All in: Gilead maps a $3.15B gene edit­ing al­liance with Sang­amo for off-the-shelf CAR-T drugs

In a block­buster en­dorse­ment of its gene-edit­ing tech­nol­o­gy, Gilead $GILD has tapped Sang­amo’s zinc fin­ger nu­cle­ase ap­proach to tai­lor­ing its next-gen pro­grams for off-the-shelf as well as per­son­al­ized ther­a­pies. And Gilead, which seized a lead­ing spot in the CAR-T world with its ac­qui­si­tion of Kite, is fronting the deal with $150 mil­lion in cash and slight­ly more than $3 bil­lion in mile­stones.

The deal gives Gilead an ex­clu­sive po­si­tion with Sang­amo $SG­MO, which has been work­ing with its ZFN gene edit­ing tech for years. While CRISPR/Cas9 and TAL­ENs have fig­ured promi­nent­ly in gene edit­ing, with ri­val off-the-shelf CAR-T de­vel­op­er Cel­lec­tis ini­tial­ly pre­fer­ring TAL­ENs, Sang­amo has been mak­ing some dra­mat­ic ad­vances in re­cent months.

Gilead, mean­while, sig­naled with its ac­qui­si­tion of Cell De­sign that it was se­ri­ous about in­vest­ing big in CAR-T 2.0, and few pro­grams are as am­bi­tious as the move to use healthy donor cells to cre­ate a sim­pler, less ex­pen­sive al­ter­na­tive to the pricey per­son­al­ized ther­a­pies now hit­ting the mar­ket from No­var­tis and Gilead.

And it’s will­ing to con­tin­ue to in­vest heav­i­ly through the de­vel­op­ment process. In a fil­ing with the SEC to­day, Sang­amo not­ed:

Of this amount (for mile­stones), ap­prox­i­mate­ly $1.26 bil­lion re­lates to the achieve­ment of spec­i­fied re­search, clin­i­cal de­vel­op­ment and first com­mer­cial sale mile­stones, and ap­prox­i­mate­ly $1.75 bil­lion re­lates to the achieve­ment of spec­i­fied com­mer­cial sales-based mile­stones if an­nu­al world­wide net sales of Li­censed Prod­ucts reach spec­i­fied lev­els. Each de­vel­op­ment- and sales-based mile­stone pay­ment is payable (i) on­ly once for each Li­censed Prod­uct, re­gard­less of the num­ber of times that the as­so­ci­at­ed mile­stone event is achieved by such Li­censed Prod­uct, and (ii) on­ly for the first ten times that the as­so­ci­at­ed mile­stone event is achieved, re­gard­less of the num­ber of Li­censed Prod­ucts that may achieve such mile­stone event. In ad­di­tion, Sang­amo will be en­ti­tled to re­ceive es­ca­lat­ing, tiered roy­al­ty pay­ments with a per­cent­age in the sin­gle dig­its based on po­ten­tial fu­ture an­nu­al world­wide net sales of Li­censed Prod­ucts. These roy­al­ty pay­ments will be sub­ject to re­duc­tion due to patent ex­pi­ra­tion, en­try of biosim­i­lar prod­ucts to the mar­ket and pay­ments made un­der cer­tain li­cens­es for third-par­ty in­tel­lec­tu­al prop­er­ty.

Now both No­var­tis $NVS — work­ing with CRISPR tech from In­tel­lia Ther­a­peu­tics and Cari­bou Bio­sciences — and Cel­gene $CELG, which just bought out Juno, have been served no­tice that the next-gen tech race in CAR-T is in full swing. How will they re­spond?

The deal marks the sec­ond big tech en­dorse­ment for Sang­amo in a lit­tle more than a month. Pfiz­er start­ed the year by ink­ing an al­liance with the gene edit­ing crew on ALS, build­ing on their orig­i­nal pact for he­mo­phil­ia A. Pfiz­er had ear­li­er al­lied it­self with Spark in a move to get in­to the lead of the gene ther­a­py field, work­ing on he­mo­phil­ia B.

“The emer­gence of gene edit­ing as a tool to ed­it im­mune cells holds promise in the de­vel­op­ment of ther­a­pies with po­ten­tial­ly im­proved safe­ty, ef­fi­ca­cy and ef­fi­cien­cy,” said Gilead CEO John Mil­li­gan in a state­ment. “We be­lieve Sang­amo’s zinc fin­ger nu­cle­as­es pro­vide the op­ti­mal gene edit­ing plat­form, and we look for­ward to work­ing with Sang­amo to ac­cel­er­ate our ef­forts to de­vel­op next-gen­er­a­tion au­tol­o­gous cell ther­a­pies, as well as al­lo­gene­ic treat­ments that can be ac­cessed more con­ve­nient­ly in the hos­pi­tal set­ting for peo­ple liv­ing with can­cer.”

Im­age: Gilead CEO John Mil­li­gan. bloomberg via get­ty im­ages

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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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.

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.

Amgen VP of R&D David Reese

Am­gen rolls out da­ta for KRAS in­hibitor com­bo study in col­orec­tal can­cer, hop­ing to move on from ug­ly ear­ly re­sults

With the first win for its KRAS inhibitor sotorasib in hand, Amgen is pushing ahead with an aggressive clinical plan to capitalize on its first-to-market standing. The drugmaker thinks combinations — in-house or otherwise — could offer a path forward, and one early readout from that strategy is bearing fruit.

A combination of Amgen’s sotorasib and its EGFR inhibitor Vectibix posted an overall response rate of 27% in 26 patients with advanced colorectal cancer (CRC) with the KRAS-G12C mutation, according to data from the larger Phase Ib/II CODEBREAK 101 study set to present at this weekend’s virtual ESMO Congress.

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Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Eu­ro­pean study finds that Gilead­'s Covid-19 an­tivi­ral remde­sivir shows no clin­i­cal ben­e­fit

Gilead’s remdesivir — or Veklury, as it’s marketed in the US — raked in around $2.8 billion last year as the only FDA-approved antiviral to treat Covid-19. But new data from a European study suggest the drug, which has been given to about half of hospitalized Covid patients in the country, has no actual benefit.

The open-label DisCoVeRy trial enrolled Covid-19 patients across 48 sites in Europe to test a handful of treatments, including remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, and hydroxychloroquine. To participate, patients had to show symptoms for seven days and require oxygen support. A total of 429 patients were randomized to receive remdesivir plus standard of care, while 428 were assigned to standard of care alone.

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Covid-19 roundup: FDA re­veals boost­er ad­comm ques­tion; Eli Lil­ly's an­ti­body cock­tail cleared for pre­ven­tion

The FDA released briefing documents this week from the agency and Pfizer each outlining their arguments for today’s Covid-19 booster shot adcomm, but one thing conspicuously missing was the question on which panel members would be voting. But late Thursday night, regulators published that question.

Adcomm members will be asked whether or not the safety and efficacy data from Pfizer/BioNTech’s original Phase III study “support approval” of a booster shot at least six months after the second dose in individuals older than 16. The question notably excludes the real-world data from Israel and other analyses that Pfizer and the Biden administration had said would be a centerpiece of their arguments for boosters.

A Pfiz­er part­ner wel­comes ex-ADC Ther­a­peu­tics CMO Jay Fein­gold to the team; Amid tough sled­ding, Im­muno­vant choos­es Eli Lil­ly alum as CFO

→ Last week we told you about the CMO revolving door at ADC Therapeutics, as Joseph Camardo replaced the departing Jay Feingold. The next opportunity for Feingold in the CMO slot has opened up at antibody-drug conjugate and mAb developer Pyxis Oncology, which has added several new execs and scientific advisory board members in recent months, including ex-Immunovant CFO Pamela Yanchik Connealy. Before his tenure at ADC, Feingold was Daiichi Sankyo’s VP of US medical affairs and chairman of the Global Medical Affairs Oversight Committee. Within weeks in March, Pyxis struck a licensing deal with Pfizer for two of its ADCs and raked in $152 million from a Series B round.

Ali Tehrani, Zymeworks CEO

Zymeworks squares up with Her­ceptin af­ter HER2 bis­pe­cif­ic aces mid-stage test in esophageal can­cer

Roche’s Herceptin has long stood as standard of care across multiple advanced cancers, but a suite of next-gen players are looking to beat the aging giant at its own game. In HER2-expressing esophageal cancer, BeiGene partner Zymeworks thinks its bispecific antibody could have the juice to get it done.

Zymeworks’ bispecific antibody zanidatamab, combined with one of two chemotherapy regimens, posted an overall response rate of 75% in patients with advanced gastroesophageal adenocarcinoma (GEA) who had not previously received a HER2-targeted cancer therapy, the Vancouver-based biotech said Thursday.

UP­DAT­ED: Gilead keeps push­ing trove of Trodelvy da­ta as it seeks to be­come new stan­dard of care in TNBC

Gilead is continuing to churn out results for its newly approved drug Trodelvy, and #ESMO21 is the latest stop on the data train.

The biopharma put out new quality of life data in second-line patients with metastatic triple-negative breast cancer, saying that a sub-analysis from their Phase III study showed significant and clinically meaningful improvements in health-related quality of life over standard of care.