Kevin Lee, Bicycle Therapeutics CEO (Bicycle)

Strug­gling Io­n­is li­cens­es Bi­cy­cle Ther­a­peu­tic­s' plat­form in a bid to de­vel­op drugs that can cross blood-brain bar­ri­er

At­tempt­ing to re­bound from set­backs ear­li­er this year, Io­n­is has en­list­ed a new part­ner in a quest to cre­ate drugs that can cross the blood-brain bar­ri­er. And the tech­nol­o­gy comes from a British biotech pri­mar­i­ly known for its ef­forts in­to on­col­o­gy.

The col­lab­o­ra­tion will see Io­n­is ex­clu­sive­ly li­cense a plat­form from Bi­cy­cle Ther­a­peu­tics to de­vel­op oligonu­cleotides tar­get­ing the trans­fer­rin re­cep­tor 1, the com­pa­nies an­nounced Tues­day morn­ing. Bi­cy­cle is nab­bing $45 mil­lion up­front and an $11 mil­lion eq­ui­ty in­vest­ment from Io­n­is.

There are al­so mile­stones for R&D and com­mer­cial­iza­tion in­volved — though the ex­act fig­ures re­main undis­closed, each mile­stone will be in the “low sin­gle-dig­it mil­lion amount,” Bi­cy­cle CEO Kevin Lee told End­points News.

Tues­day’s deal came out of an eval­u­a­tion and op­tion agree­ment the two signed last De­cem­ber, where Io­n­is gave Bi­cy­cle $3 mil­lion to use the plat­form to val­i­date po­ten­tial tar­gets, Lee said. Over the last sev­er­al months, the re­search proved fruit­ful enough where Io­n­is ex­er­cised its op­tion to ful­ly li­cense the tech. The $3 mil­lion fig­ure makes up a part of Tues­day’s up­front sum, Lee added.

Io­n­is plans to uti­lize Bi­cy­cle’s plat­form to de­vel­op what they’ve termed ad­vanced lig­and con­ju­gat­ed an­ti­sense med­i­cines, or LI­CAs, for use with oligonu­cleotides to tar­get the trans­fer­rin re­cep­tor 1. Io­n­is has been work­ing on LI­CAs for some time, and their goal is os­ten­si­bly to bring a new method to fur­ther push these com­pounds’ de­vel­op­ment.

Trans­fer­rin re­cep­tor 1 plays a role in the body’s nat­ur­al abil­i­ty to ship iron be­tween the blood-brain bar­ri­er and in­to skele­tal mus­cle, Lee not­ed.

Bi­cy­cle’s plat­form al­lows for the cre­ation of syn­thet­ic short pep­tides that are con­strained to form two loops. The struc­ture is key in drugs that can de­liv­er pay­loads to their tar­gets ef­fec­tive­ly, and Lee said Bi­cy­cle has done this on its own to cre­ate can­cer drugs de­signed to bet­ter re­tain such car­go with­in sol­id tu­mors.

The biotech’s strat­e­gy thus far has been to fo­cus in­ter­nal re­sources in­to on­col­o­gy and part­ner with oth­er com­pa­nies who are in­ter­est­ed in us­ing them in oth­er fields, Lee said. Tues­day’s oligonu­cleotide deal is em­blem­at­ic of that strat­e­gy, he added, as Bi­cy­cle re­tains full rights to the plat­form.

“They’ve tak­en on most of the risk,” Lee said of Io­n­is. “But it’s still re­al­ly ex­cit­ing in terms of what they plan to do with the tech­nol­o­gy and what they can de­rive from these agents with oligonu­cleotide de­liv­ery … in do­ing so we can har­ness the po­ten­tial of the tech­nol­o­gy.”

Bi­cy­cle had been work­ing on adapt­ing the plat­form for trans­fer­rin re­cep­tor 1 since 2019 in a part­ner­ship with the De­men­tia Dis­cov­ery Fund, and with the new deal, Io­n­is can build on that foun­da­tion. It’s not the first col­lab­o­ra­tion Bi­cy­cle has en­tered to ex­pand the plat­form be­yond on­col­o­gy. Back in 2016, it teamed up with As­traZeneca in a pact worth about $1 bil­lion and has since signed on to part­ner­ships with Roche and the UK gov­ern­ment.

For Io­n­is, the deal marks part of an ef­fort to re­bound from two high-pro­file miss­es ear­li­er this year, af­ter a Hunt­ing­ton’s can­di­date failed in March and af­ter the com­pa­ny scrapped its ear­ly-stage cys­tic fi­bro­sis pro­gram in May. And in 2020, Io­n­is re­ab­sorbed the biotech Akcea af­ter spin­ning it out three years ear­li­er, and soon put 70% of its work­force on the chop­ping block.

MedTech clinical trials require a unique regulatory and study design approach and so engaging a highly experienced CRO to ensure compliance and accurate data across all stages is critical to development milestones.

In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

Avance Clinical is the Australian CRO for international biotechs providing world-class clinical research services with FDA-accepted data across all phases. With Avance Clinical, biotech companies can leverage Australia’s supportive clinical trials environment which includes no IND requirement plus a 43.5% Government incentive rebate on clinical spend. The CRO has been delivering clinical drug development services for international biotechs for FDA and EMA regulatory approval for the past 24 years. The company has been recognized for the past two consecutive years with the prestigious Frost & Sullivan CRO Best Practices Award and a finalist in Informa Pharma’s Best CRO award for 2022.

Ted Love, Global Blood Therapeutics CEO

Up­dat­ed: Pfiz­er scoops up Glob­al Blood Ther­a­peu­tics and its sick­le cell ther­a­pies for $5.4B

Pfizer is dropping $5.4 billion to acquire Global Blood Therapeutics.

Just ahead of the weekend, word got out that Pfizer was close to clinching a $5 billion buyout — albeit with other potential buyers still at the table. The pharma giant, flush with cash from Covid-19 vaccine sales, apparently got out on top.

The deal immediately swells Pfizer’s previously tiny sickle cell disease portfolio from just a Phase I program to one with an approved drug, Oxbryta, plus a whole pipeline that, if all approved, the company believes could make for a $3 billion franchise at peak.

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FDA commissioner Rob Califf (Tom Williams/CQ Roll Call via AP Images)

With drug pric­ing al­most done, Con­gress looks to wrap up FDA user fee leg­is­la­tion

The Senate won’t return from its summer recess until Sept. 6, but when it does, it officially has 18 business days to finalize the reauthorization of the FDA user fee programs for the next 5 years, or else thousands of drug and biologics reviewers will be laid off and PDUFA dates will vanish in the interim.

FDA commissioner Rob Califf recently sent agency staff a memo explaining how, “Our latest estimates are that we have carryover for PDUFA [Prescription Drug User Fee Act], the user fee funding program that will run out of funding first, to cover only about 5 weeks into the next fiscal year.”

Pascal Soriot, AstraZeneca CEO (David Zorrakino/Europa Press via AP Images)

As­traZeneca and Dai­ichi Sankyo sprint to mar­ket af­ter FDA clears En­her­tu in just two weeks

Regulators didn’t keep AstraZeneca and Daiichi Sankyo waiting long at all for their latest Enhertu approval.

The partners pulled a win on Friday in HER2-low breast cancer patients who’ve already failed on chemotherapy, just two weeks after submitting a supplemental BLA. While this isn’t the FDA’s fastest approval — Bristol Myers Squibb won an OK for its blockbuster checkpoint inhibitor Opdivo in just five days back in March — it comes well ahead of Enhertu’s original Q4 PDUFA date.

GSK and IQVIA launch plat­form of US vac­ci­na­tion da­ta, show­ing drop in adult rates

Throughout the Covid-19 pandemic, the issue of vaccine uptake has been a point of contention, but a new platform from GSK and IQVIA is hoping to shed more light on vaccine data, via new transparency and general awareness.

The two companies have launched Vaccine Track, a platform intended to be used by public health officials, medical professionals and others to strengthen data transparency and display vaccination trends. According to the companies, the platform is intended to aid in increasing vaccine rates and will provide data on trends to assist public health efforts.

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Ab­b­Vie sur­veys emo­tion­al im­pact of chron­ic leukemia con­di­tion, finds 'roller coast­er' of emo­tions

Rare diseases often have more than just physical effects on patients — especially when it comes to chronic conditions. In the case of the rare slow-growing blood cancer chronic lymphocytic leukemia (CLL), AbbVie wanted to try to assess the mental and emotional toll on patients.

So it surveyed more than 300 CLL patients, caregivers and physicians. While each group differed in how they felt — caregivers overwhelmingly (81%) felt positive about their role, for instance — patients described a “roller coaster” of emotions traversing diagnosis to treatment to remission and even relapse for some.

David Reese, Amgen R&D chief

UP­DAT­ED: In a fresh dis­ap­point­ment, Am­gen spot­lights a ma­jor safe­ty is­sue with KRAS com­bo

Amgen had hoped that its latest study matching its landmark KRAS G12C drug Lumakras with checkpoint inhibitors would open up its treatment horizons and expand its commercial potential. Instead, the combo spurred safety issues that blunted efficacy and forced the pharma giant to alter course on its treatment strategy, once again disappointing analysts who have been tracking the drug’s faltering sales and limited therapeutic reach.

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Bernhardt Zeiher, outgoing Astellas CMO (Astellas)

Q&A: Astel­las' re­tir­ing head of de­vel­op­ment re­flects on gene ther­a­py deaths

For anyone who’s been following discussions about the safety alarms surrounding the adeno-associated viruses (AAV) commonly used to deliver gene therapy, Astellas should be a familiar name.

The Japanese pharma — which bought out Audentes Therapeutics near the end of 2019 and later built a gene therapy unit around the acquisition — rocked the field when it reported three patient deaths in a trial testing AT132, the lead program from Audentes designed to treat a rare muscle disease called X-linked myotubular myopathy (XLMTM).

When the company restarted the trial, it adjusted the dose and instituted a battery of other measures to try to prevent the same thing from happening again. But tragically, the first patient to receive the new regimen died just weeks after administration. The therapy remains under clinical hold, and just weeks ago, Astellas flagged another safety-related hold for a separate gene therapy candidate. In the process of investigating the deaths, the company has also taken flak about the way it disclosed information.

Big questions remain — questions that can have big implications about the future of AAV gene therapies.

Bernhardt Zeiher did not imagine any of it when he first joined Astellas as the therapeutic area leader in inflammation, immunology and infectious diseases. But his ascent to chief medical officer and head of development coincided almost exactly with Astellas’ big move into gene therapy, putting him often in the driver’s seat to grapple with the setbacks.

As Zeiher prepares to retire next month after a 12-year tenure — leaving the unfinished tasks to his successor, a seasoned cancer drug developer — he chatted with Endpoints News, in part, to discuss the effort to understand what happened, lessons learned and the criticism along the way.

The transcript has been lightly edited for length and clarity.

Endpoints: I want to also ask you a bit about the gene therapy efforts you’ve been working on. Astellas has really been at the forefront of discovering the safety concerns associated with AAV gene therapy. What’s that been like for you?

Zeiher: Well, I have to admit, it’s been a bit of a roller coaster. We acquired Audentes. Huge amount of enthusiasm. What we saw with AT132 — that was the lead program in XLMTM — was just remarkable efficacy. I mean, kids who went from being on ventilators, not able to eat for themselves, sit up, do things like that, to off ventilators, walking, you know, really — one investigator called it this Lazarus-like effect. It was just really dramatic efficacy. And then to have the safety events that occurred. So they actually occurred within that first year of the acquisition. So we had the three patient deaths. Me and my organization became very, very much involved. In fact, Ed Conner, who had been the chief medical officer, he left after some of the deaths, but I stepped in as the kind of acting chief medical officer, we had another chief medical officer who was involved, and then we had a fourth death, and I became acting again for a period of time.

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Doug Ingram, Sarepta CEO

Sarep­ta li­cens­es next-gen AAV tech from Broad In­sti­tute in deal cov­er­ing five in­di­ca­tions — in­clud­ing Duchenne

Sarepta’s research agreement with the Broad Institute is taking the next step Monday.

The biotech will license a new group of adeno-associated viruses from the institute for an undisclosed upfront payment and milestone promises, the pair announced Monday morning. Under the agreement, Sarepta will have the rights to five neuromuscular and cardiac indications, including Duchenne muscular dystrophy, where it’s already well-versed.