Cereno Sci­en­tif­ic is dri­ving a new par­a­digm of throm­bo­sis pre­ven­tion with­out as­so­ci­at­ed bleed­ing-risks

Cereno Sci­en­tif­ic is cur­rent­ly in the clin­i­cal phase of de­vel­op­ing a new drug with the po­ten­tial to re­de­fine throm­bo­sis pre­ven­tion with­out caus­ing an in­creased risk of bleed­ing. This is wide­ly known as the ‘holy grail’ of an­ti­co­ag­u­la­tion ther­a­py and has his­tor­i­cal­ly caused sig­nif­i­cant com­mo­tion in the in­vest­ment and Big Phar­ma com­mu­ni­ty. To­day, all mar­ket­ed treat­ments are lim­it­ed by the bleed­ing side-ef­fects that they cause. Pre­ven­tive treat­ments present­ly on the mar­ket (e.g. War­farin; non-vi­t­a­min K oral an­ti­co­ag­u­lants or NOACs) act di­rect­ly by in­ter­ven­ing in the co­ag­u­la­tion cas­cade, while Cereno Sci­en­tif­ic’s can­di­date CS1 is aimed at pre­vent­ing throm­bo­sis by strength­en­ing the body’s own de­fense against blood clots, as it strikes a bal­ance be­tween the clot­ting and the an­ti-co­ag­u­lant fac­tors.

This bal­ance is key not on­ly for pre­vent­ing blood clots from form­ing, but al­so for man­ag­ing ex­ces­sive bleed­ing, which is a ma­jor side ef­fect of treat­ments cur­rent­ly on the mar­ket. This would make CS1 a safer and more ef­fec­tive treat­ment over­all. Fur­ther­more, Cereno Sci­en­tif­ic be­lieves that the unique mech­a­nism of ac­tion of its can­di­date could make it a valid treat­ment for pa­tients who are al­ready tak­ing oth­er an­ti-co­ag­u­lant drugs, mean­ing that CS1 has the po­ten­tial to reach a larg­er pa­tient group com­pared to NOACs or War­farin, thus in­creas­ing its mar­ket po­ten­tial.

Sten R. Sörensen, CEO, Cereno Sci­en­tif­ic

The ac­tive in­gre­di­ent in CS1 is val­proic acid (VPA), which has long been used, at a high­er dose than CS1, in the treat­ment of epilep­sy and has a well-doc­u­ment­ed safe­ty pro­file in hu­mans. This arms Cereno Sci­en­tif­ic with a sol­id foun­da­tion for the prod­uct’s ex­pect­ed safe­ty pro­file, while re­duc­ing the risk of safe­ty be­ing an ob­sta­cle stand­ing in be­tween CS1 and a mar­ket ap­proval. Mar­ket un­cer­tain­ties about CS1 are thus more re­lat­ed to ef­fi­ca­cy. An epi­demi­o­log­i­cal study pub­lished in 2011 showed a strong as­so­ci­a­tion be­tween VPA treat­ment and the re­duced risk of my­ocar­dial in­farc­tion, in more than 100 000 pa­tients, which ex­plains why Cereno Sci­en­tif­ic has a keen in­ter­est in this com­pound. In ad­di­tion, there is in vi­vo da­ta from an­i­mals sup­port­ing the com­pa­ny’s an­ti­co­ag­u­la­tion the­o­ry of VPA. Over­all, this is a good ba­sis for Cereno’s prod­uct strat­e­gy, which will in­volve low drug de­vel­op­ment risks com­pared with a new class of sub­stances, there­by en­abling a faster route-to-mar­ket.

In­deed, the com­pa­ny has been mov­ing for­ward quick­ly with CS1: a phase I study show­ing pos­i­tive da­ta was com­plet­ed in June of this year, and a phase II study has been planned and is set to be­gin dur­ing the sec­ond half of 2019, with re­sults ex­pect­ed to come in 2020. The tri­als will be per­formed by the OCT Group, which have re­cent­ly signed an agree­ment with Cereno Sci­en­tif­ic. Pa­tients from 20 clin­ics through­out Rus­sia and Bul­gar­ia who have un­der­gone or­thopaedic surgery, which in­creas­es the risk of de­vel­op­ing blood clots, are ex­pect­ed to par­tic­i­pate in the study.

Cereno is fol­low­ing a reg­u­la­to­ry path with high re­sem­blance to cur­rent mar­ket lead­ers, such as Xarel­to and Eliquis. In essence, this in­volves achiev­ing a clin­i­cal proof of con­cept in a small and well-de­fined pa­tient pop­u­la­tion be­fore ad­dress­ing the larg­er pop­u­la­tion that has made these two prod­ucts in­to block­busters. The choice of pre­vent­ing throm­bo­sis in the deep veins of the legs and in the lungs of pa­tients un­der­go­ing planned or­thopaedic surgery as study pop­u­la­tion for the phase II tri­als is con­sid­ered very cost ef­fec­tive. Not on­ly does this strat­e­gy al­low CS1 to reach a sta­tis­ti­cal sig­nif­i­cance based on a small­er num­ber of pa­tients com­pared to an in­di­ca­tion like stroke or my­ocar­dial in­farc­tion, it al­so short­ens the re­quired fol­low-up study pe­ri­od, thus short­en­ing the to­tal time­line while low­er­ing over­all costs.

In ef­fect, this pro­vides a good ba­sis for its reg­u­la­to­ry strat­e­gy, which in­volves CS1 achiev­ing mar­ket ap­proval for ve­nous throm­boem­bolism (VTE) first. This en­ables Cereno Sci­en­tif­ic to fo­cus on widen­ing its mar­ket ei­ther as a se­quen­tial or a par­al­lel track with the in­tent to in­clude pre­ven­tive treat­ment for stroke and my­ocar­dial in­farc­tion on the same prod­uct la­bel. This re­flects the paths tak­en by oth­er an­ti-co­ag­u­lant sell­ers in terms of reg­u­la­to­ry strat­e­gy.

The mar­ket po­ten­tial for CS1 is sig­nif­i­cant. Ac­cord­ing to IMS Health, throm­bo­sis pre­ven­ta­tive drugs were worth an es­ti­mat­ed 23,5 BUSD in 2013, and this num­ber is ex­pect­ed to in­crease to 25,9 BUSD in 2018. This gives Cereno a sol­id ba­sis for its fu­ture sales prospects. More­over, a patent for CS1 was re­cent­ly ap­proved in the US, thus in­creas­ing the can­di­date’s fu­ture com­mer­cial­i­sa­tion pos­si­bil­i­ties as the US con­sti­tutes al­most half of the glob­al mar­ket. Not to men­tion, Chi­na is al­so ex­pect­ed to be a main mar­ket for an­ti­co­ag­u­lant drugs as the sales in the coun­try ex­ceed­ed 12,4 BUSD in 2014 and are ex­pect­ed to grow even fur­ther. In ad­di­tion, there is cur­rent­ly an en­dem­ic un­der­use of an­ti­co­ag­u­lant ther­a­pies in Chi­na be­cause of a fear among physi­cians to in­crease the risk of caus­ing bleed­ing. This both in­di­cates that the Chi­nese mar­ket has tremen­dous growth po­ten­tial and that an agent with­out the as­so­ci­at­ed bleed­ing risk may ad­dress an un­met clin­i­cal need per­ceived as high­ly im­por­tant.

The most sig­nif­i­cant chal­lenge fac­ing the com­pa­ny at this point is ac­tu­al­ly its de­clin­ing stock price. Cereno Sci­en­tif­ic signed a con­vert­ible loan agree­ment worth 82-106 MSEK with the Eu­ro­pean High Growth Op­por­tu­ni­ties Se­cu­ri­ti­za­tion Fund (EHGO) in April of this year. While the agree­ment se­cured fi­nanc­ing for the up­com­ing phase II study, Cereno’s stock price has fall­en by just over a third thanks to EHGO sell­ing its con­vert­ed shares, a phe­nom­e­non com­mon­ly re­ferred to as death spi­ral fi­nanc­ing.

This move has put Cereno’s mar­ket cap at a mere 40 MSEK, or ap­prox­i­mate­ly 4.5 mil­lion USD, which is like­ly a sig­nif­i­cant un­der­es­ti­ma­tion con­sid­er­ing the multi­bil­lion-dol­lar mar­ket po­ten­tial and CS1’s cur­rent phase of clin­i­cal de­vel­op­ment. This could of course be seen as good news for any par­ty in­ter­est­ed in in­vest­ing or ac­quir­ing Cereno Sci­en­tif­ic. A quick glance on deal val­ues and val­u­a­tions of in­vest­ment rounds in the same space, as Cereno Sci­en­tif­ic, in­di­cates that a 4.5 mil­lion USD mar­ket cap may be a tem­po­rary anom­aly. In fact, in­vestors will prob­a­bly take note of the fact that if Cereno Sci­en­tif­ic should get a pos­i­tive da­ta read­out from its phase II tri­als, the like­li­hood of strik­ing a sig­nif­i­cant part­ner­ship deal will in­crease sub­stan­tial­ly, thus bring­ing a lot of at­ten­tion to the com­pa­ny and in­creas­ing its val­ue.

Over­all, while Cereno Sci­en­tif­ic in­deed faces a num­ber of chal­lenges and risks re­lat­ed to com­mu­ni­cat­ing its val­ue to share­hold­ers and ap­ply­ing for and achiev­ing sta­tis­ti­cal sig­nif­i­cance in its up­com­ing phase II study, the com­pa­ny has a sol­id sci­en­tif­ic base and has se­cured fi­nanc­ing from which to move for­ward with con­fi­dence. First­ly, CS1 is based on an al­ready ap­proved ac­tive com­pound with a strong safe­ty pro­file that could pos­si­bly en­able it to quick­ly en­ter the mar­ket; sec­ond­ly, the col­lab­o­ra­tion with OCT Group adds im­por­tant knowl­edge and ex­pe­ri­ence which will prove use­ful in the up­com­ing phase II study; third­ly, Cereno has es­tab­lished a patent es­tate around its pro­pri­etary for­mu­la­tion and the med­ical use of VPA that en­sures sub­stan­tial ex­clu­siv­i­ty on the mar­ket.

If CS1 can come out of the phase II tri­als with pos­i­tive re­sults, it has the po­ten­tial to low­er costs, im­prove health and gen­er­ate sig­nif­i­cant health-eco­nom­ic ben­e­fits, thus be­com­ing a First-in-Class drug rep­re­sent­ing a par­a­digm shift for throm­bo­sis pre­ven­tion. This could make it a dom­i­nant treat­ment, in health-eco­nom­ics terms, when com­pared to avail­able treat­ment al­ter­na­tives, see­ing that the al­ter­na­tives would no longer be eco­nom­i­cal­ly jus­ti­fied. With such po­ten­tial, CS1 has high prospects of achiev­ing a sig­nif­i­cant share of the mar­ket.

A full sta­tus re­port on Cereno Sci­en­tif­ic can be viewed here.

Im­age: Cereno Sci­en­tif­ic team

How small- to mid-sized biotechs can adopt pa­tient cen­tric­i­ty in their on­col­o­gy tri­als

By Lucy Clos­sick Thom­son, Se­nior Di­rec­tor of On­col­o­gy Pro­ject Man­age­ment, Icon

Clin­i­cal tri­als in on­col­o­gy can be cost­ly and chal­leng­ing to man­age. One fac­tor that could re­duce costs and re­duce bar­ri­ers is har­ness­ing the pa­tient voice in tri­al de­sign to help ac­cel­er­ate pa­tient en­roll­ment. Now is the time to adopt pa­tient-cen­tric strate­gies that not on­ly fo­cus on pa­tient needs, but al­so can main­tain cost ef­fi­cien­cy.

The top 10 block­buster drugs in the late-stage pipeline — Eval­u­ate adds 6 new ther­a­pies to heavy-hit­ter list

Vertex comes in for a substantial amount of criticism for its no-holds-barred tactical approach toward wresting the price it wants for its commercial drugs in Europe. But the flip side of that coin is a highly admired R&D and commercial operation that regularly wins kudos from analysts for their ability to engineer greater cash flow from the breakthrough drugs they create.

Both aspects needed for success in this business are on display in the program backing Vertex’s triple for cystic fibrosis. VX-659/VX-445 + Tezacaftor + Ivacaftor — it’s been whittled down to 445 now — was singled out by Evaluate Pharma as the late-stage therapy most likely to win the crown for drug sales in 5 years, with a projected peak revenue forecast of $4.3 billion.

The latest annual list, which you can see here in their latest world preview, includes a roster of some of the most closely watched development programs in biopharma. And Evaluate has added 6 must-watch experimental drugs to the top 10 as drugs fail or go on to a first approval. With apologies to the list maker, I revamped this to rank the top 10 by projected 2024 sales, instead of Evaluate's net present value rankings.

It's how we roll at Endpoints News.

Here is a quick summary of the rest of the top 10:

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John Reed at JPM 2019. Jeff Rumans for Endpoints News

Sanofi's John Reed con­tin­ues to re­or­ga­nize R&D, cut­ting 466 jobs while boost­ing can­cer, gene ther­a­py re­search

The R&D reorganization inside Sanofi is continuing, more than a year after the pharma giant brought in John Reed to head the research arm of the Paris-based company.
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John Chiminski, Catalent CEO - File Photo

'It's a growth play': Catal­ent ac­quires Bris­tol-My­er­s' Eu­ro­pean launch pad, ex­pand­ing glob­al CD­MO ops

Catalent is staying on the growth track.

Just two months after committing $1.2 billion to pick up Paragon and take a deep dive into the sizzling hot gene therapy manufacturing sector, the CDMO is bouncing right back with a deal to buy out Bristol-Myers’ central launchpad for new therapies in Europe, acquiring a complex in Anagni, Italy, southwest of Rome, that will significantly expand its capacity on the continent.

There are no terms being offered, but this is no small deal. The Anagni campus employs some 700 staffers, and Catalent is planning to go right in — once the deal closes late this year — with a blueprint to build up the operations further as they expand on oral solid, biologics, and sterile product manufacturing and packaging.

This is an uncommon deal, Catalent CEO John Chiminski tells me. But it offers a shortcut for rapid growth that cuts years out of developing a green fields project. That’s time Catalent doesn’t have as the industry undergoes unprecedented expansion around the world.

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Arc­turus ex­pands col­lab­o­ra­tion, adding $30M cash; Ku­ra shoots for $100M raise

→  Rare dis­ease play­er Ul­tragenyx $RARE is ex­pand­ing its al­liance with Arc­turus $ARCT, pay­ing $24 mil­lion for eq­ui­ty and an­oth­er $6 mil­lion in an up­front as the two part­ners ex­pand their col­lab­o­ra­tion to in­clude up to 12 tar­gets. “This ex­pand­ed col­lab­o­ra­tion fur­ther so­lid­i­fies our mR­NA plat­form by adding ad­di­tion­al tar­gets and ex­pand­ing our abil­i­ty to po­ten­tial­ly treat more dis­eases,” said Emil Kakkis, the CEO at Ul­tragenyx. “We are pleased with the progress of our on­go­ing col­lab­o­ra­tion. Our most ad­vanced mR­NA pro­gram, UX053 for the treat­ment of Glyco­gen Stor­age Dis­ease Type III, is ex­pect­ed to move in­to the clin­ic next year, and we look for­ward to fur­ther build­ing up­on the ini­tial suc­cess of this part­ner­ship.”

UP­DAT­ED: Chica­go biotech ar­gues blue­bird, Third Rock 'killed' its ri­val, pi­o­neer­ing tha­lassemia gene ther­a­py in law­suit

Blue­bird bio $BLUE chief Nick Leschly court­ed con­tro­ver­sy last week when he re­vealed the com­pa­ny’s be­ta tha­lassemia treat­ment will car­ry a jaw-drop­ping $1.8 mil­lion price tag over a 5-year pe­ri­od in Eu­rope — mak­ing it the plan­et’s sec­ond most ex­pen­sive ther­a­py be­hind No­var­tis’ $NVS fresh­ly ap­proved spinal mus­cu­lar at­ro­phy ther­a­py, Zol­gens­ma, at $2.1 mil­lion. A Chica­go biotech, mean­while, has been fum­ing at the side­lines. In a law­suit filed ear­li­er this month, Er­rant Gene Ther­a­peu­tics al­leged that blue­bird and ven­ture cap­i­tal group Third Rock un­law­ful­ly prised a vi­ral vec­tor, de­vel­oped in part­ner­ship with the Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter (MSK), from its grasp, and thwart­ed the de­vel­op­ment of its sem­i­nal gene ther­a­py.

Neil Woodford. Woodford Investment Management via YouTube

Wood­ford braces po­lit­i­cal storm as UK fi­nan­cial reg­u­la­tors scru­ti­nize fund sus­pen­sion

The shock of Neil Wood­ford’s de­ci­sion to block with­drawals for his flag­ship fund is still rip­pling through the rest of his port­fo­lio — and be­yond. Un­der po­lit­i­cal pres­sure, UK fi­nan­cial reg­u­la­tors are now tak­ing a hard look while in­vestors con­tin­ue to flee.

In a re­sponse let­ter to an MP, the Fi­nan­cial Con­duct Au­thor­i­ty re­vealed that it’s opened an in­ves­ti­ga­tion in­to the sus­pen­sion fol­low­ing months of en­gage­ment with Link Fund So­lu­tions, which tech­ni­cal­ly del­e­gat­ed Wood­ford’s firm to man­age its funds.

Gilead baits new al­liance with $45M up­front, div­ing in­to the busy pro­tein degra­da­tion field

Gilead is jump­ing on board the pro­tein degra­da­tion band­wag­on. And they’re turn­ing to a low-pro­file Third Rock start­up for the ex­per­tise. But if you were look­ing for a trans­for­ma­tion­al deal to kick up fresh en­thu­si­asm for Gilead, you’ll have to re­main pa­tient.

This one will have a long way to go be­fore they get in­to the clin­ic.

The big biotech said Wednes­day morn­ing that it is pay­ing $45 mil­lion up­front and re­serv­ing a whop­ping $2.3 bil­lion in biotech bucks if San Fran­cis­co-based Nurix can point the way to new can­cer ther­a­pies, as well as drugs for oth­er, un­spec­i­fied dis­eases.

A new num­ber 1 drug? Keytru­da tapped to top the 10 biggest block­busters on the world stage by 2024

Analysts may be fretting about Keytruda’s longterm prospects as a host of rival therapies elbow their way to the market. But the folks at Evaluate Pharma are confident that last year’s $7 billion earner is headed for glory, tapping it to beat out the current #1 therapy Humira as AbbVie watches that franchise swoon over the next 5 years.

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