Samantha Du, Zai Lab CEO

Up­dat­ed: Any­one still look­ing for a CD47? Zai Lab shelves PhI pro­gram af­ter re­view­ing 'com­pet­i­tive land­scape'

Over the past few years, the promise of block­ing CD47 — a “don’t eat me” sig­nal co-opt­ed by can­cer cells — has sent drug­mak­ers big and small in­to a fren­zy. But one biotech is now bow­ing out.

Zai Lab is de­pri­or­i­tiz­ing ZL-1201, its CD47 in­hibitor, scrap­ping plans for a Phase II tri­al. It will now “pur­sue out-li­cens­ing op­por­tu­ni­ties,” the com­pa­ny said in its Q2 up­date. The de­ci­sion was based on a re­view of the com­pet­i­tive land­scape, it added.

Josh Smi­ley

In an in­ter­view with End­points News, Josh Smi­ley — who re­cent­ly joined as COO af­ter an ethics scan­dal forced his res­ig­na­tion from the CFO post at Eli Lil­ly — said giv­en that Gilead is like­ly to move for­ward with ma­grolimab, its fron­trun­ning can­di­date from its Forty Sev­en buy­out, Zai Lab doesn’t see a “best in class” op­por­tu­ni­ty.

“With CD47, our view is it’s a good mol­e­cule,” he said. “So I mean, I think we feel good about what we saw in Phase I, got to a dose se­lec­tion, but I think when we look com­pet­i­tive­ly we don’t see a dif­fer­en­ti­a­tion right now.”

But oth­ers could well have a dif­fer­ent view, he added, and as­sess­ments can change over time.

The move comes as the fever pitch ap­pears to have died down, with clin­i­cal holds on ma­grolimab throw­ing cold wa­ter on the field. Just weeks ago, Ab­b­Vie ter­mi­nat­ed an ex­plorato­ry study of a CD47 drug it got from a $3 bil­lion al­liance with I-Mab, cit­ing “strate­gic rea­sons.” It had test­ed lem­zopar­limab as both monother­a­py or in com­bo with oth­er drugs as a mul­ti­ple myelo­ma treat­ment.

Like oth­er lat­er ef­forts, Zai Lab was fa­mil­iar with the chal­lenges of this space, es­pe­cial­ly on the safe­ty side, go­ing in­to the ZL-1201 pro­gram. As re­searchers wrote in an AACR ab­stract last year:

Block­ade of the CD47/SIR­Pα in­ter­ac­tion us­ing an­ti­bod­ies against CD47 or SIR­Pα-Fc fu­sion pro­teins pro­motes phago­cy­to­sis and tu­mor cell de­struc­tion, which rep­re­sents a promis­ing strat­e­gy for tu­mor im­munother­a­py. How­ev­er, CD47 is ubiq­ui­tous­ly ex­pressed on all cells in­clud­ing ery­thro­cytes and platelets, which form a large an­ti­body sink and lead to po­ten­tial hema­to­log­i­cal tox­i­c­i­ties. In fact, ane­mia and throm­bo­cy­tope­nia have been ob­served in non-hu­man pri­mates and tu­mor pa­tients that are sub­ject­ed to an­ti-CD47 treat­ment in pre­clin­i­cal and clin­i­cal stud­ies.

ZL-1201 was thus “en­gi­neered to re­duce Fc-me­di­at­ed an­ti­body ef­fec­tor func­tion,” and they re­port­ed that it did bind to CD47 while hav­ing a bet­ter safe­ty pro­file than the bench­mark an­ti­body.

The com­pa­ny has a Phase I tri­al test­ing the drug in sol­id tu­mors, and it’s al­ready de­cid­ed on a rec­om­mend­ed Phase II dose.

Smi­ley not­ed that it’s all about “dis­ci­pline” as Zai Lab con­tin­ues to mar­ket in-li­censed drugs in Chi­na and push­es ahead with in­ter­nal as­sets.

“We’ve got a pret­ty rich port­fo­lio,” he said. “So I think as we look at our in­ter­nal as­sets, we’re go­ing to use the same hur­dle for them that we use for every deal that we do.”

The Fac­tors Dri­ving a Rapid Evo­lu­tion of Gene & Cell Ther­a­py and CAR-T Clin­i­cal Re­search in APAC

APAC is the fastest growing region globally for cell & gene therapy trials representing more than a third of all cell & gene studies globally, with China leading in the region. 

APAC is the leading location globally for CAR-T trials with China attracting ~60% of all CAR-T trials globally between 2015-2022. The number of CAR-T trials initiated by Western companies has rapidly increased in recent years (current CAGR of about 60%), with multiple targets being explored including CD19, CD20, CD22, BCMA, CD30, CD123, CD33, CD38, and CD138.

The End­points 11; blue­bird's $3M gene ther­a­py; Bio­gen tout new neu­ro da­ta; Harsh re­views for can­cer drugs; 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.

Reading about John Carroll’s pick of biotech’s most promising startups has become a treasured tradition. If you ever get curious about previous classes of the Endpoints 11, you can find all of them (plus a number of our other regular specials) here.

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EMA warns of short­ages of two Boehringer heart drugs due to a spike in de­mand

The EMA is putting EU member states on alert over the shortage of two drugs that counter heart attacks due to an uptick in demand.

On Friday, the EMA sent out a warning that two Boehringer Ingelheim drugs are experiencing a shortage: Actilyse and Metalyse. The drugs are used as emergency treatments for adults experiencing acute myocardial infarction, or a heart attack, by dissolving blood clots that have formed in the blood vessels.

The End­points 11: The top pri­vate biotechs in pur­suit of new drugs. Push­ing the en­ve­lope with pow­er­ful new tech­nolo­gies

Right around the beginning of the year, we got a close-up look at what happens after a boom ripples through biotech. The crash of life sciences stocks in Q1 was heard around the world.

In the months since, we’ve seen the natural Darwinian down cycle take effect. Reverse mergers made a comeback, with more burned out shells to go public at a time IPOs and road shows are out of favor. And no doubt some of the more recent arrivals on the investing side of the business are finding greener pastures.

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Mene Pangalos (AstraZeneca via YouTube)

As­traZeneca shuts the PhI­II door for Ion­is' PC­SK9 drug de­spite pos­i­tive PhI­Ib

When Ionis and AstraZeneca unveiled the first round of mid-stage data for their antisense PCSK9 drug, Mene Pangalos, AstraZeneca’s EVP of biopharmaceuticals R&D, underscored the drug’s “potential best-in-class efficacy profile.”

But now that the second batch is in, it appears AZD8233 isn’t hitting the mark after all.

Ionis announced Friday morning that although the candidate, also dubbed ION449, met the primary endpoint in the Phase IIb SOLANO trial, its partners at AstraZeneca have decided not to move it into Phase III studies because the “results did not achieve pre-specified efficacy criteria.”

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Up­dat­ed: Bio­gen throws it­self back in­to mud­dled da­ta ar­gu­ments with more de­tails on its an­ti­sense ALS drug

With a highly watched FDA decision deadline coming in late January, Biogen and Ionis dropped the full data on the Phase III study of their ALS drug tofersen in the New England Journal of Medicine on Wednesday.

Biogen is looking for approval for tofersen in a very small subset of ALS patients — some 2%, according to the paper — who have a SOD1 gene mutation, which has previously been linked to ALS. Tofersen is meant to reduce levels of mutant SOD1 proteins.

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As­traZeneca, Mer­ck cull one Lyn­parza in­di­ca­tion in heav­i­ly pre­treat­ed ovar­i­an can­cer pa­tients

Just one day after blockbuster Lynparza got access to another indication in China, its Big Pharma owners have decided to withdraw it in certain patients after reviewing Phase III data.

The two companies that work together on Lynparza decided to recall one of the indications several weeks ago in a specific type of ovarian cancer, Lynparza’s first indication when it was first FDA-approved in 2014. Initial data showed that rates of overall survival in patients with at least three rounds of chemo before getting on the PARP inhibitor were lower than in patients with less previous chemo treatment.

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Solicitor General Elizabeth Prelogar

Should SCO­TUS hear Am­gen's Repatha case? So­lic­i­tor gen­er­al says no

Back in April, Amgen said it was encouraged by the solicitor general’s anticipated review of its Supreme Court petition to rehear a Repatha patent case. They’re likely much less optimistic about the outcome now.

Solicitor General Elizabeth Prelogar wrote in a recent 27-page brief that Amgen’s arguments “lack merit and further review is not warranted.”

The case traces back to a suit filed in 2014 against Sanofi and Regeneron’s Praluent, which ended up beating Amgen’s PCSK9 blockbuster Repatha to market by a month just a year later.

Phil Sharp, Nobel Prize laureate (L), and John Carroll, Endpoints News co-CEO (via Michael Last)

The End­points 11: Fire­side chat with No­bel Prize lau­re­ate Phil Sharp

On Thursday evening in Boston I had the great good fortune to talk about the creation of the biotech industry with Nobel Prize-winning scientist Phil Sharp. I learned quite a bit about the early days of Genentech, Biogen and Alnylam, which all helped birth this unusual drug development ecosystem. And that’s why we can do things like the Endpoints 11. Here’s my talk with Phil Sharp, which you can either watch or read below.

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