ADC maker Callio Therapeutics secures US$187m in Series A round

The goal of Frazier, Jeito Capital and participating life sciences investors including Novo Holdings A/S, Omega Funds, ClavystBio, Platanus, Norwest, Pureos Bioventures, SEEDS Capital and EDBI is to achieve clinical proof-of-concept of Hummingbird’s HER-2-targeted dual-payload ADC HMBD-802 and a second undisclosed ADC programme that have been licenced to be co-developed by Callio Therapeutics. No details on the conditions of the licence deal have been disclosed

The deal came after Hummingbird demonstrated preclinically that HMBD-802, which combines a topoisomerase 1 payload with inhibitor of the DNA damage checkpoint kinase ATR (ATRi) in a 1:1 DAR (drug-to-antibody ratio), is tolerated at a no observed adverse events level (Noael) of 30 mg/kg/dose, which is several times higher as the therapeutic dose that inhibited further tumour growth. The working hypothesis is that ATR inhibition overcomes tumour insensivity by triggering premature mitotic entry, genomic instability and apoptosis in the more than 85% of gastric cancer patients and 65% of breast cancer patients that express HER2 even after having been treated with an Topoisomerase I-ADC-monotherapy. Data were shown at last year’s EORTC-NCI-AACR conference.

Rachel Mears, Partner at Jeito will join Callio’s Board of Director as Board member. Dr Piers Ingram, co-founder and Chief Executive Officer of Callio Therapeutics, concluded: „Multi-payload ADCs have the potential to enable the targeted delivery of rational drug combinations to cancer cells, and may provide significantly enhanced efficacy. This new generation of ADC therapies may meaningfully improve outcomes for patients.“

Experts at PEGS Europe 2024 in Barcelona told European Biotechnology that a major problem of the drug class of ADCs are on- and off-target toxicities and immune reactions that narrow the therapeutic window of antibody drug conjugates. Developers address toxicity issues by using multispecific ADC-prodrugs with stable linkers that are (partly enzymatically) activated when entering the acidic tumour microenvironment and by using novel payloads.