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.”

Grow­ing ac­cep­tance of ac­cel­er­at­ed path­ways for nov­el treat­ments: but does reg­u­la­to­ry ap­proval lead to com­mer­cial suc­cess?

By Mwango Kashoki, MD, MPH, Vice President-Technical, and Richard Macaulay, Senior Director, of Parexel Regulatory & Access

In recent years, we’ve seen a significant uptake in the use of regulatory options by companies looking to accelerate the journey of life-saving drugs to market. In 2018, 73% of the novel drugs approved by the U.S. Federal Drug Administration (FDA) were designated under one or more expedited development program categories (Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval).ᶦ

Sanofi out­lines big API plans as coro­n­avirus out­break re­port­ed­ly threat­ens short­age of 150 drugs

As the world becomes increasingly dependant on Asia for the ingredients of its medicines, Sanofi sees business to be done in Europe.

The French drugmaker said it’s creating the world’s second largest active pharmaceutical ingredients (API) manufacturer by spinning out its six current sites into a standalone company: Brindisi (Italy), Frankfurt Chemistry (Germany), Haverhill (UK), St Aubin les Elbeuf (France), Újpest (Hungary) and Vertolaye (France). They have mapped out €1 billion in expected sales by 2022 and 3,100 employees for the new operations headquartered in France.

Mickey Kertesz, KidsandArtOrg via YouTube

Soft­Bank's newest, $165M biotech in­vest­ment looks for in­fec­tious traces in the blood

SoftBank has found its newest biotech investment.

The Japanese bank has invested $165 million into Karius, a company that uses blood tests to diagnose infectious diseases, as part of its new Vision Fund 2. The full scope of the new fund has yet to be announced, but the first and newly-beleaguered Vision Fund poured $100 billion into technology companies, including the biotechs Vir Biotechnology and Roivant and the sequencing company 10x Genomics.

UP­DAT­ED: NGM Bio takes leap for­ward in crowd­ed NASH field

South San Francisco-based NGM Bio may have underwhelmed with its interim analysis of a key cohort from a mid-stage NASH study last fall — but stellar topline data unveiled on Monday showed the compound induced significant signs of antifibrotic activity, NASH resolution and liver fat reduction, sending the company’s stock soaring.

There are an estimated 50+ companies focused on developing drugs for non-alcoholic steatohepatitis, or NASH, a common liver disease that has long flummoxed researchers. The first wave of NASH drug developers struggled with efficacy as well as safety — and companies big and small have crashed and burned.

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Methicillin-resistant Staph aureus (Shutterstock)

FDA grants ‘break­through’ sta­tus to an­tibi­ot­ic al­ter­na­tive as Con­tra­Fect rush­es to join fight against su­per­bug

An experimental drug that promises to be the first anti-infective agent to prove superior to vancomycin — an antibiotic approved in 1958 — has notched the FDA’s “breakthrough” status.

ContraFect said the designation was based on Phase II data in which exebacase was tested against a superbug known as methicillin-resistant Staph aureus, or MRSA. In a subgroup analysis, the clinical responder rate at day 14 was 42.8% higher than that among those treated with standard of care, the company said (p=0.010).

Zhong Nanshan, CGTN via YouTube

Har­vard joins coro­n­avirus fight with $115 mil­lion and a high-pro­file Chi­nese part­ner

For two months, as the novel coronavirus swelled from a few early cases tied to a Wuhan market to a global epidemic, most of the world’s focus and dollars have flowed toward emergency initiatives: building vaccines at a record pace, plucking experimental antivirals out of freezers to see what sticks and immunizing mice for new antibodies.

Now a new and well-funded collaboration between Harvard and a top Chinese research institute will play the long game. In a 5-year, $115 million initiative backed by China Evergrande Group, researchers from the Harvard Medical School, Harvard T.H. Chan School of Public Health and Guangzhou Institute for Respiratory Health will study the virus in an effort to develop therapies against infections by the novel coronavirus, known as SARS–CoV-2, and to prevent new ones.

No­var­tis gets a boost in block­buster mul­ti­ple scle­ro­sis race with Roche

In the first step of what’s likely to be a long and uphill battle for the drugmaker, the FDA has accepted Novartis’s BLA submission for a new multiple sclerosis drug and given it priority review. The PDUFA date for the potential blockbuster drug is in June.

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Juergen Horn

An­i­mal health vet Juer­gen Horn makes new an­ti­body play for pets, rak­ing $15M in Se­ries A haul

Zoetis forked over $85 million in 2017 to acquire Nexvet Biopharma and its pipeline of monoclonal antibodies. Juergen Horn, Nexvet’s former chief product development officer, has now secured $15 million for his own biologic company for animals: Invetx.

Buoyed by emerging advances in gene therapies for humans, scientists have started looking at harnessing the technology for animals setting up companies such as Penn-partnered Scout Bio and George Church-founded Rejuvenate Bio. But akin to Nexvet, Invetx is working on leveraging the time-tested science of monoclonal antibodies to treat chronic diseases that afflict man’s best friend.

As coro­n­avirus out­break reach­es 'tip­ping point,' GSK lends ad­ju­vant tech to Chi­nese part­ner armed with pre­clin­i­cal vac­cine

As the coronavirus originating out of Wuhan spreads to South Korea, Italy and Iran, stoking already intense fears of a pandemic, GlaxoSmithKline has found another pair of trusted hands to place its adjuvant system. China’s Clover Biopharmaceuticals will add the adjuvant to its preclinical, protein-based vaccine candidate against SARS-CoV-2.

Clover, which is based in the inland city of Chengdu, boasts of a platform dubbed Trimer-Tag that produces covalently-trimerized fusion proteins. Its candidate, COVID-19 S-Trimer, resembles the viral spike (S)-protein found in the virus.