Ro­bot­ic pill tech found to be safe, tol­er­a­ble in ear­ly hu­man study, paving ground for oral bi­o­log­ics

Trans­form­ing in­jecta­bles in­to pills is hard­ly a nov­el idea, but a string of phar­ma­ceu­ti­cal/chem­i­cal ef­forts to evade the en­zymes that break down the oral drug be­fore it can be ab­sorbed have large­ly hit a wall. Ear­li­er this month, an an­i­mal study cap­tured the spot­light for the po­ten­tial of its blue­ber­ry sized ro­bot­ic pill de­signed to de­liv­er an in­sulin shot in­side the stom­ach — but Cal­i­for­nia-based Rani Ther­a­peu­tics on Thurs­day said it has suc­cess­ful­ly test­ed its ro­bot­ic pill for safe­ty and tol­er­a­bil­i­ty in hu­mans, paving the way for ef­fi­ca­cy stud­ies that could open the door to a colos­sal mar­ket to en­hance treat­ment com­pli­ance, di­min­ish the need for physi­cian-led ther­a­peu­tic ad­min­is­tra­tion and pla­cate nee­dle-pho­bic pa­tients.

Mir Im­ran

The com­pa­ny’s prod­uct — called the Ra­niP­ill — has un­der­gone over 100 pre­clin­i­cal stud­ies, in­clud­ing large an­i­mal tri­als. The cap­sule has an en­teric coat­ing that pro­tects it from the acidic am­bi­ence of the stom­ach, and once it moves in­to the in­tes­tine and pH lev­els rise, the coat­ing dis­solves and a chem­i­cal re­ac­tion takes place which in­flates a bal­loon. Pres­sure in the bal­loon push­es a dis­solv­able mi­cronee­dle filled with the drug in­to the in­testi­nal wall.

In­testines don’t have pain re­cep­tors, and the in­testi­nal sub­strate — which is de­signed to ab­sorb nu­tri­ents — is high­ly vas­cu­lar­ized, mak­ing it the ide­al lo­ca­tion for the drug-en­gorged in­jec­tion to de­ploy, Rani chief Mir Im­ran told End­points News, adding that in the hand­ful of drugs the com­pa­ny test­ed as part of the Ra­niP­ill in an­i­mal stud­ies, the ab­sorp­tion of the drug was gen­er­al­ly equal or high­er than that of a sub­cu­ta­neous in­jec­tion.

Fol­low­ing suc­cess­ful an­i­mal stud­ies, Rani ini­ti­at­ed a study in healthy hu­mans last year to eval­u­ate the fea­si­bil­i­ty of the prod­uct. Two groups of 10 sub­jects each (with one arm hav­ing fed, and the oth­er arm hav­ing fast­ed) were giv­en a drug-free ver­sion of the Ra­niP­ill. Re­sults re­vealed nei­ther group felt the im­pact of the cap­sule in­flat­ing or de­ploy­ing, and each pa­tient suc­cess­ful­ly ex­punged the rem­nants. The cap­sule was well tol­er­at­ed and the pres­ence (or ab­sence) of food in the stom­ach had no im­pact on the per­for­mance of the cap­sule, the com­pa­ny said.

“This is the first time a ro­bot­ic pill was swal­lowed by hu­mans — this re­al­ly paves the way for the next study which will have a drug, and we will be able to mea­sure drug lev­els,” Im­ran said.

The com­pa­ny has cho­sen to use a pill loaded with oc­treotide, an off-patent bi­o­log­ic that treats the hor­mon­al dis­or­der acromegaly, for the up­com­ing study, which the com­pa­ny ex­pects will com­mence in the com­ing months.

“If we’re suc­cess­ful in our next study, it re­al­ly means that we can de­liv­er any drug…in­clud­ing in­sulin and Hu­mi­ra and treat­ments for a whole host of oth­er dis­eases such as mul­ti­ple scle­ro­sis, he­mo­phil­ia and oth­er chron­ic con­di­tions,” he added.

But there’s a long road ahead. Each drug loaded in­to the cap­sule will re­quire a sep­a­rate study be­fore Rani can pe­ti­tion the FDA for ap­proval.

Mean­while, rat and pig da­ta on the oth­er ro­bot­ic pill — cre­at­ed by a team of re­searchers at MIT (in­clud­ing the pro­lif­ic drug de­liv­ery mae­stro Robert Langer) and No­vo Nordisk $NVO — an­nounced ear­li­er in Feb­ru­ary, has an al­ter­na­tive mech­a­nism of ac­tion.

The de­vice, called So­ma, en­cap­su­lates a nee­dle in­side a pill made of com­pressed freeze-dried in­sulin that is de­signed to ori­ent it­self when it comes in con­tact with the stom­ach lin­ing — in­spired by a leop­ard tor­toise, which bran­dish­es a shell that al­lows the African rep­tile to right it­self if it rolls on­to its back. Up­on con­tact with the wet in­ner lin­ing of the stom­ach (which is al­so de­void of pain re­cep­tors), a sug­ar disk hold­ing the nee­dle in place is dis­solved, mak­ing way for the nee­dle to re­lease its con­tents. The prod­uct is then en­gi­neered to dis­in­te­grate and trav­el harm­less­ly through the di­ges­tive sys­tem and even­tu­al­ly be elim­i­nat­ed, the re­searchers wrote in their re­port in Sci­ence. 

“One big dif­fer­ence is that we pre­date the MIT ef­fort by at least 5 years and our IP re­al­ly cov­ers every­thing they’re do­ing…their (So­ma’s) spring loaded de­liv­ery is some­thing we have very strong patents on, so I think they are go­ing to step on our IP. The de­sign of the nee­dle we have very strong patents on, and their nee­dle looks ex­act­ly like our nee­dle,” Im­ran said, em­pha­siz­ing the size of Rani’s patent port­fo­lio, which he claimed in­cludes 70 is­sued patents.

“The MIT group as far as we can tell has two patent ap­pli­ca­tions and nei­ther has been is­sued. Cer­tain­ly for us we see that (com­pe­ti­tion) as a pos­i­tive be­cause it val­i­dates our ap­proach in a very fun­da­men­tal way — not that we need that val­i­da­tion thanks to our an­i­mal stud­ies — but it’s re­al­ly nice to have Bob Langer on my heels.”

In re­sponse to Im­ran’s com­men­tary, Langer sug­gest­ed it was un­clear whether the MIT ap­proach is in­fring­ing on Rani’s patents.

Bob Langer

“I think it’s un­clear at this time — rec­og­niz­ing that we, Rani, and I’m sure oth­ers have a num­ber of patent ap­pli­ca­tions in this area — whether, for some ap­pli­ca­tions we are step­ping on their patents, they are step­ping on ours, and/or there are patents by oth­ers which will be im­por­tant,” he said in an emailed state­ment.

“Our goal in pub­lish­ing our work in a top peer re­viewed sci­en­tif­ic jour­nal (Sci­ence) was to get the sci­en­tif­ic prin­ci­ples we de­vel­oped out to the sci­en­tif­ic com­mu­ni­ty in the hopes that it can get to pa­tients. If that hap­pens through us, our col­lab­o­ra­tors at No­vo Nordisk, Rani, or some­one else, we will have achieved our goal.”

Found­ed in 2012, Rani Ther­a­peu­tics has raised $142 mil­lion in fund­ing from a slate of in­vestors in­clud­ing GV (the in­vest­ment arm of Al­pha­bet), and counts No­var­tis and Shire as its part­ners.

On a glob­al romp, Boehringer BD team picks up its third R&D al­liance for Ju­ly — this time fo­cused on IPF with $50M up­front

Boehringer Ingelheim’s BD team is on a global deal spree. The German pharma company just wrapped its third deal in 3 weeks, going back to Korea for its latest pipeline pact — this time focused on idiopathic pulmonary fibrosis.

They’re handing over $50 million to get their hands on BBT-877, an ATX inhibitor from Korea’s Bridge Biotherapeutics that was on display at a science conference in Dallas recently. There’s not a whole lot of data to evaluate the prospects here.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,000+ biopharma pros reading Endpoints daily — and it's free.

Part club, part guide, part land­lord: Arie Bellde­grun is blue­print­ing a string of be­spoke biotech com­plex­es in glob­al boom­towns — start­ing with Boston

The biotech industry is getting a landlord, unlike anything it’s ever known before.

Inspired by his recent experiences scrounging for space in Boston and the Bay Area, master biotech builder, investor, and global dealmaker Arie Belldegrun has organized a new venture to build a new, 250,000 square foot biopharma building in Boston’s Seaport district — home to Vertex and a number of up-and-coming biotech players.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,000+ biopharma pros reading Endpoints daily — and it's free.

Servi­er scoots out of an­oth­er col­lab­o­ra­tion with Macro­Gen­ics, writ­ing off their $40M

Servier is walking out on a partnership with MacroGenics $MGNX — for the second time.

After the market closed on Wednesday MacroGenics put out word that Servier is severing a deal — inked close to 7 years ago — to collaborate on the development of flotetuzumab and other Dual-Affinity Re-Targeting (DART) drugs in its pipeline.

MacroGenics CEO Scott Koenig shrugged off the departure of Servier, which paid $20 million to kick off the alliance and $20 million to option flotetuzumab — putting a heavily back-ended $1 billion-plus in additional biobuck money on the table for the anti-CD123/CD3 bispecific and its companion therapies.

Den­mark's Gen­mab hits the jack­pot with $500M+ US IPO as small­er biotechs rake in a com­bined $147M

Danish drugmaker Genmab A/S is off to the races with perhaps one of the biggest biotech public listings in decades, having reaped over $500 million on the Nasdaq, as it positions itself as a bonafide player in antibody-based cancer therapies.

The company, which has long served as J&J’s $JNJ key partner on the blockbuster multiple myeloma therapy Darzalex, has asserted it has been looking to launch its own proprietary product — one it owns at least half of — by 2025.

FDA over­rides ad­comm opin­ions a fifth of the time, study finds — but why?

For drugmakers, FDA advisory panels are often an apprehended barometer of regulators’ final decisions. While the experts’ endorsement or criticism often translate directly to final outcomes, the FDA sometimes stun observers by diverging from recommendations.

A new paper out of Milbank Quarterly put a number on that trend by analyzing 376 voting meetings and subsequent actions from 2008 through 2015, confirming the general impression that regulators tend to agree with the adcomms most of the time — with discordances in only 22% of the cases.

Norbert Bischofberger. Kronos

Backed by some of the biggest names in biotech, Nor­bert Bischof­berg­er gets his megaround for plat­form tech out of MIT

A little over a year ago when I reported on Norbert Bischofberger’s jump from the CSO job at giant Gilead to a tiny upstart called Kronos, I noted that with his connections in biotech finance, that $18 million launch round he was starting off with could just as easily have been $100 million or more.

With his first anniversary now behind him, Bischofberger has that mega-round in the bank.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,000+ biopharma pros reading Endpoints daily — and it's free.

Novotech CRO Ex­pands Chi­na Team as Biotech De­mand for Clin­i­cal Tri­als In­creas­es up to 79%

An increase in demand of up to 79% for clinical trials in China has prompted Novotech the Asia-Pacific CRO to rapidly expand the China team, appointing expert local clinical executives to their Shanghai and Hong Kong offices. The company is planning to expand their team by 30% over the next quarter.

Novotech China has seen considerable demand recently which is borne out by research from GlobalData:
A global migration of clinical research is occurring from high-income countries to low and middle-income countries with emerging economies. Over the period 2017 to 2018, for example, the number of clinical trial sites opened by biotech companies in Asia-Pacific increased by 35% compared to 8% in the rest of the world, with growth as high as 79% in China.
Novotech CEO Dr John Moller said China offers the largest population in the world, rapid economic growth, and an increasing willingness by government to invest in research and development.
Novotech’s 23 years of experience working in the region means we are the ideal CRO partner for USA biotechs wanting to tap the research expertise and opportunities that China offers.
There are over 22,000 active investigators in Greater China, with about 5,000 investigators with experience on at least 3 studies (source GlobalData).

UP­DAT­ED: With loom­ing ‘apoc­a­lypse of drug re­sis­tance,’ Mer­ck’s com­bi­na­tion an­tibi­ot­ic scores FDA ap­proval on two fronts

Merck — one of the last large biopharmaceuticals companies in the beleaguered field of antibiotic drug development — on Wednesday said the FDA had sanctioned the approval of its combination antibacterial for the treatment of complicated urinary tract and intra-abdominal infections.

To curb the rise of drug-resistant bacteria and maintain the efficacy of the therapy, Recarbrio (and other antibacterials) — the drug must be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible gram-negative bacteria, Merck $MRK said.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,000+ biopharma pros reading Endpoints daily — and it's free.

John McHutchison in 2012. Getty Images

The $1.1M good­bye: Gilead CSO John McHutchi­son is out as Daniel O’Day shakes up the se­nior team

Just a little more than a year after John McHutchison grabbed a promotion to become CSO at Gilead in the wake of Norbert Bischofberger’s exit, he’s out amid a shakeup of the senior team that is also triggering the departure of two other top execs.

Gilead stated that McHutchison “has decided to step down” from the job as of August 2nd. And their SEC filing notes that he’ll be getting a $1.1 million check to settle up on his contract.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,000+ biopharma pros reading Endpoints daily — and it's free.