One of the Holy Grails in the boom­ing im­muno-on­col­o­gy re­search field right now in­volves find­ing an IL-2 drug that can be used safe­ly and ef­fec­tive­ly to com­bat can­cer, with­out the im­mense tox­i­c­i­ty that has large­ly side­lined the orig­i­nal IL-2 Pro­leukin. Bris­tol-My­ers Squibb paid Nek­tar $1.85 bil­lion in up­front cash to part­ner on NK­TR-214 — which has since come un­der a cloud of un­cer­tain­ty over flail­ing re­sponse rates in their key demon­stra­tion study com­bin­ing it with Op­di­vo.

Now a group of sci­en­tists at the Uni­ver­si­ty of Wash­ing­ton says they built an IL-2 pro­tein ther­a­py all their own, and they’ve launched a new biotech — Ne­oleukin — to take it for­ward from mouse stud­ies to­ward the clin­ic.

Umut Ulge

De­scrib­ing their work to a writer at UW Med­i­cine, the group says they de­signed their pro­tein to bind specif­i­cal­ly to IL-2  be­ta and gam­ma re­cep­tors to whip up a more po­tent T cell re­sponse to can­cer while steer­ing clear of CD25 to cir­cum­vent the tox­ic re­ac­tion. By do­ing that they cre­at­ed a lab mod­el of the drug that the sci­en­tists were able to ratch­et up the dose on with­out the lethal re­ac­tion.

They al­so added a com­ple­men­tary com­po­nent for IL-15 to in­crease the ef­fi­ca­cy and dubbed the drug Neo-2/15, de­scrib­ing it as par­tic­u­lar­ly small and sta­ble. And the game plan is to con­tin­ue to use their com­pu­ta­tion­al skills to im­prove the drug.

“Neo-2/15 has ther­a­peu­tic prop­er­ties that are at least as good as or bet­ter than nat­u­ral­ly oc­cur­ring IL-2, but it was com­pu­ta­tion­al­ly de­signed to be much less tox­ic,” said Umut Ulge, one of the lead au­thors of a pa­per pub­lished in Na­ture.

An il­lus­tra­tion de­pict­ing how the new pro­tein, in red, binds on­ly to the be­ta and gam­ma re­cep­tors, and not to cells with a third kind of re­cep­tor. (UW MED­I­CINE)

Click on the im­age to see the full-sized ver­sion

Ne­oleukin, though, is hard­ly the on­ly ri­val to the throne that Nek­tar and Bris­tol-My­ers Squibb have been striv­ing for. Lau­ra Shawver’s Syn­thorx has al­so been an­gling for the clin­ic — in H1 of this year — with their drug can­di­date Syn­thorin IL-2, backed by Or­bimed and Medicxi. The biotech $THOR went pub­lic just a few weeks ago, rais­ing $150 mil­lion.

Last No­vem­ber Nek­tar Ther­a­peu­tics $NK­TR man­aged to add 1 more pa­tient out of its 38 evalu­able stage 4 melanoma pa­tients to the win col­umn with its close­ly-watched 3-month up­date on Op­di­vo/NK­TR-214’s ob­jec­tive re­sponse rate. That man­aged to nudge up the ORR from 50% — a fig­ure that rout­ed Nek­tar’s stock at AS­CO — to 53%. But the sci­en­tists al­so pushed up the com­plete re­sponse rate to 24%, main­tain­ing they were sat­is­fied with the im­proved re­sponse they were see­ing.

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

The standard for-profit model in drug development is straightforward. Spend millions, even billions, to develop a medicine from scratch. The return on investment (and ideally a tidy profit) comes via volume and/or price, depending on the disease. But the string of big pharma exits and slew of biotech bankruptcies indicate that the model is sorely flawed when it comes to antibiotics.

The industry players contributing to the arsenal of antimicrobials are fast dwindling, and the pipeline for new antibiotics is embarrassingly sparse, the WHO has warned. Drugmakers are enticed by greener pastures, compared to the long, arduous and expensive path to antibiotic approval that offers little financial gain as treatments are typically priced cheaply, and often lose potency over time as microbes grow resistant to them.

A couple years ago, Amber Salzman got a call as she was returning East full-time after a two-year stint running a gene therapy company in California.

It was from someone at Flagship Pioneering, the deep-pocketed biotech venture firm. They had a new company with a new way of thinking about sperm. It had been incubating for over a year, and now they wanted her to run it.

“It exactly fit,” Salzman told Endpoints News. “I just thought I had to do something.”

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. And their lawsuit is asking that Shkreli — with several years left on his prison sentence — be banned permanently from the pharma industry.

Incyte’s efforts to breathe a second life into ruxolitinib — its JAK inhibitor sold in pill form as Jakafi — has been greeted with clear, if preliminary and unsurprising, Phase III success.

Topline data from the TRuE-AD2 cements ruxolitinib’s foundational importance for Incyte, and gives analysts hope that there might yet be room for growth in a pipeline that’s suffered multiple R&D setbacks.