89Zr/225Ac-labeled antibody radioconjugates as theranostic against EGFR-positive colorectal cancer – a clinical trial enabling study  

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Project of $3,604,528 over 3years

• Supported by CQDM through:
  Ministère de l’Économie, de l’Innovation et de l’Énergie du Québec (MEIE)
• And by co-funding partners:
  – ACT225 BioTherapeutics Corporation
  – Fonds de Recherche Québec (Oncopole)

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Challenge:

Epidermal growth factor receptor I (EGFR) is a protein overexpressed in many aggressive cancers particularly in 80 – 85% of colorectal cancer (CRC). Metastatic CRC (mCRC) has one of the worst overall survivals (5-year survival of <10% for stage IV) of any cancer. With nearly 2 million new CRC diagnoses annually and more than 600,000 deaths, it is important to develop more effective treatments urgently. The standard of care which includes the addition of anti-EGFR monoclonal antibody to chemotherapy has a complete response (cure) rate of just 0.5% of patients. The market launch of a more efficient anti-EGFR theranostic agent is essential and will represent an unprecedented market opportunity worth over 21 billion dollars. 

Solution:

Utilization of [²²⁵Ac]Ac-ACT-Tx01, a powerful and specific EGFR antibody containing numerous cytotoxic agents would be one of the solutions envisaged. Preclinical studies demonstrated that [²²⁵Ac]Ac-ACT-Tx01 considerably improves the survival of mice bearing CRC tumors, including complete cures, and is safe. [⁸⁹Zr]Zr-ACT-Dx01, a PET/CT agent was also developed as a diagnostic tool to permit the precise selection of patients that will respond to treatment using [²²⁵Ac]Ac-ACT-Tx01. For this project, [²²⁵Ac]Ac-ACT-Tx01 and [⁸⁹Zr]Zr-ACT-Dx01 drugs will be developed and following approval will be tested a in phase 1 clinical trial.

Expected Achievements/Impact:

If finally approved, this theranostic agent will lead to drastic improvements in the care of CRC patients, with 7,300 new diagnoses each year in Quebec. ACT225 BioTherapeutique Corporation will be the principal actor for the development and commercialization of this drug in Quebec and will undoubtedly attract new investors. This thriving business will attract and train highly qualified personnel in the field of translational radiopharmaceutical sciences, essential to the leadership of Quebec and Canada in the life science domain.