Ex­elix­is, Bris­tol-My­ers mount piv­otal study of Cabo/Op­di­vo com­bo for front­line kid­ney can­cer

Fouad Namouni, Bris­tol-My­ers Squibb

Just days af­ter re­view­ing a promis­ing start com­bin­ing Bris­tol-My­ers Squibb’s check­point in­hibitor Op­di­vo (nivolum­ab) with Cabome­tyx (cabozan­ti­nib), Ex­elix­is is rolling out a late-stage part­ner­ship that will take the com­bo in­to a piv­otal Phase III study as a front­line ther­a­py for kid­ney can­cer. And not sat­is­fied with the one check­point tie-up, the South San Fran­cis­co-based biotech al­so an­nounced a deal this morn­ing to col­lab­o­rate with Roche on a com­bi­na­tion of its drug Tecen­triq (ate­zolizum­ab) and cabo.

Ex­elix­is $EX­EL and Bris­tol-My­ers $BMY are split­ting the costs on their Phase III pro­gram, which will ex­plore the com­bo, ei­ther alone or with Yer­voy (ip­il­i­mum­ab), in kid­ney can­cer as well as blad­der can­cer, he­pa­to­cel­lu­lar car­ci­no­ma and pos­si­bly oth­er tu­mor types. The ear­ly stage work was done un­der an agree­ment with the NCI’s Can­cer Ther­a­py Eval­u­a­tion Pro­gram. This new pact marks Ex­elix­is’ and Bris­tol-My­ers’ first R&D col­lab­o­ra­tion in I/O.

Ex­elix­is shares jump 6% on the news.

Ten days ago Ex­elix­is un­veiled the first snap­shot of ef­fi­ca­cy da­ta for the dou­ble and triple com­bo in gen­i­touri­nary tu­mors.

In­ves­ti­ga­tors con­clud­ed:

Among the 43 pa­tients who were evalu­able for re­sponse, the ob­jec­tive re­sponse rate (ORR) for all tu­mor types was 30 per­cent (38 per­cent for the dou­blet dos­ing sched­ule and 18 per­cent for the triplet dos­ing sched­ule), with a 7 per­cent com­plete re­sponse (CR) rate and a 23 per­cent par­tial re­sponse (PR) rate. Sta­ble dis­ease (SD) was re­port­ed in 56 per­cent of pa­tients. The ORR for pa­tients with mUC was 38 per­cent, and 2 of 16 pa­tients achieved a CR, while 2 pa­tients with squa­mous cell car­ci­no­ma of the blad­der had ob­jec­tive re­spons­es (1 CR and 1 PR). In the mUC co­hort, 15 of 16 pa­tients had a CR, PR or SD as their best re­sponse.

“Com­bin­ing our Im­muno-On­col­o­gy port­fo­lio with promis­ing agents which tar­get dif­fer­ent and com­ple­men­tary path­ways is a key com­po­nent of our strat­e­gy to im­prove treat­ment out­comes for pa­tients,” said Fouad Namouni, MD, head of De­vel­op­ment, On­col­o­gy, Bris­tol-My­ers Squibb.

Bris­tol-My­ers — the one-time leader in check­point in­hibitors — is con­tin­u­ing to dou­ble down on Op­di­vo af­ter an em­bar­rass­ing se­ries of set­backs in lung can­cer bad­ly dent­ed its share price.

Leerink’s Michael Schmidt gave the deal a quick thumbs up, hap­py to see Ex­elix­is take a shot at mov­ing to front­line use.

This is pos­i­tive news since these col­lab­o­ra­tions could po­ten­tial­ly sig­nif­i­cant­ly ex­pand Cabome­tyx com­mer­cial po­ten­tial be­yond 2nd lien RCC, while lim­it­ing ad­di­tion­al in­cre­men­tal R&D spend which is in-line with mgmt.’s busi­ness strat­e­gy. While some of the Cabome­tyx opp’ty be­yond the cur­rent­ly ap­proved in­di­ca­tion in 2nd line RCC is re­flect­ed in our mod­el and val­u­a­tion, the scope of these col­lab­o­ra­tions ex­ceeds our ex­pec­ta­tions and could po­ten­tial­ly in­crease the reg­u­la­to­ry and com­mer­cial prob­a­bil­i­ty-of-suc­cess for Cabome­tyx in 1st line RCC. Our es­ti­mates are un­der re­view.

Ex­elix­is is al­so spon­sor­ing a Phase Ib study that pairs cabo with Tecen­triq in fight­ing sol­id tu­mors. With en­roll­ment planned to be­gin in the mid­dle of this year, in­ves­ti­ga­tors have a shot at lat­er open­ing up four treat­ment co­horts: one for pre­vi­ous­ly un­treat­ed ad­vanced clear cell re­nal cell car­ci­no­ma and three co­horts of urothe­lial car­ci­no­ma, in­clud­ing plat­inum el­i­gi­ble first-line pa­tients, first- or sec­ond-line plat­inum in­el­i­gi­ble pa­tients and pa­tients pre­vi­ous­ly treat­ed with plat­inum-con­tain­ing chemother­a­py.

The da­ta from these stud­ies can be made avail­able to Ex­elix­is’ part­ners, Ipsen and Take­da, for their own de­vel­op­ment ini­tia­tives, pro­vid­ed they opt in. So far though on­ly Ipsen has signed up.

“Peo­ple with ad­vanced gen­i­toruri­nary ma­lig­nan­cies are in need of ad­di­tion­al treat­ment op­tions that can im­prove clin­i­cal out­comes,” said Suman­ta Ku­mar Pal, MD, co-di­rec­tor, Kid­ney Can­cer Pro­gram at City of Hope, and prin­ci­pal in­ves­ti­ga­tor in the study. “The com­bined ap­proach of ty­ro­sine ki­nase in­hi­bi­tion with cabozan­ti­nib along­side im­mune-check­point in­hi­bi­tion has al­ready shown promise in an ear­ly phase 1 clin­i­cal tri­al. We look for­ward to fur­ther ex­am­in­ing this po­ten­tial with cabozan­ti­nib plus ate­zolizum­ab to treat a range of gen­i­touri­nary and oth­er tu­mors.”

Lessons for biotech and phar­ma from a doc­tor who chased his own cure

After being struck by a rare disease as a healthy third year medical student, David Fajgenbaum began an arduous journey chasing his own cure. Amidst the hustle of this year’s JP Morgan conference, the digital trials platform Medable partnered with Endpoints Studio to share Dr. Fajgenbaum’s story with the drug development industry.

What follows is an edited transcript of the conversation between Medable CEO Dr. Michelle Longmire and Dr. Fajgenbaum, and it is full of lessons for biotech executives charged with bringing the next generation of medicines to patients.

Christos Kyratsous (via LinkedIn)

He built a MERS treat­ment in 6 months and then the best Ebo­la drug. Now Chris­tos Kyrat­sous turns his sights on Covid-19

TARRYTOWN, NY — In 2015, as the Ebola epidemic raged through swaths of West Africa, Kristen Pascal’s roommates sat her down on their couch and staged an intervention.

“Are you sure this is what you want to be doing with your life?” she recalls them asking her.

Pascal, a research associate for Regeneron, had been coming home at 2 am and leaving at 6 am. At one point, she didn’t see her roommate for a week. For months, that was life in Christos Kyratsous’ lab as the pair led a company-wide race to develop the first drug that could effectively treat Ebola before the outbreak ended. For Pascal, that was worth it.

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Left to right, top to bottom: Carl Gordon, Adam Stone, Peter Moglia, David Schenkein, Robert Nelsen, Carol Gallagher; Srinivas Akkaraju, Ray Debbane, Jim Flynn, Peter Kolchinsky, Thilo Schroeder, Brad Bolzon

The top 100 bio­phar­ma ven­ture in­vestors at the mega­bil­lions deal ta­ble

The VC crowd took a step back last year, but nevertheless maintained a furious pace of new investments in therapeutic tech platforms and biotech startups. And the top 100 players completely dominated the megabillions game.

Just looking at the number of deals done by each of the top 100, OrbiMed came in at the top, with 20, followed by Alexandria (18), Perceptive (16) and the ubiquitous RA Capital at 16. It’s impossible to say exactly how much they invested in total — those numbers are only rarely provided — but it is clear from the numbers assembled by Chris Dokomajilar at DealForma who’s most likely to be found sitting at the table during the go-go days of biotech investing.

Dokomajilar tracked $14.06 billion in biotech venture investing last year, a dip from the frenzied pace of $16.02 billion in 2018 and more than $10 billion higher than he recorded for 2010, as the economy was recovering from a profound economic crisis.

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Rahul Ballal, Imara

As sick­le cell pa­tients find new op­tions, NEA-found­ed Imara pitch­es mid-stage al­ter­na­tive for $86M IPO

November 2019 proved to be a fruitful month for patients with blood disorders known as hemoglobinopathies. Within days, the FDA ushered two drugs for sickle cell disease and another for beta thalassemia to the market — livening up a barren field.

Imara, a relatively young plower, is riding on that enthusiasm as it shoots for an $86.25 million IPO.

Imara emerged from New Enterprise Associates’ orphan drug accelerator Cydan in 2016 as a single-product company. $77.3 million in private financing later IMR-687 remains the sole asset in its pipeline; the difference is the drug is now in Phase II for sickle cell disease, with topline data slated for later this year and two other mid-stage beta thalassemia studies lined up.

RA joins glob­al syn­di­cate to back a $98M round for CAN­bridge

A Beijing-based rare disease and oncology player has raised $98 million to help fund the expansion of its pipeline as well as a commercial portfolio.

CANbridge put out word Tuesday that the global private equity player General Atlantic joined forces with Chinese CRO Wuxi AppTec to lead the Series D, with both ready to chip in an extra $10 million each under the right conditions. The syndicate includes RA Capital Management, Hudson Bay Capital Management, YuanMing Prudence Fund and Tigermed.

Carol Robinson, Professor Dame Carol Robinson Research Group

Drug dis­cov­ery in HD: Ox­ford spin­of­f's mass spec­trom­e­try ap­proach scores fresh fund­ing

The technology used to detect explosives at airports — mass spectrometry — is being piloted as an engine for drug discovery.

Mass spectrometry is a tool designed to measure with profound accuracy the mass of a single molecule. Typically, mass spectrometers can be used to identify unknown compounds, to quantify known compounds, and to determine the structure and chemical properties of molecules.

UP­DAT­ED: Chi­na ap­proves flu drug be­ing tout­ed as a po­ten­tial coro­n­avirus treat­ment amid a rush of clin­i­cal stud­ies

One of the three drugs that China’s Ministry of Science and Technology has tapped as potential COVID-19 treatments to watch has notched its first Chinese OK — for the flu.

While there’s no proof yet that fapilavir, or favipiravir, is the cure that patients and physicians are yearning for, it stands out for a unique constellation of qualities. It’s been commercially available in Japan for several years (unlike Gilead’s experimental remdesivir) yet it’s new to China (unlike the malaria drug chloroquine phosphate). Perhaps more importantly, a domestic biotech — Zhejiang Hisun Pharma — owns the rights to manufacture and market the drug, preempting any concerns about patents.

FDA goes on high alert as coro­n­avirus rais­es threat to drug man­u­fac­tur­ing and clin­i­cal tri­als grind to a halt

The FDA isn’t quite sure just what the coronavirus outbreak in China will mean for the US pharma industry, but it has the potential to trigger a host of troublesome issues around the supply chain the country is directly plugged into.

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Warren Buffett, AP Images

War­ren Buf­fett gets a dou­ble take as the in­vest­ment pow­er­house set­tles on its first biotech in­vest­ment

Coke. American-Express. Apple. And Biogen?

Warren Buffet’s Berkshire Hathaway, which made itself into a symbol of rock-solid investment strategy, has revealed a stake in the big biotech as it takes on one of the biggest gambles in the industry.

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