On February 15, 2024 Firefly Bio reported that the company emerged from stealth mode with a $94 million Series A financing co-led by founding investor Versant Ventures and by MPM BioImpact alongside Decheng Capital and with participation from Eli Lilly & Company (Press release, Firefly Bio, FEB 15, 2024, View Source [SID1234640173]). Firefly has developed a novel platform to treat cancer using degrader antibody conjugates (DACs).
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DACs represent the convergence of two technologies – antibody drug conjugates (ADCs) and protein degraders. Despite the power of each approach, both have important limitations. While traditional ADCs have favorable bioavailability and the ability to target cells, they often have a limited therapeutic index due to their broadly cytotoxic payloads. Additionally, ADCs lack the ability to knock down specific intracellular proteins.
With protein degraders, the converse is true – these therapies have intracellular selectivity, protein knock down, and are highly catalytic. However, they struggle with bioavailability and do not have the ability for cell-specific targeting.
Firefly’s platform combines the respective strengths of ADCs and degraders while overcoming their deficiencies. The result is a new class of therapeutics able to precisely drug a range of intracellular biological targets that were previously hampered by therapeutic index issues when delivered systemically.
"DACs are a new modality for cancer," said Firefly CEO Scott Hirsch. "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."
An Industry-Leading Platform
Firefly’s platform uses potent catalytic protein degraders as the payloads of ADCs. The company’s proprietary Firelink linker technology joins these modalities, decreasing free payload in circulation and minimizing uptake in healthy cells. This leads to lower doses needed for optimal efficacy. In preclinical studies in both solid and liquid tumors, single administration of Firefly’s DACs showed significant reductions in tumor volume at very low doses.
Firefly was incubated in close collaboration with scientists at Versant’s Ridgeline Discovery Engine in the Basel Technology Park. These efforts helped the company rapidly establish proof-of-concept and advance its lead asset.
"At Firefly, we’ve assembled a unique talent base and platform to significantly advance this promising field," said Jerel Davis, Ph.D., Managing Director at Versant and a Firefly board member. "The company has made rapid progress and is poised to become the leader in discovering clinically meaningful DACs in oncology and immunology."
"Firefly is the first company with a platform specifically suited for DACs," said Todd Foley, managing director at MPM BioImpact and a Firefly board member. "The company’s platform upgrades multiple aspects of existing linker technologies and does so all under one roof, making it ideally positioned to pioneer these new therapies."
Leadership Team and Founders
Firefly is led by experienced executives with a deep history and expertise in biotech creation, ADC development, and degrader chemistry. The team is led by CEO, Scott Hirsch who was previously Chief Operating Officer at Allakos and has overseen multiple early- and late-stage ADC programs as well as directly managed commercial, portfolio, and operations teams. Co-founder and CSO John Flygare, Ph.D., previously led ADC teams at Genentech and Merck and has advanced ADCs and degraders into the clinic. Co-founder and CTO Bernhard Geierstanger, Ph.D., is a biotherapeutics expert and previously led ADC teams at Novartis and Merck and built protein modification and conjugation platforms. Co-founder Carolyn Bertozzi, Ph.D., was awarded the 2022 Nobel Prize in Chemistry for her work in bioorthogonal chemistry and is a world expert in ADCs.