Sil­ver­back Ther­a­peu­tics gets $78M boost to 'recon­cep­tu­al­ize' an­ti­body-drug con­ju­gates

The resur­gence of an­ti­body-drug con­ju­gates (AD­Cs), in which a can­cer-killing tox­in is at­tached to a spe­cif­ic an­ti­body us­ing a biodegrad­able link­er, has of­fered the thriv­ing field of on­col­o­gy an­oth­er po­tent weapon in the fight against can­cer. But what if this tro­jan horse tech­nol­o­gy could be tweaked to link im­mune-stim­u­la­to­ry agents — as op­posed to cy­to­tox­ic pay­loads — to mon­o­clon­al an­ti­bod­ies?

Sil­ver­back Ther­a­peu­tics, which has long stayed mum about its tech­nol­o­gy plat­form, on Wednes­day mapped its mis­sion to use the strat­e­gy to tar­get im­muno­log­i­cal­ly “cold” tu­mors — and now has a fresh cap­i­tal in­jec­tion of $78.5 mil­lion to make its case.

“The ADC cat­e­go­ry has been used suc­cess­ful­ly in the past and, of course, of late has had a re­nais­sance with dif­fer­ent pay­loads that are still cy­to­tox­ic, and we kind of recon­cep­tu­al­ized the class in terms of its abil­i­ty to lo­cal­ize small mol­e­cules that can be used to mod­u­late pow­er­ful bi­o­log­ic path­ways that are not nec­es­sar­i­ly cy­to­tox­ic,” clin­i­cal on­col­o­gist and Sil­ver­back CEO Pe­ter Thomp­son told End­points News.

The Seat­tle, Wash­ing­ton-based com­pa­ny’s lead drug — SBT6050 — is an an­ti­body-drug con­ju­gate that de­liv­ers a heavy pay­load (in this case, TLR8 ag­o­nist) to HER2-ex­press­ing tu­mors. An ap­pli­ca­tion to test the drug in hu­mans is ex­pect­ed to be filed in the first half of 2020, Sil­ver­back CSO Va­lerie Ode­gard said.

“It is well known that there are a lot of myeloid cells in tu­mors, even tu­mors that have been clas­si­cal­ly de­fined as be­ing im­muno­log­i­cal­ly cold, which is ac­tu­al­ly just a ref­er­ence to the fact that they don’t have T cells, they have myeloid cells,” she not­ed. “How­ev­er, when those myeloid cells are ac­ti­vat­ed, they have a num­ber of mech­a­nisms that they un­leash that di­rect­ly kill tu­mor cells. TLR8 is the in­nate im­mune re­cep­tor ex­pressed in hu­man myeloid cells, and the abil­i­ty then to sys­tem­i­cal­ly de­liv­er an agent, whose ac­tiv­i­ty is lo­cal­ized to the site of the tu­mor and on­ly ac­ti­vates myeloid cells in the tu­mor is a very ex­cit­ing ther­a­peu­tic.”

Ex­ist­ing AD­Cs are de­signed to de­liv­er cy­to­tox­ic pay­loads such as chemother­a­pies to cells ex­press­ing the anti­gen tar­get, but Sil­ver­back’s tech­nol­o­gy has an­oth­er perk — it is en­gi­neered to work in a set­ting where on­ly a frac­tion of the cells in the tu­mor need to ex­press the tar­get anti­gen.

“Un­like cy­to­tox­ic AD­Cs where you need, by and large, ho­mo­ge­neous ex­pres­sion, for ex­am­ple, of HER2  tu­mor tar­gets in or­der to get ap­pro­pri­ate tar­get cov­er­age on the tu­mor cells in or­der to kill them — it’s a very dif­fer­ent mech­a­nism here,” said Ode­gard, who pre­vi­ous­ly worked with Juno Ther­a­peu­tics.

With SBT6050, tu­mor cell de­struc­tion is pos­si­ble even with het­ero­ge­neous HER2 ex­pres­sion, where on­ly a frac­tion of the tu­mor cells — even as low as 25% — ex­press HER2, she ex­plained.

For Thomp­son, that abil­i­ty is im­per­a­tive for the broad pop­u­la­tion of HER+ ex­press­ing can­cers the com­pa­ny plans to tar­get.

“Be­ing able to have a ther­a­peu­tic modal­i­ty that has sig­nif­i­cant po­ten­cy and of­fers the op­por­tu­ni­ty for pro­found sin­gle-agent ef­fi­ca­cy in a set­ting where on­ly a frac­tion of the cells in the tu­mor need to ex­press the tar­get anti­gen gives us great con­fi­dence go­ing in­to the clin­ic,” he said.

The drug’s safe­ty pro­file of­fers an­oth­er ad­van­tage, the ex­ec­u­tives sug­gest­ed.

“Sys­temic ad­min­is­tra­tion of TLR ag­o­nists has been tried in the past, but thwart­ed by sys­temic tox­i­c­i­ties that are en­gen­dered by the fact that you have a ton of myeloid cells all over the place, and in a non­spe­cif­ic man­ner ac­ti­vat­ing all of them is very dif­fi­cult for the host to tol­er­ate,” not­ed Thomp­son, who al­so serves as a pri­vate eq­ui­ty part­ner at Or­biMed, where the tech­nol­o­gy was cre­at­ed.

“Be­ing able to lo­cal­ize these ther­a­pies to the sites of dis­ease … in kind of a site-de­pen­dent con­text and be­ing able to ac­ti­vate these mech­a­nisms al­lows you to ac­cess the pow­er of these sys­tems, with­out the sys­temic tox­i­c­i­ties,” he added.

With­out delv­ing in­to specifics, Thomp­son said the com­pa­ny is look­ing to ad­dress HER2 ex­press­ing can­cers be­yond the breast, in­clud­ing lung and colon. Even­tu­al­ly, the ap­proach could al­so be used to ad­dress dis­eases such as chron­ic vi­ral in­fec­tions and fi­brot­ic dis­eases, he said.

Back in 2018, the com­pa­ny raised $47.5 mil­lion for its A round, led by Or­biMed, with par­tic­i­pa­tion from Cel­gene and Alexan­dria. This new Se­ries B haul was led by U.S. Ven­ture Part­ners, with par­tic­i­pa­tion from new in­vestors in­clud­ing Nex­tech In­vest, Hunt In­vest­ment Group, Pon­tif­ax Ven­ture Cap­i­tal, Colt Ven­tures LP, and NS In­vest­ment. Ex­ist­ing in­vestors — Or­biMed, Bris­tol My­ers Squibb (which has swal­lowed Cel­gene) and Alexan­dria — all al­so jumped in.

The com­pa­ny is named Sil­ver­back in ref­er­ence to the ti­tle giv­en to the leader of a moun­tain go­ril­la troop. “We’re the 800-pound go­ril­la in a new field that we’ve cre­at­ed,” Thomp­son quipped.

The field of AD­Cs that us­es cy­to­tox­ic pay­loads is al­so fair­ly hefty. Roche’s ADC Kad­cy­la gen­er­at­ed block­buster sales in 2019; Seat­tle Ge­net­ics’ Pad­cev was ap­proved late last year and oth­er armed an­ti­bod­ies part­nered with Gen­mab and Take­da in the pipeline; Dai­ichi Sankyo’s As­traZeneca-part­nered En­her­tu, tout­ed to gen­er­ate bil­lions in peak sales, was ap­proved by the FDA months ahead of sched­ule in 2019 and da­ta that could ex­pand the use of the ther­a­py has al­so been pub­lished. Oth­er com­pa­nies in the space in­clude the apt­ly named ADC Ther­a­peu­tics, Icon­ic Ther­a­peu­tics, and Sutro Bio­phar­ma.

So­cial im­age: Pe­ter Thomp­son, Sil­ver­back Ther­a­peu­tics (Or­biMed Ad­vi­sors Pho­to)

Nick Galakatos, Blackstone global head of life sciences

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The Blackstone team has neatly tied up the largest private fund ever raised in life sciences for making big dreams come true in biopharma. Late Thursday, Blackstone put out word that they had closed their highly anticipated fund with the projected $4.6 billion all in.

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UP­DAT­ED: Bio­gen shares spike as ex­ecs com­plete a de­layed pitch for their con­tro­ver­sial Alzheimer's drug — the next move be­longs to the FDA

Biogen is stepping out onto the high wire today, reporting that the team working on the controversial Alzheimer’s drug aducanumab has now completed their submission to the FDA. And they want the agency to bless it with a priority review that would cut the agency’s decision-making time to a mere 6 months.

The news drove a 10% spike in Biogen’s stock $BIIB ahead of the bell.

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Gilead is surging again off data that suggest its antiviral remdesivir might improve survival.

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The FDA’s ODAC — the Oncologic Drugs Advisory Committee — has a well-known bias in favor of adding new cancer drugs to the market, even if efficacy is at best marginal and serious safety issues demand careful management.

Doctors want as many arrows in their quiver as they can get. And when patients are dying after failing multiple drugs, why not give it a go one more time?

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