TxCell — Update 31 May 2016

TxCell is a pioneer in regulatory T-cell (Treg) therapy and so offers a rare investment opportunity in this emerging technology space. Treg cells prevent harmful activity by the immune system so can be used, in concept, to control multiple chronic autoimmune and inflammatory diseases like Crohn’s disease, multiple sclerosis and lupus nephritis. If the resumed Ovasave Phase IIb delivers a clear and positive primary endpoint success by early 2018, this should validate the general concept of using Tregs to control autoimmune disease and inflammation, two major markets with remaining unmet medical needs. Management aims to enter platform and preclinical Treg deals in 2016 and 2017. The company is based in the south of France near Nice and has 50 employees. TxCell has raised €66m of capital including private equity; this was restructured in 2014 and is now reported at €32.5m in the 2015 accounts. The 2015 accounts show a cumulative loss of €20.9m.

TxCell’s value depends largely on Ovasave as the sole clinical-stage project. The overall Ovasave probability of success is 28%, which is a combination of 33% clinical and 85% manufacturing process probabilities. A core assumption is that a partner to fund Phase III is signed in 2018 in a €175m+ deal plus 16.5% royalties. An orphan product for uveitis (eye inflammation) is in preclinical with a 7.5% probability but with direct sales potential. The CAR Treg platform could become the main value driver due to its versatility and deal potential and is assigned a nominal value of €20m; lupus nephritis is the lead, research-stage indication. This gives a prefunding value of €7.08/share. If CAR progresses and Ovasave enters Phase III with a partner in a deal worth at least €175m in 2018, the indicative market value could rise to over €300m. TxCell also plans to enter at least one preclinical or platform deal per year from 2016.

At 31 March 2016, TxCell had €5m cash with a €3m tax credit due. The 2015 core operating cash costs were €12.3m. Management has stated that TxCell expects a €15m cash burn over 2016. Cash expenditure will rise in H2 as the Phase IIb trial restarts; this study is costed by management at €15m over three years, with €4.5m assumed by Edison in 2016. There is investment into the CAR Treg programme, which should steadily rise as the platform develops.

The major sensitivity relates to the resumed CATS29 Phase II and TxCell’s ability to fund the €15m study and ongoing R&D including the important CAR Treg cell platform. French tax credits are expected to pay about 30% of each year’s cost; this cash is received in the following year. The Crohn’s market is complex with uncertainties in patient numbers and significant regional market differences. A core value assumption is that an Ovasave partner is found by the end of 2018 at a significant overall deal value of at least €175m with at least a €25m upfront payment. The project may not progress into Phase III unless a deal occurs. Steroid resistant Uveitis (eye inflammation) is a niche market with a candidate in late preclinical with no trial timeline announced. TxCell plans to sell directly, capturing extra value, but will need to fund the trials. Finally, the new CAR Treg opportunity appears to be potentially applicable to many indications but as a technology platform it is hard to value and is at least three years from a clinical trial. TxCell patents are now being filed. There is no guarantee that an academic blocking CAR Treg patent application under option till June 2016 will be secured.

Regulatory T-cells (Tregs) naturally block autoimmune and inflammatory disorders and control the cell-killing T-cell immune response. The Treg area is underdeveloped and TxCell offers a rare investment opportunity, targeting major conditions like Crohn’s disease and, in future, Lupus through direct immune control. TxCell has two technology platforms, Exhibit 1.

TxCell originated in 2001 as a spin-out from INSERM1 to develop Tr1 Regulatory T-cell technology; this was discovered and published in 1997. The company ran a Phase I/IIa in patients with Crohn’s disease over 2008-2010 with Ovasave; established a manufacturing site in Besançon (near the Swiss border) in 2013; did a pre-IPO deal with Ferring (later transferred to Trizell) in early 2014; and started the Ovasave Phase II in late 2014. TxCell completed its IPO on Paris Euronext on 11 April 2014 at €5.58 per share raising €16.2m gross in cash and converting €3.5m of bonds to shares.

TxCell was restructured from Q215 after Stéphane Boissel was appointed as CEO. Over 2015, TxCell paused the Phase II, closed the Besançon site, contracted out manufacturing to MaSTherCell, and bought out the Trizell constraining partnering deal. In November 2015, an option was signed (expiring at the end of June 2016) to license an original 2008 patent application on CAR Treg technology; note that TxCell is developing this regardless but the patent would give a good blocking position over the CAR Treg area generally.

The investment case for 2016 is consequently on a revised basis relative to the 2014 IPO. The company has regulatory approval (May 2016) to restart the CATS29 Phase IIb on Ovasave using a redesigned protocol. It is developing a commercial manufacturing process; plans to progress a second product into clinical development, and, ideally, sign a preclinical/platform deal by the year end. Further funding is required for the CATS29 trial and CAR technology platform development.

The immune system needs to protect against pathogenic bacteria and viruses in the intestine but also needs to tolerate the many benign bacteria and food components as a reaction to these stimuli can cause intestinal damage. In 1997, Groux et al published a paper in Nature on a new type of regulatory T-cell.2 Asseman 1998 provides a good commentary. The area has been recently reviewed by Zeng (2015).

Groux showed that naïve CD4+ T-cells exposed to a specific food antigen produced a subset of T-cells, which he named T regulatory cells type 1 (Tr1). These prevented effector T-cells from responding to specific foreign food antigens so causing a pathological response to the intestine. Tr1 cells therefore have a crucial antigen-specific protective effect Tr1 cells are characterised by production of very high levels of IL-10. The high IL-10 levels stopped other T-cell cell types (Th1, Th2) from developing. Groux et al used ovalbumin as the antigen. Antigen presenting cells (APCs) ‘present’ specific antigens to naïve CD4+ T-cells so they become Tr1. Tr1 can also protect against autoimmune diseases for example Pot 2011.

As a natural cell, Tr1 cannot be patented but the process of generating Tr1 cells against a specific antigen can be protected. TxCell holds a granted process patent, EP1739166B1 (expiry 1 July 2025), and has filed a patent application, WO 2009068575 A1 (expiry 28 November 2028). The patent claims “at least one human Tr1 cell population directed against a food antigen from common human diet”. The ASTrIA method involves harvesting leukocytes from human blood and stimulating them with antigen. For Ovasave the antigen is ovalbumin. The resulting ovalbumin-specific Tr1 cells are then cultured, harvested, purified and frozen in single dose aliquots. A blood sample of 150ml is stated to produce between 30 and 50 doses: about a three-year supply. The cells are autologous, that is they are injected back into the donor, who is also the patient.

The method described in these two core patents can be applied to a variety of antigens. The pipeline is summarised in Exhibit 2. The immediate focus is Ovasave in inflammatory bowel disease (Foussat 2003) specifically Crohn’s. There is also published preclinical work using the ovalbumin model on central nervous system inflammation (Barrat 2002).

Exhibit 3 shows possible localised mechanisms of action (MoA) suggested by TxCell. As with most cell therapies, the cells probably exert an effect through multiple routes.

The concept behind the use of ovalbumin is that, as a common food antigen, it will be frequently present in the intestine and some will be absorbed by special immune areas in the intestine wall called Peyer’s patches. These are specialised structures in the intestine wall that take in antigens to induce tolerance (food) or activate an immune response (pathogens). Antigens are passed to the mesenteric lymph nodes that protect the body from infection originating in the intestine.

For efficacy, ovalbumin has to pass through the intestine lining, be taken up and processed by APCs and then displayed as fragments in MHCII to stimulate the Ova-Treg cells to exert some form of localised immune regulation. The Ova-Treg cells need to migrate from the administration site to the intestine lining and the intestinal mesenteric lymph nodes. Ovalbumin does not affect the migration but T cells migrate to areas of inflammation due to other cytokine signals.

To get regular ovalbumin in the diet, the Phase I/IIa patients “ingested an ova-enriched diet in the form of a daily meringue cake”. Note that there is no clinical meringue dose response curve but that animal studies indicate that only a trace amount is required. A normal diet may be adequate.

It would seem likely that patients have frequently been exposed to ovalbumin and may already have endogenous Ova-Tregs. Native ovalbumin is resistant to proteolytic cleavage in the stomach (Walker 1978) and in mouse models, high levels of radiolabelled ovalbumin pass along the small and large intestines (Oliveira 2007). Oliveira et al also showed that ovalbumin locates to Peyer’s patches and moves to mesenteric lymph nodes. This is important for a systemic effect since Crohn’s disease commonly occurs in the lower small intestine and large bowel and rectum whilst most intact ovalbumin in the intestine will be in the upper bowel. Cooking of ovalbumin, as in meringue, exposes new proteolytic sites in the protein to enzyme action (Nyemb 2014) and bile salts and lipids in the duodenum (upper small bowl) increase digestion (Martos 2010). Golias et al (2012) found that cooking altered ovalbumin digestion and allergic response.

The Ovasave Phase I ran between 2008 and 2010 and was published in 2012 (Desreumaux 2012). Details and comments on the study are in Exhibit 4.

The Phase I and II studies use the CDAI score as an endpoint (Exhibit 5). This was devised in 1977 (Best 1976) and has been widely used since. The system has no specific upper limit, but a score under 150 points is deemed remission, and over 450 points is severe disease. Crohn’s is a condition subject to sudden flares then remission, so variability is expected. Note that the data is not controlled and could be subject to small number effects (in a small group, one or two outliers make a big difference to the average; in a large group, such outliers are averaged out and we see reversion to the mean).

Exhibit 6 shows the average scores for the 106 group – the optimal identified dose, but this conceals some very erratic scores. A simplified per patient data plot is in Exhibit 6. The data in Exhibit 5 was used to set the Phase IIb endpoint at Week 6, with the assumption that efficacy declines thereafter as the ova-Treg cells die.

An issue with the CDAI is that it does not provide a measure of inflammation such as CRP. CDAI has been critiqued as a marker for testing biological therapies, for example Binion 2010.

The CATS29 study is a randomised, double-blind, placebo-controlled study to evaluate the performance of a single 106 cell dose of Ovasave in refractory Crohn’s disease patients over six weeks, Exhibit 8. It is designated Phase IIb by TxCell. A second, open-label phase of the trial is then planned to provide additional safety data and possibly some uncontrolled data on efficacy and responses. Adding this open-label study where all are treated is designed to aid recruitment. The redesigned study protocol has regulatory approval and will restart soon with data in Q118.

The role of the CATS29 Phase II is to get enough clinical evidence to gain a strong partnering deal. The weakness of CATS29 is that it only tests a single dose and at only one dose level. Patients are not supposed to take other therapies but this might be hard to control and will result in them being counted as therapy failures if detected.

MaSTherCell, a contract manufacturing organisation (CMO) based in Belgium, was contracted to supply Ovasave during 2015 and technology transfer is underway. Regulatory approval of this move, expected by mid-2016, is needed before CATS29 can restart. A five-year strategic agreement was signed in December 2015 so that MaSTherCell will supply all TxCell cell products.

In July 2015, TxCell gained an FDA fast track and open IND for Ovasave, so it could add a US centre into the CATS29 study. PCT, a Caladrius subsidiary, was appointed in March 2016 as TxCell’s contract manufacturing partner in the US. It is likely that some US patients in one or two centres will be enrolled in CATS29 when it restarts.

A positive primary endpoint by Q118 should enable a partnering deal, perhaps by late 2018. Timing of such deals is hard to forecast. Assuming this timeline is met, the trial protocol and manufacturing system needs to be in place before any Phase III can start. However, it is probable that a small multi-dose Phase IIb will be required before a multi-dose Phase III. Note that a few patients have already received multiple Ovasave doses, two for up to a year. Management expect the Phase III to be funded by a global partner that will also manufacture.

Manufacturing of Tr1 autologous cells is a multistep process. TxCell is working hard to reduce the number of stages, optimise the yield of each stage and reduce manual interventions required. It is working with the UK Cell Catapult, a government-backed centre of expertise, and various equipment manufacturers. As a final concept, a fully automated system is desirable with Tr1 cell culture in sealed units. This should provide optimum yields, an ability to scale up throughput (each patient is one batch so the process is replicated), and get a low cost of goods, perhaps about 10% of the average revenue. However, it is not certain how automated the final system will be. The partner will need to transfer this optimised process to its own facility or designated CMO and gain regulatory approval, although they could use TxCell’s current contractors for the trials. A US product requires a US cell manufacturing site; this can take at least nine months to establish and validate. A deal in Q418 therefore implies a trial start in H219 or later.

A multi-dose Phase III with 12-month dosing could take three years, so if started in H219, data might be reported in late H222. We forecast sales from late 2023, but 2024 is realistic.

The success probability of Ovasave is hard to assess. Classical Phase IIb projects have a 20-40% probability. Although TxCell views the probability of success as being very high, the limited Phase I data (three clinical remission cases out of eight by week five) suggests a clinical 33% probability in line with our general caution about cell therapy. We have applied a further 85% probability of developing an automated manufacturing system on time and to acceptable regulatory and commercial standards. This gives a combined 28% probability.

The current definable market for Ovasave is in Crohn’s disease where patients have received biological therapy but have proved either refractory or relapsed or have experienced severe side effects. Exhibit 9 gives the Edison summary market assessment. Exhibit 10 shows the assumptions and sources used. Although Europe should have a similar or greater number of cases, lower diagnosis and biological therapy use rates compared to the US lower the market potential.

At least 25% of the above patients might have perianal disease (de Zoeten 2013), of whom half have fistulas, channels between the intestine and skin or vagina. It is not certain how Ovasave therapy would relate to these complications. The assumption made is that perianal disease does not affect Ovasave use. Stem cells have already been shown to be useful in Crohn’s: the Phase III study of Cx601 from TiGenix has shown that it accelerates complex perianal fistula healing.

A commercial analogy to Ovasave might be Entyvio (vedolizumab, Takeda) approved for Crohn’s disease by the FDA and EMA when other treatments have failed. The UK NICE organisation issued guidance in August 2015 that Entyvio is useful, but only at a discounted price (undisclosed), for active Crohn’s disease if biological therapies have failed. Entyvio has a UK list price of £2,050 per 300mg dose, costing about €25,830 in year one, then about €18,450 for subsequent years if the disease remains active and Entyvio continued to be effective. In the US, prices are higher, with Entyvio costing $43,371 for the first year (€37,750) and $33,733 subsequently. Remicade before biosimilar erosion costs $31,856 in year one and $24,777 subsequently. TxCell notes that other current biological agents cost €22,000.

Our forecast assumes (see Exhibit 10) an EU list price for Ovasave of €30,000 based on a premium to the cost of the first year of Entyvio, The US price assumed is €45,000. The average biological price will fall in future as biosimilars enter the market, but the Ovasave market segments should not be affected by this and may expand if biological use becomes more affordable and widespread. This would create more refractory patients - but maybe these will be more price sensitive. Inflation of 2% is assumed from 2018.

TxCell assumes that 80% of patients will receive regular six-weekly doses of Ovasave in year one, dropping to 60% in year two and 30% in year three. These appear to be arbitrary assumptions, but seem reasonable and have been followed by Edison. The current production system produces in effect three years’ worth of therapy in one run. This makes the economics for TxCell’s partner front-loaded: the first dose has a very high cost of goods as custom made but subsequent doses just carry storage and logistics costs. We also assume that a core of 25% of patients stay on Ovasave therapy in year four, declining at 25% year-on-year. It is known that some patients remain on anti-TNF therapy for long periods. Longer-term use will require a further cell batch to be made.

The figures in Exhibit 9 are for prevalence. We assume that there is a turnover rate of 20% of biological patients per year; the incidence rate overall is about 5% of the prevalence rate. If the Ovasave market share is over 20%, the prevalence number reduces assuming patients try a course of Ovasave once only (note they receive multiple doses for up to three years from each custom manufactured batch). Turnover is due to the episodic nature of the disease and by the restraints imposed by healthcare providers to avoid substantial long-term costs with no clinical gain. Exhibit 11 shows the time course with patients often cycling between biological agents.

This might be offset commercially by longer periods of use. To model these potentially longer-term patients, we assume a fourth year of use by 20% of patients, with the number declining at 25% per year. All these are simplistic assumptions for the purposes of modelling.

The effects are shown in Exhibits 12 (EU) and Exhibit 13 (US) for the number of patients. Note that the x-axis shows years after launch, assumed to be 2023-4 for valuation, but uncertain.

At this stage in Ovasave’s development, it is not feasible to assess the competitive profile fully. The few possible alternatives are all yet to produce definitive data. In the cell area, Mesoblast has a Phase III study with Prochymal, due to report mid-2017, in resistant Crohn’s disease.

The main action in biosimilar development will not affect Ovasave and might expand the market. In the area of anti-TNF resistant Crohn’s disease, AbbVie has a major, 210-patient Phase II dose finding study running with a small molecule JAK inhibitor, ABT494 (NCT02365649). This reports in December 2017 and could reach the market before Ovasave, but the primary indication will be rheumatoid arthritis. It could be a powerful competitor if it works well, since as a small molecule it could be less expensive and easy to administer. Roche has a “dual-action anti-integrin” antibody, Etrolizumab, similar to Entyvio, which is targeting both anti-TNF naive and -refractory patients (NCT02394028). This trial reports in 2018 so could be marketed from 2020.

Non-infectious uveitis is an inflammatory eye condition. It is mostly acute and low level, but serious cases can result in blindness. It is an orphan drug indication. Exhibit 14 has background details. TxCell has published a paper on its preclinical work in this indication (Asnagli 2015) using antigen- directed Treg cells. The Tr1 cells are targeted against Type II collagen.

Note that Collagen Type II is a self-antigen rather than a foreign food antigen like Ovalbumin. Self-protein fragments are normally presented in MHCI and recognised by effector T-cells (CD8+) while foreign antigens are brought into cells and presented in MHCII – although there is “crossover”, which is not well understood. This might be clinically important as antigen-specific Tr1 cells (CD4+) are only stimulated by antigens presented in MHCII. The clinical mode of action therefore relies on adequate Collagen Type II antigen presentation in MHCII.

An immune reaction to Type II collagen has been claimed in the middle eye disease pars planitis, an intermediate form of uveitis characterised by infiltration of white cells to the vitreous (these clumps of cells are known as “snowballs”). The concept is that Col-Tregs will migrate to the eye, be activated there by Type II collagen and then suppress inflammation. This theory needs to be tested clinically. TxCell has indicated that it is planning a Phase I study.

At this time, the market for Col-Treg does not seem clearly defined by the literature. Uveitis is a disparate set of conditions so TxCell needs to define a target subgroup for initial clinical studies, possibly steroid refractory chronic non-infectious uveitis. Currently, it is hard to assess what proportion of uveitis cases could be treated with Tr1 therapy and for how long and at what price. Edison uses a TxCell guided figure of 15,000 cases per year but has not been able to verify this.

The big advantage of CAR Tregs (Exhibit 15) is that the genetically modified Treg cells can be easily cultured to give a homogeneous product. The CAR Tregs are targeted to the antigen so therapy design is much more flexible and direct.

TxCell is developing its own protected technology platform in this area and is building a strong science team to exploit this technology. In addition, TxCell has a licensing option, excisable up to 30 June 2016, over a patent application for CAR Treg cells (filed in 2007 by Professor Eshhar) from the Weizmann Institute of Science, Israel. Financial terms on the option have not been disclosed but are understood not to be material.

Although of high potential, the CAR Treg area will take some years to develop into a set of clinical-stage projects. TxCell has entered that a collaboration with a leading European immunology institute, the San Raffaele Scientific institute in Milan. The collaboration aims to develop a Treg product for lupus nephritis. There is some evidence (Le Buanec 2011) that Interferon-alpha in lupus might downregulate the standard Treg immune repression allowing an autoimmune response. Autologous Tregs have already been used in small, usually academic trials to treat autoimmune disease such as Type I diabetes, for example, Bluestone 2015. Caladrius Bioscience has an autologous Treg trial (the Phase II T-rex) and FDA orphan designation in Type I diabetes.

CAR Treg cells are genetically modified, which adds regulatory complexity, but the effector CAR T-cell area in cancer provides regulatory precedents. No CAR Treg has been clinically tested, so initial trials, possibly in the 2019-2020 period, will be slow, patient by patient and safety focused. Development could then accelerate if CAR Tregs prove potent in lead indications. Other possible indications could include multiple sclerosis, according to TxCell.

The major sensitivity relates to the current CATS29 Phase II and TxCell’s ability to fund the €15m study and ongoing R&D including the important CAR Treg cell platform. French tax credits are expected to pay about 30% of each year’s cost; the cash is received in the following year. The Crohn’s market is complex to forecast, with uncertainties in patient numbers, about 100,000 possible, and significant regional market differences. Incidence is 5% of prevalence so the market renews slowly. The level of long-term Ovasave use is crucial to value but uncertain. Edison assumes some long-term use and a level of churn in patients starting and stopping biological agents. A core assumption is that a partner is found by the end of 2018. Ovasave may not progress unless this occurs.

Steroid resistant Uveitis (eye inflammation) is a niche market of about 15,000 cases per year where TxCell could sell Col-Treg directly. However, it will need to fund the trials. The evidence here is less clear overall and the product is in preclinical development with no disclosed timeline to a Phase I.

Finally, the new CAR Treg opportunity appears to be potentially applicable to many indications in theory but as a technology platform it is hard to value and is at least three years from a clinical trial, possibly for lupus nephritis, the current lead. The 2008 academic blocking patent under option till June may not be granted or secured although TxCell is filing new patents. The CAR platform does have a high deal potential, probably from 2017.

The valuation of TxCell currently depends on Ovasave as the sole clinical-stage project. This combines two success probabilities; a clinical risk set at 33% multiplied by an 85% probability of achieving a commercial manufacturing system by late 2018. This gives a 28.05% combined probability. If the Phase IIb, which has yet to restart, shows a positive primary endpoint, the probability could rise to 45%. Edison has assumed a €25m upfront in a €175m overall deal with a 16.5% royalty. This is lower than the level of some deal upfronts paid for CAR T-cell cancer therapies but this is a less prominent indication although it offers a valuable, orphan market. Exhibit 16 shows the overall market (including Japan) by value (before probability adjustment).

The second product, for uveitis, is still preclinical, so has a standardised 7.5% probability. Uveitis has a high value relative to its market as it might be marketed directly by TxCell. Partnering would limit this value. However, whereas costs for Ovasave truncate after partnering, TxCell is assumed to fund the full uveitis study programme to launch in 2024.

The important CAR Treg platform is valued at a nominal €20m, reflecting its importance to the company but noting that it is currently not possible to value it on the basis of candidate products. As a CAR area, it has the potential for substantive deals perhaps of €300m overall value although no substantive deal is expected before 2020.

This gives a current pre-dilution value of €7.08/share. A funding need of €27m net of current cash is projected until late 2017, with more possible thereafter. The valuation summary is in Exhibit 17. Cash (March 2016) of €5m could add €0.38/share.

The tax rate used is 24%. This is below the French standard rate of 33%, but TxCell will have ongoing costs from further projects to offset taxes.

An important aspect is the potential for value development. If the value of the CAR Treg platform rises to €50m nominal and Ovasave progresses to a Phase III with a partner and a deal worth at least €175m with a €25m minimum upfront, the indicative market value by late 2018 could rise to over €300m. Note that this is one of several possible value scenarios and is not a forecast. TxCell management expects significantly higher deal values if Proof of Concept is obtained on the Ovasave project in Phase IIb leading to overall validation of the regulatory T-cell concept.

At year-end 2015, TxCell had €9.2m cash; cash on 31 March 2016 was €5m with a €3m tax credit due. Financial estimates are in Exhibit 18. Cash expenditure will rise once the Phase IIb trial resumes in H216; this trial is costed by management at €15m with €4.5m assumed by Edison in 2016. The 2015 core operating cash costs (before funding) were €12.3m. TxCell has stated that the cash burn in 2016 will be €15m. This covers increased investment in the CAR Treg area and the resumed CATS29 trial costs; some cost savings are from closure of the manufacturing site in 2015. To cover all cash requirements and give a cash cushion for 2018, Edison assumes that €36m in cash will be needed over the next two years (after tax credit funding) with €9.2m cash available at the 2015 year end. This implies a funding gap of €27m. Edison treats future funding as illustrative long-term debt and additional capital of €7m in 2016 and €20m in 2017 is assumed.

TxCell has a liquidity contract worth €200k. As of 31 December 2015, €95k had been used to buy 16,280 shares leaving €105k in cash.

In December 2015, the partnering deal with Trizell was terminated by agreement. TxCell paid €2m immediately with €2m due in late 2017 and a further €2m in late 2018. A further €9m payment is based on successful commercialisation and assumed to be paid in 2025, although some portion of any new partnering deal might be due. The buyout was expensive, but Trizell put little into development, €1m upfront with about €2m in 2015, and was not a strong future development partner. The buyout also enabled a smaller Phase IIb trial to be run with only one dose arm as opposed to the larger three dose plus placebo study originally planned.

The original 2014 deal with Ferring enabled the IPO to take place. It was billed as worth €76m. The agreement was transferred to Trizell in early 2015. Trizell and Ferring are both owned by the Dr Frederik Paulsen Foundation.