Implementation

This section provides a detailed vision of the future of our project after the iGEM competition. We have met several entrepreneurs, startup incubators, and experts in clinical trials to get their expertise in entrepreneurship. (Please consult our IHP page for more information on people we have met). Also based on bibliographical research, we have drawn our strategy for the next 10 years.

2023

Proof of Concept

• Unlock the full potential of CALIPSO, in collaboration with our university and partner laboratory.
• Patent deposit on CALIPSO platform.
• Start-up creation.
• Team’s capital contribution.
• Support: Partner laboratory, Toulouse Tech Transfer organization.

2025

Research & Development

• Implementation of our startup at Pierre Potier Center.
• Optimization of the CALIPSO platform, production of data for the patent, in collaboration with an IP law firm.
• Patent on the drug candidate.
• Recruitment: a technician & a business developer.
• Fundraising: 550 000€.
• Support: Eurobiomed, driving the growth of the healthcare sector in the South of France.

2026

Pre-clinical and toxicity trials in vitro

• Pre-clinical trials and toxicity assays on cells in our laboratory.
• Restarting the R&D program to explore new applications of the CALIPSO platform.
• Fundraising: 3 000 000 €.
• Support: business angels.

2028

Pre-clinical and toxicity trials in vivo

• Pre-clinical trials and toxicity assays on animals, in collaboration with Contract Research and Manufacturing Organisations (CRO & CMO).
• Fundraising: 3 000 000 €.
• Recruitment: a secretary.
• Support: business angels.

2029

Phase I clinical trials

• Phase I clinical trials in collaboration with the CRO and CMO.
• Fundraising: 26 500 000 €.
• Support: business angels & private equity fund.

2030

Phase II clinical trials

• Phase II clinical trials in collaboration with the CRO and CMO.
• Fundraising: 31 500 000 €.
• Support: business angels & private equity fund.

2032

END of the phase II clinical trials

• Selling the patent for the drug candidate to a pharmaceutical major company.
• Starting pre-clinical trials for a new drug candidate against other cancers.
• Support: funds generating from the patent sale.

Proof of concept and R&D optimization: 2023 - 2025

After 4 months of experimentation, the next immediate step for our team will be to strengthen our proof of concept. We will thoroughly test the main CALIPSO modules and assess their limits. As explained in our best measurement page, many experimental controls will have to be done to confirm the results we obtained during our internship. This should be completed within a maximum duration of one year and half working part time alongside our studies. As agreed with our university and TBI (Toulouse Biotechnology Institute) laboratory, we will utilize their facilities to conduct these experiments.

The next priority will be to file a patent on the combination of all our different modules (anchoring, biosensing and anticancer drug production) into one liposomal platform targeting tumor cells. Even if some molecules we use are already patented, the combination of these three modules is the true innovation. While exposing our results on the wiki could be incompatible with intellectual property protection, we did not work yet on the total assemblage of our project and therefore we feel free to present the main modules to receive valuable feedback on them.

For future iGEMers, we advise taking a closer look at intellectual property considerations from the very beginning of the project.

In order to carry out these researches and ensure their legal protection, we will need to secure fundings. As described in the Finances section on our entrepreneurship page, we will seek private and public funding sources such as grants and innovation competitions for the first three years of our R&D activity.

We will also create a Simplified Joint-Stock Company (Société par Actions Simplifiées SAS) as it allows us to tailor the company to our specific needs. Our startup will be created by the eight members of our current team. For more information about our company organization, please refer to our entrepreneurship page.

To support the development of our startup, we will collaborate with startup incubators. We aspire to receive support from Eurobiomed, an organization that drives the growth of the healthcare sector in the South of France [1]. It brings together a vast network comprising over 400 industrial stakeholders, including major corporations, SMEs, startups, research laboratories and universities. Joining Eurobiomed offers numerous advantages, including access to potential partners by having access to targeted networking opportunities and strategic information essential for the growth of the company. We could be assisted in promoting and adding value to our project, and aided in preparing our applications for public funding.

In addition to these considerations, we've learned from many experienced entrepreneurs the significance of undergoing training to effectively communicate with experts in fields where we may not possess expertise. For instance, Julien Durand, the co-founder of a startup in biotechnologies, highly recommended the DeepTech Founders training program as a means to acquire supplementary skills across various facets of startup creation and management.

Patent deposit on our CALIPSO platform and operating license acquisition: 2023 - 2025

Once our liposomal platform is optimized and ready for patenting, we will follow the procedures to file a patent as described in the section Intellectual Property of our entrepreneurship page. Our patent will be registered under the ownership of our institution. We will then acquire the operating rights via a license. This license includes a sub-licensing clause, which enables us to sell licenses to allow others to use our platform.

Once our platform is patented, we will have an additional 18 months to optimize it for one specific type of cancer, one set of receptors and one specific drug: it corresponds to our first drug candidate. We will collaborate with an IP law firm to help us in this process. Additionally, the modularity of our platform allows for extensions. By incorporating specific targeting, biosensing, or drug production modules tailored to different tumor cells, we can explore wider applications, even beyond cancer treatment. So we will develop and patent other drug candidates over the years.

We formulated this strategy after several meetings with Yves Dudal, the CEO of our sponsor Perseo Pharma. To learn more about our patenting strategy and in which countries we decided to protect our innovation, please visit the section Intellectual Property of Product description in our entrepreneurship page.

Establishment in the Pierre Potier Center: 2025

Once our patent for our platform is registered, we aim to establish ourselves in the Pierre Potier Center at the beginning of the 18 months period. It is conveniently located in Toulouse on the Health Campus of the Future. The Pierre Potier Center provides technological platforms and features a 5000 m² rental space designed specifically for biotechnology companies [2]. It brings together various stakeholders from clinical, academic, and industrial sectors. Notable entities such as the Toulouse-Oncopole University Cancer Institute (IUCT-O), the Cancer Research Center (CRCT), and pharmaceutical groups are all situated within this dynamic ecosystem. The campus hosts numerous events to engage with other healthcare sector stakeholders.

To gain further insights into this center, we had the privilege of meeting with Hugues de Vesins, the General Director of the various Toulouse-based incubators, and Laurence Fournier, his executive assistant. Their guidance provided valuable insights that will aid in shaping our decisions and strategy for establishing our startup at this location.

• Pre-requirements for the application:

1. Establish a legal entity with incubator support (Eurobiomed).
2. Complete a detailed application with project description, business plan, and funding details.
3. Present the project to a selective board.
4. If accepted by the committee, secure a-year lease, renewable annually, with an average stay of 10 years until an industrial factory is established.

• 3D modeling of our future laboratory:

If our application is accepted, we will have access to two labs (one with a second level security for the manipulation of cancer cell lines) and one office. To project ourselves as realistically as possible, we designed our prospective research laboratory in 3D. This required a deeper understanding of the essential components necessary for a cutting-edge R&D department and allowed us to refine our equipment requirements. For more details, please consult the company finances section on the entrepreneurship page.

Consequently, we are excited to share our vision for the CALIPSO laboratory in 2025 in the following video:

Figure 2: CALIPSO headquarters 3D modeling on sketchup.

• List of equipment in our P1 lab:

Figure 3: equipment in CALIPSO P1 laboratory.

along with a Magnetic agitator, an Ice tray, Infors.

• List of equipment in our P2 lab:

Figure 4: equipment in CALIPSO P2 laboratory.

Recruitment of qualified people: 2025 - 2026

To enhance our effectiveness, we plan to recruit individuals with complementary skills. Specifically:

• We aim to hire a business developer who possesses the ability to understand our work and build a robust network, as it will be crucial for securing funding and partnerships.
• As we establish ourselves within the Pierre Potier Center, we also intend to bring on board a laboratory technician who can assist us in conducting our experiments, thereby enhancing our research capabilities.
• Following the successful development of our startup, we will consider hiring a secretary. This addition to our team will help us alleviate the administrative workload.

R&D optimization for drug candidate patenting : 2025 - 2026

As mentioned above in section 2 (“Patent deposit”), during the 18 months of optimization at the Pierre Potier Center, we will focus on reducing costs and improving our system effectiveness. Several optimization ideas are described in our best measurement page. At the conclusion of this period, we will apply for a patent covering the integration of our three modules designed for HER2+ and IDH1 mutation cancers.

Pre-clinical and clinical trials: 2026 - 2032

Today, the majority of research and development in the pharmaceutical industry is carried out by small pharmaceutical companies. They are responsible for 70% of drugs in phase III clinical trials and one-third of drugs approved by the FDA since 2009 [3]. It takes between 10 to 15 years to progress from the research and development stage to bringing a drug candidate to market [4]. This process costs between 1 and 2 billion dollars [5], and during this period, the company receives almost no return on its investment. In addition, risks of a drug candidate's development failure are very high. Only 10% of drugs developed in the preclinical phase receive market authorization following clinical trials. The cost and logistics of clinical trials increase significantly from Phase I clinical trials, where approximately $26 million are needed, to Phase III clinical trials, with its $282 million required. Thus, most of the time, startups and small companies handle all the research and development up to Phase II clinical trials. The patent or licensing of the drug candidate is then acquired by a larger company that has the financial and material resources to conduct Phase III clinical trials and market the drug [3].

As mentioned earlier in the patent section, we decided to use CALIPSO as a platform to develop new drug candidates targeting different types of cancer, and even other diseases. Our company's ambition is to take in charge the research and development of each new drug candidate right through to phase II clinical trials.

We are aware of the astronomical costs associated with preclinical and clinical trials; that is why we will carry them out as far as possible, with the assistance of our partners, until we sell the patent for our drug candidate to a bigger pharmaceutical company that has the means to take over from us. This is the standard cycle, as confirmed to us by Thomas Dubrunfaut, a clinical trials launches coordinator at ICONplc. To finance these clinical trials, we will seek private funding sources such as business angels and venture capital firms.

• Pre-clinical trials ~ $7.5 million.

We want to start preclinical trials as early as 2026, after the first patent application for our HER2+ and IDH1 mutation cancer drug candidate. The pre-clinical in vitro trials will be carried out in our P2 laboratory, where we have a cell culture room (3D modeling of the startup link). The aim of these pre-clinical trials will be to test the safety, tolerance and efficacy of our product through pharmacological (pharmacokinetic and pharmacodynamic) and toxicity studies. These trials will be followed by preclinical trials on animals. Since our laboratory does not have an animal facility, preclinical trials on animals will be carried out in collaboration with a CRO (Contract Research Organization) specialized in lipid nanoparticle-based drug delivery systems. We also need to produce the doses of our treatment on a larger scale (pilot/pre-industrial scale) than the one used for in-vitro pre-clinical trials. We will need to establish a partnership with a CMO (Contract Manufacturing Organization) with expertise in liposome production. CMOs are companies specialized in the production and formulation of specific compounds while adhering to Good Manufacturing Practices (GMP). They enable the scale-up of drug production. Additionally, they allow startups to avoid the financial risk of investing in production equipment if clinical trials are unsuccessful. These preclinical trials will involve a rodent species (rat or mouse) and pigs and/or non-human primates due to their physiology and anatomy, which closely resemble that of humans. The objective of these preclinical trials is to assess the safety, tolerance, and effectiveness of our product on animals and establish the appropriate dosage for use in phase I clinical trials on humans.

All the data collected up to this point forms a file required for CTA (Clinical Trial Authorization).

Ethics considerations: Our team is sensitive to animal welfare. That is why we want to work with Contract Research Organizations (CROs) committed to the well-being and ethical treatment of animals. Our team also aims to minimize the use of animals in pre-clinical studies and prioritize alternative approaches such as the use of organoids and 3D cell cultures.

• Clinicals Trials phase I and II: ~ $100 million.

We intend to conduct clinical trials in Europe. To do this, we will need to submit a request for authorization for clinical trials on the CTIS online platform). We hope to start clinical trials by early 2029. To conduct these clinical trials until phase II, we will need to collaborate with one or more CROs with expertise in clinical trials of lipid nanoparticle-based drug delivery systems. However, the treatment production will be handled by the same CMO as the one used for the in vivo preclinical trials.

Since 31 January 2022, the reform of European Union (EU) pharmaceutical legislation known as the Clinical Trials Regulation has modified applications for clinical trials in Europe [6]. Previously, applications for authorisation of clinical trials were made independently to the relevant national authorities. In France, the application was made to the ANSM after a favorable opinion on the assessment of the benefit/risk balance by a personal protection committee (CPP) [7]. Today, the application is made in a single step, after submitting the file online, via a single online platform called the "Clinical Trials Information System" (CTIS). This single application makes it possible to obtain authorisation to conduct a clinical trial in several European countries, after assessment by a competent national authority.

Ethics considerations: Ensuring the ethics of our clinical trials is essential for us. As we discussed with Professor Bettina Couderc, a member of the CPP, we must demonstrate integrity in our results and our application so that they can properly evaluate the benefits-to-risks ratio for patients.
Moreover, during our conversation with Thomas Dubrunfaut, he emphasized the importance of remembering that behind the protocol, there are real people. Therefore, both we and our CRO partner must ensure that decent conditions for the patients are met. Firstly, the protocol must be validated before recruiting anyone, and a thorough monitoring must be done to ensure the security of the patients. Secondly, volunteers must be fully informed before giving their consent and have the choice to leave the trial if they want. Lastly, the hospital staff must be trained in Good Laboratory Practices.

Click below for more details on the differents phases of clinical trials:

• Clinicals Trials phase I: ~ $26 million [3]
Phase I trials are carried out on 10 to 40 sick volunteers [8]. For drugs expected to have high levels of toxicity, individuals with the specific illness are involved as subjects in phase I trials. The aim of these clinical trials is to determine the maximum tolerated dose in humans and the fate of the drug in the patient's body. During these trials, the dose and frequency of administration of the drug recommended for the following studies are defined.

• Clinicals Trials phase II: ~ $62 million [3]
We would like to conduct phase II clinical trials for 2 years from 2030 to 2032. A distinction is made between IIa clinical trials in healthy volunteers and IIb clinical trials in sick volunteers [8]. Phase IIa is used to determine the tolerability of the compound, while phase IIb is used to determine the therapeutic dose. They are carried out in a hospital center as randomized, double-blind trials. Different doses are tested within the toxicity range determined in phase I. The efficacy of the treatment is compared with a placebo and a reference treatment.

At the end of this phase II, if the trials are conclusive, they will serve as sufficient proof of concept to sell the patent for the drug candidate and the license to operate the CALIPSO platform to a large pharmaceutical company. This commercialization is facilitated because these companies are established in multiple countries, either through company branches or subsidiaries. They are also advantaged by their knowledge of the legislation concerning market entry and drug regulation in each country.

• Clinical Trials phase III: ~ $282 million [3]
Phase III trials will be conducted by the pharmaceutical company that has bought back the patent. The aim of this phase is to assess the benefit/risk ratio of the drug in patients exposed to it over a longer period [8]. It is carried out on several hundreds or even thousands of targeted patients and on groups of high-risk patients (elderly patients, patients with renal failure, etc.). Following these trials, an application for marketing authorisation (MA) may be submitted.

• Clinical Trials phase IV:
Phase IV trials, often referred to as pharmacovigilance trials, may occur post the market release of a new drug. These trials aim to identify any side effects that were not observed during earlier trials and assess the drug's effectiveness over more extended usage periods compared to the earlier trial phases.

Selling of our patent and operating license to a pharmaceutical company: 2032

Once our drug candidate successfully completes Phase I and II clinical trials, our team will have the opportunity to sell the corresponding patent to a pharmaceutical company. The pharmaceutical company, interested in continuing the clinical trials and the marketing process for a specific drug candidate will also need to purchase the exploitation license for the CALIPSO platform. This sale must be carefully prepared under the experienced eye of lawyers, especially as it involves the sale of both a license and a patent.

The common steps of a license selling process are as follows [9]:

• Establishing license terms: we need to determine the terms of the license, including royalties, upfront payments, due diligence obligations, license duration and territories covered.

• Search for potential partners: we need to target pharmaceutical companies whose interests most closely align with our platform's technology and the target disease of the drug candidate.

• Negotiation: once we have found and contacted the most suitable potential customers, the negotiations can be initiated to discuss financial terms, reporting requirements and other aspects of the license.

• Evaluation & Due Diligence: for our team (i.e, the licensor), this step ensures that our future partner has the right skills and resources to develop and commercialize our candidate product. For the customer (i.e, the licensee), this phase consists of an in-depth evaluation of the product and, in particular, of the clinical results obtained with the product.

• Contract drafting: once the terms have been agreed, a license contract is drawn up, detailing all the agreed conditions, rights and responsibilities of each party.

• Signature of the deal: symbolizing the start of the partnership between the licensor and the licensee.

Prior to finalizing the contract, we will engage in parallel discussions with the same client regarding the sale of the patent associated with the drug candidate [10]. Once the value of the patent has been assessed, regarding the competitive advantages it offers and the market it targets, we will set a selling price. Together, we will begin negotiations for the patent sale, and create a comprehensive contract once terms are agreed upon. The contract will outline transaction details, warranties, payment terms, ownership transfers, and post-sale responsibilities. Upon meeting all contract conditions, the sale will be completed by signing the contract and transferring funds.

After obtaining the patent and license, monitoring compliance is vital, focusing on royalties, development, and reporting obligations. We'll oversee this through regular reporting, evaluating usage to ensure adherence. Maintaining open communication with the licensee is key throughout the partnership.

R&D on new drug candidates: 2032 - …

After successfully completing the Phase II clinical trials and selling the patent, we aim to use the experience gained to initiate trials for new drug candidates targeting different forms of cancer. Since the inception of trials, we will consistently maintain our R&D activity in parallel, allowing us to develop these candidates. Finally, in the event of a major pharmaceutical company acquiring our startup, we will have the choice to either become their employees… or embark on a new chapter in our lives.