Mir Imran, Rani Therapeutics

Rani Ther­a­peu­tics eyes po­ten­tial IPO as ro­bot­ic pill tech­nol­o­gy takes shape

Two ef­forts to trans­form in­jecta­bles in­to ro­bot­ic pills — a colos­sal mar­ket de­signed to en­hance treat­ment com­pli­ance, di­min­ish the need for physi­cian-led ther­a­peu­tic ad­min­is­tra­tion and pla­cate nee­dle-pho­bic pa­tients — got off the ground last year. Now, one of these ini­tia­tives, led by an in­ven­tor who played an in­flu­en­tial role in pi­o­neer­ing the first FDA-ap­proved au­to­mat­ic im­plantable car­diovert­er de­fib­ril­la­tor (ICD) has tak­en an­oth­er key step in its quest with a suc­cess­ful ear­ly-stage ef­fi­ca­cy and safe­ty study.

Cal­i­for­nia-based Rani Ther­a­peu­tics — un­der chief Mir Im­ran who start­ed his first com­pa­ny while in col­lege and cur­rent­ly holds more than 400 is­sued patents — on Thurs­day said its tech­nol­o­gy, chris­tened the Ra­niP­ill, had per­formed as ex­pect­ed in a tri­al with 58 healthy adult vol­un­teers.

The tech­nol­o­gy is de­cep­tive­ly sim­ple. The cap­sule has an en­teric coat­ing that pro­tects it from the acidic am­biance 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 a drug — in this case, the com­pound oc­treotide, an off-patent bi­o­log­ic that treats the hor­mon­al dis­or­der acromegaly — 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.

In the tri­al, 52 sub­jects were treat­ed with the Ra­niP­ill ver­sion of oc­treotide, while the re­main­ing 6 par­tic­i­pants were giv­en an in­tra­venous in­jec­tion of an iden­ti­cal dose of oc­treotide.

“This was the first time we were de­liv­er­ing nee­dles from the in­testi­nal wall,” Im­ran not­ed in an in­ter­view with End­points News. “And our hy­poth­e­sis from the be­gin­ning was that you wouldn’t feel any­thing. And of course, that was borne out. And then the sec­ond end­point was bioavail­abil­i­ty, which turned out to be greater than 70%. Which is what ex­act­ly we had seen in our pre­clin­i­cal test­ing.”

The plan is to con­duct a prop­er head-to-head study in the com­ing year and demon­strate equiv­a­lence or non-in­fe­ri­or­i­ty to the in­jectable ver­sion. The ear­li­est Im­ran ex­pects the prod­uct to be avail­able, as­sum­ing all goes well clin­i­cal­ly, is 2022.

This oc­treotide tri­al will be the lit­mus test for its drug-de­liv­ery plat­form, open­ing the door to a pletho­ra of in­jectable treat­ments, from in­sulin to Hu­mi­ra, and across a wide range of dis­eases. 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.

The com­pa­ny has a num­ber of such drugs in its pipeline, and ex­pects to kick off Phase I stud­ies lat­er in 2020. 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 (now owned by Take­da) as its part­ners.

As it ramps up its clin­i­cal de­vel­op­ment, fund­ing is im­per­a­tive. “The fund­ing nev­er stops. We’re con­stant­ly do­ing that,” Im­ran said, adding that an IPO is a “dis­tinct pos­si­bil­i­ty” rough­ly a year from now. The com­pa­ny al­so ex­pects to an­nounce a new li­cens­ing part­ner by the end of the year or 2021, he said.

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. Apart from the Ra­niP­ill, last year an an­i­mal study — led by MIT sci­en­tists — cap­tured the spot­light for the po­ten­tial of its blue­ber­ry sized ro­bot­ic pill de­signed to de­liv­er an in­sulin shot in­side the stom­ach.

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 — 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.

“There’s so many patent land­mines that we have placed. So we’re not re­al­ly con­cerned about MIT or any­one else,” Im­ran said.

J&J gets a fresh OK for es­ke­t­a­mine, but is it re­al­ly the game-chang­er for de­pres­sion Trump keeps tweet­ing about?

Backed by an enthusiastic set of tweets from President Trump and a landmark OK for depression, J&J scooped up a new approval from the FDA for Spravato today. But this latest advance will likely bring fresh scrutiny to a drug that’s spurred some serious questions about the data, as well as the price.

First, the approval.

Regulators stamped their OK on the use of Spravato — developed as esketamine, a nasal spray version of the party drug Special K or ketamine — for patients suffering from major depressive disorder with acute suicidal ideation or behavior.

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FDA hands Mor­phoSys and In­cyte a quick OK on their po­ten­tial block­buster CAR-T al­ter­na­tive

Nearly three years after okaying the CAR-Ts Yescarta and Kymriah, the FDA has approved a new CD19 therapy.

MorphoSys’ Monjuvi, or tafasitamab-cxix, was cleared Friday for use in refractory diffuse large B-cell lymphoma (DBLCL). The approval sets up both MorphoSys and their commercial partner Incyte to compete with Gilead and Novartis in the ultra-competitive indication, where similar trial results and far easier delivery could allow them to cut a fair share of the market.

So Covid-19 leader BioN­Tech has a can­cer vac­cine in de­vel­op­ment? Yes, and Re­gen­eron just jumped in for the PhII com­bo study

Before the coronavirus global emergency stole the R&D show in biopharma, the leaders in the race to develop new mRNA therapies had a big interest in determining if their tech could be used to create an effective cancer vaccine after all the first-gen tries had failed to impress. So perhaps it’s not surprising that an early cut of the data at frontrunner BioNTech went largely unnoticed.

Unless you were at Regeneron.

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CymaBay flash­es pos­i­tive re­sults from the tri­al they have to re­launch

Two weeks after the FDA lifted its clinical hold on their lead drug, CymaBay said it showed positive results in an aborted Phase III trial.

The drug, a small molecule known as seladelpar, had been in development for three different liver conditions before an independent review of a NASH study last year showed that it might actually be damaging patient’s liver cells. The FDA slapped a clinical hold across all three trials, only lifting it last month when an FDA review determined that the drug hadn’t caused liver damage.

Sanofi un­der for­mal in­ves­ti­ga­tion for De­pakine al­le­ga­tions; Beam li­cens­es CAR-T tech from Ox­ford Bio­med­ica

Sanofi is facing a formal investigation on manslaughter charges, due to accusations that its epilepsy drug Depakine caused birth malfunctions and slow neurological development when taken during pregnancy.

The French pharma was formally charged in February, years after evidence surfaced that the drug, sodium valproate, posed neurodevelopmental risks. Sodium valproate first hit the market in 1967 for the treatment of epilepsy and bipolar disorder, and is currently prescribed in more than 100 countries.

Covid-19 roundup: Eli Lil­ly retro­fits RVs for first-of-its-kind an­ti­body tri­al with NIH; Am­gen, Ab­b­Vie, Take­da team on a drug

Eli Lilly and the NIH are about to start a first-of-its-kind trial that researchers and developers have talked about for months as a way of providing temporary immunity to the most at-risk populations.

Lilly announced this morning that it will start a 2,400-person trial with the National Institute for Allergy and Infectious Diseases to test whether its experimental Covid-19 neutralizing antibody can prevent people in nursing homes and assisted living facilities from developing the disease. The idea, known as passive immunity, is that rather than waiting on a vaccine to induce people to develop antibodies, doctors can give them lab-grown antibodies. Ideally, those antibodies will either attack the new SARS-CoV-2 infection, if the patient has recently been exposed, or persist in the blood for several weeks and prevent infection or disease for that period.

Im­mu­nic's lead MS drug hits pri­ma­ry and key sec­ondary end­points in PhII, but ques­tions re­main

Just a week after its lead program began enrolling patients in a study to treat Covid-19, Immunic Therapeutics is making more waves.

This time, the biotech is providing a glimpse at topline data from a Phase II trial studying the efficacy of vidofludimus calcium, or IMU-838, in relapsing-remitting multiple sclerosis patients. Taken orally, the candidate met its primary endpoint in reducing the cumulative number of combined unique active MRI lesions after 24 weeks for a 45 mg dose compared to a placebo, as well as a key secondary endpoint in such reductions for the 30 mg dose.

Rich Heyman (ARCH)

Rich Hey­man joins PMV Phar­ma, a p53 biotech, as it adds $70 mil­lion in Se­ries D

Less than a year after pulling in an impressive $62 million Series C round, PMV Pharma is back at it again.

The Cranbury, NJ-based biotech announced Monday an additional $70 million in Series D financing as it seeks to develop cancer therapies targeting p53 mutations. Additionally, PMV also introduced longtime biotech entrepreneur Rich Heyman as chairman of the board of directors.

“This financing provides PMV Pharma with the resources to expand our pipeline and to potentially advance multiple p53 therapies into the clinic,” said PMV president and CEO David Mack in a statement.

Days af­ter seal­ing Sanofi pact, Kymera beats a path to the Nas­daq with $100M IPO pitch

Back in March, when Kymera Therapeutics closed $102 million in Series C funding led by Biotechnology Value Fund and Redmile Group, CEO Nello Mainolfi noted the protein degradation player was “at the cusp of transitioning” into a fully integrated R&D company. Five months and a major Sanofi pact later, he’s back asking for another little push to get there.

Kymera has penciled in $100 million in its first IPO pitch — although given the public market’s seemingly insatiable appetite for biotechs these days the final figure is anyone’s guess.