Nykode Therapeutics Asa · OSL:NYKD
Nykode Therapeutics Asa — Vaccibody AS — Investor Day (November 2019)
45 slides from Nykode Therapeutics Asa's investor day presentation, Nov 12, 2019
Slide 1: Vaccibody AS Capital Markets Day
Vaccibody AS Capital Markets Day November 12, 2019 Agnete B Fredriksen President & CSO & Michael Engsig CEO
Slide 2: Capital Markets Day - Program
Capital Markets Day - Program • 14.00-14.10 Introduction Michael Engsig • 14.10-15.00 Update on the VB N-01 study including the clinical data Agnete Fredriksen • 15.00-15.45 Status of the cancer vaccine field and development of novel immunotherapies Ulrich Granzer • 15.45-16.05 Company update Michae
Slide 3: Agenda
Agenda Introduction 1. Update on the VB N-01 study including the 2. clinical data Status of the cancer vaccine field and 3. development of novel immunotherapies 4. Company update and Q&A Non-confidential 3
Slide 4: Experienced International Management Team with Solid Drug Development Experience
Experienced International Management Team with Solid Drug Development Experience • Privately-held clinical stage immuno-oncology company, 28 employees • Proprietary, patented cancer vaccine technology and early clinical proof-of-concept • Experienced, international management team with oncology expe
Slide 5: Vaccibody Product Pipeline
Vaccibody Product Pipeline PROGRAM DISCOVERY PRE-CLINICAL PHASE I PHASE II PHASE III MELANOMA LUNG (NSCLC) BLADDER VB10.NEO RENAL HEAD AND NECK HEAD AND NECK VB10.NEO + NKTR-214 PRECANCEROUS VB10.16 CERVICAL LESIONS CERVICAL VB10.16 + Atezolizumab (CPI) Non-confidential 5
Slide 6: Agenda
Agenda Introduction 1. Update on the VB N-01 study including the 2. clinical data Status of the cancer vaccine field and 3. development of novel immunotherapies 4. Company update and Q&A Non-confidential 6
Slide 7: Vaccibody – Proprietary Vaccine Technology Platform
Vaccibody – Proprietary Vaccine Technology Platform The Vaccibody Technology Platform is developed based on the concept of targeting antigen to Antigen Presenting Cells (APCs) in order to create more efficacious vaccines Target to Antigen Presenting Cell In vivo expression Dimerization for crosslink
Slide 8: Mechanism of Action: the Multiple Effects of MIP-1α as Targeting Unit
Mechanism of Action: the Multiple Effects of MIP-1α as Targeting Unit Administration In vivo protein Target – Attract – Mature – Deliver – Cross-present (i.m.) of DNA expression plasmid and secretion MIP-1α: Skewing the immune system to a CD8+ killer T-Cell response Deltoid Muscle Direct targeting
Slide 9: Strong Correlation Between Immune Response and Lesion Size Reduction
Strong Correlation Between Strength of Induced HPV16-Specific Immune Response and Lesion Size Reduction in the Dosing Phase Cohort 1 Cohort 2 H PV16 E7 8000 8000 H PV16 E7 H PV16 E6 6000 6000 H PV16 E6 PBMCs 4000 PBMCs 4000 2000 2000 6 1000 1000 6 S F U /1 0 S F U /1 0 800 800 600 600 400 400 200 20
Slide 10: Adding an Extra Dose Increased the Immune Response
Adding an Extra Dose Increased the Immune Response 4000 E x p a n s io n C o h o rt (N = 1 7 ) D o s in g C o h o rt 1 (N = 7 ) PBMCs 3000 2000 6 S F U /1 0 1000 0 0 4 8 12 16 20 24 tim e a fte r 1 s t d o s e (w e e k ) • The vaccination regimen from cohort 1 (week 0, 3 and 6) plus a booster vaccin
Slide 11: Promising Clinical Efficacy with Excellent Safety; Improved in Expansion Phase
Promising Clinical Efficacy with Excellent Safety; Improved in Expansion Phase Best response data (At enrollment: 10 CIN3 and 7 CIN2 patients) 100 no CIN % c h a n g e le s io n s iz e 50 CIN1 CIN2 CIN3 0 -5 0 HPV16 and/or p16 clearance -1 0 0 VB10.16 as a monotherapy in HPV16-positive, precancerous
Slide 12: VB10.NEO Has a Unique Ability to Induce Strong Neoepitope-Specific CD8 T-Cell Responses
VB10.NEO Has a Unique Ability to Induce Strong Neoepitope-Specific CD8 T-Cell Responses MC38 colon carcinoma Yadav et al., 2014 mouse model VB10.NEO Peptide + poly I:C + anti-CD40 mAb 2500 2000 C D 4 re s p o n s e s c e l ls C D 8 re s p o n s e s 6 1500 I F N - γ s p o t s /1 0 1000 500 0 f k t1 q
Slide 13: Neoepitope-Specific CD8 T-cells Are Crucial for Tumour Protection
Neoepitope-Specific CD8 T-cells Are Crucial for Tumour Protection Average, all groups Individual growth curves 2 .5 PBS VB10.NEO VB10.NEO + anti-CD4 VB10.NEO+ anti-CD8 V B 1 0 .N E O 25 25 25 2 .0 V B 1 0 .N E O + a n t i- C D 4 T u m o r v o lu m e (c m ) 3 20 T u m o r le n g th (m m ) V B 1 0 .N
Slide 14: VB10.NEO Has Proven to Induce an Effective Anti-Tumour Response
VB10.NEO Has Proven to Induce an Effective Anti-Tumour Response Neoepitope-specific Neoepitope-specific Influx of cytotoxic T cells in TILs recognize and kill Tumor protective immune CD8+ T cell T cell response in tumor (TILs) tumor cells responses elicited in response in spleen tumor vaccinated mic
Slide 15: Proprietary NeoSELECT Was Developed to Match VB10.NEO’s Mode of Action
Proprietary NeoSELECT Was Developed to Match VB10.NEO’s Mode of Action In vivo mouse experiments NeoRANKTM VB10.NEO IFN-γ ELISpot Patients (CD8/CD4) Neoantigen filtering and ranking > 350 neoantigens Trained and verified on in vivo mouse data 2 mouse strains 4 tumour models Anti-tumour efficac
Slide 16: VB N-01 Clinical Trial Was Designed to Evaluate VB10.NEO in Five Indications
VB N-01 Clinical Trial Was Designed to Evaluate VB10.NEO in Five Indications VB N-01: An open labelled first human dose phase 1/2a study to evaluate safety, feasibility and efficacy of multiple dosing with individualized VB10.NEO immunotherapy in patients with locally advanced or metastatic melanoma
Slide 17: High focus on successful and fast manufacturing
High focus on successful and fast manufacturing • So far, 100% manufacturing success rate for patients providing a successful biopsy - Best in class • Top choice of 20 neoepitopes used for every patient • Proven feasibility and stability data from all initial batches • Confidence in reaching best in
Slide 18: Nine Leading Clinical Sites in Germany Are Engaged & Aimed for Initiation by Q4
Nine Leading Clinical Sites in Germany Are Engaged & Aimed for Initiation by Q4 01 NCT Heidelberg 04 Charité Campus 07 Universitätsklinikum Ulm Benjamin Franklin, Berlin Prof. Krauss* Dr. Laban Dr. Ochsenreither 02 Klinikum rechts der Isar, 05 Universitätsklinik 08 Universitätsklinikum 04 München Wü
Slide 19: Treatment Schedule for Patients Enrolled in the VB N-01 Trial
Treatment Schedule for Patients Enrolled in the VB N-01 Trial 12 months 24 months ~12 weeks 6 weeks Sequencing, Vaccination Vaccination Synthesis & Follow Up Prime Maintenance Manufacturing CPI Consent Week 0 3 6 10 14 18 22 26 30 34 38 42 46 50 treatment + >12 weeks Biopsy Dose # 1 2 3 4 5 6 7 8 9
Slide 20: Treatment Design Allows Evaluation of VB10.NEO-Induced Clinical Responses
Treatment Design Allows Evaluation of VB10.NEO-Induced Clinical Responses Not Vaccibody data • After 6 months on CPI treatment, most patients are stable or relapse (progressive) • If they progress, they normally continue to progress Tsimberidou et al., 2018 Confidential 20
Slide 21: Heavily Pre-Treated Patients Treated with CPI Monotherapy for 9-32 Months
Heavily Pre-Treated Patients Treated with CPI Monotherapy for 9-32 Months Before Adding VB10.NEO months CPI Best status at before response on status at start patient indication diagnosed age prior therapy TNM TMB VB10.NEO CPI screening VB10.NEO 01-002 SCCHN 2005 53 S, Rt, T, ct, o N2M1 low 32 SD SD
Slide 22: SCCHN (Head & Neck): Clinical Responses Observed After VB10.NEO Initiation
SCCHN (Head & Neck): Clinical Responses Observed After VB10.NEO Initiation in All Patients Tumour shrinkage or stabilization of progressing lesions 01-002 Strong immune responses in all assessed patients Disease Status Before VB10.NEO Progressive Disease Stable Disease s in c e s t a r t o f V B 1 0
Slide 23: SCCHN (Head & Neck): Change in All Individual Target Lesions
SCCHN (Head & Neck): Change in All Individual Target Lesions Before and After VB10.NEO Treatment % c h a n g e in s iz e o f a ll t a r g e t le s io n s % c h a n g e in s iz e o f a ll t a r g e t le s io n s S C C H N / 0 1 -0 0 2 S C C H N / 0 1 -0 0 4 40 40 A* A* B 20 Key Learnings (Head & Neck
Slide 24: Melanoma (Skin): VB10.NEO Induce Several de novo T Cell Responses
Melanoma (Skin): VB10.NEO Induce Several de novo T Cell Responses and Increased Tumour Shrinkage 1st dose P re -va c c VB10.NEO W eek 10 % c h a n g e in le s io n s iz e u s e d 400 20 W eek 22 0 2 -0 0 3 to s e le c t n e o a n tig e n s 300 S P U /1 0 e 6 P B M C 10 200 100 100 0 50 -1 0 0 -2 0 p
Slide 25: NSCLC (Lung): Rapid Reduction in Target Lesion Size
NSCLC (Lung): Rapid Reduction in Target Lesion Size after VB10.NEO Treatment 1st dose VB10.NEO % c h a n g e in le s io n s iz e u s e d 20 0 2 -0 0 7 * t o s e le c t n e o a n tig e n s 0 -2 0 -4 0 [w k s ] -2 4 -1 2 0 12 24 * Immune response not yet assessed (too early) NSCLC (Lung Cancer): • Rap
Slide 26: RCC (Renal): Reduced Growth and Long-Term Continuous Stable Lesions
RCC (Renal): Reduced Growth and Long-Term Continuous Stable Lesions P re -v a c c 01-001 Clinical responses after VB10.NEO initiation 10000 8000 W eek 22 6000 S P U /1 0 e 6 P B M C 6000 5000 Disease Status Before VB10.NEO s in c e s t a r t o f V B 1 0 .N E O t r e a t m e n t 4000 % c h a n g e in
Slide 27: RCC (Renal): Change Was Seen in All Individual Target Lesions
RCC (Renal): Change Was Seen in All Individual Target Lesions Before and After Treatment with VB10.NEO % c h a n g e in s iz e o f a ll t a r g e t le s io n s A ) 0 1 -0 0 1 B ) 0 1 -0 0 3 C ) 0 1 -0 0 5 % c h a n g e in s iz e o f a ll t a r g e t le s io n s % c h a n g e in s iz e o f a ll t a r
Slide 28: SCCHN Case study: A Closer Look at Tumour Cells (patient 01-002)
SCCHN Case study: A Closer Look at Tumour Cells (patient 01-002) Screening % c h a n g e in s iz e o f all ta r g e t le s io n s S C C H N / 0 1 -0 0 2 40 Biopsy A* Cervical LN B Lung Follow-up 20 C Cervical LN 0 -2 0 -4 0 [w k s ] -1 2 0 12 24 36 Strong evidence that VB10.NEO has caused killing of
Slide 29: Summary of Clinical Observations: VB10.NEO Causes Shrinkage of Tumours
Summary of Clinical Observations: VB10.NEO Causes Shrinkage of Tumours and Stabilization of Progressing Lesions VB10.NEO is the first cancer vaccine to show a strong ability to shrink tumours in multiple patients with advanced metastatic disease Kinetics: Shrinkage occurs 9-24 weeks after first do
Slide 30: Patients with High TMB Responds Better to Immunotherapies
Patients with High TMB Responds Better to Immunotherapies Most VB N-01 Strong relationship between Tumor Mutational patients Burden (TMB) and response to CPI Limits response to already existing neoantigen- specific T cell repertoire Patients with low TMB have worse prognosis on CPI Our patient popul
Slide 31: Clinical Response Was Seen Even in Patients with Low TMB
Clinical Response Was Seen Even in Patients with Low TMB, Indicating Potential in a Broad Setting and Large Number of Indications 200 S u m o f ta r g e t le s io n s [m m ] C lin ic a l re s p o n s e N o c lin c ia l re s p o n s e 150 100 Broad potential for vaccine-induced 50 clinical responses
Slide 32: Patients with Clinical Response Had a Higher Number of Neoepitopes
Patients with Clinical Response Had a Higher Number of Neoepitopes - and Thus a Better Opportunity to Select High-Quality Neoepitopes SCCHN Patient 01-006 T1 Patient 01-010 Patient 01-004 Patient 01-002 T1 T1 52 2 T1 72 2 16 9 16 2 17 2 1 5 13 5 T2 2 20 20 Vaccine T2 15 9 Vaccine T2 T2 Vaccine Vacci
Slide 33: Lower Quality Neoepitopes in Renal Cancer Patients
Lower Quality Neoepitopes in Renal Cancer Patients Make It More Difficult to Develop a Potent Vaccine RCC Patient 01-003* Patient 01-005* Patient 01-001 Patient 01-007 T2 T2 0 T1 T1 7 2 49 7 3 5 20 17 20 10 T2 10 T2* 20 Vaccine Vaccine Vaccine *Not used in neoepitope selection Vaccine Patient 01-009
Slide 34: Patients With Clinical Responses Have the Strongest Immune Response Profile
Patients With Clinical Responses Have the Strongest Immune Response Profile and Highest Frequency of High-Quality Neoepitopes Frequency of high quality neoepitopes vs change in lesion Frequency of immunogenic neoepitopes vs change in lesion size size Patients with clinical response after VB10.NEO va
Slide 35: Strong, Dominating CD8 T Cell Responses Are Correlated with Clinical Responses
Strong, Dominating CD8 T Cell Responses Are Correlated with Clinical Responses CD8 dominated CD4 dominated responses responses A ) 0 1 -0 0 1 P re -v a c c W eek 22 10000 8000 6000 S P U /1 0 e 6 P B M C 6000 5000 4000 3000 2000 1000 0 pep 10 pep 11 pep 12 pep 13 pep 14 pep 15 pep 16 pep 17 pep 18 p
Slide 36: Neoepitope-specific CD8 dominating immune responses in SCCHN patients
Neoepitope-specific CD8 dominating immune responses in SCCHN patients with clinical response 3 epitopes from 01-004 P re -v a c c W eek 22 6000 5000 4000 S P U /1 0 e 6 P B M C 3000 2000 1000 500 400 300 200 100 0 pep 10 pep 11 pep 12 pep 13 pep 14 pep 15 pep 16 pep 17 pep 18 pep 19 pep 20 pep 1 pep
Slide 37: Key Highlights
Key Highlights Ongoing basket trial across 5 solid tumour indications Breakthrough data VB10.NEO is the first cancer vaccine to show a strong ability to shrink tumours in multiple patients with advanced metastatic disease with Neoantigen Tumour shrinkage is observed even after long-term PD-1 / P
Slide 38: Agenda
Agenda Introduction 1. Update on the VB N-01 study including the 2. clinical data Status of the cancer vaccine field and 3. development of novel immunotherapies 4. Company update and Q&A Non-confidential 38
Slide 39: Vaccibody Achievements
Vaccibody Achievements • Clinical proof of principle established from VB C-01 • Ability to raise an antigen specific immune response in humans • Immune response translate into meaningful clinical improvement in pre- cancer setting • Promising initial data from VB N-01 • Developed a promising concept
Slide 40: Vaccibody’s Solid Base
Vaccibody’s Solid Base • 299 mNOK in cash and cash equivalents as of Sept 30, 2019 • Diverse and active shareholder base, approx. 280 shareholders • Raised 509 mNOK in equity since inception • Traded “over the counter” by Arctic, ABG, DNB, Carnegie • Solid IP base with multiple layers of protection
Slide 41: Update since September Capital Markets Day
Update since September Capital Markets Day VB10.NEO • First VB10.NEO clinical data released* - major de-risking factor • 100% manufacturing success rate • On track to initiate enrollment in NEKTAR arm of VB N-01during Q4 2019 • Accelerating efforts to progress VB N-01 trial - opening 6 new clinical
Slide 42: Outlook next 6 months
Outlook next 6 months Clinical trial for cancer neoantigen vaccine (VB10.NEO) • Decision of design for 1st expansion cohort Nektar collaboration • Approval of additional arm with combination of VB10.NEO and NKTR-214 • First patient dosed in clinical trial evaluating the combination Clinical trial in
Slide 43: In Summary
In Summary Achievements • Vaccibody technology platform provides best in class broad and strong immune response translating into clinical response across indications • Clinical proof of concept for both VB10.16 and VB10.NEO • Cutting edge experience in manufacturing and supply chain • Strong collabo
Slide 44: Vaccibody team ready to execute and deliver!
Vaccibody team ready to execute and deliver! Non-confidential 44
Slide 45: www.vaccibody.com
body www.vaccibody.com