IO Biotech has raised €127 million ($155 million) to fund clinical development of immune-modulating IDO and PD-L1 cancer vaccines. The series B financing round comes months after IO Biotech showed combining its IDO and PD-L1 vaccines with Opdivo triggered complete responses in 45% of stage 4 melanoma patients.
Multiple companies have targeted IDO and PD-L1 with mixed success. PD-1/L1 checkpoint inhibitors such as Bristol Myers Squibb's Opdivo and Merck’s Keytruda have improved outcomes in multiple cancer types. Drug developers identified IDO inhibitors as the next big thing in immuno-oncology and complementary to PD-1/L1 drugs, only for clinical flops at Incyte and NewLink Genetics to wipe out the field.
IO Biotech is coming at the targets, which suppress the immune system, from a different angle. The Danish biotech has created long peptide epitopes derived from antigens including IDO and PD-L1. By administering the molecules to cancer patients, IO Biotech hopes to activate and expand preexisting T cells against the immune-suppressive molecules. IO Biotech expects activated T cells to home in on tumors, attack cells that express target antigens, release cytokines and alter the microenvironment.
The approach has caught the attention of investors. HBM Healthcare Investments led the series B with the support of fellow new investors including Vivo Capital, Kurma Partners, Avoro Capital and RA Capital Management. Existing backers such as Novo Seeds, which created IO Biotech in 2015, also contributed to the round.
The financing marks a significant step up in IO Biotech’s financial firepower. IO Biotech raised a series A round five years ago, pulling in €11 million to build on a first-in-human assessment of its IDO asset in non-small cell lung cancer. Since then, IO Biotech has generated more compelling evidence of the efficacy of its therapies.
Last year, IO Biotech shared data on 30 treatment-naive stage 4 melanoma patients who received its IDO and PD-L1 vaccines, respectively known as IO102 and IO103, in combination with Bristol Myers’ PD-1 checkpoint inhibitor Opdivo. As of the data cutoff, 45% of subjects had experienced a complete response. The overall response rate was 79%, which split up into a response rate of 94% in PD-L1-positive patients and 62% in PD-L1-negative patients.
IO Biotech compared results from the single-arm clinical trial to a matched control group, extracted from the Danish Metastatic Melanoma Database, of patients who received an anti-PD-1 drug as a monotherapy. The researchers said the response rate was “significantly higher” in patients treated with the cancer vaccines, without providing data from the control group in the abstract.
Previous clinical trials of Opdivo give some indication of just how significant the difference may be. A clinical trial that gave Opdivo to stage 3 and 4 melanoma patients reported a 45% overall response rate and a 19% complete response rate.
Armed with the series B funds and a breakthrough-therapy designation, IO Biotech plans to run a large, randomized clinical trial of IO102 and IO103 with anti-PD-1 monoclonal antibodies in metastatic melanoma. Promise shown in small single-arm studies can evaporate in large randomized trials, but if IO Biotech avoids that fate it will have that most sought-after of assets: wholly owned molecules that enhance the efficacy of blockbuster checkpoint inhibitors.