Periodic Reporting for period 1 - GUTOCINS (Oral oxytocin for abdominal pain)
Reporting period: 2023-06-01 to 2024-11-30
Chronic abdominal pain is a widespread debilitating condition commonly associated with gastrointestinal disorders such as irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD). IBS and IBD affect more than 10% of the global population, leaving a severe and steadily growing socio-economic burden on society (€115 billion/year in Europe in direct and indirect health care costs). Adequate pain management for these conditions is imperative but remains challenging since classical analgesics are poorly effective, associated with adverse effects, and can even exacerbate disease progression.
In this project, we aimed to develop a new class of oral and non-opioid-based peptide analgesics to target chronic abdominal pain at its origin in the gut. This innovative treatment approach is expected to offer a new way to alleviate chronic abdominal pain with a large safety window due to its gut-specific/restricted action and negligible risks of systemic off-target effects. The project furthermore breaks new ground in developing oral peptide therapies, a long-standing challenge in the peptide drug industry (95% of peptide drugs need to be injected).
The project comprised the following work packages (WPs):
WP1: Drug lead and probe development
WP2: Drug lead evaluation in preclinical mouse models of chronic abdominal pain
WP3: Strategic partnerships, IP management, and business development plan
Through these multidisciplinary work packages, we aimed to advance a new drug class, demonstrate proof-of-concept, and establish a strong foundation for further (pre)clinical development of new gut-specific peptide therapeutics to address the unmet medical needs of patients suffering from gastrointestinal disorders.
In this project, we aimed to develop a new class of oral and non-opioid-based peptide analgesics to target chronic abdominal pain at its origin in the gut. This innovative treatment approach is expected to offer a new way to alleviate chronic abdominal pain with a large safety window due to its gut-specific/restricted action and negligible risks of systemic off-target effects. The project furthermore breaks new ground in developing oral peptide therapies, a long-standing challenge in the peptide drug industry (95% of peptide drugs need to be injected).
The project comprised the following work packages (WPs):
WP1: Drug lead and probe development
WP2: Drug lead evaluation in preclinical mouse models of chronic abdominal pain
WP3: Strategic partnerships, IP management, and business development plan
Through these multidisciplinary work packages, we aimed to advance a new drug class, demonstrate proof-of-concept, and establish a strong foundation for further (pre)clinical development of new gut-specific peptide therapeutics to address the unmet medical needs of patients suffering from gastrointestinal disorders.
Drug Lead and Probe Development (WP1):
- Designed, synthesised and optimised oxytocin (OT) analogues with superior stability, potency, and selectivity, achieving a gastrointestinal half-life exceeding 24 hours.
- Confirmed potency and selectivity toward the oxytocin receptor (OTR) versus vasopressin receptors through extensive pharmacological evaluation.
- Developed OTR-specific probes for target engagement studies, supporting fundamental research and in vitro, ex vivo and in vivo applications.
- Scaled up the most promising drug leads for in vivo and toxicity studies. No toxicity was observed.
Drug Lead Evaluation in Preclinical Mouse Models (WP2):
- Demonstrated significant reductions in visceral hypersensitivity in preclinical chronic abdominal pain mouse models following both rectal and oral administration.
- Optimised administration and analysis protocols, providing robust proof-of-concept data.
- Observed no adverse effects even at higher dosing levels, supporting a large therapeutic window.
- Published these results in Angewandte Chemie International Edition, one of the leading multidisciplinary chemistry journals (Impact Factor: 16.6 Top 5% category).
- Achieved global recognition through several awards, interviews, news articles, and social media engagement, reaching a broad audience of millions (Altmetric Score: 180, Top 5%).
Strategic Partnerships, IP Management, and Business Development (WP3):
- Secured the approval of a strong composition-of-matter patent to protect the novel drug leads and their therapeutic use.
- Conducted market research that validated the strong commercial potential of the innovation.
- Developed a business plan and confidential and non-confidential pitch decks.
- Established several new collaborations in peptide drug development and the abdominal pain field.
- Submitted applications for further funding and presented the project at pharmaceutical and biotech companies and international conferences.
- Designed, synthesised and optimised oxytocin (OT) analogues with superior stability, potency, and selectivity, achieving a gastrointestinal half-life exceeding 24 hours.
- Confirmed potency and selectivity toward the oxytocin receptor (OTR) versus vasopressin receptors through extensive pharmacological evaluation.
- Developed OTR-specific probes for target engagement studies, supporting fundamental research and in vitro, ex vivo and in vivo applications.
- Scaled up the most promising drug leads for in vivo and toxicity studies. No toxicity was observed.
Drug Lead Evaluation in Preclinical Mouse Models (WP2):
- Demonstrated significant reductions in visceral hypersensitivity in preclinical chronic abdominal pain mouse models following both rectal and oral administration.
- Optimised administration and analysis protocols, providing robust proof-of-concept data.
- Observed no adverse effects even at higher dosing levels, supporting a large therapeutic window.
- Published these results in Angewandte Chemie International Edition, one of the leading multidisciplinary chemistry journals (Impact Factor: 16.6 Top 5% category).
- Achieved global recognition through several awards, interviews, news articles, and social media engagement, reaching a broad audience of millions (Altmetric Score: 180, Top 5%).
Strategic Partnerships, IP Management, and Business Development (WP3):
- Secured the approval of a strong composition-of-matter patent to protect the novel drug leads and their therapeutic use.
- Conducted market research that validated the strong commercial potential of the innovation.
- Developed a business plan and confidential and non-confidential pitch decks.
- Established several new collaborations in peptide drug development and the abdominal pain field.
- Submitted applications for further funding and presented the project at pharmaceutical and biotech companies and international conferences.
First gut-stable oxytocin analogues:
Developed the first fully gut-stable oxytocin analogues with a gastrointestinal half-life exceeding 24 hours, compared to less than 10 minutes for native oxytocin.
Oral bioactivity demonstrated:
Successfully demonstrated that the compounds retained analgesic effects when administered orally, representing a major breakthrough for the development of oral peptide therapeutics and gut-specific analgesics.
Novel therapeutic strategy:
Provided a non-opioid, gut-specific treatment approach for chronic abdominal pain, reducing the risk of systemic side effects.
Commercialisation potential:
Strengthened IP position through comprehensive patent approval and validated market demand through stakeholder engagements. Applied for further funding opportunities and initiated advanced discussions with industry partners for licensing and further development.
By addressing key challenges in peptide drug stability and delivery, the project has created a foundation for innovative treatments in gastrointestinal health. The outcomes have the potential to revolutionise the treatment of chronic abdominal pain, providing relief to millions of patients worldwide.
Developed the first fully gut-stable oxytocin analogues with a gastrointestinal half-life exceeding 24 hours, compared to less than 10 minutes for native oxytocin.
Oral bioactivity demonstrated:
Successfully demonstrated that the compounds retained analgesic effects when administered orally, representing a major breakthrough for the development of oral peptide therapeutics and gut-specific analgesics.
Novel therapeutic strategy:
Provided a non-opioid, gut-specific treatment approach for chronic abdominal pain, reducing the risk of systemic side effects.
Commercialisation potential:
Strengthened IP position through comprehensive patent approval and validated market demand through stakeholder engagements. Applied for further funding opportunities and initiated advanced discussions with industry partners for licensing and further development.
By addressing key challenges in peptide drug stability and delivery, the project has created a foundation for innovative treatments in gastrointestinal health. The outcomes have the potential to revolutionise the treatment of chronic abdominal pain, providing relief to millions of patients worldwide.