NEXT-GENERATION RADIOIMMUNOTHERAPIES FOR NON-HODGKIN’S LYMPHOMA PATIENTS
SEPTEMBER 2019
Nordic Nanovector ASA Kjelsåsveien 168 B, 0884 Oslo, Norway www.nordicnanovector.com IR contact: [email protected] Forward-looking statements
This slide presentation contains certain forward-looking statements. These statements are based on management's current expectations and are subject to uncertainty and changes in circumstances, since they relate to events and depend on circumstances that will occur in the future and which, by their nature, will have an impact on Nordic Nanovector's business, financial condition and results of operations. The terms "anticipates", "assumes", "believes", "can", "could", "estimates", "expects", "forecasts", "intends", "may", "might", "plans", "should", "projects", "targets", "will", "would" or, in each case, their negative, or other variations or comparable terminology are used to identify forward looking statements. These forward-looking statements are not historic facts. There are a number of factors that could cause actual results and developments to differ materially from those expressed or implied in the forward-looking statements. Factors that could cause these differences include, but are not limited to, risks associated with implementation of Nordic Nanovector's strategy, risks and uncertainties associated with the development and/or approval of Nordic Nanovector's product candidates, ongoing and future clinical trials and expected trial results, the ability to commercialise Betalutin®, technology changes and new products in Nordic Nanovector's potential market and industry, Nordic Nanovector's freedom to operate (competitors patents) in respect of the products it develops, the ability to develop new products and enhance existing products, the impact of competition, changes in general economy and industry conditions, and legislative, regulatory and political factors. No assurance can be given that such expectations will prove to have been correct. Nordic Nanovector disclaims any obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.This presentation is for information purposes only and is incomplete without reference to, and should be viewed solely in conjunction with, the oral briefing provided by the Company. The information and opinions in this presentation is provided as at the date hereof and subject to change without notice. It is not the intention to provide, and you may not rely on these materials as providing, a complete or comprehensive analysis of the Company’s financial or trading position or prospects. This presentation does not constitute investment, legal, accounting, regulatory, taxation or other advice and does not take into account your investment objectives or legal, accounting, regulatory, taxation or financial situation or particular needs. You are solely responsible for forming your own opinions and conclusions on such matters and for making your own independent assessment of the Company. You are solely responsible for seeking independent professional advice in relation to the Company. No responsibility or liability is accepted by any person for any of the information or for any action taken by you or any of your officers, employees, agents or associates on the basis of such information.
2 Corporate snapshot
Nordic Nanovector is a clinical-stage biopharmaceutical company dedicated to extending and improving the lives of patients with haematological cancers through the development and commercialisation of innovative targeted radioimmunotherapies
• Founded 2009 in Oslo, Norway to develop • HQ and R&D in Oslo, with corporate offices Betalutin® for the treatment of non-Hodgkin’s in London, UK and Zug, Switzerland lymphoma (NHL) based on • 46 Employees (around 60 FTEs in total) – The Norwegian Radium Hospital is a centre of excellence for oncology biomedical research and • Listed on Oslo Stock Exchange in 2015 patient care (NANO) – R&D expertise in radioimmunotherapies • Market cap USD 220M*
*As of September 17, 2019. Exchange rate 1 USD = 8,94096 NOK. 3 Management Team with international experience
EDUARDO BRAVO TONE KVÅLE Chief Executive Officer Chief Financial Officer
LISA ROJKJAER, MD JOSTEIN DAHLE, PhD Chief Medical Officer Co-Founder, Chief Scientific Officer
MARCO RENOLDI, MD RITA DEGE Chief Operating Officer Chief Human Resources Officer
ROSEMARIE CORRIGAN MALENE BRONDBERG Chief Quality Officer Vice President, IR & Corporate Communications
4 Nordic Nanovector – experts in radioimmunotherapy
Fully owned lead asset – a novel anti-CD37 radioimmunotherapy targeting unmet needs in the two largest NHL types – FL and DLBCL – a near USD 5B* opportunity
® Betalutin A single administration of Betalutin® has demonstrated promising efficacy and safety in a 74-patient trial
Pivotal trial in 3L R/R FL underway with full enrolment expected 2H 2020; Fast-Track and Orphan Drug designations granted in US
On-going clinical programmes to access higher-value 2L FL and R/R DLBCL provide additional near-term value inflection points
R&D expertise and IP provides multiple opportunities in B-cell malignancies
FL – Follicular lymphoma; DLBCL – Diffuse large B-cell lymphoma: R/R – relapsed/refractory; 3L – 3rd line; 2L – 2nd line 5 * Pharmacor Oncology: Non Hodgkin’s Lymphoma by Decision Resources Group, 2015 Nordic Nanovector pipeline – Multiple attractive opportunities in NHL (last line has been deleted)
Candidate Targeted indication Discovery Preclinical Phase 1 Phase 2 Phase 3
Betalutin® 3L FL PARADIGME – Pivotal Phase 2b
Betalutin® 2L FL Archer-1 – Phase 1b (combination w/RTX)
Betalutin® R/R DLBCL (SCT ineligible) LYMRIT 37-05 – Phase 1
Humalutin®* NHL IND-ready
212Pb-NNV003 (anti-CD37 CLL and other NHL R&D radioimmunoconjugate)**
R&D
RTX – rituximab; DLBCL – diffuse large B-cell lymphoma: SCT – Stem cell transplant; ADC: antibody-drug conjugate; CLL: chronic lymphocytic leukaemia 6 *On hold, refocusing resources towards PARADIGME; **R&D collaboration Strategy to capture significant value in NHL
1 Clinical Development
Develop differentiated target product profile to meet requirements of regulatory and 2 reimbursement agencies Commercialisation
Single-agent Betalutin® 3L R/R FL Goal: capture value of Betalutin® in the US; First-to-market indication the largest single market FL c.$2.1B ® Betalutin + RTX Refine US commercial strategy and deploy Accelerate access to 2L FL 2L R/R FL launch readiness plan through confirmatory Phase 3 trial
Identify opportunities for ex-US regions Betalutin® DLBCL R/R DLBCL To maximize NHL opportunity in c.$2.7B largest NHL type
3 Platform Pipeline Development Leverage expertise and IP to create long-term value internally and through strategic partnerships
The slide shows the overall market potential in G7* – Source; Pharmacor Oncology: Non-Hodgkin’s Lymphoma, by Decision Resources Group, 2015 7 *Germany, France, Italy, Spain, United Kingdom, United States, Japan NHL – HIGH UNMET NEED DESPITE AVAILABLE TREATMENTS
Nordic Nanovector ASA Kjelsåsveien 168 B, 0884 Oslo, Norway www.nordicnanovector.com IR contact: [email protected] NHL – high unmet need despite available treatments
NHL • 7th most common cancer in the US1 • Median age at diagnosis is 67 years1 85% 15% • Incidence across G7* is 17 per 100,000 per year, B-cell NHL T-cell NHL resulting in >130,200 new cases in 20142 • Expected to grow by nearly 20% by 2024, as a result of population growth and aging population2 • Market potential expected to reach $28.7 billion by Indolent (iNHL) Aggressive (40% of all NHL) (60% of all NHL) 20263
• FL (~20%) • DLBCL (~40%) • Marginal zone lymphoma (MZL) • Burkitt lymphoma • Lymphoplasmacytic lymphoma • Lymphoblastic lymphoma • Chronic lymphocytic leukemia/small- • Mantle cell lymphoma cell lymphocytic lymphoma (CLL/SLL) • Primary mediastinal large B-cell lymphoma
1seer.cancer.gov 2Pharmacor Oncology: Non-Hodgkin’s Lymphoma, by Decision Resources Group, 2015 3Landscape & Forecast: Non-Hodgkin’s Lymphoma and Chronic Lymphocytic Leukemia, by Decision Resources Group, 2017 9 * France, Germany, Italy, Spain, United Kingdom, United States, Japan FL - shorter remissions with each successive therapy and no cure at present
1st line 2nd line 3rd line Later lines
Approx. 24,000 patients Approx. 16,000 patients Approx. 10,000 patients Approx. 5,000 patients
Idelalisib Anti-CD20 Anti-CD20 Clinical trials with novel drugs (Rituximab, obinutuzumab) (Rituximab, obinutuzumab) (CAR-T) + OR + Chemotherapy BSC / Palliative therapy Chemotherapy (Bendamustine, fludarabine, CHOP) Copanlisib (Bendamustine, CHOP, CVP) OR OR Anti-CD20 Duvelisib Followed by: (Rituximab)
• Rituximab maintenance + OR Immunomodulatory agents • Radioimmunotherapy Rituximab (Lenalidomide)
OR OR Radioimmunotherapy Radioimmunotherapy
Followed by: • High dose chemo + Stem Cell Transplant • Allogenic SCT • Rituximab / obinutuzumab maintenance
Treatment regimens including listed options are either approved or recommended by NCCN or ESMO guidelines Remission Remission Remission Remission Remission 10 Relapse Relapse Relapse Relapse DLBCL – limited treatment options for patients relapsing after first-line therapy
1st line 2nd line 3rd line
Approx. 46,000 patients Approx. 18,000 patients Approx. 10,000 patients
Anti-CD20 High-dose (Rituximab) 30-40% Y immunochemotherapy (R- Abicabtagene ciloleucel + DHAP, R-ESHAP, R-GDP, R- OR Chemotherapy GemOx. R-ICE) followed by: Tisagenlecleucel (CHOP, CEPP, CDOP, DA- Autologous Stem Cell EPOCH, CEOP, GCVP) Transplant OR Transplantation (in some cases eligible Pixantrone Allogeneic SCT)
OR Clinical trials with novel drugs Salvage immunochemotherapy 60-70% N (R-CEPP, R-CEOP, R-DA-EPOCH, R-GDP, R-GemOx, R-benda) OR Other drug treatment (brentuximab vedotin, R- lenalidomide, rituximab) OR Radiation therapy OR Clinical trials with novel drugs
11 Treatment regimens including listed options are either approved or recommended by NCCN or ESMO guidelines NHL – the need for new treatment options
• 40-60% of iNHL patients treated with a RTX-containing regimen are either refractory to therapy (10%) or develop resistance within five years, so having an alternative therapeutic target to CD20 is important • Relapsed/refractory patients may not tolerate chemotherapy because of age or co-morbidities, so “chemo- free” regimens are in high demand
FL: Five-year overall survival for RTX- refractory patients vs all: 58%1 vs 88%2 5 year PFS3 59%
36% ~40% of DLBCL patients relapse following 1L 26% RTX-chemo; 60-70% of these patients fail or are unsuitable for subsequent high-dose chemo + SCT
1Abdollahi S et al, Blood 2008:112 2seer.cancer.gov (2019) 12 3Rivas-Delgado A et al. EHA 2017; abstract 405 BETALUTIN® – A ONE-TIME TREATMENT FOR NHL PATIENTS
Nordic Nanovector ASA Kjelsåsveien 168 B, 0884 Oslo, Norway www.nordicnanovector.com IR contact: [email protected] Betalutin®: A novel CD37-targeting radioimmunotherapy
• CD37 is highly expressed in B-NHL1
• 177Lu: a low energy β-emitter with a half-life of 6.7 days
• Mechanism of action: – Internalization and cell death – Crossfire effect targets cells with variable CD37 expression and poorly-vascularized tumour regions
14 1. Flinn IW. Blood 2011; 118: 4007–4008; Betalutin® is specifically designed as a one-time treatment for NHL: Compelling, unique and differentiated value proposition
Alternative target to CD20, well suited for NHL patients who progress after RTX-based regimens
Betalutin® High and durable response from one-time treatment in heavily pre-treated NHL patients*
Predictable and manageable toxicity*, important for elderly NHL patients who might not be able to tolerate chemotherapy
Convenience for NHL patients – simple, one-time treatment, QoL Convenience for physicians – ready-to-use, optimised resourcing
Potential synergy from combination with anti-CD20 mAbs and other therapies
15 * Kolstad A, et al. Abstract 2879, ASH 2018. BETALUTIN® – PROMISING SAFETY AND EFFICACY IN R/R FL
Nordic Nanovector ASA Kjelsåsveien 168 B, 0884 Oslo, Norway www.nordicnanovector.com IR contact: [email protected] Clinical development optimized to deliver Betalutin® to FL patients as soon as possible
• Objective is to deliver a product with a differentiated target product profile that meets the requirements of both regulatory and reimbursement agencies
LYMRIT 37-01 PARADIGME Phase 1/2a trial Pivotal, global randomised Phase 2b trial
Phase 1 Phase 2a Comparing two dosing regimens with the goal to select the best Betalutin® dosing regimen for filing Dose-escalation cohorts to Dose expansion cohorts determine the MTD/RDE* of for confirmatory safety US Betalutin® and exploratory efficacy Filing 3L FL patients refractory to anti-CD20 therapy
74 R/R iNHL patients with a median of 3 prior therapies Target is 130 patients at 80-85 sites in approx. 20 countries Primary endpoint: ORR Secondary endpoints: DoR, PFS, OS, Safety, QoL All patients received a single administration of Betalutin® Complete patient enrolment in 2H 2020
Betalutin® + RTX: Accelerate access to 2L FL through confirmatory Phase 3 trial
17 * Maximum tolerated dose / Recommended dose for expansion LYMRIT 37-01: Promising safety and efficacy in R/R FL*
Patient characteristics (n=74) Compelling response rate in FL and MZL** patients from a single administration • Elderly (median 68 years) ORR CR • Heavily pre-treated with advanced-stage disease at All patients (n=74) 61% 28% baseline All FL patients (n=57) 65% 28% • Primarily FL (n=57) with other NHL types (n=17) Arm 1 (40/15) (n=25) 64% 32% Arm 4 (100/20) (n=16) 69% 25% FL with ≥2 prior therapies (n=37) 70% 32%
RTX*-refractory FL, ≥2 prior therapies (n=21) 62% 19% ® Betalutin was well tolerated MZL (n=9) 78% 44%
• Most common grade 3/4 AEs were transient and reversible neutropenia and thrombocytopenia mDoR updated September 2019 • Updated median duration of response: 13.6 months for all • Serious AEs occurred in 14 pts (19%) responders (n=45) and 32.0 months for complete responders • No cases of febrile neutropenia, low incidence of platelet (n=22). transfusion, and no study related deaths • Median follow-up time for responders: 30.0 months (range: 12.0 - 60.7 m)
*Kolstad A, et al. Abstract 2879, ASH 2018 18 ** MZL – Marginal Zone Lymphoma Betalutin® continues to be a novel and effective therapy among 3L FL competitors Pts.’ mDOR Mechanism of CR ORR Median Route of Administration Source (months) Action Age
32% Kolstad et al, ASH 2018 (37 Betalutin IV infusion (one-time administration), preceded by 1 70% ~13.6** 68 CD37-targeting RIT 3L FL pts.); **Latest company (Phase I/2) RTX and 1 lilotomab update (all responders)
Idelalisib* Prescribing info 8% >12.5 62 Oral, twice daily Pi3k inhibitor (Marketed) (72 patients) 54%
Copanlisib* 14% IV infusion (weekly – 3 weeks on and 1 week off) until Prescribing info (Marketed) 14.1 62 Pi3k inhibitor 59% progression (104 patients)
Duvelisib* Prescribing info 1% 10 64 Oral, twice daily, until disease progression Pi3k inhibitor (Marketed) 42% (83 patients)
Parsaclisib 59 (part A Forero-Torres et al, 21% N/A Oral, once daily Pi3k inhibitor (Phase I/II) 71% 66 (part B) ASH 2017 (4 patients)
Line Tazemetostat rd 7% Epizyme, ICML 2019 3 EZH2m+ 77% 8.3 61 Oral, twice daily EZH2 inhibitor (Phase II) (43 patients) ASCO 2019 ME401 N/A 64.5 Oral, once daily Pi3k inhibitor (Phase 1b) 75% (30 patients) 50% IV infusion of re-engineered autologous T-cells, Novartis, ASH 2016 Kymriah 15 (83%) 59 CAR-T cell therapy (Phase II) 79% preceded by leukapheresis and CT (14 patients) Anti-CD20 X Anti- # 71% Regeneron Pharma, EHA REGN1979 NR 67 Multiple dose levels of REGN1979;IV CD3 bispecific 93% 2019 (21 pts.) (Phase I) antibody
Umbralisib Matthews et al, ASH 2017 53% NR 66 Oral; daily dose; until disease progression or off study Pi3k inhibitor (Phase I) (146 pts.)
• All agents are approved based on different phase results as mentioned along with asset 19 • *Accelerated Approval basis on Phase II • Results from different trials for comparison purpose only and NOT head to head studies • # at doses ≥5 mg PARADIGME: Dose selection aligned with regulatory feedback
• Patient population: 130 patients with 3L FL who are refractory to anti-CD20 therapy
• Primary endpoint: Overall response rate (ORR)
• Secondary endpoints: Duration of response (DoR), Progression free survival (PFS), Overall survival (OS), Quality of life (QoL)
15MBq/kg Betalutin® (+ 40mg llo*) (n=65)
Interim futility Rituximab Complete patient Filing Randomisation analysis 375 mg/m2 enrolment 2H 2020 Target 1H 2020 1H 2021
20MBq/kg Betalutin® (+ 100mg/m2 llo) (n=65)
Day -14 Day 0
• 83 clinical sites are open for enrolment (as of Sep 16th, 2019)
• An interim analysis for futility is targeted for 1H 2020 20 *Ilo – lilotumab, naked anti-CD37 antibody PARADIGME – where are we today
83 sites in 24 countries (as of Sep 16th, 2019) up and running and recruiting. We will add another 10 highly motivated sites to ensure that our recruitment forecast is reached
Recruitment rate has already achieved steady state aligned with forecast and in line with previous clinical trials in similar patient populations
21 Actions to drive patient recruitment
• Close working relationship with the PARADIGME CRO (ICON)
• Programme of Nordic Nanovector Management site visits – Demonstrates Nordic Nanovector’s commitment to PARADIGME and supporting centres when needed – Increased clinical site motivation and commitment
• Maintain site engagement with NANO Medical Scientific Liaisons (MSLs) / and ICON’s Clinical Research Associates (CRAs) – Designed to keep PARADIGME at front of mind in a competitive environment for these patients
• Team of 4 Medical Scientific Liaisons (MSLs) deployed in Europe and US – Medical affairs focused on strengthening relationships with key referrers – Leveraging Lymphoma Societies / Advocacy Groups / Patient organisations
• Communication of key updates of LYMRIT 37-01 data – presentations at key congresses (ASH, ICML, AACR) – Great tool for raising awareness and gaining KOL (Key Opinion Leaders) engagement
• Rolling programme of Investigator Meetings (multi country or country specific in some cases) – Create culture of shared goal and exchange of experiences – positive response to previous events
• Referral pathways mapped out based on experience from highest recruiting centres
22 Regulatory path focused on expedite product approval
• Orphan Drug Designation granted in US and EU in 2014
• Clinical plan for Betalutin ® agreed with FDA in September 2017 (type C meeting)
• Enhance dialogue with regulators to bring Betalutin® to FL patients quicker thanks to:
– Fast-track designation granted in the US in June 2018
– Promising Innovative Medicine (PIM) designation granted in the UK in October 2018
23 BETALUTIN® – ONGOING DEVELOPMENT IN 2L FL
Nordic Nanovector ASA Kjelsåsveien 168 B, 0884 Oslo, Norway www.nordicnanovector.com IR contact: [email protected] Clinical development strategy to pursue access to 2L FL indication
LYMRIT 37-01 and PARADIGME Leverage US Confirmatory Phase 3 study operations and in 2L FL customer-facing (to be discussed with Regulatory authorities) infrastructure Archer-1
• Access significantly larger market opportunity than 3L FL – at present $1.5B • Strong rationale for combination from preclinical models* – Betalutin® + RTX significantly inhibited tumour growth and prolonged overall survival – Hypothesis: Betalutin® reverses downregulation of CD20 expression and RTX resistance
25 Repetto-Llamazares A et al. Eur J Haematol 2018 Demonstrated synergistic effect of Betalutin® in combination with RTX in a preclinical NHL model
Survival analysis of nude mice ® with s.c. Daudi xenografts • Betalutin shown to increase binding of rituximab to NHL cells in vitro and increase uptake of RTX in NHL tumours in vivo
• Strong synergistic effect of combination of Betalutin® and RTX on survival of mice with NHL (Hazard ratio = 0.024, Cox regression)
Survival • Median survival time for combination: >222 days (p < 0.05)
• Median survival time with either treatment alone was 31 - 40 days with RTX or 50 days with Betalutin®
26 Repetto-Llamazares A et al. Eur J Haematol 2018 Archer-1: Betalutin® + rituximab in R/R FL
• Patient population: 20-25 patients with FL (grade I-IIIA) ≥1 prior regimens
• Primary objective: To evaluate the safety and tolerability of Betalutin® in combination with RTX
• Secondary objective: To evaluate the preliminary anti-tumour activity of combination treatment
10MBq/kg Betalutin® SD, PR Rituximab 2 (+ 40mg llo) or CR 375 mg/m or 1400 mg s.c. Data read-out Q 12 weeks for 2 years 2H 2020 Rituximab Rituximab or or until disease progression 375mg/m2 375mg/m2 15MBq/kg Betalutin® PD (+ 40mg llo) DISCONTINUE
Day -14 Day 0 Days 7, 14, 21 and 28
• Open for enrollment in 4 countries (EU) • Preliminary results, first safety cohort (n=3) • No dose limiting toxicity • ORR 100% (3 CRs)
27 BETALUTIN® – POTENTIAL IN DLBCL
Nordic Nanovector ASA Kjelsåsveien 168 B, 0884 Oslo, Norway www.nordicnanovector.com IR contact: [email protected] Betalutin® has demonstrated efficacy in preclinical models of DLBCL
3000
100 ) 3 2000 75
volume (mm 50 Survival (%)
1000 Tumor 25
0 0 0 10 20 30 40 50 0 10 20 30 40 50 Time post-xenograft (days) Time post-xenograft (days)
NaCl 177Lu-lilotomab (100 MBq/kg) Lilotomab (0.5 mg/kg) 177Lu-cetuximab (125 MBq/kg)
• In vivo therapy of SCID mice with DOHH2 DLBCL xenografts show an improved effect of Betalutin compared with lilotomab and non-specific 177Lu-cetuximab**
* Melhus et al., EHA annual meeting, Stockholm, 2018. 29 ** Pichard, et al. Submitted to Leukemia, 2019. LYMRIT 37-05: Phase 1 dose-escalation study in R/R DLBCL patients not eligible for SCT
• Patient population: Up to 24 patients with R/R DLBCL
• Primary objective: Determine maximum tolerated dose (MTD)
• Secondary objectives: Safety and preliminary activity
20MBq/kg Betalutin® (+ 100 mg/m2 llo) (n ≥3)
® 15MBq/kg Betalutin Initial data read- Expansion Phase 2 (+ 100 mg/m llo) out with selected dose (n ≥3) 2H 2019 20 patients
10MBq/kg Betalutin® 10MBq/kg Betalutin® (+ 60 mg/m2 llo) + 100 mg/m2 llo (n ≥3) (n ≥3)
*all patients to receive RTX 375 mg/m2 on day -14
• No safety issues were identified in the first 3 cohorts
30 COMMERCIALISING BETALUTIN® – CAPTURING ITS VALUE IN NHL
Nordic Nanovector ASA Kjelsåsveien 168 B, 0884 Oslo, Norway www.nordicnanovector.com IR contact: [email protected] Insight from pre-commercial research – defining optimal commercialisation strategy for success
• The value of Betalutin® as a new treatment option in NHL is clearly perceived by stakeholders – Efficacy is seen as a major strength – The combination of efficacy, manageable toxicity and convenience of one-time administration makes Betalutin® truly appealing – Betalutin® targets unsatisfied areas of the market, and will be well positioned to serve unmet needs of patients – elderly with co-morbidities and RTX-refractory • Analogs’ case studies highlight key strategies to maximise the clinical and commercial potential of Betalutin® – Pre-launch scientific engagement of thought leaders in NHL centers of excellence on Betalutin’s benefits and positioning – Well-designed clinical development plan, aligned with health authorities’ feedback – Robust market access and reimbursement programme – Optimised referral pathway – Streamlined manufacturing and distribution via a centralised logistics partner 32 Betalutin® – a clear path to commercialisation
1 2 3 Go-to-market strategy Launch strategy Pricing strategy
• Retain Betalutin® as a • Successfully position Betalutin® in first- • Target price premium vs. wholly owned asset to-market indication (3L FL) prior radioimmunotherapies
• Actively participate in its • Expand in 2L FL with RTX combination • Align price to that of new commercialisation in the US therapy agents approved in 3L FL
• Explore potential distribution • Leverage US commercial infrastructure • Ensure price reflects agreements in selected to penetrate DLBCL market space incremental value to payers, geographies healthcare professionals • Maximize product value through life- and patients over alternative cycle management treatments
33 We have a thorough understanding of disease state, competitive landscape, patient flow and customer behaviour
Secondary Qualitative Insights Payers and Pricing Patient Insights Special Projects Research • Integration of primary / • Case study deep • Customer • US pricing and • Qualitative patient secondary market ®, dives: Xofigo SIR segmentation market access research research data with ® ® Spheres , Zevalin • Positioning and research claims data to map messaging • EU-4* pricing and outpatient physician • Categorised settings • Patient referral market access treatment of FL of care for licensed pathway research patients in US community settings administration • Patient flow • Reimbursement facilities pathway (US, EU-5**) • EU and US Customer 1:1 Discussions with • Market Access & Facing Infrastructure 1:1 Discussions with HaemOncs, RadOncs, Model Research • Deep dive into the Pricing Elasticity Patients (n = 22) NucMeds (n = 190), Health Study (US, EU-5) • Distribution and radiopharmacy Focus on patient journey, Physicists and Radio- fulfilment strategy landscape pharmacists (n = 40) role of patient and caregivers, 1:1 Discussions with buying process, leverage research Sample included HCPs Payers (n = 80) points and barriers for First five tasks completed • Research on from private clinics, ® Focus on both commercial Betalutin requirements to community hospitals/systems, 1:1 Discussions with plans and government health HemOncs, RadOncs, become an IDNs and academic centers (approx. 2/3 US, 1/3 EU) plans in the US (Medicare / NucMeds, RadioPharms, Authorised User Medicaid), and EU-4 (NHS Industry Trade Experts, reimbursement systems) Distributors (n = 84)
34 *Germany, France, Italy and Spain **Germany, France, Italy, Spain, United Kingdom Betalutin® manufacturing and supply chain
• Biological intermediates (lilotomab satetraxetan, lilotomab) and no-carrier added Lutetium-177 are sourced in Europe
• Betalutin® Drug Product is manufactured at the Institute for Energy Technology (IFE; Kjeller, Norway)
• Additional regional manufacturing site in North America scheduled to come on-line after approval
• Logistics supply chain from European production site at launch will secure 48-72 hour delivery to all administration sites – US-based logistics partner will have strong radio-pharmacy network
• Strong internal capabilities overseeing manufacturing, quality and distribution
35 Broad IP protection
Betalutin® Pre-dosing • Composition of matter patent • Cover different ways of (covers Betalutin®, pre-dosing with lilotomab Humalutin®, uses etc.) • Expires in 2037* • Expires in 2031* • Pending in serveral all • Approved in several countries countries
2010 2013 2016 2017
Betalutin® + rituximab Combination patent • Up-regulation of CD20 by • Combination of Betalutin® Betalutin® and Humalutin® with • Expires in 2034* different drug classes • Approved in EU and about • Expires in 2038* half of the countries • Pending in all countries
36 *With 5 years extension possible PIPELINE
Nordic Nanovector ASA Kjelsåsveien 168 B, 0884 Oslo, Norway www.nordicnanovector.com IR contact: [email protected] Preclinical project: 212Pb-NNV003 A novel targeted alpha therapy for treatment of B-cell malignancies
• Collaboration project with Orano Med (formerly AREVA Med) • NNV003 is a chimeric anti-CD37 mAb developed by Nordic Nanovector • 212Pb is an alpha-particle emitter with clinically attractive properties – 10.6 hr half-life; range of alpha-particle is 50-100 µm • Potential to target chronic lymphocytic lymphoma and other disseminated B-cell tumours • Safety of 212Pb has been demonstrated in clinical trials* • Well tolerated with a 90-100% survival rate in preclinical models of Chronic Lymphocytic Leukemia (CLL) and NHL** • Eurostars funding granted (NOK 6M)
38 *Meredith RF, et al. Am J Clin Oncol. 2018 Jul;41(7):716-721 ** Saidi, A. et al. Abstract #4422, ASH 2018 Alpha37 is more efficacious than daily dosing with ibrutinib in mice intravenously injected with ibrutinib resistant MEC-2 cells
Treated with Alpha37
12 mg/kg Ibrutinib 25 mg/kg Ibrutinib 15 µCi Alpha37 20 µCi Alpha37 20 µCi 212Pb-cetuximab NNV003 Saline
Control mice
39 Accepted for oral presentation at EANM meeting in October 2019 FINANCIALS
Nordic Nanovector ASA Kjelsåsveien 168 B, 0884 Oslo, Norway www.nordicnanovector.com IR contact: [email protected] Tight cost control; investment focused on clinical development and CMC activities
Operating results Distribution of total operating expenses
Q2'18 Q3'18 Q4'18 Q1'19 Q2'19 0
1H 2019: -20 23 % (1H 2018: -40 28 %)
-60 MNOK 1H 2019: -80 77 % -77 (1H 2018: -85 72 %) -90 -100 -96
-120 -111 Development* Administration
* preclinical, clinical, medical affairs, regulatory and CMC activites
41 Cash resources through to mid-2020
Net cash flow 1) Q2 2019:
200 98 • Net cash from operating activities of 100 negative NOK 102.2 million 0 MNOK -100 -71 -71 -60 -95 • Net cash flow from investing activities of -200 $ 92M* Q2 2018 Q3 2018 Q4 2018 Q1 2019 Q2 2019 NOK 0.2 million
• Net cash flow from financing activities$ 61 M** of Cash position NOK 7 million
642 700 (MUSD 83*) • Cash position of NOK 444 million as at end 600 570 539 500 444 (MUSD 52**) Q2 2019 500 440 400
MNOK • The company maintains its guidance that 300 200 current cash resources are expected to be 100 sufficient to reach mid-2020 0 Q1 2018 Q2 2018 Q3 2018 Q4 2018 Q1 2019 Q2 2019
** USD/NOK 7.75 42 1) ** USD/NOK 8.51 Net cash flow from operating, investing and financing activities plus/minus currency effect Key shareholders*
Top 5 Shareholders % ownership HealthCap VI L.P. 10.36% Folketrygdfondet 5.65% OM Holding AS 4.57% Nordnet Livsforsikring AS 3.05% Linux Solutions Norge AS 1.53%
Total 20 largest shareholders 39.93%
Total number of shares (fully diluted) 55,119,471
Average traded volume: 136,000 shares
43 *As of August 26, 2019 SUMMARY
Nordic Nanovector ASA Kjelsåsveien 168 B, 0884 Oslo, Norway www.nordicnanovector.com IR contact: [email protected] Strategic priorities focused on creating shareholder value
Complete enrolment into PARADIGME to enable BLA filing for Betalutin® with differentiated product profile
Advance clinical development of Betalutin® + RTX combination in 2L FL
Progress clinical development plan with Betalutin® in DLBCL
Develop and execute commercialisation strategy for Betalutin® in NHL in the US
Opportunistically consider partnerships to further enhance shareholder returns
Selectively extend the company’s pipeline targeting other B-cell malignancies around radioimmunotherapy expertise
Maintain rigorous capital management
45 Key company goals 2019-2021
1H 2019 Betalutin® in DLBCL LYMRIT 37-05: Enrolment completed (11 July)
2H 2019 Betalutin® in DLBCL LYMRIT 37-05: Data read-out
Betalutin® in DLBCL LYMRIT 37-05: First patient dosed (Expansion cohort)
1H 2020 Betalutin® in 3L FL PARADIGME: Interim analysis for futility
Betalutin® + rituximab in 2L FL Archer-1: Enrolment completed
Betalutin® + rituximab in 2L FL Archer-1: Data read-out 2H 2020 Betalutin® in 3L FL PARADIGME: Enrolment completed (data read-out to follow a few months later)
1H 2021 Betalutin® in 3L FL Regulatory filing
46