WHO is­sues new guide­lines for gene edit­ing; Doud­na-backed Cari­bou launch­es its first al­lo­gene­ic CAR-T tri­al

Three years af­ter news of the birth of two gene-edit­ed ba­bies shocked ethi­cists, reg­u­la­tors and bi­ol­o­gists around the world, World Health Or­ga­ni­za­tion ex­perts called for the es­tab­lish­ment of a new whis­tle-blow­ing mech­a­nism to help pre­vent fu­ture un­safe or un­eth­i­cal us­es of CRISPR and oth­er gene edit­ing tech­nolo­gies.

The rec­om­men­da­tion was one of a se­ries the WHO pan­el is­sued Mon­day in a pair of re­ports de­signed to guide glob­al gov­er­nance of gene edit­ing. The pan­el was con­vened in De­cem­ber 2018, weeks af­ter Chi­nese sci­en­tist He Jiankui an­nounced two ba­bies were born from em­bryos he edit­ed, and fol­lows a sim­i­lar ef­fort from the In­ter­na­tion­al Com­mis­sion on the Clin­i­cal Use of Hu­man Germline Genome Edit­ing, which re­leased a se­ries of rec­om­men­da­tions last year.

Both pan­els have broad­ly con­demned germline edit­ing — i.e. mak­ing her­i­ta­ble changes to DNA, by edit­ing em­bryos, sperm or eggs — not­ing the tech­nol­o­gy is not so­phis­ti­cat­ed enough for re­searchers to make such ed­its safe­ly and ar­gu­ing that, even if it be­comes pos­si­ble to do so, it should on­ly be done for se­ri­ous dis­or­ders.

In ad­di­tion to the whistle­blow­ing mech­a­nism, the new re­ports al­so call for an in­ter­na­tion­al reg­istry to track all gene edit­ing ex­per­i­ments, al­though they ac­knowl­edge that the or­ga­ni­za­tion can’t com­pel coun­tries or com­pa­nies to co­op­er­ate. Ac­cord­ing­ly, they call for new meth­ods to spot bad ac­tors, par­tic­u­lar­ly as such ex­per­i­ments be­come cheap­er and more wide­ly ac­ces­si­ble. — Ja­son Mast

Doud­na-backed Cari­bou launch­es its first al­lo­gene­ic CAR-T tri­al

Less than two weeks af­ter Cari­bou Bio­sciences, launched out of No­bel Prize win­ner Jen­nifer Doud­na’s lab, filed its IPO pa­per­work to go pub­lic, the biotech is mak­ing more waves in the cell ther­a­py world.

Rachel Hau­r­witz

Cari­bou of­fi­cial­ly launched its first in-hu­man study of an al­lo­gene­ic CAR-T with an eye on liq­uid tu­mors Mon­day morn­ing, an­nounc­ing the dos­ing of its first pa­tient in a Phase I tri­al. The ther­a­py, known as CB-010, is be­ing eval­u­at­ed to re­duce the risk of graft-ver­sus-host dis­ease in or­der to boost CAR-T an­ti­tu­mor ac­tiv­i­ty.

“We be­lieve that im­prov­ing cell per­sis­tence is the key to un­lock­ing the full po­ten­tial of these ther­a­pies,” CEO Rachel Hau­r­witz said in a state­ment. “Us­ing our tech­nolo­gies, we ed­it the genome of healthy donor-de­rived T cells to en­able high­ly spe­cif­ic and ef­fi­cient in­ser­tion or dele­tion of genes at mul­ti­ple sites.”

Cari­bou’s ap­proach in­volved a hy­brid DNA/RNA edit­ing plat­form, which Hau­r­witz calls chRD­NA (pro­nounced “chardon­nay,” like the wine). The biotech be­lieves the hy­brid guides can pre­vent off-tar­get edit­ing com­mon­ly seen in cur­rent CRISPR ap­pli­ca­tions.

The ther­a­py tar­gets CD-19 us­ing a CRISPR-based ap­proach, and in ad­di­tion al­so take out PD-1. In the­o­ry, the sec­ondary step amps up the body’s T cells even more than they would be oth­er­wise.

The study will en­roll about 50 adults with re­lapsed or re­frac­to­ry B cell non-Hodgkin lym­phoma, ac­cord­ing to clin­i­cal­tri­als.gov. In the dose-es­ca­la­tion por­tion, adults who have failed at least two lines of chemo or im­munother­a­py will be ad­min­is­tered CB-010 af­ter go­ing through a process that de­pletes their nat­ur­al T cells.

Cari­bou will fol­low a “stan­dard 3+3 dose es­ca­la­tion de­sign,” the com­pa­ny said. Those who pre­vi­ous­ly re­ceived a CD-19 ther­a­py will be ex­clud­ed. — Max Gel­man

Rayze­Bio nabs new dis­cov­ery part­ner

Rayze­Bio has seen a quick rise since launch­ing back in Au­gust 2020, and now they have a new part­ner to fur­ther their ef­forts in ra­dio­phar­ma­ceu­ti­cals.

Ken Song

The San Diego biotech is team­ing up with Cana­di­an out­fit 48Hour Dis­cov­ery to de­vel­op new pep­tide-based treat­ments for can­cer us­ing the ra­dio­phar­ma plat­form, the com­pa­nies an­nounced Mon­day. Fi­nan­cial terms of the deal were not dis­closed.

“For this col­lab­o­ra­tion project, 48Hour Dis­cov­ery will iden­ti­fy po­tent lig­ands for a se­ries of tar­gets se­lect­ed by Rayze­Bio,” Rat­mir Der­da, CEO of 48Hour Dis­cov­ery, said in a state­ment. “This project will help us fur­ther val­i­date the po­ten­tial of our bil­lion-scale mol­e­c­u­lar li­braries and cloud-based dis­cov­ery pipeline.”

Rayze­Bio CEO Ken Song hint­ed at a pos­si­ble IPO last month when the biotech com­plet­ed its Se­ries C raise, not­ing the round might be its last pri­vate fundraise. Song has al­ready led the com­pa­ny to more than $250 mil­lion across pri­vate fund­ing rounds. — Max Gel­man

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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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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As­traZeneca touts Imfinzi im­munother­a­py com­bos for lung can­cer in push to dri­ve PD-L1 drug up­take

Facing the big dogs in the PD-(L)1 space, AstraZeneca has taken its own contender Imfinzi into blockbuster territory in its four years on the market but sees even bigger things for the drug. Combinations could be the key, and early results from a mid-stage test are adding some fuel to that strategy.

Imfinzi combined with one of two investigational immunotherapies — a CD73 antibody dubbed oleclumab or an Innate’s anti-NGK2a named monalizumab — topped Imfinzi alone in terms of overall response and progression-free survival in patients with stage III non-small cell lung cancer whose tumors had not worsened during concurrent chemoradiation, according to interim data from the Phase II COAST trial set to be presented at #ESMO21.

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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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.

FDA ac­cepts In­tel­li­a's IND for CRISPR and TCR-T cell ther­a­py; San­té clos­es Fund IV at $260M

Riding the coattails of a massive $600 million cash raise in June, Intellia announced that the FDA accepted their IND application for their gene editing treatment NTLA-5001, built as a treatment for acute myeloid leukemia.

The Cambridge, MA biotech said that they have plans to start patient screening in a Phase I/IIa study by the end of 2021. The study will evaluate the effects of a single dose of the treatment in adults who have detectable AML after having received standard first-line therapy. The study will contain a dose escalation and expansion phase, with up to 54 participants.

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.