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Kadimastem Ltd. — Investor Presentation 2021
May 2, 2021
6872_rns_2021-05-02_fe64712f-dc1e-4579-b8c2-a244ae08a6a1.pdf
Investor Presentation
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May 2021 (TASE: KDST)
Disclaimer
This presentation was prepared for the sake of summary and convenience only and it cannot replace a reviewing of the prospectus and/or the periodic report and/or other reports that Kadimastem Ltd. (hereinafter: "the Company") published to the public trough the MAGNA. This presentation presents a complete set of information as of the date of their presentation, which together with all of the Company's periodic, semiannual and immediate reports reflect a complete picture of the Company.
In this presentation, the company included projections, estimates and assessments, as are known to the Company at the time of preparation of this presentation, referring to the Company and including, inter alia, forward-looking information as defined in the Securities Law, 5728 – 1968, based on subjective estimates on the part of the Company in respect of its development potential and based on initial information and documents the Company received from professional entities relevant to the Company's development plans.
Forward-looking information is uncertain and mostly is not under the Company's control and the realization or non-realization of forward-looking information will be affected, among other things, by the risk factors characterizing the Company's activity, as well as developments in the general environment and external factors affecting the Company's activity. The Company's results and achievements in the future may differ materially from those presented in this presentation and the Company makes no undertaking to update or revise such projections or estimates and does not undertake to update this presentation.
This presentation does not constitute a proposal to purchase the Company's securities or an invitation to receive such offers. Investment in securities in general and in the Company in particular bears risks. One should take into account that past performance does not necessarily indicate performance in the future.

Vision – Stem Cell Derived Therapy
Replace, restore and repair the functionality of diseased and malfunctioning cells in various degenerative diseases by transplantation of our healthy and functional cells
Proprietary cell lines optimized for the cure of Diabetes and to treat ALS

GFAP/GLAST/DAPI C-peptide/Glucagon/DAPI

Proprietary Innovative Platform
Proprietary expansion and differentiation processes of cells intended for treatment of multiple diseases


Product Platform Pipeline CLINICAL

An Active Market – Big Recent Transactions

To the best of Company's knowledge, base on the following:
- http://www.semma-tx.com/media1/vertex-to-acquire-semma-therapeutics-with-a-goal-of-developing-curative-cell-based-treatments-for-type-1-diabetes
- https://www.prnewswire.com/news-releases/lilly-and-sigilon-therapeutics-announce-strategic-collaboration-to-develop-encapsulated-cell-therapies-for-the-treatment-of-type-1-diabetes-300624199.html
- https://media.bayer.com/baynews/baynews.nsf/id/Bayer-acquires-BlueRock-Therapeutics-to-build-leading-position-in-cell-therapy
- https://finance.yahoo.com/news/sana-announces-upsized-pricing-initial-042200699.html?guccounter=1
AstroRx ®
Astrocytes for Neurodegenerative Diseases


ALS– Market and Facts
- Death of motor neurons
- Progressive loss of muscle control leads to eventual death
- 90-95% sporadic and 5-10% familial (C9orf72, hSOD1, TDP-43, FUS)
- Disease onset 50-60 years, survival from onset 2-5 years

• Current FDA approved treatments are Rilutek & Radicava with modest effect
- ALS is a fatal rare disorder with no cure
- Around 450,000 ALS patients estimated worldwide, 30,000 patients in the US1
- ALS Annual drug sales: (US, Canada, France, Germany, Italy, Spain, UK and Japan) 2
- 2019: \$282M
- Estimate 2029: \$1.04B
- US ALS Healthcare costs:
- Up to \$200K estimated annual medical expenses per patient3

-
- Amyotrophic Lateral Sclerosis (ALS): Opportunity Analysis and Forecasts to 2029. GlobalData 2020
Why Use Astrocytes for ALS - AstroRx®
AstroRx® contains functional healthy astrocytes to protect ALS-diseased motor neurons using multiple mechanisms of action
| In ALS, the patient's own | Mechanism of Action | ALS Patients' Astrocytes |
AstroRx® Healthy, Functional Astrocytes |
Synapse neuron |
|---|---|---|---|---|
| astrocytes fail to support | Secrete neurotrophic factors | |||
| motor neuron survival | Remove toxic factors (i.e. glutamate) |
|||
| Regulate oxidative stress |
Astrocyte | |||
| Immune-modulation | Capillary Astrocyte |
Israel et al, 2020 Front. Neuroscience for review Support Motor Neurons by
transplantation of healthy and functional human astrocytes - AstroRx®

Cell Therapy Using AstroRx® - The Process



Effect of AstroRx® on rat SOD1 G93A ALS model
Rat hSOD1 ALS Model:
Study measurements
- Survival
- Grip strength
- Rotarod (ambulation)
- Muscle weight loss
- Paralysis (neurological score)
AstroRx® cells were injected at day 50 and 70 of life
Intrathecal injection of AstroRx® (Lumbar puncture) between L5-L6 w/o immunosuppression

hSOD1G93A high copy number rat (ALS model)

AstroRx® Prolong Survival of hSOD1 Rats

- Significant delay in disease onset in AstroRx® treated rats (P=0.0001)
- Prolonged survival in AstroRx® treated rats

AstroRx® Improve Motor Performance

• Significant improvement in grip strength test (P<0.001)
B

• Significant improvement in rotarod test (P<0.001) and neurological score
Similar results were obtained in ALS mouse model

AstroRx® Cells Reduce Loss of Muscle Mass

Significant improvement in maintaining BW (P<0.05)

In Human Clinical Trials Using AstroRx®

AstroRx® First-in-Human Study Design
Evaluate transplantation of astrocytes derived from Human Embryonic Stem Cells, in patients with Amyotrophic Lateral Sclerosis (ALS)
- Study Site: Hadassah Ein Kerem Hospital, Jerusalem
- Phase 1/2a, open-label, single arm per dose, dose-escalating
- A single treatment administration of AstroRx® was administered by intrathecal (spinal) injection to subjects with ALS at early disease stage
- AstroRx® doses:
- 5 subjects in Cohort A (100x106 cells)
- 5 subjects in Cohort B (250x106 cells)
- Study Objectives:
- Primary: safety of escalating doses
- Secondary: efficacy by comparing Pre- and Post-treatment assessment of disease progression

AstroRx® Phase 1/2a Current Status Good Clinical Safety Profile
Study Status:
- 5 patients in Cohort A and 5 patients in Cohort B completed 6 months follow up
- Cohorts C&D were discontinued following Data Safety Monitoring Board (DSMB) recommendation due to COVID-19 pandemic
| Enrollment Characteristics: | Group | Gender | Ethnicity | Mean age | ALSFRS-R at enrollment |
|---|---|---|---|---|---|
| A | 5 males | Caucasian | 63 ± 4.4 |
39.2 ±3.5 | |
| B | 4 males, 1 female | Caucasian | 61 ± 5.5 |
40.0 ±5.3 |
Safety Results:
- Good safety profile
- No treatment-related serious adverse events
- No dose-limiting toxicities were reported

AstroRx® 3-month Follow-up Results Demonstrated a Clinically Meaningful Decline in Disease Progression
Clinical results are consistent between Cohorts A and B
ALSFRS-R slope difference between 3 months pre- and post-treatment in Cohorts A and B

* p=0.0396, **p=0.0023, *** p=0.0004 (MMRM analysis)
ALSFRS-R is a Clinically Accepted Measure of Disease State

AstroRx® Efficacy Among ALS Rapid Progressors (3-month Follow-up)
80% of rapidly progressing patients responded to treatment of AstroRx®

ALSFRS-R Slope Analysis
* p=0.0003 (MMRM analysis)
- Rapid progressors are defined as patients who deteriorate at least 1.1 points of ALSFRS-R per month in the run-in period
- Analysis of rapid progressors is particularly important since the inclusion of this sub-population of patients in clinical trials in ALS increases the likelihood of demonstrating a drug effect
- Responders are defined as showing improvement of at least 25% in the ALSFRS-R rate of decline between pre- and post-treatment periods

AstroRx® study: 6-month Follow-up Results
The results support our plan for a further clinical trial with repeated intrathecal administrations of AstroRx®, in order to prolong the clinical effect seen by a single dose
- Safe and well tolerated in both treatment doses over 6-months
- No treatment-related serious adverse events (SAEs) nor dose-limiting toxicities were reported



AstroRx® Clinical and Regulatory Plan
- A clinical development strategy to support the product intended use
- A Pre-IND meeting with FDA
- An IND supporting the approval of the next set of clinical trials
- A RMAT* designation application is planned, to enable expedited development, reviews and to accelerate approval



A Potential Functional Cure for Type 1 Diabetes


Insulin Dependent Diabetes - Market and Facts

~180 Million People worldwide suffer from Insulin-Dependent Diabetes*
Highly demanding disease management. Insulin injection treatment does not prevent long term complications**
~45 million people suffer from Type-1 Diabetes worldwide. More than 1.1 million are children and adolescents (<20 years) (US > 200,000)***

High health expenditure Type 1 Diabetes associated healthcare expenditures in the US = 16B\$ annually)**

*American Diabetes Association Standards of medical care in diabetes—2018. Diabetes Care. 2018;41(Suppl 1):S1–S159. [Google Scholar] **https://www.jdrf.org/t1d-resources/about/facts/
Unmet Need in Insulin Dependent Diabetes

Insulin Therapy and glucose Islet Transplantation management are not a cure Restoring patient's ability to naturally
Even with strict insulin treatment regimens, patients experience:
- Frequent episodes of severe, undetected hypoglycemia;
- Severe glycemic lability
- Progressive diabetic complications: Neuropathies Heart Disease Retinopathy Kidney failure Stroke

produce insulin
- Healthy and functional islet cells can produce and secrete insulin in a regulated manner
- Cadaveric donor islet cell therapy is a safe and clinically validated treatment for Insulin-Dependent Diabetes*
- Patients treated achieved Insulin independence for ~2 years following treatment**
- Main challenges remaining: a severe shortage of donor islet cells and immune suppression that is unhealthy and not always prevent immune rejection

Cure for Type 1 Diabetes using IsletRx

IsletRx - Our Solution
Functional pancreatic islets from ES cells that produce and secrete insulin and glucagon
- Overcome donor tissue availability shortage
- Replace malfunctioning patient islet cells
- Maintain continuous balanced glucose levels

• Show long term functionality, protected from host immune response, without immune suppression drugs

IsletRx - Preclinical Demonstration of Efficacy
IsletRx treated diabetic mice (STZ) demonstrated balanced and normal blood glucose levels
- Long-term therapeutic effect was achieved in an immunocompetent animal model (C57BL/6 mice)
- IsletRx cells well protected from host immune system

Molakandov et al 2020, in submission

IsletRx - Production, Purification and Encapsulation
Large Scale Production:
Scalable 3D bioreactor production
Purification & Enrichment:
Proprietary technology (IP) enables islet cell enrichment and purification, achieving well characterized cell identity
• Novel CD26-/CD49a+ signature cell surface markers are used to identify and select highly functional insulin producing cells, thereby increasing the probability of clinical efficacy
Unique Microencapsulation Technology:
Protects IsletRx cells from host immune system response, overcoming a major challenge in allogeneic cell therapy

Microencapsulated ILCs - IsletRx

Our Treatment = Cure


IsletRx Potential Advantages vs. Available Treatments
| Allogeneic Islet Transplantation |
Insulin Injections | Insulin Pumps | |
|---|---|---|---|
| Periodic Treatments, Long-term Effect |
Daily injection |
Ongoing | |
| Balanced Glucose Levels |
Manual monitoring and balancing of glucose levels |
Delay in real-time glucose measurement and insulin infusion |
|
| Personal Comfort |
Daily routine interference- injections and laborious monitoring |
External device necessitating maintenance |
|
| Compliance | Requires high-level treatment management |
External device necessitating maintenance |
|
| Prevention of Long-term Complications |

IsletRx Next Steps
- INTERACT* and Pre-IND meetings with FDA
- Implementation of 2 nd generation micro and macro encapsulation products
- Upscaling and GMP production



Leadership
Bringing extensive business, industry, and scientific experience

Prof. Michel Revel Founder & CSO
- Developed Merck's blockbuster drug REBIF® for multiple sclerosis (\$1.7B USD in sales in 2016)
- Professor Emeritus of molecular genetics at the Weizmann Institute of Science
- More than 40 years of experience in development and global commercialization of advanced biotechnological products
- Awarded Laureate of Israel Prize for Medicine in 1999 and EMET Prize for Science in 2004

Asaf Shiloni CEO
- More than 20 years of biotech executive experience and a deep knowledge of the cell therapy industry
- Mr. Shiloni served as Vice President Sales and Business development at PeproTech for 13 years, there he established collaborations and joint ventures with top US stem cell companies and leading research labs worldwide as well as led M&A processes
- Prior to PeproTech, in 2007, Mr. Shiloni sold an Israeli biotech company CytoLab, that he co-founded and led for seven years
- Mr. Shiloni holds a BA in Computer Information Systems and Business from The College of Management and an MBA from Tel Aviv University

Leadership

Asaf Shiloni CEO

Prof. Michel Revel Founder & CSO
Ronen Twito CPA
Co-Chairperson

Michal Izrael, PhD VP R&D, NDD
Arik Hasson, PhD
VP R&D
Yossi Nizhar
CFO

Kfir Molakandov, PhD Head of Diabetes Research

Veronique Bellaiche Director of Regulatory Affairs and Quality Assurance

Ruti Alon Co-Chairperson

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Thank You.


www.kadimastem.com [email protected] Tel. +972-73-7971601

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