Kadimastem Ltd.

Investor Presentation • May 28, 2024

May 2024 (TASE: KDST)

Disclaimer

This presentation does not constitute an offering to purchase or sale securities of Kadimastem Ltd. (the "Company") or an offer to receive such offerings. The presentation's sole purpose is to provide information. This presentation was prepared by the Company. The information included in the presentation and any other information provided during the presentation (the "Information") does not constitute a base for investment decisions and does not comprise a recommendation, an opinion or a substitute to the investor's sole discretion. The information provided in the presentation concerning the analysis of the Company's activity is only an extract and in order to receive the full image of the Company's activity and the risks it is facing, one should review the Company's reports to Israeli Security Authority and Tel Aviv Stock Exchange (the "Public Information"). This presentation may include information which was not presented and/or was presented differently than the way presented in the Public Information. The Company is not responsible and will not be held responsible for damages and/or any losses that might be caused as a result of using the information. The presentation may contain forward-looking statements as defined in the Israeli securities law, 5728-1968. All forward-looking statements in this presentation are not facts and are made based on Company's current and subjective expectations, evaluations and forecasts. Forward-looking statements are not certain, cannot be estimated in advance and mostly are not under the control of the Company, and they may differ materially, in part or in whole, as a result of different factors which are not under the control of the Company including, but not limited to: the Company's risk factors or the occurrence of one of the Company's risk factors, changes in market condition and general environment and in external factors which influence the Company's activity, which cannot be estimated in advance, such as regulatory changes, competitive products development, changes in currency etc. The results and achievements of the Company in the future may be materially different than those presented in the presentation. In addition, forward-looking forecasts and evaluations are based on information current held by the Company while preparing the presentation. The Company does not undertake any obligation to update forward-looking forecasts and evaluations made herein so they would reflect events and/or circumstances that could appear after preparing this presentation. Some of the market and clinical information is based on external publications. Although the Company believes that these external independent sources are reliable as of their respective dates, the information contained in them has not been independently verified and the Company cannot assure as to the accuracy or completeness of this information.

Kadimastem – Stem Cell Derived Cell Therapy

Vision – Stem Cell Derived Cell Therapy

Replace, restore and repair the functionality of diseased and malfunctioning cells in various degenerative diseases by transplantation of healthy and functional cells To

Developing proprietary cell lines optimized for the cure of Diabetes and to treat ALS

Proprietary Innovative Platform

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

Product Platform Pipeline CLINICAL

An Active Market – Key Recent Transactions

To the best of Company's knowledge, base on the following:

• https://investors.vrtx.com/news-releases/news-release-details/vertex-acquire-semma-therapeutics-goal-developing-curative-cell
• 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://www.bayer.com/media/en-us/bayer-acquires-bluerock-therapeutics-to-build-leading-position-in-cell-therapy/
• https://www.reuters.com/article/idUSKBN2A42JA/#:~:text=(Reuters)%20%2D%20Shares%20of%20gene,market%20capitalization%20of%20%246.38%20billion.
• https://stockanalysis.com/stocks/amlx/market-cap/https://companiesmarketcap.com/celularity/marketcap/
• Amylyx Pharmaceuticals Announces Pricing of Upsized Initial Public Offering of Common Stock[1].pdf

Kadimastem: History & Way Forward

AstroRx ®

Astrocytes- Cell Therapy Treatment for Neurodegenerative Diseases

• ALS is a fatal rare disorder with no cure 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 45-65 years, survival from onset of 2-5 years

• Current FDA approved treatments are Rilutek, Radicava and RELYVRIO with modest effect

• Around 450,000¹ ALS patients estimated worldwide, 30,000 patients in the US²
• Global ALS treatment market valued at US\$300 million in 2023³

North America is the largest market, with a share about 60%, followed by Japan, and Europe, both have a share over 20 percent. Estimate to reach in 2030: \$520.8 M³

• US ALS Healthcare costs:

Close to \$1.02 billion annually direct and indirect associated costs⁴ .

• 1. https://www.massgeneral.org/neurology/als
• 1. https://www.als.net/als-resources/faq/
• 10 3. https://www.360marketupdates.com/global-amyotrophic-lateral-sclerosis-als-treatment-market-27075231
• 1. https://www.tandfonline.com/doi/full/10.1080/21678421.2023.2165947

The Central Nervous System

Use Astrocytes for ALS - AstroRx®

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
astrocytes fail to support motor neuron survival	Secrete neurotrophic factors 1
	Remove toxic factors (i.e. glutamate) 1
	stress 1 Regulate oxidative
	Immune-modulation 2

1. Izrael et al, 2020 Front Neurosci. 2020; 14: 824. doi: 10.3389/fnins.2020.00824

2. Izrael et al, 2021 Front Med (Lausanne) 2021; 8: 740071. doi: 10.3389/fmed.2021.740071

Effect of AstroRx® on rat SOD1 G93A ALS model In Pre-Clinical Trials

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® Mechanism of Action

First In Human Clinical Trials Using AstroRx®

Cell Therapy Using AstroRx® - The Process

AstroRx® Phase 1/2a Status Good Clinical Safety Profile

Study Status:

• 5 patients in Cohort A and 5 patients in Cohort B completed 12 Month follow up.
• Cohorts C&D were discontinued following Data Safety Monitoring Board (DSMB) recommendation due to COVID-19 pandemic

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: 1-year 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 12-months
• No treatment-related serious adverse events (SAEs) nor dose-limiting toxicities were reported

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AstroRx® Patent Strategy

✓ DIRECTED DIFFERENTIATION OF ASTROCYTES FROM HUMAN PLURIPOTENT STEM CELLS FOR USE IN DRUG SCREENING AND THE TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS (ALS)

✓ METHODS OF GENERATING GLIAL AND NEURONAL CELLS

✓ METHODS OF GENERATING GLIAL AND NEURONAL CELLS AND USE OF SAME FOR THE TREATMENT OF MEDICAL CONDITIONS OF THE CNS

Hong Kong Europe USA Israel

AstroRx® Clinical and Regulatory Plan

• FDA has approved the IND for AstroRx® for its planned phase IIa clinical trail
• To commence the phase IIa clinical trial in the USA at multiple sites
• A clinical development strategy to support the product intended use
• A RMAT* designation application is planned, to enable expedited development, reviews and to accelerate approval

Functional Islet Cells - Potential Cure for Insulin Dependent Diabetes

Insulin Dependent Diabetes - Market and Facts

537 million adults are living with diabetes worldwide – 1 in 10*

Highly demanding disease management. Insulin injection treatment does not prevent long term complications**

In 2022, there were 8.75 million people living with type 1 diabetes globally. 1.52 million of these people were under 20 years old***

Diabetes was responsible for an estimated USD 966 billion in global health expenditure in 2021. This represents a 316% increase over the last 15 years*

\*https://diabetesatlas.org/idfawp/resource-files/2021/11/IDFDA10-global-fact-sheet.pdf **Tao et al 2010, PLoS One. 2010; 5(7): e11501. doi: 10.1371/journal.pone.0011501 \\\*Type 1 diabetes estimates in children and adults | IDF Diabetes Atlas

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

What Happens in Diabetes Type 1

Cure for Insulin Dependent Diabetes using IsletRx

Our Treatment = Cure

IsletRx - Our Solution

Functional pancreatic islets derived from hES cells that produce and secrete insulin and glucagon glucose dependently

• 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 - in development

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

IsletRx - Production, Selection and Encapsulation

Large Scale Production:

Scalable 3D bioreactor production

Selection & Enrichment:

Proprietary technology (IP) enables islet cell enrichment and selection, 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: Demonstrate positive results in protecting IsletRx cells from host immune system response, overcoming a major challenge in allogeneic cell therapy. Other macroencapsulation technologies are tested concomitantly.

Microencapsulated ILCs - IsletRx

IsletRx Potential Advantages vs. Available Treatments

	IsletRx 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 – iTolerance

Local Immune Suppression

• Regenerative medicine without the need for life-long immunosuppression
• Leverages the naturally occurring protein, Fas Ligand (FasL)
• Creating localized immune privilege
• BIRD Grant Submitted
• INTERACT Meeting with the FDA (January 2024)

Our Treatment = Cure

IsletRx Patent Strategy

✓ INSULIN PRODUCING CELLS DERIVED FROM PLURIPOTENT STEM CELLS

✓ METHODS FOR DIFFERENTIATING AND PURIFYING PANCREATIC ENDOCRINE CELLS

IsletRx Next Steps

• Expand Collaboration
• Pre-IND meetings with FDA
• Upscaling and GMP production
• IND for Clinical Trial

Leadership Team

Ronen Twito CPA

Executive Chairman & President Over 20 years of financial and managerial experience, including executive positions in NASDAQ and TASE listed companies, leading multiple IPOs and follow-on offerings on Nasdaq, as well as M&As in biotechnology.

Prof. Michel Revel

Founder, Director & CSO Developed Merck's blockbuster multiple sclerosis drug REBIF® (\$1.7 billion in US sales in 2016) and has over 40 years of experience in biotechnology, genetics, virology and CGT.

Michal Izrael, PhD VP R&D

Asaf Shiloni

CEO

Over 20 years of experience in the biotechnology industry, Sold PeproTech to Thermo Fisher in 2021 for \$1.85 billion.

Kfir Molakandov, PhD Director of Diabetes Research and Innovation

Thank You.

www.kadimastem.com info@kadimastem.com Tel. +972-73-7971601

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