Protalix BioTherapeutics Inc

Previous wording

ProCellEx consists of a comprehensive set of proprietary technologies and capabilities, including the use of advanced genetic engineering and plant cell culture technology, enabling us to produce complex, proprietary, and biologically equivalent proteins for a variety of human diseases. Our protein expression system facilitates the creation and selection of high-expressing, genetically-stable cell lines capable of expressing recombinant proteins. The system plays an important role in the execution of our corporate strategy as its allows us to develop and produce tailored complex recombinant therapeutic proteins and to genetically engineer and/or chemically

Current wording

ProCellEx consists of a comprehensive set of proprietary technologies and capabilities, including the use of advanced genetic engineering and plant cell culture technology, enabling us to produce complex, proprietary, and biologically equivalent proteins for a variety of human diseases. Our protein expression system facilitates the creation and selection of high-expressing, genetically-stable cell lines capable of expressing recombinant proteins. The system plays an important role in the execution of our corporate strategy as its allows us to develop and produce tailored complex recombinant therapeutic proteins and to genetically engineer and/or chemically modify such proteins pre- and/or post-production. The engineering and modification of the therapeutic proteins have the potential to provide added clinical benefits by improving the biological characteristics (e.g., glycosylation, half-life, immunogenicity).

Previous wording

Our ProCellEx technology can be utilized to express complex therapeutic proteins belonging to different drug classes, such as enzymes, hormones, monoclonal antibodies, cytokines and vaccines. The entire protein expression process, from initial nucleotide cloning to large-scale production of the protein product, occurs under Current Good Manufacturing Practice-, or cGMP-, compliant, controlled processes. Our plant cell culture technology uses cells, such as carrot and tobacco (BY-2) cells, which undergo advanced genetic engineering and/or chemical modifications, and are grown on an industrial scale in a disposable, flexible bioreactor system. Our system does not involve mammalian or animal-derived components or transgenic field-grown or whole plants at any point in the production process.

Current wording

Our ProCellEx technology can be utilized to express complex therapeutic proteins belonging to different drug classes, such as enzymes, monoclonal antibodies, hormones, cytokines and vaccines. The entire protein expression process, from initial nucleotide cloning to large-scale production of the protein product, occurs under Current Good Manufacturing Practice-, or cGMP-, compliant, controlled processes. Our plant cell culture technology uses cells, such as carrot and tobacco (BY-2) cells, which undergo advanced genetic engineering and/or chemical modifications, and are grown on an industrial scale in a disposable, flexible bioreactor system. Our system does not involve mammalian or animal-derived components or transgenic field-grown or whole plants at any point in the production process.

Previous wording

Gaucher disease, also known as glucocerebrosidase, or GCD, deficiency, is a rare genetic autosomal recessive disorder and one of the most common Lysosomal Storage Disorders, or LSDs, in the world. It is one of a group of disorders that affect specific enzymes that normally break down fatty substances for reuse in the cells. If the enzymes are missing or do not work properly, the substances can build up and become toxic. Gaucher disease occurs when a lipid called glucosylceramide accumulates in the cells of the bone marrow, lungs, spleen, liver, and sometimes the brain. Gaucher disease symptoms can include fatigue, anemia, easy bruising and bleeding,

Current wording

Gaucher disease, also known as glucocerebrosidase, or GCD, deficiency, is a rare genetic autosomal recessive disorder and one of the most common Lysosomal Storage Disorders, or LSDs, in the world. It is one of a group of disorders that affect specific enzymes that normally break down fatty substances for reuse in the cells. If the enzymes are missing or do not work properly, the substances can build up and become toxic. Gaucher disease occurs when a lipid called glucosylceramide accumulates in the cells of the bone marrow, lungs, spleen, liver, and sometimes the brain. Gaucher disease symptoms can include fatigue, anemia, easy bruising and bleeding, severe bone pain and easily broken bones, and distended stomach due to an enlarged spleen and thrombocytopenia. Epidemiology of Gaucher disease varies; Recent literature provides that prevalence of Gaucher disease ranges from 0.70 to 1.75 per 100,000 in the

Previous wording

severe bone pain and easily broken bones, and distended stomach due to an enlarged spleen and thrombocytopenia. Epidemiology of Gaucher disease varies; Recent literature provides that prevalence of Gaucher disease ranges from 0.70 to 1.75 per 100,000 in the general population. In people of Ashkenazi Jewish heritage, estimates of occurrence vary from approximately 1 in 400 to 1 in 850 people.

Current wording

general population. In people of Ashkenazi Jewish heritage, estimates of occurrence vary from approximately 1 in 400 to 1 in 850 people.

Previous wording

The global market for Gaucher disease, that includes Sanofi’s Cerezyme®, Shire’s Vpriv® and Sanofi’s Cerdelga®, among others, was $1.6 billion in 2023, is forecasted to be approximately $1.6 billion in 2024 and is forecasted to grow at a CAGR of approximately 1% from 2023-2029.

Current wording

The global market for Gaucher disease, that includes Sanofi’s Cerezyme®, Shire’s Vpriv® and Sanofi’s Cerdelga®, among others, was $1.6 billion in 2023, is forecasted to be approximately $1.6 billion in 2024 and is forecasted to grow at a CAGR of approximately -0.57% from 2023-2030.

Previous wording

The global market for Fabry disease, that includes agalsidase beta, Sanofi’s Fabrazyme®, agalsidase alfa, Shire’s (acquired by Takeda Pharmaceutical Company Limited) Replagal® and Amicus Therapeutics’ Galafold®, among others, is forecasted to be approximately $2.0 billion in 2023 and is forecasted to grow at a CAGR of 6.8% from 2023-2029 reaching approximately $3.1 billion in annual sales at the end of the decade.

Current wording

The global market for Fabry disease, that includes agalsidase beta, Sanofi’s Fabrazyme®, agalsidase alfa, Shire’s (acquired by Takeda Pharmaceutical Company Limited) Replagal® and Amicus Therapeutics’ Galafold®, among others, is forecasted to be approximately $2.1 billion in 2024 and is forecasted to grow at a CAGR of 7.3% from 2023-2030 reaching approximately $3.2 billion in annual sales in 2023.

Previous wording

On November 9, 2022, we, together with Chiesi, resubmitted to the FDA a BLA for PRX-102, the name we assigned to Elfabrio internally prior to its approvals, for the potential treatment of adult patients with Fabry disease. The initial BLA for PRX-102 was submitted to the FDA on May 27, 2020 under the FDA’s Accelerated Approval pathway, and the submission was subsequently

Current wording

On November 9, 2022, we, together with Chiesi, resubmitted to the FDA a BLA for PRX-102, the name we assigned to Elfabrio internally prior to its approvals, for the potential treatment of adult patients with Fabry disease. The initial BLA for PRX-102 was submitted to the FDA on May 27, 2020 under the FDA’s Accelerated Approval pathway, and the submission was subsequently accepted by the FDA and granted Priority Review designation. However, in April 2021, the FDA issued a complete response letter, or CRL, in response to the initial BLA. In preparation for the BLA resubmission, we and Chiesi participated in a Type A (End of

Previous wording

accepted by the FDA and granted Priority Review designation. However, in April 2021, the FDA issued a complete response letter, or CRL, in response to the initial BLA. In preparation for the BLA resubmission, we and Chiesi participated in a Type A (End of Review) meeting with the FDA on September 9, 2021. As part of the meeting minutes provided by the FDA, which included the preliminary comments and meeting discussion, the FDA, in principle, agreed that the data package proposed to the FDA for a BLA resubmission had the potential to support a traditional approval of PRX-102 for the treatment of Fabry disease. The data package in the BLA resubmission, given the change in the regulatory landscape in the United States, included the final two-year analyses of ourBALANCEstudy, which were completed in July 2022, and long-term data from our open-label extension study of PRX-102 in adult patients treated with a 2 mg/kg every four weeks dosage of PRX-102. The initial BLA included a comprehensive set of preclinical, clinical and manufacturing data compiled from our completed phase I/II clinical trial of PRX-102, including the related extension study, interim clinical data from our phase III BRIDGE clinical trial of PRX-102 for the treatment of Fabry disease, or theBRIDGE study, and safety data from our then on-going clinical studies of PRX-102 in adult patients receiving 1 mg/kg every two weeks.

Current wording

Review) meeting with the FDA on September 9, 2021. As part of the meeting minutes provided by the FDA, which included the preliminary comments and meeting discussion, the FDA, in principle, agreed that the data package proposed to the FDA for a BLA resubmission had the potential to support a traditional approval of PRX-102 for the treatment of Fabry disease. The data package in the BLA resubmission, given the change in the regulatory landscape in the United States, included the final two-year analyses of ourBALANCEstudy, which were completed in July 2022, and long-term data from our open-label extension study of PRX-102 in adult patients treated with a 2 mg/kg every four weeks dosage of PRX-102. The initial BLA included a comprehensive set of preclinical, clinical and manufacturing data compiled from our completed phase I/II clinical trial of PRX-102, including the related extension study, interim clinical data from our phase III BRIDGE clinical trial of PRX-102 for the treatment of Fabry disease, or theBRIDGE study, and safety data from our then on-going clinical studies of PRX-102 in adult patients receiving 1 mg/kg every two weeks.

Previous wording

TheBALANCE study (PB-102-F20, NCT02795676) was a pivotal 24-month, randomized, double blind, active control study of PRX-102 in adult Fabry patients with deteriorating renal function designed to evaluate the safety and efficacy of 1 mg/kg of PRX-102

Current wording

TheBALANCE study (PB-102-F20, NCT02795676) was a pivotal 24-month, randomized, double blind, active control study of PRX-102 in adult Fabry patients with deteriorating renal function designed to evaluate the safety and efficacy of 1 mg/kg of PRX-102 administered every two weeks compared to agalsidase beta. The Clinical Study Report for theBALANCE study was completed in July 2022. The final analysis confirmed the positive top-line results (announced in April 2022) and favorable tolerability profile. A total of

Previous wording

administered every two weeks compared to agalsidase beta. The Clinical Study Report for theBALANCE study was completed in July 2022. The final analysis confirmed the positive top-line results (announced in April 2022) and favorable tolerability profile. A total of 78 patients who were previously treated with agalsidase beta for at least one year with an eGFR slope at screening worse than -2 mL/min/1.73 m 2/year were enrolled in the study. Patients were randomized on a 2:1 ratio for switching to PRX-102 or continuing on agalsidase beta. A total of 77 patients were treated; 52 with PRX-102 and 25 with agalsidase beta. Approximately 40% of the enrolled patients were female.

Current wording

78 patients who were previously treated with agalsidase beta for at least one year with an eGFR slope at screening worse than -2 mL/min/1.73 m 2/year were enrolled in the study. Patients were randomized on a 2:1 ratio for switching to PRX-102 or continuing on agalsidase beta. A total of 77 patients were treated; 52 with PRX-102 and 25 with agalsidase beta. Approximately 40% of the enrolled patients were female.

Previous wording

Final results of the data generated in theBRIDGE study showed substantial improvement in renal function as measured by mean annualized eGFR slope in both male and female patients. Twenty of 22 patients completed the 12-month treatment duration. Eighteen of the patients who completed the study opted to roll over to a long-term extension study and continue to be treated with PRX-102. In the study, the mean annualized eGFR slope of the study participants improved from -5.90 mL/min/1.73m 2/year while on agalsidase alfa to -1.19 mL/min/1.73m 2/year on PRX-102 in all patients. Male patients improved from -6.36 mL/min/1.73m 2/year to -1.73mL/min/1.73m 2/year and female patients improved from -5.03 mL/min/1.73m 2/year to -0.21 mL/min/1.73m 2/year. Following the switch to PRX-102, there was a decrease in patients with progressing or fast progressing kidney disease which is consistent with the therapeutic goals for Fabry disease, as identified by Christoph Wanner, et. al., in 2019, and most patients achieved a stable status post-switch.

Current wording

of the patients who completed the study opted to roll over to a long-term extension study and continue to be treated with PRX-102. In the study, the mean annualized eGFR slope of the study participants improved from -5.90 mL/min/1.73m 2/year while on agalsidase alfa to -1.19 mL/min/1.73m 2/year on PRX-102 in all patients. Male patients improved from -6.36 mL/min/1.73m 2/year to -1.73mL/min/1.73m 2/year and female patients improved from -5.03 mL/min/1.73m 2/year to -0.21 mL/min/1.73m 2/year. Following the switch to PRX-102, there was a decrease in patients with progressing or fast progressing kidney disease which is consistent with the therapeutic goals for Fabry disease, as identified by Christoph Wanner, et. al., in 2019, and most patients achieved a stable status post-switch.

Previous wording

Study outcome measures show that plasma lyso-Gb 3 concentrations remained stable during the study with a mean change (±SE) of 3.01 nM (0.94) from baseline (19.36 nM ±3.35) to Week 52 (22.23 ±3.60 nM). Mean absolute eGFR values were stable during the 52-week treatment period, with a mean change from baseline of -1.27 mL/min/1.73 m 2 (1.39). Mean (SE) eGFR slope, at the end of the study, for the overall population, was -2.92 (1.05) mL/min/1.73 m 2/year indicating stability.

Current wording

Study outcome measures show that plasma lyso-Gb 3 concentrations remained stable during the study with a mean change (±SE) of 3.01 nM (0.94) from baseline (19.36 nM ±3.35) to Week 52 (22.23 ±3.60 nM). Mean absolute eGFR values were stable during the

Previous wording

As of March 1, 2023, sponsorship of the two extension studies was transferred to Chiesi, and Chiesi is now administering the extension studies.

Current wording

As of March 1, 2023, sponsorship of the two extension studies was transferred to Chiesi, and Chiesi is now the sponsor of the extension studies.

Previous wording

PRX-115 is our recombinant PEGylated uricase (urate oxidase) – a chemically modified enzyme under development for the potential treatment of patients with uncontrolled gout. The uricase enzyme converts uric acid to allantoin, which is easily eliminated through urine and does not exist naturally in humans. This recombinant enzyme, expressed via our ProCellEx system, is designed to lower uric acid levels and improve clinical manifestation of the disease while having low immunogenicity and increased half-life of the drug in the blood. Pre-clinical data demonstrates long half-life, reduced immunogenic risk and high specific activity which supports the potential of PRX-115 to be a safe and effective treatment for patients with gout. One-month multiple dosing toxicity studies in two species and 6-month multiple dosing toxicity study in one species were conducted to support single and multiple dose studies is humans.

Current wording

PRX-115 is our recombinant PEGylated uricase (urate oxidase) – a chemically modified enzyme under development for the potential treatment of patients with uncontrolled gout. The uricase enzyme, that does not exist naturally in humans, converts uric acid to allantoin, which is easily eliminated through urine. This recombinant enzyme, expressed via our ProCellEx system, is designed to lower uric acid levels and improve clinical manifestation of the disease while having low immunogenicity and increased half-life of the drug in the blood. Pre-clinical data demonstrates long half-life, reduced immunogenic risk and high specific activity which supports the potential of PRX-115 to be a safe and effective treatment for patients with gout. One-month multiple dosing toxicity studies in two species and 6-month multiple dosing toxicity study in one species were conducted to support single and multiple dose studies is humans.

Previous wording

Zealand Clinical Research (NZCR) under the New Zealand Medicines and Medical Devices Safety Authority (MedSafe) and the Health and Disability Ethics Committee (HDEC) guidelines. The study was initially designed to include sequential dosing cohorts, each composed of eight subjects (six active and two placebo), a 3:1 ratio. Subjects in each cohort, males and females aged 18 through 65, received a single dose of PRX-115 and are analyzed for safety, pharmacokinetics (PK) and pharmacodynamics (PD) (concentrations of plasma uric acid) for 85 days. As of March 31, 2024, 56 subjects with no previous exposure to PEGylated uricase have been enrolled in the study.

Current wording

Zealand Clinical Research (NZCR) under the New Zealand Medicines and Medical Devices Safety Authority (MedSafe) and the Health and Disability Ethics Committee (HDEC) guidelines. The study was initially designed to include seven sequential dosing cohorts, each composed of eight subjects (six active and two placebo), a 3:1 ratio. Subjects in each cohort, males and females aged 18 through 65, received a single dose of PRX-115 and are analyzed for safety, pharmacokinetics (PK) and pharmacodynamics (PD) (concentrations of plasma uric acid) for 85 days.

Previous wording

After a review of initial positive top-line results from the seven cohorts, and following the review and acceptance of the safety data from cohort 7 by the safety and monitoring committee for dose escalation for the FIH Study, the Company decided to expand the study by adding an eighth cohort of eight new subjects to analyze a higher dose and its potential to result in increased exposure time. In addition to the expansion of the FIH Study, the Company also decided to commence preparations for a phase II clinical trial of PRX-115.

Current wording

After a review of initial positive top-line results from the initial seven cohorts, and following the review and acceptance of the safety data from such seven cohorts by the safety and monitoring committee for dose escalation for theFIH study, we decided to expand the study by adding an eighth cohort of eight new subjects to analyze a higher dose and its potential to result in increased exposure time. As of June 30, 2024, all 64 subjects with no previous exposure to PEGylated uricase have been enrolled in the study and follow-up is ongoing. In addition to the expansion of theFIH study, we have commenced preparations for a phase II clinical trial of PRX-115.

Previous wording

Key preliminary results from the FIH Study are as follows:

Current wording

Key preliminary results from the first seven cohorts of theFIH study are as follows:

Previous wording

Uncontrolled gout occurs when oral gout therapies fail to lower serum uric acid (sUA) levels below the gout guideline goal of 6 mg/dL at the maximum medically appropriate dosage or when gout does not improve clinically with oral urate-lowering therapies (ULTs), and may involve systemic urate deposition. Uncontrolled gout is also reported to involve urate crystal deposition and associated inflammation in joints, soft tissues, and organs, such as the heart, kidneys, and eyes. Currently available ULTs can be effective in treating gout. However, low adherence, under dosing and disease progression that cause high patient burden require new, effective and safe therapies to treat these underserved uncontrolled gout patients.

Current wording

Uncontrolled gout is when serum uric acid (sUA) levels are above the maximum medically appropriate level (6.0 mg/dL) and cannot be treated with available urate lowering therapies. It is also reported to involve urate crystal deposition and associated inflammation in joints, soft tissues and organs. Currently available ULTs can be effective in treating gout. However, low adherence, under dosing, disease progression that cause high patient burden or patients that are not suitable for available therapy, require new, effective and safe therapies to treat these underserved uncontrolled gout patients.

Previous wording

To date, two variants of recombinant uricases are approved for marketing: (i) Krystexxa® (pegloticase) for treatment of chronic gout refractory to conventional therapy (gout patients who have contraindication/failure of other lowering uric acid treatments) and (ii) Elitek®, indicated for the treatment of tumor lysis syndrome but not gout. Both have a black box warning for anaphylaxis and other major side-effects. The FDA label of Krystexxa was amended in 2022 to include co-treatment of metrotrexate to prolong efficacy and increases tolerability in patients with refractory gout. Krystexxa is no longer marketed in the European Union. The EC withdrew the marketing authorization for Krystexxa in 2016 at the request of the marketing authorization holder which notified the EC of its decision not to market the product in the European Union for commercial reasons. We believe that new effective, safe therapies are needed to treat severe gout, chronic refractory and uncontrolled** **gout, regardless of treatment history.

Current wording

To date, two variants of recombinant uricases are approved for marketing: (i) Krystexxa® (pegloticase) for treatment of chronic gout refractory to conventional therapy (gout patients who have contraindication/failure of other lowering uric acid treatments) and (ii) Elitek®, indicated for the treatment of tumor lysis syndrome but not gout. Both have a black box warning for anaphylaxis and other major side-effects. The FDA label of Krystexxa was amended in 2022 to include co-treatment of methotrexate to prolong efficacy and increases tolerability in patients with refractory gout. Krystexxa is no longer marketed in the European Union. The EC withdrew the marketing authorization for Krystexxa in 2016 at the request of the marketing authorization holder which notified the EC of its decision not to market the product in the European Union for commercial reasons. We believe that new effective, safe therapies are needed to treat severe gout, chronic refractory and uncontrolled** **gout, regardless of treatment history.

Previous wording

neutrophils that trap and kill a variety of microorganisms. NETs are composed of DNA, histones, antimicrobial and pro-inflammatory proteins. Excessive formation or ineffective clearance of NETs can cause different pathological effects. NETs formation has been observed in various autoimmune, inflammatory and fibrotic conditions, diverse forms of thrombosis, cancer and metastasis. According to scientific literature, animal studies have demonstrated that DNase treatment reduces NETs toxicity. Our proprietary modified DNase I design for long and customized systemically circulating in the bloodstream, may potentially enable effective treatment of these conditions.

Current wording

PRX-119 is our plant cell-expressed PEGylated recombinant human DNase I product candidate being designed to elongate half-life in the circulation for NETs-related diseases. NETs, Neutrophil extracellular traps, are web-like structures, released by activated neutrophils that trap and kill a variety of microorganisms. NETs are composed of DNA, histones, antimicrobial and pro-inflammatory proteins. Excessive formation or ineffective clearance of NETs can cause different pathological effects. NETs formation has been observed in various autoimmune, inflammatory and fibrotic conditions, diverse forms of thrombosis, cancer and metastasis. According to scientific literature, animal studies have demonstrated that DNase treatment reduces NETs toxicity. Our proprietary modified DNase I design for long and customized systemically circulating in the bloodstream, may potentially enable effective treatment of these conditions.

Previous wording

A key element of our overall strategy is to establish a broad portfolio of patents to protect our proprietary technology, proprietary product and product candidates and their methods of use. As of March 31, 2024, we hold a broad portfolio of more than 70 patents in Europe, the United States, Israel and additional countries worldwide, as well as more than 45 pending patent applications.

Current wording

A key element of our overall strategy is to establish a broad portfolio of patents to protect our proprietary technology, proprietary product and product candidates and their methods of use. As of June 30, 2024, we hold a broad portfolio of more than 70 patents in Europe, the United States, Israel and additional countries worldwide, as well as approximately 50 pending patent applications.

Previous wording

Consistent with our corporate strategy, we are focusing on new, early-stage product candidates that treat indications for which there are high unmet needs in terms of efficacy and safety, including renal diseases. Treatments of interest will address both genetic and non-genetic diseases. We intend to use our ProCellEx platform and PEGylization capabilities, as well as other modalities such as small molecules and antibodies, to take advantage of highly innovative opportunities. We are also exploring novel platform technologies.

Current wording

Consistent with our corporate strategy, we are focusing on new, early-stage product candidates that treat indications for which there are high unmet needs in terms of efficacy and safety, including renal diseases. Treatments of interest will address both genetic and non-genetic diseases. We intend to use our ProCellEx platform and PEGylization capabilities, as well as other modalities such as small molecules and oligonucleotides, to take advantage of highly innovative opportunities. We are also exploring novel platform technologies.

Previous wording

We recorded revenues from selling goods of $3.7 million during the three months ended March 31, 2024, a decrease of $1.4 million, or 27%, compared to revenues of $5.1 million for the three months ended March 31, 2023. The decrease resulted primarily from a decrease of $1.1 million in sales to Pfizer, and of $0.3 million in sales to Brazil which decreases resulted primarily from the timing of delivery.

Current wording

We recorded revenues from selling goods of $13.3 million during the three months ended June 30, 2024, a decrease of $1.8 million, or 12%, compared to revenues of $15.1 million for the three months ended June 30, 2023. The decrease resulted primarily from a decrease of $10.0 million in sales to Chiesi, partially offset by an increase of $4.7 million in sales to Brazil and an increase of $3.5 million in sales to Pfizer. Sales to Chiesi in the three months ended June 30, 2023 were in connection with the commercial launch and inventory buildup of Elfabrio after its approval for marketing in the United States and the European Union. The increases in sales to Brazil and Pfizer during the three months ended June 30, 2024 resulted primarily from the timing of delivery.

Previous wording

We recorded revenues from license and R&D services of $0.1 million for the three months ended March 31, 2024, a decrease of $4.4 million, or 98%, compared to revenues of $4.5 million for the three months ended March 31, 2023. Revenues from license and R&D services are comprised primarily of revenues we recognized in connection with the Chiesi Agreements. The decrease resulted primarily from the completion of our research and development obligations with respect to Elfabrio and, as Elfabrio was approved in

Current wording

We recorded revenues from license and R&D services of $0.2 million for the three months ended June 30, 2024, a decrease of $19.8 million, or 99%, compared to revenues of $20.0 million for the three months ended June 30, 2023. Revenues from license and R&D services are comprised primarily of revenues we recognized in connection with the Chiesi Agreements. The revenues from license and R&D services for the three months ended June 30, 2023 were the result ofthe $20.0 million regulatory milestone payment from Chiesi in connection with the FDA approval of Elfabrio granted during that period.

Previous wording

For the three months ended March 31, 2024, our total research and development expenses were approximately $2.9 million comprised of approximately $0.5 million in subcontractor-related expenses, approximately $1.5 million of salary and related expenses, approximately $0.2 million of materials-related expenses and approximately $0.7 million of other expenses. For the three months ended March 31, 2023, our total research and development expenses were approximately $5.8 million comprised of approximately $3.5 million of subcontractor-related expenses, approximately $1.5 million of salary and related expenses, approximately $0.1 million of materials-related expenses and approximately $0.7 million of other expenses.

Current wording

For the three months ended June 30, 2024, our total research and development expenses were approximately $3.0 million comprised of approximately $0.5 million in subcontractor-related expenses, approximately $1.6 million of salary and related expenses, approximately $0.2 million of materials-related expenses and approximately $0.7 million of other expenses. For the three months ended June 30, 2023, our total research and development expenses were approximately $4.5 million comprised of approximately $1.7 million of subcontractor-related expenses, approximately $2.0 million of salary and related expenses, approximately $0.1 million of materials-related expenses and approximately $0.7 million of other expenses.

Previous wording

Total decrease in research and developments expenses for the three months ended March 31, 2024 was $2.9 million, or 50%, compared to the three months ended March 31, 2023. The decrease in research and development expenses primarily resulted from the completion of our Fabry clinical program and the regulatory processes related to the BLA and MAA review of Elfabrio by the applicable regulatory agencies.

Current wording

Total decrease in research and developments expenses for the three months ended June 30, 2024 was $1.5 million, or 33%, compared to the three months ended June 30, 2023. The decrease in research and development expenses resulted primarily from the completion of our Fabry clinical program and the regulatory processes related to the BLA and MAA review of Elfabrio by the applicable regulatory agencies.

Previous wording

Financial income, net were $0.1 million for the three months ended March 31, 2024, compared to financial expenses, net of $0.5 million for the three months ended March 31, 2023. The change resulted primarily from higher interest income on bank deposits and lower notes interest expenses due to notes conversions executed in 2023.

Current wording

Financial income, net were $0.2 million for the three months ended June 30, 2024, compared to financial expenses, net of $0.8 million for the three months ended June 30, 2023. The difference resulted primarily from higher interest income on bank deposits and lower notes interest expenses due to notes conversions executed in 2023.

Previous wording

In the three months ended March 31, 2024, we recorded a tax benefit of approximately $(0.1) million, compared to income taxes of $0.2 million for the three months ended March 31, 2023. Income taxes recorded are primarily the result of the provision for current taxes in respect of Section 174 of the TCJA.

Current wording

For the three months ended June 30, 2024, we recorded a tax benefit of approximately $0.1 million, compared to income taxes of $0.3 million for the three months ended June 30, 2023. Income taxes recorded are primarily the result of the provision for current taxes in respect of Section 174 of the TCJA.

Previous wording

the United States and the European Union in May 2023, from the completion of the regulatory processes related to the review of the BLA and the MAA for Elfabrio by the FDA and EMA, respectively.

Current wording

We recorded revenues from license and R&D services of $0.2 million for the six months ended June 30, 2024, a decrease of $24.3 million, or 99%, compared to revenues of $24.5 million for the six months ended June 30, 2023. Revenues from license and R&D services are comprised primarily of revenues we recognized in connection with the Chiesi Agreements. The revenues from license and R&D services for the six months ended June 30, 2023 includedthe $20.0 million regulatory milestone payment from Chiesi in connection with the FDA approval of Elfabrio granted during that period. The remaining decrease resulted from the completion of our revenue-generating research and development obligations with respect to Elfabrio and, as Elfabrio was approved in the United States and the European Union in May 2023, from the completion of the regulatory processes related to the review of the BLA and the MAA for Elfabrio by the FDA and EMA, respectively.

Previous wording

Our sources of liquidity include our cash and cash equivalents balances and short term bank deposits. At March 31, 2024, we had $48.5 million in cash and cash equivalents and short term bank deposits. We have primarily financed our operations through equity and debt financings, business collaborations, grants funding and revenues from selling goods.

Current wording

Our sources of liquidity include our cash and cash equivalents balances and short term bank deposits. At June 30, 2024, we had $45.0 million in cash and cash equivalents and short term bank deposits. We have primarily financed our operations through equity and debt financings, business collaborations, grants funding and revenues from selling goods.

Previous wording

During the year ended December 31, 2023, we raised gross proceeds equal to approximately $24.9 million from the sale of 12,560,150 shares of our common stock under our ATM program. All such sales were completed during the quarters ended March 31, 2023 and June 30, 2023. No sales were completed during the quarters ended September 30, 2023, December 31, 2023 or March 31, 2024.

Current wording

During the year ended December 31, 2023, we raised gross proceeds equal to approximately $24.9 million from the sale of 12,560,150 shares of our common stock under our ATM program. All such sales were completed during the quarters ended March 31, 2023 and June 30, 2023. No sales under our ATM program have been completed since the quarter ended June 30, 2023.

Previous wording

On August 25, 2021, we completed exchanges, or the Exchanges, with institutional note holders of a substantial majority of the then outstanding 7.50% Senior Secured Convertible Notes due 2021, or the 2021 Notes. The Exchanges involved the exchange of an aggregate of $54.65 million principal amount of 2021 Notes for an aggregate of $28.75 million principal amount of newly issued 2024 Notes, $25.90 million in cash and approximately $1.1 million in cash representing accrued and unpaid interest through the closing date. The initial conversion rate of the 2024 Notes is 563.2216 shares of our common stock per $1,000 principal amount of 2024 Notes, which is equivalent to an initial conversion price of approximately $1.7755 per share of common stock, subject to adjustment

Current wording

On August 25, 2021, we completed exchanges, or the Exchanges, with institutional note holders of a substantial majority of the then outstanding 7.50% Senior Secured Convertible Notes due 2021, or the 2021 Notes. The Exchanges involved the exchange of an aggregate of $54.65 million principal amount of 2021 Notes for an aggregate of $28.75 million principal amount of newly issued 2024 Notes, $25.90 million in cash and approximately $1.1 million in cash representing accrued and unpaid interest through the closing date. The initial conversion rate of the 2024 Notes is 563.2216 shares of our common stock per $1,000 principal amount of 2024 Notes, which is equivalent to an initial conversion price of approximately $1.7755 per share of common stock, subject to adjustment in certain circumstances. This initial conversion price represents a premium of approximately 32.5% relative to the closing price of the common stock on the NYSE American on August 13, 2021. After giving effect to the Exchanges, $3.27 million aggregate principal amount of the 2021 Notes remained outstanding. On November 15, 2021, all of the then outstanding 2021 Notes matured and were paid in full.

Previous wording

We believe that our cash, cash equivalents and short term bank deposits as of March 31, 2024 are sufficient to satisfy our capital needs for at least 12 months from the date that these financial statements are issued.

Current wording

We except to satisfy the outstanding principal and interest accrued under the 2024 Notes with a cash payment prior to the September 1, 2024 maturity date. We believe that our cash, cash equivalents and short term bank deposits as of June 30, 2024 are sufficient to satisfy our capital needs for at least 12 months from the date that these financial statements are issued, including the maturity payment for the 2024 Notes.

Previous wording

Net cash provided by operations was $4.2 million for the three months ended March 31, 2024. The net loss for the three months ended March 31, 2024 of $4.6 million was increased by a $3.3 million increase in inventories, a $1.4 million decrease in accounts payable and accruals and was offset by an $11.0 million increase in contracts liability, a $1.7 million decrease in accounts receivable-trade and other assets and $1.0 million in share-based compensation. Net cash used in investing activities for the three months ended March 31, 2024 was $0.6 million and consisted primarily of the purchase of property and equipment.

Current wording

Net cash provided by operations was $0.6 million for the six months ended June 30, 2024. The net loss for the six months ended June 30, 2024 of $6.8 million was increased by a $1.7 million increase in inventories, a $5.3 million increase in accounts receivable-trade and other assets and $1.0 million of financial income, net, and was offset by a $12.7 million increase in contracts liability and $2.0 million in share-based compensation. Net cash used in investing activities for the six months ended June 30, 2024 was $0.8 million and consisted primarily of the purchase of property and equipment.

Previous wording

Net cash used in operations was $3.0 million for the three months ended March 31, 2023. The net loss for the three months ended March 31, 2023 of $3.1 million was increased by a $1.4 million decrease in contracts liability and a $3.5 million increase in inventories and was partially offset by a $3.8 million decrease in accounts receivable-trade and other assets and $0.5 million in share-based compensation. Net cash provided by investing activities for the three months ended March 31, 2023 was $4.7 million and consisted primarily of proceeds from sale of short-term deposits. Net cash provided by financing activities was $14.2 million resulting primarily from the sale of common stock under our ATM program.

Current wording

Net cash generated from operations was $2.0 million for the six months ended June 30, 2023. The net income for the six months ended June 30, 2023 of $16.2 million was decreased by a $13.2 million decrease in contracts liability, a $3.1 million increase in deferred tax assets and a $2.8 million increase in inventories. The net income was increased by a $3.6 million increase in accounts payable and accruals, $1.0 million in share-based compensation and $0.6 million in depreciation. Net cash provided by investing activities for the six months ended June 30, 2023 was $4.5 million and consisted primarily of proceeds from sale of short-term deposits. Net cash provided by financing activities was $24.7 million resulting primarily from the sale of common stock under our ATM program.

Previous wording

As of March 31, 2024, the total principal amount of our 2024 Notes outstanding was $20.42 million, and 2020 Warrants to purchase 13,439,712 shares were outstanding.

Current wording

As of June 30, 2024, the total principal amount of our 2024 Notes (due on September 1, 2024) outstanding was $20.42 million, and 2020 Warrants to purchase 13,439,712 shares were outstanding.

Previous wording

As we increase our research and developments efforts with respect to our current and future product candidates, we expect to continue to incur significant expenditures. We cannot anticipate the costs or the timing of the occurrence of such costs. Although we expect the revenues generated from the sales of Elfabrio and Elelyso will increase, such revenues may not be sufficient to fund the expenditures. To the extent we need to obtain additional financing in excess of such anticipated revenues, it may be difficult for us to do so given the volatility of the price of our common stock. Our material cash needs for the next 24 months will include, among other expenses, (i) costs of preclinical and clinical trials, (ii) employee salaries, (iii) payments for rent and operation of our manufacturing facilities, (iv) fees to our consultants and legal advisors, patent advisors and fees for service providers in connection with our research and development efforts, (v) payments of principal and interest on our outstanding 2024 Notes and (vi) tax payments. We believe that the funds currently available to us are sufficient to satisfy our capital needs for at least 12 months.

Current wording

As we increase our research and developments efforts with respect to our current and future product candidates, we expect to continue to incur significant expenditures. We cannot anticipate the costs or the timing of the occurrence of such costs. Although we expect the revenues generated from the sales of Elfabrio and Elelyso will increase, such revenues may not be sufficient to fund the expenditures. To the extent we need to obtain additional financing in excess of such anticipated revenues, it may be difficult for us to do so given the volatility of the price of our common stock. Our material cash needs for the next 24 months will include, among other expenses, (i) costs of preclinical and clinical trials, (ii) employee salaries, (iii) payments for rent and operation of our manufacturing facilities, (iv) fees to our consultants and legal advisors, patent advisors and fees for service providers in connection with our research and development efforts, (v) payments of principal and interest on our outstanding 2024 Notes and (vi) tax payments. We believe that our cash, cash equivalents and short term bank deposits as of June 30, 2024 are sufficient to satisfy our capital needs for at least 12 months from the date that these financial statements are issued, including the maturity payment for the 2024 Notes.

Previous wording

Currency fluctuations could affect us through increased or decreased acquisition costs for certain goods and services and salaries expenses. We do not believe currency fluctuations have had a material effect on our results of operations during the three and nine months ended of March 31, 2024.

Current wording

Currency fluctuations could affect us through increased or decreased acquisition costs for certain goods and services and salaries expenses. We do not believe currency fluctuations have had a material effect on our results of operations during the three and six months ended June 30, 2024.