ADC Therapeutics CEO Chris Martin (L) and Overland COO/CBO Ed Zhang

Go­ing to Chi­na? ADC Ther­a­peu­tics spot­lights a new way to do it with Hill­house-backed Over­land

Chris Mar­tin and his crew at ADC Ther­a­peu­tics went in­to the JP Mor­gan Health­care con­fer­ence this Jan­u­ary armed with pos­i­tive piv­otal da­ta for its lead an­ti­body-drug con­ju­gate, lon­cas­tux­imab tesirine. Hav­ing fo­cused its de­vel­op­ment pro­gram ex­clu­sive­ly in the US and Eu­rope, it was time to find a Chi­nese part­ner.

The search, which stretched out over the next few months, cul­mi­nat­ed in six term sheets, from large phar­ma, on­col­o­gy spe­cial­ists and all. But one bid­der stood out: Over­land Phar­ma, the fledg­ling plat­form play co-found­ed by ven­ture part­ners at Hill­house Cap­i­tal, a mar­quee VC firm Mar­tin has come to re­spect.

“It was a com­plete­ly dif­fer­ent struc­ture,” he told End­points News.

In­stead of sim­ply li­cens­ing lon­ca, Over­land pro­posed start­ing a joint ven­ture — one AD­CT would own 49% of — to house the Greater Chi­na and Sin­ga­pore rights to a to­tal of four AD­Cs in the Swiss biotech’s port­fo­lio, with $50 mil­lion in up­front in­vest­ment from Hill­house. The team of 30-plus Over­land staffers would ini­tial­ly shoul­der much of the lo­cal de­vel­op­ment and reg­u­la­to­ry work, both start­ing bridg­ing stud­ies de­signed specif­i­cal­ly for the li­censed ter­ri­to­ries and loop­ing them in­to glob­al tri­als. ADC will send the same num­ber of reps to the board of di­rec­tors as Over­land.

As the bio­phar­ma world learned last week with Over­land’s de­but, the start­up is pitch­ing it­self as a spring­board for West­ern drug de­vel­op­ers to bring not just prod­ucts, but their cut­ting-edge tech­nolo­gies to Chi­na through plat­form plays.

To be sure, joint ven­tures in Chi­na are noth­ing new. In the most promi­nent ex­am­ple, CAR-T pi­o­neers Kite, Juno and the less­er known Sin­ga­pore­an cell ther­a­py biotech Tes­sa have all set up JVs with lo­cal com­pa­nies — al­beit go­ing with hefty, es­tab­lished play­ers in the phar­ma scene.

On the sur­face, Over­land is more like Zai Lab, Ever­est Med­i­cines or even Per­cep­tive’s Lian­Bio in that it’s small­er and built ex­plic­it­ly to source for­eign in­no­va­tion in­to Chi­na. But be­hind it is an ex­ten­sive ecosyt­sem, from a net­work of CROs and man­u­fac­tur­ers to a com­mer­cial sales force, that Hill­house has as­sem­bled over the years.

Both part­ners have am­bi­tious goals for Over­land AD­CT Bio­phar­ma, which Mar­tin en­vi­sions grow­ing in­to a stand­alone com­pa­ny with multi­bil­lion mar­ket cap that can file for an IPO on the Hong Kong stock ex­change in a few years’ time.

Hua Mu

“We’ve been fol­low­ing in on the land­scape of ADC close­ly,” Over­land CMO and in­ter­im CEO Hua Mu said. “We know it’s an evolv­ing tech­nol­o­gy par­tic­u­lar­ly over the re­cent 2 years.”

But the over­whelm­ing ma­jor­i­ty of pro­grams are fo­cused on sol­id tu­mors, added Ed Zhang, the COO and CBO. You can find 10 or 12 dif­fer­ent AD­Cs tar­get­ed at HER2, but lon­ca and oth­er drugs from AD­CT (name­ly AD­CT-602, AD­CT-601 and AD­CT-901) would be the first com­pounds tagged with a pyrroloben­zo­di­azepine-based pay­load aimed at hema­to­log­i­cal in­di­ca­tions.

In the lead in­di­ca­tion of third-line re­lapsed/re­frac­to­ry dif­fuse large B cell lym­phoma, lon­ca spurred an over­all re­sponse rate of 48.3%. Giv­en that the 5-year sur­vival for DL­B­CL in Chi­na is 38% com­pared to 68% in the US and Eu­rope, Mu added, the drug would fill a huge gap.

While AD­CT is sup­ply­ing the ini­tial tri­al ma­te­r­i­al so that they can move as fast as pos­si­ble, there are tech trans­fer plans to even­tu­al­ly en­able man­u­fac­tur­ing in Chi­na — both for do­mes­tic use and be­yond.

“It’s more like a step­wise or two-step ap­proach,” Mu said.

From Lau­sanne, Switzer­land, Mar­tin not­ed he’s been com­mu­ni­cat­ing with Boston-based Zhang, Seat­tle-based Mu and the team in Chi­na via “hun­dreds of Zoom calls and Teams calls” as well as pho­tos.

It helped that he’s met the founders as well as the broad­er Hill­house team, he said. In fact, they were so keen not to lose time that AD­CT start­ed work­ing with Over­land be­fore for­mal­ly putting the JV to­geth­er.

“I think you learn to trust peo­ple by see­ing whether they do what they say. I think that’s a two-way street,” he said. “I must say I’ve been ex­treme­ly im­pressed by the Over­land team, not just the lead­er­ship team but the 30 peo­ple that they have work­ing with them. They’ve been very re­spon­sive, they’ve got on well with our — well, we have quite de­mand­ing clin­i­cal de­vel­op­ment and CMC teams, they’ve got on well and been re­spon­sive and they’ve moved for­ward, ef­fec­tive­ly done what they say they would do.”

What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; and more

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President Biden and Pfizer CEO Albert Bourla (Patrick Semansky/AP Images)

Chaot­ic ad­comm sees Pfiz­er/BioN­Tech boost­ers re­ject­ed for gen­er­al pop­u­la­tion, but rec­om­mend­ed for old­er and high-risk pop­u­la­tions

With just days before President Joe Biden’s Covid-19 booster rollout is set to go into effect, an FDA advisory committee appeared on the verge of not recommending boosters for anyone in the US before a last-minute change of wording laid the groundwork for older adults to have access to a third dose.

The FDA’s adcomm on Vaccines and Related Biological Products (VRBPAC) roundly rejected Pfizer/BioNTech booster shots for all individuals older than 16 by a 16-2 vote Friday afternoon. Soon after, however, the agency posed committee members a new question limiting booster use to the 65-and-older population and individuals at high risk of disease due to occupational exposure or comorbidities.

As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

Merck Research Laboratories CMO Roy Baynes

Mer­ck­'s Keytru­da un­corks full da­ta on lat­est ad­ju­vant win — this time in melanoma — adding bricks to ear­ly can­cer wall

In recent months, the battle for PD-(L)1 dominance has spilled over into early cancer with Merck’s Keytruda and Bristol Myers Squibb’s Opdivo all alone on the front lines. Keytruda now has another shell in its bandolier, and it could spell a quick approval.

Keytruda cut the risk of relapse or death by 35% over placebo (p=0.00658) in high-risk, stage 2 melanoma patients who had previously undergone surgery to remove their tumors, according to full data from the Phase III KEYNOTE-716 presented Saturday at #ESMO21.

Chi­nese biotech Ever­est signs $550M+ li­cens­ing deal for BTK in­hibitors on heels of Covid-19 pact

Everest Medicines is on a roll with two licensing deals in one week.

The Shanghai-based biotech has paid Sinovent and SinoMab $12 million upfront for the rights to a BTK inhibitor for renal diseases, the company announced Thursday. The deal comes just days after Everest came away with rights to a Covid-19 vaccine in China, Taiwan, Singapore, Thailand and Indonesia.

Everest will pay Sinovent and SinoMab up to $549 million in milestone payments and royalties. The agreement includes tech transfer of Sinovent and SinoMab’s manufacturing process for the candidate, named XNW1011.

Mer­ck flesh­es out Keytru­da win in first-line cer­vi­cal can­cer, adding more fire­pow­er to its ear­ly can­cer push

Merck has worked hard to bring its I/O blockbuster Keytruda into earlier and earlier lines of therapy, and now the wonder drug appears poised to make a quick entry into early advanced cervical cancer.

A combination of Keytruda and chemotherapy with or without Roche’s Avastin cut the risk of death by 33% over chemo with or without Avastin (p=<0.001) in first-line patients with persistent, recurrent or metastatic cervical cancer, according to full data from the Phase III KEYNOTE-826 study presented Saturday at #ESMO21.

Gri­fols drops $1B on Ger­man hold­ing com­pa­ny in con­tin­ued plas­ma push

One Spanish biotech is beefing up its plasma therapy operations, and on Friday, it announced that it’s doing so in a billion-dollar deal.

Grifols is now the largest shareholder of Biotest, a company valued at more than $1.8 billion. By teaming up, the two will try to increase the number of plasma therapies available and increase patient access around the world, Grifols said in a press release.

The company did so by acquiring holding company Tiancheng Pharmaceutical, the Germany-based owner of nearly 90% of Biotest shares, for nearly $1.27 billion. Grifols now owns nearly 90% of Biotest voting rights and almost 45% of the total share capital of Biotest.