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.

Sur­geons suc­cess­ful­ly at­tach pig kid­ney to a hu­man for the first time, us­ing tech from Unit­ed's Re­vivi­cor

In a first, researchers reportedly successfully transplanted a pig kidney into a human without triggering an immediate immune response this week. And the technology came from the biotech United Therapeutics.

Surgeons spent three days attaching the kidney to the patient’s blood vessels, but when all was said and done, the kidney appeared to be functioning normally in early testing, Reuters and the New York Times were among those to report. The kidney came from a genetically altered pig developed through United’s Revivicor unit.

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Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty

 

I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

Man­u­fac­tur­ing woes for No­vavax’s Covid jab bad­ly dis­rupt plans for roll­out to the poor — re­port

Production problems at a Novavax facility in Maryland have led to delays in the Covax vaccine sharing program. Now, a shortage of 1 billion doses is expected, as the supplier tries to navigate producing a shot up to regulators’ standards, Politico reported Tuesday.

The company has run into trouble with the purity of the vaccine. Novavax has had trouble proving it can produce a shot consistently up to standards, and it has caused significant delays in the rollout to low- and middle-income countries. This follows several delays at Novavax that has put the executive crew on the defensive.

Break­ing: Bio­gen sells just $300K worth of Aduhelm in Q3, as ques­tions on long term vi­a­bil­i­ty re­main

Barely anyone is accessing Biogen’s controversial Alzheimer’s treatment, with the company reporting just $0.3 million in Aduhelm sales in the third quarter. Although investors will be looking to the longer term, when CMS may decide to cover the drug and open the floodgates for more coverage, use of the drug is currently stalled.

Since June, when the FDA first signed off on the drug, Biogen said Wednesday that it’s sold a total of $2 million worth of Aduhelm. The total sales numbers indicate that likely about 100 Alzheimer’s patients have so far received the drug, which is priced at $56,000 annually.

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Bill Gates at the Global Investment Summit in London, Oct. 19, 2021 (Leon Neal/Pool via AP Images)

Gates Foun­da­tion pledges $120M to ramp up gener­ic sup­ply of Mer­ck­'s Covid-19 pill while ac­tivists blast Pfiz­er's dis­pro­por­tion­ate pow­er

Merck’s molnupiravir may not be officially authorized anywhere in the world yet, but who will get access to it has shaped up to be a huge issue. The Bill & Melinda Gates Foundation is now stepping up to ensure lower-income countries won’t be left behind — and calling on others to follow its lead.

The oral antiviral pill, which was shown to dramatically cut the risk of severe Covid-19 disease and death in a Phase III study, is the latest rallying symbol in the battle against not just the coronavirus but the inequality it’s exposed.

Raymond Stevens, ShouTi Pharma CEO

A new Schrödinger-backed start­up emerges from the sci­en­tist who mapped the first hu­man GPCR

One of the most popular targets in drug development, representing about a third of existing drugs, are G-protein coupled receptors — the tiny but integral membrane proteins responsible for recognizing things like light, taste, smell, hormones and pain.

But due to challenges in mapping their structure, the protein family remains largely unexplored.

A slate of companies has emerged over the last few years to change that. If you can figure out the structure of these elusive membrane receptors, you could create small molecule drugs that overcome the limitations of, say, biologic and peptide therapies. That promise is what gets serial entrepreneur Raymond Stevens out of bed in the morning.

Carl June (Brian Ach/Getty Images for TIME 100 Health Summit)

Carl June lends 'wings' to Chi­nese CAR-T start­up led by for­mer post­doc, pur­su­ing off-the-shelf ap­proach with CRISPR fla­vor

Carl June still has plenty of energy to bring forth new iterations of CAR-T technology — wherever they’re coming from.

Adding another role to his already lengthy list of titles, June is joining the scientific advisory board at Nanjing Bioheng Biotech, where he will serve as chairman.

The appointment, if slightly out of the ordinary, is both a testament to the fruitfulness of June’s lab at the University of Pennsylvania and China’s increasing appeal to biotech entrepreneurs educated overseas.