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)

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists

President Donald Trump, who seems intent on announcing a COVID-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

Is­raeli biotech rais­es $57M to go where cur­rent BRAF in­hibitors can't, with back­ing from No­var­tis, SR One

For the blockbuster potential of Novartis’ Tafinlar and Pfizer’s Braftovi, all the BRAF inhibitors on the market so far only target V600 mutations — which accounts for roughly 50% of patients.

Israeli biotech Novellus now has $57 million to develop a drug that they say can help the other 50% who have everything else.

The Series C will fund a Phase II trial for PLX-8394, a “paradox breaker” that could block RAF without activating MAPK signaling. In a Phase I trial, a patient with a BRAF fusion saw their tumor go away after taking the drug, allowing Novellus to hit the ground running.

Jonathan Rigby, Immune Regulation group CEO

Im­mune Reg­u­la­tion, tak­ing two clin­i­cal pro­grams to 're­set' the im­mune sys­tem, nets $53M+ Se­ries B

A little under two years after a company rebranding, Immune Regulation is taking an even bigger step toward advancing its goals.

Formerly known as Peptinnovate, the British biotech announced a $53.4 million Series B early Monday morning, helping to further advance two clinical programs in rheumatoid arthritis and asthma. Though those are the two initial indications the company is focusing on, CEO Jonathan Rigby told Endpoints News he hopes the candidates can be applied to a broad swath of autoimmune disorders.

UP­DAT­ED: Two wild weeks for Grail end in $8B Il­lu­mi­na buy­out

Grail’s whirlwind two weeks have ended in the wealthy arms of its former founder and benefactors.

Illumina has shelled out $8 billion to reacquire the closely-watched liquid biopsy startup they spun out just 5 years ago and sold off much of its shares just 3 years ago. The deal comes nearly two weeks after the well-heeled startup filed for a potentially massive IPO — one that was disrupted just a week later when Bloomberg reported that Illumina was in talks to buy their former spinout for up to $8 billion.

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Roche vaults to the front of the NL­RP3 clin­i­cal race, pay­ing $448M up­front to bag In­fla­zome

Roche is going all in on NLRP3.

The pharma giant is putting down $448 million (€380 million) upfront to snatch Novartis-backed Inflazome, which makes it a clinical player in the space overnight.

Dublin and Cambridge, UK-based Inflazome is the second NLRP3-focused biotech Roche has acquired in less than two years, and although no numbers were disclosed in the Jecure buyout, this is almost certainly a much larger deal.

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Anthony Fauci (AP Images)

A press of­fi­cer at An­tho­ny Fau­ci’s NI­AID was un­masked as a hard-right Covid troll. He just re­tired to­day

William B Crews had been a public affairs specialist at the NIH’s National Institute of Allergy and Infectious Diseases.

That ended today when he informed the agency of his decision to retire, after he was identified as the managing editor at RedState, a prominent Trump loyalist website.

Crews’ RedState duties are performed under the alias streiff. While enjoying the benefits of pseudonymity, he disparaged and worked against NIAID with an incendiary level of rhetoric in the midst of a pandemic.

#ES­MO20: Bris­tol My­ers marks Op­di­vo's sec­ond ad­ju­vant win — eye­ing a stan­dard of care gap

Moving into earlier and earlier treatment lines, Bristol Myers Squibb is reporting that adjuvant treatment with Opdivo has doubled the time that esophageal or gastroesophageal junction cancer patients stay free of disease.

With the CheckMate-577 data at ESMO, CMO Samit Hirawat said, the company believes it can change the treatment paradigm.

While a quarter to 30% of patients typically achieve a complete response following chemoradiation therapy and surgery, the rest do not, said Ronan Kelly of Baylor University Medical Center. The recurrence rate is also high within the first year, Hirawat added.