Lytix Biopharma AS | Gaustadalléen 21, NO-0349 Oslo, Norway | E-mail: post@lytixbiopharma.com | Phone: +47 77 67 55 00 | Fax: +47 77 67 55 01

LTX-315, a first in class oncolytic peptide, reshapes the tumor microenvironment in the patients with advanced metastatic tumors: Results from an ongoing studyAURELIEN MARABELLE1, JEAN-FRANCOIS BAURAIN2, AHMAD AWADA3, PAAL F. BRUNSVIG4, REBECCA SOPHIE KRISTELEIT5, DAG ERIK JØSSANG6, NINA LOUISE JEBSEN7, DELPHINE LOIRAT8, ANNE ARMSTRONG9, JEROME GALON9, FABIENNE HERMITTE10, ANDREW SAUNDERS11, ØYSTEIN REKDAL11, BALDUR SVEINBJØRNSSON11, BERIT NICOLAISEN11, VIBEKE SUNDVOLD GJERSTAD11, JAMES SPICER12

1INSTITUT GUSTAVE ROUSSY, PARIS, FRANCE, 2CLINIQUES UNIVERSITAIRES ST-LUC, UCL, ST. LUC, BELGIUM, 3INSTITUT JULES BORDET, UNIVERSITÉ LIBRE DE BRUXELLES, BELGIUM, 4OSLO UNIVERSITY HOSPITAL, NORWAY, 5UNIVERSITY COLLEGE LONDON HOSPITAL, UK, 6HAUKELAND UNIVERSITY HOSPITAL, NORWAY, 7CENTRE FOR CANCER BIOMARKERS (CCBIO), UNIVERSITY OF BERGEN, NORWAY, 8INSTITUT CURIE, PARIS, FRANCE, 9THE CHRISTIE NHS FOUNDATION TRUST, MANCHESTER, UK, 10FRANCE LABORATORY OF INTEGRATIVE CANCER IMMUNOLOGY, INSERM, PARIS, FRANCE, 11HALIODX, MARSEILLE, FRANCE, 12LYTIX BIOPHARMA, NORWAY, 13KINGS COLLEGE, GUY´S HOSPITAL, LONDON, UK

Aim• Evaluate the safety and tolerability of intra-tumoral LTX-315 in monotherapy

or in combination with either ipilimumab or pembrolizumab in patients with transdermally accessible tumors

• Determine the recommended phase II dose and schedule

LTX-315 is a first in class oncolytic peptide with unique “release and reshape” MoA

CONFIDENTIAL

LTX-315 is a first in class oncolytic peptide with unique «release and reshape» MoA1-9

Preclincial studies of LTX-315 demonstrates complete regression of injected and non-injected tumors (i.e. Abscopal effect)

Immune related response (irRC) assessment

Mono VAGINAL SCC

Mono HEAD AND NECK

Mono SARCOMA

Combination BREAST

Mono BREAST

Combination MELANOMA

Mono MELANOMA

LTX-315 converts cold tumors to hot

TreatmentNo. of patients

treatedNo. of patients with biopsies

evaluable for CD8 IHC to dateNo. of patients with increased

CD8+ T cells in post treatment tumors

LTX-315 28 17 15 (88%)

LTX-315 + Pembrolizumab 9 5 4 (80%)

CONFIDENTIAL 10

melanoma leiomyo-sarcoma melanoma epidermoid cancer desmoid tumor breast cancerTumor type

010203040506070

321015 471010 321012 331030 472011 441013

Treatment # patientstreated

# patients with biopsiesevaluable for CD8 IHC to date

# patients with increasedCD8+ T cells in post treatment tumors

LTX-315 28 17 15 (88%)LTX-315 + Pembrolizumab 6 3 3 (100%)

Increase in CD8 gene expression in tumors upon LTX-315 treatment

LTX-315 converts cold tumors to hot

fold

incr

ease

CD8a

Tumor type

10

0

60

40

30

20

50

70

Fold

incr

ease

CD

8a

Melanoma Breast cancerDesmoid tumorEpidermoid cancer

MelanomaLeiomyo-sarcoma

Increase in CD8 gene expression in tumors upon LTX-315 treatment

Hierarchical Clustering of Immunosign® 21 Immune Gene Signature (HalioDx) which profiles expressions of a pre-defined set of effector T cell, Th1, chemokine, and cytokine genes.

Gene expression in tumor pre and post treatment

Duration of treatment (weeks)

LTX-315: Safety (N=51)

Study Design

Primary Endpoints • Safety (including DLTs, AEs, SAEs, lab assessments) of LTX-315

Secondary Endpoints• LTX-315 related Immune parameters in tumor and peripheral blood

• Anti-tumor activity of LTX-315 by CT scan assessment (immune-related response criteria (irRC))

*AEs occuring in ≥ 2 patients per CTC Version 4.0# No grade 4 LTX-315 related AEs reported ¥ Reported as both LTX-315 and Pembrolizumab related

Patient population• Advanced/metastatic disease (all tumor types)

• At least one transdermally accessible lesion of ≤ 10 cm in diameter

LTX-315 Monotherapy (N=36)*

LTX-315 related adverse event

Grade 1-2 (No. of pt (%))

Grade 3-4# (No. of pt (%))

Hypotension 10 (28%) -

Parasthesia 8 (22%) -

Rash 10 (28%) -

Flushing 8 (22%) -

Pruritis 4 (11%) -

Tumor pain 2 (6%) 2 (6%)

Allergic reaction 1(3%) 4 (14%)

Pain (injection site) 2 (6%) 2 (7%)

LTX-315 Combination therapy (Ipilimumab/pembrolizumab) (N=15)

LTX-315 related adverse event

Grade 1-2 (No. of pt (%))

Grade 3-4# (No. of pt (%))

Allergic reaction 4 (29%) 1 (7%)

Pain (injection site) 3 (20%) 1 (7%)

Tumor pain 2 (13%) -

Fatigue 2 (13%) -

Pneumonitis¥ - 1 (7%)

LTX-315 MonotherapyLTX-315 dose per injection No. of patients Tumor type

Single/sequential lesion injection

2-7mg (1-2 injections per lesion) 23 Melanoma (7); Breast (6); Sarcoma (3); H&N (3); Adrenal (1); Urethral (1); Desmoid (1); Pancreas

Multiple (≥ 1) lesion injection

3mg (1-8 injections per lesion) 8 Head & Neck; Breast; Vaginal SCC; melanoma; sarcoma (2); Anal Ca; Desmoid

4mg (1-6 injections per lesion) 5 Head & Neck (2);Anal Ca; Sacroma; Gastric ca

LTX-315 + Ipilimumab Metastatic melanoma

(post-PD1/L1 treatment; multiple (≥ 1) lesion injection)

LTX-315 dose per injection No. of patients

3mg (1-4 injections per lesion) 4

LTX-315 + PembrolizumabMetastatic Triple Negative Breast Cancer (2-5th line);

multiple (≥ 1) lesion injection)

LTX-315 dose per injection No. of patients

3mg (1-2 injections per lesion) 4

4mg (1-6 injections per lesion) 5

CD3D.goodTreatment status

47

20

11

-pre

PRF1.good

44

10

13

-pre

GZMK.good

32

10

12

-pre

CD8A.good

32

10

09

-pre

CXCR3.good

47

10

10

-pre

CD69.good

32

10

09

-pos

t

CCR2.good

33

10

30

-pre

CD3E.good

32

10

15

-pre

STAT4.good

47

20

11

-pos

t

ICOS.good

GZMB.good

32

10

15

-pos

t

IL15.good

32

10

12

-pos

t

CXCL10.good

33

10

30

-pos

t

CXCL11.good

47

10

10

-pos

t

CD3G.good

TBX21.good

44

10

13

-pos

t

GZMM.good

IRF1.good

GZMA.good

CCL2.good

STAT1.good

LTX-315 generates a systemic tumor specific immune responseCase study: patient 471-016, Breast cancer, Monotherapy

Tumor pre treatment• 128 T cell clones expanded in blood post treatment.

• Clones expanding in blood were predominantly detected in post-treatment tumor samples.

Tumor pre treatment

CD8

Tumor post treatment

CD8

Tumor post treatment

T ce

ll cl

ones

in b

lood

pos

t tr

eatm

ent

Contracted in bloodContracted in blood & present in tumor

Expanded in bloodExpanded in blood & present in tumor

No significant change in frequencyNot significant & in tumor

1

▪ 128 T cell clones expanded in blood post treatment.

Contracted in bloodContracted in blood & present in tumorExpanded in bloodExpanded in blood & present in tumorNo significant change in frequencyNot significant & in tumor

LTX-315 generate a systemic tumor specific immune responseCase study: patient 471-016, Breast cancer, Monotherapy

▪ Clones expanding in blood were predominantly present in treated tumor.

T CELL CLONES IN BLOOD PRE TREATMENT

TUMOR PRE TREATMENT TUMOR POST TREATMENT

T CELL CLONES IN BLOOD PRE TREATMENT

T CE

LL C

LONE

S IN

BLO

OD P

OST

TREA

TMEN

T

T CE

LL C

LONE

S IN

BLO

OD P

OST

TREA

TMEN

T

1

▪ 128 T cell clones expanded in blood post treatment.

Contracted in bloodContracted in blood & present in tumorExpanded in bloodExpanded in blood & present in tumorNo significant change in frequencyNot significant & in tumor

LTX-315 generate a systemic tumor specific immune responseCase study: patient 471-016, Breast cancer, Monotherapy

▪ Clones expanding in blood were predominantly present in treated tumor.

T CELL CLONES IN BLOOD PRE TREATMENT

TUMOR PRE TREATMENT TUMOR POST TREATMENT

T CELL CLONES IN BLOOD PRE TREATMENT

T CE

LL C

LONE

S IN

BLO

OD

POST

TRE

ATM

ENT

T CE

LL C

LONE

S IN

BLO

OD

POST

TRE

ATM

ENT

T cell clones in blood pre treatmentT cell clones in blood pre treatment

T ce

ll cl

ones

in b

lood

pos

t tr

eatm

ent

T cell clones expanded in blood are detected in post-treated tumors

• Clones expanding in blood are detected in post-treatment tumor biopsies; median 49%, 6 patients analyzed.

• In contrast, the expansion of pre-treatment-tumor associated clones is less in all but one patient; median 23%. 

• Contracted clones in blood were not detected in the tumor in 2 of the 6 patients.

300 μm 300 μm

CONFIDENTIALCONFIDENTIALCONFIDENTIALCONFIDENTIAL

irSDirPDirPRNot evaluable

Duration of treatmentMelanoma (Mono and Combo)Breast (Mono and Combo)Sarcoma (Mono)Head and Neck (Mono)Vaginal SCC (Mono)

CONFIDENTIAL

4032241680

Tumor-associated clones expanded in blood (median)

Tum

or-a

ssoc

iate

d Cl

ones

(Pro

port

ion)

ContractedExpanded

T cell clones expanded in blood are detected in post-treated tumors

1

▪ Approximately 49% (median) of clones expanding in blood are detected in post-treatment tumor biopsies (6 patients analyzed).

▪ In contrast, the expansion of pre-treatment-tumor associated clones is less in all but one patient (median 23%).

▪ Contracted clones in blood were not detected in the tumor in 2 of the 6 patients.

0

20

80

60

40

PostPre

Study Conclusions• LTX-315 converts “cold” tumors to “hot”, as evidences by increase of tumor

infiltrating lymphocytes (CD8+ T cells) and gene expression analysis.

• TCR clonality analysis of blood and tumors samples show that LTX-315 generates a systemic anti-tumor T cell response.

• LTX-315 is generally safe and tolerable. No MTD has been reached.

• Stable disease (SD) by irRC observed with LTX-315 mono therapy (8/15 pts)

• Durable SD by irRC observed (1/4 pts) with LTX-315 + ipilimumab (32 wks, ongoing)

• Partial Remission (PR) by irRC observed (1/8 pts) with LTX-315 + pembrolizumab (10 wks, ongoing)

• Results support the rationale and potential benefit of LTX-315 as a novel intratumoral immunotherapy; A phase II multi-arm combination trial is planned in 2018