1

Urodelia, a French research company focused on the development of a therapeutic vaccine in oncology, is seeking to raise 2.5 million euros in 2019 to deploy its technology in veterinary oncology and fund human health research. Its needs 6 million euros over 3 years.

Based on the expertise of founders-associates in calcium phosphates chemistry and more specifically hydroxyapatite, Urodelia has developed an autologous vaccine in veterinary medicine whose concept is based on the association between tumour proteins purified from a biopsy of the animal’s cancer cells and hydroxyapatite as a vector for immune stimulation. About ten animal studies concerning about 15 different cancers have led to the confirmation of the effectiveness of the technology on pets’ overall survival improvement and of its total safety in more than 400 animals (dogs, cats, horses).

Based on the results obtained in animals, Urodelia is now entering a decisive phase: the development of its autologous therapeutic vaccine in human oncology.

With this in mind, Urodelia is entering a phase that requires raising funds to finance clinical trials in humans and find regulatory ways to market this vaccine.The company’s ambitious five-year strategy aims to access the market of human cancer treatments as well as the deployment of apa.vac® sales in veterinary medicine.

Nicole Rouquet, President of Urodelia, who has accompanied the research teams since their first work in orthopaedics, states «We are proud of the progress made since the very beginning and very excited to take this step that seemed so far away a few years ago. The uniqueness of our research has led us to face many challenges, both scientific and economic, at every stage. These challenges have strengthened our convictions. We still have to transform the perspectives opened up by research on animals with the hope of helping people affected by cancer and in a therapeutic impasse, due to their weak immune defenses. We are aware that France is a leading country in the quality of cancer care and our dearest wish is to contribute an additional breakthrough in French innovation and bolster this leading position.”

PRESS RELEASEAT THE HEART OF RESEARCH ON THERAPEUTIC VACCINES IN IMMUNO-ONCOLOGY

PRESS CONTACTAgence Hïkou • Marion CHANSON • marion@hikou.fr • +33(6) 15 71 16 76

Cécile Dauzats • cdauzats28@orange.fr • +33(6) 32 20 23 21

Toulouse (France), February 4, 2019

2

URODELIA IS PART OF ONE OF THE MOST PROMISING AREAS OF RESEARCH IN IMMUNO-ONCOLOGY: THERAPEUTIC VACCINES1

The role of the immune system in tumor control has now been demonstrated1. Many methods have been developed to stimulate its potential. Thus, over the past decade, a better understanding of the mechanisms of cancer development has led researchers to focus on immunotherapy treatments as co-treatment to radiation and chemotherapy that kill cancer cells, but also damage healthy cells or surrounding tissues. Therapeutic vaccines are one of these promising areas of research in oncology. The principle is to stimulate the immune system to help it fight proliferation of cancer cells. Therapeutic vaccines could be used in combination with existing treatments to increase their effectiveness and reduce side effects.

Two approaches are being explored:

The therapeutic vaccine in development by Urodelia under the name apa.vac® is part of the first category. Anti-cancer treatments in the most advanced immunotherapy to date are represented by two families: immune inhibitor checkpoint (ICI) and CAR T cells2. They act in a very specific way on a particular blocking point of the patients’ immune defense, with promising results.

The therapeutic vaccine developed by Urodelia differs from other therapies due to its global action against the phenomenon of cancer cell proliferation at a given time, thus stimulating the patient’s immunity in response to the constant evolution of the disease.

Customized vaccines designed from tumor biopsies or well -identified tumor antigens, which make it ossible to redirect the immune system against the tumor.

Attenuated vaccines based ononcolytic viruses targeting tumors (ex herpes virus, Measles, adenovirus).

1 2

1 Blanc C, Granier C, Tartour É. Vaccination antitumorale. Innov Ther Oncol 2017 ; 3 : 149-157. doi : 10.1684/ ito.2017.00882 Les immunothérapies spécifiques dans le traitement du cancer. Etat des lieus et des connaissances. Rapport Mai 2018. Institut national du cancer

february 2019press kit

3

AN AUTOLOGOUS THERAPEUTIC VACCINE BASED ON AN UNPRECEDENTED APPROACH

Urodelia is a French research company based in Toulouse, specialized in calcium phosphates chemistry and more precisely hydroxyapatite. This specialization stems from the expertise of its founders who, in a first experience, developed an orthopedic application now marketed worldwide by Johnson & Johnson network.Convinced of the biomimetic properties of hydroxyapatite and reinforced by their first successful experience, the founding researchers of Urodelia have focused their work on oncology since 2005.

Hydroxyapatite has particular surface specifications that give it adsorption/desorption properties, especially with protein compounds.

Urodelia has developed an autologous therapeutic vaccine combining proteins from tumor cells to hydroxyapatite. Thanks to its surface properties hydroxyapatite is used as a separator of simple and double DNA strand and also purifies proteins. It is this last property which is used in the preparation of the vaccine. The vaccine is made up of calcium hydroxyapatite particles (HA) loaded with tumor proteins. They are re-injected into the same patient to stimulate the immune system against cancer cells development and to complete the effectiveness of treatments (chemotherapy, immunology, radiology).

The synergy of this combination increases the overall survival of the patient.

This therapeutic vaccine, tested in animals, is now on the market in veterinary medicine under the name apa.vac®.

Urodelia has developed an

autologous therapeutic

vaccine combining

proteins from tumor cells with hydroxyapatite

BUSINESS MODEL

Fabrication des kitsapa.vac® en france

Vente directe des kits apa.vac® aux vétérinaires

Vente directe des kits aux unités de fabrication par pays qui fabriquent les doses de vaccin à partir :

• des prélèvements tumoraux du patient

• du kit apa.vac®

REGARDING THIS MODEL WHY USING APAVAC® & HOW DOES IT WORK?

a vaccine adapted to match space and time tumor heterogeneity

APAVAC® is the first cancer vaccine to incorporate a mineral adjuvant which has proven to be efficient in the stimulation of innate immunity.

The HA-particles triggers a rush of antigen presenting cells in the injection site, a maturation of these cells and an activation of the inflammasome.

The Heat Shock Proteins HSPs (gp96-hsp70) which are the proteic part of the vaccine are key elements of the antigen presentation to CD8 by the APCs. HSPs are chaperone proteins. They have a role in processing its associated peptides in order that they are expressed in conjunction with MHC class I proteins (at the surface of antigen presenting cells) to stimulate the T cells against these peptides when abnormal.

Thus APAVAC® activates both the innate and adaptive immune system.

Chaperoned peptides

gp96CD91

Immune response

MHC class II

MHC class I

Peptides

CD8 T cell

Dendritic cell

Transfer of peptide to MHC class Ipresentation pathway

Induction of maturation includingexpression of MHC class I, B7,MHC class II and ICAM-1

Antigen specific

Antigen non specificTCR

IL-1, GM-CSF, TNF-α

Inductionof cytokines ICAM-1

CD28B7

4

PROVEN EFFICIENCY ON ANIMALSWITH NO SIDE EFFECTS

Through the personal investments of the research associates supported by external investors, about ten animal studies have validated the effect of the positive technology on patient survival prolongation, its safety and reproducibility of the manufacturing process.

For example, the double-blind clinical study in dogs with lymphoma B conducted by Dr. Laura Marconato3,oncology specialist, and veterinarian within the renowned center of Veterinary Oncology of Sasso Marconi in Italy, demonstrated that the treatment was improving the dog’s quality of life during the disease and extended its survival up to three times longer when compared with a treatment of chemotherapy alone, without side effects.

This innovative patented method, made in France by the company Urodelia, is presented as kits, and is marketed under the name apa.vac®, currently used by veterinary oncologists in Europe.

Today, more than 400 animals (dogs, cats, horses), covering 15 distinct pathologies, have been treated by apa.vac® since 2009.

3 Marconato L. Stefanello D. Sabattini S. Comazzi S. Riondato F. Laganga P. Frayssinet P. Pizzoni S. Rouquet N. Aresu L. Enhanced therapeutic effect of apa’vac® immuntherapy in combination with dose-intense chemotherapy in dogs with advanced indolent B-cell lymphoma. Vaccine 2015 Sep 22;33(39):5080-6

The patient’s immune system with cancer does not recognize abnormal proteins

produced by its own pathology. In the case of lymphoma, thanks to apa.vac®, the

veterinary oncologist removes a neoplasic lymph node and separates abnormal proteins. It then purifies these same

proteins and re-injects them in the animal’s body, so that it becomes by itself capable of reacting to these proteins made visible

to the organization through hydroxyapatite. The immune system is then «re-educated».

It becomes vigilant again and produces a response against its own cancer.

ACTION MODE OF APA.VAC®

8COUNTRIESPROTECTEDBY PATENTS

7YEARS OF

RESEARCH

15PATHOLOGIES

TREATED

x3SURVIVAL

GLOBAL

400PETS TREATED

BY APA.VAC®

2PUBLICATIONS DANS

REVUES SANTÉ HUMAIN

SYNOPTIQUE DE L’INDUSTRIE EN SANTÉ ANIMALE & CONCURRENCE

Industrie

Marché cible

Concurrence

Nos objectifs

Marché mondial Vétérinaire Thérapies anti cancer• 180 millions de dollars en 2017• +7,7% prévu de 2018 à 2025

Chirurgie/Chimiothérapie/RadiothérapieImmunothérapie • AcM Aratana USA 2018 (1 cancer)• Cytokines (1 cancer) MERIAL• Massivet anti tyr kinase (1 cancer) ABSci • Vaccins (recherche) KVAX

• 10 pays en europe• 43 millions de chiens et 53 millions de chats• 5 cancers chien et 2 cancers chat ????• 164 K cancers chiens et 13 K cancer chat ????• 20% éligibilité à APAVAC > 35 500 anx ???

> Potentiel de 21 M€ 2016 2017 2018 2019 2020 2021 2022 20230€

1M€

obje

ctifs

apa

.vac®

2M€

3M€

4M€

50 70 90 237

1601

4693

2963

693

5

CAPITAL INCREASE TO ACCELERATE VETERINARY ONCOLOGY DEPLOYMENT AND FUND HUMAN HEALTH RESEARCH

Urodelia is now entering an important turning point in its development with an ambitious strategic 5 year plan which should lead to the confirmation in humans of the first results obtained in animals.The company plans to raise €2.5 million in 2019. Its projected financing needs are estimated at €6 million by 2021.

This increase in capital has three objectives:

By 2023, Urodelia aims to achieve a turnover of 20 million euros for a net income of €4,795,000.

Strengthen the company’s position in the world of healthcare investors, both in France and abroad.

Provide access to the financial resources necessary to finance human clinical trial and find regulatory ways to market its vaccine autologous therapy in human oncology.

Successfully enter the global cancer treatment market, whose annual growth rate (AAGR) is estimated at 7.4% from 2017 to 2022, which is expected to reach $172.6 billion by this time.

1

2

3

Fundingrequest

6

AN AMBITIOUS DEVELOPMENT STRATEGYIN 5 YEARS

Urodelia’s business model is based on two growth drivers:

1. THE DEPLOYMENT OF APA.VAC® ON THE VETERINARY MARKET

Urodelia’s strategic plan should make it possible to drastically accelerate the marketing of apa.vac® kits on the veterinary market in 5 years, moving from 90 units marketed in 2018 to 200 in 2019 and 3,800 in 2023. This represents a turnover of €2.5M.

The direct sale of apa.vac® kits to veterinary clinics will be carried out from France. Oncology veterinarians are responsible for preparing and administrating the vaccine to the animal. Urodelia plans to concentrate the action of its vaccine on the treatment of 5 canine cancers (Lymphoma B, Osteosarcoma, Mastocytoma, Squamous cell carcinoma, Melanoma) and 2 feline cancers (Fibrosarcoma and Carcinoma). The increase in sales will also be accelerated by a deployment in Europe.

Eight countries are targeted: France, Italy, Belgium, Germany, Hungary, the United Kingdom, Portugal and Spain. They represent a potential market of 35,500 new cancer cases in animals to be treated each year.

The global market for animal cancer therapeutics products from companies was estimated at US$183.3 million in 2017 and is expected to have a robust AAGR of 7.7% over the forecast period (2017-2025).

The increasing number of research grants to initiate various veterinary anticancer treatments should be a key factor in market growth of pet cancer therapies in the near future4.

4 https://www.coherentmarketinsights.com/market-insight/pet-cancer-therapeutics-market-1284

35 500NEW CASES OF ANIMAL

CANCER TO BE TREATED EVERY YEAR

VetenarymarketCancer

therapy

8 COUNTRIES IN EUROPE

53 MILLION2 TREATED PATHOLOGIES

43 MILLION5 TREATED PATHOLOGIES

2,5M€

EXPECTEDTURNOVER 2023

SYNOPTIQUE DE L’INDUSTRIE EN SANTÉ ANIMALE & CONCURRENCE

Industrie

Marché cible

Concurrence

Nos objectifs

Marché mondial Vétérinaire Thérapies anti cancer• 180 millions de dollars en 2017• +7,7% prévu de 2018 à 2025

Chirurgie/Chimiothérapie/RadiothérapieImmunothérapie • AcM Aratana USA 2018 (1 cancer)• Cytokines (1 cancer) MERIAL• Massivet anti tyr kinase (1 cancer) ABSci • Vaccins (recherche) KVAX

• 10 pays en europe• 43 millions de chiens et 53 millions de chats• 5 cancers chien et 2 cancers chat ????• 164 K cancers chiens et 13 K cancer chat ????• 20% éligibilité à APAVAC > 35 500 anx ???

> Potentiel de 21 M€ 2016 2017 2018 2019 2020 2021 2022 20230€

1M€

obje

ctifs

apa

.vac®

2M€

3M€

4M€

50 70 90 237

1601

4693

2963

693

7

5 Ciocca D.R. Frayssinet P. F. Cuello-Carrio D. A pilot study with a therapeutic vaccine based on hydroxyapatite ceramic particles and self-antigens in cancer patients. Cell Stress & Chaperones (2007) 12 (1), 33–436 EMA: European Medecine Agency 7 FDA: Food and Drug Administration (USA)

2. A MARKETING OF ITS THERAPEUTIC VACCINE IN HUMAN HEALTH

Today, Urodelia is at the beginning of a new development stage: initiate clinical trials implementation program on its therapeutic vaccine in order to confirm on humans the first conclusions obtained in animals.

Definition of vaccine use modalities at the different stages of the disease is also one of the objectives of the clinical trial program.

The program could start in Argentina, where Urodelia has already conducted a pilot study involving about 20 patients with encouraging results5.It will then continue in Europe. Spain, Italy and Switzerland. These will probably be the first countries in which the studies will be implemented, based on the progress of ongoing contacts in these countries. This will also result in the opening of new subsidiaries on site.

Urodelia plans to file a MA submission file to the EMA6 by 2021 and FDA7 in 2023, if the clinical trials confirmed the current assumptions from animal testing.

In order to ensure the successful implementation of its strategic plan, Urodelia has decided to set up additional human resources:

• Strengthen the operational management team in technical functions, production, finance and communication. About ten specialists will strengthen the team in 2019;• Establish a scientific committee of experts based on its research in the different areas of interest;• Establish public or private partnerships with converging research teams;

The opening of a pilot manufacturing site in France is also planned in the development plan of the company as well as in the medium term, the opening of a manufacturing unit in Argentina in 2020 to support the commercialization of its human vaccine in South America, before deployment in Switzerland, Spain and the USA. By 2023, the company expects that these sales in human health represent a turnover of 18M€.

Application for Marketing

Authorization to the EMA (European

Medicines Agency,)in 2021 and to the FDA (Food and Drug

Administration) in 2023.

Confirmation of the efficiency of its concept of an autologous therapeutic

vaccine for humans OU human medicine

Validation of the same totalsafety of the vaccine in humans

as in animals