Nykode Therapeutics ASA · OSL:NYKD
Nykode Therapeutics ASA — Investor Presentation (November 2023)
72 slides from Nykode Therapeutics ASA's investor presentation, November 2023
Slide 1: Company Presentation November 2023
Company Presentation November 2023
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: Global leader in APC-targeted immunotherapy technology
Global leader in antigen presenting cell (APC)-targeted immunotherapy technology NYKODE THERAPEUTICS (NYKD-OL, MKT CAP ~$560M1) Differentiated immunotherapies targeting antigens to Antigen-Presenting Cell (APC) to direct tailor-made immune responses with focus on oncology and autoimmune diseases Str
Slide 4: Nykode executive management
Nykode executive management Experienced and international management team MICHAEL ENGSIG AGNETE FREDRIKSEN MIKKEL W. PEDERSEN KLAUS EDVARDSEN HARALD GURVIN Chief Executive Officer Chief Business Officer & Chief Scientific Officer Chief Development Officer Chief Financial Officer Co-founder Nykode Th
Slide 5: Top-tier collaborations for cancer and infectious disease vaccines
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 6: Rich and diversified pipeline
Rich and diversified pipeline Upcoming Asset Indication Rights Preclinical Phase 1 Phase 2 Phase 3 Catalyst Oncology 1 Initiate trial HPV16+ cervical cancer (Q4 2023) 2 Dose level VB10.16 HPV16+ head and neck cancer recommendation (H2 2024) 2 Off-the-shelf HPV16+ locally advanced Protocol in cervica
Slide 7: Modular vaccine technology allows APC-targeting
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: 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 | Company Presentation 8
Slide 9: 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 10: VB10.16 in HPV16+ cancers
VB10.16 in HPV16+ cancers Nykode Therapeutics | Company Presentation 10
Slide 11: 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 12: HPV+ cancer incidence expected to increase
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 13: 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 14: Recent clinical progress in advanced cervical cancer, 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 15: 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 16: VB10.16 was generally well-tolerated
VB10.16 was generally well-tolerated VB10.16 plus atezolizumab tolerability profile was consistent with checkpoint inhibitor monotherapy1 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 favour
Slide 17: 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 18: VB10.16 coupled with CPI led to lasting responses
VB10.16 coupled with CPI led to lasting 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 | Company Presentation 18
Slide 19: Prolonged overall survival in advanced cervical cancer
VB10.16 led to prolonged overall survival in advanced cervical cancer patients 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 7.3 months No
Slide 20: VB10.16 induced HPV16-specific T cell responses correlated with 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 21: 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 CTDNA DYNAMICS (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
Slide 22: 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 23: 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 24: VB10.16 C-02 data compare strongly to CPI monotherapy and SoC
VB10.16 C-02 data compare strongly to CPI monotherapy as well as expected SoC in 2L r/m cervical cancer CPI Monotherapy in r/m CC VB10.16 plus Atezolizumab in Pembrolizumab in Cemiplimab in Tisotumab vedotin Endpoint atezolizumab PD-L1+††† PD-L1+** PD-L1+ †† (PD-L1 agnostic) ‡ ‡ in PD-L1+ Skyscraper
Slide 25: C-02 data supports patient selection for registrational study
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 26: Maximizing shareholder value by diversifying offerings
Maximizing shareholder value by diversifying offerings and broadening therapeutic scope Building a cancer vaccine franchise following strong clinical validation Validation Today Future Opportunities Adjuvant Settings Move earlier to expand patient population and Indication Expansions explore long-te
Slide 27: Portfolio of targeted vaccines for HPV16+ cancers
Creating a portfolio of targeted vaccines for HPV16+ cancers VB10.16 portfolio C-02 C-03 C-04 C-05 r/m head and neck r/m Cervical Cancer, ≥2L r/m Cervical Cancer, Locally Advanced Indication cancer (HNSCC), PD-L1+, 2L Cervical Cancer (LACC) PD-L1+, 1L Up to 9 mg in 3 mg in combination with combinati
Slide 28: 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 29: VB-C-04 VB10.16+atezolizumab or placebo in 2L recurrent CC
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 30: Locally advanced cervical cancer a new opportunity for immunotherapy
Locally advanced cervical cancer represents a new opportunity for immunotherapy Press release Nykode Therapeutics | Company Presentation 30
Slide 31: VB C-05: VB10.16+CPI 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 32: VB10.NEO - Individualized cancer immunotherapy
VB10.NEO- Individualized cancer immunotherapy Nykode Therapeutics | Company Presentation 32
Slide 33: VB10.NEO: Nykode's individualized cancer vaccine
VB10.NEO: Nykode’s individualized cancer vaccine Broad clinical experience 2 clinical trials in more than 10 cancer indications in recurrent metastatic setting Promising immunogenicity data VB10.NEO Broad and durable T cell responses in the Fully individualized vaccine against the clinic multipl
Slide 34: VB10.NEO programs
VB10.NEO programs Safety clearance of 9 mg dose with no safety concerns and no dose limiting toxicities observed N-01 N-02 r/m Melanoma, non-small cell lung cancer (NSCLC), clear renal cell carcinoma, urothelial Indication r/m cancer, covering more than ten indications cancer or squamous cell carcin
Slide 35: 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 36: VB10.NEO amplifies pre-existing T-cell responses and induces novel specificities
VB10.NEO amplifies pre-existing T-cell responses and induces multiple novel T-cell specificities Expansion of pre-existing and induction of novel T cells De novo response Expansion of both pre-existing and novel Amplified response T-cell responses in most patients (at least Indication Stable respons
Slide 37: Majority of neoepitopes activates 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 38: 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 39: 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 40: 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 | Company Presentation 40
Slide 41: 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 42: Autoimmunity and Further platform potential
Autoimmunity and Further platform potential Nykode Therapeutics | Company Presentation 42
Slide 43: Antigen specific tolerance by targeting tolerogenic APCs
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 44: 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 45: Vaccibodies prevent disease in MS-like mouse model
45 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 brai
Slide 46: Low dose prevents MS disease symptoms
Low dose prevent MS disease symptoms, with a dose-dependent decrease in disease associated cytokines differentiated from Ag alone 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 47: Disease prevention in EAE with alternative target
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 48: DNA vaccination prevents type 1 diabetes in mouse model
48 DNA vaccination with Vaccibody targeting tolerogenic APCs 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 Non-Obese
Slide 49: Business model validated and ready to accelerate in autoimmune diseases
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 50: 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 51: Unlocking the full potential of cancer vaccines
Unlocking the full potential of cancer vaccines Nykode Therapeutics | Company Presentation 51
Slide 52: Vaccibodies induce potent T cell responses across central tolerance levels
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 | Company Pres
Slide 53: APC-targeted technology offers improvement over mRNA vaccines
Nykode’s APC-targeted technology offers improvement of mRNA based vaccines Stronger T cell responses to a wider variety of MC38 T cell epitopes Prime vaccination only (D14) Prime + boost vaccination (D28) ✱ p=0.0473 ✱ p=0.0192 25000 2000 N01 N01 N02 N02 N03 N03 N04 N04 20000 N05 N05 1500 N06 N06 N07
Slide 54: Strong responses driven by broad CD8 T cell specificity
The strong responses by Nykode’s APC-targeted technology is primarily driven by broad CD8 T cell specificity The strong responses by Nykode’s vaccine are primarily CD8 driven and includes both effector and memory subtypes Nykode pDNA vs Ag mRNA Nykode mRNA vs Ag mRNA Nykode pDNA mRNA-Ag 80μg 5μg 800
Slide 55: Dedicated to a sustainable cancer vaccine platform
Nykode is dedicated to fill the gaps and offer a sustainable cancer vaccine platform CONTROL OF WHICH CELLS THAT TAKE UP THEANTIGEN AND HOW IT IS PRESENTED TO T CELLS THROUGHAPC-TARGETING Superior immunogenicity • Broad response to multiple epitopes and reduced risk of tumor escape • Proven abilit
Slide 56: 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 57: Modular platform to unlock multiple applications
Nykode’s modular platform is designed to unlock multiple applications across targets and therapeutic areas APC-specific Ag delivery and stimulation Expanded use of modularity Infectious Building Novel Cancer disease additional combinations and immunotherapies immunotherapies modules structures Immun
Slide 58: Outlook
Outlook Nykode Therapeutics | Company Presentation 58
Slide 59: Strong financial foundation for achieving our vision
Strong financial foundation for achieving our vision Cash position of $159m end Q3 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 | Company
Slide 60: Subsequent events
Subsequent events Private placement Tax matter Norwegian Tax Authorities (NTA) reiterated Successfully raised $45m in private placement their position that upfront payments received Aim to broaden the existing shareholder base under a license agreement entered into in with international invest
Slide 61: Upcoming milestones
Upcoming milestones Q4 VB10.16 Initiate potentially registrational VB-C-04 trial in the U.S. in patients with 2023 Cervical Cancer recurrent/metastatic disease and PD-L1 positive tumors Q4 Undisclosed Nomination of an additional oncology development candidate for a new internal 2023 Oncology oncolog
Slide 62: 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 63: Unlocking the future of medicine
UNLOCKING THE FUTURE OF MEDICINE Contact: Alexandra Deschner Head of Investor Relations [email protected] Nykode Therapeutics | Company Presentation
Slide 64: VB-C-01
VB-C-01
Slide 65: VB C-01: First trial with VB10.16 monotherapy in precancerous lesions
VB C-01: First trial with VB10.16 as monotherapy for treatment of HPV16+ precancerous lesions VB C-01 Exploratory, open labelled, multi-centre study in patients with HPV16+ High Grade Cervical Intraepithelial Neoplasia (HSIL, CIN 2/3) Dosing phase (3mg per dose) Expansion phase 8 patients Cohort 1:
Slide 66: Correlation of T cell response strength and lesion size reduction
VB10.16: Strong correlation with strength of induced HPV16- specific immune response and lesion size reduction 13 of 14 patients showed COHORT 1: COHORT 2: LESION SIZE REGRESSION increased T cell responses 0 – 3 – 6 WEEKS 0 – 4 – 12 WEEKS CORRELATES WITH STRONG after vaccination with HPV-16 SPECIF
Slide 67: Homologous booster dose induced strong T cell responses
VB10.16: homologous booster dose induced strong T cell responses in all patients in the expansion cohort HOMOLOGOUS BOOST ENSURE STRONG AND LONG-LASTING T STRONG HPV16-SPECIFIC T CELL REPSONSES IN ALL CELL RESPONSE PATIENTS IN THE EXPANSION COHORT The vaccination regimen from cohort 1 (Q3W) plus a
Slide 68: Correlation between T cell responses and lesion size across cohorts
VB10.16: highly significant correlation between vaccine induced HPV16-specific T cell responses and lesion size across all cohorts LESION SIZE REGRESSION SIGNIFICANT CORRELATION OBSERVED WITH % LESION SIZE REDUCTION AND CORRELATES WITH HPV-16 SPECIFIC # SFU/MILL RESPONSES • Cohort 1 • Cohort 2 • Exp
Slide 69: Promising clinical data as monotherapy in pre-cancerous lesions
Promising clinical data as monotherapy in pre-cancerous lesions Lesion size reduction observed in majority of subjects (16 of 17) in the Expansion cohort CIN regression to CIN1 or no CIN in 10 subjects HPV16 and/or p16 clearance in 8 subjects Upregulation of PD-L1 in lesions post-vaccination
Slide 70: VB-C-03
VB-C-03
Slide 71: 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 72: 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
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