developing first-in-class treatments in haematologic cancers · 2017. 9. 4. ·...

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Developing First-in-Class Treatments in Haematologic CancersDNB Healthcare Conference, Thursday December 15th, 2016


Forward-looking statements

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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 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.


Nordic Nanovector at a glance

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• Focused on the development of targeted therapies for haematological cancers

• Pipeline led by Betalutin® for treating non-Hodgkin lymphoma (NHL)

• Clear plan to bring Betalutin® to market

• Deep pipeline of targeted therapies for haematological cancers

• Listed on the Oslo Stock Exchange (OSE: NANO) – market cap. approx. NOK 4.8 billion*

• IPO March 2015, raising gross proceeds of NOK 575 million

• Private placement December 2016, raising gross proceeds of NOK 499 million

* As at 14 December 2016


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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

Betalutin®

Leveraging expertise to develop a broad pipeline of targeted therapies for haematological cancers


Multi-cell kill approach

• Localized tumor cell kill (40-cell radius) from irreparable double strand DNA breaks

• Cytotoxic effect on poorly perfused or non-antigen expressing cells

• Expected to deliver better treatment outcomes than anti-CD20 therapies and chemotherapy (single cell kill approach)

• Highly expressed in B-cells

• Antibody internalization anchors the payload to cancer cells, resulting in prolonged irradiation of nucleus

• Different target ideally suited to be effective for patients previously treated with CD20-based therapies

• Beta-emitting radionuclide with half-life (6.7 days) matching the circulation time of the antibody

• Mean range 0.23mm

• Payload properties are well suited for treating NHL while limiting unnecessary side effects

Design Property Differentiation

Lutetium-177 –ideal radionuclide

CD37 –a validated target for B-cell NHL

Betalutin® is specifically designed to treat NHL

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

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Potential for new CD37-targeting ARCs in FL

Decision Resources, 2015

Betalutin® Combination with rituximab

Betalutin®Single agent

2L FL$1.5 billion

approx. 8,980 (US) + 7,000 (EU-5) patients

in 2014

3L FLUSD 0.6 billion approx. 5,750 (US) +

4,480 (EU-5) patients in 2014

+

2L and 3L segments combined exceed USD 2 billion and are expected to grow 50% in the next 10 years

+1L FL

USD 1.4 billionapprox. 13,700 (US) + 10,670 (EU-5) patients

in 2014

Lu177-conjugated chimeric anti-CD37 ARC

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Tumour response confirms Betalutin®’s potential as single dose in monotherapy, with a median DOR of 20.7 months

7

ORR = Overall response rate, CR = Complete response, PR = Partial response, SD = Stable disease, PD = Progressive disease Tumour response assessed according to Cheson criteria 2007n = 35 One patient with a transformed lesion has been excluded from the efficacy analysis of the 15MBq/kg group but included the incidence of DLTsASH 2016, Poster version of the Abstract 1780, Prof. A. Kolstad et al.


ORR and CR rates in pts. receiving Betalutin® 15MBq/kg and 40mg lilotomab confirm efficacy of currently tested dosing regimen

Response rate in all patients receiving 15 MBq/kg and 40 mg lilotomab pre-dosing (n=21)

8Kolstad A et al. abstract 1780, ASH 2016

Response rate in Phase 2 patients receiving 15 MBq/kg and 40 mg lilotomab pre-dosing (n=16)


Betalutin® monotherapy offers competitive profile vs. existing and upcoming competitors in R/R FL

• * 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

Copanlisib(Phase 2)

Betalutin®(Phase 1/2)

Ibrutinib(Phase 2)3

rdLi

ne

2n

dLi

ne

74%

48%

41%

29%

40%

54%

46%

30%

73%

63%

15%

6%

11%

10%

8%

23%

3%

64%

29%

CR ORR

Nivolumab(Phase 1)

Idelalisib(Launched)

Rituximab(Launched)

Ibritumomab tiuxetan(Launched)

Duvelisib*(Phase 2)

MOR208(Phase 2)

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CTL019(Phase 2)

Kolstad et al, 2016(35 patients – ASH 2016)

Novartis, 2015(11 patients)

Bartlett et al, 2014(40 patients)

Dreyling et al, 2014(33 patients)

Gopal et al, 2014(125 patients)

Lesokhin et al, 2016(10 patients)

Jurczak et al, 2016(45 patients)

Infinity Pharma, 2016(129 patients)

McLaughlin et al, 1998(166 patients)

Witzig et al, 2002(57 patients)

Source


A higher lilotomab pre-dosing regimen (Arm 4) may positively impact haematologic toxicity

Kolstad A et al. abstract 1780, ASH 201610


Goal to improve clinical profile further for testing in pivotal PARADIGME trial

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• Phase 1 identified 20 MBq/kg as most efficacious dose yet with DLT

• Lilotomab pre-dosing crucial for use of higher and potentially more efficacious Betalutin® doses‒ Blocks Betalutin® binding to CD37 antigen on healthy

cells

‒ No impact on therapeutic levels of Betalutin® absorbed by NHL tumours

• Now recruiting to test 20 MBq/kg Betalutin® and 100 mg/m2 lilotomab (Arm 4)

• PARADIGME expected to start in Europe in 2H 2017

• Achieving Breakthrough Drug Designation from US FDA crucial to entering accelerated approval process

• Accelerated approval would enable potential first filing in 1H 2019


Betalutin®’s unique value proposition in FL is based on important differentiating factors

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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

• Suitable for more elderly and more frail patients, incl. those with co-morbidities

Convenience for patients and physicians

• One-time therapy: 100% patient compliance and improved convenience vs. oral TKIs

• No repeat visits to cancer center: improved QoL for patient

• Optimised healthcare resource utilisation

New target and combination potential

• New target (CD37) ideal for patients who progress after rituximab (anti-CD20)-based regimens

• Potential synergy from combination with anti-CD20 mAbs

TKI: Tyrosine Kinase Inhibitor

*ASH 2016, Poster version of the Abstract 1780, Prof. A. Kolstad et al


Exploring potential of Betalutin® in DLBCL, the most prevalent NHL with the greatest unmet medical need

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• Phase 1 open label, single injection, ascending dose study

• Investigate various Betalutin® doses and lilotomab pre-dosing regimens in up to 24 patients in the US and Europe

• Objective to identify an optimal dosing regimen for Phase 2

• Initial clinical centres activated, patient screening underway

*estimate market value by 2024, Decision Resources, 2015

DLBCLUSD 4.5 billion*

approx. 9,500 patients in the US and 8,170 in EU relapsed

to 2L in 2014, 70% of whom are ineligible for

stem cell transplant


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Betalutin® + rituximab increased survival in a preclinical NHL model*

*ASH 2016, Poster version of the Abstract 1489, Repetto-Llamazares et al.

• Betalutin® increased binding of rituximab to NHL cells and uptake of rituximab in NHL tumours

• Stronger anti-tumour effect in combination compared to control groups and each of the treatments alone

• Median survival time in combination: >222 days (p < 0.05)

• Survival time with either treatments alone 31 days with rituximab and 60 days with Betalutin®

Time after first treatment injection (days)

0 50 100 150 200 250

Surv

ival

0,0

0,2

0,4

0,6

0,8

1,0

5 x NaCl

177Lu-lilotomab + 4xNaCl

177Lu-lilotomab + 4 x rituximab

177Lu-lilotomab + 1 x rituximab

NaCl + 4 x rituximab

NaCl + 1 x rituximab

Survival analysis of nude mice with s.c. Daudi xenografts

Endpoint: tumour diameter ≤ 20mm N = 9-10/group


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177Lu-conjugated chimeric anti-CD37 ARC presents opportunity to target 1L NHL

• Preclinical studies confirm potential ‒ Less immunogenic – potential safer repeat dosing in NHL

patients

‒ Similar internalisation and selectivity to human lymphoid tissues as lilotomab

‒ Higher antibody dependent cellular cytotoxicity (ADCC)

• First GMP batch of chimeric antibody (NNV003) completed at contract manufacturer in USA

• Divisional Betalutin® patent application has been granted in Europe and USA

• First clinical trials expected to begin in 2017

Preclinical data

EANM 2016, Poster version of the Abstract, J. Dahle et al


177Lu-conjugated chimeric anti-CD37 ARC is the base of research collaborations to develop new targeted therapies for leukemias

16CLL: chronic lymphocytic leukaemia, AML: acute myeloid leukaemia; ADCs- antibody drug conjugates

• 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

• 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

ADCs

ARCs


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Solid cash position, further strengthened by share issue in December

• Private placement completed on December 7th

2016

• Gross proceeds NOK 499 million

• Intention for use of proceeds:‒ Fund Phase 2 combination study with Rituximab

‒ Fund Phase 1 study and GMP manufacturing for 177Lu-conjugated chimeric antibody

‒ Develop new proprietary antibody production technology

‒ Accelerate pipeline of pre-clinical assets to clinical trials

‒ Prepare for commercial launch of Betalutin®

‒ General corporate purposes

Cash flow as of 30 September 2016

* USD/NOK 8.06


Key development milestones through 2019

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• Dose-regimen selection for PARADIGME 1H 2017

• First patient treated in PARADIGME study 2H 2017

• Clinical study of Betalutin®/rituximab combo in 2L FL (start/prelim. read out) 2H 2017/2H 2018

• Clinical study of chimeric ARC in 1L FL (start/prelim. read out) 2H 2017/2H 2019

• Preliminary read out of PARADIGME study 2H 2018

• First filing for Betalutin® in 3L FL 1H 2019

• Preliminary read out of DLBCL Phase 1 study 2H 2018

• New preclinical programmes in other B-cell malignancies (leukaemias/MM) 2017-2019

Betalutin® in FL

DLBCL

Pipeline


Nordic Nanovector investment proposition

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Market Substantial unmet medical need and orphan drug opportunities, a growing NHL market worth over USD 12 billion*

Leading product First in a new class of Antibody-Radionuclide-Conjugates, designed to deliver better treatment outcomes for NHL patients with a single dose

Evidence Promising clinical data from Phase 1/2 study indicates the potential for a competitive target product profile

Strategy Well thought-out clinical strategy - unencumbered asset with all options open to maximise shareholder value

Team Management team with extensive industry experience in both development and commercialisation of anticancer drugs

*Technavio 2014, Global NHL Therapeutics Market

Pipeline Novel targeted therapies with potential to capture further value in NHL and in other B-cell malignancies

\\AD.JEFCO.COM\BANKING\HEALTHCARE INTL\DEALS\NOR45600IB - TARGET\2. FROM COMPANY\011216 UPDATED NANO TARGET DECK\NANO - TARGET LC V5 - MHN.PPTX 12/2/16 7:55 PM\\AD.JEFCO.COM\BANKING\HEALTHCARE INTL\DEALS\NOR45600IB - TARGET\2. FROM COMPANY\011216 UPDATED NANO TARGET DECK\NANO - TARGET LC V5 - MHN.PPTX 12/2/16 7:55 PM

Nordic Nanovector ASA

Kjelsåsveien 168 B, 0884 Oslo, Norway

www.nordicnanovector.com

IR contact: [email protected]

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