Deaths spur par­tial hold for Xen­cor’s CD3 bis­pe­cif­ic for leukemia, part­nered with No­var­tis in $2.5B deal

Re­searchers at Xen­cor have slammed the brakes on re­cruit­ing more pa­tients for an ear­ly-stage study of XmAb14045, a CD123 x CD3 bis­pe­cif­ic an­ti­body in the race for acute myeloid leukemia. 

The com­pa­ny says that the FDA dropped the hold on them af­ter they tracked 2 deaths in the study that could be linked to the bis­pe­cif­ic — one from cy­tokine re­lease syn­drome and an­oth­er from acute pul­monary ede­ma fol­low­ing sev­er­al dos­es. The CRS case was com­pli­cat­ed by the pa­tient’s de­ci­sion to with­draw from the study, ac­cord­ing to the com­pa­ny.

Bassil Dahiy­at

CD3 bis­pecifics are all the rage these days, in­spir­ing a $2.5 bil­lion deal with No­var­tis back in 2016 that was front­ed with a $150 mil­lion cash pay­ment. That gave the phar­ma gi­ant dibs on XmAb14045 and XmAb13676. Iron­i­cal­ly, No­var­tis opt­ed to hand back rights to XmAb13676 just weeks ago while keep­ing its ties with Xen­cor $XN­CR on ‘14045.

This isn’t the first time a CD123 x CD3 has run in­to a clin­i­cal hold. J&J’s AML study for JNJ-63709178 was put on a full hold by the FDA back in 2016 — though the com­pa­ny wouldn’t say at the time what ad­verse events were in­volved. Macro­Gen­ics, mean­while, had its own par­tial hold to deal with for its B7-H3 × CD3 bis­pe­cif­ic late last year af­ter re­searchers spot­ted signs of liv­ery tox­i­c­i­ty in pa­tients.

Now you can ex­pect plen­ty of more ques­tions about what kind of safe­ty is­sues these bis­pecifics pose as de­vel­op­ers race each oth­er to the fin­ish line. That could be es­pe­cial­ly trou­bling for Xen­cor, par­tic­u­lar­ly af­ter J&J dropped it drug ta­la­co­tuzum­ab (JNJ-56022473/CSL362) for acute myeloid leukemia in 2017. That Phase III drug, orig­i­nal­ly from CSL, us­es Xen­cor’s an­ti­body tech.

Bassil Dahiy­at, pres­i­dent and chief ex­ec­u­tive of­fi­cer at Xen­cor, not­ed this morn­ing: 

“We are work­ing with the in­ves­ti­ga­tors and the FDA and will pro­vide an up­date when more in­for­ma­tion about re­sum­ing en­roll­ment can be shared. Our on­go­ing Phase 1 stud­ies eval­u­at­ing our oth­er CD3 bis­pe­cif­ic an­ti­bod­ies, XmAb13676 and XmAb18087, are not af­fect­ed.”

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Roivant par­lays a $450M chunk of eq­ui­ty in biotech buy­out, grab­bing a com­pu­ta­tion­al group to dri­ve dis­cov­ery work

New Roivant CEO Matt Gline has crafted an all-equity upfront deal to buy out a Boston-based biotech that has been toiling for several years now at building a supercomputing-based computational platform to design new drugs. And he’s adding it to the Erector set of science operations that are being built up to support their network of biotech subsidiaries with an eye to growing the pipeline in a play to create a new kind of pharma company.

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Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

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J&J ad­comm live blog: J&J work­ing on vac­cine for vari­ants, tri­al sched­uled for sum­mer

This week, Moderna announced it would begin testing a modified version of their mRNA vaccine to tackle the vaccine-resistant B1.351 variant that popped up in South Africa. Pfizer said it would test giving people an extra boost of its original vaccine to accomplish the same.

J&J revealed at the adcomm that they, too, have been working on a modified vaccine to tackle emerging variants.

The company didn’t reveal much detail, including how they modified the vaccine or if they were targeting the same B 1.351 variant, but Johan van Hoof said they would begin testing a new construct in the summer. The FDA has said they would allow modified vaccines for variants to be authorized after quick immunological studies that track whether the vaccine elicits antibodies against the new variant.

Genen­tech plots $53M dis­cov­ery quest aimed at spark­ing a 'Holy moly' piv­ot in neu­ro R&D

Genentech has committed $53 million to back a 10-year quest aimed at going back to the drawing board to use new technology and fresh scientific insights to generate a pipeline of drugs for neurological diseases.

Roche’s big South San Francisco hub will mix it up with the scientists drawn together for the Weill Neurohub — formed in 2019 as a joint research partnership involving UCSF, Berkeley and the University of Washington — in an exploration of the field to develop new therapies for some of the toughest diseases in drug R&D: Alzheimer’s, Parkinson’s, Huntington’s, ALS and autism.

Am­gen, As­traZeneca speed to­ward fil­ing next-gen an­ti­body for asth­ma af­ter un­cork­ing full late-stage da­ta

On the hunt for a novel competitor to Sanofi and Regeneron’s Dupixent in severe asthma, Amgen and AstraZeneca posted “exciting” results from their next-gen antibody late last year. Now, the partners are showing their hands, and the results look good enough for approval.

Amgen and AstraZeneca’s tezepelumab plus standard of care cut the rate of severe asthma attacks by 56% at the one-year mark compared with SOC alone, according to full data from the Phase III NAVIGATOR study presented Friday at the virtual American Academy of Allergy, Asthma & Immunology meeting. And those significant results were consistent regardless of patients’ baseline eosinophil counts.

With dust set­tled on ac­tivist at­tack, Lau­rence Coop­er leaves Zio­pharm to a new board

Laurence Cooper has done his part.

In the five years since he left a tenured position at Houston’s MD Anderson Cancer Center to become CEO of Boston-based Ziopharm, he’s steered the small-cap immunotherapy player through patient deaths in trials, clinical holds, short attacks and, most recently, an activist attack on the board.

So when the company has “fantastic news” like an IND clearance for a TCR T cell therapy program, he’s ready to pass on the baton.

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Tal Zaks, Moderna CMO (AP Photo/Rodrique Ngowi, via still image from video)

CMO Tal Zaks bids Mod­er­na a sur­prise adieu as biotech projects $18.4B in rev­enue, plots post-Covid ex­pan­sion

How do you exit a company after six years in style? Developing one of the most lucrative and life-saving products in pharma history is probably not the worst way to go.

Tal Zaks, Moderna’s CMO since 2015, will leave the mRNA biotech in September, the biotech disclosed in their annual report this morning. The company has already retained the recruitment firm Russell Reynolds to find a replacement.

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