Jingwu Zang, I-Mab founder and chairman

#AS­CO21: Ab­b­Vie-part­nered Chi­nese biotech with first-in-class am­bi­tions show­cas­es ear­ly da­ta on CD73 an­ti­body

Weeks af­ter Gilead-part­nered Ar­cus whipped up some cheers from an­a­lysts around its small mol­e­cule CD73 in­hibitor — pre­sent­ing pre­lim­i­nary da­ta at AACR that “ex­ceed­ed ex­pec­ta­tions” — a Chi­nese biotech is un­veil­ing its own ear­ly re­sults us­ing an an­ti­body ap­proach that it says puts more weight be­hind the tar­get.

I-Mab tout­ed a 23% ob­jec­tive re­sponse rate in the US Phase I dose es­ca­la­tion study, among 13 evalu­able pa­tients with sev­er­al dif­fer­ent types of ad­vanced can­cers. All were giv­en a com­bi­na­tion of uliledlimab and Roche’s PD-L1, Tecen­triq.

While it’s still ear­ly, founder and chair­man Jing­wu Zang said the num­bers mark “a very in­ter­est­ing start­ing point for us to build on.”

CD73, he said, has been on top of I-Mab’s tar­get list as it hunts im­muno-on­col­o­gy agents that can help pa­tients who don’t re­spond to check­point in­hibitors. Oth­ers, in­clud­ing As­traZeneca and ORIC, are al­so pur­su­ing it. Be­cause it is part of the im­muno­sup­pres­sive adeno­sine path­way, block­ing it is the­o­rized to turn a cold tu­mor hot, there­by cre­at­ing a bet­ter mi­croen­vi­ron­ment for T cells to kill can­cer.

The com­pa­ny’s claim to fame lies in the crowd­ed CD47 field, where it boasts of a “dif­fer­en­ti­at­ed” an­ti­body that drew Ab­b­Vie in for a $3 bil­lion pact. CD73 is nowhere near­ly as pop­u­lar — Zang counts on­ly five an­ti­bod­ies around the world that’s reached clin­i­cal stage — but I-Mab sim­i­lar­ly be­lieves it has a unique drug on its hands.

In par­tic­u­lar, in­ves­ti­ga­tors re­port­ed no “hook ef­fect” in the Phase I tri­al, mean­ing the an­ti­body po­ten­cy seemed to in­crease pro­por­tion­ate with the dose rather than los­ing in­hi­bi­tion at a high­er dose, an is­sue ob­served with cer­tain oth­er drugs in the class.

“This is not com­plete­ly by de­sign,” Zang said, ex­plain­ing that they had on­ly in­tend­ed to avoid the epi­topes tar­get­ed by oth­ers.

The re­sult­ing an­ti­body ap­pears safe and pleas­ant­ly sur­prised him with the clin­i­cal ac­tiv­i­ty — both in PD-(L)1 treat­ment naïve and re­frac­to­ry cas­es. A pa­tient with ovar­i­an can­cer achieved a com­plete re­sponse, two oth­ers saw a par­tial re­sponse, while an­oth­er three had sta­ble dis­ease.

In­ter­est­ing­ly, in­ves­ti­ga­tors not­ed that the three re­spon­ders were al­so the on­ly ones whose tu­mors had high ex­pres­sion of both CD73 and PD-L1 — bio­mark­ers that I-Mab will like­ly start us­ing to screen and strat­i­fy pa­tients for fu­ture tri­als.

Zang not­ed that they will con­tin­ue mon­i­tor­ing pa­tients this tri­al (there are 20 in to­tal), while al­so test­ing uliledlimab in a Chi­nese Phase II tri­al to­geth­er with Jun­shi’s PD-1 Tuoyi, look­ing at non-small cell lung can­cer as well as oth­er metasta­t­ic can­cers. Oth­er com­bos are on the ta­ble.

Al­though he ac­knowl­edges that Ar­cus’ da­ta — with the first cut sug­gest­ing a 41% ORR — look promis­ing, Zang be­lieves an­ti­bod­ies are bet­ter at pro­vid­ing the per­sis­tent and com­plete in­hi­bi­tion need­ed to shut down a tar­get that’s ex­pressed abun­dant­ly as CD73. The an­swers ul­ti­mate­ly will have to come in fu­ture tri­als.

“We’re mov­ing for­ward with full speed,” he said.

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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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.

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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Fu­ji­film con­tin­ues CD­MO ex­pan­sion, break­ing ground on $435M UK site

Fujifilm’s CDMO arm, Fujifilm Diosynth, has been on a roll this month as the company has recently broken ground on a major project in Europe and it appears to be keeping up the momentum.

Fujifilm Diosynth announced that it has kicked off an expansion project for its microbial manufacturing facility at its campus in the town of Billingham, UK, in the northeast of England.

The 20,000 square-foot, £400 million ($435 million) expansion will add clean rooms, purification suites and a packing area along with more space for the manufacturing itself.