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)

Ven­ture Cap­i­tal as a Strate­gic Part­ner: Fu­el­ing In­no­va­tion be­yond Fi­nance

The average level of investment required for a biotech start-up to succeed is increasing every year, elevating the pressure even further on venture capital to make smart financial investments. Financial investment alone, however, does not always guarantee that exciting innovations can be transformed into real businesses that make a meaningful difference to patients.

Beyond just capital

At Astellas Venture Management (AVM) – a wholly-owned venture capital organization within Astellas, headquartered in the San Francisco Bay Area – capital is just one of the ingredients we offer to add value to our biotechnology investments and partnerships. We generally take a strategic investor approach for companies in our invested portfolio, providing access to expertise, technology and/or resources in addition to the injection of finance. An equity investment from AVM can include access to Astellas’ research and development (R&D) capabilities and expertise, and a global network of partner academic institutions and biotechnology companies, to help advance and accelerate the start-up’s innovation.

UP­DAT­ED: Ver­tex joins Mer­ck, Pfiz­er — re­vamp­ing multi­bil­lion-dol­lar tri­al strat­e­gy as biotech R&D crum­bles

You can add Pfizer, Merck and — as we found out Friday morning — Vertex to the growing list of pharma giants hitting the pause button on a range of clinical trials. But not everyone in R&D is getting a red light.

Vertex says that it’s doing its best to keep working its pipeline strategy, coming up with a plan “to enable virtual clinic visits and home delivery of study drug to ensure study continuity and medical monitoring, and to facilitate study procedures.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 76,900+ biopharma pros reading Endpoints daily — and it's free.

Covid-19 roundup: In­ter­cept, blue­bird and a grow­ing list of biotechs feel the pain as pan­dem­ic man­gles FDA, R&D sched­ules

Around 100 staffers at Boston area hospitals have now tested positive for Covid-19, spotlighting the growing risk that the pandemic will sideline many of the most essential workers in healthcare as caseloads peak in the US and around the globe. With more than 3,400 deaths, Spain has become the latest country to surpass the official death count attributed to the new coronavirus in China, where the outbreak originated. As of Thursday morning, confirmed global cases had crossed 470,000 and the death count eclipsed 21,000.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 76,900+ biopharma pros reading Endpoints daily — and it's free.

Af­ter crit­ics lam­bast­ed Gilead for grab­bing the FDA's spe­cial rare drug sta­tus on remde­sivir, they're giv­ing it back

Two days after Gilead won orphan drug status for remdesivir as a potential treatment for Covid-19, they’re handing it back.

The company was slammed from several sides after Gilead reported that the FDA had come through with the special status, which comes with 7 years of market exclusivity, the waiver of FDA fees and some tax credits as well. Typically, everyone who can get orphan status lands it without much of a fuss, but Democratic presidential candidate Bernie Sanders, Public Citizen and other consumer groups were outraged.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 76,900+ biopharma pros reading Endpoints daily — and it's free.

Mod­er­na CEO Stéphane Ban­cel out­lines a short path for emer­gency use of a coro­n­avirus vac­cine

NIAID director Anthony Fauci has left no doubts that it takes 12 to 18 months to get a new vaccine tested and in commercial use, in the best of circumstances. But in times of a global emergency — like these — maybe there’s another, faster route to follow.

In an SEC filing on Tuesday, Moderna $MRNA staked out a record-setting pathway to getting their mRNA vaccine into the frontline of the healthcare response as early as this fall. The SEC filing notes that CEO Stéphane Bancel told Goldman Sachs that an emergency use approval could allow the vaccine to go to healthcare workers and certain individuals in a matter of months — presumably provided the NIH sees the safety and efficacy data they would need from the Phase I.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 76,900+ biopharma pros reading Endpoints daily — and it's free.

Caught in a Covid-19 mael­strom, Eli Lil­ly locks down clin­i­cal tri­als as multi­bil­lion-dol­lar R&D ops de­rail

The Covid-19 pandemic has derailed Eli Lilly’s $6 billion R&D operations.

The pharma giant reported Monday morning that it has decided to hit the brakes on most new study starts and pause enrollment for most ongoing studies. Lilly adds that it is continuing dosing for ongoing studies, “but with study-by-study consideration.”

The pandemic has severely disrupted healthcare systems around the globe, says Lilly, making it difficult or impossible to conduct studies at many research sites. And there’s no timeline for when it expects to get back on track.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 76,900+ biopharma pros reading Endpoints daily — and it's free.

As share buy­backs come un­der scruti­ny, what's in store for the bio­phar­ma in­dus­try?

Stock buybacks are not to be permitted for companies that will be bailed out in the coronavirus stimulus package, Congressional leaders have signaled. To what degree the biopharma industry has relied on buybacks for earnings growth in recent years, and if the trend continues, are the big questions as scrutiny into the practice heightens and balance sheets weaken with the coronavirus pandemic wreaking havoc on global economies.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 76,900+ biopharma pros reading Endpoints daily — and it's free.

A Sin­ga­pore VC rais­es $200M for a new round, but will Covid-19 pre­vent it from rais­ing the rest?

A top Singaporean biotech venture fund is nearly halfway toward its largest ever fund, but in a sign of what could be in store for VCs amid a global economic freeze, said they could face headwinds raising the other half.

Vickers Venture Partners has secured $200 million out of a targeted $500 million for its 6th fund, first announced in early 2018. They’ve given themselves 13 months to complete the financing, Vickers founder Finian Tan told Deal Street Asia, but the financial frost settling amid the Covid-19 pandemic could slow efforts.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 76,900+ biopharma pros reading Endpoints daily — and it's free.

Strug­gling Unum ex­ecs are ready to con­sid­er a sale, merg­er or any deal that comes its way

Unum $UMRX is working its way through a survival plan of sorts.

After getting hit with a trio of FDA holds in its brief public history and triggering its second pivot to a new lead drug program while laying off 60% of the staff, the troubled penny stock biotech Unum Therapeutics has hatched new plans to secure financial backing while lining up a go-forward strategy for the company.

First, Lincoln Park Capital Fund has agreed to buy up to $25 million of the long-suffering stock, as Unum directs. And the executive team — led by CEO Chuck Wilson — has put everything on the table for consideration: a sale, acquisition, merger, licensing deal, you name it. The ACTR707 program, meanwhile, is being formally wrapped up — their second failed lead program.