I-Mab —A Biotech on the Rise with In­spired Sci­ence

For Dr. Jer­ry Zhengyi Wang the jour­ney to dis­cov­ery start­ed with a quest for a new way to lever­age the im­mune sys­tem against can­cer. His ba­sic re­search on the role of macrophages in the an­ti-tu­mor im­mu­ni­ty led him to CD47, which acts as a “don’t eat me” sig­nal that en­ables can­cer cells to evade de­tec­tion.

Dr. Wang is among the I-Mab sci­en­tists be­hind lem­zopar­limab, a high­ly dif­fer­en­ti­at­ed an­ti-CD47 mon­o­clon­al an­ti­body for the treat­ment of mul­ti­ple can­cers. The an­ti­body is at the cen­ter of the glob­al strate­gic part­ner­ship be­tween I-Mab and the Chica­go-based bio­phar­ma com­pa­ny Ab­b­Vie, an­nounced last Sep­tem­ber and val­ued at about $3 bil­lion. The po­ten­tial of his team’s work to trans­form the treat­ment of can­cer pa­tients fu­eled an in­tense­ly fo­cused in­ves­ti­ga­tion that be­gan in 2016. And the en­tire process has been an in­cred­i­bly ful­fill­ing one, ac­cord­ing to Dr. Wang, Vice Pres­i­dent of Dis­cov­ery.

“I have worked for multi­na­tion­als, and you tend to just work at your own po­si­tion; rarely do you have a chance to be in­volved in the en­tire drug de­vel­op­ment process,” said Wang. “Here at I-Mab you have a chance to dis­cov­er some­thing by your­self, and you can see how your own dis­cov­ered drug de­vel­ops and brings the ben­e­fits to the pa­tients.”

Typ­i­cal­ly, CD47 is hin­dered as a can­cer ther­a­py by its side ef­fect of se­vere ane­mia caused by nat­ur­al RBC bind­ing be­hav­ior.¹ I-Mab’s de no­vo dis­cov­ery process took a unique ap­proach to ad­dress this prob­lem. Dr. Wang and his col­leagues uti­lized a naïve hu­man an­ti­body li­brary with around 10 bil­lion di­ver­si­fied se­quences and pri­or­i­tized nor­mal RBC bind­ing as­say in their screen­ing to iden­ti­fy a unique clone with min­i­mum RBC bind­ing prop­er­ty and com­pa­ra­ble tu­mor cell bind­ing abil­i­ty. Ini­tial monother­a­py re­sults of US Phase I clin­i­cal tri­al da­ta re­leased in No­vem­ber demon­strat­ed a dif­fer­en­ti­at­ed safe­ty and PK pro­file as well as ef­fi­ca­cy sig­nal for this an­ti­body.

I-Mab is now ex­pand­ing its US clin­i­cal tri­al of lem­zopar­limab to par­al­lel com­bi­na­tion stud­ies in sol­id tu­mors and non-Hodgkin lym­phoma. In Chi­na, a sep­a­rate clin­i­cal study in pa­tients with AML/MDS is pro­gress­ing well and has moved to­wards the high­est dose (30mg/kg).

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Dr. Jing­wu Zang, I-Mab Founder and Chair­man

Dr. Wang is just one of many sci­en­tists who fol­lowed Dr. Jing­wu Zang, I-Mab’s Founder and Chair­man, to the com­pa­ny. Be­fore found­ing I-Mab in 2016 and trans­form­ing it in­to a clin­i­cal stage com­pa­ny with a glob­al­ly com­pet­i­tive pipeline in just four short years, Dr. Zang held posts as Se­nior Vice Pres­i­dent and head of R&D Chi­na for Glax­o­SmithK­line, R&D head at Sim­cere Phar­ma­ceu­ti­cals, and found­ing di­rec­tor of the In­sti­tute of Health Sci­ences and the In­sti­tute of Pas­teur Shang­hai. Both in­sti­tutes are among the top re­search in­sti­tu­tions in Chi­na. Dr. Wang trained in Dr. Zang’s lab in the In­sti­tute of Health Sci­ences and lat­er joined him at I-Mab.

A sig­nif­i­cant fac­tor be­hind I-Mab’s ac­cel­er­at­ed growth is the fo­cus on in­clu­sive lead­er­ship and cul­ti­va­tion of its peo­ple.

“I-Mab was found­ed with the idea that we could, and should, be tru­ly in­no­v­a­tive in build­ing our dif­fer­en­ti­at­ed pipeline,” said Dr. Zang. “In our pur­suit of in­no­v­a­tive drug pro­grams, we at­tract and mo­ti­vate a pre­cious, grow­ing tal­ent pool of pro­fes­sion­als with both glob­al and lo­cal R&D ex­per­tise. This, cou­pled with crit­i­cal mass of CRO ser­vices op­er­at­ing ac­cord­ing to glob­al stan­dards, gives us re­mark­able pow­er and speed in de­vel­op­ing in­no­v­a­tive med­i­cines.”

In­deed, long be­fore the spot­light of CD47, I-Mab was al­ready gain­ing in­dus­try at­ten­tion and ac­co­lades for its unique busi­ness mod­el—which com­bines a fast-to-proof of con­cept glob­al ap­proach in par­al­lel with a fast-to-mar­ket Chi­na ap­proach—to ac­cel­er­ate de­liv­ery on a pipeline of more than 15 as­sets in clin­i­cal and pre­clin­i­cal stages of de­vel­op­ment. Sev­en Phase I clin­i­cal tri­als are on­go­ing in the US and Chi­na, with an­oth­er five Phase II and III tri­als in Chi­na and one Phase II/III tri­al in US. They in­clude TJ107/HyLeukin-7™ for lym­phopenic pa­tients with new­ly-di­ag­nosed glioblas­toma mul­ti­forme (GBM) and TJ210, a nov­el an­ti­body that blocks C5aR by bind­ing to a unique epi­tope.

While it has been on a fast track since its es­tab­lish­ment, I-Mab blew through sev­er­al mile­stones in 2020, start­ing in Jan­u­ary when it be­came the first Chi­na-based glob­al biotech com­pa­ny to suc­cess­ful­ly com­plete a US IPO since 2017. Sub­se­quent­ly, I-Mab’s Amer­i­can De­pos­i­to­ry Shares (ADS) were se­lect­ed for in­clu­sion in the Nas­daq Biotech­nol­o­gy In­dex (Nas­daq: NBI).

In Sep­tem­ber, I-Mab com­plet­ed one of the largest PIPE fi­nanc­ing rounds in re­cent biotech his­to­ry, rais­ing ap­prox­i­mate­ly US$418 mil­lion through a pri­vate place­ment by a con­sor­tium of in­sti­tu­tion­al in­vestors led by Hill­house Cap­i­tal. This news came in par­al­lel with the Ab­b­Vie deal.

“I-Mab’s progress as a com­pa­ny has been re­mark­able, es­pe­cial­ly over the last year,” said Michael Yi, Co-Chief In­vest­ment Of­fi­cer of Hill­house Cap­i­tal. “This is a biotech to watch as it has shown that it can pro­duce re­al in­no­va­tion.”

Re­al­iz­ing its vi­sion of be­com­ing a ful­ly in­te­grat­ed glob­al biotech, I-Mab al­so be­gan con­struc­tion of its own state-of-the-art bi­o­log­ics man­u­fac­tur­ing fa­cil­i­ty in Hangzhou, Chi­na. Es­tab­lish­ing its own GMP man­u­fac­tur­ing process is a strate­gic move by I-Mab to en­sure qual­i­ty, se­cure pro­duc­tion slots, and max­i­mize cost-ef­fec­tive­ness for clin­i­cal tri­al ma­te­ri­als and com­mer­cial sup­plies, bol­ster­ing its abil­i­ty to ex­pand quick­ly in the years ahead.

An­oth­er strat­e­gy for long-term growth is defin­ing an in­clu­sive cul­ture. Amidst sig­nif­i­cant pipeline achieve­ments and ne­go­ti­a­tion of part­ner­ships, I-Mab al­so launched a Women’s Lead­er­ship Coun­cil (WLC) glob­al­ly. Ac­knowl­edg­ing the fact that phar­ma­ceu­ti­cal and biotech com­pa­nies have the op­por­tu­ni­ty—and man­date—to cre­ate a health­i­er world by bring­ing more in­clu­sive rep­re­sen­ta­tion in­to the drug re­search and de­vel­op­ment process, the unique pro­gram aims to sup­port the or­ga­ni­za­tion’s fu­ture fe­male lead­ers to ac­cel­er­ate their ca­reer and per­son­al de­vel­op­ment. This is be­ing done through am­bi­tious tar­gets for more glob­al lead­er­ship op­por­tu­ni­ties, ex­po­sure to the in­dus­try, and knowl­edge shar­ing across bor­ders.

“Our ap­proach to our in­ter­nal pro­grams mir­rors our ap­proach to sci­ence in a sense. I-Mab’s cul­ture strives to be mind­ful of the chang­ing world around us as well as tak­ing ac­tion on the ur­gent needs that we can ad­dress with our col­lec­tive skillset,” said Dr. Joan Shen, CEO of I-Mab. “Look­ing in­to 2021, we look for­ward to more am­bi­tious growth and cross bor­der col­lab­o­ra­tions to ac­cel­er­ate in­no­va­tion.”

¹ Huang Y, Ma Y, Gao P, Yao Z. Tar­get­ing CD47: the achieve­ments and con­cerns of cur­rent stud­ies on can­cer im­munother­a­py. J Tho­rac Dis. 2017;9(2):E168-E174. doi:10.21037/jtd.2017.02.30