Targeting Solid Tumors

Success in Phase II Pancreatic Cancer

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We can extend and improve patients’ lives

• Success in Phase 1 and the ongoing multinational Phase 2 in pancreatic cancer

• Clinical evidence of superiority in disease halting and life extension

• Effective silencing of the KRAS oncogene with our proprietary LODER platform

• No safety concerns and multiple additional successful results including pain reduction

• Phase 2 for combination with Roche’s Tecentriq® is in preparation in Europe

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Positioned to reach the market by 2022

Pancreatic cancer market is growing fast

• $4.8B in 2026 (Research and Markets 2019)

• Strong efficacy results pave the way for collaborations

• Eliminating safety concerns can enable faster approval

Orphan designation approved

FDA IND and Orphan Drug

Designation approved

9 patents granted

Valid until 2029-2035

Marketing approval in 2022

Fast Track and ConditionalMarketing in process with FDA

In-house manufacturing

cGMP – ready manufacturing facilities, scalable for market needs

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41 patients out of 80 enrolled in ongoing Phase 2 trial* Target patients: Stage 3, locally advanced pancreatic cancer

Israel

USA

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PI: Eileen O’Reilly , MD Memorial Sloan Kettering

*Original design: Randomized Control Trial (CRT); In Dec 2019 FDA confirmed change to Single Arm Trial (SAT)

The KRAS-LODER platform

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• siKRAS (the drug substance) is a small interfering RNA (siRNA) designed to specifically target the mutated KRAS (G12X mutations (G12D, G12C, G12V…)) oncogene

• KRAS-LODER is a smooth, miniature, rod–shaped polymeric tube embedded with the drug substance

5.5±1mm

0.8±0.04mm

siKRAS siRNA

Polymric matrix (FDA approved)

LODER preserves the siRNA drug, releasing it over months

No protein coverage on surface; Avoiding drug trap, enabling drug distribution over the entire tumor

Surface presents only tiny holes, which assures blocking of RNAse penetration. Drug degradation over months is avoided

LODER stays intact over months

(image from mouse 60 days post- insertion)

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LODER is inserted by standard Endoscope Ultrasound (EUS)

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LODER Insertion

EUSEndoscope

• Inserted into the pancreatic tumor by standard

Endoscope Ultrasound using off-the-shelf biopsy

needles US facility, with no need for surgery

The LODER is implanted in a simple, routine, minimally invasive FDA-approved procedure

• 0.35mg of drug in each LODER

• 12 weeks release

• 1- 8 LODERs (approx. 3mg) are implanted every

cycle (every 3 months)

KRAS-LODER is designed for regional, targeted and continuous release of drug over 3 months

Phase 2 design

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LODERLODERLODER LODER 6

months

LODER 3

months

Lo

ca

lly A

dva

nc

ed

Pa

nc

rea

tic

Ca

nc

er

(LA

PC

; Sta

ge

3)

Arm 2

Gemcitabine + nab-Paclitaxel

40 pts

Arm 1

LODER +

Gemcitabine + nab-Paclitaxel

40pts

Rand 1:1

LODER every 3 months

until progress

ion

Single Arm

LODER x 3 + Chemotherapy SOC:

Chemotherapy =

Gemcitabine + nab-Paclitaxel

Or

FOLFIRINOX

Or

Modified FOLFIRINOX

PEP:ORR at 6 months

From 1/2020

LODER Day

0

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Tumor response in first 12 patients:

• 66.7% in study group

• 16.7% in control

Encouraging signs of QOL, PFS (not reported)

Study group showed longer duration of response close to 1 year compared to a short 4 months in control group.

Encouraging efficacy in Interim Report to FDA (July 18, 2019)

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Superiority in Overall Survival (OS) at 15 months (Jan 3rd, 2020)

LODER: 90% OS (15mo)+ Gem/Abraxane; without radiation

Superiority in OS demonstrated vs. Historical data*

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Suker et al., 2016 – Meta Analysis of 315 pts, 13 studies

Suker 2016: FOLFIRINOX, Radiation

LODER: + Gem/Abr;

without radiation

90% (LODER) vs. 72% (Suker 2016)

* Silenseed LODER + Gemcitabine + nab Paclitaxel

Historical data SOC: FOLFIRINOX +/-- radiation

Superiority in OS demonstrated vs. Historical data*

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NEOLAP study: 58% (Not resected)/64% (Resected)Gem/Abr, FOLFIRINOX, Radiation

NEOLAP study final results, ESMO 2019, Barcelona

LODER: + Gem/Abr;

without radiation

90% (LODER) vs. 58% (NEOLAP study)

* Silenseed LODER + Gemcitabine + nab Paclitaxel

Historical data SOC: FOLFIRINOX +/-- radiation

90% (LODER) vs. 74% (SEER - Operated)

Superiority in OS demonstrated vs. wide SEER surveys

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SEER data Ansari et al., 2016 –EOPC (Early Onset of Pancreatic Cancer, patient age at disease onset <50 years vs. LOPC (≥ 50 years))

LODER + Gem/Abr; without radiation

Ansari 2019: 74%Operated LOPC Patients

Ansari 2019: 20%Non-Operated LOPC Patients

90% (LODER) vs. 20% (SEER - Non-Operated)

Superiority in overall response rate (ORR)

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LODER: 53.8% (7/13)Control: 37.5% (3/8)

• Patients ≥4 months in trial• Patients with partial response

or becoming resectable at <4 months

Tumor shrinkage in LODER arm is stronger

Data update: Jan 3, 2020

Deeper and longer tumor response

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Tumor response in the LODER Arm is

Deeper

DOR is longer

In some cases is late

Late response: 23.1% (3/13) patients in the LODER arm show evidence of late response ~6 months post first LODER

Data update: Jan 3, 2020

Dual

Our building blocks assure effective treatment

Silencing the target KRAS oncogene; directed to the tumor

Avoiding side effectsDramatic reduction in dose

Drug distributed only within the tumor

Avoiding systemic effects, eliminating adverse events

Effective controlled prolonged release over months

Replacing ineffective injections

Administration by Routine EUS every 3 months

Avoiding multiple injections and hospitalizations

Localized Prolonged SimpleTargeting

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Mutations in the KRAS gene switch “ON” the KRAS protein, converting it to an active cancer driver ‘oncogene’.

Once mutated, the KRAS oncogene activates downstream signal transduction pathways (RAF, PI3K…), accelerating cell proliferation and differentiation, which induces tumor growth.

Mutations in the KRAS oncogene

/ 18Nature Biotechnology volume 38, 2020

KRAS is the oncogene to target in pancreatic cancer

94% of pancreatic cancers are

driven by the KRAS oncogene, which

until recently was considered

‘undruggable’.

CDKN2A

SMAD4

TP53

KRAS

100%75%50%0% 25%

63.9

20.8

94.1

17

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LODER silences all G12X KRAS mutations (G12D, G12C, G12V…)

Induces necrosis and apoptosis

LODER induces KRAS silencing, cell death, and tumor permeability

LODER elevates void volume;

Improves tumor permeability and enables T-cell penetration

50µm

Normal pancreas Empty-LODERTM-treated

Untreated tumor treated-TMLODER-D12siG

KRAS-LODER ( 7 days post implantation )

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Average void volume (%) in LODER-treated tumor tissues after 20 days

18

30

5

10

15

20

25

KRAS-LODER siLuc LODER

Empty LODER ( 7 days post implantation )

LODER impedes metastases and regional invasion

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Impedes metastases

Halts perineural invasion

Developing Tumors Implanting Tumors in naïve mice

Tumors Placebo LODER

Untreated

KRAS- LODER

% of macro-metastases in lung, liver and spleen

63%

50%

0% (9 mice)

1 month 1 month

Dorsal Root Ganglion (DRG)

Pancreatic Cancer Cells

Control: Invasion

KRAS Silenseed: No invasion

Safety confirmed in Interim Report to FDA (July 18, 2019)

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No Drug-Related SAEs

All ECGs showed no significant change in QT/QTc intervals (all within the normal range)

Negligible levels of siG12D in the peripheral blood (PK).

No induced systemic release of cytokines in the blood

In-house manufacturing

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Manufacturing

• Class A clean room environment

• Designed to fulfill FDA cGMP requirements for

clinical trial use

Capacity

• Current: 12,000 units/year

(for all clinical development and marketing up

to 2021)

• Future: 48,000 units/year

• 6 months to modify facility

• Production employee headcount doubled

• $400K-$600K for Capex and re-validation

Pipeline: multiple indications; multiple oncogenes

24*In preparation with Roche/Genentech

Marketing (Conditional) 2022

Phase 3 CommercializationPhase 2Phase 1Pre-ClinicalResearch

LODER (KRAS) + Chemotherapy Pancreatic Cancer (IND)

LODER (KRAS) + Tecentriq® (PD-L1, Pancreatic cancer)

nano-LODER for GBM

LODER (HSP90, BMI-1) Prostate

LODER (KRAS) + IO (Lung)

KR

AS

No

n-K

RA

S

Shukui Qin , MD. Prof. Senior Vice President of Chinese Society of Clinical Oncology (CSCO)Chair of Chinese Society of Clinical Oncology Foundation (CSCO Foundation) Senior Vice President of Chinese Nanjing BayiHospital Director of Chinese PLA Cancer Center & National Drug Clinical Trial Institution C.

Extension of Phase 2/3 in China

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Medical sites: Prof. Wang Liweifrom Shanghai RenjiHospital

Dr. Feng Wang : Attending physician of Oncology Department in Fuda Cancer Hospital, Guangzhou

Dr. Rongping Guo : the director of Hepato-biliary surgery Dept. Sun Yat-Sen University cancer center, Guangzhou

• Silenseed is currently selecting some medical center partners and preparing submission to the China-FDA (now called NMPA).

• The process includes adjusting the protocol

to comply with NMPA requirements and

submission per the China regulations as class

1 (e.g. language, local legal entity)

• Target enrollment: A total of ~100 patients.

Deal Structure

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Round: $15MM - $30MM

Use of proceeds

Complete Phase 2 (Total 80 patients, 41 enrolled)

Enable smooth continuation to Phase2/3

Additional activities, including KRAS-LODER + IO combination in Lung and Pancreatic cancer

Prospect

Inflection point ~50 patients (>3mon follow up) Q2 2020

Expected range of valuation at inflection point $300mm-$1B

$21M raised, led by strong team

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* Esperante ventures (UK, Ferring), Prof. Michael Sela, Prof. Ruth Arnon (TEVA Copaxone®), Dr. Shmuel Cabilly (Cabilly Patents), Belsize Investments (UK), Esther Pirak (Erbitux®).

Non-diluting Funds also raised from the Israel Innovation Authority (IIA)

Shareholders

28%: Bonderman family (TPG)

18%: Ilan Shiloah (The TIME)

11%: Amotz Shemi (Founder)

43%: Others*

Team

Amotz Shemi , PhD , CEO (Medinol, ColorChip) Yaniv Zilber, CPA, VP finance (EY) Irit Hillman, MSc, CRA Clinical Shay Rotkopf, PhD, Pre-Clinical Rachel Malka Gabai, PhD, Formulation Revital Maor Aloni, PhD, Quality assurance Ronen Shemesh, PhD, Scientific director (QBI, Teva) Ruth Wolfson, PhD, VP regulatory affairs (Kamada; KMDA)

Eithan Galun, PhD, MD, Head of Scientific advisory board Esther Pirak, PhD, Director, Advisor, drug development (Erbitux®) Abraham J. Domb, PhD, Active advisor, formulation (Gliadel®) Yechezkel Barenholz, PhD, Advisor, drug development (Doxil®)

New hope for a healthy future:To pancreatic cancer and beyond

Thank you!

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