Af­ter build­ing a rep as an ar­chi­tect of ex­per­i­ments, Rx­Cel­er­ate plants its flag in Amer­i­ca

When XO1 was bought out by J&J a cou­ple of years ago, the seed in­vestors at In­dex, now Medicxi, made it Ex­hib­it A for their busi­ness mod­el on cre­at­ing a port­fo­lio of as­set-based biotechs.

What start­ed off with a bit of sci­en­tif­ic sleuthing by a pair of re­searchers at Cam­bridge Uni­ver­si­ty — Trevor Baglin and Jim Hunt­ing­ton — led to an an­ti­body pro­gram for a drug dubbed ichor­cum­ab that promised to po­ten­tial­ly act as an an­ti­co­ag­u­lant, with­out the in­her­ent risk of se­vere bleed­ing that in­evitably haunts the class.

Patrick Ver­heyen, who was run­ning the J&J In­no­va­tion of­fice in Lon­don at the time, called this deal a prime ex­am­ple of the way the phar­ma gi­ant was able to reel in top sci­en­tif­ic pro­grams around the world.

But be­tween the chance dis­cov­ery based on an odd med­ical case dat­ing back to 2008 and J&J’s ac­qui­si­tion, XO1, with­out build­ing a staff or do­ing all the nor­mal things as­so­ci­at­ed with biotech star­tups, had to push through a crit­i­cal pre­clin­i­cal study that could prove it had some­thing of re­al val­ue.

Richard Ma­son

“What we re­al­ly need­ed to do in XO1,” XO1 for­mer chief and sole full time staffer Richard Ma­son tells me, “was to show this an­ti­body we cre­at­ed was an an­ti­co­ag­u­lant that didn’t in­crease bleed­ing risk.”

That’s nev­er been done in any sim­i­lar de­vel­op­ment pro­gram be­fore, by any­one.

To do that, Ma­son re­lied on a group in Cam­bridge, UK called Rx­Cel­er­ate. Co-found­ed by David Grainger, a Medicxi part­ner who al­so act­ed as chief sci­en­tif­ic of­fi­cer for XO1, the lab staff didn’t just run a pre­clin­i­cal study un­der con­tract. They built the study from the ground up, ques­tion­ing every step along the way in a field be­set by ques­tions of le­git­i­ma­cy and in­tegri­ty.

Says Ma­son: “They are the ar­chi­tects of the ex­per­i­ment.”

XO1’s ex­pe­ri­ence un­der­scores one of the hard truths about drug dis­cov­ery projects. The lit­er­a­ture is of­ten mis­lead­ing, the mod­els in use may be sus­pect, some­times some of the hard­ware de­scribed doesn’t even ex­ist, says Ma­son. And all of that was on dis­play in their ground­work on an­ti­co­ag­u­la­tion.

A sci­en­tist by train­ing, Grainger and his col­leagues at Medicxi have carved out a rep­u­ta­tion for com­bin­ing sci­en­tif­ic rig­or in ear­ly-stage re­search with a rep for carv­ing the hard costs of do­ing a start­up down to the bare es­sen­tials — in­clud­ing the cre­ative use of out­sourc­ing to keep their star­tups vir­tu­al.

Now Rx­Cel­er­ate has opened up a Boston/Cam­bridge of­fice to in­tro­duce their work un­der US EVP Lau­ra Hamil­ton, the for­mer BD chief at Mass­Bio.

David Grainger

“We are not a CRO,” Grainger tells me lev­el­ly. So I asked for a look at one case to ex­plain what they do. And that led me to Ma­son, who didn’t just do a deal with J&J — a few months lat­er he took Ver­heyen’s job run­ning J&J In­no­va­tion in Lon­don. (Ver­heyen was pro­mot­ed to run BD for all of J&J. Hunt­ing­ton, mean­while, caught the se­r­i­al en­tre­pre­neur bug and has since launched a se­ries of biotech up­starts out of his Cam­bridge lab.)

The way Rx­Cel­er­ate works, Ma­son says, “it starts with the ba­sic sci­ence and takes noth­ing for grant­ed.”

Jill Reck­less — the CEO at Rx­Cel­er­ate, who left with a group of re­searchers at Cam­bridge to launch the lab at Rx­Cel­er­ate with Grainger — start­ed by re­view­ing the lit­er­a­ture on throm­bo­sis and bleed­ing mod­els.

“We found that many of those pa­pers had some prob­lems with them,” says Ma­son. Then there was the rat tail clip mod­el used to mea­sure bleed­ing in ro­dents.

“We found sub­stan­tial prob­lems with the way that was done in the lit­er­a­ture,” adds Ma­son. “Prob­lems with re­pro­ducibil­i­ty.”

Rather than repli­cate bad sci­ence, Rx­Cel­er­ate cre­at­ed new mod­el ex­per­i­ments where nec­es­sary, and dou­bled down with larg­er an­i­mal mod­els to demon­strate po­ten­tial in hu­mans.

“What we are try­ing to of­fer is the abil­i­ty to out­source the think­ing be­hind drug de­vel­o­ment,” says Grainger. CROs are great for de­fined tasks, he adds, but when it comes to do­ing the ar­chi­tec­ture: “CROs don’t do that very well.”

Jill Reck­less

It’s the kind of work that ap­peals to any­one in a cash con­strained en­vi­ron­ment, says Reck­less, whether that’s a biotech start­up or a ma­jor bio­phar­ma, work­ing on a bud­get to see where it has as­sets of re­al val­ue to pur­sue. It’s all about stay­ing fo­cused while re­main­ing skep­ti­cal about what’s come be­fore.

“By not do­ing the things that don’t need to be done,” says Grainger,  “that’s where the bulk of the cost sav­ings come.”

How’s J&J’s team do­ing with XO1’s drug, now dubbed “9375”?

So far so good, says Ma­son, who vis­it­ed with the group in charge at J&J as they look for a next-gen­er­a­tion an­tithrom­bin to fol­low Xarel­to. They’re through Phase I and ex­am­in­ing next steps for Phase II.

Says Ma­son: “Stay tuned.”

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Rev­o­lu­tion Med shoots for $100M+ IPO — and di­vulges some se­crets about that Warp Dri­ve buy­out

Biotech investors who like to wager on the race to the front of the KRAS market now have a new team to consider.

Revolution Medicines, which extended its reach on RAS with a deal to acquire Warp Drive Bio about 18 months ago, filed their S-1 in search of $100 million-plus. And they gave up a few secrets in the process.

The main clinical claim to fame that Revolution has centers on the SHP2 inhibitor RMC-4630, partnered with Sanofi back in the summer of 2018 — just after John Reed was named the incoming R&D chief. We already knew that the pharma giant handed over $50 million in cash plus a commitment of hundreds of millions more to align itself with Revolution as it makes a fresh foray into oncology. Now we know that Sanofi is also footing 80% of Revolution’s R&D bill on the program, while setting up a smorgasbord of $235 million in development milestones and $285 million in commercial bonuses.

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Turn­ing the cor­ner on treat­ing the root cause of sick­le cell dis­ease

Early in my career, as a medical resident, I saw first-hand the enormous challenges faced by children and adults with sickle cell disease (SCD), a genetic blood disorder that historically has lacked adequate treatment options. People living with this life-long disease are mainly those with ancestors from sub-Saharan Africa, as well as people of Hispanic, South Asian, Southern European and Middle Eastern descent. These patients suffer from devastating physical symptoms, including progressive, eventually fatal, organ damage and excruciating pain. In addition, they encounter emotional, mental and social burdens – non-physical aspects of living with SCD that also take a serious toll on patients and their caregivers.

Olivier Brandicourt, AP Images

#JPM20 ex­clu­sive: Olivi­er Brandi­court fol­lows the Big Phar­ma CEO path to pri­vate eq­ui­ty, join­ing Black­stone ahead of a mam­moth fund de­but

Nick Galakatos Blackstone

Seven months after Olivier Brandicourt’s surprise “early retirement” from Sanofi, he’s back in the game, this time taking meetings at JP Morgan to discuss his new role at Blackstone, where he’s quietly begun work with Nick Galakatos and the life sciences crew.

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Video Re­play: End­points at #JPM20 — news­mak­ers on deal­mak­ing, pric­ing and man­u­fac­tur­ing

On Monday, we held our fourth annual #JPM event — and the team hit a key milestone that I’d like to share with the entire Endpoints News audience: We live-streamed the conversation and had nearly triple the number of executives watching online than we had in the sold-out crowd of 320.

For a media company on a mission to connect the biopharma world in bigger and better ways, we’re proud of how we were able to extend the reach of our franchise event. Paid subscribers were given access to the stream in real time, and now, two days later, we’re opening it up to everyone in this post.

Endpoints@JPM: (left to right) Steve Pearson, Nick Leschly, Bari Talente, Stephen Ubl, John Carroll

#JPM20: 'The NPV is al­ways wrong.' Take­da preps an­oth­er spin­out — this time on psych

Editor’s Note: Endpoints News is reporting live from #JPM20 after kicking things off with an action-packed event, which you can replay here. What follows is a stream of tidbits we have collected while wandering around Union Square in San Francisco. Check back in throughout the week for updates by John Carroll and Jason Mast.

SAN FRANCISCO — A year ago Takeda CEO Christophe Weber and R&D chief Andy Plump arrived at JP Morgan right on the heels of closing their big Shire buyout. Now they’re back after shaking up the portfolio, boosting R&D spending by about 50% to $4.5 billion and adjusting the pipeline — a task which isn’t quite finished yet.

Nick Leschly at Endpoints News' panel at the 2020 JP Morgan Healthcare Conference. Credit: Jeff Rumans

At #JPM20, two CEOs, two rad­i­cal­ly dif­fer­ent ther­a­pies, and a fight to chase down sick­le cell

SAN FRANCISCO – Few CEOs tell a story better than bluebird’s Nick Leschly.

He cuts a Jeff Bezos figure on stage at the Colonial Room, the JP Morgan presentation hall for A-list biotechs: lean and bald, fast-talking and vest-wearing. He explains in simple language, apologizing when he has to brush on the data. It helps that he has a good story to tell.

“We treated them one time,” Leschly tells a packed crowd, gesturing to the slide behind him. “Look what happened.”

The slide shows 9 horizontal bars studded with diamonds. Each bar, he explained, represented a sickle cell patient, and each diamond represented a severe medical event, such as a pain crisis. The diamonds stud one side – before the therapy – and vanish on the other, afterward.

“A 99% reduction in these events — this is a functional cure for sickle cell disease,” Leschly says. “This is unprecedented data.”

Upstairs and an hour later, Ted Love stands before a narrow conference room in his suit and polka-dot tie. Love, the CEO of Global Blood Therapeutics, is a 60-year-old physician. His voice trails off at the end of sentences, and the story he tells is less compelling. There are no cured patients.

“This is the first drug that addresses the root cause of sickle cell disease,” Love says, speaking in front of a slide showing a white pill bottle for GBT’s new drug Oxbryta. “Right in the label, it says that this drug inhibits polymerization.”

In the 60 years after scientists discovered the cause of sickle cell, almost no treatments emerged, even as the condition debilitated hundreds of thousands of Americans, most of them black or Hispanic. But the last few years have seen a resurgence of interest as new technologies have made the disease seem newly beatable.

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Neon Ther­a­peu­tics makes one last re­treat, sell­ing it­self cheap in a bar­gain base­ment M&A deal

Crushed by weak data for what had been their lead drug, Neon Therapeutics is being bought for parts this morning.

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Mark Pruzanski

#JPM20: Af­ter a year of NASH col­laps­es, all eyes on two biotechs

SAN FRANCISCO – It’s not quite Dewey defeats Truman, but Goldman Sachs calling 2019 “The Year of NASH” may well go down in the annals of worst biotech predictions.

Goldman Sachs slapped the label on weeks before 2019’s JP Morgan conference, projecting that long-discussed treatments for the obesity-driven condition suspected to lurk in millions of Americans would begin to bear fruit and investors would move accordingly. That did not quite happen.

“If you look at 2019, it was just a string of disappointing news,” Pascal Prigent, CEO of NASH-focused biotech Genfit, told Endpoints News in an interview.

The Year of NASH, or nonalcoholic steatohepatitis, became a year of NASH failures. Gilead failed two large Phase III trials. CymaBay went from a $1 billion company to a $100 million company after they found their drug was killing patients’ liver cells. Cirius withdrew an $86 million IPO bid after a disastrous readout. Industry-wide, there were few acqusitions in a market often projected to be worth $35 billion.

Gilead, after dominating the NASH discussion at the 2019 JPM, gave one quick mention to the program in their 2020 presentation before pivoting to other drugs.

“As promising as some of the mechanisms looked in earlier stages, when push comes to shove in large study settings, they just haven’t proven out,” Mark Pruzanski, CEO of the NASH-focused biotech Intercept, told Endpoints in an interview.

As biotech turns from 2019, the failures have refocused eyes away from Gilead and back toward two startups, both facing key events in the coming months: Intercept, which first alerted investors to NASH at JPM 2014, and the France-based Genfit.

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