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.”

2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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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.

Wuhan virus out­break trig­gers in­evitable small-biotech ral­ly

Every few years, a public health crisis (think Ebola, Zika) spurred by a rogue pathogen triggers a small-biotech rally, as drugmakers emerge from the woodwork with ambitious plans to treat the mounting outbreak. In most cases, that enthusiasm never quite delivers.

Things are no different, as the coronavirus outbreak in Wuhan, China takes hold. There have been close to 300 confirmed human infections in China, and at least four deaths. Coronaviruses are a large family of viruses, which include MERS and SARS. On Tuesday, the CDC reported the virus was detected in a US traveler returning from Wuhan.

Hal Barron and Emma Walmsley, GSK

GSK’s ‘break­through’ BC­MA can­cer drug gets a pri­or­i­ty re­view — and a big win for the on­col­o­gy R&D team

After largely whiffing the past 2 years on the pharma R&D front, GlaxoSmithKline research chief Hal Barron has seized boasting rights to a key win that puts them back in the cancer drug development game.

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Who are the young bio­phar­ma lead­ers shap­ing the in­dus­try? Nom­i­nate them for End­points' spe­cial re­port

Update: Nominations open through end of day, Monday, January 27

Two years ago, when we did our first Endpoints 20-under-40, we profiled a set of up-and-comers who promised to help reshape the industry as we know it. Now we’re back and once again looking for the top 20 biopharma professionals under the age of 40. We’ll be profiling folks who have accomplished a lot at a young age but seem on the verge of accomplishing so much more.

John Oyler, Endpoints

BeiGene lines up its first shot at crack­ing the megablock­buster PD-1 mar­ket for lung can­cer. But can they over­come un­der­dog sta­tus?

BeiGene took another big step towards challenging Merck, Bristol-Myers Squibb, AstraZeneca and some other Big Pharma heavyweights for a share of the lucrative lung cancer market for the PD-(L)1s racking up billions in annual revenue.

The China-based biotech $BGNE run by CEO John Oyler posted positive top-line progression-free survival results for their pivotal Chinese study on their PD-1 antibody tislelizumab combined with chemo for squamous non-small cell lung cancer in frontline cases. Squamous NSCLC accounts for about 30% of the overall lung cancer market.

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Brex­it fears, Wood­ford woes over­shad­owed UK biotech and cut 2019 fi­nanc­ing by al­most half

The venture tide might have subsided, the IPO window may be closing and certain listed biotechs may be having a tough time amid Neil Woodford’s well-publicized demised, but there’s still plenty to celebrate in the UK BioIndustry Association’s eyes.

Overall investment in UK biotech last year fell from the record-breaking £2.2 billion levels of 2018 to £1.3 billion — including £679 million in venture capital, a meager £64 million in IPOs plus £596 million when you add up all public financings, according to a new report from the BIA.

Blue­print Med­i­cines po­ten­tial­ly de­lays Ay­vak­it de­ci­sion; Con­trol beats treat­ment in mesothe­lioma tri­al

→ Blueprint Medicines filed an amendment to its application to get the gastrointestinal stromal tumor (GIST) drug Ayvakit approved in fourth-line GIST, the company disclosed in the prospectus for a new $325 million public offering.  Blueprint got a big accelerated OK on the drug this month in a particular mutation, but because the FDA decided to split their review in two, they didn’t hear on fourth-line GIST. They were supposed to hear before February 14, but this amendment could push that date back by 3 months. Blueprint wrote that the amendment is designed to allow the company to comply with the FDA’s request for data from the Phase III VOYAGER before they give a judgment.