A can­cer-fight­ing con­cept from the in­ven­tor of the first can­cer vac­cine is near­ing prime time, and its biotech de­vel­op­er has re­ceived a sig­nif­i­cant new in­fu­sion of cash to get it there.

Bolt Bio­ther­a­peu­tics an­nounced a $93.5 mil­lion Se­ries C round led by Sofinno­va In­vest­ments and joined by more than 9 oth­ers, in­clud­ing Pfiz­er Ven­tures and RA Cap­i­tal Man­age­ment. That mon­ey will go to­ward push­ing the San Fran­cis­co biotech’s plat­form of in­nate im­mune-boost­ing war­heads through its first tri­al on metasta­t­ic sol­id tu­mors and in­to sev­er­al more.

Randy Schatz­man

It’s “a fair­ly el­e­gant but sim­ple mol­e­cule,” CEO Randy Schatz­man told End­points News. “It’s ba­si­cal­ly an off-the-shelf ther­a­peu­tic that physi­cians can call on to treat their pa­tients with­out all the per­son­al­iza­tion and man­u­fac­tur­ing dif­fi­cul­ties that many of the I/O ap­proach­es have to­day.”

The ex­per­i­men­tal drug is what Bolt calls an im­mune-stim­u­lat­ing an­ti­body con­ju­gate. It’s based on a con­cept from Stan­ford im­mu­nol­o­gist Edgar En­gle­man, who in­vent­ed the first can­cer vac­cine in Provenge, a treat­ment for prostate can­cer. That vac­cine in­volves a mul­ti-step process where in­nate im­mune cells called den­drit­ic cells are ex­tract­ed, ex­posed to a pro­tein from the pa­tients’ own tu­mors (as you would ex­pose the im­mune sys­tem to a vi­ral or bac­te­r­i­al pro­tein in a tra­di­tion­al vac­cine) and then re­in­fused.

Bolt’s plat­form is de­signed to di­rect­ly ac­ti­vate den­drit­ic cells around tu­mors with­out the need for re­moval, treat­ment and re-in­fu­sion. The ther­a­py is an an­ti­body drug con­ju­gate sim­i­lar to those pro­duced by Seat­tle Ge­net­ics, ADC Ther­a­peu­tics, and Im­munomedics, each of which con­tain an an­ti­body to guide the ther­a­py like a war­head to the tu­mor. The dif­fer­ence is that in­stead of strap­ping a chem­i­cal to the an­ti­body that will kill cells in the area, Bolt’s drug has an ag­o­nist that will bind to re­cep­tors on the den­drit­ic cells and ac­ti­vate them to at­tack the tu­mor.

Edgar En­gle­man

If it works, the drug would turn the en­vi­ron­ment around the tu­mor from an im­muno-sup­pres­sive to one that could not on­ly kill the tu­mors once but pre­vent re­cur­rence. Their first can­di­date us­es a Her­ceptin biosim­i­lar to tar­get HER2, but in the­o­ry, Schatz­man said, it should work with an an­ti­body tar­get­ed at any onco­gene and Bolt is ex­plor­ing those op­tions, both in­ter­nal­ly and with part­ner­ships.

In Feb­ru­ary, five years af­ter the com­pa­ny’s foun­da­tion, they launched their first tri­al, putting the drug — known as BDC-1001 — in­to a Phase I/II tri­al for metasta­t­ic tu­mors that are HER2+, in­clud­ing gas­tric and breast can­cer. That tri­al will test the drug both as a sin­gle-agent ther­a­py and in com­bi­na­tion with Mer­ck’s Keytru­da. The idea is that ac­ti­vat­ing the im­mune sys­tem in two dif­fer­ent ways might make for a more ef­fec­tive treat­ment.

De­spite some ear­ly con­cerns, Schatz­man says, the com­pa­ny has not seen any de­lays in that tri­al from Covid-19.

Af­ter the first da­ta emerge from the Phase I/II tri­al, the com­pa­ny will move in­to tri­als specif­i­cal­ly for gas­tric and breast can­cer, look­ing to see if it can not on­ly clear can­cers ini­tial­ly but al­so, by keep­ing the im­mune sys­tem on guard, ward off re­cur­rence, an event that can come quick­ly for pa­tients with these late-stage tu­mors.

”We’re go­ing to see some quick an­swers in go­ing past what is the cur­rent stan­dard of care,” Schatz­man said. “I’d like to think it will take a long time to know where the end of this is, be­cause in that sense, we’ll have been very ef­fec­tive at treat­ing these pa­tients.”

89bio said its drug was better than placebo at lessening fibrosis without worsening nonalcoholic steatohepatitis, or NASH, in two of three dose groups.

The San Francisco biotech said it thinks the Phase IIb data pave the way for a potential Phase III, following in the footsteps of another biotech in its drug class, Akero Therapeutics. To fund a late-stage study, CEO Rohan Palekar told Endpoints News 89bio “would need to raise additional capital,” with the company having about $188 million at the end of last year.