Increasing infiltration to solid tumors,

reducing on-target/off-tumor interactions

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Tarom Innovative Technologies

▪ Tarom Innovative Technologies Ltd. is an entrepreneurial private incubator, focusing

on identifying break-through innovations in Life Sciences and providing pre-seed
investment to structure and advance these early-stage projects to demonstrate initial
proof of concept, thus becoming attractive for further investment.
▪ It is a sister company to Tarom Applied Technologies, a well-established and reputed
local importer and distributor of diagnostic tools, research reagents and process
equipment for the Life Sciences industry.
▪ Leveraging on the immense brainpower and ingenuity of the Israeli scientific
community, Tarom identifies, selects, invests-in and develops multiple high added-
value technologies, products and inventions, based on IP acquired from local research
institutions.
▪ Our portfolio includes medical devices, pharmaceuticals, biologics and diagnostics.
▪ Main fields of focus are cancer, ophthalmology and diagnostics.
▪ Entering projects in their early-stage enables identification of potentially
groundbreaking discoveries and disruptive technologies and reaching high valuation
milestones through relatively modest investments.
▪ The following slide deck presents Remission, a company under the Tarom Umbrella.

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How We Created Remission

▪ Remission is a project that combines independent innovations and knowhow from 3

Israeli reputed institutions: The Rambam Medical Center, The Ichilov-Sourasky
Medical Center and the Weizmann Institute of Science.
▪ The Weizmann-Ichilov team are experts on CAR-T technology and were part of the
pioneering team that developed the CAR-T concept and one of the leading academic
teams in the field over the past decades.
▪ The Rambam Team found means to increase infiltration of T-cells (and potentially
other immune cells) into solid tumors.
▪ Tarom has invested to advance Rambam’s discovery and to show in vitro that the
mechanisms shown in mice cells are general and apply also for human cells, thus
paving the way to the crystallization of the hereby presented concept.
▪ Tarom has licensed-in the technologies, structured the presented development
approach and harmonized the collaborative research teams of the different
institutions and is supervising the project for PoC and the further preclinical and
clinical development.
▪ Currently, Remission is a project under Tarom and will be spun-off immediately upon
seed investment by a third party to enable the independent company to develop the
project with a dedicated team.
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Snapshot

• A for solid tumors, based

on CAR-T cells with improved efficacy and safety

• Preliminary demonstrated in animal

models

indication: Ovary Cancer - an unmet

need with significant market

• Led by
with proven track record

• Preclinical development is planned for 2.5 years,

of which the first 1.5 years are dedicated to
showing efficacy in animal models and require an
investment of about 1M USD
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Team
Zvi Barr
Owner and Managing Director of
Tarom Applied Technologies, a
leading local distributor for well-
known international manufacturers of
diagnostic tools, research reagents
and process equipment for the
Life Sciences industry. Founder
and Chairman of Tarom Innovative
Technologies, a private portfolio
company, focusing on break-through
innovations in Life Sciences.
Dr. Dror Melamed
Experience of over 20 years in senior
executive management positions in the
biopharmaceutical industry, for all
aspects of start-up and growth company
management, including business
and technological development. Led
multiple development and partnering
projects. Dr. Melamed holds a Ph.D. in
molecular and cellular biology from the
Faculty of Virology at the Weizmann
Institute of Science and MBA from
Bar-Ilan University.
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Team
Dr. Anat
Globerson Levin
PhD from the Weizmann Institute of Science at Prof.
Zelig Eshhar’s group. Moved with Eshhar’s group to
TASMC, now managing the lab. Her current focus is
on increasing the potency of CAR-T in solid tumors
and new targeted T cells for treating different
cancers.
Received multiple grants (ISF, CRBC, ROI-NIH, Spark,
Kamin). Leading the development of new CARs
into the clinic, together with the Immunotherapy
Center at the hospital (I-ACT) as well as conducting
basic research.
Dr. Igal
Louria-Hayon
Recipient of the Israel Scientific Foundation (ISF) grant
and serves as a reviewer and a member of the judging
committee in the field of hemato-oncology for the
Chief Scientist Office in the Ministry of Health. Scientific
director of the Research and Innovation Center for
Medicinal Cannabis at Rambam. Dr. Louria-Hayon holds
a Ph.D. in the field of tumor immunology from the
Hadassah Medical School at the Hebrew University.
Performed postdoctoral research in the field of cancer
signaling and cell communication at Mount Sinai
Hospital, Toronto, Canada.
Dr. Ishay
Ophran, MD
Former Director of leukemia service at Rambam
Health Care Campus, Chair of the Israeli Leukemia
Working Group and member of the ECOG-ACRIN
leukemia core committee. Dr Ofran holds a research
position, and together with Dr Louria-Hayon leads the
laboratory for leukemia and immune response at the
Rambam Research and Innovation Center and serves
as Clinical Assistant Professor at the Technion's faculty
of medicine.
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Chimeric Antigen Receptor
(CAR) T Cell Therapy
Harnessing the patient’s own
immunological defense

is based on modifying T cells to recognize cancer cells in order to more

effectively target and destroy them

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CAR-T Cell Therapy for Solid
Tumors: an Unmet Need

CAR-T cell therapy has garnered significant excitement due

to its success in treating hematological malignancies, with
3 FDA approved products.

90%

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Market and Opportunity
The CAR-T market is booming with over 300 CAR-T registered
clinical trials, focused on blood cancers. There is huge
for efficient solutions for treating

Partner with
By &

Remission’s target:
The unmet market
of solid tumors

By By

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The Challenge
Immunotherapeutic Barriers to Treating Solid Tumors

Identifying appropriate target antigens that

demonstrate between normal
tissue and tumor

Once CAR-T cells are infused into a patient, an immediate

obstacle is the

CAR-T cells that reach the tumor should be able to

overcome the tumor’s immunosuppressive
microenvironment

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Remmision’s Solution:
Increasing CAR-T infiltration
into the tumor mass

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• Our scientists discovered that one of the mechanisms
preventing the infiltration of activated T cells into solid
tumors is a protein called LNK

• LNK blocks a signal that is transduced from the T cell

surface into the cytoplasm and activates T cell
infiltration

• By silencing the expression of the LNK protein, this

blockade is relieved and the cells are capable of
efficiently infiltrating deeply into the tumor solid
mass

• T cell infiltration results in reduced tumor volume

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2
Remmision’s Solution:
Reducing toxic interactions
with normal tissues

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• We design a genetically modified T cells platform with a
dual specificity, expressing two chimeric receptors for a
specific and effective treatment of ovarian cancer

• Dual-CAR is a new approach that addresses the major

challenge of 'off-tumor on-target' toxicity in CAR therapy
(risk of damage to healthy tissues)

• While normal tissues may singly express each of these

antigens, only cancer cells express both of them

• The CAR-T cells are activated only upon simultaneous

binding to the two cancer antigens

which are co-expressed

by the tumor, but not by normal tissues,

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Collaboration with Leading World Experts

LNK manipulation experts World's pioneering team in CAR-T

Research and Development

The Leukemia Laboratory The Immunology Laboratory

RAMBAM medical center Ichillov-Sourasky medical center

tation by Dr. Michael Mendicino

Ex-FDA Commissioner’s Fellow

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First Indication to be
Developed – Ovarian Cancer

• most common cause of cancer-related death among females in the US

• About people may receive a diagnosis of ovarian cancer

• Around people are from this condition1

• No effective screening tests; Five-year

• FDA may grant an to therapies aimed at ovarian cancer

• Ovarian cancer market valued at and it is expected to grow to

with a 2

• CAR-T has been extensively investigated for ovarian cancer treatment, until now with
3

1 OCRA, Ovarian cancer research alliance website https://ocrahope.org/patients/about-ovarian-cancer/statistics/

2 Global Data, October 2019

3 Yan, W. et al. 2019. Advances Of Chimeric Antigen Receptor T Cell Therapy In Ovarian Cancer. Onco Targets Ther.

12: 8015–8022

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Competitive Advantage

for the treatment of : compatible

solid tumors with CAR-T cells with most CAR-T technologies

enabling
Dual CAR-T on-target/off-
enhanced infiltration of CAR-T cells into
tumor interactions and related
solid tumors

Enables
First demonstration will be made on
to augment CAR-T efficacy (e.g.
with unmet need
checkpoint inhibitors, STING, etc.)

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The Business Opportunity

• for proof of concept of a potentially ground

breaking technology with

• Significant multiplier in case of successful proof of concept

within a short time

• Potential collaboration with multiple leading big pharma companies

within a short time, and potential
for investors

• Own orphan indication product, enabling independent development

and further

• Excellent research team with proven track record

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Remission in Motion

WATCH HERE

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Summary
• A novel approach to activate tumor infiltration of immune cells
via Lnk knockdown

• Combined with dual CAR-T, designed to reduce toxicity

• Potential to overcome the limitations of current CAR-T therapies

in treating solid tumors

• Prone to all solid tumors - the majority of cancer types with high
need and huge market

• Strong IP

• Excellent R&D support team

• State-of-the-art clinical support (Rambam Hospital;

Ichilov Hospital)

• First in human demonstration planned in ovarian cancer -

unmet need, orphan designation, significant market

• A platform technology, for different types of solid tumors -

partnering with big pharma

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