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.

Adap­tive De­sign Meth­ods Of­fer Rapid, Seam­less Tran­si­tion Be­tween Study Phas­es in Rare Can­cer Tri­als

Rare cancers account for 22 percent of cancer diagnoses worldwide, yet there is no universally accepted definition for a “rare” cancer. Moreover, with the evolution of genomics and associated changes in categorizing tumors, some common cancers are now characterized into groups of rare cancers, each with a unique implication for patient management and therapy.

Adaptive designs, which allow for prospectively planned modifications to study design based on accumulating data from subjects in the trial, can be used to optimize rare oncology trials (see Figure 1). Adaptive design studies may include multiple cohorts and multiple tumor types. In addition, numerous adaptation methods may be used in a single trial and may facilitate a more rapid, seamless transition between study phases.

Marianne De Backer (L) and Jeff Hatfield

Bay­er nabs star biotech Vi­vid­ion with a $2B buy­out and an ‘arms-length’ pact, pulling a part­ner out of the IPO con­ga line

Vividion is canceling that IPO it filed. Instead of following the industry-wide migration to Nasdaq, the biotech that has captured considerable attention for its still-preclinical work finding cryptic pockets to bind to on proteins is going to work for Bayer now.

The pharma giant is putting out word today that it has bought out Vividion for $1.5 billion in cash and another half-billion dollars in milestones.

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Josh Hoffman, outgoing Zymergen CEO (Zymergen)

UP­DAT­ED: Syn­bio uni­corn Zymer­gen jet­ti­sons found­ing CEO, cuts guid­ance as cus­tomers re­port lead prod­uct does­n't work

Zymergen, just months off a $500 million IPO that put the synthetic bio firm in rarified air, has now ejected its founding CEO and downgraded its revenue forecasts after customers reported its lead film product doesn’t work as advertised, the company said Tuesday afternoon.

CEO Josh Hoffman will leave his role and sacrifice his board seat immediately in favor of Jay Flatley, the former CEO of Illumina who will take the lead role on an interim basis as the company conducts a search for its next leader.

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Nader Pourhassan, CytoDyn CEO (Photo by Jeff Kravitz/FilmMagic for CytoDyn’s Pro)

Cy­to­Dyn faces DOJ, SEC sub­poe­nas af­ter pro­mot­ing failed Covid-19 drug

The little, PR-happy drug company publicly called out by the FDA is now getting attention from both the SEC and the Department of Justice.

CytoDyn, a one-time penny stock that has gained both money and notoriety for aggressively pushing an old HIV drug as a treatment for Covid-19, disclosed in a regulatory filing Friday the SEC and DOJ have separately subpoenaed the company and “certain of its executives” as part of investigations into the company’s promotion and marketing practices.

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Zymergen co-founders Zach Serber, Josh Hoffman, and Jed Dean (Zymergen via website)

Zymer­gen's sud­den im­plo­sion shocked biotech. A lin­ger­ing loan could make things even worse

As former synbio unicorn Zymergen picks up the pieces from its spectacular implosion Tuesday, an outstanding loan from Perceptive Advisors — the only blue-chip biotech crossover investor to touch Zymergen’s fundraising efforts — could make the situation worse, according to public documents.

In December 2019, more than a year before Zymergen filed for what would eventually become a $500 million IPO, the “biofacturing” firm signed a $100 million credit facility with Perceptive to help supplement the nearly $700 million the company had raised across four VC rounds.

Lan Huang, BeyondSpring CEO

Shares of Be­yond­Spring sky­rock­et on new, pos­i­tive can­cer drug tri­al re­sults

Sometimes results come along that shock even a biotech’s believers.

On Wednesday, BeyondSpring, a small New York biotech with an offbeat approach to immunotherapy, announced its lead drug significantly extended non-small cell lung cancer patients’ lives in a large trial. Although the company did not release the exact survival data, it said that nearly twice as many patients were alive after two years on the drug arm than on the standard-of-care arm.

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Pfiz­er puts the pres­sure on Eli Lil­ly's JAK in­hibitor Olu­mi­ant with new da­ta in alope­cia area­ta

As Eli Lilly looks to secure a win for its blockbuster Olumiant in alopecia areata, going where no JAK inhibitor has gone before, Pfizer is coming up from behind with Phase IIb/III results suggesting its own candidate can help regrow hair lost due to the autoimmune disease.

On Wednesday, Pfizer unveiled topline results from the ALLEGRO trial, which enrolled 718 patients 12 years and older with alopecia areata, a condition that can cause sudden, severe and patchy hair loss. While the patients’ episodes of alopecia areata varied in length, they all had one thing in common: They had lost at least half the hair on their scalps.

Bio­gen, Ei­sai are push­ing for an­oth­er ac­cel­er­at­ed Alzheimer's OK — this time for BAN2401

Now that the door at the FDA has been opened wide for Alzheimer’s drugs that can demonstrate a reduction in amyloid, Biogen and its partners at Eisai are pushing for a quick OK on the next drug to follow in the controversial path of aducanumab.

In a presentation to analysts, Eisai neurology chief Ivan Cheung outlined some bullish expectations for their newly-approved treatment and set the stage for what he believes will be a fast follow for BAN2401 (lecanemab) — after a dry spell in new drug development that’s lasted close to 20 years.

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Samantha Du, Zai Lab CEO (Zai Lab)

Saman­tha Du's Zai Lab inks sur­pris­ing re­search col­lab with Schrödinger for DNA dam­age drug

Headed by Samantha Du, Chinese oncology specialist Zai Lab has made no qualms about its aggressive in-licensing strategy to drive Western drugs into regional markets. That strategy has been profitable so far, but that doesn’t mean Du’s team isn’t willing to try something new.

In a surprising volte-face, Zai Lab has signed its name to a research collaboration with physics-based discovery outfit Schrödinger looking for an oncology candidate targeting the DNA damage repair pathway, the partners said Wednesday.