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AXENIS Humanized Mice – Innovation towards industrial scale-up

Periodic Reporting for period 1 - HUMICE (AXENIS Humanized Mice – Innovation towards industrial scale-up)

Okres sprawozdawczy: 2015-05-01 do 2015-10-31

AXENIS HUMICE - Humanized mice as innovative tools for transversal biomedical research & preclinical validation.

Biomedical research faces a variety of ‘Grand Challenges’ in vaccine development & infectious diseases, control of chronic diseases with inflammation-related pathology, and definition of innovative cancer treatment strategies. Among these challenges, validation of new therapeutic approaches increasingly depends on access to relevant experimental models to screen human-dedicated, clinical products in a preclinical, in vivo setting. In the era of personalized molecular medicine, rodent models that do not properly reflect human cell physiology or do not efficiently translate into advances for human health are still used too often in biomedical research, therefore limiting the capacity to generate new and efficient therapeutic advances.

As a spin-off of the renowned Institut Pasteur (Paris, France), AXENIS is an innovative company exploiting cutting-edge humanized, immuno-deficient mouse models for research and development (R&D) preclinical studies. AXENIS goal is to become the ‘first-to-market’ with its forefront innovative tools that represent a major technological breakthrough in the huge market of vaccine and drug discovery/development. AXENIS mission is to develop and offer to the biopharmaceutical community rigorous, reproducible and standardized animal models that give access to prospective ‘read-out’ of human immune functions.

The unique AXENIS chimeric mouse models harboring components of the human immune system (a.k.a. ‘Human Immune System’ [HIS] mice) are intended to overcome the well-documented limitations of species barriers for bio-therapeutics testing in existing animal models – including standard rodent models and non-human primates.

AXENIS HIS mice dramatically broaden the scope of pre-clinical testing of human immune cell behavior, with numerous potential applications in fields such as immunology, infectious diseases, stem cell biology, inflammation or immuno-oncology – affecting ≥10 million new patients per year worldwide and a preclinical testing market of ~2500M€ in 2012. Overall, HIS mice represent a crucial tool for this large, transversal market.

A mature technology & a right timing for market penetration
The HIS mouse models marketed by AXENIS are backed up by approximately 30 years of research with key technologies protected by patents granted to the Institut Pasteur (owners). AXENIS has secured exclusive, worldwide licenses for these patents and ‘know-how’ until 2022. HIS mouse models require highly specific expertise in their handling and in results interpretation. They are the main focus of AXENIS internal R&D efforts. AXENIS aims at being the principal actor in this area within the next 5 years and at staying at the forefront of this rapidly evolving field in biology by constantly developing its products, its market penetration, and collaborative strategies.

Over the past 5 years, AXENIS has developed its commercial activity in two directions, namely:
(i) Direct sales of HIS mice to international customers, e.g. large biopharmaceutical companies, contract research organizations (CRO), biotech small & medium enterprises (SME) and academic institutions;
(ii) Hosting of R&D projects outsourced by customers (CRO activity);

As a result, AXENIS currently valorizes several proof-of-concept results that clearly demonstrate the added value of HIS mice over the existing models, as a family of predictive models for the screening of therapeutic molecules and identification of human biomarkers. This major achievement is the outcome of collaborative joined forces with academic partners (research collaborations; academic technology transfer; public incentives and consortia) and private customers (~10 different biotech companies and one CRO). Technology-wise, AXENIS has also validated its products & services development strategy.

Action plan
Facing increasing worldwide market demands for accessing its products (HIS mice) & services (CRO), AXENIS aims at scaling up its production capacity while maintaining its quality standards. Over the next 3 years, the major goal of AXENIS is therefore to enhance both direct sales and CRO operations, in terms of production facilities, commercial organization and company structuration into respectively dedicated business units (BU). To achieve these objectives, the overall company project focuses on building a ‘first-in-class’ humanized mouse factory for increased distribution capacity and the support of its CRO/R&D activity. Humanized mice produced in this ‘humanization’ BU will offer all compliance features (reliability, reproducibility, quality, ethics) required for biomedical R&D.

To value this scale-up strategy, AXENIS aims at setting-up a ‘beta-testing’ program with big players in the aforementioned application fields (a biopharmaceutical company – e.g. Sanofi – and a large CRO – e.g. EVOTEC), and therefore anticipate market evolutions that will determine internal and external R&D efforts. Market dissemination of such innovative in vivo models is expected to take some time (3 years). The European Union (EU) support to AXENIS development plan is therefore of utmost importance at this initial stage to guaranty its positioning visibility, success at the international level and in attracting additional private investors.

The investments required for the development of the next generation of HIS mouse models and up scaling of AXENIS’ operations have been estimated at ~5.1M€ over the 2016-2018 time frame (including ~3.5M€ eligible costs in the context of the H2020-SME call). The development strategy of AXENIS takes into account the logistic and regulation compliance related to animal experimentation and shipment of living animals. The company aims at consolidating its position on the European market (2015-2017) before establishing joint ventures in North America (NA) and Asia (2018+) to facilitate the distribution channels and operations.

HIS mouse models as unique research tools represent a small but essential ‘missing link’ in the drug discovery/development and preclinical processes. This positions AXENIS as an excellent European company candidate to receive the support of EU and attract new investors.
Between May 1st and October 29th 2015, the AXENIS team mobilised resources in order to draft a detailed Business Plan allowing to describe the positioning and strategy of the company to seize new opportunities. This concrete deliverable is a strong first achievement since it crystallizes many ideas that have been developed to make Axenis' ambition a reality within the next 5 years.

While the company identified some major opportunities in the field of humanized, immuno-deficient mouse models, the management needed (1) further reflection on the best strategy forward, (2) to better definition of a clear action plan and (3) more business contacts to make the plans more realistic.

The following work has been performed:
1- Drafting of a detailed Business Plan comprising six sections.
2- Establishing or pursuing business contacts with suppliers (facility) and prospects (CROs).
3- Identifying resources to assist the company in carrying out deployment and Business Development activities.

I- Business Plan structure and content.

The Business Plan is a realistic description of Axenis innovation plan, summarised in a 50-pages document.

The following elements have been designed, discussed, challenged, defined / decided and finally described in the business plan:
1 Executive summary
2 Business model
3 Products and services
4 Research, development and innovation
5 Marketing and sales strategies
6 Organization and management
7 Financial and funding requirements

The Business Plan has been prepared with the assistance of several business experts, specialised in start-up development, business development and collaborative approaches.

II- Development of Business contacts to prepare the scaling-up phase

During the reporting period, Axenis' management has intensified the development of contacts in order to secure and prepare the scaling-up phase.


Several meetings have been organised in Toulouse and Paris with EVOTEC in order to discuss the conditions for hosting Axenis animal facility in optimal conditions and to ensure EVOTEC could accompany the growth of AXENIS in case of success of its implementation plan.

The implementation of the BU #1 is a pre-requisite to upscale the HIS mouse production capacity of AXENIS and provide HIS mouse models ‘on the shelf’ to significantly reduce the delays between customer demands and actual product/service delivery (few weeks, as compared to current 4-6 months delay on average). AXENIS has already set-up a BRGS mouse colony on the premises of EVOTEC (Toulouse, France) and will set-up and equip a humanization facility on site. Importantly, all the selected sites for AXENIS activities are secured areas, with restricted access to laboratories and animal facilities.

II.2 - Prospects and customers

AXENIS has collected data from Charles River Laboratory and has tested its business model by meeting several prospects during the reporting period.

These meetings allowed to fine-tune the pricing list and development models of the company.

III- Identification of resources

In the 6-months of the project, AXENIS has developed a complete organigram and has identified the required functions and profiles of people needed to assist in the scaling-up phase.

This planning and mapping, together with the selection of a recruitment company will allow AXENIS to be operational as soon as the first funding for scaling-up will be available.
Overall, the commercial perspectives at the horizon 2020 are as follows:
- Expected annual revenues (EU market, excluding joint ventures): 5.6M€.
- Expected annual profit (operating income): 0.84M€.
- Expected market shares: 65% of the EU market (HIS mouse direct sales).
- Expected establishment in markets of North America (which represents ~60% of the worldwide market) and Asia, via 2 local joint ventures (JV).
- Total direct full-time equivalent (FTE) job creations (employees): 19.

AXENIS’ scale-up time-lines correspond to a 3-year investment plan, ventilated as follows:
• 2 years for a pilot (‘demonstrator’) of the humanization factory (scale-up to the level of 100 HIS mice produced per month). The onset of the pilot demonstrator will take place during Q1 2016.
• 3 years (overlapping) for R&D and ‘beta-testing’ (to complete the production line).
• 2 years (overlapping) for transferring & developing a ‘humanization factory’ in a US joint venture and a Chinese joint venture – once the EU ‘humanization factory’ becomes fully operational. The joint ventures activities will take advantage of the process developed on the EU pilot ‘humanization factory’ and comply with the local regulations.

After the scale-up phase (2016-2017), the gross margin represents around 50% – taking into account the lease of EVOTEC animal facilities (⅓ of the costs) and the supply of human CD34+ cells (⅓ of the costs). AXENIS plans to implement costs and production process management that would allow maintaining this ratio even if the competition forces to lower the prices.
Axenis New Business Model