PROTHENA CORP PUBLIC LTD CO

Previous wording

In addition to historical information, this Quarterly Report on Form 10-Q contains forward-looking statements which may cause our actual results to differ materially from expectations, plans and anticipated results discussed in forward-looking statements. Factors that could cause our actual results to differ materially include, but are not limited to, the risks and uncertainties set forth in the “Summary of Risks Affecting Our Business” at the beginning of this Quarterly Report on Form 10-Q, Part II Item 1A “Risk Factors” of this Quarterly Report on Form 10-Q, and in our other filings with the U.S. Securities and Exchange Commission.

Current wording

In addition to historical information, this Quarterly Report on Form 10-Q contains forward-looking statements which may cause our actual results to differ materially from expectations, plans and anticipated results discussed in forward-looking statements. Factors that could cause our actual results to differ materially include, but are not limited to, the risks and uncertainties set forth in the “Summary of Risks Affecting Our Business” at the beginning of this Quarterly Report on Form

Previous wording

Fueled by our deep scientific expertise built over decades of research, we are advancing a pipeline of therapeutic candidates for a number of indications and novel targets for which our ability to integrate scientific insights around neurological dysfunction and the biology of misfolded proteins can be leveraged. Our wholly-owned programs include birtamimab for the potential treatment of AL amyloidosis, and a portfolio of programs for the potential treatment of Alzheimer’s disease including PRX012, which targets amyloid beta (Aβ), and PRX123, a novel dual Aβ-tau vaccine. Our partnered programs include prasinezumab, in collaboration with Roche for the potential treatment of Parkinson’s disease and other related synucleinopathies, and programs that target tau (BMS-986446, formerly PRX005), TDP-43, and an undisclosed target (PRX019) in collaboration with Bristol Myers Squibb (BMS) for the potential treatment of Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and other neurodegenerative diseases, respectively. We are also entitled to certain potential milestone payments pursuant to our share purchase agreement with Novo Nordisk pertaining to our ATTR amyloidosis business (NNC6019, formerly PRX004).

Current wording

Fueled by our deep scientific expertise built over decades of research, we are advancing a pipeline of therapeutic candidates for a number of indications and novel targets for which our ability to integrate scientific insights around neurological dysfunction and the biology of misfolded proteins can be leveraged. Our wholly-owned programs include birtamimab for the potential treatment of AL amyloidosis, and a portfolio of programs for the potential treatment of Alzheimer’s disease including PRX012, which targets amyloid beta (Aβ), and PRX123, a novel dual Aβ-tau vaccine. Our partnered programs include prasinezumab for the potential treatment of Parkinson’s disease and other related synucleinopathies that targets alpha-synuclein in collaboration with Roche. In addition we have partnered BMS-986446 (formerly PRX005) for the potential treatment for Alzheimer’s disease that targets tau and PRX019 for the potential treatment of neurodegenerative diseases with an undisclosed target in two separate license agreements with Bristol Myers Squibb (BMS). We are also entitled to certain potential milestone payments pursuant to our share purchase agreement with Novo Nordisk pertaining to our ATTR amyloidosis business (inclusive of coramitug, formerly PRX004).

Previous wording

AFFIRM-AL is an ongoing global, multi-center, double-blind, placebo-controlled, 2:1 randomized, time-to-event trial expected to enroll approximately 150 newly diagnosed, treatment naïve patients with AL amyloidosis categorized as Mayo Stage IV. It has been designed to evaluate the primary endpoint of time to all-cause mortality with a significance level of p<0.10. Secondary endpoints will assess change from baseline to month 9 in functional capacity as measured by 6MWT distance and quality of life as measured by SF-36v2 PCS.

Current wording

AFFIRM-AL is an ongoing global, multi-center, double-blind, placebo-controlled, 2:1 randomized, time-to-event trial expected to enroll up to approximately 220 newly diagnosed, treatment naïve patients with AL amyloidosis categorized as Mayo Stage IV. It has been designed to evaluate the primary endpoint of time to all-cause mortality with a significance level of p<0.10. Secondary endpoints will assess change from baseline to month 9 in functional capacity as measured by 6MWT distance and quality of life as measured by SF-36v2 PCS.

Previous wording

An interim analysis will be conducted when approximately 50% of the events have occurred, allowing the independent data monitoring committee to recommend either continuing the trial or stopping early for overwhelming efficacy. Patients will receive 24 mg/kg of birtamimab or placebo by intravenous infusion every 28 days, with all patients receiving concurrent standard of care therapy consisting of a first line bortezomib-containing regimen.

Current wording

An interim analysis is conducted when approximately 50% of the events have occurred, allowing the independent data monitoring committee to recommend either continuing the trial or stopping early for overwhelming efficacy. Patients will receive 24 mg/kg of birtamimab or placebo by intravenous infusion every 28 days, with all patients receiving concurrent standard of care therapy consisting of a first line bortezomib-containing regimen.

Previous wording

NNC6019 (formerly PRX004) for the Potential Treatment of ATTR Amyloidosis

Current wording

Coramitug (formerly PRX004) for the Potential Treatment of ATTR Amyloidosis

Previous wording

NNC6019 (formerly PRX004) is an investigational antibody designed to deplete amyloid associated with disease pathology in hereditary and wild type ATTR amyloidosis, without affecting the native, normal tetrameric form of the protein.

Current wording

Coramitug is an investigational antibody designed to deplete amyloid associated with disease pathology in hereditary and wild type ATTR amyloidosis, without affecting the native, normal tetrameric form of the protein.

Previous wording

NNC6019’s proposed mechanism of action is to deplete both circulating non-native TTR to prevent further deposition and deposited amyloid to improve organ function. NNC6019 has been shown in preclinical studies to inhibit amyloid fibril formation, neutralize soluble aggregate forms of non-native TTR, and promote clearance of insoluble amyloid fibrils through antibody-mediated phagocytosis. This differentiated depleter mechanism of action could be developed as a monotherapy approach to ATTR amyloidosis and might also complement existing therapeutic approaches which either stabilize or reduce production of the native TTR tetramer.

Current wording

Coramitug’s proposed mechanism of action is to deplete both circulating non-native TTR to prevent further deposition and deposited amyloid to improve organ function. Coramitug has been shown in preclinical studies to inhibit amyloid fibril formation, neutralize soluble aggregate forms of non-native TTR, and promote clearance of insoluble amyloid fibrils through antibody-mediated phagocytosis. This differentiated depleter mechanism of action could be developed as a monotherapy approach to ATTR amyloidosis and might also complement existing therapeutic approaches which either stabilize or reduce production of the native TTR tetramer.

Previous wording

We completed a Phase 1 clinical trial with NNC6019 in patients with hereditary forms of ATTR amyloidosis, in which NNC6019 was demonstrated to be safe and well tolerated.

Current wording

We completed a Phase 1 clinical trial with coramitug in patients with hereditary forms of ATTR amyloidosis, in which coramitug was demonstrated to be safe and well tolerated.

Previous wording

In July 2021, we announced that we and Novo Nordisk entered into a definitive purchase agreement under which Novo Nordisk acquired our clinical stage antibody NNC6019 (formerly PRX004) and broader ATTR amyloidosis business.

Current wording

In July 2021, we announced that we and Novo Nordisk entered into a definitive purchase agreement under which Novo Nordisk acquired our clinical stage antibody coramitug and broader ATTR amyloidosis business.

Previous wording

Under the terms of the definitive purchase agreement, Novo Nordisk acquired our wholly-owned subsidiary and gained full worldwide rights to the intellectual property and related rights of our ATTR amyloidosis business and pipeline. The aggregate purchase price consists of an upfront paymentand development and sales milestone payments totaling up to $1.23 billion. We have earned approximately $100 million to date, including a $40 million clinical milestone payment that we announced in November 2022.

Current wording

Under the terms of the definitive purchase agreement, Novo Nordisk acquired our wholly-owned subsidiary and gained full worldwide rights to the intellectual property and related rights of our ATTR amyloidosis business and pipeline. The aggregate purchase price consists of an upfront paymentand development and sales milestone payments totaling up to $1.23 billion. We have earned approximately $100 million to date.

Previous wording

A Phase 2 clinical trial of NNC6019 in patients with ATTR cardiomyopathy is being conducted by Novo Nordisk (NCT05442047).

Current wording

A Phase 2 clinical trial of coramitug in approximately 99 patients with ATTR cardiomyopathy is being conducted by Novo Nordisk (NCT05442047).

Previous wording

In June 2021, we announced that BMS exercised its option under the global neuroscience research and development collaboration to enter into an exclusive U.S. license for BMS-986446. BMS paid Prothena $80 million for this option following the execution of a US License Agreement for BMS-986446 and transfer of the underlying license. In July 2023, we entered into the Tau Global License Agreement, which as discussed above supersedes and replaces the Tau US License Agreement in its entirety. We received the associated option exercise fee of $55 million in August 2023.

Current wording

In July 2021, we entered into an exclusive US license agreement for BMS-986446 and we received an associated option exercise fee of $80 million. In July 2023, we entered into an exclusive global license agreement for BMS-986446, which as discussed above supersedes and replaces the US license agreement in its entirety and we received an associated option exercise fee of $55 million. We are eligible to receive regulatory and sales milestone payments of up to$563 million, as well as tiered royalties on annual, worldwide net sales.

Previous wording

A multiple ascending dose (MAD) portion of the Phase 1 clinical trial was ongoing at the time BMS acquired the global rights to the program and control of the Phase 1 trial. In September 2023, BMS reported that Phase 1 data supports moving BMS-986446 into a Phase 2 clinical trial. All program updates going forward, including results from ongoing and any future BMS-986446 clinical trials, will be reported by BMS.

Current wording

A multiple ascending dose (MAD) portion of the Phase 1 clinical trial was ongoing at the time BMS acquired the global rights to the program and control of the Phase 1 trial. All program updates going forward, including results from ongoing and any future BMS-986446 clinical trials, will be reported by BMS.

Previous wording

We are advancing our lead candidate, PRX012, as a next-generation approach for subcutaneous administration to improve access for patients with Alzheimer’s disease. In March 2022, we announced the FDA clearance of the IND for PRX012 and the initiation of a Phase 1 single ascending dose trial to investigate the safety, tolerability, immunogenicity, and pharmacokinetics of PRX012 in both healthy volunteers and patients with Alzheimer’s disease. In April 2022, we announced that the FDA granted Fast Track designation for PRX012 for the treatment of Alzheimer’s disease. The FDA’s Fast Track designation program is designed to expedite the development and review of drugs intended to treat a serious condition, such as Alzheimer’s disease, with evidence demonstrating the potential to address an unmet medical need. In January 2024, we announced that topline Phase 1 data from the single-ascending dose (SAD) trial and the initial multiple-ascending dose (MAD) cohort (70 mg) supports once-monthly subcutaneous treatment and dose escalation. The ongoing Phase 1 trial continues as planned.

Current wording

We are advancing our lead candidate, PRX012, as a next-generation approach for subcutaneous administration to improve access for patients with Alzheimer’s disease. In March 2022, we announced the FDA clearance of the IND for PRX012 and the initiation of a Phase 1 single ascending dose trial to investigate the safety, tolerability, immunogenicity, and pharmacokinetics of PRX012 in both healthy volunteers and patients with Alzheimer’s disease. In April 2022, we announced that the FDA granted Fast Track designation for PRX012 for the treatment of Alzheimer’s disease. The FDA’s Fast Track designation program is designed to expedite the development and review of drugs intended to treat a serious condition, such as Alzheimer’s disease, with evidence demonstrating the potential to address an unmet medical need. In January 2024, we announced that topline Phase 1 data from the single ascending dose trial and the initial multiple dose cohort (70 mg) supports once-monthly subcutaneous treatment and dose escalation. The ongoing Phase 1 trial continues as planned.

Previous wording

In December 2023, the FDA cleared the IND application for PRX019, a potential treatment of neurodegenerative diseases with an undisclosed target. PRX019 is one of the three programs that are the focus of our collaboration with BMS.

Current wording

PRX019 is an investigational antibody for the potential treatment of neurodegenerative diseases with an undisclosed target.

Previous wording

We are also advancing several discovery and preclinical-stage programs for neurological diseases with significant unmet medical needs such as TDP-43, an undisclosed target for amyotrophic lateral sclerosis (ALS) and one of the three programs that are the focus of our collaboration with BMS.

Current wording

We are also advancing several discovery and preclinical-stage programs for neurological diseases with significant unmet medical needs.

Previous wording

There were no significant changes to our critical accounting policies and estimates during the three months ended March 31, 2024, from the critical accounting policies and estimates disclosed in Management's Discussion and Analysis of Financial Condition and Results of Operations in our 2023 Form 10-K.

Current wording

There were no significant changes to our critical accounting policies and estimates during the six months ended June 30, 2024, from the critical accounting policies and estimates disclosed in Management's Discussion and Analysis of Financial Condition and Results of Operations in our 2023 Form 10-K.

Previous wording

Except as described in Note 2 to the Condensed Consolidated Financial Statements under the heading “Recent Accounting Pronouncements”, there have been no new accounting pronouncements or changes to accounting pronouncements during the three months ended March 31, 2024, as compared to the recent accounting pronouncements described in our 2023 Form 10-K, that are of significance or potential significance to us.

Current wording

Except as described in Note 2 to the Condensed Consolidated Financial Statements under the heading “Recent Accounting Pronouncements”, there have been no new accounting pronouncements or changes to accounting pronouncements during the six months ended June 30, 2024, as compared to the recent accounting pronouncements described in our 2023 Form 10-K, that are of significance or potential significance to us.

Previous wording

Comparison of Three Months Ended March 31, 2024 and 2023

Current wording

Comparison of three and six months ended June 30, 2024 and 2023

Previous wording

Collaboration revenue from BMS was nil, compared to$2.1 million for the three months ended March 31, 2024 and 2023, respectively. Collaboration revenue for the three months ended March 31, 2023 included revenue from BMS for US Development Services related to the Tau/PRX005 program. As of March 31, 2024, the Company does not have any remaining Tau US Development Services Obligations and has recognized all revenue from this performance obligation as of December 31, 2023. See Note 7, “Significant Agreements” to the Condensed Consolidated Financial Statements regarding the Collaboration Agreement with BMS for more information.

Current wording

Collaboration revenue was $132.0 million and$132.0 million for thethree and six months ended June 30, 2024, compared to $4.0 million and$6.1 million for thethree and six months ended June 30, 2023, respectively. Collaboration revenue of$132.0 million for thethree and six months ended June 30, 2024, was related to revenue recognized under our Collaboration Agreement with BMS of which,$107.0 million was from the PRX019 Global License Agreement and PRX019 Phase 1 Clinical Trial Obligation and$25.0 million was related to BMS’s material rights for the US Rights and Global Rights for the TDP-43 Collaboration Target that were fulfilled on May 24, 2024 as a result of the expiration of the research term of the Collaboration Agreement. Collaboration revenue for the three and six months ended June 30, 2023, included revenue from BMS for US Development Services related to the Tau/PRX005 program. As of June 30, 2024, the Company does not have any remaining Tau US Development Services Obligations and has recognized all revenue from this performance obligation as of December 31, 2023. As of June 30, 2024, the Company has $15.4 million of deferred revenue related to the remaining performance obligations under the PRX019 Global License Agreement related to PRX019 Phase 1 Clinical Trial Obligations. See Note 7, “Significant Agreements” to the Condensed Consolidated Financial Statements regarding the Collaboration Agreement with BMS for more information.

Previous wording

License and intellectual property revenue for the three months ended March 31, 2024 and 2023 included $50,000 in each period, respectively, in license fees recognized under the License Agreement entered into on March 1, 2020, between the Company's wholly owned subsidiary, Prothena Biosciences Limited, and F. Hoffmann-La Roche Ltd.

Current wording

License and intellectual property revenue for the six months ended June 30, 2024, and 2023 included $50,000 in each period, respectively, in license fees recognized under the License Agreement entered into on March 1, 2020, between the Company's wholly owned subsidiary, Prothena Biosciences Limited, and F. Hoffmann-La Roche Ltd.

Previous wording

Assuming no significant change in our business, we expect our 2024 revenue to decline over the prior year as our 2023 revenue was primarily comprised of nonrecurring revenue.

Current wording

Assuming no significant change in our business, we expect our 2024 revenue to increase over the prior year.

Previous wording

Total operating expenses consist of R&D expenses, general and administrative (“G&A”) expenses. Our operating expenses were $81.6 million and$58.5 million for the three months ended March 31, 2024 and 2023, respectively.

Current wording

Total operating expenses consist of R&D expenses, general and administrative (“G&A”) expenses. Our operating expenses were $73.6 million and $70.5 million for the three months ended June 30, 2024, and 2023 respectively, and $155.2 million and$129.0 millionfor thesix months ended June 30, 2024, and 2023 respectively.

Previous wording

Our R&D expenses increased by $19.4 million or 43%, for the three months ended March 31, 2024, compared to the same period in the prior year. The increase for the three months ended March 31, 2024, compared to the same period in the prior year was primarily due to higher clinical trial expenses primarily related to the PRX012 and birtamimab programs, higher personnel expenses, and higher manufacturing expenses related primarily to the birtamimab and PRX012 programs.

Current wording

Our R&D expenses increased by$1.5 million or 3% for the three months ended June 30, 2024, and increased by$20.9 million or 21%, for the six months ended June 30, 2024, compared to the same period in the prior year. The increase for thethree and six months ended June 30, 2024, compared to the same period in the prior year was primarily due to higher clinical trial expenses primarily related to the PRX012 and birtamimab programs and higher personnel expenses offset in part by lower manufacturing expenses.

Previous wording

The following table sets forth the R&D expenses for our major programs (specifically, any active program with successful first dosing in a Phase 1 clinical trial, which were birtamimab, prasinezumab, NNC6019 (PRX004), BMS-986446 (PRX005), PRX012 and other R&D expenses for thethree months ended March 31, 2024, and 2023, and the cumulative amounts to date (in thousands):

Current wording

The following table sets forth the R&D expenses for our major programs (specifically, any active program with successful first dosing in a Phase 1 clinical trial), which were birtamimab, prasinezumab, NNC6019 (PRX004), BMS-986446 (PRX005), PRX012 and other R&D expenses for the three and six months ended June 30, 2024, and 2023, and the cumulative amounts to date (in thousands):

Previous wording

(3) On July 8, 2021, we sold shares of one of our wholly-owned subsidiaries to Novo Nordisk. In connection with the transaction, Novo Nordisk acquired our ATTR amyloidosis business, including the clinical stage antibody NNC6019 (PRX004). Expenses incurred in 2024 and 2023 relate to certain close out activities and transition services provided to Novo Nordisk.

Current wording

(3) On July 8, 2021, we sold shares of one of our wholly-owned subsidiaries to Novo Nordisk. In connection with the transaction, Novo Nordisk acquired our ATTR amyloidosis business, including the clinical stage antibody coramitug (PRX004). Expenses incurred in 2024 and 2023 relate to certain close out activities and transition services provided to Novo Nordisk.

Previous wording

We expect our R&D expenses to be relatively flat in 2024 over the prior year.

Current wording

We expect our R&D expenses to increase moderately in 2024 over the prior year due to an increase in expenses for our clinical programs.

Previous wording

Our G&A expenses increased by $3.7 million, or 27%, for the three months ended March 31, 2024, compared to the same period in the prior year. The increase for the three months ended March 31, 2024, compared to the prior year, was primarily due to higher personnel expenses and higher consulting expenses.

Current wording

Our G&A expenses increased by $1.6 million or 11% for the three months ended June 30, 2024, and increased by $5.3 million, or 19%, for the six months ended June 30, 2024, compared to the same period in the prior year. The increase for thethree and six months ended June 30, 2024, compared to the prior year, was primarily due to higher personnel expenses and higher consulting expenses.

Previous wording

Interest income increased by $0.5 million, or 7%, for the three months ended March 31, 2024, compared to the same period in the prior year, primarily due to higher interest income from our cash and money market accounts resulting from higher interest rates.

Current wording

Interest income decreased by $1.2 million or 15% for the three months ended June 30, 2024, anddecreased by $0.7 million, or 5%, for the six months ended June 30, 2024, compared to the same period in the prior year, primarily due to lower interest income from our cash and money market accounts resulting from lower cash balances.

Previous wording

Other expense, net for the three months ended March 31, 2024 and 2023, was primarily foreign exchange losses from transactions with vendors denominated in Euros.

Current wording

Other expense, net for thethree and six months ended June 30, 2024, and 2023, was primarily foreign exchange losses from transactions with vendors denominated in Euros.

Previous wording

The benefit from income taxes decreased by $0.7 million, or (24)%, for the three months ended March 31, 2024, compared to the same period in the prior year. The decrease in benefit from income taxes for the three months ended March 31, 2024, compared to the same period in the prior year, was primarily due to a decrease in the net amount capitalized as deferred tax assets related to Section 174 R&D Capitalization.

Current wording

The benefit from income taxes decreased by $2.3 million or 53% for thethree months ended June 30, 2024, and decreased by$3.0 million, or 41%, for the six months ended June 30, 2024, compared to the same period in the prior year. The decrease inbenefit from income taxes for thethree and six months ended June 30, 2024, compared to the same period in the prior year, was primarily due to a decrease in the net amount capitalized as deferred tax assets related to Section 174 R&D Capitalization.

Previous wording

Working capital was $522.6 million as of March 31, 2024, a decrease of $59.8 million from working capital of$582.4 million as of December 31, 2023. This decrease in working capital during the three months ended March 31, 2024, was primarily attributable to cash use of $81.6 million for operating expenses (adjusted to exclude non-cash charges) offset in part by net proceeds received from stock option exercises of approximately $0.9 million and interest income on investments of $7.2 million.

Current wording

Working capital was $539.2 million as of June 30, 2024, a decrease of $43.2 million from working capital of$582.4 million as of December 31, 2023. This decrease in working capital during the six months ended June 30, 2024, was primarily attributable to cash use of $155.2 million for operating expenses (adjusted to exclude non-cash charges) offset in part by$80.0 million option exercise payment from BMS, net proceeds received from interest income on investments of $13.7 million and to a lesser extent, stock option exercises of approximately $1.5 million.

Previous wording

As of March 31, 2024, we had $546.5 million in cash and cash equivalents. Although we believe, based on our current business plans, that our existing cash and cash equivalents will be sufficient to meet our obligations for at least the next twelve months, we anticipate that we will require additional capital in the future in order to continue the research and development of our drug candidates. Additionally, in order to develop and obtain regulatory approval for our potential products we will need to raise substantial additional funds. We expect to raise any such additional funds through public or private equity or debt financings, colla borative agreements with corporate partners, or other arrangements, including pursuant to the Amended Distribution Agreement (See Note 8, “Shareholders’ Equity” to the Condensed Consolidated Financial Statements for more information). We cannot assume that such additional financings will be available on acceptable terms, if at all, and such financings may only be available on terms dilutive to our shareholders.

Current wording

As of June 30, 2024, we had $564.1 million in cash and cash equivalents. Although we believe, based on our current business plans, that our existing cash and cash equivalents will be sufficient to meet our obligations for at least the next twelve months, we anticipate that we will require additional capital in the future in order to continue the research and development of our drug candidates. Additionally, in order to develop and obtain regulatory approval for our potential products we will need to raise substantial additional funds. We expect to raise any such additional funds through public or private equity or debt financings, colla borative agreements with corporate partners, or other arrangements, including pursuant to the Amended Distribution Agreement (See Note 8, “Shareholders’ Equity” to the Condensed Consolidated Financial Statements for more information). We cannot assume that such additional financings will be available on acceptable terms, if at all, and such financings may only be available on terms dilutive to our shareholders.

Previous wording

In managing our liquidity needs in Ireland, we do not rely on unrepatriated earnings as a source of funds. As of March 31, 2024, $226.2 million of our outstanding cash and cash equivalents related to U.S. operations are considered permanently reinvested. We do not intend to repatriate these funds. However, if these funds were repatriated back to Ireland, we would incur a withholding tax from the dividend distribution.

Current wording

In managing our liquidity needs in Ireland, we do not rely on unrepatriated earnings as a source of funds. As of June 30, 2024, $234.7 million of our outstanding cash and cash equivalents related to U.S. operations are considered permanently reinvested. We do not intend to repatriate these funds. However, if these funds were repatriated back to Ireland, we would incur a withholding tax from the dividend distribution.

Previous wording

The adequacy of our cash resources depends on many assumptions, including assumptions with respect to our expenses. These assumptions may prove to be wrong, and we could use our available capital resources sooner than we currently expect. Because of the numerous risks and uncertainties associated with the development and commercialization of our product candidates, we are unable to estimate the amounts of increased capital outlays and operating expenses associated with completing the development of our product candidates. Our future capital requirements will depend on numerous factors, including, without limitation, the timing of initiation, progress, results and costs of our clinical trials; the results of our research and nonclinical studies; the costs of clinical manufacturing and of establishing commercial manufacturing arrangements; the costs of preparing, filing and prosecuting patent applications and maintaining, enforcing and defending intellectual property-related claims; the costs and timing of capital asset purchases; our ability to establish research collaborations, strategic collaborations, licensing or other arrangements; the costs to satisfy our obligations under current and potential future collaborations; the costs of any in-licensing transactions; and the timing, receipt, and amount of revenues or royalties, if any, from any approved drug candidates.

Current wording

Because of the numerous risks and uncertainties associated with the development and commercialization of our product candidates, we are unable to estimate the amounts of increased capital outlays and operating expenses associated with completing the development of our product candidates. Our future capital requirements will depend on numerous factors, including, without limitation, the timing of initiation, progress, results and costs of our clinical trials; the results of our research and nonclinical studies; the costs of clinical manufacturing and of establishing commercial manufacturing arrangements; the costs of preparing, filing and prosecuting patent applications and maintaining, enforcing and defending intellectual property-related claims; the costs and timing of capital asset purchases; our ability to establish research collaborations, strategic collaborations, licensing or other arrangements; the costs to satisfy our obligations under current and potential future collaborations; the costs of any in-licensing transactions; and the timing, receipt, and amount of revenues or royalties, if any, from any approved drug candidates.

Previous wording

Net cash used in operating activities was $73.1 million for the three months ended March 31, 2024, which was primarily due to ongoing research and development activities and general and administrative expenses to support those activities for a total of $81.6 million in operating expenses (adjusted to exclude non-cash charges of approximately $10.5 million), cash paid for accounts payable, accruals and other liabilities and prepaid expenses, partially offsetby proceeds received from interest income on investments of $7.2 million, cash from collection of accounts receivable and proceeds from stock option exercises of approximately $0.9 million.

Current wording

Net cash used in operating activities was $57.1 million for the six months ended June 30, 2024, which was primarily due to ongoing research and development activities and general and administrative expenses to support those activities for a total of $155.2 million in operating expenses (adjusted to exclude non-cash charges of approximately $20.6 million), cash paid for accounts payable, accruals and other liabilities and prepaid expenses, partially offsetby proceeds received from interest income on investments of $13.7 million, cash from collection of accounts receivable and proceeds from stock option exercises of approximately $1.5 million.

Previous wording

Net cash used in investing activities was$103,000 for thethree months ended March 31, 2024, which primarily consisted of expenditures to purchase property and equipment.

Current wording

Net cash used in investing activities was$246,000 for thesix months ended June 30, 2024, which primarily consisted of expenditures to purchase property and equipment.

Previous wording

Net cash provided by financing activities was $0.8 million for thethree months ended March 31, 2024, primarily from proceeds from issuances of ordinary shares upon exercises of stock options of $0.9 million.

Current wording

Net cash provided by financing activities was $1.3 million for thesix months ended June 30, 2024, primarily from proceeds from issuances of ordinary shares upon exercises of stock options of $1.5 million.

Previous wording

Refer to “Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations — Liquidity and Capital Resources” in our first quarter 2023 Quarterly Report on Form 10-Q for a discussion of the cash flows for the three months ended March 31, 2023.

Current wording

Refer to “Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations — Liquidity and Capital Resources” in our second quarter 2023 Quarterly Report on Form 10-Q for a discussion of the cash flows for the six months ended June 30, 2023.

Previous wording

Our contractual obligations as of March 31, 2024, consisted of minimum cash payments under operating leases of $14.3 million, purchase obligations of $11.4 million (of which $6.7 million is included in current liabilities), and contractual obligations under license agreements of $0.3 million (of which nil is included in current liabilities). Purchase obligations consist of non-cancelable purchase commitments to suppliers. Operating leases represent our future minimum rental commitments under our non-cancelable operating leases. For additional information regarding the timing for our contractual obligations see Note 6, “Commitments and Contingencies” to Condensed Consolidated Financial Statements.

Current wording

Our contractual obligations as of June 30, 2024, consisted of minimum cash payments under operating leases of $13.7 million, purchase obligations of $7.9 million (of which $3.6 million is included in current liabilities), and contractual obligations under license agreements of $0.3 million (of which nil is included in current liabilities). Purchase obligations consist of non-cancelable purchase commitments to suppliers. Operating leases represent our future minimum rental commitments under our non-cancelable operating leases. For additional information regarding the timing for our contractual obligations see Note 6, “Commitments and Contingencies” to Condensed Consolidated Financial Statements.