strictly confidential information folder 2020 © eurrus ... · year 2012 2014 2018 2020 2021 2022f...

Strictly Confidential Information Folder 2020

© EURRUS BIOTECH GMBH

© EURRUS BIOTECH GMBH 2

*

1. Executive Summary………………….p. 3-6

2. Company ………………………………….p. 7-12

3. Product Description …………………p. 12-16

4. Development Plan …………………..p. 17-20

5. Competitive Analysis ……………….p. 21

6. Market Analysis ………………………..p. 22

7. Budget/ Investment Proposal…..P. 23-26

Project Name: “XC-8”

* Medical indication: Eosinophilic Asthma Bronchiale

* EURRUS BIOTECH GMBH is granted a worldwide and unlimited development and exploitation patent license from Pharmenterprise LLC for XC-8 including patent utilization/sale with the exception of Russia and CIS.

* Patent is granted in Russia (RU 2562773) in 2013/ worldwide application ongoing since 2014 (PCT/RU2014/000264) by Pharmenterprise, LLC Moscow

* The target for this project is the clinical development Phase III up to the international registration of the active ingredient XC-8

* Already present (approved or confirmed) is the completed preclinical development in accordance with international EMA standards, CP I and CP IIa

* Next step: CP IIb to strengthen eosinophilooic efficacy data and prove enhanced efficacy in 200mg range.

* The aim is an exit to a strategic partner/investor in 2-3 years.

3© EURRUS BIOTECH GMBH

*Completed Development Steps:1. Preclinical Development and Documentation

2. Safety (Toxicological) Studies

3. Galenic Development incl. GMP upscale

4. Clinical Phase I (completed 2017)

5. Clinical Phase IIa (completed 2018)

*Outstanding Development Steps:1. Clinical Phase IIb (planned 2019/20)

2. Genotoxicity Study/ Reprotox Study

3. Clinical Phase III (by an strategic partner)



Discovery Preclinic

Phase I Phase IIa Phase IIb Phase III

Roadmap XC-8

Year 2012 2014 2018 2020 2021 2022f

• Partnership withPharmaenterprise LLC, Moscow

• New ownership in Austrian entity (EURRUS BIOTECH GmbH, Tulln)

• €2.7m financing secured

• Successful Completion ofCP ICP IIa

• Joint EU/ Russian Study • Sponsor: EURRUS

• 80% success ratio (= industry standard)

• Capital demand app. €10m in phase IIb

• With strategic partner


* Project USP:

* Until 2020 all development steps completed and documented according to EMA conform Investigational Brochure

* Substantial reduction of the attrition rate after having successfully completed CP IIa

* Project in the highly valued biotech sector


* Product USP:

* Therapeutic effect statistically proven for * eosinophilic Asthma

* non responding high IFNgamma patients which do not have any treatment at the moment

* No side effects proven

* Easy to use by oral administration compared to sprays, etc.

* Substantial cost reduction in production versus aerosols

* High contribution margin expected


* Oral drug for treatment of eosinophilic non responding high IFNgamma asthma patients Targeting patients which do not have any treatment at the moment except very costly antibody treatments

* Oral drug for treatment of severe uncontrolled eosinophilic asthmaCompetitive advantage over biologics due to oral administration route, low cost of goods and high safety

* Oral drug for treatment of partly controlled eosinophilic asthmaTargeting less severe paediatric patients that are not yet eligible for biologics due to invasive mode of administration, high cost and side effects of the latter

* Oral treatment of asthma for athletesMost existing asthma medications are banned for doping reasons.


*

Ownership structure

HesostenikHoldingGesmbH

JosefRagger

HerbertRoth

AT – Tulln

EberhardDürrschmid

7 otherminority

shareholders

• EURRUS Biotech GmbH ("Eurrus") is incorporated inTulln, Austria

• Founded in 2006 the existing partners joined in 2012

• The shares are held by Hesostenik HoldingGesmbH, Mr Ragger, Mr Roth, Mr Dürrschmid, andseven other minority shareholders

• Eurrus has concluded a patent licenseagreement with Pharmenterprises, LLC,incorporated in Moscow, Russia, for a worldwideand unlimited development and exploitationpatent license including patent utilization / salewith the exception of Russia and CIS

29.07% 23.04% 18.54% 9.61% 19.74%


*

Name Function Experience

Helmut Schmutz, Mag.iur. CEO Entrepreneur, many years experience in starting anddeveloping companies in the field of Biotechnology, Medical Devices, Functional Food

Julia Romanova, Dr. R&D Biochemist, more than 20 yearsexperience in development ofpharmaceutical ingredients

Boris Ferko, Dr. R&D, Immunology PhD in Microbiology, since 1989 involved in multiple scientificbiochemical projects


*

Name Experience

Wolfgang Pohl, Prof.Dr.Prim. Medical Head of Department of Pneumology at KH Hietzing, Vienna; Professor of University of Vienna, Member of European Respiratory Society, German Society for Pneumology and several otherinternational scientific societies related withPneumology; several publications

Michelle Epstein, Prof.Dr. Head of Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Doctor of Allergy and Clinical Immunology; several publications


*

Hesostenik Holding Gmbh 29,07% 32.769,89

Hr. Roth 18,54% 20.896,46

Hr. Ragger 23,04% 25.973,35

Hr. Knoglinger 3,56% 4.012,91

Hr. Schneller-Scharau 3,74% 4.211,02

Hr. Dürrschmid 9,61% 10.831,23

Hr. Krczal 5,55% 6.250,57

Hr. Kolbabek 2,37% 2.673,50

BrainCap Beteiligungs- und Consulting GmbH 2,12% 2.389,39

Elbrus Holding GmbH 1,53% 1.725,00

Ablinger Sports GmbH 0,88% 1.540,00

100% 112.723,86

*

* Patent Licensor:

* LLC “CHEMIMMUNE“, Russia

* Drug Substance Producer:

* Farmak a.s., CfR

* Drug Product producer:

* Hennig Arzneimittel GmbH&Co KG, Germany

* Packaging and release:

* Nuvisan GmbH, Germany

* CRO:

* FGK Clinical Research GmbH, Germany

* Clinical Partners:

* ITEM, Hannover

* KH Hietzing, Vienna


XC8* Chemical formula:

1-[2-(1H-imidazol-4-yl)ethyl]piperidine-2,6-dione

* Synonyme: Histamine Glutarimide* CAS number : 1464897-15-1* Description: a white to almost white crystalline powder with a brown-

yellow shade.* Solubility: soluble in 96% ethanol and water, sparingly soluble in

acetonitrile* Melting temperature : 148 - 152°C (Koffler apparatus)

*14© EURRUS BIOTECH GMBH

Monocyte

Macrophage Neutrophil

Th1

Mastcell

B-cellMCP-1 MCP-3

MCP-4MCP-1

Dendritic cell

MCP-1

Eosinophil

XC8 XC8 XC8Broncho-constrictionMuscle hypertrophy

Bronchial hyperreactivityMucus hypersecretionMucosal edema

Steroid-resistanceTissue destructionAirway wall Thickening

* Pathogenesis and MoA© EURRUS BIOTECH GMBH

*16

• XC8 inhibits QPCT (glutaminyl cyclase) – enzyme that catalyzes maturation of MCP-family chemokines. Without XC8, QPCT catalyzes maturation of MCP chemokines which in turn facilitates inflammation. Immature forms of cytokines (i.e. not pyroglutaminated) undergo proteolysis and possess significantly reduced chemotactic activity.

• Thus, blockade of QPCT by XC8 leads to decrease of migration of eosinophils, decreased degranulation of mast cells and reduced bronchial hyperreactivity

• On the model of Sephadex-induced migration of eosinophils in rats, XC8 decreased the content of eosinophils in the BAL fluid, 2.6-6.4 times. The obtained results confirmed the ability of XC8 to reduce the migration of eosinophils

• XC8 also reduces hyperactivity of the lungs and respiratory macrophages in animal asthma models, the obtained results show that the determined activity is one of anti-asthmatic mechanisms.


17

Treatment GroupEosinophilic asthma? (Eos >300, cells/µl)

FEV1, lMean difference(95% CI)

FEV1, % predicted, absolute changesMean difference (95% CI)

FEV1, % predicted, relative changesMean difference (95% CI)

XC8 100 mgEos (n=12)

+0.39*(0.18; 0.59)

+11.33*#(3.61; 19.06)

+16.07*#(5.29; 26.85)

Non-Eos (n=17)+0.14

(-0.03; 0.31)+4.59

(-0.13; 9.31)+6.54

(-0.28; 13.36)

Placebo

Eos (n=10)+0.07

(-0.21; 0.36)+1.2

(-6.58; 8.98)+1.51

(-8.94; 11.96)

Non-Eos (n=18)+0.18

(0.03; 0.33)+5.89*

(0.99; 10.79)+8.37*

(1.43; 15.32)

* - differences are statistically significant compared with baseline FEV1 levels in patients with the same eosinophilic status, p <0.05, Uncorrected Fisher's LSD# - differences are statistically significant compared with placebo in patients with the same eosinophilic status, p <0.05

* XC8 value proposition #1: Treatment of eosinophilic asthma – improvement in FEV1


18

Cytokine production by PBMCs of patients with Steroid Sensitive (●) and

Steroid Resistant (☐) asthma1

1: Chambers et al, J Allergy Clin Immunol 20152: Yang M., J Immunol. 2009

• “…cooperative signaling between IFN-gamma and TLR4/MyD88 constitutes a previously unrecognized pathway that regulates macrophage-dependent steroid-resistant airway hyperresponsiveness2“

• Hypothesis: high IFN-gamma results in resistance to corticosteroid therapy

* XC8 value proposition #2:Treatment of steroid-resistant, high-IFN-gamma asthma


19

Higher IFN level predicts worse response to SoC, but not to XC8

XC8 effect is dependent on IFN-gamma level

* XC8 value proposition #2: Treatment of steroid-resistant, high-IFN-gamma asthma


20

XC8 improves FEV1 values in

high IFN-gamma patients



21

XC8 improves FEV1 values in high IFN-

gamma patients



22

Eosinophilic Non-eosinophilicSteroid-resistant (IFNγ>100 pg/ml)

0,50 L#

PP0,21 L

NPSteroid-sensitive (IFNγ<100 pg/ml) 0,13 L

PN-0,15 L

NN

XC8 100 mg over placeboFEV1 relative

improvement, L

# - statistically significant, XC8 100 mg vs placebo, Week 12 – Week 0PP – Eos+, IFNγ>100 pg/ml; NP – Eos-, IFNγ>100 pg/mlPN – Eos+, IFNγ<100 pg/ml; NN – Eos-, IFNγ<100 pg/ml

* XC8 value proposition #3: Treatment of Eos+, IFN-high (steroid resistant) patients


23

* XC8 value proposition #4: prevention of viral asthma exacerbations


1. Mild-to-moderate eosinophilic asthma: XC8 100 mg significant increased FEV1 by 16,1% or 0,386 l from baseline

2. Steroid-resistant [high-IFN] asthma: XC8 improves FEV1 values in high-IFN patient group (+8,7%) which showed decrease in FEV1 on basis therapy (-3,1%)

3. Eosinophilic, steroid-resistant asthma: XC8 provides strong therapeutic benefit (improvement in FEV1 0,36 L after 12 weeks, relative improvement in FEV1 0,50 L vs Placebo, p<0,05 difference)

4. Risk of respiratory viral infections in asthma patients: ХС8 100 mg decreases relative risk of URVI in asthmatic patients (RR=0.34, p<0.05)

* XC8 value propositions summary



*

CP IIbGenotoxReprotox

CP III

2020 (12-18 months) 2021 2022 2023


*

A Phase-IIb multicenter, randomized, double-blind, placebo-controlled clinical trial to assess efficacy and safety of 100/ 200 mg XC8 in patients with partly controlled eosinophilic asthma

Sponsor: Eurrus Biotech GmbH

Study Location: Medical Centers in EU, Medical Centers in Russia

Study Date: 2019-2020 (18-24 months)

Study CRO: FGK Clinical Research, Germany; i-pharma LLC, Russia;

Study Design:

* To evaluate the effect of XC8 100 mg and 200 mg vs. Placebo on the absolute change in pre-bronchodilator forced expiratory volume in 1 second (FEV1) in mL at Week 24 from baseline in patients with eosinophilic asthma and high IFN gamma

* Number of Subjects: 225 patients: Non-smoking adults from 18 to 65 years old with confirmed clinical diagnosis of eosinophilic asthma.


*

Competing Products:* Fasenra (Benralizumab/ Antibody)

* Advair/Seretide (fluticasone propionate and salmeterol)

* Symbicort (budesonide/formoterol fumarate)

* Singulair (montelukast sodium)

* Timapiprant (CRTH2 antagonist)

* Astra Zeneca’s Fasenra has to be seen as biggest competitor (market approval 2018); intravenous treatment with antibodies which is seen as state of the art approach despite extremely high treatment costs; target is complementing treatment to highly dosed corticoids

* Nevertheless, Advair, Symbicort and Singulair are close to expiring their patents 2010-2018. In the five largest European markets, the Seretide patent expired in 2013; the patent expired in the USA in 2010.

* Teva Pharmaceutical Industries has reported major regulatory hurdles in the registration of the generic version of Advair. Despite this, the market is likely to be followed by generic products for Advair / Seretide, Singulair and Symbicort after 2014

Asthma therapy market, Forecasts, GlobalData, Research pipeline


*

* The global asthma therapeutics market accounted for USD 20.7 billion as of 2015 and is anticipated to reach USD 56 billion in 2025.

* According to the estimates published by the Global Initiative for Asthma (GINA), in the year 2013, around 300 million patients globally were reported to be afflicted with this disease and the number is expected to grow in the coming years.

* North America dominated the overall asthma therapeutics market in terms of revenue share in 2014 at over 50.0%. The European market is set to witness steady growth mainly due to the presence of a considerably developed pharmaceutical industry and the significant demand for asthma-relatedtherapeutics. With the increasing geriatric population, susceptible to acquire respiratory conditions, such as asthma, will further support to the growth of regional market in EU and U.S.

Grand View Research, 2018Research and Markets, 2018


*

Budget XC-8 - Eurrus Biotech GmbH

2020 2021

Administration 27.300 27.846

Scientific Employees 84.084 85.766

Regulatory+Projektmanagement 145.600 148.512

CEO 97.110 97.110

CFO 42.000 42.840

Personalaufwand 396.094 402.074

CRO, Study Surveillance 1.500.000 1.000.000

Geno-, Reprotoxstudy 1.000.000

External Study costs, Services + drug product 3.500.000 2.500.000

Legal Advisor 40.000 30.000

Office/Laboratory 49.000 50.470

Structural Cost 90.000 92.700

Sum 5.575.094 5.075.244

Grand Total Equity/ Funding 5.575.094 4.075.244 9.650.338


*

*Existing Investor group is looking for Investors for thefinalization of product development (CP IIb) and preparation of next stages/exit.

*Budget for finalization CP IIb: € 10.000.000,-

*Current company evaluation based on market value and project development status


*

* EURRUS Biotech GmbH ("Eurrus Biotech", "Eurrus", or the "Company") and its shareholder have authorizedand requested Mag. Helmut Schmutz to distribute this Information Memorandum (the "Memorandum") to assistrecipients in deciding whether to investigate a possible investment comprising up to 100% of the shares of theCompany.* This Memorandum is not to be taken to be a recommendation to purchase a shareholding in the Company. It doesnot constitute an offer or invitation for the sale or purchase of securities and it is not an offeringmemorandum and neither this Memorandum nor anything contained herein is sufficient to engage in a purchasecontract.* The Memorandum is intended as a guide only and does not purport to contain all information the recipient mayrequire in an investigation of the transaction. No representation or warranty, express or implied, is or will bemade, and no responsibility or liability is or will be accepted, by the Company, its shareholder or by any of theirrespective officers, directors, members of the management, employees or representatives as to or in relation tothe accuracy, correctness or completeness of this Memorandum or any other written or oral information madeavailable to any interested party or its advisors. Any liability, therefore, is hereby expressly disclaimed tothe fullest extent permitted by law. In particular, no representation or warranty is given as to the achievementor reasonableness of any future projections, management estimates, prospects or returns. These forward- lookingstatements have been made after reasonable inquiries and to the best knowledge and belief of the Company; theyonly speak as of the date hereof. The Company, its shareholder, undertake no obligation to provide therecipient with access to additional information or to update this Memorandum or correct any data which turn outto be inaccurate or inapplicable contained herein. Only those particular representations and warranties which may bemade in a sale and purchase agreement (which will not contain any representations or warranties related to thisMemorandum) when and if it is finally executed, and subject to such limitations and restrictions as may be agreed,shall have any legal effect.* By accepting this Memorandum, the recipient also acknowledges that the recipient should receive legal, tax,accounting and any other independent advice from advisors with appropriate expertise to assess relevant risks.* This Memorandum is being made available only to parties who have signed and returned a confidentialityundertaking and recipients are therefore bound by the confidentiality undertaking in respect of all informationcontained herein. The Company, its shareholders reserve the right, without advance notice, to change theprocedures of the investment process or terminate negotiations at any time without giving any reasons.* This Memorandum shall not be copied, reproduced, distributed or passed to others at any time without the priorwritten consent of UBS.* This Memorandum is governed by and to be construed in accordance with (substantive) Austrian Law. Exclusiveplace of jurisdiction is St. Pölten.


Helmut Schmutz, Mag.CEO

EURRUS BIOTECH GMBHTechnopark 1 Gebäude C3430 Tulln, Austria

Phone +43 (0)2272 62 766Mobile +43 (0)676 344 51 53Fax +43 (0)2272 62 766-99Email [email protected]

FN 274263 d

strictly confidential information folder 2020 © eurrus ... · year 2012 2014 2018 2020 2021 2022f...

Documents