Cytokinetics gets the Royalty treatment, snagging up to $450M to support closely watched heart programs

Cy­to­ki­net­ics stum­bled a bit with its close­ly watched lead heart drug over the last year or so, los­ing two phar­ma part­ners af­ter miss­ing a key sec­ondary end­point in a Phase III study. But things are look­ing up in 2022, as Roy­al­ty Phar­ma is reach­ing a lit­tle deep­er in­to its wal­let to bol­ster that pro­gram and an­oth­er heart can­di­date.

Roy­al­ty Phar­ma has agreed to lend up to $300 mil­lion to sup­port the po­ten­tial com­mer­cial­iza­tion of Cy­to­ki­net­ics’ lead can­di­date, ome­cam­tiv mecar­bil, and de­vel­op­ment of its oth­er heart pro­gram, afi­camten. The cash will come in five tranch­es, in­clud­ing an ini­tial tranche of $50 mil­lion up­on clos­ing and four oth­ers up­on cer­tain reg­u­la­to­ry and clin­i­cal mile­stones. Each tranche has an in­ter­est-free and pay­ment-free pe­ri­od of six cal­en­dar quar­ters, fol­lowed by 34 cal­en­dar quar­ters of in­stall­ment re-pay­ments to­tal­ing 1.9 times the amount drawn.

In ad­di­tion, Roy­al­ty is putting down $50 mil­lion up­front and an­oth­er $100 mil­lion in biobucks for a roy­al­ty on afi­camten of 4.5% on sales up to $1 bil­lion and 3.5% on sales above $1 bil­lion, sub­ject to cer­tain po­ten­tial step-downs.

Cy­to­ki­net­ics’ stock $CYTK was down near­ly 4% on Fri­day morn­ing, with shares pric­ing in at $37.25 apiece. The deal ex­pands on a ‘fruit­ful re­la­tion­ship’ that dates back to 2017, ac­cord­ing to Cy­to­ki­net­ics CEO Robert Blum, when Roy­al­ty bought a 4.5% roy­al­ty on world­wide sales of ome­cam­tiv mecar­bil for $90 mil­lion and bought an­oth­er $10 mil­lion worth in eq­ui­ty. ‘Our his­to­ry has taught us that do­ing a deal opens the door on an­oth­er deal,’ Blum said dur­ing an in­vestor call on Fri­day, adding that the com­pa­ny is con­sid­er­ing go­ing af­ter part­ner­ships in oth­er ter­ri­to­ries like Japan and Eu­rope.

Just a cou­ple of weeks ago, the South San Fran­cis­co biotech an­nounced an ex­pand­ed part­ner­ship with Shang­hai biotech Ji Xing Phar­ma­ceu­ti­cals to de­vel­op and com­mer­cial­ize ome­cam­tiv mecar­bil in Chi­na, Hong Kong, Macau and Tai­wan.

‘It was our goal to com­plete a struc­tured fi­nanc­ing trans­ac­tion to fur­ther bol­ster our bal­ance sheet to sup­port the de­vel­op­ment and ex­pan­sion of our car­dio­vas­cu­lar pro­grams and po­ten­tial fran­chise,’ Blum said. ‘To­day’s an­nounce­ment puts a punc­tu­a­tion point on a struc­tured fi­nanc­ing deal cam­paign that we launched last year, and which ul­ti­mate­ly had us ac­tive­ly en­gag­ing with over a dozen dif­fer­ent in­vest­ment funds, most of which we took in­to de­tailed dis­cus­sions of terms.’

Fif­teen years af­ter en­ter­ing the clin­ic, Cy­to­ki­net­ics read out the Phase III da­ta for ome­cam­tiv mecar­bil back in No­vem­ber 2020. The drug tech­ni­cal­ly worked, meet­ing its pri­ma­ry end­point, but it flopped on a key sec­ondary end­point — re­duc­tion of car­dio­vas­cu­lar death. Am­gen shrugged off its 14-year al­liance with Cy­to­ki­net­ics just over a week lat­er. Then in May, Astel­las walked out of its own part­ner­ship on skele­tal sar­com­ere ac­ti­va­tors for dis­eases as­so­ci­at­ed with mus­cle weak­ness. Cy­to­ki­net­ics re­turned that same month with post-hoc da­ta (which can be a dif­fi­cult sell at the FDA) sug­gest­ing ome­cam­tiv mecar­bil works bet­ter in sick­er pa­tients. In the analy­sis, Cy­to­ki­net­ics sep­a­rat­ed pa­tients from the Phase III GALAC­TIC-HF study in­to four quar­tiles based on ejec­tion frac­tion, a mea­sure­ment of how well the left ven­tri­cle pumps blood with each heart­beat. Pa­tients in the low­er two quar­tiles — those with an EF of 22% or low­er, and be­tween 29% to 32% — saw a 15% and 17% rel­a­tive risk re­duc­tion of heart fail­ure events and car­dio­vas­cu­lar death com­bined, Cy­to­ki­net­ics re­port­ed at ACC. No dif­fer­ence was seen in the up­per two quar­tiles.

The com­pa­ny had said it hoped to sub­mit an NDA in Q4 2021, though no fur­ther up­dates have been giv­en.

‘We ex­pect to com­ment up­on its po­ten­tial ac­cep­tance with the FDA,’ a spokesper­son told End­points News on Fri­day.

Then there’s afi­camten, Cy­to­ki­net­ics’ car­diac myosin in­hibitor tar­get­ing hy­per­trophic car­diomy­opa­thy (HCM). Cy­to­ki­net­ics read out some pos­i­tive Phase II da­ta back in Ju­ly, show­ing pa­tients tak­ing the can­di­date for 10 weeks saw ‘sub­stan­tial and sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tions’ from base­line in the av­er­age rest­ing left ven­tric­u­lar out­flow tract pres­sure gra­di­ent (LVOT-G) and the av­er­age post-Val­sal­va LVOT-G, com­pared to place­bo.

That drug is in main com­pe­ti­tion with Bris­tol My­ers Squibb’s mava­camten, which was hit with a ma­jor set­back in No­vem­ber when the FDA ex­tend­ed its PDU­FA date three months, from Jan. 28 to April 28.

Their Staying Power Lies in their Patient-Centricity

Decentralized clinical trials (DCTs) were traditionally utilized in an isolated fashion prior to the COVID-19 pandemic. To continue their research within the constraints of the pandemic, sponsors and clinical investigators pivoted to a decentralized model out of necessity. At the onset, regulatory agencies offered some guidance on the digital approaches that are acceptable to ensure DCT approaches are applied in a way that maintains patient safety, as well as data quality and integrity.

Exscientia CEO Andrew Hopkins and Sanofi CEO Paul Hudson

Drug R&D has for years had an abysmal track record of success, with the vast majority of drug candidates never making it to market. The promise of AI to shorten the discovery time for new drugs and up their chances of success has more big drugmakers buying in — and Sanofi is the latest.

Sanofi will pay $100 million upfront with a potential $5.2 billion in downstream milestones for access to up to 15 small molecule drugs from Exscientia, a red-hot UK deep learning company at the forefront of the so-called ‘AI-discovered’ drug R&D movement, the partners said Friday.

Unlock this story instantly and join 127,600+ biopharma pros reading Endpoints daily — and it’s free.

A district court in Texas will likely tie up the FDA’s FOIA office for months, as the court ruled late Thursday that the agency must release all documents related to its review of Pfizer-BioNTech’s Covid-19 vaccine.

The order from district judge Mark Pittman, handed down late Thursday, notes that while the Court recognizes the ‘unduly burdensome’ challenges that this FOIA request may present to the FDA, there also ‘may not be’ a more important issue at the FDA right now than the pandemic, the Pfizer vaccine, getting every American vaccinated, and making sure to the American public that the process was not rushed.

Unlock this story instantly and join 127,600+ biopharma pros reading Endpoints daily — and it’s free.

Scott Clarke, Ambagon Therapeutics CEO

The saying goes necessity is the mother of invention — and few areas of drug development are in greater need than oncology. A new startup is now repurposing promising technology to tackle the hardest-to-drug proteins, and a suite of big-name backers are buying in.

Ambagon Therapeutics launched Friday with an $85 million A round and a world-class group of researcher-founders building what are known as ‘molecular glues’ to crack the code on a class of elusive cellular proteins, the biotech said.

Unlock this story instantly and join 127,600+ biopharma pros reading Endpoints daily — and it’s free.

In the year-plus since Roger Perlmutter left his post leading Merck’s R&D efforts, the Big Pharma’s new leadership has continued to pursue an aggressive dealmaking strategy. On Friday, Merck enlisted a new partner as the spree shows no signs of slowing down.

Merck signed a pair of collaborations with Absci aiming to bolster its AI research capabilities, the companies announced Friday. The first is a relatively modest deal on Merck’s end — there are no details about the upfront or milestone payments but the duo said it could lead to more.

Unlock this story instantly and join 127,600+ biopharma pros reading Endpoints daily — and it’s free.

Regeneron has held high hopes for evinacumab, a rare cholesterol disorder drug that earned a first-in-class nod from the FDA early last year, as a centerpiece of its cardiometabolic franchise. Now, the company is tapping an ultra-rare specialist to take evinacumab to the next level abroad.

Regeneron will receive $30 million in upfront cash and a potential $63 million in downstream milestones from Ultragenyx for ex-US licensing rights to Evkeeza (evinacumab), an ANGPTL3 blocker with an FDA approval to treat a rare cholesterol disorder alongside LDL-C lowering therapy and diet, the companies said Friday.

New year, same Fujifilm Diosynth.

The CDMO giant hit the ground running at full speed this year, announcing it will expand its BioProcess Innovation Center in Research Triangle Park, NC. The move will double its existing laboratory footprint in the Tar Heel State, and add another 145 skilled jobs to the site by 2024. Another 89,000 square feet will be added, which will allow for a more robust commercial process.

Aligos Therapeutics took a beating Thursday after reporting it is stopping development on its lead program for chronic hepatitis B.

The biotech’s shares $ALGS closed down 57% and fell into penny stock territory Thursday, following a morning press release saying Aligos’ ALG-010133 program did not prove efficacious at the dose tested in a Phase I study. Additionally, the company concluded that higher doses were also unlikely to be effective, and ultimately decided to axe the candidate altogether.

Unlock this story instantly and join 127,600+ biopharma pros reading Endpoints daily — and it’s free.

Marc Dunoyer, Alexion CEO (AstraZeneca via YouTube)

AstraZeneca — or, more specifically, its rare disease subsidiary Alexion — is serious about getting into ATTR amyloidosis.

Just weeks after licensing a late-stage antisense candidate from Ionis, AstraZeneca has struck another deal to pick up a Phase Ib antibody hitting the same target, this time from Swiss biotech Neurimmune.

The upfront from Alexion comes in at $30 million, with the potential to add up to $730 million in milestones. Alexion is hoping the program would tackle transthyretin amyloid cardiomyopathy, or ATTR-CM, which is characterized by cardiac buildup of toxic amyloid fibrils.
https://endpts.com/cytokinetics-gets-the-royalty-treatment-snagging-up-to-450m-to-support-closely-watched-heart-programs