Af­ter a run of CT­LA-4 com­bo fail­ures, sci­en­tists spot­light a way to make it work — in se­lect pa­tients

CT­LA-4/PD-(L)1 com­bi­na­tions have been one of the El Do­ra­dos of on­col­o­gy, its promise for­ev­er be­hind that next hill but ap­par­ent­ly un­at­tain­able af­ter a se­ries of piv­otal clin­i­cal fail­ures. But re­searchers at New York’s Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter and the Tech­ni­cal Uni­ver­si­ty of Mu­nich think they may know how to fix what’s wrong and boost the dri­ve to next-gen can­cer com­bos.

In a pre­clin­i­cal an­i­mal re­search pro­gram, re­searchers found that with­in a cell, check­points re­ly on a spe­cif­ic mol­e­cule — RNA-sens­ing mol­e­cule RIG-I — to work. If that sounds fa­mil­iar, it’s be­cause it has al­ready been iden­ti­fied as a tar­get for boost­ing im­mune re­spons­es and was sub­ject to at least one Phase I/II tri­al. Pfiz­er in De­cem­ber al­lied it­self with Kine­ta with $15 mil­lion up­front and $505 mil­lion in po­ten­tial mile­stones to de­vel­op RIG-I im­munother­a­pies, and three years ago Mer­ck pur­chased Ger­man up­start Rigontec for $137 mil­lion up­front and over $400 mil­lion in po­ten­tial mile­stones for the same pur­pose.

The sci­ence team’s work helps spot­light what they’re af­ter.

Pub­lish­ing in Sci­ence Im­munol­o­gy, the re­searchers found that high ex­pres­sion of the gene for RIG-I (gene DDX58) her­ald­ed re­spon­sive­ness to CT­LA-4 ther­a­py and sug­gest­ed doc­tors might test for RIG-I ex­pres­sion in tu­mors to pre­dict who will re­spond to the ther­a­py. They could then tai­lor treat­ments to that pop­u­la­tion. The study al­so sug­gests that com­bin­ing  PD-1/CT­LA-4 with a RIG-I ag­o­nist might boost the ef­fec­tive­ness of the hereto­fore of­ten dis­ap­point­ing ther­a­py.

CT­LA-4 and PD-1 ther­a­pies, which won their prin­ci­pal founders 2018’s No­bel Prize in med­i­cine, work by tar­get­ing a re­cep­tor on T cells that stop the cell’s “check­point,” if you will – by block­ing the re­cep­tor, it es­sen­tial­ly re­leas­es the brakes on the im­mune sys­tem and al­lows the body’s T cells to start a full high-speed chase on the tu­mor(s). Sev­er­al such im­munother­a­pies have been ap­proved in the past few years, be­gin­ning with ip­il­i­mum­ab for melanoma in 2011, but the ec­sta­t­ic promise has turned up a lot of dry wa­ter beds of late. Tri­als from the ma­jor play­ers, in­clud­ing Bris­tol-My­ers Squibb, As­traZeneca, and Sanofi,  at­tack­ing small cell lung can­cer, head and neck car­ci­no­ma, and non-small cell lung can­cer with a mix of PD-1 and CT­LA-4 in­hibitors have all failed.

This is not the first study look­ing at how to im­prove and tai­lor CT­LA-4 ther­a­pies. Last year, re­searchers work­ing on mice found that they could “im­age” the re­sponse with a ra­dioac­tive trac­er that latch­es to OX40, a mol­e­cule on­ly found in ac­ti­vat­ed T cells, and thus the­o­ret­i­cal­ly learn ear­ly on if a pa­tient is re­spond­ing to the ther­a­py.

So­cial im­age: Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter

A New Fron­tier: The In­ner Ear

What happens when a successful biotech venture capitalist is unexpectedly diagnosed with a chronic, life-disrupting vertigo disorder? Innovation in neurotology.

That venture capitalist was Jay Lichter, Ph.D., and after learning there was no FDA-approved drug treatment for his condition, Ménière’s disease, he decided to create a company to bring drug development to neurotology. Otonomy was founded in 2008 and is dedicated to finding new drug treatments for the hugely underserved community living with balance and hearing disorders. Helping patients like Jay has been the driving force behind Otonomy, a company heading into a transformative 2020 with three clinical trial readouts: Phase 3 in Ménière’s disease, Phase 2 in tinnitus, and Phase 1/2 in hearing loss. These catalysts, together with others in the field, highlight the emerging opportunity in neurotology.
Otonomy is leading the way in neurotology
Neurotology, or the treatment of inner ear neurological disorders, is a large and untapped market for drug developers: one in eight individuals in the U.S. have moderate-to-severe hearing loss, tinnitus or vertigo disorders such as Ménière’s disease.1 With no FDA-approved drug treatments available for these conditions, the burden on patients—including social anxiety, lower quality of life, reduced work productivity, and higher rates of depression—can be significant.2, 3, 4

Af­ter 4 years of furor, the FTC and New York state ac­cuse Mar­tin Shkre­li of run­ning a drug mo­nop­oly. And this time they plan to squash it

Pharma bro Martin Shkreli was jailed, publicly pilloried and forced to confront some lawmakers in Washington riled by his move to take an old generic and move the price from $17.50 per pill to $750. But through 4 years of controversy and public revulsion, his company never backed away from the price — left uncontrolled by a laissez faire federal policy on a drug’s cost.

Now the FTC and the state of New York plan to pry his fingers off the drug once and for all and open it up to some cheap competition.

Patrik Jonsson, the president of Lilly Bio-Medicines

Who knew? Der­mi­ra’s board kept watch as its stock price tracked Eli Lil­ly’s se­cret bid­ding on a $1.1B buy­out

In just 8 days, from December 6 to December 14, the stock jumped from $7.88 to $12.70 — just under the initial $13 bid. There was no hard news about the company that would explain a rise like that tracking closely to the bid offer, raising the obvious question of whether insider info has leaked out to traders.

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Short at­tack­er Sahm Ad­ran­gi draws crosshairs over a fa­vorite of Sanofi’s new CEO — with PhII da­ta loom­ing

Sahm Adrang Kerrisdale

Kerrisdale chief Sahm Adrangi took a lengthy break from his series of biotech short attacks after his chief analyst in the field pulled up stakes and went solo. But he’s making a return to drug development this morning, drawing crosshairs over a company that’s one of new Sanofi CEO Paul Hudson’s favorite collaborators.

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UP­DAT­ED: Ac­celeron of­fers thumbs up on a PhII suc­cess for would-be block­buster drug — and shares rock­et up

There’s no public data yet, but Acceleron $XLRN says that its first major trial readout of 2020 is a success.

In a Phase II study of 106 patients with pulmonary arterial hypertension (PAH), Acceleron’s experimental drug sotatercept hit its primary endpoint: a significant reduction in pulmonary vascular resistance. The drug also met three different secondary endpoints, including the 6-minute walking test.

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Civi­ca and Blue Cross Blue Shield launch new ven­ture to low­er gener­ic prices

Five years after Martin Shkreli put a smug face to the volatile prices companies can charge even for generic drugs, payers and governments are coming up with outside-the-box solutions.

The latest fix is a new venture from the Blue Cross Blue Shield Association, 18 of its members and Civica, the generics company founded in 2018 by hospitals fed up with high prices for drugs that had long-since lost patent protection. While Civica focused on drugs that hospitals purchased, the new company will aim to lower prices on drugs that, like Shkreli’s Daraprim, are purchased by individuals.

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Merck Invests in State-Of-The-Art Biotech Development Facility in Switzerland

Mer­ck KGaA match­es lofty R&D goals with €250M in­vest­ment in­to a new clin­i­cal man­u­fac­tur­ing site in Switzer­land

As Merck KGaA strives to prove itself as a capable biopharma R&D player, it has begun construction on a €250 million facility dedicated to developing and manufacturing drugs for use in clinical trials.

The German drugmaker chose a location at Corsier-sur-Vevey, Switzerland, where it already has a commercial manufacturing site, in order to “bridge together research and manufacturing.”

“This investment in the Merck Biotech Development Center reflects our commitment to speed up the availability of new medicines for patients in need, and confirms the importance of Switzerland as our prime hub for the manufacturing of biotech medicines,” CEO Stefan Oschmann said at the groundbreaking ceremony, according to a statement.

Breast can­cer ap­proval in tow, As­traZeneca, Dai­ichi armed an­ti­body scores in key gas­tric can­cer study

AstraZeneca kicked off Monday with a flurry of good news. Apart from unveiling positive results on its stroke trial testing its clot-fighter Brilinta, and welcoming its experimental IL-23 inhibitor brazikumab back from Allergan — the British drugmaker also disclosed some upbeat gastric cancer data on its HER2-positive oncology therapy it is collaborating on with Daiichi Sankyo.

Buoyed by the performance of its oncology drugs, last March AstraZeneca chief Pascal Soriot bet big to partner with Daiichi on the cancer drug, with $1.35 billion upfront in a deal worth up to roughly $7 billion. Roughly 8 months later, as 2019 drew to a close, the FDA swiftly approved the drug — trastuzumab deruxtecan — for use in breast cancer, months ahead of the expected decision date.

Sor­ren­to shrugs off an anony­mous pri­vate eq­ui­ty group’s $1B of­fer to buy the com­pa­ny

San Diego-based Sorrento Therapeutics isn’t going the M&A route — at least not today.

The biotech caused quite a stir when it put out word a few weeks ago that an unidentified private equity group was bidding a billion dollars-plus for the company. The news drove a quick spike in the company’s share price as investors hooked up for the ride — that didn’t happen.

The update sparked a 5% drop in the share price $SRNE ahead of the bell. It’s now trading just above $4, without any evidence that the $7 price looked like it was firm.