Shots

• Mai-Britt talked about the P-I/II clinical trial data and study design of its lead candidate in metastatic melanoma in an e-poster presentation at AACR 2022
• She also spoke about IO Biotech’s unique platform with tumor defense mechanisms to kill cancer cells
• The interview gives a profound understanding of how IO Biotech is advancing to explore various ways for the treatment of cancer

Smriti: What exactly is the T-win technology platform?

Mai-Britt: IO Biotech’s proprietary T-win® platform is a novel approach to cancer immunotherapy designed to activate naturally occurring effector T cells already in the body to target and disrupt multiple immunosuppressive mechanisms. These infiltrating T cells can modulate the suppressive tumor microenvironment (TME) to transform it into a more pro-inflammatory environment to kill cancer. We believe our T-win platform offers a novel approach that targets both tumor cells as well as genetically stable host immunosuppressive cells, in order to avoid immune escape.  T-win is the first experimental approach that we know, that directly induces a potent immune response to target TME cells which express immune-suppressive proteins. Our T-win technology is built upon our team’s deep understanding of both TME and a tumor’s ability to evade surveillance and destruction by the immune system.

Smriti: Explain the details (MOA, ROA, formulations, etc.) of IO102-IO103

Mai-Britt: IO Biotech’s lead candidate, IO102-IO103, is a novel peptide vaccine that simultaneously targets indoleamine 2,3-dioxygenase (IDO) and anti-programmed death ligand 1 (PD-L1), proteins found in cells of the TME. IDO and PD-L1 are often dysregulated and over-expressed in a wide range of solid tumors and are correlated with poor prognosis. IO102-IO103 is designed to alter the immunologically unfavorable TME environment into a pro-inflammatory milieu, thereby enhancing effective anti-tumor T cell responses.

The drug works by activating and expanding T cells to attack both tumor cells and genetically stable immunosuppressive cells such as myeloid-derived suppressor cells and regulatory T cells. This strategy effectively results in the release of proinflammatory cytokines, increasing inflammation of the TME and allowing tumor-specific T cells to further eradicate the tumor. 

Additionally, IO Biotech’s IDO approach has a differentiated mechanism of action compared to previous IDO inhibitors. Prior IDO therapies using small molecules inhibited single immunosuppressive pathways, which only partially blocked IDO function, resulting in less efficacy. IO Biotech’s platform is designed to directly kill all IDO expressing cells, eliminating all its suppressive functions. 

Smriti: Discuss the study design of the Phase 1/2 (MM1636) clinical trial

Mai-Britt: The MM1636 trial (ClinicalTrials.gov: NCT03047928), is a Phase 1/2 investigator-led trial at the Copenhagen University Hospital, Herlev, that enrolled 30 patients with metastatic melanoma. In this clinical trial, patients received IO102-IO103 in combination with PD-1 antibody nivolumab as first-line treatment. Patients were treated with nivolumab according to the approved label for melanoma (3mg/kg bi-weekly for up to two years). IO102-IO103 was given from the start of administration of nivolumab and every second week for the first six weeks and thereafter, every fourth week for 41 weeks. The primary trial objectives were to assess safety, immune response in blood and biopsies as well as efficacy.

Smriti: What were the key findings of the Phase 1/2 (MM1636) clinical trial?

Mai-Britt: IO102-IO103 has shown very promising clinical activity as well as an attractive safety profile to date. Updated clinical data were presented at the 2022 American Association for Cancer Research annual meeting that included a new data cut as of December 1, 2021.

Patients with metastatic melanoma on IO102-IO103 had a three-year survival probability of 73.3% in combination with nivolumab and a median progression-free survival of 25.3 months. The confirmed overall response rate was 73.3% with 46.7% of patients obtaining complete responses in poor prognosis patients. In a subgroup analysis, a response rate of 94.1% was observed in PD-L1+ patients (mPFS: 30.9 months) and 61.5% in PD-L1(-) patients (mPFS: 7.2 months). 

Overall, the clinical activity demonstrated in the MM1636 trial with the combination of IO102-IO103 with nivolumab compared favorably with that seen historically with nivolumab monotherapy. Immune-related adverse events were also comparable to those in patients receiving nivolumab monotherapy.  Local injection site reactions were the most common adverse event.

We believe that IO102-IO103 in combination with a PD-1 inhibitor could be an effective treatment for patients with metastatic melanoma and we look forward to advancing it through the clinic for patients in need.

Smriti:  How do you anticipate this treatment will benefit patients with a poor prognosis of metastatic melanoma?

Mai-Britt: Patients with unfavorable prognostic baseline characteristics at inclusion such as a high lactate dehydrogenase (LDH) level in the blood as well as classified as M1c (distant metastasis to non–central nervous system visceral sites) also achieved impressive and durable response rates without additional toxicity after treatment with IO102-IO103 plus nivolumab. A response rate of 81.8% (mPFS: 30.9 months) was seen in patients with elevated baseline LDH levels and the response rate was 88.2%, (mPFS: 25.6 months) in patients classified as M1c at baseline.

We are encouraged by the clinical data to date and believe they support the potential for IO102-IO103 as a promising treatment for patients living with advanced melanoma who have poor prognosis. 

Smriti:  Are there any other indications for which the company is evaluating IO102-IO103 apart from metastatic melanoma?

Mai-Britt: IO Biotech is enrolling patients into a Phase 3 global trial in combination with pembrolizumab (anti-PD-1) as first-line treatment in advanced melanoma as well as a Phase 2 multi-cohort basket trial as first-line treatment of metastatic solid tumors (non-small cell lung cancer, head, and neck cancer (NSCLC) and bladder cancer). The first patients have been dosed with IO102-IO103 in combination with pembrolizumab in metastatic NSCLC in the Phase 2 basket trial.

IO Biotech will also begin a Phase 2 trial evaluating IO0102-IO103 in combination with pembrolizumab as neoadjuvant and adjuvant/post-surgical treatment in patients with resectable tumors, such as melanoma and squamous cell carcinoma of the head and neck. 

Source: Canva

About the Author: 

Mai-Britt Zocca is the President and CEO at IO Biotech. She has more than 20 years of experience in industry and oncology drug development. Dr. Zocca is also a life sciences entrepreneur, with experience in corporate strategy, financing, and management. Dr. Zocca received her M.Sc in Biochemistry as well as a Ph.D. in Medicine (Immuno-Oncology) from the University of Copenhagen and NIH, NCI, MD, US

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