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MAGIC (MAnufacturing of Gene delivery tools for Industrial and Clinical applications)

Periodic Reporting for period 1 - LentiFactory (MAGIC (MAnufacturing of Gene delivery tools for Industrial and Clinical applications))

Reporting period: 2017-03-01 to 2017-08-31

Founded in 2005, Vectalys is a biotech company that develops world leading gene delivery technologies for industrial and therapeutic applications. Vectalys has built a state-of-the-art proprietary lentiviral vectors (LV) production platform to provide its customers and partners with the highest quality of LV. Based on 10 years of collaborative research, the resulting LV purity is now recognized as a key success factor for cutting-edge stable cell engineering on primary and stem cells. In parallel, thanks to its deep understanding of market needs, Vectalys has developed and patented a game-changing class of RNA carriers called LentiFlash (LF), a new generation of non-integrating LV dedicated to gene-editing applications requiring a transient expression.

Based on recent results of early CAR-T cells clinical trials, mainly in the US, the market will now need an extensive scale-up capacity to produce GMP grade LV and LF. From a non-regulatory pre-clinical stage market, Vectalys has the capacity to move forward into the clinical stage market as a GMP grade value provider. For this reason, the planned steps of development plan are:
- Phase I: to assess the technical feasibility and commercial potential of GMP production through the industrial process design, a market study, the intellectual property exploration and meet regulatory compliance demands.
- Phase II: to set up a GMP pilot facility to move forward into the clinical stage market, by scaling-up the production line to a manufacturing level.

During the LentiFactory project (SME Instrument Phase I), Vectalys’ objectives were therefore to perform a techno-economic feasibility study to define the strategic plan for the next years, for bringing cost-effective products to the market, and prepare industrial scaling-up. To prepare clinical grade solution suitable, the Phase I LentiFactory project has been dividing into 2 major sections: (i) an industrial strategy development plan, (ii) and an IP & market study and analysis.

The company is now committed to producing these tools at a clinical grade in order to transform the lives of patients with severe genetic and rare diseases as well as untreated cancers.
The first part of the project was dedicated to industrial strategy development plan.
Indeed, the objective was to define all operating steps required both to industrialize the process of production and to transfer the process into GMP. The goal was to review the whole manufacturing process, including incoming, in-process and final quality controls and the facilities design, with the specifications given by the regulatory requirements of the targeted applications. By developing a compliant manufacturing offer for clinical applications, both ex vivo and in vivo whatever the customer’s sequence of interest, Vectalys positions itself to cover most of the clinical lentiviral market. Thanks to this study, Vectalys’ drivers have been set to: (i) establish the next GMP production unit for producing lentiviral vector; (ii) increase production capacity to 30 mL or 60 mL batch size with 2 suites of virus production; (iii) establish a sterile process from cell culture to filling operation through transfection and purification operation; (iv) be compliant with European Medicines Agency (EMA) and Food and Drug Administration (FDA) regulations; (v) propose a flexible and efficient production unit allowing to adapt some technologies choice depending on closed or open processes selected or virus production equipment. This all study will be helpful to describe the next step regarding LentiFactory project development, especially regarding SME Instrument phase II implementation.
During the industrial strategy development plan. Vectalys also worked on Quality Control (QC) to define which ones where necessaries for ex vivo and in vivo applications, in order to be able to dimension the cost according to the characteristics of the vectors produced to customer. On the other side, Vectalys obtained the confirmation of the HCB (“Haut Conseil des Biotechnologies” - public French organism in charge of GMO declaration) in a letter that specify that LentiFlash tool is not considered as GMO (Genetically Modified Organisms), which is a strategic and differentiating information that highlight the innovative vector and derived engineered cells.

The second part of the project was dedicated to IP & Marketing study.
Regarding IP strategy, the different studies performed since 2016 have shown that (i) Vectalys owns 5 patents that protect its innovative activities; (ii) Vectalys owns essential licences and sub-licenses for its proper functioning and activity; (iii) the IP strategy has been generated and validate by 3 different IP sub-contractors that confirm the current freedom to operate.
Concerning the two market studies, one was to define a go-to-market strategy regarding LentiFlash technology. Based on analysis of clinical study and technological advancements, Vectalys identified own therapeutic programs and listed potential licensing partners for licensing agreements, based on a gateway and value indications study.
The other market study objective was to analyse receptivity and economic potential of Vectalys’ GMP grade LV production offer, and to analyse the economic potential of LentiFlash applications based on the previous value and indication selected.
The results obtained during this study are confidentials. They will be exploited during the next step of the project, which will be subject to SME Instrument phase II call for proposals. Indeed, to pursue its project and lead as soon as possible its GMP grade production capacity to the market, Vectalys will now need:
- to invest in the factory production line
- pursue regulatory compliance to obtain GMP certificate as regard to its production process
- work on dissemination and exploitation of the results/project to ensure market penetration and validate its financial projection.

In addition to the technical content of the Phase 1 feasibility study, actions were performed to refine Vectalys’ strategy for next steps. Initial business plan presented in Phase 1 remains globally relevant, with slight adjustments and consolidations in terms of timing, production volumes and product pricing.

Regarding economic model and expected potential impact, Vectalys changed its strategy by the creation of a new entity, FlashCell. Indeed, the different studies performed by Vectalys have led to the conclusion that:
- Vectalys should be consider as a lentiviral tools manufacturing company, that is to say a manufacturing platform from R&D to GMP grades;
- The development of LentiFlash technology should be driven by another entity that should be recognized as a therapeutic unit developing tools for therapeutic applications (FlashCell).

FlashCell’s creation automatically involves changes in the exploitation of the results section. FlashCell is going to be an important lever in Vectalys’ development and a partner of choice regarding business activities. Every FlashCell’s sub-licencing and partnerships regarding R&D and clinical activities will involve Vectalys, as Vectalys is the dedicated manufacturer that will be attached to vector production, for each grade of the pre-clinical and clinical stage.
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