Process development and manufacturing
Raw material
The drug substance in LIB-01 was originally identified in the roots of the Neobeguea Mahafalensis tree found in Madagascar. Dicot has purified the molecules that are said to increase sexual ability. When the active molecules were finally identified, it was noted that they had not previously been documented, whereupon Dicot's founder Jarl Wikberg named the molecular group Libiguins.
The roots cannot be used for large-scale production as they contain too low levels of Libiguin and cannot be harvested in a sustainable way. Dicot has therefore identified similar molecules, so-called phragmalins, that can be extracted from seeds from other species of trees. The phragmalins themselves do not have the desired pharmacological effect, but when Dicot further synthesized them in a number of steps, they have taken the form of the Libiguin molecule.
The trees grow in the wild in a number of sub-Saharan African countries and the seeds are not used to any appreciable extent by the local population, thus Dicot is not competing for the source of the raw material. Seeds can be harvested in a sustainable way and contribute to the benefit of the countries and villages during the development stage as well as in the subsequent commercialization of the drug, for example by creating seasonal work for the local population.
The activities related to seed collection are coordinated by Dicot's partner Parceval in South Africa, https://parceval.co.za/.
In the production of the raw material, Dicot follows the "Nagoya protocol on Access and Benefit Sharing", https://www.cbd.int/abs/. The Nagoya Protocol regulates how the genetic resource is obtained, how it is used in research and product development and how benefits from this use are shared
Manufacturing
After the Libiguin molecules were identified, a lot of time and resources have been spent on developing and scaling up the production of the drug substance LIB-01. Extraction processes have been optimized and analytical methods have been developed. Process development has taken place for the different synthesis steps that converted phragmalins to Libiguins in order to improve the final yield.
It is important to scale up the manufacturing process to obtain sufficient drug substance for the planned pre-clinical trials. Therefore, great effort has been made on this upscaling. Initially, the production outcome was measured in grams. Now Dicot has devised a process with an output just over 1 kg of the drug substance per batch.
Formulation development
Formulation determines in which way a drug can be administered to the body. Ingestion of medicine in the form of tablets is the most common.
Dicot uses an oral formulation in the ongoing clinical development program. Before the start of a phase 2b trial, Dicot intends to develop the current oral formulation into a tablet. The starting point will be to use the already developed formulation and adapt it further for tablet production. The tablet's properties and manufacturability will be in focus.
Dicot uses international and established contract manufacturers in the manufacture of LIB-01, with Anthem Biosciences in India manufacturing the drug substance. GMP manufacturing of the oral formulation is done by Thermo Fischer Scientific in the USA.