DEVELOPING FIRST-IN-CLASS TREATMENTS IN HAEMATOLOGIC CANCERS

Transcription

1 DEVELOPING FIRST-IN-CLASS TREATMENTS IN HAEMATOLOGIC CANCERS DEUTSCHE BANK 42ND ANNUAL HEALTH CARE CONFERENCE MAY 4, 2017 LUIGI COSTA, CEO Nordic Nanovector ASA Kjelsåsveien 168 B, 0884 Oslo, Norway IR contact:

2 Disclaimer 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 forwardlooking statements. 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

3 Nordic Nanovector at a glance Focused on the development of targeted therapies for haematological cancers Leveraging proprietary Antibody Radionuclide Conjugate (ARC) technology to build a pipeline of candidates 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 favourable safety profile Clear plan to bring Betalutin to market Designed to enhance Betalutin s chances of gaining regulatory approval with a competitive product profile Intend to independently commercialize Betalutin in major markets Deep pipeline of targeted therapies for haematological cancers Listed on the Oslo Stock Exchange (OSE: NANO) market cap. approx. NOK 3.9 billion ( $ 457 M) IPO March 2015, raising gross proceeds of NOK 575 million ($ 67 M) Private placement December 2016, raising gross proceeds of NOK 499 million ($ 59 M) 3 USD/NOK 8.53

4 A promising pipeline of targeted therapies for haematological cancers Indication Product candidate Discovery Preclinical Phase 1 Phase 2 Phase 3 Current NHL FL, 3 rd line FL, 2 nd line FL, 1 st line Betalutin Betalutin + anti-cd20 Chimeric ARC Future NHL R/R DLBCL, ineligible for ASCT R/R DLBCL, conditioning Other NHL Betalutin Betalutin Betalutin + anti-cd20 Future Haematology Leukaemia (CLL, AML) Leukaemia (CLL, AML) Multiple myeloma NNV003 ARCs NNV003 ADCs Affilutin 4 ADC: antibody-drug conjugate; ARC: antibody-radionuclide conjugate; ASCT: autologous stem cell transplant; DLBCL: diffuse large B-cell lymphoma; FL: follicular lymphoma; NHL: non-hodgkin lymphoma

5 Betalutin is specifically designed to treat NHL DESIGN PROPERTY DIFFERENTIATION CD37 a validated target for B-cell NHL Highly expressed in B-cells Antibody internalization anchors the payload to cancer cells, resulting in prolonged irradiation of nucleusarial Different target ideally suited to be effective for patients previously treated with CD20-based therapies Lutetium-177 ideal radionuclide Beta-emitting radionuclide with half-life (6.7 days) matching the circulation time of the antibody A mean penetration depth of 0.23mm Payload properties are well suited for treating NHL while limiting unnecessary side effects Multi-cell kill approach Localised tumour cell kill (40-cell radius) from irreparable double strand DNA breaks Cytotoxic effect on poorly perfused or nonantigen expressing cells Expected to deliver better treatment outcomes than anti-cd20 therapies and chemotherapy (single cell kill approach) Lilotomab pre-dosing Prioritises Betalutin binding to CD37 on NHL cells Binds CD37 on B-cells and blocks Betalutin binding minimises side effects Enhances attractiveness of CD37 as target for new NHL therapy 5

6 Follicular Lymphoma (FL) represents a large unmet medical need with no cure Newly Diagnosed (1st line) Relapsed / Refractory (2nd line) Double Relapse / Refractory (3rd line) Late Stage / Double Refractory (Later lines) Approx. 24,000 patients (US + EU5) Approx. 16,000 patients (US + EU5) Approx. 10,000 patients (US + EU5) Approx. 5,000 patients (US + EU5) Anti-CD20 (Rituximab, obinutuzumab) + + Chemotherapy (Bendamustine, CHOP, CVP) Followed by: Rituximab maintenance Radioimmunotherapy + Anti-CD20 (Rituximab, obinutuzumab) Chemotherapy (Bendamustine, fludarabine, CHOP) OR Anti-CD20 (Rituximab, obinutuzumab) Immunomodulatory agents (Lenalidomide) Idelalisib (Mono) OR Rituximab (Mono) OR Radioimmunotherapy OR Clinical trials with novel drugs (CAR-T) BSC / Palliative therapy OR Radioimmunotherapy Followed by: High dose chemo + Stem Cell Transplant Allogenic SCT Rituximab / Obinutuzumab maintenance + Rituximab Lenalidomide OR Ibrutinib (Mono) Remission Remission Remission Remission Remission 6 Relapse Relapse Relapse Relapse

7 Betalutin s Phase 1/2 study in NHL will enable the selection of optimal dosing regimen for Phase 2 PHASE 1 PHASE 2 ARM 1 10MBq/kg (- llo + R0) N = 1 10MBq/kg (+ 40mg llo) N = 3 ARM 2 20MBq/kg (+ 40mg llo) N = 3 15MBq/kg (- llo) N = 2 ARM 3 15MBq/kg (+ 100mg/m 2 llo) N = 3 ARM 4 15MBq/kg (+ 40mg llo) N = 6 10MBq/kg (- llo) N = 1 15MBq/kg (- llo + R0) N = 3 20MBq/kg (+ 100mg/m 2 llo) N 3 15MBq/kg (+ 40mg llo) N = 24 Discontinued Discontinued ARM 1: Determine Betalutin safety/efficacy using a lower lilotomab pre-dose ARM 2: Determine the role of pre-dosing treatment with lilotomab cold antibody ARM 3: Determine the role of pre-dosing with rituximab ARM 4: Determine Betalutin safety/efficacy using a higher lilotomab pre-dose 7 MBq: Megabecquerel; llo: lilotomab; R0: rituximab predosing on day 0; Completed step (all patients enrolled).

8 ASH 2016 update: Tumour response rates confirm Betalutin s potential to deliver clinical benefits Response rate all patients treated in Phase 1/2* ORR = Overall response rate, CR = Complete response, PR = Partial response, SD = Stable disease, PD = Progressive disease. Tumour response assessed according to Cheson criteria One patient with a transformed lesion has been excluded from the efficacy analysis of the 15MBq/kg group but included the incidence of DLTs. ASH 2016, Poster version of the Abstract 1780, Prof. A Kolstad et al. 8 * Data from 38 heavily pre-treated NHL patients presented (Dec 2016). 38 evaluable for safety.

9 The efficacy of Betalutin 15MBq/kg with 40mg lilotomab pre-dosing was confirmed in Phase 2 Response rate in all patients receiving 15 MBq/kg and 40 mg lilotomab pre-dosing (n=21) Response rate in Phase 2 patients receiving 15 MBq/kg and 40 mg lilotomab pre-dosing (n=16) 9 ASH 2016, Poster version of the Abstract 1780, Prof. A Kolstad et al.

10 Tumor reduction observed in 89% of patients with a DOR of almost 21 months Tumor size reduction Median Duration of Response* * Arm 1 patients 10 ASH 2016, Poster version of the Abstract 1780, Prof. A Kolstad et al.

11 2 nd Line 3 rd Line Betalutin as a single agent holds significant edge over existing and upcoming competitors in R/R FL CRR ORR mdor (months) mpfs (months) mos (months) Source Betalutin (Phase I) 29% 63% ~21m Kolstad et al, 2016 (35 patients - ASH 2016) CTL019 (Phase II) 50% 79% 15m 83% 15m ~65% -- Novartis, ASH 2016 (14 patients) Ibrutinib (Phase II) 3% 30% -- ~10m -- Bartlett et al, 2014 (40 patients) Copanlisib (Phase II) 14% 59% ~12m Bayer Press Release, 2017 (141 pts., of which 104 FL) Duvelisib* (Phase II) 0% 41% Versatem Pharma, 2016 (83 patients) Idelalisib (Launched) 8% 54% >12.5m -- ~20.3m Gopal et al, 2014 (125 patients) Nivolumab (Phase I) 10% 40% Lesokhin et al, 2016 (10 patients) MOR208 (Phase II) 11% 29% >16m 12m >40% -- Jurczak et al, 2016 (45 patients) Rituximab (Launched) 6% 48% -- ~13m -- McLaughlin et al, 1998 (166 patients) Ibritumomab; tiuxetan (Launched) 15% 74% ~6.5m ~7m -- Witzig et al, 2002 (57 patients) 11 * Data read-out suggests not very strong results. Infinity is still in touch with FDA to look for future action. All agents are approved based on different phase results as mentioned along with asset. Results from different trials for comparison purpose only and NOT head to head studies

12 % Tumor Reduction In most patients Betalutin has a prolonging effect in reducing tumor size Change in tumor size over time* Pre-treatment Month 3 Month 6 Month 9 Month 12 Month 18 Month 24 Month MBq/kg 15 MBq/kg 20 MBq/kg Still in follow-up Progressed and withdrawn Time Since Betalutin Treatment * Arm 1 patients 12 ASH 2016, Poster version of the Abstract 1780, Prof. A Kolstad et al.

13 Betalutin s unique value proposition in FL is based on important differentiating factors New target New target (CD37) ideal for patients who progress after rituximab (anti-cd20)-based regimens High and durable response* Significantly higher Complete Response than current and future competitors, as a single agent Sustained Duration of Response in heavily pre-treated patients Predictable and manageable toxicity* Minimal non-haematological toxicity Predictable, transient and reversible cytopenias Convenience for patients and physicians One-time therapy: 100% patient compliance and superior convenience No repeat visits to cancer centre: improved QoL for patient Optimised healthcare resource utilisation Combination potential Potential synergy from combination with anti-cd20 mabs and others 13 *ASH 2016, Poster version of the Abstract 1780, Prof. A. Kolstad et al.

14 S u r v i v a l Betalutin + rituximab significantly decreases tumor growth and increases survival in a preclinical NHL model* Average volume of s.c. Daudi xenografts in nude mice Survival analysis of nude mice with s.c. Daudi xenografts Median survival time in combination: >222 days (p < 0.05) vs. 31 and 40 days 14 Endpoint: tumour diameter 20 mm. N = 9-10/group *ASH 2016, Poster version of the Abstract 1489, Repetto-Llamazares et al.

15 Exploring market potential of Betalutin in DLBCL, the most prevalent NHL with the greatest unmet medical need 10 MBq/kg (+ 60mg/m 2 llo) N = 3 10 MBq/kg (+ 100mg/m 2 llo) N = 3 Lymrit Phase 1 15 MBq/kg (+ 60 or 100mg/m 2 llo) N = 3 20 MBq/kg (+ 60 or 100mg/m 2 llo) N = 3 DLBCL $4.5B* approx. 9,500 patients in the US and 8,170 in EU relapsed to 2L, 70% of whom are ineligible for stem cell transplant One of the most common forms of NHL with unmet medical need Phase 1 open label, single injection, ascending dose study Investigate various Betalutin doses and lilotomab pre-dosing regimens in up to 24 patients Study open for enrolment in the US and EU, patient screening underway Objective to identify an optimal dosing regimen for Phase 2 15 N = 3-24 llo:lilotomab - CD37 B-cell seeking antibody Day -14: rituximab; Day 0: Intermediate dose llo; Day 0: High dose llo; Day 0: Betalutin* *estimate market value by 2024, Decision Resources, 2015

16 177 Lu-conjugated chimeric anti-cd37 ARC: base of research collaborations to develop new targeted therapies for leukemias ARCs Develop new ARCs optimised for treating leukaemias, e.g. CLL, AML >50,000 patients relapse every year worldwide Market estimated to grow to USD 5 billion by 2020 Supported by grant funding from the Research Council of Norway ADCs Early stage R&D collaborations to develop new ADCs optimised for treating leukaemias Leveraging CD37 targeting and biologics expertise of Nordic Nanovector and complementary technologies of partners 16 CLL: chronic lymphocytic leukaemia, AML: acute myeloid leukaemia; ADCs- antibody drug conjugates

17 MNOK Cash position strengthened by successful share issue in December Private placement completed on December 7 th 2016, gross proceeds NOK 499 million ($ 59 M) Cash flow 2016 Strong international interest Intention for use of proceeds: Fund a Phase 2 combination study of Betalutin and rituximab Fund a Phase 1 study for 177Lu-conjugated chimeric antibody (anti-cd37 ARC) Develop new proprietary antibody production technology $ 118 M* Accelerate pipeline of preclinical assets to clinical trials Prepare for commercial launch of Betalutin General corporate purposes 0 Cash Operating activities Investing and financing activities FX Net proceeds share issue Cash USD/NOK 8.64

18 MNOK Operating loss reflecting development activities Operating loss Operating expenses distribution FY , ,8-51,1-62,9-33,3-52,7-48,1-50,3-65,3 30 % 70 % -52,5-70 Q1'15 Q2'15 Q3'15 Q4'15 Q1'16 Q2'16 Q3'16 Q4'16 Development* Administration Operating expenses impacted by high level of clinical trial activity and preclinical R&D activities 18 *Development costs: preclinical, clinical, regulatory and CMC activities

19 Key development milestones through H 2017 Dose-regimen selection for PARADIGME 2H 2017 First patient treated in PARADIGME study 2H 2017/2H 2018 Clinical study of Betalutin /rituximab combo in 2L FL (start/prelim. read out) 2H 2017/2H 2019 Clinical study of chimeric ARC in 1L FL (start/prelim. read out) 2H 2018 Preliminary read out of PARADIGME study 1H 2019 First filing for Betalutin in 3L FL Betalutin in FL DLBCL Pipeline New preclinical programmes in other B-cell malignancies (leukaemia/mm) 2H 2018 Preliminary read out of DLBCL Phase 1 study 19

20 Nordic Nanovector s mission is to extend and improve the lives of patients with haematological cancers by developing and commercialising innovative Antibody Radionuclide Conjugates (ARC) Nordic Nanovector ASA Kjelsåsveien 168 B, 0884 Oslo, Norway IR contact: tkvale@nordicnanovector.com