Ver­tex sharp­ens fo­cus on gene-edit­ing in li­cens­ing deal with Mer­ck KGaA

Two years ago Mer­ck KGaA splurged $230 mil­lion to li­cense all the rights to four on­col­o­gy pro­grams, in­clud­ing a DNA-de­pen­dent pro­tein ki­nase (DNA-PK) in­hibitor, from cys­tic fi­bro­sis drug­mak­er Ver­tex. On Thurs­day, the Ger­man drug­mak­er al­lowed Ver­tex ac­cess to the com­pound via a li­cens­ing deal for use in the field of gene edit­ing.

No fi­nan­cial de­tails were pro­vid­ed for the new trans­ac­tion, which al­so en­ables Ver­tex to ac­cess to an undis­closed pre­clin­i­cal com­pound. The DNA-PK in­hibitor — M9831 (for­mer­ly known as VX-984) — and the pre­clin­i­cal drug were li­censed to Mer­ck from Ver­tex in Jan­u­ary 2017 and are now part of the Darm­stadt-based com­pa­ny’s ar­se­nal of DNA Dam­age Re­sponse (DDR) in­hibitors.

Dam­age to the DNA in cells oc­curs every day and con­se­quent­ly the DDR mon­i­tors im­pact, ini­ti­ates re­pair and halts cell growth dur­ing the re­build­ing process. But in pa­tients with can­cer there is a high fre­quen­cy of DDR de­fects which cul­mi­nate in the ac­cu­mu­la­tion of DNA dam­age, giv­ing rise to mu­ta­tions that pro­mote un­bri­dled can­cer cell growth and/or en­able nor­mal cells to evade apop­to­sis. Al­though can­cer cells may ben­e­fit from DDR de­fects, oth­er func­tion­ing DNA re­pair sys­tems are re­quired for sur­vival. DDR in­hibitors thus of­fer an op­por­tu­ni­ty to fight can­cer by se­lec­tive­ly killing can­cer cells via the sup­pres­sion of stand­by DDR mech­a­nisms and spar­ing nor­mal healthy cells that are not de­pen­dent on these path­ways.

Mer­ck’s port­fo­lio of DDR in­hibitors in­cludes two ATR in­hibitors, an ATM in­hibitor and an in­ves­ti­ga­tion­al small-mol­e­cule of DNA-PK, which is a key en­zyme that could po­ten­tial­ly en­hance the ef­fi­ca­cy of DNA-dam­ag­ing agents such as ra­dio­ther­a­py and chemother­a­py. Pre­clin­i­cal da­ta has shown DNA-PK in­hi­bi­tion can al­so aug­ment CRISPR/Cas9-me­di­at­ed gene edit­ing, the com­pa­ny said.

With this deal, Ver­tex is sharp­en­ing its fo­cus in­to gene edit­ing. The Boston biotech, which oust­ed its COO and in­ter­im CFO Ian Smith for im­prop­er per­son­al con­duct on Wednes­day, is al­ready col­lab­o­rat­ing with CRISPR Ther­a­peu­tics to eval­u­ate the lat­ter’s CRISPR gene edit­ing tech­nol­o­gy to po­ten­tial­ly fix the mu­ta­tions in the CFTR gene un­der­stood to re­sult in the de­fec­tive pro­tein that caus­es cys­tic fi­bro­sis, as well as oth­er ge­net­ic dis­or­ders. Their ex­per­i­men­tal treat­ment, CTX001, was grant­ed fast track sta­tus by the FDA ear­li­er this month for sick­le cell dis­ease.

Un­der the new Mer­ck/Ver­tex deal, Mer­ck will re­ceive an up­front pay­ment and is el­i­gi­ble to re­ceive mile­stone pay­ments and  roy­al­ties from po­ten­tial drug sales, and Ver­tex has the op­tion to add in­di­ca­tions to the li­cense grant. Over­all, Mer­ck re­tains the rights to both as­sets in all oth­er dis­ease ar­eas, in­clud­ing on­col­o­gy, and can de­vel­op both these com­pounds in-house, or li­cense them to oth­er com­pa­nies for use in the gene edit­ing field.

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.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,600+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,600+ biopharma pros reading Endpoints daily — and it's free.

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.

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.

Multiple antibiotic resistant Pseudomonas aeruginosa bacterium

A new way to in­fil­trate (and de­stroy) some of the dead­liest drug-re­sis­tant bugs

About four years ago, Ruben Tommasi, the gregarious scientific chief of antibiotics startup Entasis, walked into a meeting with his top chemist and top biologist to chew over another batch of unchanging results.

“It felt like we were running the same experiment over and over,” Tommasi told Endpoints News. “We had all sort of come to that point in time where we felt like we were banging our heads against the wall.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,600+ biopharma pros reading Endpoints daily — and it's free.

Take­da scores a win for a rare type of lung can­cer, gear­ing up for a show­down with J&J

Four months after J&J’s infused drug Rybrevant scored the industry’s first win in a rare type of non-small cell lung cancer (NSCLC), Takeda is following up with an oral option for the small but desperate patient population.

The FDA granted an accelerated approval to Takeda’s oral TKI inhibitor Exkivity (mobocertinib) in metastatic NSCLC patients with EGFR exon 20 gene mutations who had previously undergone platinum-based chemotherapy, the company announced on Wednesday.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,600+ biopharma pros reading Endpoints daily — and it's free.