The class of cancer therapies known as antibody drug conjugates showed toxic drug payloads can be delivered to tumors in a targeted way. The first ADCs delivered chemotherapy, but the field is also testing other payloads. Firefly Bio, a Versant Ventures-backed startup, is now out of stealth with $94 million, joining a growing cohort of companies working to expand the ADC field.
An ADC is modular, comprised of a targeting antibody and a drug payload that are hitched together by a chemical linker. The ADCs currently available and many more that are in development employ chemo as the drug payload. South San Francisco-based Firefly is offering an ADC with a twist. Its therapies carry drug payloads that work by degrading a disease-causing protein. This new types of ADC is called a degrader antibody conjugate, or DAC.
Firefly aims to overcome some of the limitations of traditional ADCs. The powerful cancer-killing ability of an ADC’s chemo drug payload means the therapy has a limited therapeutic index, the dose range that balances safety and efficacy, the company said. Also, ADCs lack the ability to address specific proteins within a cell. Meanwhile, protein degraders can selectively address protein targets within a cell, eliminating them. But Firefly notes that one limitation of degraders is their bioavailability, or how much of a drug is available in the body’s circulation to offer a therapeutic effect. Degraders also do not have the ability for cell-specific targeting.
By combining an ADC with a degrader overcomes, Firefly aims to overcome the limitations of each modality. The startup employs a proprietary linker technology called Firelink that it says decreases how much of the drug payload goes into the circulation, where it can be picked up by healthy tissue. Consequently, a Firefly therapy requires a lower dose to achieve optimal efficacy. According to the company, preclinical research in both solid and liquid tumors showed a single administration of a Firefly DAC led to “significant reductions in tumor volume at very low doses.”
“DACs are a new modality for cancer,” Firefly CEO Scott Hirsch said in a prepared statement. “They give us the ability to hit biologically validated targets with minimal collateral damage. Our platform enables DACs at scale and vastly expands the number of payloads for ADCs.”
In a report issued earlier this month, Leerink Partners analyst Christopher Liu said that despite the targeting ability of the antibody component of an ADC, these drugs are known for toxicities. DACs could be safer than ADCs while still being efficacious. He added that this emerging class of drugs is drawing interest from some larger pharma companies, which see them as a way to expand beyond traditional ADCs.
Last September, protein degrader developer Nurix Therapeutics struck up a research alliance with ADC-specialist Seagen, now a part of Pfizer. The targets of the collaboration were not disclosed. Last November, Bristol Myers Squibb paid $100 million up front to acquire an Orum Therapeutics DAC candidate ready for Phase 1 testing in blood cancers. In December, Merck entered DAC R&D through an alliance with C4 Therapeutics. The cancer target of this alliance remains undisclosed. The companies said the pact could expand to additional targets.
Firefly’s Series A round was co-led by Versant and MPM BioImpact. Decheng Capital and Eli Lilly also joined the financing. Firefly has not disclosed the targets of its research. In the financing announcement, Jeral Davis, managing director at Versant and a Firefly board member, said the startup is discovering DACs for use in oncology and immunology.
Firefly was incubated at Ridgeline Discovery Engine, Versant’s startup creation entity in Switzerland. There the company said it established proof-of-concept for its lead asset. Firefly has not offered any timelines for reaching clinical testing with this asset.
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