Nykode Therapeutics Asa · OSL:NYKD
Nykode Therapeutics Asa — Investor Day (September 2023)
110 slides from Nykode Therapeutics Asa's investor day presentation, Sep 20, 2023
Slide 1: Capital Markets Day
CAPITAL MARKETS DAY Thompson Central Park New York September 20, 2023 Nykode Therapeutics |
Slide 2: Forward-looking statement
Forward-looking statement This announcement and any materials distributed in connection with this presentation may contain certain forward- looking statements. By their nature, forward-looking statements involve risk and uncertainty because they reflect the company’s current expectations and assumpt
Slide 3: Welcome & opening remarks
01 Welcome & opening remarks Michael Engsig, Chief Executive Officer Nykode Therapeutics | Capital Markets Day 2023
Slide 4: Present today
Present today MICHAEL AGNETE MIKKEL W. KLAUS HARALD BRADLEY J. ENGSIG FREDRIKSEN PEDERSEN EDVARDSEN GURVIN MONK Chief Executive Chief Business Chief Scientific Chief Development Chief Financial M.D., Ph.D Officer Officer & Co-founder Officer Officer Officer Nykode Therapeutics | Capital Markets Day
Slide 5: Global leader in APC-targeted immunotherapy technology
Global leader in antigen presenting cell (APC)-targeted immunotherapy technology NYKODE THERAPEUTICS (NYKD-OL, MKT CAP ~$800M) Differentiated immunotherapies targeting antigens to Antigen-Presenting Cell (APC) to direct tailor-made immune responses with focus on oncology and autoimmune diseases Stra
Slide 6: Rich and diversified pipeline
Rich and diversified pipeline Asset Indication Preclinical Phase 1 Phase 2 Phase 3 Rights Oncology 1 VB10.16 HPV16+ cervical cancer 2 VB10.16 HPV16+ head and neck cancer Off-the-shelf 3 Regeneron Undisclosed programs Internal Undisclosed 4 Melanoma, lung, bladder, renal, VB10.NEO head and neck cance
Slide 7: Modular vaccine technology allows APC-targeting to direct immune responses
Modular vaccine technology allows APC-targeting to direct immune responses DNA plasmid Targeting unit to attract and bind APCs encoding Ability to tailor the targeting unit enables induction of different immune response Nykode vaccine profiles to specific diseases1 Dimerization unit for crosslinking
Slide 8: APCs determine the immune response to the antigen
APCs determines the immune response to the antigen by presenting antigens to different effector T cells Nykode’s APC targeted technology make sure the antigen is delivered to the selected subset of APCs and are presented to the desired T cells CANCER Effector T cell Targeting unit Treg Dimerization
Slide 9: Cancer vaccine platform induces rapid, robust CD8 T cell response
Nykode’s cancer vaccine platform induces a rapid, robust and long-lasting CD8 T cell response against cancer cells MECHANISM OF ACTION – T CELL INDUCTION Nykode Therapeutics | Capital Markets Day 2023 9
Slide 10: Top-tier collaborations valued potentially more than $1.64 billion
Top-tier collaborations for cancer and infectious disease vaccines valued potentially more than $1.64 billion plus royalties Partner Collaboration Terms Clinical Development $925M~ Regeneron to develop and potentially Multi-target license and $30M upfront commercialize products collaboration agree
Slide 11: On the agenda today
On the agenda today Update on VB10.16 program • Additional immune response data supporting development strategy • Layout of ambitious VB10.16 development program Evolving treatment paradigm for advanced cervical cancer and VB10.16 C-04 trial design conducted in collaboration with GOG VB10.NEO update
Slide 12: VB10.16 program update
02 VB10.16 program update Klaus Edvardsen, Chief Development Officer Nykode Therapeutics | Capital Markets Day 2023
Slide 13: VB10.16: therapeutic vaccine candidate for HPV16+ cancers
VB10.16: therapeutic vaccine candidate for HPV16+ cancers Targeting unit Off-the-shelf therapeutic cancer DNA vaccine CCL3L1 against HPV16 induced malignancies HPV16 is the most prevalent oncogenic HPV strain VB10.16 Targeting the cancer-specific full-length HPV16 E7 and E6 Off-the-shelf vaccine
Slide 14: HPV+ cancer incidence expected to increase despite prophylactic vaccination
HPV+ cancer incidence is expected to increase despite prophylactic HPV vaccination HPV16+ cancers are a significant unmet need HPV+ cervical cancer HPV-related cancer incidence is expected to grow • 4th most common cancer in women worldwide HPV+ cervical cancer HPV+ HNSCC • 4th leading cause of canc
Slide 15: VB-C-02: VB10.16 plus atezolizumab in advanced cervical cancer
VB-C-02: VB10.16 plus atezolizumab (Tecentriq®) in advanced cervical cancer A Multi-Centre, Single Arm, Open-label Phase 2a Trial of the Combination of VB10.16 and atezolizumab in Patients with Advanced or Recurrent, Non-resectable HPV16 Positive Cervical Cancer (NCT04405349) Objectives: Safety/to
Slide 16: Recent progress in advanced cervical cancer survival, room for improvement
Recent clinical progress has increased survival outcomes in advanced cervical cancer patients, but room for significant improvement remains Patients that have failed 1 or more line of systemic treatment have limited Progression Free Survival and Overall Survival with current approved treatments Sign
Slide 17: VB10.16 evaluated in pretreated advanced cervical cancer patients
VB10.16 evaluated in pretreated advanced cervical cancer patients, with ~40% PD-L1 negative Baseline characteristics PATIENT CHARACTERISTICS1 SAF2 (n = 52) Median age, years (range) 47.5 (27-83) Histology Squamous cell carcinoma 81% (42/52) Adenocarcinoma 15% (8/52) Adenosquamous carcinoma 2%
Slide 18: Strong anti-tumor effect leading to prolonged overall survival
Strong anti-tumor effect leading to prolonged overall survival (compared to CPI alone)1 High mOS of >25 months (not reached) and mPFS 6.3 months in PD-L1+ patients Endpoint All patients2 PD-L1+ 3 Value 95% CI Value 95% CI Strong and durable anti-tumor efficacy ORR 19% (9%-33%) 29% (13%-51%) across
Slide 19: Tolerability profile consistent with checkpoint inhibitor monotherapy
VB10.16 plus atezolizumab tolerability profile was consistent with checkpoint inhibitor monotherapy1 VB10.16 generally well-tolerated Treatment-related Adverse Events assessed as related to VB10.16 VB10.16 in combination with atezolizumab was generally (n = 52) well-tolerated and showed a favourable
Slide 20: VB10.16 coupled with CPI led to durable responses
VB10.16 coupled with CPI led to durable responses All (n = 47) By PD-L1 status (n = 40) Note: 7 out of 47 responders had PD-L1 unknown status, 40 out of 47 had known PD-L1 status Nykode Therapeutics | Capital Markets Day 2023 20
Slide 21: VB10.16 Ph2 data compared with current and future SoC
Data from the VB10.16 Ph2 trial compared with relevant current and future SoC as evaluated in third-party trials Cemiplimab in PD-L1+ Tisotumab vedotin VB10.16 plus atezolizumab Pembrolizumab in PD-L1+ Endpoint (Empower-Cervical 1, (PD-L1 agnostic) in PD-L1+ (n = 24) (Keynote-158, n = 82)** n = 82,
Slide 22: C-02 data supports patient population selection
C-02 data supports patient population selection for potentially registrational study Clinical activity observed across all endpoints, with strongest results in PD-L1+ patients with 1 prior line of systemic therapy Duration of response data in PD-L1+ patients show potential for competitive positi
Slide 23: HPV16 ctDNA dynamics associated with clinical response
HPV16 circulating tumor DNA dynamics is associated with clinical response ALL PATIENTS WITH CLINICAL RESPONSE PER RECIST 1.1 EARLY CTDNADYNAMICS (WEEK 9-11) ASSOCIATED WITH HAVE MOLECULAR RESPONSE IMPROVED CLINICAL OUTCOME DCR PD Increase Decrease Disease control N=16 5 (31%) 11 (69%) All patients w
Slide 24: VB10.16 induced T cell responses correlate with clinical response
VB10.16 induced HPV16-specific T cell responses that are significantly correlated with clinical response HIGHER FOLD INCREASED T CELL HIGHER PEAK T CELL RESPONSES IN RESPONSES IN PATIENTS WITH DISEASE PATIENTS WITH DISEASE CONTROL CONTROL 1500 p=0.0113 50 p=0.0346 1000 500 SFU/106 PBMC250 10 Fold ch
Slide 25: T cell responses remain strong and long-lasting
T cell responses remain strong and long-lasting T cell clonotype analysis EXPANSION OF NOVEL AND EXPANDED RAPID AND PERSISTENT EXPANSION OF T CELL CLONES CLONES ON TREATMENT • Novel expanded clones constituted a median of • Rapid and persistent on-treatment T cell expansion 0.66% of the peripheral T
Slide 26: Patient case: longitudinal T cell clonal expansion
Patient case: longitudinal T cell clonal expansion Persistent expansion of novel and pre-existing clones throughout the treatment FREQUENCY OF EXPANDED CLONOTYPES NUMBER OF EXPANDED CLONES A persistent expansion of Pre-exising expanded novel and pre-existing Novel clones throughout the treatment p
Slide 27: VB10.16 with atezolizumab showed promising clinical profile
VB10.16 in combination with atezolizumab showed promising clinical profile with favorable tolerability in patients with advanced HPV16+ cervical cancer, an area of high unmet medical need Clinically relevant endpoint mPFS was 4.1, 6.3 and 16.9 months for all, PD-L1+ and PD-L1+ with one prior treat
Slide 28: VB10.16 has broad potential across HPV-driven cancers
VB10.16 has broad potential across HPV-driven cancers FINALIZED. REPORTED ONGOING. REPORTED EXPANSION PLANNED FOR 2023 FURTHER POTENTIAL POSITIVE DATA POSITIVE INTERIM DATA C-01 C-02 C-03 Earlier lines Ph 1/2a Pre- C-04 Ph 2a Ph 1/2a Head and other cancerous Ph 2 Cervical Cervical and Neck HPV+ driv
Slide 29: Locally advanced cervical cancer represents a new opportunity
Locally advanced cervical cancer represents a new opportunity for immunotherapy Nykode Therapeutics | Capital Markets Day 2023 29
Slide 30: VB C-05: VB10.16+CPI with CRT in locally advanced cervical cancer
VB C-05: VB10.16+CPI as concurrent treatment to CRT in Locally Advanced Cervical Cancer Randomized Phase 2 PoC trial in a HPV16+ LACC setting Concurrent Adjuvant HPV 16+ High-risk locally advanced cervical cancer CRT + CPI + CPI + Primary endpoint (FIGO 2018) defined as VB10.16 VB10.16 PFS and OS st
Slide 31: The treatment landscape for cervical cancer
03 The treatment Professor, Division of Gynecologic Oncology University of Arizona College of Medicine landscape for Creighton University School of Medicine Phoenix, USA cervical Director, Principal Investigator, Community Research Development, HonorHealth Research Institute Vice President and Membe
Slide 32: Financial relationships disclosure
I have the following financial relationships with ACCME defined ineligible companies to report over the past 24 months: Cancer Type Commercial Interest What was received Role Cervical Agenus Honorarium Consultant Cervical Akeso Bio Honorarium Consultant Cervical, uterine, ovarian AstraZeneca Honorar
Slide 33: Estimated 13,960 cases of invasive cervical cancer in the US in 2023
An Estimated 13,960 Cases of Invasive Cervical Cancer in the US in 20232 ✓ Death rate in 2016 (2.2 per 100,000) was less than half that in 1975 4,310 deaths (5.6 per 100,000) ✓ From 2007 to 2016, the death rate decreased by about 1% per year in women >50 years of age and older, but was stable in <50
Slide 34: Advanced/Recurrent Cervical Cancer: a high unmet clinical need
Advanced/Recurrent Cervical Cancer: A HIGH UNMET CLINICAL NEED! Winslow T. www.aacrfoundation.org/CancerTypes/Pages/PDQs/Cervical-Cancer-Treatment-PDQ.aspx. Accessed 15 January 2018.
Slide 35: First targeted agent approved in a gynecologic cancer
First Targeted Agent Approved in a Gynecologic Cancer: 3rd Landmark Discovery 1-L Bevacizumab Approved by FDA on August 14, 2014 Tewari KS et al. N Engl J Med. 2014;370(8):734-743. Tewari KS et al. Lancet. 2017;390(10103):1654-1663.
Slide 36: Second-line approval of pembrolizumab
Second-Line Approval of Pembrolizumab for CPS PD-L1+ Cohort (CPS ≥ 1) >1 Endpoint ORR (95% CI) N=77 14.3% (7.4-24.1) • US FDA Accelerated Complete response 2.6% Partial response 11.7 11.7 Approval of Median duration (mos) Not reached (4. – 18.6+) Pembrolizumab % with duration ≥ 6 mos 91% Median foll
Slide 37: N Engl J Med. 2021 Sep 18. doi: 10.1056/NEJMoa2112435. Online ahead of print.
N Engl J Med. 2021 Sep 18. doi: 10.1056/NEJMoa2112435. Online ahead of print.
Slide 38: Full approval pembrolizumab first line
Full Approval Pembrolizumab and Line First Line FDA Approves Pembrolizumab Combination for the First-Line Treatment of Cervical Cancer On October 13, 2021, the Food and Drug Administration approved pembrolizumab in combination with chemotherapy, with or without bevacizumab, for patients with persist
Slide 39: Tisotumab Vedotin: 5th landmark discovery
Tisotumab Vedotin: (5th Landmark Discovery) • Transmembrane receptor for Fully human mAb coagulation factor VII/VIIa[a-c]: Targets tissue factor Linker • Expressed on subendothelial vessel Protease-cleavable val-citrulline wall cells maleimidocaproyl linker • Normal physiological Conjugated to monoc
Slide 40: Bringing TV to the clinic in 2-L
Bringing TV to the Clinic in 2-L • FDA filing of the tisotumab vedotin BLA (Biologics License Application) for accelerated approval announced in April 21 • Under the PDUFA (Prescription Drug User Fee Act), the FDA has set a target action date 10 October 21 (priority review) • FDA approved Sept 20, 2
Slide 41: EMPOWER-Cervical 1 trial design
EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 (2-L) (NCT03257267) Trial Recurrent and metastatic cervical cancer resistant to Primary endpoint: OS platinum-based Cemiplimab, 350 mg chemotherapy ≥ 2L Once every 3 wk via IV ECOG PS ≤ 1[a,b] Secondary endpoints: PFS, ORR, DOR, safety, QOL IC chemotherapy N = 6
Slide 42: EMPOWER-Cervical 1 overall survival
EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 (2-L) (NCT03257267) Trial Overall Survival, All Patients Tewari KS, Monk BJ et al. N Engl J Med. 2022;386:544-555.
Slide 43: EMPOWER-Cervical 1 SCC and AC populations
EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 (2-L) (NCT03257267) Trial SCC Population AC Population † Tewari KS, Monk BJ et al. N Engl J Med. 2022;386:544-555.
Slide 44: EMPOWER-Cervical 1 overall response rates
EMPOWER-Cervical 1/GOG-3016/ENGOT cx9 (2-L) Overall response rates Overall Population By Investigator Assessment Cemiplimab Chemotherapy ORR of SCC (n = 304) (n = 304) population Response ▪ Cemiplimab: 17.6% ORR (CR + PR), No. (%) 50 (16.4) 19 (6.3) (95% CI: 13.0, 23.0) 95% CI for ORR (12.5, 21.1) (
Slide 45: Incremental improvements in survival in 1L cervical cancer
Incremental Improvements in Survival (OS) in Treating 1L Metastatic and Recurrent Cervical Cancer with Combinations and Biomarkers Chemotherapy backbone (platinum + taxane) 2009 Adding bevacizumab 2014 GOG 204 Adding pembrolizumab in established the biomarker positive (PD-L1 22c3) 2023 GOG 240 added
Slide 46: innovaTV 301 trial study design
GOG-3057/ENGOT-cx12/innovaTV 301: Trial Study Design • Phase 3, randomized trial of tisotumab vedotin vs investigator's choice chemotherapy in second- or third-line recurrent cervical cancer Primary endpoints: OS Tisotumab vedotin Secondary endpoints: PFS (Inv), confirmed ▪ Progressed during or 2 mg
Slide 47: VB-C-04
VB-C-04 Randomized Phase 2 selection trial in r/m cervical cancer progressing on 1st line SOC (pembrolizumab + chemotherapy +/- bevacizumab)
Slide 48: VB10.16 led to prolonged overall survival in VB-C-02
VB10.16 led to prolonged overall survival in advanced cervical cancer patients in VB-C-02 Median overall survival of 16.9 months in overall population, mOS not reached (> 25 months) in PD-L1+ patients Overall survival Overall survival (PD-L1+ vs. PD-L1-) mOS N.R. (> 25 months) mOS 16.9 months mOS 7.
Slide 49: Nykode committed to progress VB10.16 with GOG Foundation
Nykode committed to progress VB10.16 in recurrent cervical cancer together with GOG Foundation Nykode Therapeutics | Capital Markets Day 2023
Slide 50: VB-C-04 trial in advanced HPV16-positive cervical cancer
VB-C-04 trial in advanced HPV16-positive cervical cancer Randomized Phase 2 selection trial in recurrent cervical cancer progressing on 1st line SOC (pembrolizumab + chemotherapy +/- bevacizumab) Dosing schedule VB10.16 vaccine (i.m.) Key eligibility criteria Q3W for 5 cycles (induction period
Slide 51: VB-C-04 randomized Phase 2 selection design
VB-C-04 VB10.16+atezolizumab or placebo in 2L recurrent CC Overview: randomized Phase 2 selection design Part 1 Part 2 a) b) Arm A: Enroll Final analysis ( n = 100) VB10.16 + another 70 Interim for futility recurrant (stage IVB) CC atezolizumab pts in (n = 60) (n = 30) superior arm • HPV-16+ • PD-L1
Slide 52: Summary and Conclusions
Summary and Conclusions 1. Cervical cancer is a chemo-sensitive solid tumor 2. Cervical cancer is susceptible to antiangiogenic interventions 3. Immunotherapy (IO) is active as a single agent in the 2-L and with chemotherapy in the 1-L 4. Anti-body drug conjugates are active in the 2-L 5. Innovative
Slide 53: VB10.NEO Program Update
04 VB10.NEO Program Update Klaus Edvardsen, Chief Development Officer Nykode Therapeutics | Capital Markets Day 2023
Slide 54: VB10.NEO: Nykode's individualized cancer vaccine
VB10.NEO: Nykode’s individualized cancer vaccine Targeting antigen presenting cell Proprietary neoantigen selection method Majority of selected neoepitopes are immunogenic Frequency of high-quality neoepitopes in vaccine and VB10.NEO Fully individualized immune responses correlate with responses
Slide 55: VB-N-02 Phase 1b dose escalation trial
VB-N-02 Phase 1b dose escalation trial Safety clearance of 9 mg dose with no safety concerns and no dose limiting toxicities observed N-01 N-02 Melanoma, non-small cell lung cancer (NSCLC), clear renal cell carcinoma, urothelial cancer or Locally advanced and metastatic tumors covering Indication sq
Slide 56: T cell responses to majority of selected neoepitopes
T cell responses to majority of % immunogenic Neoepitopes per patient selected neoepitopes Indication UC All patients across five indications SCCHN 60 51% % of neoepitopes showed a response to at least one neoepitope 35% 40 24% RCC On average, 53% of selected 20 15% 10% neoepitopes were immunogenic,
Slide 57: Neoepitopes activate CD8 T cells
Preliminary immune phenotyping shows that the majority of neoepitopes activates CD8 T cells CD8 T cells response detected Selected patients No CD8 T cells response detected T cell responses are characterized by both CD8 and CD4 T cells 53% 100% 75% 100% 100% 80% The majority of tested 01-001 01-
Slide 58: Multiple vaccinations boost breadth and magnitude of T cell responses
Multiple vaccinations boost the breadth and magnitude of functional T cell responses Patients completing 1-Year of treatment Breadth Magnitude 20 40000 Increase in the breadth and 30000 magnitude of functional T cell Number of increased neoantigens responses observed over time. Stacked SFU/106 PBMCs
Slide 59: Vaccine-specific T cells remain functional up to 1 year
Vaccine-specific T cells remain functional and immunogenic up to 1-year after last vaccination VB10.NEO induces a favorable and long-lasting T cell memory phenotype 14 48% of the treatment-induced de 10 patients were 12 novo T cell responses were still de novo responses followed for immune 10 functi
Slide 60: VB10.NEO key differentiators
Solid manufacturing chain Safety ✓ Safety profile similar to ✓ 100% successful checkpoint inhibitor monotherapy vaccine production ✓ No increase in immune-related ✓ Robust supply chain adverse events NeoSELECT Immune response ✓ High fraction of VB10.NEO ✓ Induces broad and strong immunogenic neoanti
Slide 61: VB-N-02 Phase 1b dose escalation trial
VB-N-02 Phase 1b dose escalation trial Safety clearance of 9 mg dose with no safety concerns and no dose limiting toxicities observed N-01 N-02 Melanoma, non-small cell lung cancer (NSCLC), clear renal cell carcinoma, urothelial cancer or Locally advanced and metastatic tumors covering Indication sq
Slide 62: Q&A
Q&A Klaus Edvardsen, Nykode CDO Dr. Bradley Monk, GOG Nykode Therapeutics | Capital Markets Day 2023
Slide 63: 20' Break
20’ BREAK Nykode Therapeutics | Capital Markets Day 2023
Slide 64: Research & innovation update
05 Research & innovation update Mikkel Wandahl Pedersen, Chief Scientific Officer Nykode Therapeutics | Capital Markets Day 2023
Slide 65: Antigen presenting cells - the portal to adaptive immunity
Antigen presenting cells - the portal to adaptive immunity Activation of the adaptive immune system is key to REGULATION OF ADAPTIVE IMMUNITY obtain effective and long-term immune responses cDC1 cDC2 moDC iDC tDC APCs are the gatekeepers to adaptive immunity APCs comes in different “flavors” w
Slide 66: Modular vaccine technology allows APC-targeting
Modular vaccine technology allows APC-targeting to direct immune responses Module 1: Targeting unit to attract and bind APCs DNA plasmid encoding Ability to tailor the targeting unit enables induction of different immune response Vaccibody profiles to specific diseases1 Module 2: Dimerization unit f
Slide 67: Vaccines induce rapid, robust CD8 T cell response
Nykode vaccines induce a rapid, robust and long-lasting CD8 T cell response against cancer cells MECHANISM OF ACTION – T CELL INDUCTION Nykode Therapeutics | Capital Markets Day 2023 67
Slide 68: Controlled cross-presentation induces broader CD8 responses
Controlled cross-presentation by specific APC receptor targeting induces broader & stronger CD8 responses than non-targeted technologies such as mRNA- and peptide vaccines Comparison with peptide and RNA vaccination strategies shows broader CD8 Addition of strong CD8 responses to epitopes and CD4 re
Slide 69: APC targeted HPV16 vaccine drives superior anti-tumor responses
APC targeted HPV16 vaccine drives superior anti-tumor responses in a E6+E7 positive tumor model E6+E7 POSITIVE TC1 TUMOR MODEL VB10.16 compared to non-targeted vaccine E7 peptides IFN- spots/106 splenocytes 1500 Induction of significantly stronger HPV16 P = 0.0001 In vivo TC1 tumor growth curves
Slide 70: T cell responses long-lasting, memory responses generated
Vaccibody T cell responses are long-lasting and effective memory responses are generated PERSISTENCE OF T CELL RESPONSES Vaccine-induced T cell responses remain strong more than two months after 30000 25 µg 50 µg vaccination with a SARS-COV2 RBD vaccine 25000 An additional boost at day 89 induce
Slide 71: Nykode's research and innovation strategy
Nykode’s research and innovation strategy The Innovation Strategy encapsulates our vision of finding new ways of coding medicine by breaking down conventional drug design Creating novel differentiated platform technologies applicable to fuel multiple products and optimize value-creation Coding novel
Slide 72: Flexibility of DNA platform allows additional modules
Flexibility of DNA platform allows additional modules 4TH MODULE DATA – GM-CSF VB CT26 vaccine APC infiltration DNA sequences encoding additional polypeptide(s) can be added to vaccines Inclusion of ribosome skipping sequence(s) ensure production of separate molecules Potential for boosting an
Slide 73: Tolerance - a new therapeutic focus area
Tolerance - a new therapeutic focus area Nykode Therapeutics | Capital Markets Day 2023
Slide 74: Tolerance induction by inverse vaccination
Tolerance induction by inverse vaccination IMMUNE BALANCE Regular vaccines educate the immune system to recognize and attach bacteria, viruses or cancer cells creating immunological memory Inverse vaccination aims at doing the opposite by removing the immune system’s memory of antigens causing u
Slide 75: Mechanism of action: tolerance induction
Induction of antigen specific tolerance can be achieved by targeting disease causing epitopes to tolerogenic APCs MECHANISM OF ACTION – TOLERANCE INDUCTION (INVERSE VACCINATION) Cells transfected with DNA plasmid vaccine CD4+ Treg Tol APC CD4+ Treg Tol APC Effector T Effector T cell cell Cells encod
Slide 76: Modular design for antigen-specific immune tolerance
Modular design with multiple targeting and 4th modules able to ensure antigen-specific immune tolerance Module 1: Multiple targeting units for receptors on tolerizing APCs identified including natural ligands and other targeting molecules Module 3: Auto-antigens or allergens known to elicit unwanted
Slide 77: Vaccibodies prevent disease in MS-like mouse model
Recombinant Vaccibodies targeting tolerogenic DCs prevents serious disease in a MS-like mouse disease model Daily clinical scores Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) day -7 day -3 day 0 day 29 where the immune system attacks nerve cells in the brain a
Slide 78: Low dose vaccine prevents MS symptoms
Low dose recombinant Vaccibody vaccine prevent MS disease symptoms with a dose-dependent decrease in disease associated cytokines EAE MODEL Daily clinical scores day -7 day -3 day 0 day 15 Immune parameter read-out at day 15 (at peak of disease) Disease Termination and induction immune analyses MOG(
Slide 79: Disease prevention with alternative target on tolerizing APCs
Disease prevention in the EAE model can also be achieved by targeting an alternative target on tolerizing APCs EAE MODEL Paralysis VB vaccine TV004 5 ✱✱✱ Untreated 80 35 µg VB vaccine TV004 Targeting unit 1 4 Target 1 60 EAE score AUC (5-29) 3 40 2 20 EAE 1 0 antigen ed ne 0 e at c ci r va Tol 6 8 1
Slide 80: DNA vaccination prevents type 1 diabetes in mouse model
DNA vaccination with Vaccibodies targeting tolerogenic DCs prevents type 1 diabetes in a spontaneous mice model Monitoring glucose levels Type 1 diabetes is an autoimmune disease where the immune system attacks insulin producing cells in the pancreas Day 0 day 7 day 14 Mouse age w21 The NOD diabetes
Slide 81: Tolerance Highlights
Competition Opportunities ✓ Autoimmune disease ✓ Limited competition within antigen specific tolerance ✓ Allergies ✓ Organ transplantation Partnership opportunities Medical Need ✓ New platform allows product Tolerance ✓ High unmet medical need areas specific collaborations ✓ Existing therapies are b
Slide 82: Summary and conclusions tolerance
Summary and conclusions tolerance Numerous exploratory “inverse” vaccines built on a diversity of modules and evaluated experimentally • Works with different targeting units, antigens and 4th modules • Several patent applications covering these concepts filed Recombinant Vaccibodies designed to targ
Slide 83: Expanding the discovery pipeline
Expanding the discovery pipeline Nykode Therapeutics | Capital Markets Day 2023
Slide 84: Growing a pipeline of differentiated vaccine candidates
Growing a pipeline of differentiated vaccine candidates Exploit platform Take advantage of uniqueness and flexibility of our APC targeted vaccine approach and ability to include further modules Two therapeutic growth areas Oncology and Tolerance Product differentiation Oncology: Push boundaries - op
Slide 85: Update Regeneron collaboration
Update Regeneron collaboration Multitarget collaboration with the aim of using Nykode’s modular vaccine platform combined with Regeneron’s unique antigen selection expertise to discover and develop Two vaccine programs within infectious diseases Three vaccine programs within oncology The collabo
Slide 86: Vaccibodies induce potent T cell responses against various targets
Vaccibodies induce potent T cell responses against targets subject to various degrees of central tolerance Potential immunogenicity High thymic expression Low thymic expression No thymic expression Mouse melanocyte genes Mouse MAGE-like genes Mouse PRAME-like genes Nykode Therapeutics | Capital Mark
Slide 87: Platform allows tailoring of immune response
Nykode’s platform allows tailoring of the immune response by targeting different APC populations Nykode Therapeutics | Capital Markets Day 2023 87
Slide 88: Business Model
06 Business Model Agnete B. Fredriksen, Chief Business Officer & Co-founder Nykode Therapeutics | Capital Markets Day 2023
Slide 89: Nykode's Vision and Business Model
Nykode’s Vision and Business Model Unlocking unlimited possibilities for the future of medicine «Building the leading immunotherapy company developing game changing medicine across an expanding range of therapeutic areas.» Nykode leverage the unique immunology expertise to create proprietary new c
Slide 90: Building a cancer vaccine franchise
Building a cancer vaccine franchise following strong clinical validation 2L cervical cancer provides near-term validation with an opportunity to significantly expand the addressable patient population in adjuvant tumor settings Validation Today Future Opportunities Adjuvant Settings Move earlier to
Slide 91: Future offering all cancer patients a vaccine at diagnosis
Unlocking possibilities for a future offering all cancer patients a vaccine at diagnosis Exploring the full range of cancer antigens INDIVIDUALIZED OFF-THE-SHELF Viral Antigens Tumor-specific Tumor-associated Neoantigens Antigens VB10.16 Undisclosed Undisclosed VB10.NEO Future in house and partnered
Slide 92: Strategic partnerships to maximize platform value
Using strategic partnerships to maximize the value of the broader proprietary Nykode platform and products Platform: Products: Accelerate and De-risk, accelerate expand the pipeline and offload costs $925M $715M~ $30M upfront+ $20M equity $200M upfront/near term $875M in milestone payments $
Slide 93: Business model ready to accelerate autoimmune development
Nykode’s successful business model validated and ready to accelerate development in autoimmune diseases Expand candidate to all addressable Expansion into the First in patients broad potential of house autoimmune disorders, candidate towards the allergies and organ Clinical market transplantation Po
Slide 94: Autoimmune indications attractive platform expansion category
Autoimmune indications are an attractive platform expansion category Scientific Greenfield opportunity of APC- therapeutic Attractive Ability to add targeted vaccines to opportunity with commercial sizeable commercial drive antigen- broad range of opportunity; Top 10 potential to specific immune pot
Slide 95: Build on business model and continue innovation
Dedicated to build on the business model and continue innovation to generate novel platforms and products Nykode has proven its ability to generate groundbreaking platform technologies and leverage this by advancing in house and partnered programs in parallel leading to a validated and advanced
Slide 96: Final remarks
07 Final remarks Michael Engsig, Chief Executive Officer Nykode Therapeutics | Capital Markets Day 2023
Slide 97: Rich calendar of milestones expected in next months
Rich calendar of milestones expected in the next 12 months VB10.16 ✓ H1 2023 Final results from VB-C-02 Phase 2 study; 12 month treatment follow-up Cervical Cancer First patient dosed in VB-C-03 trial with KEYTRUDA® in patients with PD-L1 Q3 VB10.16 2023 positive 1st line unresectable recurrent or m
Slide 98: Strong financial foundation for achieving our vision
Strong financial foundation for achieving our vision Cash position of $174m end Q2 2023 Financially well positioned to execute the Company’s strategy over the next years Nykode continues to explore a potential listing on the Nasdaq Global Market in the United States Nykode Therapeutics | Capital
Slide 99: Our conviction in Nykode's platform has never been stronger
Our conviction in Nykode’s platform has never been stronger Differentiated APC targeting immunotherapy platform validated and de-risked through clinical data and top tier US biopharma partnerships Clinical durability and survival data further supported today by long lasting immune response with both
Slide 100: Q&A
Q&A • Michael Engsig, CEO • Agnete Fredriksen, CBO & Co-founder • Mikkel W. Pedersen, CSO • Klaus Edvardsen, CDO • Harald Gurvin, CFO Nykode Therapeutics | Capital Markets Day 2023
Slide 101: Thank you for joining us
THANK YOU FOR JOINING US! Nykode Therapeutics | Capital Markets Day 2023
Slide 102: Unlocking the future of medicine
UNLOCKING THE FUTURE OF MEDICINE Contact: Alexandra Deschner Head of IR IR@nykode.com Nykode Therapeutics | Capital Markets Day 2023
Slide 103: VB-C-02
VB-C-02
Slide 104: Changes in immunosuppressive cells associated with clinical outcome
Changes in immunosuppressive cells post treatment is associated with clinical outcome CHANGE IN MYELOID CELLS IS Best Disease Progressive PROGRESSION-FREE SURVIVAL ASSOCIATED WITH CLINICAL OUTCOME Overall control disease Response (n=28) (n=19) p = 0.001 Myeloid decrease Increase 11 (39%) 15 (79%) My
Slide 105: Stronger T cell responses with decrease in immunosuppressive cells
Stronger HPV16-specific T cell responses in patients with a decrease in immunosuppressive cells DECREASE OF MYELOID CELLS IS ASSOCIATED INCREASE OF T CELL/MDSC RATIO CELLS IS WITH STRONGER T CELL RESPONSES ASSOCIATED WITH STRONGER T CELL RESPONSES n=36 n=21 p = 0.0379 p = 0.0339 1500 1500 1000 1000
Slide 106: VB-C-03
VB-C-03 A Phase 1/2a, Open-label, Dose-finding Trial to Evaluate Safety, Immunogenicity, and Anti- tumor Activity of VB10.16 and Pembrolizumab in Patients With Unresectable Recurrent or Metastatic HPV16-positive Head-Neck Squamous Cell Carcinoma (NCT06016920)
Slide 107: VB-C-03 trial in advanced HPV16+ HNSCC
VB-C-03 trial in advanced HPV16+ HNSCC Combination treatment of VB10.16+pembrolizumab* in 1L HPV16+ R/M HNSCC Dose-escalation (Phase 1) with randomized dose-expansion (Phase 2a) trial Key eligibility criteria Dosing schedule VB10.16 vaccine Recommended Phase 2 set (RP2S): Randomization (1:2) o
Slide 108: VB-C-03 clinical trial design
VB-C-03 Clinical trial design Combination treatment of VB10.16+pembrolizumab in 1L HPV16+ R/M HNSCC Phase 1 Dose escalation phase Phase 2a Dose expansion phase 9 9m 9 mg g mg RP2D* Interim analysis Cohort A: OBD** Final analysis No DLT RP2S VB10.16 9 9 9 mg mg mg VB10.16 dosing R No DLT 6 6 6 DLT 6
Slide 109: VB-N-01
VB-N-01
Slide 110: T cell responses per patient
T cell responses per patient Total T cell responses De novo T cell responses Patients grouped in lower and higher than median immune responses Patients included are overlapping between EFR and FAS (N=32). Nykode Therapeutics | Capital Markets Day 2023