Introducing a First-in-Class treatment for Non-Hodgkin Lymphoma Carnegie Healthcare Conference, March 17, 2016 Marco Renoldi, Chief Business Officer Nordic Nanovector ASA Kjelsåsveien 168 B, 0884 Oslo, Norway - www.nordicnanovector.com 1
Forward-looking statements This presentation may contain certain forward-looking statements and forecasts based on uncertainty, 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, will, would or, in each case, their negative, or other variations or comparable terminology are used to identify forward-looking statement. There are a number of factors that could cause actual results and developments to differ materially from those expressed or implied in a forward-looking statement or affect the extent to which a particular projection is realised. Factors that could cause these differences include, but are not limited to, implementation of Nordic Nanovector s strategy and its ability to further grow, risks associated with the development and/or approval of Nordic Nanovector s products candidates, ongoing clinical trials and expected trial results, the ability to commercialise Betalutin, technology changes and new products in Nordic Nanovector s potential market and industry, 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. 2
Nordic Nanovector at a glance Focused on the development of treatments for haematological cancers Leveraging the unique Antibody Radionuclide Conjugate (ARC) technology Pipeline led by Betalutin for treating Non-Hodgkin Lymphoma (NHL) Novel anti-cd37 ARC in Phase 1/2 clinical trials Promising efficacy with sustainable duration of response Confirmed favorable side effect profile Clear development pathway New plan, introduced in October 2015, designed to enhance the chances of Betalutin gaining regulatory approval with a competitive product profile Corporate Established in 2009, IPO in March 2015 (OSE: NANO) Cash end 2015: NOK 743 (USD 87.9m*); IPO proceeds NOK 575m (USD 68m*) * US Dollar/Norwegian Krone 8.45 3
Betalutin : the first-in-class antibody-radionuclide conjugate (ARC) Tumor-seeking monoclonal anti-cd37 antibody + conjugated radionuclide (Lu-177) Effective therapeutic payload and multi-cell kill approach Specifically designed for the treatment of B-cell tumors 4
Betalutin is specifically designed to treat NHL CD37: a validated target for B-cell NHL Lutetium-177: ideal therapeutic and safety properties Multi-cell kill approach CD37 is a useful therapeutic target for novel therapies in NHL patients that have relapsed after CD20-based therapy Internalization of the antibody anchors the payload to the cancer cells, resulting in a prolonged irradiation of the cancer cell nucleus Beta-emitting particles with half-life (6.7 days) matching the antibody s circulation time, long enough to ensure that tumour mass is irradiated Mean range of radiation treats bulky tumors while limiting damage to health tissue Prolonged irradiation of tumour cells within ~50-cell radius enables multi-cell kill effect, that destroys even malignant cells that do not express CD37 or have limited blood supply ARC s could deliver better treatment outcomes than immunotherapies (monoclonal antibodies or ADC s), which rely on a single cell kill approach 5
NHL, a family of different blood cancers, represents a significant unmet need NHL can be divided into several subtypes NHL represents a significant unmet need NHL B-cell NHL 85% T-cell NHL 15% Indolent lymphomas ~41% Aggressive lymphomas ~59% Follicular lymphoma (~59%*) Small lymphocytic lymphoma MALT lymphoma Lymphoblastic lymphoma Lymphoplasmacytic lymphoma Diffuse large B-cell lymphoma (~61%**) Mantle cell lymphoma Burkitt lymphoma Primary mediastinal large B-cell lymphoma A cancer of the white blood cells (lymphocytes)/immune system 10th most common cancer: ~ 850,000 prevalent patients with B-cell NHL 66% of diagnosed patients age 55-74 years High mortality rate, despite available treatments Over $12B market opportunity by 2018 Sources: DataMonitor Pipeline Insight: Lymphomas, Multiple Myeloma and Myelodysplastic Syndromes DMHC2595/ Published 03/2010, National Cancer Institute at the National Institutes of Health, seer.cancer.gov/, annonc.oxfordjournals.org/content/19/3/570.full 6
Betalutin s Unique Value Proposition is based on important differentiating factors 1. Improved CR and DOR as single agent 2. Manageable haematological toxicity and minimal non-haematological toxicities 3. One-time therapy with simple administration schedule 4. Potential synergy from combination with anticd20 moab (rituximab) and with other immuno-oncology treatments 5. Improved quality of life 7
In what NHL patients can Betalutin fill the unmet medical need? Relapsed NHL No standard therapy past second-line Rituximab resistance Patients who have developed resistance to CD20-targeted antibody Older patients Patients aged >65 years not able to tolerate some chemotherapies Co-morbidities Some co-morbidities can impact tolerability of current treatments Lack of response Patients with a poor response to first- or second-line treatment 8
Positive clinical results support Betalutin s potential in NHL Complete metabolic response (FDG PET/CT) at 3 months in patient 007 with follicular lymphoma at dose level 20 MBq/kg Complete metabolic response (FDG PET/CT) at 6 months in patient 008 with follicular lymphoma at dose level 15 MBq/kg This patient is still in complete remission This patient is still in complete remission FDG PET CT: fluorodeoxyglucose positron emission tomography-computer tomography; FL: follicular lymphoma; MBq: megabecquerel FDG PET/CT: fluorodeoxyglucose positron emission tomography-computer tomography; FL: follicular lymphoma; MBq: megabecquerel; SPECT: single-photon emission computerized tomography 9
Number of patients Positive response data from Betalutin Phase 1/2 study (LYMRIT 37-01) were presented at ICML 2015 Betalutin achieved a 64% ORR with 36% CR rate 1,2 8 7 6 5 4 3 2 1 0 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 64% 36% 28% 18% 18% ORR CR PR SD PD Betalutin is effective across all dosages with 100% ORR at 20MBq/Kg 10MBq/Kg 20MBq/Kg 15MBq/Kg ORR DLT 1. Best Response Rate 2. One patient had confirmed transformed lymphoma at 3 months; this patient was excluded from Response Rate assessment (11 out of 12 patients evaluable for efficacy). MBq: megabecquerel, Kolstad A et al. ICML 2015; Abstract 287 10
Data from the same phase 1/2 study show Betalutin s duration of response is sustained Median response duration not yet reached Response is still ongoing in 5/7 responders to Betalutin treatment 20 MBq/ kg b.w. 15 MBq/ kg b.w. 10 MBq/ kg b.w. Not evaluated Complete response Partial response Stable response Progression Time of progression Durable responder Continued response 0 3 6 9 12 18 24 Time (months) Tumor response assessed according to Cheson criteria 2007 Kolstad A et al. ICML 2015; Abstract 287 11
Betalutin has the potential to be best in class vs. existing competition Launched Products Clinical Efficacy Targets in Follicular Lymphoma Phase 1/2 Betalutin Preliminary Results* Ibritumomab tiuxetan (ORR: 74%, CR: 15%, DOR: 6,4 months) Idelalisib (ORR: 54%, CR: 14%, DOR: 11,8 months) Bendamustine (ORR: 75%, CR: 14%, DOR: 9,2 months) 3L FL ORR 70-75% CR 35-40% DOR 9-12 months ORR 64% CR 36% Median DOR not yet reached *ICML 2015 Sources: Scientific publications, publicly available information, please see prospectus for detailed sources 12
Key 2015 deliverables have been achieved Betalutin in FL Understand the role of HH1 as predosing Amend Phase 1/2 study to enable higher, more effective doses Add sites in Phase 1/2 study to meet new timelines Accelerate patient enrollment in approved studies Completed Arm 2 in Phase 1/2 Protocol amendment approved in Austria, Sweden, Norway, Poland and UK* Arms 3 and 4: 6 new sites qualified (10 total) Phase 2: 5 new sites qualified (19 total) Patient enrollment on track Start dosimetry study in Germany Dosimetry study submitted and approved Betalutin in DLBCL Pipeline R&D Start study in a new NHL indication Advance pre-clinical studies: chhh1 and CD20 upregulation DLBCL protocol submitted and approved New compelling data presented at EANM and ASH 13
Nordic Nanovector is committed to invest in a broad development and discovery pipeline Indication FL, 3rd line FL, 2nd line DLBCL, ineligible for ASCT DLBCL, conditioning Other NHL FL, 1st line Leukemia Multiple myeloma Product candidate Discovery Preclinical Phase 1 Phase 2 Phase 3 Betalutin Betalutin + CD20 Betalutin Betalutin Betalutin + CD20 177 Lu-chHH1 ARC 177 Lu-chHH1 ARC Affilutin 1 1. Collaboration with Affibody ARC: antibody -radionuclide conjugate; ASCT: autologous stem cell transplant; chhh1: chimeric HH1 antibody; DLBCL: diffuse large B-cell lymphoma; FL: follicular lymphoma; NHL: non-hodgkin lymphoma 14
Our strategic imperatives are focused on maximizing shareholders value 1. 1 Obtain Betalutin s approval in 3L (and subsequently 2L) Follicular Lymphoma 2. 2 Expand indication in DLBCL as soon as possible 3. 3 Selectively extend the Company s pipeline around core expertise (ARC/ADC, haematologyoncology) to embrace innovative technologies and de-risk the company 4. 4 Independently commercialize Betalutin and follow-on compounds in major markets 5. 5 Opportunistically consider partnerships to leverage position of strength 15
Betalutin s clinical development plan in FL is designed to maximize efficacy Lymrit 37-01 Phase 1/2 trial Phase 1 Phase 2 Pivotal Phase 2 trial Arm 1 10MBq (- HH1 R0) N=1 10MBq (+ HH1 50mg) N=3 20MBq (+ HH1 50mg) N=3 15MBq (+ HH1 50mg) N=6 15MBq (+ HH1 50mg) N=9 17.5MBq* (+ HH1 50mg) N=3 Arm 2 15MBq (- HH1) N=2 10MBq (- HH1) N=3 to 6 Discontinued First Patient: 2H 2017 Dose TBD N=85 Last Patient: 2H 2018 MBq = Megabecquerel (radioactivity measurement unit) HH1 = CD37 B-cell seeking antibody R0 = rituximab predosing on day 0 n= Number of patients Arm 3 15MBq (- HH1 R0) N=3 to 6 15MBq (+ HH1 125mg/m 2 ) Arm 4 N=3 to 6 17.5MBq or 20MBq* (- HH1 R0) N=3 to 6 17.5MBq or 20MBq* (+ HH1 125mg/m 2 ) N=3 to 6 Regulatory submission: 1H 2019 * Dose decision based on safety data and Safety Review Board s recommendation PARADIGME dose decision: Q1 2017 16
Betalutin is also being investigated in relapsed, ASCT-ineligible, DLBCL Lymrit 37-05 Phase 1 Pivotal Phase 2 trial n = 3-18 Day -14: rituximab Day 0: HH1 125mg/m 2 Day 0: Betalutin* 20 or 17.5MBq/kg* (HH1 125mg/m 2 ) Several combinatorial approaches to be explored (CAR-T, check - point inhibitors, BCL - inhibitor) 10MBq/kg (HH1 125mg/m 2 ) 15MBq/kg* (HH1 125mg/m 2 ) 3+3 3+3 First Patient: 2H 2018 Single arm Dose TBD N=70-90 Last Patient: 2H 2019 3+3 Regulatory submission: 2H 2020 Protocol design pending SAB and regulatory validation * Dose decision based on safety data and Safety Review Board s recommendation Phase 2 dose decision: 2H2017 17
Preclinical data suggest potential synergy from combination of Betalutin with rituximab Treatment with rituximab-containing regimens can result in disappearance of the CD20 antigen expression, leading to reduced clinical effect CD20 antigen levels are upregulated after treatment with Betalutin, increasing binding of rituximab to NHL cells Survival of SCID mice intravenously injected with Rec-1 Mantel cell lymphoma cells is increased by the Betalutin + rituximab combination (ASH poster, 2015) The efficacy of rituximab is boosted by a combination of effects after treatment with Betalutin 18
Chimeric HH1 opens up new opportunities for frontline treatment of B-cell malignancies Similar internalisation and selectivity to human lymphoid tissues as the HH1 antibody Higher Antibody Dependent Cellular Cytotoxicity (ADCC) Less immunogenic, enabling safer repeated use SCID mice with MCL xenografts treated 2/wk. with 100 mg chhh1, 100 mg HH1 or 100 ml of NaCl for 4 weeks (black arrows). After 180 days 100 % of the mice treated with chhh1 were still alive, vs. 70 % with HH1. (EANM abstract, 2015) 19
Nordic Nanovector holds a solid cash position 20
Key milestones Initiate DLBCL clinical program Start arm 3 and 4 in Phase 1/2 FL study 1Q 2016 First patient treated in DLBCL Phase 1 study 2Q 2016 Dose selection for pivotal Phase 2 / PARADIGME 1Q 2017 Dose selection for DLBCL pivotal trial 2H 2017 PARADIGME enrollment completed 2H 2018 First regulatory submission for 3L FL 1H 2019 21
Thank you for your attention! Nordic Nanovector ASA Kjelsåsveien 168 B, 0884 Oslo, Norway www.nordicnanovector.com IR contact: tkvale@nordicnanovector.com