UP­DAT­ED: Astel­las walks away from $450M+ Cy­to­ki­net­ics pact af­ter tak­ing a few ex­tra months to see progress

Months af­ter los­ing long­time part­ner Am­gen on its lead heart drug, Cy­to­ki­net­ics is wav­ing good­bye to an­oth­er al­ly — and with it, more than $450 mil­lion in po­ten­tial mile­stones.

Cy­to­ki­net­ics said in an SEC fil­ing last week that Astel­las is of­fi­cial­ly walk­ing away from a pact to re­search skele­tal sar­com­ere ac­ti­va­tors for dis­eases as­so­ci­at­ed with mus­cle weak­ness. The com­pa­nies had ex­tend­ed the re­search term of their part­ner­ship — which was ini­tial­ly set to ex­pire on Dec. 31 — through March of this year to fin­ish work they couldn’t get done dur­ing the pan­dem­ic, Cy­to­ki­net­ics CEO Robert Blum told End­points News. But on April 27, Astel­las gave writ­ten no­tice that it’s hit­ting the ex­it.

Ac­cord­ing to the fil­ing, Astel­las is giv­ing up “all li­cens­es and oth­er rights” grant­ed through the pact.

The re­search, de­vel­op­ment and com­mer­cial­iza­tion pact was ini­tial­ly struck back in 2013. But in April 2020, Astel­las re­turned the rights to relde­sem­tiv, Cy­to­ki­net­ics’ can­di­date to treat mus­cle wast­ing, and oth­er fast skele­tal reg­u­la­to­ry ac­ti­va­tor (FS­RA) com­pounds that were sub­ject to the orig­i­nal agree­ment. Astel­las agreed to pay one-third of the out-of-pock­et costs for Cy­to­ki­net­ics’ con­tin­ued Phase III tri­al for the drug in ALS, in re­turn for “low- to mid-sin­gle dig­it” roy­al­ties in the US, Cana­da, UK and EU for ei­ther 10 years af­ter the first sale, or un­til 2034, ac­cord­ing to an SEC fil­ing.

“The re­search pro­gram that was ex­tend­ed was done with joint agree­ment, just so we could wind down on a cou­ple of mat­ters that we agreed we want­ed to put to bed be­fore we stepped away,” Blum said“We joint­ly de­cid­ed that we were go­ing to fin­ish the re­search to­geth­er, and then go our sep­a­rate ways.”

End­points reached out to Astel­las, but did not re­ceive a re­sponse as of press time.

Cy­to­ki­net­ics is left with­out the op­por­tu­ni­ty to scoop up some ma­jor mile­stones laid out in the orig­i­nal deal. Ac­cord­ing to the deal, Astel­las could have nabbed ex­clu­sive rights to co-de­vel­op and sell the skele­tal sar­com­ere ac­ti­va­tors in all in­di­ca­tions, leav­ing Cy­to­ki­net­ics the right to co-pro­mote and do cer­tain sales work in the US, Cana­da and/or Eu­rope “un­der agreed sce­nar­ios.”

If Astel­las want­ed to take any of the can­di­dates for­ward on its own, it would have owed Cy­to­ki­net­ics $25 to $35 mil­lion per prod­uct, plus up to $250 mil­lion more for all prod­ucts and an­oth­er $200 mil­lion in com­mer­cial mile­stones. On top of all that, Cy­to­ki­net­ics would have been set to re­ceive roy­al­ties in the “mid-sin­gle-dig­it lev­el to low dou­ble-dig­its.”

The news comes about two years af­ter relde­sem­tiv flopped in a Phase II ALS tri­al. At the time, in­ves­ti­ga­tors said the study failed on change from base­line in slow vi­tal ca­pac­i­ty (SVC) af­ter 12 weeks of dos­ing (p=0.11). The analy­sis al­so showed poor p-val­ues for the ALS Func­tion­al Rat­ing Scale and slope of the Mus­cle Strength Mega-Score.

But de­spite fail­ing the pri­ma­ry end­point, the com­pa­ny ar­gued that the da­ta re­flect­ed “clin­i­cal­ly mean­ing­ful mag­ni­tudes of ef­fect” across all dose lev­els, and main­tained that the place­bo group de­clined at a slow­er rate than ex­pect­ed, which didn’t help.

“Re­sults from FOR­TI­TUDE-ALS are among the most im­pres­sive we have seen in a Phase II clin­i­cal tri­al in ALS,” lead in­ves­ti­ga­tor Je­re­my Shefn­er said back in 2019.

That wasn’t the first or last time Cy­to­ki­net­ics has tout­ed weak or failed da­ta. Back in No­vem­ber, the com­pa­ny cheered a Phase III read­out for its Am­gen-part­nered heart drug ome­cam­tiv mecar­bil. But while the can­di­date met the pri­ma­ry com­pos­ite end­point, it missed a sec­ondary end­point which an­a­lysts had been fol­low­ing as a key mark­er for suc­cess — re­duc­tion of car­dio­vas­cu­lar death.

Lat­er that month, Am­gen shrugged off its 14-year al­liance with Cy­to­ki­net­ics, leav­ing the com­pa­ny to sol­dier on alone.

“Car­dio­vas­cu­lar dis­ease is one of the most sig­nif­i­cant pub­lic health is­sues in the world which means pa­tients need more in­no­va­tion, not less,” Am­gen said in a state­ment. “… Un­for­tu­nate­ly, the re­sults of GALAC­TIC-HF did not meet the high bar we had set for the pro­gram.”

The DCT-OS: A Tech­nol­o­gy-first Op­er­at­ing Sys­tem - En­abling Clin­i­cal Tri­als

As technology-enabled clinical research becomes the new normal, an integrated decentralized clinical trial operating system can ensure quality, deliver consistency and improve the patient experience.

The increasing availability of COVID-19 vaccines has many of us looking forward to a time when everyday things return to a state of normal. Schools and teachers are returning to classrooms, offices and small businesses are reopening, and there’s a palpable sense of optimism that the often-awkward adjustments we’ve all made personally and professionally in the last year are behind us, never to return. In the world of clinical research, however, some pandemic-necessitated adjustments are proving to be more than emergency stopgap measures to ensure trial continuity — and numerous decentralized clinical trial (DCT) tools and methodologies employed within the last year are likely here to stay as part of biopharma’s new normal.

Roger Perl­mut­ter’s new gig, Covid-19 IP dra­ma, Vivek Ra­maswamy's coach on the SPAC train, and more

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UP­DAT­ED: EMA safe­ty com­mit­tee seeks more in­fo on heart in­flam­ma­tion fol­low­ing Pfiz­er Covid-19 vac­cine

The European Medicines Agency’s safety committee said Friday that it’s aware of cases of inflammation of the heart muscle and inflammation of the membrane around the heart, mainly reported following vaccination with Pfizer’s Covid-19 vaccine, known in Europe as Comirnaty.

“There is no indication that these cases are due to the vaccine,” the EMA’s Pharmacovigilance Risk Assessment Committee said.

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Onno van de Stolpe, Galapagos CEO (Thierry Roge/Belga Mag/AFP via Getty Images)

Gala­pa­gos chops in­to their pipeline, drop­ping core fields and re­or­ga­niz­ing R&D as the BD team hunts for some­thing 'trans­for­ma­tive'

Just 5 months after Gilead gutted its rich partnership with Galapagos following a bitter setback at the FDA, the Belgian biotech is hunkering down and chopping the pipeline in an effort to conserve cash while their BD team pursues a mission to find a “transformative” deal for the company.

The filgotinib disaster didn’t warrant a mention as Galapagos laid out its Darwinian restructuring plans. Forced to make choices, the company is ditching its IPF molecule ’1205, while moving ahead with a Phase II IPF study for its chitinase inhibitor ’4617.

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'Chang­ing the whole game of drug dis­cov­ery': Leg­endary R&D vet Roger Perl­mut­ter leaps back in­to work as a biotech CEO

Roger Perlmutter needs no introduction to anyone remotely involved in biopharma. As the R&D chief first at Amgen and then Merck, he’s built a stellar reputation and a prolific career steering new drugs toward the market for everything from cancer to infectious diseases.

But for years, he’s also held a less known title: science partner at The Column Group, where he’s regularly consulted about the various ideas the VCs had for new startups.

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Angela Merkel (AP Photo/Michael Sohn)

Covid-19 roundup: Pfiz­er sub­mits vac­cine for full ap­proval; Merkel op­pos­es Biden pro­pos­al to sus­pend IP for vac­cines

Pfizer and BioNTech said Friday that they’ve submitted a biologics license application to the FDA for full approval of their mRNA vaccine for those over the age of 16.

How long it will take the FDA to decide on the BLA will be set once it’s been formally accepted by the agency.

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, previously told Endpoints News that the review of the BLA should take between three and four months, but it may be even faster than that.

As­traZeneca caps PD-L1/CT­LA-4/chemo com­bo come­back with OS win. Is treme­li­mum­ab fi­nal­ly ready for ap­proval?

AstraZeneca’s closely-watched POSEIDON study continues to be the rare bright spot in its push for an in-house PD-L1/CTLA-4 combo.

Combining Imfinzi and tremelimumab with physicians’ choice of chemotherapy helped patients with stage IV non-small cell lung cancer live longer, the company reported — marking the first time the still-experimental tremelimumab has demonstrated an OS benefit.

For AstraZeneca and CEO Pascal Soriot, the positive readout — which is devoid of numbers — offers much-needed validation for the big bet they made on Imfinzi plus tremelimumab, after the PD-L1/CTLA-4 regimen failed multiple trials in head and neck cancer as well as lung cancer.

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Ron DePinho (file photo)

A 'fly­over' biotech launch­es in Texas with four Ron De­Pin­ho-found­ed com­pa­nies un­der its belt

In his 13 years at Genzyme, Michael Wyzga noticed something about East Coast drugmakers. Execs would often jet from Boston or New York to San Francisco to find more assets, and completely miss the work being done in flyover states, like Texas or Wisconsin.

“If it doesn’t come out of MGH or MIT or Harvard, probably not that interesting,” he said of the mindset.

Now, he and some well-known industry players are looking to change that, and they’ve reeled in just over $38 million to do it.

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As­traZeneca, Dai­ichi Sankyo un­cork new TNBC da­ta for 2nd part­nered ADC — and it's adding more heat un­der Gilead­'s Trodelvy

After the approval of their partnered anti-HER2 antibody-drug conjugate earlier this year, AstraZeneca and Daiichi Sankyo are riding high on the promise of their blooming partnership. Now a second ADC is showing promise in hard-to-treat breast cancer, and the companies have their eyes set on their only approved competitor in the space.

AstraZeneca and Daiichi Sankyo’s next-gen ADC datopotamab deruxtecan posted a 43% response rate and five confirmed complete or partial responses among 21 patients with triple-negative breast cancer, according to cohort data from the TROPION-PanTumor01 Phase I study presented Saturday at the virtual ESMO Breast annual meeting.