Kevin Boyle, Kuur

Months af­ter a ma­jor re­brand­ing around CAR-NKT cells, Ku­ur Ther­a­peu­tics is of­fer­ing a peek at ear­ly re­sults

Sev­er­al months af­ter a name change and ma­jor re­struc­tur­ing, Ku­ur Ther­a­peu­tics has of­fered an ear­ly glimpse at re­sults from a small num­ber of pa­tients treat­ed with their CAR-NKT cell ther­a­pies de­vel­oped with the Bay­lor Col­lege of Med­i­cine.

Out of 10 evalu­able neu­rob­las­toma pa­tients dosed with Ku­ur’s lead can­di­date, an au­tol­o­gous GD2-tar­get­ing CAR-NKT ther­a­py, re­searchers not­ed one com­plete re­sponse, one par­tial re­sponse, and three pa­tients with sta­ble dis­ease, ac­cord­ing to the Hous­ton-based biotech.

The pa­tient with a com­plete re­sponse had pre­vi­ous­ly achieved a par­tial re­sponse be­fore re­ceiv­ing a sub­se­quent dose of the drug. The drug ap­peared safe, ac­cord­ing to Ku­ur, with one case of Grade 2 cy­tokine re­lease syn­drome (CRS) oc­cur­ring in the Phase I tri­al, dubbed GI­NAKIT2.

“We have some very good ear­ly signs of NKT cells be­ing safe, hom­ing to the site of tu­mor, which is very im­por­tant go­ing af­ter sol­id tu­mors … and now we’re show­ing signs of ef­fi­ca­cy as well,” CEO Kevin Boyle told End­points News. “So, based on that, we want the com­pa­ny to be fo­cused on just this plat­form.”

The drug con­sists of nat­ur­al killer T cells en­gi­neered with a CAR tar­get­ing GD2, a ma­jor gan­glio­side ex­pressed on many neu­rob­las­toma tu­mors. It’s de­signed to se­crete IL-15, which has been shown to bol­ster the ef­fi­ca­cy and per­sis­tence of CAR-NKT cells in the im­muno­sup­pres­sive tu­mor mi­croen­vi­ron­ment.

NKT cells are rare lym­pho­cytes that aren’t fre­quent­ly found in the pe­riph­er­al blood, and as a re­sult, re­searchers tend not to work with them, Boyle ex­plained. The sci­en­tist lead­ing Bay­lor’s re­la­tion­ship with Ku­ur has been work­ing with the cells for two decades, he said.

Kurt Gunter

“One rea­son that we like this cell type is it homes nat­u­ral­ly to the tis­sue in sol­id tu­mors… It al­so has an in­vari­ant T-cell re­cep­tor… and that means it’s the same in every­one so it won’t cause graft-ver­sus-host dis­ease when we use it in an­oth­er per­son as off-the-shelf ther­a­py. And that means we don’t need to gene ed­it the TCR and that puts us in a fun­da­men­tal­ly dif­fer­ent po­si­tion from the peo­ple work­ing with CAR-T cells,” CMO Kurt Gunter said.

Ku­ur’s sec­ond can­di­date, an off-the-shelf CD19-di­rect­ed CAR-NKT ther­a­py, achieved a PR and CR in the two pa­tients with hema­to­log­i­cal ma­lig­nan­cies who were evalu­able in the Phase I study, AN­CHOR. The re­searchers saw no CRS cas­es, and no ev­i­dence of graft ver­sus host dis­ease (GvHD) — a con­di­tion where donor cells at­tack their host, the com­pa­ny said.

Boyle, who took the helm last March dur­ing a ma­jor re­struc­tur­ing, ex­pects to read out full da­ta from both the Phase I stud­ies next year. And if all goes well, he’s plan­ning to launch a Phase II ex­pan­sion tri­al of the AN­CHOR study in 2021.

Un­til last March, Ku­ur went by the name Cell Med­ica. The Lon­don-based up­start had lo­ca­tions across two con­ti­nents and three coun­tries, Boyle said. But in­stead of work­ing on a va­ri­ety of cell ther­a­pies, the com­pa­ny chose to laser-fo­cus on the CAR-NKT pro­gram un­der an ex­clu­sive li­cense with Bay­lor. It set­tled on one lo­ca­tion in Hous­ton, right next door to their col­lab­o­ra­tors, and for­mer CEO Chris Now­ers was re­placed by Boyle, who had pre­vi­ous­ly served as CFO.

The com­pa­ny hopes to close a pri­vate fi­nanc­ing round this quar­ter, Boyle hint­ed, some of which will be used to trans­form the sin­gle-cen­ter stud­ies in­to mul­ti-cen­ter stud­ies.

“The sit­u­a­tion with neu­rob­las­toma is still kind of bleak es­pe­cial­ly for these high risk re­lapsed re­frac­to­ry pa­tients,” Gunter said. “They have gen­er­al sur­vivals of less than one year, once they’ve re­lapsed,” he con­tin­ued, adding that he be­lieves the com­pa­ny can bring a sig­nif­i­cant ben­e­fit to pa­tients.

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Voting in the 2020 election (AP Images)

The right to vote is fun­da­men­tal — a let­ter from biotech­nol­o­gy in­dus­try lead­ers

Biotech Voices is a collection of exclusive opinion editorials from some of the leading voices in biopharma on the biggest industry questions today. Think you have a voice that should be heard? Reach out to senior editors Kyle Blankenship and Amber Tong.

We oppose all attempts to introduce laws that reduce the rights of US citizens to vote or that restrict them from exercising that right. The right to vote is fundamental to democracy. States that have enacted, or are proposing to enact, legislation to restrict voting are undermining our democracy and posing a threat to our nation. As leaders of the life sciences industry, we stand for what we believe is right for our country, our enterprises, our employees and those who benefit from our work. We join the first groups of business leaders who have challenged these laws and will continue to make our collective voices heard on this matter.

Pascal Soriot (AstraZeneca via YouTube)

Af­ter be­ing goad­ed to sell the com­pa­ny, Alex­ion's CEO set some am­bi­tious new goals for in­vestors. Then Pas­cal So­ri­ot came call­ing

Back in the spring of 2020, Alexion $ALXN CEO Ludwig Hantson was under considerable pressure to perform and had been for months. Elliott Advisers had been applying some high public heat on the biotech’s numbers. And in reaching out to some major stockholders, one thread of advice came through loud and clear: Sell the company or do something dramatic to change the narrative.

In the words of the rather dry SEC filing that offers a detailed backgrounder on the buyout deal, Alexion stated: ‘During the summer and fall of 2020, Alexion also continued to engage with its stockholders, and in these interactions, several stockholders encouraged the company to explore strategic alternatives.’

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Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

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Launched by MIT grads, a small start­up gets $20M to back a ro­bot­ics rev­o­lu­tion in cell ther­a­py man­u­fac­tur­ing

As co-director of an experimental cellular therapy process development and manufacturing group at UCSF specializing in T cell therapies for autoimmune conditions, Jonathan Esensten has learned a lot about the challenges involved when his group hand-fashions a cell therapy. Esensten — who was a postdoc in Wendell Lim’s lab and counts the legendary Jeffrey Bluestone as a mentor — gives them all high marks at being great at what they do, but time and again there are variations in the treatments they construct.

Anand Shah (FDA)

For­mer head of FDA’s med­ical and sci­en­tif­ic af­fairs on Covid: ‘FDA has nev­er been test­ed like this’

Anand Shah has served the American public in a unique way, crisscrossing over the last two administrations between serving as an attending radiation oncologist focused on prostate cancer at NIH, serving as CMO at the Center for Medicare and Medicaid Innovation, and most recently, leading the FDA’s operations on medical and scientific affairs from within the commissioner’s office.

Shah, who stepped down from the FDA in January, caught up with Endpoints News in a phone interview on Tuesday afternoon, offering his thoughts on the agency’s latest decision to pause the J&J vaccinations in the US, and reflecting on his time at an agency during this once-in-a-lifetime pandemic.

Stéphane Bancel, Moderna CEO (Jeff Rumans)

'Learned a lot last year': Af­ter Covid-19 suc­cess, Mod­er­na's Stéphane Ban­cel plans to give rest of pipeline a big push

A year ago, Stéphane Bancel would have described Moderna as cautious — walking step-by-step to investigate whether mRNA vaccines could prevent a host of viruses. Then the pandemic hit, and the Cambridge, MA-based biotech got a multibillion-dollar windfall to produce the world’s second-ever authorized mRNA vaccine in a matter of months.

What’s next? Bancel is planning a big acceleration and expansion of the rest of the pipeline, including the company’s Phase III-ready candidate for cytomegalovirus (CMV), which was the lead program before Covid-19 came around.

UP­DAT­ED: J&J paus­es vac­cine roll­out as feds probe rare cas­es of blood clots

The FDA and CDC have jointly decided to stop administering J&J’s Covid-19 vaccine after reviewing data involving six reported US cases of a rare and severe type of blood clot in individuals after receiving the vaccine.

CDC will convene a meeting of its Advisory Committee on Immunization Practices on Wednesday to further review these cases and assess their potential significance. “FDA will review that analysis as it also investigates these cases. Until that process is complete, we are recommending a pause in the use of this vaccine out of an abundance of caution,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research and Anne Schuchat, Principal Deputy Director of the CDC, said in a joint statement Tuesday morning.

Patrizia Cavazzoni, new CDER director

Pa­trizia Cavaz­zoni named per­ma­nent di­rec­tor of CDER, adding to ques­tions around where Wood­cock will end up

Patrizia Cavazzoni on Monday became the permanent director of the FDA’s Center for Drug Evaluation and Research, which puts to rest the idea that Janet Woodcock, Cavazzoni’s predecessor, might return to lead CDER if she isn’t made permanent commissioner.

Woodcock, who’s currently serving as acting commissioner and principal medical advisor to the commissioner, a position she was detailed to last year, may not make the move to permanent commissioner because of lingering questions from Senate Democrats. She previously served as director of CDER since 1994. Cavazzoni took over as acting director of CDER when Woodcock moved over to Operation Warp Speed to run the therapeutics side of the Trump-era program.

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