Op-ed: What we’re watch­ing close­ly as an un­usu­al #ASH21 kicks off in At­lanta

Re­mem­ber when med­ical meet­ings were live and in per­son?

Kyle Blanken­ship

Step­ping off the plane from Austin in­to this year’s Amer­i­can So­ci­ety of Hema­tol­ogy an­nu­al meet­ing in At­lanta, I can’t help but feel some of the ex­cite­ment and sense of in­tel­lec­tu­al fer­ment we used to feel around the biggest con­fer­ences of the year — but it’s un­de­ni­able this year is dif­fer­ent.

No longer re­strict­ed to a wonky In­ter­net plat­form, #ASH21 has adopt­ed a live-vir­tu­al hy­brid mod­el, and I em­braced the chance to re­turn to my first live meet­ing in rough­ly two years — vaxxed, boost­ed and masked, of course. It’s good to be back, but I, like the rest of the world, am still ad­just­ing to the new nor­mal.

Where be­fore my week­end might be packed with side­bars with bio­phar­ma ex­ec­u­tives shared over luke­warm cups of cof­fee from the me­dia room, quick meet-and-greets with fel­low journos and PR flacks, and wolf­ing down a sand­wich from the buf­fet bar, this year’s event al­ready feels more mut­ed and a lit­tle more somber.

The cof­fee and sand­wich­es still flow freely, and a cou­ple of folks are still brav­ing a short sit­down and in­tro­duc­tion, but most of my calls have al­ready hap­pened this week on the now-fa­mil­iar con­fines of Zoom and Mi­crosoft Teams. So where some of the ex­cite­ment is gone, this meet­ing has al­so giv­en me some time ahead to re­flect on what is still a fas­ci­nat­ing time in hema­tol­ogy.

In con­ver­sa­tion with more than a dozen bio­phar­ma ex­ecs and re­searchers, I’ve com­piled a bit of a self-guide to some of the biggest trends and ab­stracts ex­pect­ed at this year’s #ASH21. Many of the biggest names in this space are cer­tain­ly throw­ing their weight around, but there are still a few un­der­told sto­ries float­ing around out there that are worth watch­ing.

If you’re com­fort­able at home in your PJs or cram­ming your­self in­to sud­den­ly too-small work clothes in At­lanta (pag­ing: me), I hope you en­joy my list of what I’m watch­ing this week­end.

As cur­rent-gen CAR-T scours for more pa­tients, a spate of next-gen drugs vie for a break­through

Ear­li­er to­day, Bris­tol My­ers Squibb and Gilead’s Kite read out com­pet­ing da­ta for their cur­rent-gen CAR-Ts in sec­ond-line B cell lym­phoma as head-to-head chal­lenges to an ug­ly stan­dard of care.

Those read­outs are big news in that they rep­re­sent a big ad­vance for the cur­rent gen­er­a­tion of CAR-Ts — with oner­ous safe­ty pro­files and the weight of the un­known on their shoul­ders — look­ing to break new ground in ear­li­er lines of ther­a­py. And this isn’t the end for those am­bi­tions, ei­ther. Kite is al­so pre­sent­ing more da­ta for Yescar­ta in first-line, high-risk LB­CL pa­tients on Mon­day, which will be some­thing to watch not on­ly for in­ter­me­di­ate ef­fi­ca­cy mark­ers but al­so whether physi­cians will be able to stom­ach a cell ther­a­py so ear­ly in the treat­ment par­a­digm.

That bat­tle may come down to safe­ty, where Bris­tol My­ers’ Breyanzi ap­pears to show a safer pro­file over Kite’s ri­val. Time will tell on whether that gap holds up.

But as the es­tab­lished CAR-Ts duke it out over what could be a siz­able slice of pa­tients and sales, a grow­ing menagerie of biotechs and phar­mas look­ing for break­throughs in next-gen cell ther­a­py for can­cer are al­so loud­ly shop­ping their wares this week­end.

This list runs long and in­cludes some drug­mak­ers that have re­cent­ly made waves. The field has shown some ear­ly ef­fi­ca­cy promise, but con­cerns over dura­bil­i­ty and a cou­ple sur­pris­es in the clin­ic have churned out mixed re­sults, so far. Take Al­lo­gene, for in­stance.

One of the pre­mier names in craft­ing al­lo­gene­ic — or “off-the-shelf” — cell ther­a­pies de­rived from donor cells rather than a pa­tient’s own, Al­lo­gene was re­cent­ly hit with a clin­i­cal hold for its AL­LO-501 pro­gram af­ter some pa­tients re­port­ed chro­mo­so­mal ab­nor­mal­i­ties. The com­pa­ny has an up­date on those Phase I tri­als Mon­day so at least we’ll know whether they were on the right track.

Mean­while, you have a com­pa­ny like Fate, which is read­ing out da­ta on its CAR-NK pro­gram FT596 — ef­fec­tive­ly strap­ping a CAR on­to nat­ur­al-killer cells de­rived from donor stem cells. Ear­li­er this year, Fate turned out da­ta ques­tion­ing the dura­bil­i­ty of that drug de­spite some promis­ing ef­fi­ca­cy num­bers.

All of these sto­ries are part of a greater push in­to the fu­ture of cell ther­a­py — par­tic­u­lar­ly drugs that lever­age the in­nate im­mune sys­tem. It will be in­ter­est­ing to watch how that de­vel­ops.

New an­swers in he­mo­phil­ia

An ab­stract to watch close­ly on Tues­day is Sanofi’s up­date on fi­tusir­an, an siR­NA ther­a­py that si­lences the SER­PINC1 gene lead­ing to he­mo­phil­ia A/B, could prove a game chang­er in treat­ing that hema­to­log­i­cal dis­ease.

Ear­ly da­ta in the Phase III set­ting from this pro­gram showed a whop­ping 90% re­duc­tion in an­nu­al­ize bleed­ing rate, which would like­ly prove to be best-in-class ef­fi­ca­cy if it holds up. Mean­while, the safe­ty pro­file for the drug has shown some hur­dles, par­tic­u­lar­ly on the clot­ting front.

Mean­while, there are a range of po­ten­tial gene ther­a­pies in the works for this pro­gram. Just this week, uniQure read out piv­otal da­ta for its gene ther­a­py en­tranaco­gene deza­parvovec hit­ting its pri­ma­ry non-in­fe­ri­or­i­ty end­point in an­nu­al­ized bleed­ing rate (ABR) af­ter 18 months com­pared to base­line Fac­tor IX pro­phy­lac­tic ther­a­py. Fac­tor IX is a pro­tein that’s nat­u­ral­ly pro­duced in the body to help form blood clots and stop bleed­ing, and com­mon treat­ments to­day are de­signed to re­place the pro­tein to achieve ad­e­quate clot­ting.

It’s worth not­ing that ASH isn’t just a blood can­cer con­fer­ence but a hema­tol­ogy con­fer­ence as well, and this race will prove one to watch.

CD19/20 still dom­i­nates blood can­cer drug de­vel­op­ment, but new tar­gets are catch­ing eye­balls

An­oth­er big late-break­ing ab­stract on Tues­day is an up­date on Roche’s Po­livy, an an­ti­body-drug con­ju­gate tar­get­ing the CD79b pro­tein.

Po­livy is one of a rare group of blood can­cer meds ap­proved to tar­get any­thing but CD19 or CD20, two of the most high­ly val­i­dat­ed tar­gets in can­cer care that have been the back­bone for a range of ap­provals for decades. Roche, with a his­to­ry dri­ving three of the in­dus­try’s most suc­cess­ful can­cer drugs in Avastin, Her­ceptin and Rit­ux­an, knows that CD19/20 will play a big role in the fu­ture but is al­so will­ing to dab­ble in some in­ter­est­ing ex­per­i­ments.

One to watch is an up­date from Roche on com­bi­na­tions of Po­livy with its in­ves­ti­ga­tion­al CD20xCD3 bis­pe­cif­ic an­ti­bod­ies mo­sune­tuzum­ab and glofitimab. There are lots of com­pet­ing bis­pecifics work­ing off those tar­gets, and Roche is get­ting ag­gres­sive in pur­su­ing com­bi­na­tions to get ahead.

Late Fri­day ap­proval; Trio of biotechs wind down; Stem cell pi­o­neer finds new fron­tier; Biotech icon to re­tire; 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.

I hope your weekend is off to a nice start, wherever you are reading this email. As for me, I’m trying to catch the tail of the Lunar New Year festivities.

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Pfiz­er lays off em­ploy­ees at Cal­i­for­nia and Con­necti­cut sites

Pfizer has laid off employees at its La Jolla, CA, and Groton, CT sites, according to multiple LinkedIn posts from former employees.

The Big Pharma confirmed to Endpoints News it has let go of some employees, but a spokesperson declined to specify how many workers were impacted and the exact locations affected. Earlier this month, the drug developer had confirmed to Endpoints it was sharpening its focus and doing away with some early research on areas such as rare disease, oncology and gene therapies.

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Jake Van Naarden, Loxo@Lilly CEO

Lil­ly en­ters ripe BTK field with quick FDA nod in man­tle cell lym­phoma

Eli Lilly has succeeded in its attempt to get the first non-covalent version of Bruton’s tyrosine kinase, or BTK, inhibitors to market, pushing it past rival Merck.

The FDA gave an accelerated nod to Lilly’s daily oral med, to be sold as Jaypirca, for patients with relapsed or refractory mantle cell lymphoma.

The agency’s green light, disclosed by the Indianapolis Big Pharma on Friday afternoon, catapults Lilly into a field dominated by covalent BTK inhibitors, which includes AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeiGene’s Brukinsa.

No­var­tis' ap­proved sick­le cell dis­ease drug fails to beat place­bo in PhI­II

Novartis’ sickle cell drug, approved in 2019 and branded as Adakveo, has failed an ongoing Phase III, according to preliminary results.

The Swiss pharma giant unveiled early data from the ongoing STAND Phase III study on Friday, saying that crizanlizumab showed no statistically significant difference between the drug at two different dose levels compared to placebo in annualized rates of vaso-occlusive crises that lead to a healthcare visit over the first year since being randomized into the trial.

Filip Dubovsky, Novavax CMO

No­vavax gets ready to take an­oth­er shot at Covid vac­cine mar­ket with next sea­son plans

While mRNA took center stage at yesterday’s FDA vaccine advisory committee meeting, Novavax announced its plans to deliver an updated protein-based vaccine based on new guidance.

Vaccines and Related Biological Products Advisory Committee (VRBPAC) members voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all future vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

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FDA ap­proves an­oth­er in­di­ca­tion for Keytru­da, this time in the ad­ju­vant NSCLC set­ting

Merck’s blockbuster cancer treatment Keytruda has been handed another indication by the FDA.

The US regulator announced on Thursday that it has approved Keytruda to serve as an adjuvant treatment for non-small cell lung cancer (NSCLC), which is its fifth indication in NSCLC and 34th indication overall.

According to a Merck release, the approval is based on data from a Phase III trial, dubbed Keynote-091, which measured disease-free survival in patients who received chemotherapy following surgery. The data from Merck displayed that Keytruda cut down on the risk of disease recurrence or death by 27% versus placebo.

Ying Huang, Legend CEO

J&J, Leg­end say Carvyk­ti beat stan­dard ther­a­py in ear­li­er-line blood can­cer

J&J and Legend Biotech’s next step in turning their CAR-T therapy Carvykti into a potential megablockbuster has succeeded, the companies said Friday.

Carvykti achieved the primary endpoint — progression-free survival — in an open-label Phase III study testing the treatment in second- to fourth-line multiple myeloma patients. The CARTITUDE-4 trial, for which there aren’t any hard data yet, represents the biggest development for Carvykti’s ability to compete with Bristol Myers Squibb’s Abecma since its approval last February.

Dutch biotech starts liq­ui­da­tion af­ter end­ing PhI­II in GVHD

A 13-year-old Dutch biotech is going through a liquidation process after an unexpected end to its Phase III trial testing whether its combination of two monoclonal antibodies was superior to Incyte’s Jakafi.

Xenikos had hoped to prove its investigational therapy, named T-Guard, was better than Jakafi at garnering a complete response in patients experiencing life-threatening complications in which new cells from a hematopoietic stem cell transplant begin to fight the body. Jakafi was approved for the indication, steroid-refractory acute graft-versus-host disease, in May 2019.

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Eliot Forster, F-star CEO (Rachel Kiki for Endpoints News)

F-star gets down to the wire with $161M sale to Chi­nese buy­er as na­tion­al se­cu­ri­ty con­cerns linger

With the clock ticking on F-star Therapeutics’ takeover by a Chinese buyer, the companies are still scrambling to remove a hold on the deal from the US government’s Committee on Foreign Investment in the United States.

F-star and invoX Pharma said they are “actively negotiating” with CFIUS “about the terms of a mitigation agreement to address CFIUS’s concerns regarding potential national security risks posed by the transaction.”

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