The European Medicines Agency (EMA) and the Spanish Medicines and Medical Devices Agency (AEMPS) confirmed that REMAB’ strategy was very relevant and a potential solution to combat antimicrobial resistance and prompted us to advance with this development. SME1 allowed REMAB to define and compile the strategic regulatory roadmap in a final document submitted to the AEMPS in the modality of scientific advice. The AEMPS validated the following critical aspects of RA-01 preclinical and clinical development:
1- the submitted quality strategy for RA-01 was deemed as acceptable by the AEMPS
2- the AEMPS the starting materials presented by REMAN as acceptable key starting materials in the synthesis of RA-01.
3- the AEMPS agreed on the use of Cynomolgus monkey as a single species. REMAB also optimized the preclinical program to integrate as much as possible the safety pharmacology package within the 4-week toxicity study followed by a recovery period.
4- The AEMPS agreed with REMAB’ approach as long as existing information can justify not performing during the preclinical program the photosafety testing, in vitro metabolism and in vitro hERG channel assay.
5- The AEMPS agreed that main components of RA-01 will not need genotoxicity assessment for human administration.
During SME1, the regulatory large-scale synthesis of RA-01 was reviewed and technically validated by different Contract Manufacturing Organization (CMO). REMAB already carried out the large-scale production of initial small-medium batches of starting materials and the final API for preclinical development. REMAB has evaluated these lots with very good results in terms of efficacy and reproducibility batch to batch. The quality plan for RA-01 and the starting materials was already defined and the CMOs are working on analytical methods validation, and the initial stability programs. We also defined the possible options for drug product presentation, the consumption of vials in the release and sample analysis of each batch and the stability program, the number of vials planned for clinical administration, and the consumption of RA-01 for the entire development plan until Phase 2 clinical trials. Based on this analysis REMAB is starting the pre-formulation studies, formulation development, containers and ICH stability studies. Part of these activities are ongoing with initial RA-01 batches produced by the corresponding CMO and will be last to Q1/2020 with the production of the clinical lot.
Finally, REMAB performed two market studies, one quantitative to determine the market size and impact in countries/regions as well a qualitative study with round of interviews, where we have confirmed the willingness to pay from the main actors in the supply chain.
Europe is estimated to have 69.331 ICU beds. If we use an average stay, in the low range, of 5, this represents 5.061.163 ICU admissions yearly only in Europe. With the collected data on admission, average stay, and infections rate in ICU by country we can conclude that: the use of RA-01, would represent a SAVING for the European national healthcare systems above 1.600 Million Euros yearly, and worldwide above 5.000 Million. Without mentioning the improve in the healthcare of patients as well as the increase in efficiencies like more beds available due to the reduction of length of stay, medical staff burden due healthcare complication in patients and so on.
As part of the Feasibility Study we have also carried out an in-depth Qualitative Market Research. In summary, the survey supported by the SME1 allowed us to see there is a clear market fit for the company for the following reasons:
1. REMAB focuses on a real problem, 100% of the interviewed were aware of the growing problem and the cost it generates. Since RA-01 is a novel solution expected to reach market we see a general acceptance regarding price and possibility to be implemented.
2. REMAB helps to solve the problem
3. REMAB offers a flexible and affordable solution against the expensive, and limited market solutions.
4. REMAB has a marketplace in terms of pricing, and the public sector seems to be willing to pay for its products, although some education might be needed.
REMAB confirmed business model, which is still the standard one for a biotech early-stage company. It is based on the licensing-out of the current and future IP to a big pharma. Due the high cost of phase-3 clinical trials, and the commercial capabilities of pharmas, the obvious business model for RA-01 is licensing-out.
