Nykode Therapeutics ASA · OSL:NYKD
Nykode Therapeutics ASA — mRNA Cancer Vaccine Summit 2023
30 slides from Nykode Therapeutics ASA's conference presentation, Oct 12, 2023
Slide 1: Antigen presenting cell targeted vaccines
Antigen presenting cell targeted vaccines mRNA Cancer Vaccine Summit October 12, 2023 Boston, MA
Slide 2: Global leader in APC-targeted immunotherapy technology
Global leader in antigen presenting cell (APC)-targeted immunotherapy technology NYKODE THERAPEUTICS Differentiated immunotherapies targeting antigens to Antigen-Presenting Cell (APC) to direct tailor-made immune responses with focus on oncology and autoimmune diseases Strategic partnerships with to
Slide 3: Rich and diversified pipeline
Rich and diversified pipeline Asset Indication Preclinical Phase 1 Phase 2 Phase 3 Oncology VB10.16 HPV16+ cervical cancer VB10.16 HPV16+ head and neck cancer Off-the-shelf Regeneron Undisclosed programs Internal Undisclosed Melanoma, lung, bladder, renal, VB10.NEO head and neck cancer; locally Indi
Slide 4: 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 come in different “flavors” wi
Slide 5: Modular vaccine technology allows APC-targeting to direct immune responses
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 6: Nykode vaccines induce a rapid, robust and long-lasting 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 | mRNA Cancer Vaccines Summit, Boston 10-12 October 2023 6
Slide 7: 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 8: APC targeted HPV16 vaccine drives superior anti-tumor responses
APC targeted HPV16 vaccine drives superior anti-tumor responses in an 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 9: 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 10: 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 | mRNA Cancer Vaccines Summit, Boston 10-12 October 2023 10
Slide 11: C-02 data supports patient population selection for potentially 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 12: VB10.16 induced HPV16-specific T cell responses correlated 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 13: VB10.16 with atezolizumab showed promising clinical profile with favorable tolerability
VB10.16 in combination with atezolizumab showed promising clinical profile with favorable tolerability in patients with advanced HPV16+ cervical cancer Clinically relevant endpoint mPFS was 4.1, 6.3 and 16.9 months for all, PD-L1+ and PD-L1+ with one prior treatment line, respectively Clinically
Slide 14: Part 1: In vivo comparison of Vaccibody DNA and mRNA-LNP delivery
Part 1 In vivo comparison of Vaccibody DNA and mRNA-LNP delivery of MC38 NeoAntigens 14
Slide 15: mRNA and LNP platforms used in our preclinical studies
mRNA and LNP platforms used in our preclinical studies • In the clinical setting, we so far leveraged the benefits of needle free delivery of Vaccibodies by DNA to induce CD8+ responses with high tolerability • We are exploring other delivery modes guided by disease specific applications mRNA N1-Met
Slide 16: MC38 NeoAntigen vaccine: Vaccibody as pDNA compared to mRNA-LNP antigen
MC38 NeoAntigen vaccine: Vaccibody delivered as pDNA compared to antigen delivered as mRNA-LNP Constructs used Experimental setup Dimerization domain C57BL/6 CCL3L1 domain pDNA-VB-MC38neo n=5 per group Antigen unit: 20x 27-mer NeoAntigens Week 0 (Day 1) Prime Week 3 (Day 21) Boost Week 2 (Day 14) We
Slide 17: pDNA-VB and mRNA-AG drive strong MC38neo immunogenicity
pDNA-VB and mRNA-AG drive strong MC38neo immunogenicity after prime+boost regimen IFN-γ + responses upon delivery of MC38 antigens with pDNA-VB VS mRNA-AG D14_Prime vaccination D28_Boost vaccination N01 pDNA-VB mRNA-AG pDNA-VB mRNA-AG 15000 -MC38neo -MC38neo -MC38neo -MC38neo N02 N03 • pDNA-VB induc
Slide 18: Vaccibodies delivered as pDNA generate broader T cell responses
Vaccibodies delivered as pDNA generates broader T cell responses to MC38 NeoAntigens DNA-encoded vaccibody induced responses to a greater number of neoantigens 4000 3500 Untreated VB-MC38neo DNA 80 µg 3000 NeoAntigens >100 SFU (average) MC38 mRNA 5 µg 2500 14 SFU/106 Splenocytes 2000 12 10 1500 Numb
Slide 19: DNA vaccibody immunization generates strong CD8+ driven prime responses
DNA vaccibody immunization generates strong CD8+ driven prime responses against multiple MC38 NeoAntigens Strong prime responses seen with DNA-VB vaccination are CD8 driven pDNA-VB mRNA-AG 7000 D14_Prime vaccination N01 80μg 5μg 8000 pDNA-VB mRNA-AG N02 N03 6000 7000 N04 N05 5000 N06 6000 N07 SFU/mi
Slide 20: Conclusions Part 1
Conclusions Part 1 • DNA vaccination with Vaccibodies containing NeoAntigens result in broader T cell responses compared to mRNA-LNP delivery of the same NeoAntigens • DNA vaccination with Vaccibodies containing NeoAntigens generates superior T cell responses following a single vaccination driven pr
Slide 21: Part 2: Vaccibody delivery by mRNA in LNP
Part 2 Vaccibody delivery by mRNA in LNP 21
Slide 22: mRNA-LNP delivered Vaccibodies encoding viral antigens are immunogenic
mRNA-LNP delivered Vaccibodies encoding viral structural antigens are intact and highly immunogenic Design and In vitro characterization In vivo RBD mRNA-LNP Vaccibodies elicit dose-dependent strong antiviral antibody and T cell responses, and RBD demonstrate boost effect CCL3L1 domain Antigen unit:
Slide 23: mRNA-LNP Vaccibodies encoding a NeoAntigen cassette are immunogenic
mRNA-LNP delivered Vaccibodies encoding a NeoAntigen cassette are intact and highly immunogenic Design and in vitro characterization Strong and broad T cell responses mRNA-VB-MC38neo Vaccination with 1ug of the Vaccibody neoantigen vaccine resulted in a broad T cell response in IFN-γ Fluorospot assa
Slide 24: MC38 NeoAntigen vaccine: Vaccibody compared to antigen alone as mRNA-LNP
MC38 NeoAntigen vaccine: Vaccibody compared to antigen alone when both are delivered as mRNA-LNP Constructs used Experimental setup Dimerization domain CCL3L1 domain C57BL/6 mRNA-VB-MC38neo n=5 per group Antigen unit: 20x 27-mer NeoAntigens Week 0 (Day 1) Prime Week 3 (Day 21) Boost Week 2 (Day 14)
Slide 25: Vaccibody induces stronger immune responses than neoantigen-only vaccine
Vaccibody induces stronger immune responses than a neoantigen-only vaccine IFN-γ+ fluorospot responses to MC38 neoantigens Prime vaccination only (D14) Prime + boost vaccination (D28) ✱ p=0.0473 25000 ✱ p=0.0192 2000 N01 N01 N02 N02 N03 N03 N04 N04 20000 N05 N05 1500 N06 N06 N07 N07 N08 SFU/million
Slide 26: Vaccibody generates a broader T cell response
Vaccibody generates a broader T cell response mRNA-encoded vaccibody induced responses to a greater number of neoantigens 8000 7000 Untreated 6000 mRNA-VB-MC38neo 5000 mRNA-AG-MC38neo NeoAntigens >100 SFU (average) SFU/106 Splenocytes 4000 14 3000 12 2000 10 Number 1000 8 1000 6 800 4 2 600 0 400 o
Slide 27: Flow cytometry confirms a strong Vaccibody mRNA-LNP CD8 T cell response
Flow cytometry analysis confirms a strong Vaccibody mRNA-LNP CD8 T cell response mRNA-VB-MC38neo results in a higher percentage of activated CD8+ effector cells Flow cytometry analysis of peptide-stimulated splenocytes Activated CD8+ effector cells Activated CD8+ effector cells (IFNg+, Ki67+) (IFNg+
Slide 28: Conclusions Part 2
Conclusions Part 2 • Vaccibodies encoding T cell epitopes or structured antigens can be delivered by mRNA and generate strong T cell and antibody responses in animals • mRNA vaccination with Vaccibodies containing NeoAntigens results in broader and stronger T cell responses compared to mRNA delivery
Slide 29: Acknowledgements
Acknowledgements Gunnstein Norheim Inga Patrycja Winge Håkan Norell Brian Weinert Mirjam Dürkoop Eirik Solbakken Lise Skullerud Katarzyna Kuczkowska Stine Granum Judith Jing Wen Wong Maria Lyngaas Torgersen Elisabeth Stubsrud Synne Hougsnæs Anna Lunde Marit Renee Myhre Nykode Therapeutics | mRNA Can
Slide 30: Thank you
Contact Mikkel Wandahl Pedersen CSO MWPedersen@nykode.com THANK YOU Nykode Therapeutics | mRNA Cancer Vaccines Summit, Boston 10-12 October 2023
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