What changed in this filing

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Item 2. Management’s Discussion and Analysis

2023-08-01 compared with 2023-05-09 · 329 added, 139 removed, 175 unchanged (73% of the section changed)

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GAAP”) and unless otherwise indicated are presented in U.S.

We are a leader in the field of gene therapy with a mission to reimagine the future of medicine by delivering innovative cures that transform human lives.

We are advancing a pipeline of innovative gene therapies, including our clinical candidates for the treatment of Huntington’s disease and amyotrophic lateral sclerosis (“ALS”), as well as preclinical product candidates including candidates for the treatment of refractory temporal lobe epilepsy (“rTLE’) and Fabry disease.

In November 2022 and February 2023, our internally developed HEMGENIX®, a gene therapy for the treatment of hemophilia B, was approved for commercialization by the United States Food and Drug Administration (“FDA”) and the European Medicines Agency (“EMA”), respectively.

In June 2020, we agreed to license HEMGENIX® to CSL Behring LLC (“ CSL Behring”), which is now responsible for commercialization of HEMGENIX®.

We are manufacturing HEMGENIX® for CSL Behring and are entitled to specific milestone payments and royalties on net sales.

We are a leader in the field of gene therapy, seeking to deliver to patients suffering from rare and other devasting diseases single treatments with potentially curative results.

We are advancing a focused pipeline of innovative gene therapies, including our clinical candidates for the treatment of Huntington’s disease and amyotrophic lateral sclerosis (“ALS”), as well as preclinical product candidates including candidates for the treatment of refractory temporal lobe epilepsy (“rTLE”) and Fabry disease.

In November 2022 and February 2023, our internally developed HEMGENIX®, a gene therapy for the treatment of hemophilia B, was approved for commercialization by the United States Food and Drug Administration (the “FDA”) and the European Medicines Agency (“EMA”), respectively.

In June 2020, we agreed to license HEMGENIX® to CSL Behring LLC (“CSL Behring”), pursuant to a commercialization and license agreement (the “Commercialization and License Agreement”), which is now responsible for commercialization of HEMGENIX®.

We are manufacturing HEMGENIX® for CSL Behring and are entitled to specific milestone payments and royalties on net sales under the Commercialization and License Agreement.

In May 2023, one of our wholly-owned subsidiaries entered into a royalty purchase agreement (the “Royalty Purchase Agreement”) with HemB SPV, L.P.

(the “Purchaser”) for the sale of a portion of the royalty rights due to us from CSL Behring under the Commercialization and License Agreement.

We believe our validated technology platform and manufacturing capabilities provide us distinct competitive advantages, including the potential to reduce development risk, cost, and time to market.

We produce our Adeno-associated virus (“ AAV”) -based gene therapies in our own facilities with a proprietary, commercial-scale, current good manufacturing practices (“cGMP”) -compliant, manufacturing process.

We believe our Lexington, Massachusetts-based facility is one of the world’s most versatile gene therapy manufacturing facilities.

We produce our Adeno-associated virus (“AAV”) based gene therapies in our own facilities with a proprietary, commercial-scale, current good manufacturing practices compliant, manufacturing process.

We believe our Lexington, Massachusetts-based facility is one of the world’s leading, most versatile, gene therapy manufacturing facilities.

Business developments

Below is a summary of our recent significant business developments:

Amyotrophic Lateral Sclerosis (AMT-162)

On January 31, 2023, we announced that we have entered into a global licensing agreement with Apic Bio for a one-time, intrathecally administered gene therapy for ALS caused by mutations in superoxide dismutase 1 (“SOD1”), a rapidly progressing, rare motor neuron disease that leads to loss of everyday functions and is uniformly fatal.

With this agreement, we have added to our pipeline of gene therapies to treat neurological disorders.

The FDA has cleared the investigational new drug application for APB-102 and has granted Orphan Drug and Fast Track designation.

Mutations in the SOD1 gene of ALS account for approximately one-fifth of all inherited forms of this fatal disease.

APB-102 is comprised of a recombinant AAVrh10 vector that expresses a miRNA designed to knock down the expression of SOD1 with the goal of slowing down or potentially reversing the progression of ALS in patients with SOD1 mutations.

We made an initial cash payment of $10.0 million to Apic Bio that was recognized as research and development expense.

Huntington’s disease program (AMT-130)

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We are currently conducting a randomized, controlled, and blinded Phase I/II clinical trial for AMT-130 in the U.S.

The lower-dose cohort of this trial includes 10 patients, of which six patients received treatment with AMT-130 and four patients received imitation surgery.

The higher-dose cohort includes 16 patients, of which 10 patients received treatment with AMT-130 and six patients received imitation surgery.

Patients receiving imitation surgery have the option to cross over after 12 months if they meet the inclusion criteria for the study.

We are also conducting an open-label Phase Ib/II study in the EU, which includes six patients in the lower-dose cohort and nine patients in the higher-dose cohort.

The low-dose cohort of this trial includes 10 patients, of which six patients received treatment with AMT-130 and four patients received imitation surgery.

The high-dose cohort includes 16 patients, of which 10 patients received treatment with AMT-130 and six patients received imitation surgery.

Patients in the high-dose cohort that received imitation surgery had the option to cross over after 12 months if they met the inclusion criteria for the study.

We are also conducting an open-label Phase Ib/II study in the EU, which includes six patients in the low-dose cohort and nine patients in the high-dose cohort.

All 15 patients in the EU study will receive AMT-130.

On March 21, 2022, we announced that we completed the enrollment of all 26 patients in the first two cohorts of our Phase I/II clinical trial of AMT-130 in the U.S.

In July 2022, we began crossing over patients who received the imitation surgical procedure.

Three of the six control patients in the higher-dose cohort have now crossed over to treatment.

Two of these three patients have received the higher dose of AMT-130.

On June 23, 2022, we announced that 10 patients in our Phase Ib/II study in the EU had been treated with AMT-130.

On June 23, 2022, we announced safety and biomarker data from the 10 patients enrolled in the low-dose U.S.

AMT-130 was generally well-tolerated with no serious adverse events related to AMT-130 reported in the treated patients.

In the four treated patients with evaluable data, mean levels of mutant Huntingtin protein in the cerebral spinal fluid (“CSF mHTT”) declined at all timepoints compared to baseline, and decreased by 53.8% at 12 months of follow-up.

In the six treated patients, measurements of neurofilament lights chain in the cerebral spinal fluid (“CSF NfL”) initially increased as expected following the AMT-130 surgical procedure and declined thereafter, nearing baseline at 12 months of follow-up.

Select research programs

In the third quarter of 2022, we initiated a Good Laboratory Practices (“GLP”) toxicology study in non-human primates for AMT-260, a gene therapy product candidate for the treatment of refractory temporal lobe epilepsy (“rTLE”).

In the third quarter of 2022, we initiated a GLP toxicology study in non-human primates for AMT-191, a gene therapy product candidate for the treatment of Fabry disease.

CSL Behring commercialization and license agreement (“CSL Behring Agreement”)

In November 2022, the FDA approved the marketing application for HEMGENIX ® in the U.S., and in February 2023 the European Medicines Agency (“EMA”) approved the marketing application for the EU.

In July 2022, we began crossing over patients in the high-dose cohort who received the imitation surgical procedure.

Four of the six control patients in the high-dose cohort have been crossed over to treatment (three patients received the high dose and one patient received the low dose).

The remaining two control patients in the high-dose cohort did not meet all the inclusion criteria for the study and were not eligible for crossover.

All four crossover patients received a short course of immunosuppression therapy concurrent with the administration of AMT-130.

On June 23, 2022, we announced that all six patients in the low-dose cohort in our Phase Ib/II study in the EU had been treated with AMT-130.

We have continued to make progress enrolling the second, high-dose cohort of nine patients.

On June 21, 2023, we announced interim data, including up to 24-month follow-up, from 26 patients enrolled in the ongoing U.S.

Phase I/II clinical trial of AMT-130.

Efficacy and biomarker data from the crossover patients are not included in the summary below.

Safety and tolerability

We believe AMT-130 was generally well-tolerated, with a manageable safety profile in patients treated with the lower dose of 6x10 12 vector genomes and the higher dose of 6x10 13 vector genomes.

The most common adverse events in the treatment groups were related to the surgical procedure.

No treatment emergent adverse events led to discontinuation of patient follow-up.

As previously reported, there were two serious adverse events (“SAEs”) unrelated to AMT-130 (post-operative delirium and major depression) in the low-dose cohort, one SAE in the high-dose cohort (back pain), and one SAE (deep vein thrombosis) in the control group.

In addition, there were two suspected unexpected serious adverse events (severe headache, central nervous system inflammation) in the high-dose cohort.

All the events have resolved to our knowledge.

Exploratory efficacy data

We believe early clinical data demonstrate promising trends.

Compared to baseline measurements, clinical function was generally preserved at 24 months for patients in the low-dose cohort and at 12 months for patients in the high-dose cohort.

Compared to natural history, patients in both dose cohorts demonstrated benefits in each of Total Motor Score (“TMS”), Total Functional Capacity (“TFC”) and the composite Unified Huntington’s Disease Rating Scale (“cUHDRS”).

Compared to natural history:

● TMS of patients in the lower dose cohort showed a mean improvement of 1.8 points at 24 months and patients in the higher dose cohort demonstrated a mean improvement of 2.7 points at 12 months;

● TFC of patients in the lower dose cohort showed a mean 0.8 point improvement at 24 months and patients in the higher dose cohort demonstrated a mean 0.5 point improvement at 12 months;

● the cUHDRS of patients in the lower dose cohort showed a mean 0.9 point improvement in cUHDRS at 24 months and patients in the higher dose cohort demonstrated a mean 1.0 point improvement at 12 months.

Patients in the control group appear to experience a worsening of TMS at 12 months compared to baseline and natural history.

TFC and cUHDRS was preserved in control patients at 12 months.

Patients experienced a transient increase in neurofilament lights chain in the cerebral spinal fluid (“CSF NfL”) related to the procedure that peaked at approximately one month after administration.

These transient increases were not dose-dependent, and all patients experienced subsequent declines in CSL NfL.

Mean CSF NfL for the lower dose cohort was 12.9% below baseline compared to a predicted 22.9% increase in the natural history, with four of the five patients in the lower dose cohort having CSF NfL levels below baseline.

CSF NfL levels in the higher dose cohort were more variable through 12 months, with a mean increase of 51.5% compared to baseline.

Four of the eight patients in the higher dose cohort with at least 12 months of follow-up had NfL levels below baseline.

Two patients in the higher dose cohort with 18 months of follow-up demonstrated a continued decline in CSF NfL to 27.4% above baseline.

In the control group, mean CSF NfL was relatively stable and was 6.83% below baseline at 12 months.

Mutant huntingtin protein in the cerebral spinal fluid (“CSF mHTT”) for patients in the lower dose cohort remained below baseline with a mean reduction of 8.1% at 24 months.

CSF mHTT for patients in the higher dose cohort was more variable with a mean increase of 39.7% above baseline at 12 months compared to a 4.7% increase in the control group.

Three of nine evaluable patients in the higher dose cohort had CSF mHTT reduction below baseline at their last measurement.

The mean total brain volume for the control, lower dose and higher dose cohorts declined 0.74%, 1.02% and 1.23%, respectively at 12 months and were not significantly different from each other or from the natural history.

The mean total brain volume for the control, low-dose and high-dose cohorts declined 0.74%, 1.02% and 1.23%, respectively at 12 months and do not appear to be significantly different from each other or from the natural history.

CSL Behring commercialization and license agreement

In June 2023, the first sale of HEMGENIX® in the U.S.

occurred, and in July 2023 we collected the $100.0 million owed to us under the CSL Behring Agreement.

Royalty Financing Agreement

On May 12, 2023, we entered into the Royalty Financing Agreement with the Purchaser.

Under the terms of the Royalty Financing Agreement, we received an upfront payment of $375.0 million in exchange for the Purchaser’s rights to the lowest royalty tier on CSL Behring’s worldwide net sales of HEMGENIX® for certain current and future royalties due to us.

We are also eligible to receive an additional $25.0 million milestone payment under the Royalty Financing Agreement if 2024 net sales of HEMGENIX® exceed a pre-specified threshold.

The Purchaser will receive 1.85 times the upfront payment (or $693.8 million) and 1.85 times the $25.0 million milestone payment (if paid) until June 30, 2032 (“First Hard Cap Date”) or, if such cap is not met by June 30, 2032, up to 2.25 times the upfront and milestone payment (if paid) through December 31, 2038.

If 2024 net sales do not exceed a pre-specified threshold, we will be obligated to pay $25.0 million to the Purchaser but only to the extent that we achieve a future sales milestone under the CSL Behring Agreement.

If such milestone payment is not due from CSL Behring, we are not obligated to pay any amounts to the Purchaser.

We retained the rights to all other royalties, as well as contractual milestones totaling up to $1.5 billion, under the terms of the CSL Behring Agreement.

As a result of this transaction and the first U.S.

sale of HEMGENIX® in which we collected $100.0 million owed to us, we believe our cash and cash equivalents will fund our operations through the second quarter of 2026.

Hercules Amendment

On May 12, 2023 we and Hercules amended the 2021 Restated Facility (“2023 Amended Facility”).

The 2023 Amended Facility extends the maturity date and interest-only period from December 1, 2025 to January 5, 2027.

Amyotrophic Lateral Sclerosis (AMT-162)

On January 31, 2023, we announced that we had entered into a global licensing agreement with Apic Bio, Inc.

(“Apic Bio”) for a one-time, intrathecally administered investigational gene therapy for ALS caused by mutations in superoxide dismutase 1 (“SOD1”), a rapidly progressing, rare motor neuron disease that leads to loss of everyday functions and is uniformly fatal.

With this agreement, we have added to our pipeline of gene therapies to treat neurological disorders.

The FDA has cleared the investigational new drug application for APB-102 and has granted Orphan Drug and Fast Track designation.

Mutations in the SOD1 gene of ALS account for approximately one-fifth of all inherited forms of this fatal disease.

APB-102 is comprised of a recombinant AAVrh10 vector that expresses a micro ribonucleic acids (“miRNA”) designed to knock down the expression of SOD1 with the goal of slowing down or potentially reversing the progression of ALS in patients with SOD1 mutations.

We made an initial cash payment of $10.0 million to Apic Bio that was recognized as a research and development expense.

We owe up to $43.0 million in milestone payments to Apic Bio if AMT-162 is approved for commercialization in the U.S.

Financial Overview

Key components of our results of operations include the following:

Three months ended March 31,

Three months ended June 30,

Six months ended June 30,

(in thousands)

Total revenues

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Selling, general and administrative expenses

As of March 31, 2023 and December 31, 2022, we had cash and cash equivalents and investment securities of $315.3 million and $392.8 million, respectively.

We had a net loss of $77.2 million in the three months ended March 31, 2023, compared to net loss of $46.7 million for the same period in 2022.

As of March 31, 2023 and December 31, 2022, we had accumulated deficits of $659.2 million and $581.9 million, respectively.

As of June 30, 2023 and December 31, 2022, we had cash and cash equivalents and investment securities of $628.6 million and $392.8 million, respectively.

We had a net loss of $68.5 million and $145.7 million in the three and six months ended June 30, 2023, respectively, compared to net loss of $39.1 million and $85.7 million for the same period in 2022.

As of June 30, 2023 and December 31, 2022, we had accumulated deficits of $727.6 million and $581.9 million, respectively.

We anticipate that our expenses will increase for the foreseeable future and will include costs related to:

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● advancing our gene therapy programs for rTLE, SOD1-ALS and Fabry disease into Phase I/II clinical studies;

● making potential future milestone payments related to the acquisition of Corlieve Therapeutics SAS (“uniQure France SAS”), if any;

● potentially acquiring or in-licensing rights to new therapeutic targets, product candidates and technologies.

● advancing preclinical research and development for gene therapy product candidates targeting diseases other than those listed above;

● making potential future milestone payments related to the acquisition of Corlieve Therapeutics SAS (“Corlieve”), if any;

● continuing to invest in expanding, developing and optimizing our manufacturing capabilities and other enabling technologies, such as next-generation viral vectors, promoters and re-dosing.

See “Results of Operations” below for a discussion of the detailed components and analysis of the amounts above.

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A summary of our critical accounting policies as well as a discussion of our critical accounting estimates are presented in our Annual Report .

There were no material changes to our critical accounting policies during the three months ended March 31, 2023 or reasonably possible changes of our critical accounting estimates as of March 31, 2023 that could have had a material impact on our results of operations for the three- month period ended March 31, 2023.

There were no material changes to our critical accounting policies during the six months ended June 30, 2023 or reasonably possible changes of our critical accounting estimates as of June 30, 2023 that could have had a material impact on our results of operations for the three and six months ended June 30, 2023.

Cost of contract manufacturing

We entered into a development and commercial supply agreement with CSL Behring in June 2020.

Since April 1, 2022, we recognize cost to manufacture HEMGENIX® under such agreement as cost of contract manufacturing.

Since April 1, 2022, we recognize the cost to manufacture HEMGENIX® under such agreement as cost of contract manufacturing.

Research and development expenses

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● costs associated with research activities for enabling technology platforms, such as next-generation vectors, promoters and re-administration of gene therapies;

● costs associated with the rendering of collaboration services as well as the continued development of etranacogene dezaparvovec (the “Product”);

● costs associated with the rendering of collaboration services;

● payments related to identifiable intangible assets without an alternative future use;

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● facilities, depreciation, and other expenses, which include direct and allocated expenses for rent and maintenance of facilities, insurance, and other supplies;

● changes in the fair value of liabilities recorded in relation to our acquisition of Corlieve.

● changes in the fair value of liabilities recorded in relation to our acquisition of uniQure France SAS.

Our R&D expenses may vary substantially from period to period based on the timing of our research and development activities, including manufacturing campaigns, regulatory submissions, and enrollment of patients in clinical trials.

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We incurred expenses associated with operating as a public company, including expenses for personnel, legal, accounting and audit fees, board of directors’ costs, directors' and officers' liability insurance premiums, Nasdaq listing fees, expenses related to investor relations and fees related to business development and maintaining our patent and license portfolio.

Our selling costs include advisory fees related to obtaining the CSL Behring Agreement.

Other items, net

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Our other expense primarily consists of expenses we incur in relation to our subleasing income.

Comparison of the three months ended March 31, 2023 and 2022

The following table presents a comparison of our results of operations for the three months ended March 31, 2023 and 2022.

Three months ended March 31,

Results of Operations

Comparison of the three months ended June 30, 2023 and 2022

The following table presents a comparison of our results of operations for the three months ended June 30, 2023 and 2022.

Three months ended June 30,

(in thousands)

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Operating expenses:

Cost of contract manufacturing

Research and development expenses

Selling, general and administrative expenses

Total operating expenses

Other expense

Loss from operations

Other non-operating items, net

Net loss before income tax (expense) / benefit

Income tax (expense) / benefit

Our revenue for the three months ended June 30, 2023 and 2022 was as follows:

Three months ended June 30,

(in thousands)

License revenues

Contract manufacturing revenues

Collaboration revenues

Total revenues

License revenue

We recognize royalty revenues from CSL Behring, related to HEMGENIX® sales, when earned.

For the three months ended June 30, 2023, we recognized $0.8 million of license revenues (nil for the same period in 2022).

Contract manufacturing revenues

We recognize contract manufacturing revenue related to contract manufacturing HEMGENIX® for CSL Behring.

Contract manufacturing revenue is realized when earned upon sales of HEMGENIX® to CSL Behring.

We recognized $1.3 million contract manufacturing revenues in the three months ended June 30, 2023, compared to nil for the same period in 2022.

We did not recognize such revenues in the three months ended June 30, 2022, as we started contract manufacturing activities to supply CSL Behring with launch supplies of HEMGENIX® following their submission of a Biologics License Application (“BLA”) and MAA in the spring of 2022 .

Collaboration revenues

We provide services to CSL Behring in accordance with the CSL Behring Agreement.

We entered into collaboration, research, and license agreements with Bristol-Myers Squibb (“BMS”) in 2015 which were terminated on February 21, 2023.

For the three months ended June 30, 2023, we recognized $0.3 million and nil of collaboration revenue for CSL Behring and BMS, respectively.

For the three months ended June 30, 2022, we recognized nil and $0.5 million of collaboration revenue for CSL Behring and BMS, respectively.

Cost of contract manufacturing

We incurred $1.4 million of cost of contract manufacturing related to the manufacture of HEMGENIX® in the three months ended June 30, 2023, compared to $0.8 million cost of contract manufacturing in the three months ended June 30, 2022.

R&D expenses for the three months ended June 30, 2023 were $46.0 million, compared to $46.2 million for the same period in 2022.

Other research and development expenses are separately classified in the table below.

These other expenses are not allocated as they are deployed across multiple projects under development.

R&D expenses for the three months ended June 30, 2023 were $46.0 million, compared to $46.2 million for the same period in 2022.

Other research and development expenses are separately classified in the table below.

These other expenses are not allocated as they are deployed across multiple projects under development.

Three months ended June 30,

(in thousands)

Huntington's disease (AMT-130)

Temporal lobe epilepsy (AMT-260)

Amyotrophic lateral sclerosis (AMT-162)

Fabry disease (AMT-191)

Etranacogene dezaparvovec (AMT-060/061)

Programs in preclinical development and platform related expenses

Total direct research and development expenses

Employee and contractor-related expenses

Facility expenses

Share-based compensation expense

Other expenses

Fair value changes related to contingent consideration

Total other research and development expenses

Total research and development expenses

Direct research and development expenses

Huntington’s disease (AMT-130)

In the three months ended June 30, 2023 and June 30, 2022, our external costs for the development of AMT-130 were primarily related to the execution of our Phase I/II clinical trials in the United States and in Europe.

Temporal lobe epilepsy (AMT-260)

In the three months ended June 30, 2023 and June 30, 2022, we incurred $2.5 million and $6.3 million respectively, for the preclinical development of AMT-260.

Our expenses in the three months ended June 30, 2022 included additional costs related to a toxicology study.

Amyotrophic Lateral Sclerosis caused by mutations in SOD1 (AMT-162)

On January 31, 2023, we entered into a global licensing agreement with Apic Bio for AMT-162.

In the three months ended June 30, 2023, we incurred $0.6 million of costs (nil in the prior period), related to our preclinical activities for AMT-162.

Fabry disease (AMT-190)

In the three months ended June 30, 2023 and June 30, 2022, we incurred $0.4 million and $0.5 million of costs, respectively, related to our preclinical research of AMT-190.

Etranacogene dezaparvovec (AMT-060/061)

We have incurred external costs for our hemophilia B program related to the execution of our Phase III clinical trial and the long-term follow-up of patients in our Phase I/II clinical trial of AMT-060 and our Phase IIb clinical trial of etranacogene dezaparvovec.

CSL Behring is responsible for the clinical and regulatory activities and commercialization of the Product.

However, we managed the trials on behalf of CSL Behring until such responsibilities were transitioned to CSL Behring in December 2022.

Direct research and development expenses related to clinical development and other regulatory activities and commercialization expenses incurred in the three months ended June 30, 2023 and June 30, 2022 are presented net of reimbursements due from CSL Behring and include settlement amounts from the transition.

Preclinical programs & platform development

In the three months ended June 30, 2023, and June 30, 2022, we incurred $2.3 million and $1.7 million of costs, respectively, primarily related to our preclinical activities associated with product candidates for various other research programs and technology innovation projects.

Other research & development expenses

● We incurred $17.8 million in personnel and contractor-related expenses in the three months ended June 30, 2023, compared to $15.1 million for the same period in 2022.

The increase was primarily a result of an increase in personnel and contractor-related expenses to support our growth;

● We incurred $7.7 million in operating expenses and depreciation expenses related to our rented facilities in the three months ended June 30, 2023, compared to $5.4 million in the same period in 2022.

The increase primarily related to additional sites in Lexington, Massachusetts which commenced in May and November 2022;

● We incurred $5.9 million in disposable costs in the three months ended June 30, 2023, compared to $4.5 million for the same period in 2022;

● We incurred $4.7 million in share-based compensation expenses in the three months ended June 30, 2023, compared to $4.3 million for the same period in 2022;

● We incurred $1.8 million of other expenses for the three months ended June 30, 2023, compared to $2.1 million for the same period in 2022;

● We incurred $0.2 million of expenses in the three months ended June 30, 2023 related to an increase in the fair value of contingent consideration associated with the acquisition of uniQure France SAS, compared to $0.2 million decrease in fair value for the same period in 2022.

Selling, general and administrative expenses

Selling, general and administrative expenses for the three months ended June 30, 2023 were $21.2 million, compared to $12.5 million for the same period in 2022.

● We incurred $6.4 million in personnel and contractor-related expenses in the three months ended June 30, 2023, compared to $5.2 million in the same period in 2022.

The increase was primarily as a result of an increase in personnel and contractor-related expenses to support our growth;

● We incurred $4.0 million in share-based compensation expenses in the three months ended June 30, 2023, compared to $3.4 million in the same period in 2022.

The increase was primarily a result of an increase in awards granted, including those to newly recruited personnel;

● We incurred $2.5 million in professional fees in the three months ended June 30, 2023, compared to $1.5 million in the same period in 2022.

We regularly incur accounting, audit and legal fees associated with operating as a public company;

● We incurred $3.8 million in financial advisory fees in relation to our licensing transaction with CSL Behring in the three months ended June 30, 2023 (nil in prior period);

● We incurred $3.

2 million in other operating expenses in the three months ended June 30, 2023, compared to $1.9 million in the same period in 2022.

The increase was primarily a result of an increase in information technology expenses to support operational improvements within the Company.

Other items, net

We recognized $1.2 million in other income from payments received from European authorities to subsidize our research and development efforts in the Netherlands in the three months ended June 30, 2023, compared to $2.6 million for the same period in 2022.

Other items, net for the periods presented primarily related to income from the subleasing of our Amsterdam facility and expenses we incur in relation to the subleasing facility.

Other non-operating items, net

Our other non-operating items, net, for the three months ended June 30, 2023 and 2022 were as follows:

Three months ended June 30,

(in thousands)

Interest income

Interest expense

Foreign currency gains, net

Other non-operating losses

Total other non-operating income, net

We recognize interest income associated with our cash and cash equivalents and investment securities.

We recognized $3.2 million in interest income in the three months ended June 30, 2023, compared to $0.0 million in the same period in the prior year.

Our interest income increased by $3.2 primarily due to the interest income earned on investment securities as well as cash on hand during the three months ended June 30, 2023.

We recognized $6.8 million in interest expense for the three months ended June 30, 2023 and $2.7 million for the three months ended June 30, 2022.

Our interest expense in 2023 increased due to an increase in market interest rates related to the Hercules debt as well as the recognition of $3.2 million of interest expense related to the Royalty Financing Agreement.

We hold monetary items and enter into transactions in foreign currencies, predominantly in euros and U.S.

We recognize foreign exchange results related to changes in these foreign currencies.

We recognized a net foreign currency gain, related to our borrowings from Hercules, the Royalty Financing Agreement and our cash and cash equivalents and investment securities as well as loans between entities within the uniQure group, of $0.4 million during the three months ended June 30, 2023, compared to a net gain of $19.4 million during the same period in 2022.

We recognized fair value changes related to the derivative financial liability related to a contingent payment due to BMS upon the consummation of a change of control transaction in the period ended June 30, 2022 (nil in the period ended June 30, 2023).

As of December 31, 2022, we derecognized the derivative financial liability.

Income tax benefit

We recognized $0.2 million of deferred tax expense in the three months ended June 30, 2023, and $0.3 million of deferred tax benefit for the same period in 2022.

Comparison of the six months ended June 30, 2023 and 2022

The following table presents a comparison of our results of operations for the six months ended June 30, 2023 and 2022:

Six months ended June 30,

(in thousands)

Total revenues

Operating expenses:

Cost of contract manufacturing revenues

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Income tax benefit

Our revenue for the three months ended March 31, 2023 and 2022 was as follows:

Three months ended March 31,

Our revenue for the six months ended June 30, 2023 and 2022 was as follows:

Six months ended June 30,

(in thousands)

License revenues

Contract manufacturing revenues

1 unchanged sentence

Total revenues

Collaboration revenues

We entered into collaboration, research, and license agreements with Bristol-Myers Squibb (“BMS”) in 2015 which were terminated on February 21, 2023.

For the three months ended March 31, 2023, we recognized $0.4 million and nil of collaboration revenue for CSL Behring and BMS, respectively.

For the three months ended March 31, 2022, we recognized $1.4 million and $0.4 million of collaboration revenue for CSL Behring and BMS, respectively.

License revenue

We recognize royalty revenues from CSL Behring, related to HEMGENIX® sales, when earned.

For the six months ended June 30, 2023, we recognized $0.8 million of license revenue (nil for the same period in 2022).

Contract manufacturing revenues

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Contract manufacturing revenue is realized when earned upon sales of HEMGENIX® to CSL Behring.

We recognized $4.9 million contract manufacturing revenues in the three months ended March 31, 2023, compared to nil for the same period in 2022.

We did not recognize such revenues in the three months ended March 31, 2022, as we started contract manufacturing activities to supply CSL Behring with launch supplies of HEMGENIX® following their submission of a BLA and MAA in the spring of 2022 .

We recognized $6.2 million contract manufacturing revenues in the six months ended June 30, 2023, compared to nil for the same period in 2022.

We did not recognize such revenues in the six months ended June 30, 2022, as we started contract manufacturing activities to supply CSL Behring with launch supplies of HEMGENIX® following their submission of a BLA and MAA in the spring of 2022 .

Collaboration revenues

We provide services to CSL Behring in accordance with the CSL Behring Agreement.

We entered into collaboration, research, and license agreements with Bristol-Myers Squibb (“BMS”) in 2015 which were terminated on February 21, 2023.

For the six months ended June 30, 2023, we recognized $0.7 million and nil of collaboration revenue for CSL Behring and BMS, respectively.

For the six months ended June 30, 2022, we recognized $1.4 million and $0.8 million of collaboration revenue for CSL Behring and BMS, respectively.

Cost of contract manufacturing

We incurred $2.4 million of cost of contract manufacturing related to the manufacture of the Product in the three months ended March 31, 2023, compared to nil cost of contract manufacturing in the three months ended March 31, 2022.

R&D expenses for the three months ended March 31, 2023 were $60.8 million, compared to $45.0 million for the same period in 2022.

We incurred $3.8 million of cost of contract manufacturing related to the manufacture of HEMGENIX® in the six months ended June 30, 2023, compared to $0.8 million cost of contract manufacturing in the six months ended June 30, 2022.

R&D expenses for the six months ended June 30, 2023 were $106.8 million, compared to $91.2 million for the same period in 2022.

Other research and development expenses are separately classified in the table below.

These other expenses are not allocated as they are deployed across multiple projects under development.

Three months ended March 31,

Six months ended June 30,

(in thousands)

Amyotrophic lateral sclerosis (AMT-162)

Temporal lobe epilepsy (AMT-260)

Huntington's disease (AMT-130)

Programs in preclinical development and platform related expenses

Temporal lobe epilepsy (AMT-260)

Fabry disease (AMT-191)

Etranacogene dezaparvovec (AMT-060/061)

Programs in preclinical development and platform related expenses

Total direct research and development expenses

8 unchanged sentences

Amyotrophic Lateral Sclerosis caused by mutations in SOD1 (AMT-162)

On January 31, 2023, we announced that we entered into a global licensing agreement with Apic Bio for AMT-162.

We have incurred $10.0 million expenses recorded to research and development expense in relation to the

acquisition of assets without an alternative future use during the three-month period ended March 31, 2023.

If and when we complete research and development activities for AMT-162 and AMT-162 is approved in the U.S.

and Europe, we will expense up to $43.0 million in milestone payments contractually owed to Apic Bio.

On January 31, 2023, we entered into a global licensing agreement with Apic Bio for AMT-162.

We have incurred $10.6 million expenses recorded to research and development expense in relation to the acquisition of assets without an alternative future use during the six-month period ended June 30, 2023.

Huntington’s disease (AMT-130)

In the six months ended June 30, 2023 and June 30, 2022, our external costs for the development of AMT-130 were primarily related to the execution of our Phase I/II clinical trials in the U.S.

and in Europe.

Temporal lobe epilepsy (AMT-260)

In the three months ended March 31, 2023 and March 31, 2022, we incurred $4.3 million and $2.6 million respectively, for the preclinical development of temporal lobe epilepsy.

Huntington disease (AMT-130)

In the three months ended March 31, 2023 and March 31, 2022, our external costs for the development of AMT-130 were primarily related to the execution of our Phase I/II clinical trial in the United States and in Europe.

Preclinical programs & platform development

In the three months ended March 31, 2023, and March 31, 2022, we incurred $1.9 million and $1.3 million of costs, respectively, primarily related to our preclinical activities associated with product candidates for various other research programs and technology innovation projects.

In the six months ended June 30, 2023 and June 30, 2022, we incurred $7.3 million and $8.9 million respectively, for the preclinical development of AMT-260.

Fabry disease (AMT-190)

In the three months ended March 31, 2023 and March 31, 2022, we incurred $1.1 million and $0.6 million of costs, respectively, related to our preclinical activities for the treatment of Fabry disease (AMT-190).

Hemophilia B (AMT-060/061)

In the six months ended June 30, 2023 and June 30, 2022, we incurred $1.5 million and $1.1 million of costs, respectively, related to our preclinical research of AMT-190.

Etranacogene dezaparvovec (AMT-060/061)

CSL Behring is responsible for the clinical and regulatory activities and commercialization of the Product.

However, we managed the existing trials on behalf of CSL Behring until such responsibilities were transitioned to CSL Behring in December 2022.

Direct research and development expenses related to clinical development and other regulatory activities and commercialization expenses incurred in the three months ended March 31, 2023 and March 31, 2022 are presented net of reimbursements due from CSL Behring and include settlement amounts from the transition.

However, we managed the trials on behalf of CSL Behring until such responsibilities were transitioned to CSL Behring in December 2022.

Direct research and development expenses related to clinical development and other regulatory activities and commercialization expenses incurred in the six months ended June 30, 2023 and June 30, 2022 are presented net of reimbursements due from CSL Behring and include settlement amounts from the transition.

Preclinical programs & platform development

In the six months ended June 30, 2023, and June 30, 2022, we incurred $4.1 million and $3.0 million of costs, respectively, primarily related to our preclinical activities associated with product candidates for various other research programs and technology innovation projects.

Other research & development expenses

● We incurred $18.7 million in personnel and contractor-related expenses in the three months ended March 31, 2023, compared to $16.2 million for the same period in 2022.

● We incurred $36.5 million in personnel and contractor-related expenses in the six months ended June 30, 2023, compared to $31.2 million for the same period in 2022.

The increase was primarily a result of an increase in personnel and contractor-related expenses to support our growth;

● We incurred $6.8 million in operating expenses and depreciation expenses related to our rented facilities in the three months ended March 31, 2023, compared to $5.3 million in the same period in 2022.

● We incurred $14.5 million in operating expenses and depreciation expenses related to our rented facilities in the six months ended June 30, 2023, compared to $10.7 million in the same period in 2022.

The increase primarily related to additional sites in Lexington which commenced in May and November 2022;

● We incurred $4.4 million of other expenses for the three months ended March 31, 2023, compared to $2.6 million for the same period in 2022.

The increase primarily related to contractual payments of $3.1 million we owed to a licensor upon the Europeans Medicines Agency approval of HEMGENIX® in February 2023 partially offset by a reduction in consultant-related expenses;

● We incurred $4.3 million in share-based compensation expenses in the three months ended March 31, 2023, compared to $4.1 million for the same period in 2022;

● We incurred $3.9 million in disposable costs in the three months ended March 31, 2023, compared to $4.5 million for the same period in 2022;

● We incurred $1.0 million of expenses in the three months ended March 31, 2023 related to an increase in the fair value of contingent consideration associated with the acquisition of Corlieve, compared to $2.2 million for the same period in 2022.

● We incurred $9.8 million in disposable costs in the six months ended June 30, 2023, compared to $9.1 million for the same period in 2022;

● We incurred $9.0 million in share-based compensation expenses in the six months ended June 30, 2023, compared to $8.4 million for the same period in 2022;

● We incurred $5.7 million of other expenses for the six months ended June 30, 2023, compared to $4.7 million for the same period in 2022.

The increase primarily related to contractual payments of $3.1 million we owed to a licensor upon the Europeans Medicines Agency approval of HEMGENIX® in February 2023, which were partially offset by a reduction in consultant-related expenses;

● We incurred $1.2 million of expenses in the six months ended June 30, 2023 related to an increase in the fair value of contingent consideration associated with the acquisition of uniQure France SAS, compared to $2.0 million for the same period in 2022.

Selling, general and administrative expenses

Selling, general and administrative expenses for the three months ended March 31, 2023 were $17.8 million, compared to $11.0 million for the same period in 2022.

● We incurred $5.9 million in personnel and contractor-related expenses in the three months ended March 31, 2023, compared to $4.4 million in the same period in 2022.

Selling, general and administrative expenses for the six months ended June 30, 2023 were $39.0 million, compared to $23.5 million for the same period in 2022.

● We incurred $12.4 million in personnel and contractor-related expenses in the six months ended June 30, 2023, compared to $9.5 million in the same period in 2022.

The increase was primarily as a result of an increase in personnel and contractor-related expenses to support our growth;

● We incurred $3.7 million in share-based compensation expenses in the three months ended March 31, 2023, compared to $2.8 million in the same period in 2022.

The increase was primarily a result of an increase in awards granted, including those to newly recruited personnel as well as an increase in expense related to performance share units;

● We incurred $3.2 million in professional fees in the three months ended March 31, 2023, compared to $1.1 million in the same period in 2022.

● We incurred $7.8 million in share-based compensation expenses in the six months ended June 30, 2023, compared to $6.2 million in the same period in 2022.

The increase was primarily a result of an increase in awards granted, including those to newly recruited personnel;

● We incurred $5.7 million in professional fees in the six months ended June 30, 2023, compared to $2.7 million in the same period in 2022.

We regularly incur accounting, audit and legal fees associated with operating as a public company.

The increase from the prior period is primarily related to an increase in professional fees related to our global licensing agreement with Apic Bio.

The increase from the prior period includes an increase in professional fees related to our global licensing agreement with Apic Bio;

● We incurred $3.8 million in financial advisory fees in relation to our licensing transaction with CSL Behring in the six months ended June 30, 2023 (nil in prior period);

● We incurred $2.4 million in intellectual property fees including registration and professional fees in the six months ended June 30, 2023 compared to $0.7 million in the same period in 2022.

The increase mainly related to an increase in professional fees;

● We incurred $6.

2 million in other operating expenses in the six months ended June 30, 2023, compared to $3.9 million in the same period in 2022.

The increase was primarily a result of an increase in information technology expenses to support operational improvements within the Company.

Other items, net

We recognized $1.3 million in other income from payments received from European authorities to subsidize our research and development efforts in the Netherlands in the three months ended March 31, 2023, compared to $0.0 million for the same period in 2022.

We recognized $2.5 million in other income from payments received from European authorities to subsidize our research and development efforts in the Netherlands in the six months ended June 30, 2023, compared to $2.7 million for the same period in 2022.

Other items, net for the periods presented, primarily related to income from the subleasing of our Amsterdam facility and expenses we incur in relation to the subleasing facility.

Other non-operating items, net

Our other non-operating items, net, for the three months ended March 31, 2023 and 2022 were as follows:

Three months ended March 31,

Our other non-operating items, net, for the six months ended June 30, 2023 and 2022 were as follows:

Six months ended June 30,

(in thousands)

5 unchanged sentences

We recognize interest income associated with our cash and cash equivalents and investment securities.

We recognized $1.7 million in interest income in the three months ended March 31, 2023, compared to $0.0 million in the same period in the prior year.

Our interest income increased by $1.7 primarily due to the interest income earned on investment securities made during the three months ended December 31, 2022.

We recognized $3.6 million in interest expense for the three months ended March 31, 2023 and $2.5 million for the three months ended March 31, 2022.

Our interest expense in 2023 increased due to an increase in market interest rates.

We recognized $4.9 million in interest income in the six months ended June 30, 2023, compared to $0.1 million in the same period in the prior year.

Our interest income increased by $4.8 million primarily due to the interest income earned on investment securities as well as cash on hand during the six months ended June 30, 2023.

We recognized $10.4 million in interest expense for the six months ended June 30, 2023 and $5.2 million for the six months ended June 30, 2022.

We hold monetary items and enter into transactions in foreign currencies, predominantly in euros and U.S.

We recognize foreign exchange results related to changes in these foreign currencies.

We recognized a net foreign currency loss, related to our borrowings from Hercules and our cash and cash equivalents and investment securities as well as loans between entities within the uniQure group, of $2.4 million during the three months ended March 31, 2023, compared to a net gain of $8.6 million during the same period in 2022.

We recognized fair value changes related to the derivative financial liability related to a contingent payment due to BMS upon the consummation of a change of control transaction in the period ended March 31, 2022 (nil in the period ended March 31, 2023).

We recognized a net foreign currency loss, related to our borrowings from Hercules, the Royalty Financing Agreement and our cash and cash equivalents and investment securities as well as loans between entities within the uniQure group, of $2.0 million during the six months ended June 30, 2023, compared to a net gain of $28.0 million during the same period in 2022.

We recognized fair value changes related to the derivative financial liability related to a contingent payment due to BMS upon the consummation of a change of control transaction in the six months ended June 30, 2022 (nil in the same period ended June 30, 2023).

As of December 31, 2022, we derecognized the derivative financial liability.

Income tax benefit

We recognized $1.2 million of deferred tax benefit in the three months ended March 31, 2023, and $0.6 million of deferred tax benefit for the same period in 2022.

We recognized $1.0 million of deferred tax benefit in the six months ended June 30, 2023, and $0.9 million of deferred tax benefit for the same period in 2022.

Financial Position, Liquidity and Capital Resources

As of March 31, 2023, we had cash and cash equivalents, restricted cash and investment securities of $318.5 million.

As of June 30, 2023, we had cash and cash equivalents, restricted cash, and investment securities of $631.8 million.

U ntil such time, if ever, as we can generate substantial cash flows from successfully commercializing our proprietary product candida tes, we expect to finance our cash needs through a combination of equity offerings, debt financings, collaborations, strategic alliances and marketing, royalty monetization financings, distribution, and licensing arrangements.

We believe that our cash and cash equivalents will fund our operations into 2025 assuming the achievement of $100.0 million of first commercial sale milestone in the United States and into the first half of 2025 if the $75.0 million of first commercial sale milestone in any of the five contractually defined European countries as of or prior to July 2, 2023 under the CSL Behring Agreement.

We believe that our cash and cash equivalents and investment securities will fund our operations into the second quarter of 2026.

Our material cash requirements include the following contractual and other obligations:

As of March 31, 2023, we had an outstanding loan amount owed to Hercules Capital, Inc.

As of June 30, 2023, we had an outstanding loan amount owed to Hercules Capital, Inc.

(“Hercules”) for an aggregate principal amount of $100.0 million.

Future interest payments and financing fees associated with the loan total $53.4 million, with $13.2 million payable within 12 months.

We are contractually required to repay the $100.0 million in full in December 2025.

We are contractually required to repay the $100.0 million in full in January 2027.

Royalty Financing Agreement

In May 2023, we entered into the Royalty Financing Agreement with the Purchaser.

Under the Royalty Financing Agreement, we received an upfront cash payment of $375.0 million in exchange for the lowest royalty tier on CSL Behring’s worldwide net sales of HEMGENIX® for certain current and future royalties due to us, up to 1.85 times (or $693.8 million) of this upfront cash payment until June 30, 2032 or, if such cap is not met by June 30, 2032, up 2.25 times the upfront cash payment (or $843.8 million) through December 31, 2038.

We are eligible to receive an additional $25.0 million milestone payment if 2024 net sales of HEMGENIX® exceed a pre-specified level.

If 2024 net sales do not exceed the pre-specified threshold, we will be obligated to pay $25.0 million to the Purchaser but only to the extent that we achieve future sales milestones under the CSL Behring Agreement.

We entered into lease arrangements for facilities, including corporate, manufacturing and office space.

As of March 31, 2023, we had fixed lease payment obligations of $58.8 million, with $8.1 million payable within 12 months.

Commitments related to Corlieve acquisition (nominal amounts)

In relation to the Corlieve acquisition, we entered into commitments to make payments to the former shareholders upon the achievement of certain contractual milestones.

As of June 30, 2023, we had fixed lease payment obligations of $56.7 million, with $8.2 million payable within 12 months.

Commitments related to uniQure France SAS acquisition (nominal amounts)

In relation to the uniQure France SAS acquisition, we entered into commitments to make payments to the former shareholders upon the achievement of certain contractual milestones.

The commitments include payments related to post-acquisition services that we agreed to as part of the transaction.

As of March 31, 2023, our commitment amounts include up to $43.5 million in potential milestone payments through Phase I/II development and $174.0 million in potential milestone payments associated with Phase III development and the approvals of AMT-260 in the United States and European Union.

As of June 30, 2023, our commitment amounts include up to $43.5 million in potential milestone payments through Phase I/II development and $174.2 million in potential milestone payments associated with Phase III development and the approvals of AMT-260 in the U.S.

and European Union.

The timing of achieving these milestones and consequently the timing of payments, as well as whether the milestone will be achieved at all, is generally uncertain.

These payments are owed in Euro and have been translated at the foreign exchange rate as of March 31, 2023, of $1.09/€1.00.

As of March 31, 2023, we expect these obligations will become payable between 2023 and 2031.

These payments are owed in Euro and have been translated at the foreign exchange rate as of June 30, 2023, of $1.09/€1.00.

As of June 30, 2023, we expect these obligations will become payable between 2023 and 2031.

If and when due, up to 25% of the milestone payments can be settled with our ordinary shares.

Commitments related to licensors and financial advisors

We have obligations to make future payments to third parties that become due and payable on the achievement of certain development, regulatory and commercial milestones (such as the start of a clinical trial, filing of a BLA, approval by the FDA or product launch) or as a result of collecting payments related to our sale of the exclusive global rights to the Product to CSL Behring.

We also owe payments to a financial advisor related to any payments we will collect under the CSL Behring Agreement.

The table below summarizes our consolidated cash flow data for the three months ended:

Three months ended March 31,

We have obligations to make future payments to third parties that become due and payable on the achievement of certain development, regulatory and commercial milestones (such as the start of a clinical trial, filing of a BLA, approval by the FDA or product launch) or because of collecting payments related to our sale of the exclusive global rights to the Product to CSL Behring.

We also owe payments to a financial advisor related to certain payments we will collect under the CSL Behring Agreement.

The table below summarizes our consolidated cash flow data for the six months ended:

Six months ended June 30,

(in thousands)

5 unchanged sentences

Cash, cash equivalents and restricted cash at the end of period

We had previously incurred losses and cumulative negative cash flows from operations since our business was founded by our predecessor entity AMT Therapeutics (“AMT”) Holding N.V.

in 1998, with the exception of generating income in 2021 after receiving the upfront payment upon Closing of the CSL Behring Agreement.

We had previously incurred losses and cumulative negative cash flows from operations since our business was founded by our predecessor entity AMT Therapeutics Holding N.V.

(“AMT”) in 1998, except for generating income in 2021 after receiving the upfront payment upon closing of the CSL Behring Agreement in 2021.

We continue to incur losses in the current period.

We recorded a net loss of $77.2 million in the three months ended March 31, 2023, compared to a net loss of $46.7 million during the same period in 2022.

As of March 31, 2023, we had an accumulated deficit of $659.2 million.

We recorded a net loss of $68.5 million and $145.7 million in the three and six months ended June 30, 2023, respectively, compared to a net loss of $39.1 million and $85.7 million during the same period in 2022.

As of June 30, 2023, we had an accumulated deficit of $727.6 million.

Sources of liquidity

From our first institutional venture capital financing in 2006 through the current period, we funded our operations primarily through private and public placements of equity securities and convertible and other debt securities as well as payments from our collaboration partners.

In May 2021, we received a $462.4 million cash payment due from CSL Behring upon Closing.

We have collected $55.0 million related to CSL Behring’s global regulatory submissions for etranacogene dezaparvovec in March and April 2022, and are eligible to receive additional milestone payments, as well as royalties on net sales from CSL Behring.

On March 1, 2021, we entered into a Sales Agreement with SVB Leerink LLC (“SVB Leerink”) with respect to an at the market (“ATM”) offering program, under which we may, from time to time in our sole discretion, offer and sell through SVB Leerink, acting as agent, our ordinary shares, up to an aggregate offering price of $200.0 million.

From our first institutional venture capital financing in 2006 through the current period, we funded our operations primarily through private and public placements of equity securities, debt securities, payments from our collaboration partners as well as from selling a portion of royalties due from our collaboration partner CSL Behring.

In May 2021, we received a $462.4 million cash payment due from CSL Behring.

We have collected $55.0 million related to CSL Behring’s global regulatory submissions for etranacogene dezaparvovec in March and April 2022, and $100.0 million in July 2023 related to the first sale milestone of HEMGENIX® in the U.S., and are eligible to receive additional milestone payments, as well as royalties (to the extent not owed to settle the liability from royalty financing) on net sales of HEMGENIX®.

We will pay SVB Leerink a commission equal to 3% of the gross proceeds of the sales price of all ordinary shares sold through it as a sales agent under the Sales Agreement.

We did not issue ordinary shares under the Sales Agreement for the three months ended March 31, 2023 and March 31, 2022.

We are subject to certain covenants under our December 2021 amendment with Hercules Capital, Inc (“2021 Restated Facility”) and may become subject to covenants under any future indebtedness that could limit our ability to take specific actions, such as incurring additional debt, making capital expenditures, or declaring dividends, which could adversely impact our ability to conduct our business.

In addition, our pledge of assets as collateral to secure our obligations under the 2021 Restated Facility may limit our ability to obtain debt financing.

The 2021 Restated Facility permits us to issue up to $500.0 million of convertible debt as well as to enter into a transaction to sell the royalties under the CSL Behring agreement subject to certain conditions .

We did not issue ordinary shares under the Sales Agreement for the six months ended June 30, 2023 and June 30, 2022.

On May 12, 2023 we and Hercules amended the 2021 Restated Facility.

The 2023 Amended Facility extends the maturity date and interest-only period from December 1, 2025 to January 5, 2027.

We are required to repay the entire principal balance of $100.0 million on the maturity date.

The interest rate is adjustable and is the greater of (i) 7.95% and (ii) 7.95% plus the prime rate less 3.25% per annum.

Under the 2023 Amended Facility, we owe a back-end fee of $4.9 million on December 1, 2025 and a back-end fee of $1.3 million on the maturity date.

We are subject to certain covenants under the 2023 Amended Facility and may become subject to covenants under any future indebtedness that could limit our ability to take specific actions, such as incurring additional debt, making capital expenditures, or declaring dividends, which could adversely impact our ability to conduct our business.

In addition, our pledge of assets as collateral to secure our obligations under the 2023 Amended Facility may limit our ability to obtain debt financing.

The 2023 Amended Facility permits us to issue up to $500.0 million of convertible debt.

To the extent we need to finance our cash needs through equity offerings or debt financings, such financing may be subject to unfavorable terms including without limitation, the negotiation and execution of definitive documentation, as well as credit and debt market conditions, and we may not be able to obtain such financing on terms acceptable to us or at all.

If financing is not available when needed, including through debt or equity financings, or is available only on unfavorable terms, we may be unable to meet our cash needs.

If we raise additional funds through collaborations, strategic alliances or marketing, royalty monetization financings, distribution, or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams or product candidates or grant licenses on terms that may not be favorable to us.

If financing is not available when needed, including through debt or equity financing, or is available only on unfavorable terms, we may be unable to meet our cash needs.

If we raise additional funds through collaborations, strategic alliances or marketing, distribution, or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams or product candidates or grant licenses on terms that may not be favorable to us.

If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves, which could have a material adverse effect on our business, financial conditions, results of operations and cash flows.

Net Cash used in operating activities

Net cash used in operating activities was $78.3 million for the three months ended March 31, 2023 and consisted of net loss of $77.2 million adjusted for non-cash items, including depreciation and amortization expense of $2.5 million, share-based compensation expense of $8.1 million, changes in the fair value of contingent consideration of $1.0 million, unrealized foreign exchange losses of $1.2 million and a change in deferred taxes of $1.2 million.

Net cash used in operating activities was $135.3 million for the six months ended June 30, 2023 and consisted of net loss of $145.7 million adjusted for non-cash items, including depreciation and amortization expense of $5.1 million, share-based compensation expense of $17.0 million, changes in the fair value of contingent consideration of $1.2 million, unrealized foreign exchange losses of $0.9 million, $3.2 million of interest expense related to the royalty financing and a change in deferred taxes of $1.0 million.

Net cash generated from operating activities also included unfavorable changes in operating assets and liabilities of $15.1 million.

There was a net increase in accounts receivable, prepaid expenses, and other current assets and receivables of $0.9 million.

There was a net decrease in accounts receivable, prepaid expenses, and other current assets and receivables of $0.9 million.

There was an increase in inventory balances of $3.3 million.

These changes also relate to a net decrease in accounts payable, accrued expenses, other liabilities, and operating leases of $12.6 million, primarily related to a decrease of $4.9 million from personnel related accruals.

Net cash used in operating activities was $25.7 million for the three months ended March 31, 2022 and consisted of a net loss of $46.7 million adjusted for non-cash items, including depreciation and amortization expense of $2.1 million, share-based compensation expense of $6.9 million, changes in the fair value of contingent

consideration and the derivative financial liability of $1.5 million, unrealized foreign exchange gains of $7.4 million and a change in deferred taxes of $0.6 million.

Net cash used in operating activities was $41.4 million for the six months ended June 30, 2022 and consisted of a net loss of $85.7 million adjusted for non-cash items, including depreciation and amortization expense of $4.1 million, share-based compensation expense of $14.7 million, changes in the fair value of contingent consideration and the derivative financial liability of $1.4 million, unrealized foreign exchange gains of $24.5 million and a change in deferred taxes of $0.9 million.

Net cash generated from operating activities also included favorable changes in operating assets and liabilities of $49.4 million.

There was a net decrease in accounts receivable and contract asset, prepaid expenses, and other current assets and receivables of $17.2 million, primarily related to the collection of $20.0 million of the contract asset related to CSL milestones of $55.0 million in March 2022.

There was a net decrease in accounts receivable and contract asset, prepaid expenses, and other current assets and receivables of $46.5 million, primarily related to the collection of $55.0 million of the contract asset related to CSL milestones of $55.0 million in March 2022 and April 2022.

These changes also relate to a net increase in accounts payable, accrued expenses, other liabilities, and operating leases of $6.3 million.

Net cash generated from / (used in) investing activities

In the three months ended March 31, 2023, we generated $3.0 million in our investing activities compared to using $4.9 million for the same period in 2022.

Three months ended March 31,

In the six months ended June 30, 2023, we generated $48.8 million in our investing activities compared to using $9.5 million for the same period in 2022.

Six months ended June 30,

(in thousands)

2 unchanged sentences

Build out of Lexington site

Acquisition of Corlieve, net of cash acquired

Acquisition of uniQure France SAS, net of cash acquired

Total investments

During the three months ended March 31, 2023, we received $5.3 million from the repayment of investment securities (nil for three months ended March 31, 2022).

The build out of the Amsterdam site and Lexington site consumed $0.7 million and $1.7 million cash respectively during the three months ended March 31, 2023, compared to $3.7 million and $0.3 million for the same period in 2022.

We paid EUR 0.9 million ($0.9 million) to acquire remaining outstanding shares of Corlieve in February 2022 (nil in current period).

During the six months ended June 30, 2023, we received $52.2 million from the repayment of investment securities (nil for six months ended June 30, 2022).

The build out of the Amsterdam, Netherlands and Lexington, Massachusetts sites consumed $1.3 million and $2.1 million, respectively, during the six months ended June 30, 2023, compared to $6.4 million and $2.2 million for the same period in 2022.

Net cash generated from financing activities

In the three months ended March 31, 2023, we generated $0.1 million from financing activities compared to $0.5 million for the same period in 2022.

Three months ended March 31,

In the six months ended June 30, 2023, we generated $370.3 million from financing activities compared to $0.5 million for the same period in 2022.

Six months ended June 30,

(in thousands)

Cash flows from financing activities

Proceeds from royalty financing agreement, net of debt issuance costs

Proceeds from issuance of shares related to employee stock option and purchase plans

Net cash generated from financing activities

During the three months ended March 31, 2023, we received $0.1 million from the exercise of options to purchase ordinary shares in relation to our share incentive plans compared to $0.5 million for the same period in 2022.

In June 2023, we received $370.1 million net proceeds from the Royalty Financing Agreement.

During the six months ended June 30, 2023, we received $0.2 million from the exercise of options to purchase ordinary shares in relation to our 2014 Plans compared to $0.5 million for the same period in 2022.

Funding requirements

1 unchanged sentence

● contractual milestone payments and royalties we might be owed in accordance with the CSL Behring Agreement;

● earnout payments we might owe the former shareholders of Corlieve, which are subject to the achievement of specific development and regulatory milestones;

● earnout payments we might owe the former shareholders of uniQure France SAS, which are subject to the achievement of specific development and regulatory milestones;

● the scope, timing, results, and costs of our current and planned clinical trials, including those for AMT-130 in Huntington’s disease;

● the scope of any equity, debt or royalty monetization financings;

● the scope, obligations and restrictions on our business related to our existing equity, debt or royalty monetization financings and underlying agreements;

● the extent to which we acquire or in-license other businesses, products, product candidates or technologies;

9 unchanged sentences

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-Q

Item 2. Management’s Discussion and Analysis