Protalix BioTherapeutics : PLX Corporate Presentation (May 2024)

PROTALIX BIOTHERAPEUTICS

C O R P O R A T E P R E S E N T A T I O N M a y 2 0 2 4

Disclaimers

Third-Party Information

This presentation also contains estimates and other data made by independent parties and Protalix relating to market size and growth and other data related to the industry in which Protalix operates. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. Neither Protalix nor any other person makes any representation as to the accuracy or completeness of such data. In light of the foregoing, you are urged not to rely on any forward-looking statement or third-party data in reaching any conclusion or making any investment decision about any securities of the Company. The appropriateness of a particular investment or strategy will depend on an investor's individual circumstances and objectives. We recommend that investors independently evaluate specific investments and strategies.

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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 Exchange Act. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on management's current expectations or plans projections for future operating and financial performance based on assumptions currently believed to be valid. 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. The forward-looking statements in this presentation include, among other things, statements regarding our cash runway and the commercialization of our product. 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), our approved product for the treatment of adult patients with Fabry disease; Elfabrio's revenue, expenses and costs may not be as expected; Elfabrio's market acceptance, competition, reimbursement and regulatory actions, including as a result of the boxed warning contained in the U.S. Food and Drug Administration, or the FDA, approval received for the product; the regulatory approval and commercial success of our other product and product candidates, if approved; risks related to our expectations with respect to the potential commercial value of our products and product candidates; failure or delay in the commencement or completion of our preclinical studies and clinical trials, which may be caused by several factors, including: slower than expected rates of patient recruitment; unforeseen safety issues; determination of dosing issues; lack of effectiveness during clinical trials; inability to satisfactorily demonstrate non-inferiority to approved therapies; inability or unwillingness of medical investigators and institutional review boards to follow our clinical protocols; inability to monitor patients adequately during or after treatment; and/or lack of sufficient funding to finance our clinical trials; delays in the approval or potential rejection of any applications we file with the FDA, EMA or other health regulatory authorities for our other product candidates, and other risks relating to the review process; our ability to manage our relationship with our collaborators, distributors or partners, including, but not limited to, Pfizer Inc., and Chiesi; the amount and sufficiency of our cash and cash equivalents; and other factors described in our 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, Protalix undertakes no obligation to update or revise the information contained in this presentation whether as a result of new information, future events or circumstances or otherwise.

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Investment Highlights

A strong foundation to further expand into the Rare Disease space

Two Approved Drugs

Elelyso® (alfataliglicerase in Brazil): FDA approved, commercially marketed drug for Gaucher disease.

Elfabrio® (pegunigalsidase alfa) has been approved for marketing by the FDA and the European Commission for Fabry disease.(1)

Clinically-Validated Platforms

Proprietary ProCellEx® platform for recombinant protein expression cGMP(2) manufacturing facility successfully inspected and audited by multiple regulatory agencies, including the FDA & EMA.

Strong Partnerships

Chiesi Farmaceutici S.p.A.

Pfizer Inc.

Fundação Oswaldo Cruz (Fiocruz)

Clinical and Regulatory Expertise in Rare Genetic Space

Strong clinical and regulatory expertise for biologics and world-class network of Lysosomal Storage Disorder disease experts.

Development Pipeline

Uricase (PRX-115) for the treatment of severe gout.

Long Acting DNase I (PRX-119) for the treatment of NETs-related diseases, as well as other product candidates, in discovery and preclinical phases.

Revenue-Generating

Multiple revenue streams, including sales to Pfizer, Fiocruz (Brazil) and Chiesi.

1. For the treatment of adult patients with Fabry disease
2. cGMP = Current Good Manufacturing Practice

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Product Pipeline

Recombinant proteins designed to have potentially improved therapeutic profiles that target unmet medical needs and established pharmaceutical markets

	Discovery and Preclinical	Phase I	Phase II	Phase III	Marketing Application
Elelyso®
Gaucher Disease				Approved in 23 markets
(taliglucerase alfa)
Elfabrio®	Fabry Disease				Approved (US and EU)
(pegunigalsidase alfa)

PEGylated Uricase (PRX-115)

Uncontrolled Gout

Expanding to 8th cohort; phase II planning in progress

Long Acting (LA) DNase I	NETs-Related
(PRX-119)	Diseases
Research Programs	Rare
Diseases

Note: Current pipeline candidates are generally recombinant proteins expressed via our proprietary ProCellEx® system

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Elelyso® for Gaucher Disease

First plant cell derived recombinant protein approved by the FDA

Gaucher Disease

• Rare autosomal recessive disorder: affects 1 in 40,000 people
• Glucocerebrosidase (GCD) enzyme deficiency resulting in accumulation of glucosylceramide, a lipid, in bone marrow, lungs, spleen, liver and sometimes brain

Product

• Elelyso (alfataliglicerase in Brazil) is a proprietary, recombinant form of GCD for long-term treatment of patients with a confirmed diagnosis of type 1 Gaucher disease

• Expressed through our ProCellEx® platform

Symptoms and Treatment

• Possible symptoms include enlarged liver and spleen, various bone disorders, easy bruising and bleeding and anemia
• Left untreated, it can cause permanent body damage and decreased life expectancy
• Standard of Care: Enzyme Replacement Therapy

Commercial Potential

• Approved in 23 markets
• Worldwide exclusive license agreement with Pfizer in 2009, amended in 2015 (excluding Brazil)
• Sales ~$10.4M in Brazil (FY2023) via Fundação Oswaldo Cruz
• Market share in Brazil: ~27%

1. Approved in 23 markets including the US, Australia, Canada, Israel, Brazil, Russia and Turkey. In 2010, the European Committee for Medicinal Products for Human Use (CHMP) gave a positive opinion but also concluded that the medicine cannot be granted marketing authorization in the EU because of the market exclusivity that had been granted to Vpriv® (Shire), which was authorized in August 2010, for the same condition. The orphan market exclusivity expired in August 2022.

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Elfabrio® for Fabry Disease

Second plant cell derived recombinant protein approved by the FDA

Fabry Disease

• Rare X-linked disease: affecting about one in every 40,000 to 60,000 men worldwide
• α-galactosidase-Aenzyme deficiency leads to accumulation of the fatty substance globotriaosylceramide (Gb3) in blood and blood vessel walls throughout the body

Symptoms and Treatment

• Progressive disease that can lead to renal failure, cardiomyopathy with potentially malignant cardiac arrhythmias, and strokes
• Symptoms such as abdominal and neuropathic pain can appear in patients as young as two years old
• Standard of Care: Enzyme Replacement Therapy (Replagal® or Fabrazyme®1,2)

Product

• Elfabrio (pegunigalsidase alfa): Chemically Modified, Plant Cell Derived, PEGylated, Covalently Linked Homodimer
• Approved for marketing by the EC, FDA and others
• Expressed through our ProCellEx® platform

Commercial Potential

• Fabry: ~$2B (2023) expected to reach ~$3.1B (2030) Poised to capture significant global market share (15-20%)
• Will potentially be entitled to $120M-$150Mroyalties per year from Chiesi3
• 1. Does not include Galafold®, a small molecule drug indicated for adult Fabry patients with an amenable GLA variant.
  2. Replagal® is not approved in the U.S.
  3. Based on projected 20-25% share of projected market size increase to ~$3.1 billion by 2030.

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Fabry Disease Competitive Landscape

~$2B market (2023) expected to reach over $3.1B (2030), CAGR of 6.8%

Product Name	Fabrazyme®	Replagal®	Galafold®	Elfabrio®
Parent
Company
Mechanism	ERT	ERT	Pharmacological chaperone	ERT
Approved for	Adults and pediatric patients 2+	Adults (E.U. only)	Accelerated approval in adults	Adults (U.S., E.U. and others)
	years (U.S.);		(U.S.)
	Adults, children and adolescents
	aged 8+ years. (E.U.)		Adults and adolescents 16+ years
			(E.U.)
Dosing	1 mg/kg every 2 weeks	0.2 mg/kg every 2 weeks	123 mg every other day	1 mg/kg every 2 weeks
Administration	Intravenous infusions	Intravenous infusions	Oral	Intravenous infusions
mode
Approval Date	Full approval in 2021; accelerated
	approval in 2003 (U.S.); 2001	Not approved in U.S.; 2001 (E.U.)	2018 (U.S.); 2016 (E.U.)	2023 (U.S. and E.U.)
	(E.U.)

Elfabrio is poised to capture meaningful global market share (15-20%)

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Committed Commercial Partner

Global Partnership with

Chiesi Farmaceutici S.p.A.

• International research-focused biopharmaceutical group with sales in excess of $3B in 2023 (reflecting 10% growth year-on-year
• Operating in close to 30 countries with over 7,000 employees
• Strong sales and marketing partner poised to maximize the market potential of pegunigalsidase alfa as the centerpiece of their new strategic U.S.-based Orphan Drug division

• Committed global partner with experienced sales team

• Strategic focus on rare diseases
• Specific expertise in Fabry disease
• Ideally suited to bring Elfabrio® to

patients with Fabry disease(1)

(1) Tiered royalties of 15-35%(ex-U.S.);15-40% (U.S.)

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Gout

Most Common Inflammatory Arthritis

Accumulation of Excess Uric Acid

Systemic Disease

Currently Available Therapies

Gout affects approximately 14 million people in the U.S.

~5% (estimated) of the gout population is considered to have chronic refractory gout

Hyperuricemia leads to deposition of monosodium urate crystals (tophi) in joints, tendons and other tissues

Triggers recurrent episodes of pronounced acute inflammation, known as gout flares

Gout flares can lead to substantial morbidity, severe pain, reduced quality of life, decreased physical function

Co-morbidities associated with gout include hypertension, cardiovascular disease, renal impairment, diabetes, obesity, hyperlipidemia, and frequently in a combination known as the metabolic syndrome

First-line xanthine oxidase inhibitors (XOIs): Allopurinol and Febuxostat

One recombinant uricase approved for chronic gout in adult patients refractory to conventional therapy as every two-week injection: Krystexxa® 1

1 Krystexxa has a "Black Box" safety warning for anaphylaxis and infusion reactions. It is not approved for use in the E.U.

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