Presentation of the 4th financing round of
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Presentation of the 4th financing round of CEBIOTEX October - December 2020 Objetives: • Finish Clinical phase 2a, activity, in adult Sarcomas (STS). • Initiate Clinical Phases in pediatric cancer, in collaboration with SJD Pediatric Cancer Center Barcelona. • FDA: ODD (Orphan Drug Designation) – preIND meeting
Company introduction • CEBIOTEX S.L., is a spin-off of the Sant Joan de Déu Hospital of Barcelona (HSJD) and the Polytechnic University of Catalonia (UPC). It started its activity in 2015, based at Pier01 Barcelona. Innovative SME and Technology-Based Company, focused on providing new and innovative solutions to the HEALTH Sector, with a high social and economic impact.. • The Cebiotex Project arises when Sara, a 6-year- old girl, leaves us after fighting cancer for 4 years. At that time, as a result of impotence in the fight against cancer, J.Bertran, founder of the Company, decided to investigate new drugs, based on biomembranes, The 1st drug that emerged from the CEBIOTEX® that provide medical solutions and specifically technological platform is “CEB-01”. Indicated for the solutions to cancer, including pediatric cancer. local control of the surgical beds after an oncological surgical intervention in the indication of Soft Tissue • The CEBIOTEX® platform is the first Bio-Material Sarcoma (STS). The efficacy results in animals and developed and patented by Cebiotex together with toxicology have been extremely promising in the Drug HSJD and UPC. It aims to provide an innovative and Discovery, in-vivo and Pre-Clinical Regulatory phases. effective solution to the "Local Drug Delivery" of drugs and biologics. The “First in Men” (Clinical Phase I, safety) just started, and results so far are that no toxicity or side effect • It is part of the Company's Mission to develop its appeared in the patients. products for the health of both adults and children. This round of funding should allow us to start the Clinical Phase 2a, activity, of CEB-01 with 21 adult patients in Soft Tissue Sarcoma
Table of contents 1. Product 2. Business model 3. Market/portfolio 4. Competitors 5. Intelectual property rights 6. Milestones achieved 7. Team 8. Shareholders 9. 4th funding round 10. Exit strategy Image: surgeons Lucas Krauel and José Antonio González after CEB-01 first implantation in human, August 2020
1. Product. Medical need – Cebiotex solution: CEB-01 When the Oncological Surgeon removes a cancerous tumor, there is a MEDICAL NEED to ensure that the surgical site is free of cancer cells. CEB-01 aims to SOLVE this medical need, with local control after oncological surgery, avoiding the viability of possible cancer cells that may have remained after the surgical intervention. This is implanted in the surgical act in just 4 minutes, and makes a therapeutic "RELEASE" WITHOUT TOXICITY, from minute 0 to 4-5 weeks, which are those in which there is no type of treatment at present. CEB-01 (categorised as a medicinal product) is formed by a 3D structure of nano-fibers of biocompatible and biodegradable material (PLGA), loaded with the cytostatic SN-38. The membrane, after releasing the cytostatic locally, biodegrades and disappears. SN-38 is extremely effective in 30 different types of cancer, including Sarcomas, Neuroblastoma, Ewing sarcoma, Glioblastoma, pancreas, ovary, breast, kidney, liver among other. January 2021, 4th financing round, Cebiotex summary
Product. CEB-01, extremely promising efficacy • The results obtained in the in-vivo tests, efficacy animal models, confirm the antitumor therapeutic effect of SN-38 loaded in the CEB- 01 membrane and released locally, in tumor lines of the Pancreas, soft tissue sarcomas Invivo efificacy Pancreas + and Ewing Sarcoma. chemotherapy • The data obtained at the beginning of Clinical Phase I in humans, so far, corroborates the release of SN-38 observed in animal models. • Observing a release, in humans, slightly more sustained over time, with respect to Invivo efficacy STS + animal models. Being able to arrive 4 - 5 chemotherapy weeks of therapeutic release . Invivo efficacy Ewing Sarcoma January 2021, 4th financing round, Cebiotex summary
Product. CEB-01 neither toxicity, nor side effects In GLP regulatory toxicity studies in animals, it was observed that: a) The histological findings are the typical changes described in the literature associated with the “bioresorption” of PLGA and are observed very frequently in operated patients in whom this material is used. b) No differences have been evidenced between membranes The Regulatory Toxicology Tests, developed at MPI loaded with drug and those Research (USA), have confirmed the results of non-systemic without drug, so it can be toxicity and foreign body reaction in local toxicology, which assumed that in the organs allowed us to initiate the Clinical Phases. studied, without underlying ✓ In the Clinical Phases in humans, started in august, 2020, pathology, SN-38 does not so far, no toxicity or side effect has been observed, produce discernible histological confirming the results obtained in animals. effects with optical microscopy study. January 2021, 4th financing round, Cebiotex summary
Product, Regulatory CEB-01: • CTA approved by the AEMPS; • Started the Clinical Study in STS indication ✓CTA approved by the AEMPS (Spanish agency of medicinal and health products). ✓ Obtained the Orphan Drug certification for CEB-01 "Orphan Designation or ODD", by the EMA / EC. ✓ The Phase I Clinical Study, safety, started with 9 patients at the Sant Pau Hospital in Barcelona. ✓ Incorporated into SAB Cebiotex the main world medical and surgical key opinion leaders in STS. The objectives of the current funding round (October 2020) are: o Complete Clinical Phase 2a, activity, in Sarcomas (STS), total: 21 adult patients. o Initiate the Clinical Phase in Childhood cancer, hand in hand with SJD Pediatric Cancer Center Barcelona with the approval of the PIP. o FDA: ODD (Orphan Drug Designation) – preIND meeting. January 2021, 4th financing round, Cebiotex summary
Product. Technology and manufacturing process: GMP granted CEBIOTEX has developed and manufactured its own production technology, with the collaboration of UPC. The manufacturing technology, property of Cebiotex are installed in the facilities of the pharmaceutical company PrasFarma, for the production of the Pharmaceutical Batches, which are delivered to the Sant Pau Hospital for their implantation in the patients of the Clinical Study. CEB-01 production process have been granted with the GMP Certificate from the AEMPS, mandatory requirement to start clinical trials. The CEBIOTEX® Technology Platform, GMP, is property of Cebiotex. Forming part of its industrial property, being the only one of its kind in the market. The objectives for the present funding round are: 1. Production of the required CEB-01 batches to complete the clinical objectives 2. Develop the industrial scalability of production equipment to adapt them to the production needs of clinical batches in phase IIb and the subsequent production required once CEB-01 is marketed. January 2021, 4th financing round, Cebiotex summary
2. Modelo de Negocio DRUG IN-VIVO PRE-CLINICAL PHASE I PHASE II PHASE III DISCOVERY DEAL CEBIOTEX's Business Model is based on developing its products until reaching a sub-license agreement (DEAL), or a sale with a Company interested in them. In the pharmaceutical sector, it is currently common to reach the DEAL once the products have reached Phases I / II of clinical development, that is, they have been tested in humans, with licensed or purchasing Pharmaceutical Companies developing the product up to Phase III , register and launch it on the market. a) LICENSE either: 1. First candidate CEB-01 2. CEBIOTEX® platform, applied to oncology 3. CEBIOTEX® platform, oriented to other medical applications (Antibiotics, Cell Therapy) b) M&A, totally or partially the Company. January 2021, 4th financing round, Cebiotex summary
Product portfolio (current and forecast) Cebiotex, due to its birth motivation, has the intention to support that the products that it develops for adults arrive to pediatric application DRUG IN-VIVO PRE-CLINICAL PHASE I PHASE II PHASE III DISCOVERY Adult Pediatric SOFT TISSUE NEUROBLASTOMA CEB-01 SARCOMA EWING SARCOMA GLIOBLASTOMA CEB-01 GLIOBLASTOMA MULTIFORME Other cancer DRUG indications DISCOVERY CEB-03 Infections, advanced therapies January 2021, 4th financing round, Cebiotex summary
CEB-01 market Our TAM (Total Available Market) considers global patients for potential first-line indications for CEB-01: STS, glioblastoma, lung, breast, colorectal, pancreas, and ovarian cancer worldwide. There are about 7,333,426 patients. Our SAM (Serviceable Available Market) includes all STS patients in the US and EU5. The main developed markets considered the US and EU5 (France, Germany, Italy, Spain, UK) account for 74% of spending on cancer drugs. These will also be our initial target markets (which will later expand to the rest of Europe, LATAM and Asia Pacific). Our SOM (Serviceable Obtainable Market) considers that based on our own “Patient Model” we can reach Cancer type New cases Deaths 5 years survival in 2028 (1st year of commercialization) an rates obtainable market of 1,525 patients in the EU5 and the USA, considering a patient participation of 2.5% STS 250.000 97.500 < 50% in new patients and 0.8% in patients previously Glioblastoma 296.851 241.037 20% diagnosed with STS. This proportion of patients will grow exponentially during the following Small cell lung 6% commercialization years with 2032 as the peak year 2.093.876 1.761.007 cancer (10% 2028, 20% 2039, 40% 2030 and 60% 2031 in new STS patients and 3% 2028, 7% 2029, 13% 2030 Breast 2.088.849 626.679 90% and 20% 2031 in patients previously diagnosed with Colorectal 1.849.518 880.792 63% STS). Pancreas 458.918 432.242 9% Ovarian 295.414 184.799 47% Total 7.333.426 4.224.056 January 2021, 4th financing round, Cebiotex summary
4. CEB-01 Competitors. Products already in the market Gliadel wafer: Indicated for the local control of the surgical bed after cranial surgery of glioma multiforme (does not apply to any other indication). PV $ 31,000 in US and € 10,000 EU. The Medicine Agencies authorize its use because it gives an additional life expectancy of 2 months to treated patients. Side effects and toxicity are very important, which implies that it is in clear decline in the market. Radiotherapy and Local Radiotherapy Manufacturers are investing in the development of new equipment that is more effective in radiating the areas to be treated in a more controlled and precise way. Faced with this type of therapy, it is worth noting the "terrible" side effects of radiation therapy. By all known. Likewise, the cost of acquisition (approx. € 20M depending on models) and maintenance of the equipment are very high. Very few hospitals can purchase equipment and prepare operating rooms to administer Local Radiotherapy. NBTX-TOPO: nano-particles formulated as a gel, which are previously introduced into the area to be treated by radiotherapy. Giving greater efficiency and reducing its toxicity. January 2021, 4th financing round, Cebiotex summary
CEB-01 competitors in early development Teams of researchers, worldwide, are working on the development of new products based on nano-technology, in order to deliver anti-cancer molecules directly to tumor cells. Examples: Prodrug and nanomedicine approaches for the delivery of the camptothecin analogue SN38. (Ian Wark Research Institute, University of South Australia, Mawson Lakes, SA, Australia; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), Australia). Nanoparticle delivery of an SN38. (The Children's Hospital of Philadelphia) 3D Superhydrophobic Electrospun Meshes as Reinforcement Materials for Sustained Local Drug Delivery Against Colorectal Cancer Cells. (Departments of Biomedical Engineering and Chemistry, Boston University, Boston). January 2021, 4th financing round, Cebiotex summary
Main drawbacks of the competitors already in the market: Current adjuvant treatments Main drawbacks § Toxicities to healthy tissues/organs. Systemic chemotherapy. § Low achievable drug concentrations at tumour sites. Drugs given 4 weeks after surgery. § Generate drug resistant mechanisms. External beam radiotherapy. § Destroys healthy cells, many very serious side-effects. Radiation given 2-3 weeks after surgery § Very costly: ~15.000€. Brachytherapy § Cumbersome administration, nearby tissue effects. Radioactive seeds or wires are placed in § Problems with radiation handling and toxicity, limited availability surgery site after resection § Very costly: 7.500€-19.000€ plus costs of the associated surgery. § Requires complex shielding to internal organs and surgical team. § Needs substantial training. Intraoperative radiotherapy § Damages to surrounding healthy cells/tissues. Radiation applied during surgery § Very costly (~15.000e). § Not common at hospitals (e.g. only 2 units in Spain). § Has begun to be studied for STS therapy but is not yet approved. Proton Therapy § Damages surrounding healthy cells/tissues. Radiotherapy that uses energy from § Very costly (30.000€-120.000€). positively charged particles (protons) § Considered one of the single most expensive medical devices. January 2021, 4th financing round, Cebiotex summary
Main drawbacks of the competitors currently in development phase Emerging treatments under Main drawbacks development § Their manufacturing process should generate serious issues in terms of polymer/solvent/active-substance interaction Wafers, hydrophobic meshes, hydrogels § The drug delivery rate is restricted by the polymer and nanofibers/ microcapsules degradation rate. Local delivery systems in early phase of § They usually lack a controlled release or mechanical stability. development § Very difficult to enter in medical practice in the next several years. § Very costly and require a technically difficult process. Cell immunotherapy § Its effects only observed in a limited number of patients. § No significant clinical benefit described in patients with STS. January 2021, 4th financing round, Cebiotex summary
CEB-01 competitive advantages CEB-01 is the first local control system for STS whose safety, tolerability and efficacy have been demonstrated and validated in preclinical regulatory studies. Furthermore, the first results from phase I of the First in Man clinical trial indicate that the patients did not have toxicity or postsurgical complications associated with CEB-01. Finally, we have our own GMP qualified machine for production, and the production process and final product are GMP certified. There is no other product like this on the market. CEB-01 exhibits the following best results compared to the existing state of the art: 1) Reduction of tissue margins to be removed from the tumor site. 2) Prevent mutilation surgeries that can drastically affect the functionality of a limb (for example, mobility in STS located within a muscle bundle). 3) Reducing the risk or even avoiding the recurrence of STS. 4) Decrease in the use of adjuvant radiotherapy and reduction of postoperative chemotherapy. 5) Reduction of general treatment costs. 6) Increase the life expectancy of patients and the quality of life by extending the time they are free of disease.
5. Intelectual Property Rights Protecting the product and local drug delivery system: Nonwoven membrane as a drug delivery Granted EP2644191B1 Applic. # EP12162338 Europe system; priority March 30, 2012 (08/2016) Nonwoven membrane as a drug delivery Granted US 9,561,190 B2 Applic. # 14/389,330 USA system (07/2017) Nonwoven membrane as a drug delivery Granted EP3108881B1 Applic. # EP16178875.5 Europe system (07/2017) Applic. # Nonwoven membrane as a drug delivery Granted CN104321051B China CN201380027164.7A system (09/2018) Nonwoven membrane as a drug delivery Granted CN108992432A Applic. # EP12162338.3A China system; divisional patent (12/2018) Beaded non-woven membrane as a PCT Inter- TBD Applic. # EP18382589 drug delivery system; priority Aug. 30, (08/2019) national 2018 Protecting the production system and method: Sistema y método para producir fibras Granted ES2534491B1 Applic. # P201300654 Spain por electro-hilado (03/2016) January 2021, 4th financing round, Cebiotex summary
6. Main milestones achieved by Cebiotex: ü CEBIOTEX® technology platform, patented in the EU, USA and China. ü Last PCT patent, granted in 2019, national phases: February 2021. ü ODD granted by EC / EMA in STS indication for CEB- 01. Renovated in August 2020 ü GMP certification granted to produce Matrix Implants, CEB-01. The technology and production processes are the property of Cebiotex, an industrial secret. ü CTA - Authorization to start Clinical Trials of CEB-01 in STS indication, Phase I (safety-dose), 9 patients, plus extension of 12 patients, Phase 2a (activity). ü Clinical trials started in August, 2020, at the Sant Pau Hospital in Barcelona, with extremely promising results. ü Cebiotex has raised € 4.3M since the start of activity in 2015, with 3 financing rounds. January 2021, 4th financing round, Cebiotex summary
7. Team Joan Bertran, MBA (CEO, Co-founder). Textile Industrial Engineer with more than 20 years of experience in the textile sector, mainly as Manager of Operations, but also in R&D and Product Development. Joan holds a master’s in Operations Management from EADA and an MBA from the Catalan Institute of Technology. José Antonio Tornero, PhD (CTO, Co-founder). PhD in engineering, mechatronics Engineer. Expert in electro spinning nanofiber production. Director of the Systems and Process Laboratory at the Institute for Textile Research (INTEXTER) at the Polytechnic University of Catalonia (UPC). Lucas Krauel, MD, PhD (CMO, Co-founder). A paediatric surgeon for over ten years, he studied medicine at the University of Barcelona and now leads the paediatric oncology surgery program at Sant Joan de Déu Hospital. He was a Fellow in Paediatric Surgical Oncology at Memorial Sloan Kettering Cancer Center. Jaume Mora MD PhD. Medical doctor, co-founder and Chairman in the Scientific Advisory Committee. Scientific director in the area of Onco-Hematologi of the Hospital Sant Joan de Déu de Barcelona. Alumni Pediatric Hematology and Oncology; Molecular Pathology. Memorial Sloan Kettering Cancer Center, New York. January 2021, 4th financing round, Cebiotex summary
Luc Marti, PhD, MBM (COO, shareholder). Holds a PhD in Pharmacology and a Master’s in Biotech Management. Was VP, R&D Operations at Artax Biopharma (USA) where he developed a therapy for autoimmune up to phase Ib. He cofounded Genmedica Therapeutics which developed an antidiabetic up to phase IIa. Over 25 years’ experience in pharmacology, of which 15 in drug development. Obtained 7 clinical trial authorisations. Imma Barber (CBO). Biologist, MBA, Postgraduate in Marketing Management and Specialized in Entrepreneurship and Innovation. Pharmaceutical executive with more than 20 years of experience in national and international senior positions on several therapeutic diseases – Oncology, Central Nervous System, etc – mainly in big pharma. Expert in Alliance Management had been involved in a list of product evaluations, due diligences, acquisitions, and co-promotions. Júlia Dotras (Communication Manager). Master’s degree in Media Practice for Development and Social Change at the University of Sussex. Work experience in digital health communications, creating and developing written and visual content, supporting a range of projects as well as digital and social media campaigns. Javier Merino PhD. (Legal Advisor), Secretario del Consejo Administración de Cebiotex y Cebfunding. Institut Superieur de Gestion, Paris. Dedicación parcial. Fundador y Managing Partner de Innovatech Law Firm. Anteriormente, Baker&McKenzie; Clifford Cance LLP; Osborne Clarke. Ha ejercido como docente en temas relacionados con la Protection of Industrial and Intellectual Property, Technology transfer and Licensing, Personal Data. January 2021, 4th financing round, Cebiotex summary
Advisors Xavier Luria MD. Cebiotex Drug Development Regulatory Affers Advisor. Senior consultant DDR Barcelona-London. He has been exposed to this area from a triangle perspective: as a hospital’s medical doctor with postgraduate training in internal medicine, as clinical researcher and management and leadership positions in pharma industry and, finally, as relevant European Medicines Agency (EMA) manager. Jordi Petit Salamó. Licenciado ADE y MBA, Esade (Barcelona). CEMS master, HEC (París). Cebiotex Financial Advisor. Twenty-five years of corporate finance experience, with a focus on investment and strategy, particularly for SMEs in development and expansion. Served as partner at Vantum Corporate, with past positions at KPMG, Akzo Nobel, Caixa Capital Risc and Oryzon Genomics. Antonio Perez, MD, PhD. Director of Development, Medical Director and/or Coordinator of the Scientific Committee in several pharmaceutical companies and/or biotechs, in oncology, infectious diseases, digestive, nervous system, orphan indications, among other areas, including international clinical developments, from phase 1 to 4 , registered and/or sold in the most important markets (Europe, USA, Asia, Africa). January 2021, 4th financing round, Cebiotex summary
Scientific Advisory Board Dr. Antonio López Pousa MD PhD Clinical Head & Senior Consultant Medical Oncology Dept. Hospital de la Santa Creu i Sant Pau de Barcelona. Dr. José Antonio González MD PhD Jefe Cirugía Servicio de Oncología Médica. Hospital de la Santa Creu i Sant Pau de Barcelona.. Dra. Ana Sebio MD, PhD Oncología Médica en Sarcomas. Hospital de la Santa Creu i Sant Pau de Barcelona. Dra. Silvia Stacchiotti MD PhD Works in Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori. She is the Principal Investigator and Coinvestigator of several trials on Sarcoma and GIST. She is a member of Soft Tissue & Bone Sarcoma Group, ESMO, CTOS and of ASCO. She has authored more than 100 scientific publications on sarcoma. Dr. Alessandro Gronchi, MD PhD Fondazione IRCCS Istituto Nazionale dei Tumori Milan. Memorial Sloan Kettering Cancer Center NY in 2002. He has been chair of the Sarcoma Service at the National Cancer Institute He serves as chair of the STS committee of the ISG, … ; he is a member of ESSO, ASCO, … He is one of the initiators of Trans-Atlantic RetroPeritoneal Sarcoma Working Group. He has authored more than 280 scientific publications. Dr. Robert Maki MD PhD FACP Sarcoma Program Lead; Director, Center for New Cancer Therapies; Monter Cancer Center, Northwell Health and Cold Spring Harbor Laboratory; Cornell University Medical College; Nueva York. January 2021, 4th financing round, Cebiotex summary
8. Shareholders The Cebfunding S.L. groups together the minority partners of Cebiotex. It is made up of 292 partners, focusing its activity solely on investing and collecting benefits from CEBIOTEX S.L. Joan Bertran is its Sole Administrator. The Institutions, the Sant Joan de Déu Foundation of Barcelona and the Polytechnic University of Catalonia, are part of the company CEBIOTEX S.L. The Ship2B Foundation, VC and 2 Family Offices are also part of Cebiotex. January 2021, 4th financing round, Cebiotex summary
9. 4th Financing round, funding needs: DRUG IN-VIVO PRE-CLINICAL PHASE I PHASE II PHASE III DISCOVERY January 2021, 4th financing round, Cebiotex summary
4th Financing round, conditions: DRUG IN-VIVO PRE-CLINICAL PHASE I PHASE II PHASE III DISCOVERY Value of the financing round:1,60M€. ✓ Closed with over financing of € 2.22 million, (December 2020) Once the investment round is closed with € 2.22 million of capital, the objective is to achieve a public financial leverage of at least 50%. a) Scientific Objective: Clinical Phase 2 (activity) in Sarcomas (STS), adults. (Hospital Sant Pau in Barcelona - Dr. Antonio López Pousa MD PhD). b) Business Objective: 1st window of opportunity for EXIT in 2023. Licensing, or, M&A. c) Strategic Objective: Initiate Clinical Phases in Childhood cancer, hand in hand with SJD Paediatric Cancer Centre Barcelona; ODD and preIND meeting in FDA. January 2021, 4th financing round, Cebiotex summary
10. Estrategia de Salida, EXIT Comparable License agreements that have been closed with pharmaceutical companies in recent years include: The exit strategy for investors, as mentioned Development in point 2. Business Model, is as follows: Year Company Buyer/license Deal Terms Stage a) LICENSE either: 2010 Biocompatibles BTG Market M&A. $ 283 M 1. First candidate CEB-01 2014 Nordion BTG Market Asset transaction. $ 200M. 2. CEBIOTEX® platform, applied to $2M in shares + $2M trade-payables oncology Azaya 2016 Citori Phase I/II + $ 100M cap +5year lease 3. CEBIOTEX® platform, oriented to Therapeutics manufacturing & dev. facility other medical applications (Antibiotics, Cell Therapy) $13M investment + $343 regulatory & 2017 CytRx Nantcell Phase III commercial milestones + royalties ( b) M&A, totally or partially the Company. Phase III In this 4th Funding Round, there is a 1st exit Karyopham Antengene Corp. Targeted $12M + $150M in milestones + 2018 opportunity estimated for 2023-24. Therapeutics royalties) therapy A set of Licenses is contemplated for CEB- 2018 Sirtex Varian Medical Market M&A. $1.3 bn. 01, or an M&A, estimating an approximate total value of about 60MM EUR and a return $20M (for minority stake) + up to Taiwan LiposomeJixi Agrosino for investors x10. 2018 Phase II $50M before drug approval + $60M Company (TLC) Biotech milestones Taiwan Liposome 2019 3SBio R&D - Phase I $25M/product+ milestones+ royalties. Company (TLC) January 2021, 4th financing round, Cebiotex summary
Contacto: CEBIOTEX S.L. Joan Bertran Llavina (CEO) Pier01, Barcelona Tech City Email: jbertran@cebiotex.com Plaça de Pau Vila, 1 Email: info@cebiotex.com 08039 Barcelona
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