Protalix BioTherapeutics : KOL Presentation Prof Aleš Linhart Fabry

for Fabry Disease

Professor Aleš Linhart, MD, DrSc., FESC

General University Hospital in Prague

and 1st Faculty of Medicine, Charles University

Prague, Czech Republic

June 26, 2024

KOL Presentation I June 2024

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Disclaimer

• Speaker´s and consultancy honoraria
• • Chiesi; Sanofi; Takeda; Amicus Therapeutics
• Research grant
• • Sanofi
• Board member
• • Fabry Registry, FollowMe Next Registry
• Clinical trials
• • Protalix / Chiesi, Sanofi
• Imaging from files of the General University Hospital, Prague, CZ; patients gave their consent for data and imaging use for teaching and research

KOL - Investor Presentation I June 2024

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Prof. Aleš Linhart, MD, DrSc., FESC

Graduated in Medicine at Charles University in Prague, Czech Republic

Training in cardiology and vascular medicine at General University Hospital in Prague and Broussais Hospital in Paris, France

Board certified specialist in Cardiology, Vascular Medicine, Internal Medicine

Research focusing mainly on metabolic cardiomyopathies, noninvasive cardiac imaging, and atherosclerosis

Author or co-author of > 450 scientific papers, 80 book chapters and 3 monographs In 2004 appointed Professor at Charles University in Prague

Since 2005 - Head 2nd Department of Internal Cardiovascular Medicine, First Faculty of Medicine, Charles University, Prague, Czech Republic

Immediate past president of the Czech Society of Cardiology

Past President of Myocardial and Pericardial Working Group of the European Society of Cardiology

KOL Presentation I June 2024

Disclaimer

The data discussed in this presentation are not intended to establish noninferiority or superiority to any other marketed drug product on the basis of safety or efficacy. The FDA has indicated that the magnitude of drug effect of agalsidase beta in a study population similar to that of BALANCE cannot be sufficiently quantified and as such, a non-inferiority margin cannot be determined for the BALANCE study.

Additionally, the FDA relied on the estimated mean eGFR slope and concluded the two arms were comparable (-2.4 for PRX-102 and -2.3 for agalsidase beta), and the estimated treatment difference was -0.1 (95% CI: -2.3, 2.1) mL/min/1.73 m2/year.

Elfabrio® was approved by the FDA with a boxed warning for hypersensitivity reactions/anaphylaxis, consistent with Enzyme Replacement Therapy (ERT) class labeling, and Warnings/Precautions providing guidance on the signs and symptoms of hypersensitivity and infusion- associated reactions seen in the clinical studies as well as treatments to manage such events should they occur. The Warnings/Precautions for membranoproliferative glomerulonephritis (MPGN) alert prescribers to the possibility of MPGN and provide guidance for appropriate patient management. Overall, the FDA review team concluded that in the context of Fabry disease as a rare, serious disease with limited therapeutic options that may not be suitable to all individual patients, the benefit-risk of Elfabrio is favorable for the treatment of adults with confirmed Fabry disease.

Clinical studies have not shown that a long half-life results in a medicine working better or more safely.

Approval Package

Information regarding the FDA's approval of Elfabrio is available on the FDA's website. For more information see the FDA Approval Package:

• Multi-disciplineReview issued by the FDA's Center for Drug Evaluation and Research, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/761161Orig1s000MultidisciplineR.pdf
• Other Reviews issued by the FDA's Center for Drug Evaluation and Research,https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/761161Orig1s000OtherR.pdf

Refer to the Full Prescribing Information for Elfabrio for more information, https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761161s000lbl.pdf.

KOL - Investor Presentation I June 2024

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Note Regarding Forward-Looking Statements

This presentation contains forward-looking statements that involve risks and uncertainties within the meaning of Section 27A of the Securities Act of 1933, as amended, or the Securities Act, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements are neither historical facts nor assurances of future performance. Forward-looking statements can be identified by the use of words such as "anticipate," "believe," "estimate," "expect," "can," "continue," "could," "intend," "may," "plan," "potential," "predict," "project," "should," "will," "would" and other words or phrases of similar import, as they relate to Protalix, its subsidiaries or its management, are intended to identify forward- looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements are subject to many risks and uncertainties that could cause our actual results to differ materially from any future results expressed or implied by the forward-looking statements, including, but not limited to: risks related to the commercialization of Elfabrio® (pegunigalsidase alfa-iwxj); the inherent risks and uncertainties in developing drug platforms and products of the type Protalix is developing; the impact of development of competing therapies and/or technologies by other companies and institutions; potential product liability risks, and risks of securing adequate levels of product liability and other necessary insurance coverage; and other factors described in Protalix's filings with the U.S. Securities and Exchange Commission. In addition, new risk factors and uncertainties may emerge from time to time, and it is not possible to predict all risk factors and uncertainties. Given these uncertainties, investors should not place undue reliance on these forward-looking statements. Except as required by law, no obligation has been undertaken to update or revise the information contained in this presentation whether as a result of new information, future events or circumstances or otherwise.

KOL - Investor Presentation I June 2024

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Fabry Disease

KOL - Investor Presentation I June 2024

KOL - Investor Presentation I June 2024

Lysosomal function in cells

Cytosol

/ Mannose receptor

0.2 - 0.5 μm

pH ~ 7.2

pH ~ 5.0

ACID HYDROLASES

Nucleases

Proteases

Glycosidases

Lipases

Phosphatases

Sulphatases

Phospholipases

H+

H+ pump

ATP		ADP	+ Pi

Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P.

Molecular Biology of the Cell, 4th edition New York: Garland Science; 2002.

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KOL - Investor Presentation I June 2024

Lysosomal function in cells

0.2 - 0.5 μm

Cytosol		pH ~ 7.2
		pH ~ 5.0
	ACID HYDROLASES
			Nucleases
			Proteases
		Glycosidases
				Lipases
	Phosphatases
		Sulphatases
	Phospholipases
					H+
									H+ pump
							+ Pi
	ATP					ADP

Electron microscopy: Charles University, Prague

Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P.

Molecular Biology of the Cell, 4th edition New York: Garland Science; 2002.

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Lysosomal function in cells

0.2 - 0.5 μm

	Cytosol		pH ~ 7.2
			pH ~ 5.0
		ACID HYDROLASES
				Nucleases
				Proteases
			Glycosidases
					Lipases
		Phosphatases
			Sulphatases
		Phospholipases
						H+
										H+ pump
								+ Pi
http://www.trashitman.com/		ATP					ADP

Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. KOL - Investor Presentation I June 2024 Molecular Biology of the Cell, 4th edition New York: Garland Science; 2002.

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Timeline of Fabry disease manifestations in hemizygous male patients

Stroke

Proteinuria, renal failure

Cardiomyopathy

Angiokeratomas, hypohidrosis

GI symptoms

Pain, febrile crises

Age

0

10

20

30

40

50

Vertigo, tinnitus

Stroke sequalae

Swelling, Hemodialysis

Shortness of breath

Palpitations

Angina

Impact on sexual life

Exercise intolerance

Diarrhea

Abdominal pain

Fatigue, Exercise intolerance Social and economic impacts Depression

GI, gastrointestinal

KOL - Investor Presentation I June 2024

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Linhart A and Elliott PM. Heart. 2007;93(4):528-35