Startups 2025
Emerging Startup
Citrapeutics
Innovation & Business Idea
ACOD1 recently emerged as an important resistance factor of a variety of tumors against treatment with immune checkpoint inhibitors (ICI) and thus constitutes a novel drug target for cancer immunotherapy. We have identified citraconic acid (CA) as the worldwide first inhibitor of ACOD1 and subsequently developed modified molecules (early leads) with improved potency and improved pharmacological properties. We now aim to conduct further lead optimization work and all necessary preclinical studies that will enable an IND submission. Ultimately, Citrapeutics will develop
clinically approved medications that treat “ACOD1-high” cancer indications by boosting immune responses against tumor cells and inhibiting
proliferation of cancer cells. Why?
ACOD1 synthesizes the small molecule itaconate in an activated immune system and many tumor cells. Itaconate suppresses function of nearby immune effector cells, notably CD8+ cytotoxic T lymphocytes. Hereby, it causes a state of immune paralysis in tumor tissue, which counteracts the efficacy of cancer treatment with ICI. In addition, ACOD1/itaconate enhance growth and spread of diverse tumor types by providing a source of nutrients and reactive oxygen species. ICI cancer treatment faces three major problems. (i) Approximately 40% of all cancer patients are deemed eligible for ICI treatment, but less than 30% of patients treated with ICIs experience a clinical benefit. (ii) Due to the nature of existing ICIs, the frequency of adverse effects (often related to hyperinflammatory or autoimmune processes) is high and they are the most common reason for discontinuing ICI therapy. (iii) ICIs are antibodies that are expensive to produce and need to be administered intravenously. ACOD1 inhibitors might circumvent these problems in 3 ways. (i) By removing an additional inhibitory signal (itaconate) from the tumor microenvironment, they would act to enhance anti-tumor immunity by a different mechanism. (ii) ACOD1/itaconate can act as direct growth factor(s) for certain tumors and as a proangiogenic factor. (iii) Our CA analogs are orally bioavailable small molecules that are easy to synthesize; they are easily taken up by human and murine cells, and in vivo PK studies in mice have shown that they are easily absorbed after oral administration.
Contact
Prof. Dr. Dr. med. Frank Pessler
Frank.pessler@helmholtz-hzi.de
