vaccibody · complete tumour regression . of large, established tumours long-term memory responses...

Vaccibody

NORWEGIAN BIOTECH ONCOLOGY SEMINAR

ABG Sundal Collier

June 11, 2019

Martin Bonde, [email protected]

mailto:[email protected]

Vaccibody AS in summary

• Founded in 2007 in Oslo, Norway

• Privately held clinical stage immuno-oncology company, spun-out from Oslo University, 25 employees

• Proprietary, patented vaccine technology

• Experienced, international management team with oncology expertise and biotech pedigree driving development

• Raised € 52 mill in equity since inception, € 32 mill in cash, market cap approx. € 240 mill (traded stock)

Martin Bonde,CEO

Agnete B. Frederiksen,Founder, President and CSO

Mads B. Axelsen,CMO

2

Mette Husbyn,CTO

Vaccibody Product Pipeline

PROGRAM DISCOVERY PRE-CLINICAL PHASE I PHASE II PHASE III

MELANOMALUNG (NSCLC)BLADDERRENALHEAD AND NECK

VB10.16

VB10.NEO

VB10.NEO + NKTR-214HEAD AND NECK

PRECANCEROUS CERVICAL LESIONS

VB10.16 + Atezolizumab (CPI)CERVICAL

3

The key target of T cells in patients that experience clinical benefit from cancer immunotherapies like immune checkpoint inhibitors

Neoantigens: New tumour-specific antigens

Neoantigens: New tumour-specific antigens«Recognition of random somatic mutations is the «final common pathway» explaining cancer regression from immune oncology therapies for solid tumors»*

Source: Khalil DN et al., Nat Rev Clin Oncol. 2016 Mar 15*From Steven Rosenberg’s presentation at SITC2019 4

Non-Confidential

1. Tumour biopsy and sequencing

2. Neoepitope selection (TSNA)

3. Vaccine manufacturing

(n=1)

4. Vaccine administration and

immunogenicity

The Workflow of Personalised Cancer Treatment

Time, cost, efficacy?

5

Vaccibody – Proprietary Vaccine Technology Platform

Antigen moiety

Target to Antigen Presenting Cell

Dimerization for crosslinking target

receptor

Vaccibody DNA Vaccine Plasmid

VB10.NEO

Vaccibody in Protein Format

Exchangeable DNA Cassette

n=x

In vivo expression

The Vaccibody Technology Platform was developed based on the concept of targeting antigen to APC in order to create more efficacious vaccines.

DeltoidMuscle

Mechanism of action: Intrinsic adjuvant for direct targeting

Administration (i.m.) of DNA

plasmid

In vivo protein expression and

secretion

Target – Attract – Mature – Deliver – Cross-presentSkewing the immune system to a CD8+ killer T-Cell response

Direct targeting & attraction of antigen presenting cells, high local vaccine concentration

Enhanced T cell immunity obtained with fewer and lower doses

Faster and longer lasting immune responses

Stronger potential to kill cancer cells

Tumour

The Vaccibody uses the muscle cell as a factory

Targeting is elicited by the MIP-1α chemokine7

• VB10.NEO induces a broader and stronger

response than Peptide + Poly (I:C) Adjuvant

vaccines after a single immunization.

• VB10.NEO vaccinated animals respond to all

10 neoepitopes after a single immunization.

• Immunodominant neoepitopes differ between

delivery vehiclesV B 1 0 .N

E O B

1 6 -X, 2

0 µ g

P e p t ide m

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P e p M 1

P e p M 2

P e p M 3

P e p M 4

P e p M 5

P e p M 6

P e p M 7

P e p M 8

P e p M 9

P e p M 1 0

VB10.NEO induces Rapid, Broad and Strong responses to multiple Neoepitopes by single Vaccination

B16 melanoma

Successful development of a strong proprietary neoepitope selection method NeoSELECTTM

0%

10%

20%

30%

40%

50%

60%

Version 1 Version 2 Vaccibody's NeoSELECT

Immunogenic neoepitopes identified by different prediction methods during development

• Vaccibody has since 2017 successfully developed a proprietary neoepitope selection method able to identify a high number of immunogenic neoepitopes when used in VB10.NEO vaccines

• Competitors present in general 0.1-20% immunogenic neoepitopes for their prediction analysis

• This method, NeoSELECT, is used in the VB N-01 clinical trial

Immunogenic neoepitopes

Strongly immunogenic neoepitopes

Confidential

Vaccibody Induces Tumor Protection as Monotherapy

0 5 1 0 1 5 2 0 2 5 3 0 3 5 4 0 4 5 5 00

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%)

V B 1 0 .N E O C T 2 6 -X X v

V B 1 0 .N E O C T 2 6 -X X

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Vaccibody vaccination induces strong CD8+ T cell responses and tumour protection as Monotherapy

Combination with anti-PD-1 immunotherapy induced enhanced anti-tumour responses in mice involving complete tumour regression of large, established tumours

Long-term memory responses ensure effective anti-tumour responses after a 2nd tumour challenge in surviving mice with no sign of tumour growth

Control

Vaccibody

PBS

0 7 1 4 2 1 2 8 3 5 4 2 4 9 5 6

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5

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1 5

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Vaccibody Combination Therapy

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th (

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)

Vaccibody Monotherapy

40% tumour free

70% tumour free

N=10 N=10N=10

Re-challenged mice are protectedCT26 coloncarcinomamodel




VB10.16

VB10.NEO



VB10.16 + Atezolizumab (CPI)*CERVICAL

*Tecentriq® (Atezolizumab) is Roche’s proprietary anti-PD-L1 checkpoint inhibitor (CPI)11

Confidential 12

Strong, long-lasting immune responses elicited to HPV16, VB C-01

• The vaccination regiment from cohort 1 (week 0, 3 and 6) plus a booster vaccination at W16 was introduced in phase IIa

• 16 of 17 patients (94%) from phase IIa elicited increased HPV16-specific T cell responses after vaccination with VB10.16.

• Rapid, strong and long-lasting

0 4 8 1 2 1 6 2 0 2 40

8 0 01 0 0 0

1 5 0 0

2 0 0 0

2 5 0 0

t im e a fte r 1 s t d o s e (w e e k )

SF

U/1

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PB

MC

s

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 )

-1 0 0

-5 0

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% c

ha

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ion

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Promising clinical efficacy with excellent safety, VB C-01

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HPV16 clearance

VB10.16 as a monotherapy in HPV16-positive, precancerous cervical lesions induces:

• Lesion size reduction in all patients followed >4 months• CIN regression to CIN1 or no CIN in 10 patients• HPV16 clearance in 6 patients

Best response data(At enrollment: 10 CIN3 and 7 CIN2 patients)

no CIN

CIN1

CIN2

CIN3

conizated

Preliminary phase IIa results

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• 5 of 6 patients that were CIN2/3 after completing the study (12M) showed upregulation of PD-L1 ≥10% (1 patient 5%)

• PD-L1 is upregulated by a strong local T cell response and may inhibit an efficacious long-term immune response

• Anti-PD-1/PD-L1 inhibitors blocks the brake and activates the immune system to attack PD-L1+ tumour cells

• VB10.16 induces a strong T cell response and creates a target for PD-1/PD-L1 inhibitors. Thus, there is a strong rationale for combination of VB10.16 with an anti-PD-1/PD-L1 checkpoint inhibitor to improve its effect, especially in PD-L1 negative patients

CPI: checkpoint inhibitor

VB10.16 upregulates PD-L1, suggesting effect of combination therapy

-1 0 0

0

1 0 0

% c

ha

ng

e l

es

ion

siz

e

PD-L1 post vaccination

20 50 10 10 5 50

CIN2/3 patients at 12 M

CIN2

CIN3

Preliminary phase IIa resultsConfidential

• Dosing of VB10.16 in combination with Atezolizumab (Tecentriq®)

• Purpose is to assess the safety/tolerability, immunogenicity and the efficacy of multiple doses of 3 mg VB10.16 immunotherapy incombination with Atezolizumab

• First patient, first visit is est. in Q1 2020

• Up to 50 patients are planned to be enrolled

• The study will be conducted in Europe at est. 20 clinical sites

• 6 months interim data from first few patients in Q4, 2020

6 weeks

12 months

VaccinationInduction

VaccinationMaintenance Follow Up

24 months

Advanced or Recurrent, Non-Resectable HPV16-Positive Cervical Cancer

Proposed study design for VB10.16 + Tecentriq®In patients with advanced or recurrent, non-resectable HPV16+ cervical cancer

Confidential

VB10.NEO: Cancer neoantigen vaccine in clinical trial (VB N-01)

VB N-01: An open labelled first human dose phase 1/2a study to evaluate safety, feasibility and efficacy of multiple dosing with individualised VB10.NEO immunotherapy in patients with locally advanced or metastatic melanoma, NSCLC, clear renal cell carcinoma, urothelial cancer or squamous cell carcinoma of head and neck, who did not reach complete responses with current standard of care immune checkpoint blockade

VB10.NEO

Melanoma

NSCLC

Clear Renal Cell Carcinoma

Urothelial Cancer

Squamous Cell Carcinomaof the Head and Neck

• Approved CPI as SOC• Moderate to high mutational load

VB N-01

n=40-91

Unique Study Design and Treatment Schedule VB N-01

6 weeks

12 months

Sequencing, Synthesis &

Manufacturing

VaccinationPrime

VaccinationMaintenance Follow Up

24 months

0 3 6

1 2 3

10 14 18 22 26 30 34 38 42 46 50

4 5 6 7 8 9 10 11 12 13 14

Consent +

Biopsy

Week

Dose #

CPI treatment>12 weeks

Confidential

• Inclusion criteria: previous treatment with CPI for >12 weeks and stable disease (or partial response or mixed response) at enrollment. Limited tumour reduction expected from continous CPI treatment only

Tsimberidou et al., 2018 17

Plan to open expansion cohort in 2H 2019

100% vaccine manufacturing success for all patients with a successful biopsy so far

20 neoepitopes selected for all patients in the trial

First expansion cohort could be initiated in H2, 2019

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Vaccibody’s Solution to Personalised Cancer Treatment

Vaccibody provide a Rapid, Cost-effectiveand Efficacious solution

NeoSELECTTM

-Needle-free

-Target, Attract, Mature, Deliver, Cross-present

-Rapid, strong, long-lasting

-unique CD8 dominatedresponses

-DNA: Robust, rapid, cost-effective, stable, safe, up to 40 neoepitopes

DNA plasmid as therapeutic modality enables competitiveCOGS for personalized neoantigen vaccine

1st Clinical Trial(s) On Market

Manufacturer • CMOs • Dedicated manufacturing unit(s)

Services • Variety of suppliers • All under one roof

Capacity • 120 - 150 vaccines per year • Matching market demand

Time from biopsy to immunization

• 12-14 weeks • Target: 4-6 weeks

Cost per batch • > 100.000 EUR • ~15 000 EUR




VB10.16

VB10.NEO



VB10.16 + Atezolizumab (CPI)CERVICAL

21

www.vaccibody.com

vaccibody · complete tumour regression . of large, established tumours long-term memory responses...

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