ASH POSTER: LYMRIT UPDATE

Transcription

1 ASH POSTER: LYMRIT UPDATE DECEMBER 2018 EDUARDO BRAVO, CEO LISA ROJKJAER, MD, CMO Nordic Nanovector ASA Kjelsåsveien 168 B, 0884 Oslo, Norway IR contact:

2 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 2

3 Introduction Betalutin is a novel beta-emitting anti-cd37 antibody-radionuclide conjugate (ARC) in a ready-touse formulation for single-dose administration Betalutin has a Fast Track designation for relapsed or refractory follicular lymphoma (R/R FL) patients who have received 2 prior therapies (US), and a Promising Innovative Medicine (PIM) designation in the UK for advanced R/R FL The Phase 1/2 LYMRIT study was designed to determine the best way to administer Betalutin, and to assess the safety, pharmacokinetics and activity of Betalutin in patients with relapsed indolent NHL (inhl) Results for 74 patients are reported in this analysis (presented at ASH), with a minimum of 6 months of follow-up (data cut-off of 2 November 2018) 3 Kolstad A, et al. Abstract 2879, ASH ASH American Society of Hematology annual meeting December 2018, San Diego, CA, USA.

4 LYMRIT study design: 74 inhl patients were enrolled Phase 1 dose-escalation cohorts (3 + 3 design) Phase 2a doseexpansion cohorts Pre-dose Betalutin ARM 1 Rituximab Rituximab Lilotomab 375 mg/m mg/m 2 40 mg 10, 15, 20 MBq/kg RDE*: 15 MBq/kg Betalutin n=30 ARM 2 Rituximab Rituximab 10, mg/m mg/m 2 No pre-dose Arm closed MBq/kg ARM 3 Rituximab Rituximab 375 mg/m mg/m 2 15 MBq/kg Arm closed ARM 4 Rituximab Lilotomab 15, 20 RDE: 20 MBq/kg 375 mg/m mg/m 2 MBq/kg Betalutin n=12 ARM 5 Rituximab Lilotomab 375 mg/m 2 60 mg/m 2 20 MBq/kg Study Day Day -28 Day -21 Day -14 Day 0 * RDE recommended dose for expansion 4 Kolstad A, et al. Abstract 2879, ASH 2018.

5 Elderly, heavily-pre-treated, primarily FL patients with advanced stage disease at baseline All Patients (n=74) FL (n=57) Other * (n=17) Median age, years (range) 65, n (%) 68 (38-87) 51 (69%) 69 (40-80) 36 (63%) 68 (57-88) 12 (70%) Ann Arbor stage at diagnosis ** I/II III/IV Unknown 5 (12%) 27 (64%) 10 (24%) 5 (17%) 18 (62%) 6 (21%) 0 (0%) 9 (69%) 4 (31%) Prior regimens, median (range) 2 prior regimens Prior alkylating agent Rituximab refractory 3 (1-9) 48 (65%) 60 (81%) 33 (44%) 3 (1-9) 37 (65%) 44 (77%) 30 (53%) 3 (1-7) 11 (65%) 16 (94%) 3 (18%) * Mantle cell lymphoma (MCL; n=7), marginal zone lymphoma (MZL; n=9), small lymphocytic lymphoma (SLL; n=1) ** Info available for Phase 2 patients only (n=42) 5 Kolstad A, et al. Abstract 2879, ASH 2018.

6 Most common grade 3/4 adverse events were transient, reversible neutropenia and thrombocytopenia G3/4 AEs occurring in 2 or more patients Adverse Event G3 n (%) G4 n (%) Overall, Betalutin was well-tolerated Neutropenia 26 (35%) 14 (19%) Thrombocytopenia 21 (25%) 15 (20%) Leukopenia 30 (40%) 4 (5%) Lymphopenia 23 (31%) 2 (3%) Infections Urinary tract infection Pneumonia Sepsis/neutropenic sepsis Bleeding Epistaxis Hematuria Hyperglycemia Lymphoma progression 1 (1%) 1 (1%) 1 (1%) 1 (1%) 2 (3%) 4 (5%) (3%) (1%) SAEs occurred in 14 patients (19%). SAES in 2 patients were atrial fibrillation, thrombocytopenia, NHL progression and sepsis (all n=2) No cases of febrile neutropenia Low incidence of platelet transfusions (5 in total; 2 for bleeding) 18 months after subsequent treatment with bendamustine (24 months after Betalutin ), MDS/CMML was reported in 1 patient with prior alkylating agent exposure No study drug-related deaths occurred in the treatment period 6 Kolstad A, et al. Abstract 2879, ASH *SAEs: Serious Adverse Events **MDS/CMML: Myelodysplastic Syndrome/Chronic Myelomonocytic Leukemia

7 Overall response rates (ORR=CR+PR) for all patients (n=74): Promising ORRs in follicular (FL) and marginal zone lymphoma (MZL) Subtype ORR* n (%) CR* n (%) PR* n (%) SD* n (%) PD* n (%) FL (n=57) 37 (65%) 16 (28%) 21 (37%) 10 (18%) 10 (18%) MZL (n=9) 7 (78%) 4 (44%) 3 (33%) 2 (22%) -- MCL (n=7)** 1 (14%) 1 (14%) -- 2 (28%) 4 (57%) SLL (n=1)** Total 61% 28% 32% 19% 20% * ORR Overall Response Rate; CR Complete Response; PR Partial Response; SD Stable Disease; PD Progressive Disease ** MCL - Mantle Cell Lymphoma SLL Small Lymphocytic Lymphoma 7 Kolstad A, et al. Abstract 2879, ASH 2018

8 Highly active in advanced follicular lymphoma and in FL patients who are refractory to rituximab ORR (CR + PR) CR All FL patients (n=57) 65% 28% 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% * RTX: rituximab 8 Kolstad A, et al. Abstract 2879, ASH 2018

9 Percentage change in tumour size (SPD)* Poster # % of evaluable patients had a decrease in tumour size Kolstad A, et al. Abstract 2879, ASH *SPD = sum of the products of the diameters. ** Change in size of target lesion is beyond the scale for this figure (n=2). ** Individual Patients Follicular (FL) (n=57) Marginal zone (MZL) (n=9) Mantle cell (MCL) (n=5) 4 patients (1 FL, 1 SLL, 2 MCL) had clinical disease progression without CT scan 1 patient with no measurable target lesion at baseline

10 Median duration of response (9 months for all patients with CR or PR; n=45) More durable responses for patients with a CR (20.7 months) All pts (9.0 m) With CR (20.7 m) 10 Kolstad A, et al. Abstract 2879, ASH 2018.

11 Response duration for all pts (CR, PR, SD) by NHL subtype (n=59) 34% of all 74 patients remain free of disease progression for 12 months 11 Kolstad A, et al. Abstract 2879, ASH 2018.

12 Individual patients Adapted from Poster # 2879 Complete responders have long lasting responses (20.7 months) 12 out of 21 CRs are still in follow up CR Response episode end Continued response Months after start of treatment 12 Kolstad A, et al. Abstract 2879, ASH 2018.

13 3 rd Line Betalutin : Promising clinical profile from a one-time treatment CR ORR DoR (months) Source Mechanism of action Route of administration Additional care required Betalutin * (Phase 2) 32% 70% 9.0 Kolstad et al, ASH 2018 (37 3L FL pts) CD37-targeting RIT IV infusion (one time administration), preceded by 1 RTX and 1 lilotomab No - convenient one-time administration Idelalisib** (Launched) 8% 54% 12.5 Prescribing info (125 pts) Pi3k inhibitor Oral, twice daily Combination with other treatments may increase toxicity Copanlisib** (Launched) 14% 59% 12.2 Prescribing info (104 pts) Pi3k inhibitor IV infusion (weekly 3 weeks on and 1 No week off) until progression Duvelisib** (Launched) 1% 43% 7.9 Zinzani et al (83 pts - EHA 2017) Pi3k inhibitor Oral, twice daily, until disease progression No INCB (Phase 2) 21% 59% 71% n/a ASH 2017 (14 pts) Pi3k inhibitor Oral, once daily No Tazemetostat EZH2m+ (15-20% FL) (Phase 2) 11% 71% 9 Epizyme, EHA 2018 (82 pts) EZH2 inhibitor Oral, twice daily No ME-401 (Phase 2) 21% 86% n/a ASCO 2018 (30 pts) Pi3k inhibitor Oral, once daily No Tisagenlecleucel (Phase 2) 50% 79% 15 (83%) Novartis, ASH 2016 (14 pts) CAR-T cell therapy IV infusion of re-engineered autologous T-cells, preceded by leukapheresis and CT Not all patients eligible; leukapheresis may not yield enough T cells; few institutions can deliver this treatment 13 Results from different trials for comparison purpose only and NOT head to head studies RIT radioimmunotherapy; RTX: rituximab; IV: intravenous; CT: chemotherapy * Data is from the LYMRIT trial (Phase I/IIa) presented at ASH December 2018 ** Accelerated Approval based on Phase II

14 Summary Single-agent Betalutin is effective and well-tolerated in elderly, heavily pre-treated population of patients with recurrent inhl: Overall response rate of 61% (CR 28%) Highly active in FL patients with 2 prior therapies (ORR 70% CR 32%), and RTX-refractory FL (ORR 62% CR 19%) Durable responses, especially for patients with a CR (20.7 months for all patients) Betalutin has a distinct safety profile that is favorable compared to standard immunochemotherapy or PI3K inhibitors, especially with respect to infections Follow-up for DoR is on-going With its promising clinical profile, ready-to-use formulation and one-time administration, Betalutin has the potential to be a novel, safe and effective therapy for recurrent B-cell lymphoma Two recommended dosing regimens are now being compared in a randomised Phase 2b cohort ( PARADIGME ) in relapsed, anti CD20-refractory FL patients who have received 2 prior therapies 14 Kolstad A, et al. Abstract 2879, ASH 2018.