A Partnering opportunity to create a new healthcare market

March 2020

Summary of Partner ing Opportuni ty • Biohope is an early commercial stage R&D company dedicated to the development of p r e c i s i o n

m e d i c i n e I V D tools and unique patient knowledge for chronic inflammatory conditions. Founded in 2015, it has received 3.8M EUR funding through the European Commission’s H2020 program, more than 2M EUR through private funding . It employs 19 professionals in R&D, IT, Medical Affairs, Financial, Legal, Regulatory, Quality Control and BD&L.

• Biohope lead product, I m m u n o b i o g r a m ® , is a novel and unique, patented in vitro diagnostic device which generates a report for the physicians to optimize each individual immunosuppressive therapy. It is a combination of a bioassay and database analysis tools.

• I m m u n o b i o g r a m ® i n Kidney Transplantation is the first product from our technological platform:

• A National and an International clinical study (performed in Spain, USA, Germany, Denmark, Poland) has demonstrated the effectiveness of Immunobiogram®

• Patent published for EU, PCT ongoing; ISO 13485 in Q4 2019, CE mark by Q3 2020

• RUO sales in 2020.

• Current Pipeline: Based on Immunobiogram® technology, adaptation is ongoing for Rheumatoid Arthritis , and planned for Nefritis Lupica, and for any patient on IMS.

Biohope & Partners

What is Biohope seeking from a Partner:

• A worldwide/local partner to fully achieve with Immunobiogram® the full market potential in renal transplant.

• A worldwide/local partner to fully develop with us our pipeline in autoimmune diseases, provided there is a huge market potential.

IMMUNOBIOGRAM® RENAL TRANSPLANTImmunobiogram® - a novel IVD Device for a Smart Personalization of

Immunosuppressive Medication

1 USRDS Annual Report 2018

The Prob lem:Graft loss and resistance to current medications is still a major problem in KT

Near 50% of patients will suffer the lost of the kidney graft at 10 years of KT 1

The graft immune rejection is the most frequent cause of graft lost, and to avoid it patients take a continuous treatment with immunosuppressive drugs (IMS), which are associated with severe adverse events

The resistance to these immunosuppressive drugs is related to a bad clinical evolution

Close to 60% of high risk patients may be resistant to their current medication, and will need a change in medication and/or upgrade in dosages

The sensitivity to these immunosuppressive drugs is related to a good clinical evolution

Close to 80% of low risk patients may be sensitive to their current medication, allowing for downscaling most sensitive drugs

Currently IS selection and adjustment is done empirically by physicians, based only on clinical guidelines and IMS pharmacokinetic levels and appearance of IMS side effects.

Sometimes patients with KT can receive an inadequate or insufficient IMS treatment, having a higher risk of graft rejection. On the other hand, patients may receive more IMS treatment than needed, presenting a higher risk of severe side effects like cancer or opportunistic infections.

Physicians think that there is great room for improvement.

The Problem: Today’s treatment practice is suboptimal

The Solution: IMMUNOBIOGRAM®

Better clinical outcomes

Reduct ion of s ide e f f e c t s

Improved patient quality of life

Reduct ion of health costs

A simple, proven , and unique blood-based in vitro diagnostic device enablingphysicians to provide a P E R S O N A L I Z E D immunosuppressant therapy by selecting the optimal combination of drugs and dosage.

Competitive Environment: IMMUNOBIOGRAM®

capabilities are unrivaled

provides information about global excess or

scarcity ofimmunosuppression.

IMMUNOBIOGRAM® is the only IVD test allowing the selection of theoptimal immunosuppressive therapy (combination of drugs / dosage)for each patient.

Which drugs? Which doses? For Renal T ransplants

Rheumatoid Arthritis

Current Standard of Care*: Today’s monitoring practice ismissing important, complementary and actionable information.

* According to “KDIGO Renal Transplant Guidelines”

Patients Follow-up: TIMING*

MONTHLY between 7-12 months after transplant

QUARTERLY > 1 year after transplant

Patients Follow-up: OBJECTIVES

To check for renal damage & rejection signals

To check for adverse AEs

X WHAT DRUGS?

X WHICH DOSES?

Plasma Levels(pharmacokinetics)

Change & AdjustIMS TREATMENT

Standard Monitoring New PersonalizedApproach

NON ACTIONABLE

• Serum creatinine• Glomerurar filtration rate• Proteinuria, albuminuria• Ecography• De novo DSA• Virus BK• AE check up• Biopsy (specific

circumstances)

ACTIONABLE

(pharmacodynamics)

The Techno logy: Overall process

User Report for Doctors: Self-explanatory, recommendations. Signed by Immunology Specialist

Blood sample

Biological process BIOHOPE SOFTWARE

(Algorithm & Database)Web page

Says if patient is sensitive or resistant to medication.

Resistance Index formonitoring

Laboratory - Fluorimeter

The Product : Blood immune cells culture + software/database

1 2 3 HOSPITALCENTRAL LABS

The Product : Clear and Useful Patient Report

Two distinct parts:• Identification of patient &

hospital, with key clinical data

• Test Results: Resistance MAP (all IMS) & Resistance Ladder (current medication), with expert comments

IMBG

YEARLYKIDNEY TRANSPLANTATION

6 MONTHSPOSTRANSPLANT

12 MONTHSPOSTRANSPLANT

ANY MOMENT IF:Any rejection signal

dnDSA +dd-cfDNA

Renal Function DeteriorationPosit ive Biopsy

IMBG IMBG

IMBG

Monitorization frequency with IMBG will depend upon the patient profile. Any patient with >1 year after transplant is suitable.

• An IMBG should be done to all patients at baseline, once the immunological system has got stabilized after the induction therapy (6 months post KT).

• In the maintenance phase it is estimated 2 IMBG yearly in high immunological risk patients and 1 in low risk patients. • In patients who present any kind of rejection signals • Before treatment adjustments

The Product ( I I I ) : When to use it

Clinical studies in KT: IMBG has been clinically tested in patients after more than one year of KT, as the major challenge for clinicians

to improve graft survival after one year reducing the risk of rejection

BH Pilot Study 2015: proof of concept study in 70 patients with KT, 2 Clinical Hospitals, Spain.

TRANSBIO Study: international study with 200 patients with KT, 9 European and US Clinical Hospitals

Objectives:

• To ensure that IMBG is ready for implementation in the clinical laboratory and reproducible.

• To compare IMBG in KT patients with good vs bad clinical evolution.

Pharmacoeconomic Study: Health Care Savings in Kidney Transplanted Patients by the use of the novel IVD IMMUNOBIOGRAM©

• To estimate the economic impact (savings) that the use of Immunobiogram in KT patients can generate to the

Spanish National Health System (NHS) by helping physicians to personalize the immunosuppressive treatment in

their patients

The Product : Finished studies in Renal Transplant

TRANSBIO CLINICAL CENTERS

• Prof. Julio Pascual. Medical Director and Head of Nephrology Department and Kidney TransplantationProgram Hospital del Mar, Parc de Salut Mar. Barcelona Spain.

• Prof Daniel Serón. Head of Department of Nephrology at Hospital Vall d´Hebron (Spain).

• Dr. Carlos Jimenez. Section Chief of Transplantation. Department of Nephrology at Hospital La Paz (Spain).

• Prof José María Portolés. Head of Department of Nephrology at Hospital Universitario Puerta de Hierro (Madrid, Spain).

• Prof Amado de Andrés. Section Chief of Transplantation. Department of Nephrology at Hospital 12 de Octubre (Spain).

• Prof. Oliver Witzke. Head of Infectious diseases. Universitätsklinikum Essen.Germany

• Prof. Soren S. Sorensen. Head of Department of Nephrology. Rigshospitalet. Copenhagen (Denmark).

• Prof. Magdalena Krajewska. Head of Dept. of Nephrology and Transplantation Medicine. Wroclaw Medical University, Poland

• Prof. Camille Kotton. Head of Department of Infectious diseases. Massachusetts General Hospital, Harvard Medical School (Boston).

27th International Congress of the Transplantation Society, TTS 2018 (1-5th July, Madrid) :• “IMMUNOBIOGRAM®: A Novel Precision Medicine Tool to Help Guidance of Immunosuppression in Renal Transplantation. Results of “BH-Pilot 2015” Proof-of-

Concept Clinical Study” (L&L session)

5th European Congress of Immunology, ECI 2018, (2-5th September 2018, Amsterdam):• ‘IMMUNOBIOGRAM® a new immunological tool to personalize immunosuppressive therapy in kidney transplant recipients”. (Oral presentation)• “IMMUNOBIOGRAM® as a diagnostic assay for detection of resistance to immunomodulatory treatment in patients with chronic inflammatory diseases” (poster)

Basic Science Transplantation Congress BST 2018 (11-13 October 2018, Rotterdam):• “IMMUNOBIOGRAM®: a new immunological tool to personalize immunosuppressive therapy in kidney transplant recipients”.

American Transplant Congress ATC 2019 (1-6th June 2019) • “IMMUNOBIOGRAM®: A New IVD Immunoassay To Test The Sensitivity Profile Of Kidney Transplant Recipients To Immunosuppressive Drugs: Further

Results From BH-pilot Study” (Award Poster)

European Society of Organ Transplantation ESOT 2019 (Sept 2019, Copenhagen)• “Analytical robustness and clinical consistency evaluation of a new in vitro diagnostic BIOtechnological immunoassay to help decision-making in adjustment of

immunosuppressant therapy for kidney TRANSplantation”

International Society for Pharmacoeconomics and Outcomes Research ISPOR 2019 ( 2-6 November 2019, Copenhagen) • “Economic evaluation of an in vitro diagnostic assay (Immunobiogram) in the selection and dose titration of immunosuppressive therapy (IS) in kidney transplant

patients in Spain. “

BH-Pilot Study Publications: Well-known International Transplant Congresses

TRANSBIO Study Publications 2020: Well-known Transplant Congresses

Dr./a. Teresa Diez teresa.diez@biohope.eu Es un placer comunicarle que su trabajo, con referencia Nº 28 y título: Inmunobiograma, un nuevo inmunoensayo de diagnóstico in-vitro para facilitar el ajuste individualizado del tratamiento inmunosupresor en trasplante renal: Estudio TRANSBIO. Ha sido aceptado para su presentación como comunicación POSTER en el 6º Congreso Nacional de la Sociedad Española de Trasplante, que tendrá lugar en Málaga, en el Palacio de Ferias y Congresos de Málaga (FYCMA), los días 8, 9 y 10 de mayo de este año 2020.

SPANISH SOCIETY OF TRANSPLANTSAMERICAN TRANSPLANT CONGRESS

Results: Supporting the utility of Immunobiogram®

Key results of the National and International clinical studies conducted indicate that Immunobiogram® :

• Provides an individualized patient response pattern to the available immunosuppressive medication. Sensitivity/resistance profile can be determined in each patient for each of the drugs and doses tested.

• Allows to identify patients with bad prognosis due to low sensitivity tospecific immunosuppressants. Correlation between resistance and bad clinicaloutcome.

• Resistance Index: Each incremental point increases by 28% the probability ofhaving a bad clinical outcome (p=0,02)

•

Key results of the Expert Panel Consultation Meetings:• 90% would use the Immunobiogram®• The Expert Panel expects that the use of Immunobiogram® would reduce

kidney rejection by 50%

Key results of the Pharmacoeconomic model study: • The routine use of the Immunobiogram in patients one year after their kidney

transplant would reduce the risk of renal graft failure and AEs associated with IMSs with considerable savings for the NHS.

• Hospitals from Madrid and Barcelona (Spain), Boston (USA), Essen (Germany), Copenhaguen (Denmark) and Wroclaw (Poland) have been involved in theImmunobiogram® clinical studies so far.

Endorsements: Medical Leaders, Health Ministry, EU KT

“With this product the Beneficiary will revolutionize kidney transplantation market and will become a key player in this system.”

(2018 European Commission Report)

IP & Trademark:EU Patent granted, PCT ongoing in KT

TRADEMARK GRANTED EU PATENT GRANTED

PCT & US ONGOING

Regu la tory Status: ISO & CE Markin KT

READY BY 3Q 2020ISO GRANTED

Manufactur ing & C l in i ca l Lab serv icemode ln KT

CLINICAL LAB CERTIFICATION BY 3Q 2020MANUFACTURING LICENCE BY 3Q 2020

Business Model

Partners

B i o h o p e C o reB usiness

• R+D• IP & Regulatory• Medical Af fa i res • Business Dev.• IT

USA: Advanced conversations with 3 CompaniesEU: 1 Term Sheet signed in Italy, advanced conversations with 2 CompaniesLATAM & APAC: Starting conversations for Brasil, Mexico, Israel and Japan

IN EUROPE AMERICA & APAC

IMBG AS A SERVICE IMBG AS A KIT/LDT

MANUFACTURING

PROCESSING IMMUNO ASSAY

REPORT ELABORATION

MARKETING-SALES-ACCESS

MANUFACTURING

PROCESSING IMMUNO ASSAY

REPORT ELABORATION

MARKETING-SALES-ACCESS

Partner

Partner

Partner

Current Revenue: RUO Sales 2020-2021blem in KT

MADRID

MONTERREY

WARSAW

SAO PAULO

LILLE

BOLONIA

CALIFORNIA

TEL AVIV

TOKIO

IN PROGRESS

IN CONVERSATION

Management and Staff (1)

Dr. Isabel Portero FOUNDER & CEO

MD PhD in Innovative Medicines, expert in Biomedical developments at both Biotech and Pharma Industry with a strong transversal experience across functions and Departments. Designed and leaded EMA-granted scientific plans and created & leaded several teams. She has served as Medical and R&D Director for MSD and Roche. She has practiced medicine and taught at the University.

Ricardo Brage BUSINESS DEVELOPMENT DIRECTOR

Economist, with MBAs from the University of Houston, ESADE, and the University of Chicago. He has extensive experience in senior management positions in pharma companies like Sanofi and MSD, in business development and institutional relations, and as General Manager of Sanofi Pasteur - MSD Spain 2011-2017 (vaccine JV). Second largest individual investor in Biohope, after the family office that provided the seed capital.

STAFFFrancisco Tejera FINANCIAL DIRECTOREconomist with broad experience in the Pharma sector (financial and quality areas). Project Manager Professional (PMI) and ITIL/ISO 20000 Practitioner certificate (APMG). Deep background in finance, SOX, tax law and GxPquality guidelines regulations. More than 20 years of experience as CFO in multinational environments.

Management and Staff (2)Gerardo Entrena LEGAL AFFAIRS DIRECTORLawyer with twenty-five years providing legal advice in Legal Firms and large companies of regulated sectors, mainly telecommunications and energy. His professional background enables to offer an overall strategic vision of companies, outstandingly in civil matters and corporate matters, and solution of legal problems through Alternative Disputes Resolution and, if necessary, in High Courts.

Carlo Zanotti TECHNICAL AND PRODUCT DEVELOPMENT DIRECTOR

Carlo holds a Degree in Biological Science from the Autonomous University of Madrid and is specialized in biochemistry and molecular biology. He also holds a Master’s Degree in Healthcare and Pharmacy Business Administration. Carlo Zanotti has developed his professional career in the field of diagnostics for more than 17 years. During his career, Carlo has held different marketing positions in laboratory diagnostics and biotechnology companies such as Chiron Diagnostics, Bayer Diagnostics, and Miltenyi Biotec. Since 2004 he has held different product development positions for a new treatment based on the use of stem cells from adipose tissue, an inmmunoassay based test and a first in class Raman spectroscopy based IVD device.

Dr. Teresa Díaz. MEDICAL DIRECTOR

She holds a Medical Degree from Autonoma University and the speciality of Family Medicine in Hospital Ramón y Cajal, both in Madrid, Spain. She is also Magister Public Health by the Technische Universität in Berlin, Germany. Teresa has worked for some years in the clinical practice and has built up an extensive experience in management positions in pharmas like GSK, Pfizer, AstraZeneca and Merck in the area of Medical Affairs, in Spain and abroad.

STAFF

Five Reasons to Partner with BIOHOPE

Potentially huge ROI by creating new very

powerful tools to manage chronic

inflammatory conditions.

B reakthrough precision medic ine

product adding value to physicians,

patients and payers. Helping

millions of people!

Sol id and focused business model , managed by a

strong pro fessional and highly committed

Team

High level of scientific partnersand Heal th Care

Institutions.

1 2 3 4 5

Large, growing, profitable, and

unsatisfied markets, with non-

exist ing competitors

PRECISION MEDICINE GIVING HOPE