Periodic Reporting for period 1 - chemGLIO (Chemical synthesis of a new drug family to treat glioblastoma multiforme (GBM), the highest global unmet need in oncology)
Okres sprawozdawczy: 2020-11-01 do 2021-10-31
Summary
Hemispherian expects to gain highly specialised expertise through the IA, which will transform our internal CMC capabilities. Through the one-year project chemGLIO, the innovation associate will directly contribute to the development of our innovative chemical synthesis method, and in the long-term bringing our game-changing drug to the market. Not only will the IA bring much needed expertise, but she will also become an integral part of the team at HEMI, through mutually beneficial training. We expect the innovation associate to bring strong expertise in organic chemistry and CMC methods and will supplement this, for example, by providing training in specific oligonucleotide synthesis and regulatory affairs related areas to create an indispensable team member.
Objectives:
1) The optimal chemical synthesis process is utilised for our lead drug GLIX1, ensuring scalability, cost- effectiveness, and ultimately increasing our profit margin for selling the drug (or attractiveness for buy-out).
2) A cost-effective chemical synthesis process for oligonucleotides has the potential to radically change the way these currently high-cost compounds are made.
3) In-house expertise in CMC and regulatory affairs, ensuring less third-party dependence that could delay development of GLIX1 and/or increase costs.
Hemispherian expects to gain highly specialised expertise through the IA, which will transform our internal CMC capabilities. Through the one-year project chemGLIO, the innovation associate will directly contribute to the development of our innovative chemical synthesis method, and in the long-term bringing our game-changing drug to the market. Not only will the IA bring much needed expertise, but she will also become an integral part of the team at HEMI, through mutually beneficial training. We expect the innovation associate to bring strong expertise in organic chemistry and CMC methods and will supplement this, for example, by providing training in specific oligonucleotide synthesis and regulatory affairs related areas to create an indispensable team member.
Objectives:
1) The optimal chemical synthesis process is utilised for our lead drug GLIX1, ensuring scalability, cost- effectiveness, and ultimately increasing our profit margin for selling the drug (or attractiveness for buy-out).
2) A cost-effective chemical synthesis process for oligonucleotides has the potential to radically change the way these currently high-cost compounds are made.
3) In-house expertise in CMC and regulatory affairs, ensuring less third-party dependence that could delay development of GLIX1 and/or increase costs.
Main work activities at the beginning of the employment included organizing and adapting existing laboratory space into a functional lab where organic synthesis can be performed. Laboratory space and some equipment was available initially, but majority had to be purchased or assembled. IA participated in planning of installment of laboratory bench and drawers dedicated for storage space together with ShareLab personnel and construction workers. In addition, some adaptations were required for the water supply in the laboratory and IA participated in planning of these. After this work had been done, other laboratory equipment, such as glassware, heating blocks and condensers was purchased.
While laboratory was not available for the experimental work, IA conducted a literature search on the Hemispherian’s compounds of interest, investigating possible routes for optimization of the synthesis of lead compounds, the status of intellectual property related to lead compounds, new potential structures of interest and synthetic routes for their preparation. Reports were made upon completion of tasks.
When the laboratory became available for conducting experiments, IA investigated reported synthetic routes for the preparation of the lead compounds, and experimented upon optimizing the existing methods, which resulted in comprehensive report. In addition, IA performed an extensive analytical work on the lead compounds, which yielded in several new HPLC methods suitable for characterizing several compounds from the series. IA also continued work started in Hemispherian team in studying the properties of the lead compounds, such as stability in different conditions. Further experimental work yielded in preparation and characterization of the two new compounds which will be studied for their biological effects on different tumor cell lines, by Hemispherian team. In addition, IA prepared a larger amount of one of the lead compounds, GLIX5, which will be used in preclinical studies.
Finally, IA participated in interviews and selection of the supplier for the preparation of kilogram scale of one of the lead compounds, GLIX1. After supplier was selected and confirmed, IA served as a technical lead, providing initial experimental package and literature reports. After the initiation of the project, IA was following weekly reports from the supplier team and participated in discussion of experimental issues.
While laboratory was not available for the experimental work, IA conducted a literature search on the Hemispherian’s compounds of interest, investigating possible routes for optimization of the synthesis of lead compounds, the status of intellectual property related to lead compounds, new potential structures of interest and synthetic routes for their preparation. Reports were made upon completion of tasks.
When the laboratory became available for conducting experiments, IA investigated reported synthetic routes for the preparation of the lead compounds, and experimented upon optimizing the existing methods, which resulted in comprehensive report. In addition, IA performed an extensive analytical work on the lead compounds, which yielded in several new HPLC methods suitable for characterizing several compounds from the series. IA also continued work started in Hemispherian team in studying the properties of the lead compounds, such as stability in different conditions. Further experimental work yielded in preparation and characterization of the two new compounds which will be studied for their biological effects on different tumor cell lines, by Hemispherian team. In addition, IA prepared a larger amount of one of the lead compounds, GLIX5, which will be used in preclinical studies.
Finally, IA participated in interviews and selection of the supplier for the preparation of kilogram scale of one of the lead compounds, GLIX1. After supplier was selected and confirmed, IA served as a technical lead, providing initial experimental package and literature reports. After the initiation of the project, IA was following weekly reports from the supplier team and participated in discussion of experimental issues.
The innovation associate program has been a success for Hemispherian and for the innovation associate. The benefits to Hemispherian and accomplishments by the innovation associate include:
1) An optimized synthesis method for our lead compound.
2) A scaled up procedure for the synthesis of our lead compound.
3) CMC and regulatory affairs documentation.
4) A scaled up synthesis of Hemispherian’s lead compound.
5) Standard operating procedures for the abovementioned accomplishments.
Benefits to the innovation associate include:
1) Experience in industrial chemical synthesis procedures.
2) Extensive coursework related to industrial manufacturing and quality control procedures.
3) Experience in industrial process design and scale up.
1) An optimized synthesis method for our lead compound.
2) A scaled up procedure for the synthesis of our lead compound.
3) CMC and regulatory affairs documentation.
4) A scaled up synthesis of Hemispherian’s lead compound.
5) Standard operating procedures for the abovementioned accomplishments.
Benefits to the innovation associate include:
1) Experience in industrial chemical synthesis procedures.
2) Extensive coursework related to industrial manufacturing and quality control procedures.
3) Experience in industrial process design and scale up.