On September 28, 2021 NH TherAguix, a French biotechnology company specialising in the development of innovative nano medicines for the radiotherapy treatment of cancer indications, reported the launch of its initial public offering with a view to listing its shares on the Euronext Growth market (ISIN code: FR0013105954-ticker: ALNHT) (Press release, NH TherAguix, SEP 28, 2021, View Source [SID1234590544]). On 27 September 2021, the French financial markets authority (Autorité des Marchés Financiers-AMF) approved the Prospectus under number 21-416, comprising the Registration Document, approved on 10 September 2021 under number I.21-048, the supplement to this Registration Document approved on 27 September 2021 under number I.21-055, a Securities Note and a summary of the Prospectus (included in the Securities Note).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Géraldine Le Duc, Chief Executive Officer of NH TherAguix, says: "NH TherAguix aims to demonstrate that its candidate drug AGuIX increases the effectiveness of radiotherapy on solid tumours, while sparing the surrounding healthy tissues. It offers new hope for cancer patients and our ambition is to make AGuIX the new standard of care in the treatment of certain cancers with radiotherapy. To do this, we have developed AGuIX so that it can be integrated into all current care protocols, without changing patient treatment. The indications that we are primarily targeting include pancreatic cancer, glioblastoma, the most comment brain cancer found in adults, and brain metastases. This planned IPO will allow us, on the one hand, to consolidate the Company’s financial position and, on the other, to obtain additional resources to be able pursue the development of the candidate drug AGuIX, and more specifically to develop the current pipeline of clinical trials (covering in particular glioblastoma, pancreatic cancer and brain metastases) with a view to registration trial, for which the Company would act as sponsor. I hope I can count on the support of many institutional and retail investors in this human and entrepreneurial adventure." Press Release Should not be published, transmitted or distributed directly or indirectly in the United States of America, Canada, Japan or Australia 2 Pushing the current boundaries of radiotherapy In the fight against cancer, radiotherapy is one of the standard care treatments. 60% of patients with cancer are treated with radiotherapy during their care pathway.
However, despite advances in technology and the continuous improvement of equipment, radiotherapy has limitations due to the harmful effects it causes on healthy tissue close to the tumour. These side effects limit the effectiveness of certain treatments and sometimes make radiotherapy unsuitable for certain forms of cancer. A theranostic1 approach for precision radiotherapy Increasing the x-ray dose differential between the tumour and surrounding healthy tissue is now the most promising way of improving radiotherapy.
Based on this observation, NH TherAguix has developed an innovative theranostic1 approach in nanomedicine: AGuIX. Designed to be able to increase the dose differential between the tumour and healthy tissues and therefore to increase the efficacy of radiation therapy, AGuIX also allows more accurate imaging guidance after targeting the tumour. The combination of these three properties (targeting, imaging and treatment) paves the way for a new generation of precision radiotherapy.
The first "triple action" candidate drug By injecting a single dose, AGuIX works in three complementary ways:
1. Targeting: Nanoparticles are injected intravenously. Thanks to their size of 5 nanometers, they accumulate naturally and exclusively in the tumour through a biodistribution process (effect known as EPR2).
2. Imaging: The presence of gadolinium atoms in the structure of AGuIX ensures that the tumour is clearly visible via magnetic resonance imaging prior to radiotherapy, allowing the tumour to be delineated in order to calibrate radiation therapy.
3. Treatment: Its radiosensitising properties enable AGuIX to amplify the effect of radiation directed against the tumour through a physical interaction. By creating a dose differential between the cancer and adjacent tissues, the radiation therapy could become more effective. A candidate drug adapted to the patient care pathway Intravenous administration of AGuIX is a key component of its therapeutic effectiveness as it makes it easy to use by healthcare staff. It does not disrupt the treatment pathway, and does not require any specific equipment or training. It is also possible to combine
AGuIX with all current and future radiotherapy technologies.
1 Theranostics: therapeutic approach combined with better diagnosis.
2 Enhanced Permeability Retention effect: nanoparticles tend to accumulate more in the tumour than in healthy tissues, mainly due to 2 biological phenomena: abnormal blood vessel development and inefficiency of lymphatic drainage in cancerous tissues. Press Release Should not be published, transmitted or distributed directly or indirectly in the United States of America, Canada, Japan or Australia
3 Strong proof of concept The first study in humans was conducted in the Phase 1b trial on brain metastases in 15 patients, NANORAD 1, which first helped to established the absence of toxicity and adverse effects of AGuIX.
In addition to the safety parameters, this study demonstrated a clinical benefit with encouraging overall survival rates and confirmed the triple effect of AGuIX after injection (targeting, imaging and treatment). A dose effect has also been highlighted: the higher the concentration of AGuIX in brain metastases, the lower their size and therefore the better their response to treatment.3 Preliminary observations of the ongoing NANORAD 2, Phase 2 trial on brain metastases show tolerance and contrast entirely consistent with the Phase 1 trial results. It also seems that the activity signals of AGuIX already cited, namely a radiosensitisation response related to improved control of tumour volume and survival, can be observed here. These very preliminary observations reveal a trend that needs to be confirmed or invalidated based on the existence of the control arm and the statistical strength of the trial if sufficient. A potential pan-cancer treatment deployed through 8 Phase 1 and 2 clinical trials, 3 of which are already recruiting, 4 of which have been authorised by health authorities and one of which is being prepared The properties of AGuIX show pan-cancer potential: intravenous injection combined with the ability of AGuIX to accurately target the tumour enables the treatment of cancers that are difficult to access by intratumoral injection. At this stage, all injected tumours have been visible via MRI (49 patients). Markus Loeffler, NH TherAguix Medical Director, comments: "The results of the Phase 1 study are very encouraging. NH TherAguix has now entered Phase 2 with 2 clinical trials focusing on radiotherapy for brain metastases, either by whole brain radiotherapy (NANORAD 2), or as a complementary treatment by radiosurgery (NANOBRAINMETS), and also has a Phase 1 trial on advanced cervical cancer (NANOCOL).
The launch of other trials in Europe and the United States, in partnership with internationally renowned cancer research institutes, is a very important strategic step for NH TherAguix." 3Targeting brain metastases with ultrasmall theranostic nanoparticles, a first-in-human trial from an MRI perspective. Verry C et al. Science Advances. 2020 Theranostic AGuIX nanoparticles as radiosensitizer: A phase I, dose-escalation study in patients with multiple brain metastases (NANO-RAD trial) Verry C. et al. Radiotherapy & Oncology, 2021 Press Release Should not be published, transmitted or distributed directly or indirectly in the United States of America, Canada, Japan or Australia 4 By the end of 2021, AGuIX technology should be in use in 7 Phase 1 and 2 clinical trials, 3 of which are already recruiting and 4 of which have been authorised by health authorities: *ODD (Orphan Drug Designation): orphan candidate drug status obtained in the United States, allowing for fast track recording in case of conclusive outcomes.
Clinical Development Strategy The clinical development strategy of AGuIX aims to exploit its pan-cancer potential with the objective of recording as quickly as possible primary and orphan cancers such as pancreatic cancer or glioblastoma, for which the therapeutic arsenal is very limited and which represent a significant market opportunity. For these indications, the Company operates in partnership with recognised institutes such as Dana-Farber Cancer Institute and Harvard. The Company is also targeting a broader market, namely the treatment of brain metastases, an indication in which the Company has already acquired results and the potential of which is significant due to its impact, and in which the number of competitors is limited.
Finally, the Company is considering the development of AGuIX to treat other indications. It is therefore promoting the implementation of clinical trials funded by research grants as part of academic collaborations to enable it to collect clinical and scientific data while preserving its financial resources. Press Release Should not be published, transmitted or distributed directly or indirectly in the United States of America, Canada, Japan or Australia 5 Financial and industrial support In 2019, the company experienced strong growth, having raised Series A funding of €12.3 million from recognised venture capital funds (BPI Innobio2, Arbevel, Omnes and Supernova). Thanks to this funding, the Company was able to launch its Phase 2 clinical trials and fund the scaling of production of its experimental drug, in partnership with Sanofi, the laboratory that produces the AGuIX nanoparticle. Offering eligible for PEA and PEA-PME equity savings plans NH TherAguix complies with the eligibility criteria for PEA-PME equity savings plans specified by the provisions of Articles L.-221-32-2 and D.221-113-5 et seq. of the French Monetary and Financial Code. As a result, NH TherAguix’s shares can be fully integrated into equity savings plans (PEAs) as well as PEA-PME accounts which enjoy the same tax benefits as traditional PEAs*.
Availability of the Prospectus Copies of the Prospectus approved by the AMF on 27 September 2021 under number 21-416 are available free of charge upon request from the Company and can also be consulted on the websites of the AMF (View Source) and NH TherAguix (View Source). Approval of the Prospectus should not be considered as a favourable opinion on the securities offered or admitted for trading on the Euronext Growth market in Paris. Risk Factors The risks associated with pursuing the effective progress of AGuIX’s clinical development, and more generally the risk factors to which the Company is exposed are presented in Chapter 3 "Risk Factors" of the Registration Document and in Section 3 "Risk factors related to the Offering" in the Securities Note. The occurrence of one or more of these risks is liable to have a significant adverse impact on the activities, assets, financial position, results or outlook of NH TherAguix, as well as on the market price of the Company’s shares.
Financial intermediaries and advisers Global Coordinator and Joint Bookrunner Joint Bookrunner Financial Communication Agency Legal counsel Statutory Auditors Statutory Auditors Press Release Should not be published, transmitted or distributed directly or indirectly in the United States of America, Canada, Japan or Australia
6 MAIN TERMS OF THE TRANSACTION ▪ SHARE CAPITAL BEFORE THE ISSUE A public limited company (société anonyme) with a board of directors, with share capital of €244,081.00 divided into 6,102,025 shares with a par value of €0.04 each.
▪ CHARACTERISTICS OF THE SHARES
• Title: NH TherAguix
• Ticker: ALNHT
• ISIN: FR0013105954
• Listing market: Euronext Growth Paris
• ICB classification: 20103010-Biotechnology
• LEI: 9695007Z8UJ5AFRZQN66
• Eligible for the PME-ETI equity savings plan
▪ INDICATIVE PRICE RANGE Between €15.50 and €18.90 per new share. This information is provided for information purposes only and is in no way indicative of the price of the Offering, which may be set outside this indicative range. ▪ INITIAL SIZE OF THE OFFERING The Offering will be made by placing on the market 1,744,187 new shares to be issued, which may be increased to 2,005,815 new shares in the event of full exercise of the extension clause and 300,872 additional new shares in the event of full exercise of the overallotment option, i.e. a maximum of 2,306,687 shares offered in the event of full exercise of the extension clause and the overallotment option.
▪ GROSS TRANSACTION AMOUNT Approximately €30 million, which may be increased to approximately €34.5 million in the event of full exercise of the extension clause and approximately €39.7 million in the event of full exercise of both the extension clause and the overallotment option (based on the midpoint of the indicative price range of the Offering, i.e. €17.20). ▪ NET PROCEEDS FROM THE OFFERING Approximately €27.2 million, which may be increased to approximately €31.4 million in the event of full exercise of the extension clause and approximately €36.3 million in the event of full exercise of both the extension clause and the overallotment option (based on the midpoint of the indicative price range of the Offering, i.e. €17.20). Press Release Should not be published, transmitted or distributed directly or indirectly in the United States of America, Canada, Japan or Australia
7 ▪ STRUCTURE OF THE OFFERING The offered shares will be distributed as part of a global offering (the "Offering"), comprising:
• An offering to the public in France in the form of an open-price offering, mainly intended for private individuals (the "Open-Price Offering" or "OPO"), where: o the orders will be broken down according to the number of shares requested: A1 order fraction (from 1 share up to 250 shares) and A2 order fraction (over 250 shares); o the A1 order fractions will receive preferential treatment relative to the A2 order fractions in the event that all orders cannot not be entirely satisfied.
• A global placement mainly intended for institutional investors (the "Global Placement"), comprising: o a placement in France; o an international private placement in certain countries, excluding in particular the United States of America, Japan, Canada and Australia; and o a private placement in the United States for a limited number of qualified institutional buyers as defined in Rule 144A of the U.S. Securities Act of 1933 (as amended) (the "Securities Act"), in the context of the exemption of private placements from the registration provisions pursuant to Article 4(a)(2) of the Securities Act. If permitted by the request expressed under the OPO, the number of shares allocated in response to orders issued under the OPO will be at least equal to 10% of the number of shares offered under the Offering (before any exercise of the extension clause and the overallotment option).
▪ LOCK-UP COMMITMENTS AND CONSERVATION Company lock-up agreement: 180 calendar days following the settlement/delivery date of the Offering, subject to certain exceptions. Commitment by the Company’s shareholders to hold on to their shares: all shareholders and holders of securities giving access to the Company’s share capital shall make a commitment to the joint bookrunners to conserve the shares they hold on the date on which the Offering Price is set for a period of 270 calendar days following the settlement-delivery date of the Offering, subject to certain usual exceptions.
▪ SUBSCRIPTION COMMITMENTS FPCI InnoBio 2, represented by Bpifrance Investissement, FCPI Arbevel Life Sciences Crossover I, represented by Financière Arbevel, and FCPI Supernova 2, represented by Supernova Invest, have each committed to place a subscription order in the order book for a maximum amount of €3.00 million, €2.35 million and €1.50 million respectively. In addition, Guerbet, a French company with international expertise in medical imaging (diagnostic and interventional) and listed on Euronext Paris, has made a commitment to place an order of €3.00 million in the order book. These orders, which therefore represent 32.8% of the gross proceeds of the Offering (if the Offering is 100% subscribed and excluding the exercise of the extension clause and the overallotment option) are intended to be served in priority and in their entirety, subject to reduction in accordance with usual allocation principles (mainly if the subscriptions received are way over the number of shares offered).
Press Release Should not be published, transmitted or distributed directly or indirectly in the United States of America, Canada, Japan or Australia 8 Guerbet’s investment comes as both companies have started to work together on artificial intelligence for clinical trials on pancreatic cancer and glioblastoma, as developed by the Company. Last July, the Company and Guerbet tendered together for State funding (as an Important Project of Common European Interest (IPCEI)) in this area. Regardless of the (limited) chances of obtaining such funding, the agreement signed on 23 September 2021 on Guerbet’s subscription commitment suggests that the two companies will discuss the scope of collaboration work on the AGuIX platform and will subsequently negotiate a collaboration agreement to that effect in good faith.