Periodic Reporting for period 1 - CB24 (Development of a natural therapeutic treatment for late-stage lung cancer patients)
Okres sprawozdawczy: 2023-10-01 do 2024-09-30
Non-small cell lung cancer (NSCLC) destroys lives worldwide, with traditional treatments targeting life extension and overall survival measured in months. Surgery, chemotherapy, radiotherapy and even newer gene & immune-therapies present challenges in terms of side effects and patient response, especially for those in advanced stages. With this in mind, Celtic Biotech Ireland developed CB-24, a naturally derived receptor binding protein from rattlesnake venom that targets nicotine receptors on cancer cells. Nicotine and nicotine derivatives are known to promote the spread of cancer cells. The drug is delivered as a user friendly at-home monotherapy using infusion pumps, In small scale Phase I safety trials, it has revealed unprecedented efficacy, safety and minimal side effects, challenging the status quo of NSCLC treatment. The EIC-funded CB-24 project aims to establish increased bulk CB-24 manufacturing capacity, undertake clinical drug manufacturing and complete our innovative Phase Ic clinical trial to advance further towards regulatory approval of this game-changing cancer therapeutic.
With the release of EIC funds the company initiated the first phase of its operation to establish manufacturing capabilities in the EU and prepare for the commencement of our Phase 1c clinical trial in France.
1. The initial priority was to secure the supply of rattlesnake venom and create a breeding colony that would provided the raw material needed to support early commercialization activities. The company completed the purchase of additional South American rattlesnakes and doubled the side of its snake colony to 100 animals: sufficient to launch a breeding program to provide enough material for Phase II clinical trials and early commercialisation plans.
2. Celtic Biotech contracted with the UK company, Immunoclin Ltd - formerly our contract clinical organisation, to manufacture the bulk drug active. Celtic Biotech transferred its standard operating procedures (SOPs) and helped support the implementation of good manufacturing processes (GMP) system. Immunoclin was able to successfully complete a drug manufacturing test run including formulation of the final drug product to meet the required clinical standards. Having completed this process Immunoclin has submitted an application to the UK Medicines Health and Controls Agency (MHRA) for the required manufacturing permit to produce the bulk CB-24 active: the review of the permit is now pending.
3. To complete the manufacturing logistics, Celtic Biotech was able to identify a UK MHRA licensed and certified GMP sterile contract manufacturing organisation to complete the production of its sterile intravenous drug. The site will complete its GMP audit in November and scheduling of the clinical drug manufacturing can then be undertaken.
4. In parallel to these activities, our Clinical Director, in liaison with our Medical Director and clinical investigators was able to finalise the clinical trial Phase 1c protocol. The clinical protocol was successfully submitted for ethics board approval and, subsequently approved by the French regulators. Celtic Biotech chose to move to using electronic case report forms (eCRFs) over the laborious and difficult to manipulate manual forms. The forms have been designed and programming started in October. Additional clinical sites have been identified to assist in accelerating recruitment to the trial, which is due to start in Jan 2025.
5. Efforts to create a snake-free source of CB-24 has been initiated by our Director of R&D: this process is in its early stages and ahead of schedule. Genes for the two CB-24 subunits were designed and cloned into bacteria. Proteins were successfully expressed by these genes and now studies are underway to assess the comparability of the cloned (recombinant) products to the snake-derived wildtype drug. Celtic Biotech is also in communication with peptide synthesis organizations to determine if the subunits can be chemically assembled from amino acid building blocks.
6. Finally, the company had submitted CB-24 to the Broad Institute for testing in cancer cells in an effort to assess the feasibility of developing a bioassay that would determine a patient's likely response to treatment with CB-24. Results from this research effort are expect before December 2024
1. The initial priority was to secure the supply of rattlesnake venom and create a breeding colony that would provided the raw material needed to support early commercialization activities. The company completed the purchase of additional South American rattlesnakes and doubled the side of its snake colony to 100 animals: sufficient to launch a breeding program to provide enough material for Phase II clinical trials and early commercialisation plans.
2. Celtic Biotech contracted with the UK company, Immunoclin Ltd - formerly our contract clinical organisation, to manufacture the bulk drug active. Celtic Biotech transferred its standard operating procedures (SOPs) and helped support the implementation of good manufacturing processes (GMP) system. Immunoclin was able to successfully complete a drug manufacturing test run including formulation of the final drug product to meet the required clinical standards. Having completed this process Immunoclin has submitted an application to the UK Medicines Health and Controls Agency (MHRA) for the required manufacturing permit to produce the bulk CB-24 active: the review of the permit is now pending.
3. To complete the manufacturing logistics, Celtic Biotech was able to identify a UK MHRA licensed and certified GMP sterile contract manufacturing organisation to complete the production of its sterile intravenous drug. The site will complete its GMP audit in November and scheduling of the clinical drug manufacturing can then be undertaken.
4. In parallel to these activities, our Clinical Director, in liaison with our Medical Director and clinical investigators was able to finalise the clinical trial Phase 1c protocol. The clinical protocol was successfully submitted for ethics board approval and, subsequently approved by the French regulators. Celtic Biotech chose to move to using electronic case report forms (eCRFs) over the laborious and difficult to manipulate manual forms. The forms have been designed and programming started in October. Additional clinical sites have been identified to assist in accelerating recruitment to the trial, which is due to start in Jan 2025.
5. Efforts to create a snake-free source of CB-24 has been initiated by our Director of R&D: this process is in its early stages and ahead of schedule. Genes for the two CB-24 subunits were designed and cloned into bacteria. Proteins were successfully expressed by these genes and now studies are underway to assess the comparability of the cloned (recombinant) products to the snake-derived wildtype drug. Celtic Biotech is also in communication with peptide synthesis organizations to determine if the subunits can be chemically assembled from amino acid building blocks.
6. Finally, the company had submitted CB-24 to the Broad Institute for testing in cancer cells in an effort to assess the feasibility of developing a bioassay that would determine a patient's likely response to treatment with CB-24. Results from this research effort are expect before December 2024
1. One of the key deliverables of this project was to develop the capacity to purify enough CB-24 to treat 1000 patients annually, equivalent to 20g of CB-24 per month. Production of CB-24 at this scale has not been achieved previously and we are pleased that further optimisation of the production process is attainable allowing greater availability of the drug when commercialisation commences. A key facit of that supply is access to venom, which the company expects to increase once full colony expansion is triggered with an aim to increase the number of animals to 5,000.
2. The company engaged regulatory expects to assess the opportunity for using regulatory protections in the EU and US to protect the markets for CB-24 from competitors using the drug active. As CB-24 have not received marketing approval in either the EU or US territories, it was confirmed that it would qualify for new active substance and new biological entity.
3. The initial assessment of our recent patent application, "Stable Formulation of Crotoxin", has patentable claims. Patent attorney has determined that a secondary application could be made to allow for the pursuit of additional claims. These patents will be useful in protecting our markets where South American rattlesnakes are indigenous.
4. A review of prior clinical trial participants indicated that 2 subjects completed the initial dose escalation Phase 1c protocol without significant issue and a maximum tolerated dose was reported. It provided confidence that the revised dosing protocol (approved in Dec 2023) will likely be successful.
2. The company engaged regulatory expects to assess the opportunity for using regulatory protections in the EU and US to protect the markets for CB-24 from competitors using the drug active. As CB-24 have not received marketing approval in either the EU or US territories, it was confirmed that it would qualify for new active substance and new biological entity.
3. The initial assessment of our recent patent application, "Stable Formulation of Crotoxin", has patentable claims. Patent attorney has determined that a secondary application could be made to allow for the pursuit of additional claims. These patents will be useful in protecting our markets where South American rattlesnakes are indigenous.
4. A review of prior clinical trial participants indicated that 2 subjects completed the initial dose escalation Phase 1c protocol without significant issue and a maximum tolerated dose was reported. It provided confidence that the revised dosing protocol (approved in Dec 2023) will likely be successful.