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.

Image courtesy of The Janssen Pharmaceutical Companies of Johnson & Johnson.

Pro­tect­ing the glob­al phar­ma­ceu­ti­cal in­no­va­tion ecosys­tem – what’s at stake?

We are living in a new era of healthcare that is rapidly advancing progress impacting patient outcomes and experiences. We’ve seen a remarkable pace of transformational innovation, applied research, and advanced clinical development over the last decade.

Despite this tremendous progress, there is much more work to be done, and patients are counting on us – now more than ever – to continue that momentum. At the heart of our industry is a focus on developing and delivering medicines for some of the world’s most challenging diseases, including those that have few or no effective treatments today.

Roger Perl­mut­ter lines up deals, fresh fund­ing at Eikon; Sec­ond RSV vac­cine ap­proved; Sev­er­al biotechs flash­ing red; and more

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As you come back to our website this weekend for ASCO news, don’t forget to check out our updated event lineup at BIO, which will cover everything from the current state of VC investing in biotech to top pharma R&D chiefs discussing how to make pipeline decisions.

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Full TIG­IT da­ta from Gilead, Ar­cus show low­er PFS rates than De­cem­ber read­out: #AS­CO23

CHICAGO — Gilead and Arcus unveiled a fuller snapshot of a Phase II study testing their experimental cancer immunotherapy combo that showed lower progression-free survival rates than its previous update, results that are likely to spark further debate over the closely-watched clinical trial.

Last December, the anti-TIGIT/anti-PD-L1 combo, positioned as a first-line treatment for non-small cell lung cancer, recorded data that drew mixed reactions. The latest analysis, presented Saturday afternoon at ASCO, included only a handful more patients than the previous update, but PFS rates fell — in one cohort by nearly three months.

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Bris­tol My­er­s' Op­di­vo keeps can­cer at bay in more lym­phoma pa­tients than Seagen's Ad­cetris in PhI­II: #AS­CO23

CHICAGO — In a study pitting Seagen’s Adcetris against Bristol Myers Squibb’s Opdivo in newly diagnosed patients with advanced classic Hodgkin lymphoma, a greater proportion of those who received Opdivo saw no cancer growth at one year compared to those who got Adcetris.

In addition, patients in the Opdivo arm of the Phase III trial reported reduced toxicities, according to lead investigator Alex Herrera, a hematologist-oncologist at City of Hope’s cancer cancer in Duarte, CA. Notably, the trial included more than 200 children across both arms. Generally, more than half of children with advanced Hodgkin lymphoma receive radiation therapy, but in this trial, dubbed SWOG S1826, only a handful of patients in the two arms received radiotherapy, sparing many children from long-term side effects of radiation.

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Servi­er’s vo­rasi­denib stalls pro­gres­sion of brain can­cer by 61% in piv­otal PhI­II IN­DI­GO study: #AS­CO23

An experimental pill from Servier Pharmaceuticals showed potentially practice-changing results in a narrow group of brain cancer patients, cutting the risk of their cancers progressing by 61%, according to a late-stage clinical trial.

The drug, vorasidenib, is a precision medicine that only works in certain people whose cancer carries mutations in one of two genes called IDH1/2. Doctors hope that the therapy will delay the need for chemotherapy or radiation, which are often used to combat relapses in patients who’ve previously undergone surgery to remove brain tumors.

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As­traZeneca tri­al shows mod­est ben­e­fit in ovar­i­an can­cer, but doc­tors say it's hard to ap­ply find­ings: #AS­CO23

CHICAGO — Adding AstraZeneca’s Imfinzi and Lynparza to the treatment regimen for patients with advanced ovarian cancer and no BRCA mutation extended progression-free survival (PFS) by five months, according to interim data released at the ASCO annual meeting Saturday morning.

However, the design of the Phase III study obscures how much Imfinzi is contributing to the PFS extension, doctors said, making it difficult to apply the findings to clinical practice.

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Keytru­da be­fore and af­ter lung can­cer surgery cuts re­lapse risk by 42%, but doesn’t im­prove sur­vival: #AS­CO23

CHICAGO — Merck has found partial success with its latest effort to more aggressively treat earlier stages of lung cancer.

On Saturday the pharma giant announced results from a large trial in which patients received Merck’s immunotherapy Keytruda plus chemotherapy before surgeons removed their tumors, followed by another course of Keytruda afterward.

The Phase III study, called KEYNOTE-671, enrolled 800 people with the early stages of the most common kind of lung cancer: non-small cell lung cancer, or NSCLC. Everyone got chemo before surgery, and half also got Keytruda before and after. At two years, 62.4% of those who got Keytruda kept their cancer at bay, compared to 40.6% who got a placebo.

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Grail’s blood test charts path for di­ag­nos­ing pa­tients sus­pect­ed of hav­ing can­cer in large study: #AS­CO23

Grail’s vision is simple but bold. The blood testing company has long held that people are often diagnosed with cancer too late. If seemingly healthy people were screened for early signs of the disease before symptoms appear, they may be able to get more effective treatments that nip cancer in the bud.

That premise is the basis of Grail’s commercial blood test, Galleri, which searches for the genetic fingerprints of cancer in the blood. The test, launched in 2021, reaped $55 million in sales last year, but now the company is setting its sights on a new market: patients suspected of having cancer due to symptoms such as abdominal pain, rectal bleeding or unexplained weight loss. Rather than administering expensive scans or conducting invasive biopsies right away, Grail hopes doctors will consider a simple blood test.

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Take­da ax­es gene ther­a­py deal with Po­sei­da Ther­a­peu­tics amid broad­er re­think

Less than two years after Takeda inked a collaboration with Poseida Therapeutics to develop six liver-directed and hematopoietic stem cell-directed in vivo gene therapies, Takeda will end the partnership on July 30, the company confirmed to Endpoints News.

The breakup is not unexpected, coming on the heels of Takeda’s April announcement that it planned to stop discovery and preclinical work in AAV gene therapy, as well as research and preclinical work on rare hematology. A representative for Takeda confirmed that the partnership ended because of the company’s decision to stop that work.

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