping a group of liver cancer patients live longer in a Phase III study, the company reported, meeting the primary endpoint.

Specifically, the two drugs extended overall survival for patients with unresectable hepatocellular carcinoma who had not received prior systemic therapy and were not eligible for localized treatment.

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FDA+ roundup: Marks on Wood­cock­'s tenure as act­ing com­mis­sion­er; FDA lead­ers of­fer per­spec­tive on bar­ri­ers to di­ver­si­ty in re­search

CBER director Peter Marks praised Janet Woodcock’s work as acting FDA commissioner, and while noting that Biden needs to nominate someone to fill the role permanently by Nov. 16, he said he has “no idea” when that actually might occur.

“Dr. Woodcock has been at the agency for over three decades and she, during that time, has proven herself to be a remarkably capable manager,” Marks said at the Alliance for Regenerative Medicine’s meeting Tuesday. “And she’s been managing as if she’s commissioner, unlike some previous acting [commissioners] who are afraid to actually do things. She doesn’t appear to be afraid to do things. I have not felt any different now from when we had a commissioner in place,” he added.

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