What changed in this filing

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Item 2. Management’s Discussion and Analysis

2024-05-07 compared with 2023-11-07 · 148 added, 353 removed, 175 unchanged (74% 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, 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.

In August 2023, the FDA cleared the Investigational New Drug (“IND”) application for AMT-260, our gene therapy candidate for refractory mesial temporal lobe epilepsy (“MTLE”).

On October 5, 2023, we announced a Reorganization (see definition below) of our research and technology programs.

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 compliant, manufacturing process.

We are a leader in the field of gene therapy, seeking to deliver to patients suffering from rare and other devastating 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, amyotrophic lateral sclerosis (“ALS”), refractory mesial temporal lobe epilepsy (“MTLE”) and Fabry disease.

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

The approval of HEMGENIX® follows more than a decade of research and clinical development, represents a major milestone in the field of gene therapy and ushers in a new treatment approach for patients living with hemophilia B.

We license HEMGENIX® to CSL Behring LLC (“CSL Behring”), which is responsible for its commercialization.

We are manufacturing HEMGENIX® for CSL Behring and are entitled to specific milestone payments and royalties on net sales of the product, a portion of which we sold to a royalty acquisition company in 2023 in exchange for up-front cash.

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

We produce our adeno-associated virus-based gene therapies in our own facilities with a proprietary, current good manufacturing practices (“GMP”) -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:

Reorganization

On October 5, 2023, we announced that we are implementing a reorganization plan (the “Reorganization”).

As a result of the Reorganization, we will be discontinuing investments in more than half of our research, including AMT-210 for the treatment of Parkinson’s disease, and technology projects.

Following the Reorganization, we intend to prioritize advancing our clinical-stage programs, including AMT-130 for the treatment of Huntington’s disease, AMT-260 for the treatment of refractory mesial temporal lobe epilepsy, AMT-162 for the treatment of SOD1 amyotrophic lateral sclerosis and AMT-191 for the treatment of Fabry disease to proof of concept.

As a result of the Reorganization, we will eliminate approximately 20% of our total workforce and close our research laboratory in Lexington, MA.

We expect to complete the Reorganization by the end of fiscal year 2023 and expect to incur costs of approximately $2.3 million, consisting primarily of cash expenditures related to employee severance costs.

We also anticipate that there could be costs associated with the lab to be closed in Lexington and associated fixed assets if the carrying value is determined to not be recoverable as of the cease-use date, which is expected to be later in the fourth quarter of 2023.

As part of the Reorganization we will also consolidate all good manufacturing practices (“GMP”) manufacturing into our Lexington, MA manufacturing facility and consolidate process and analytical development into our Amsterdam, Netherlands facility.

As a result of the significant reduction in research activities, Ricardo Dolmetsch, Ph.D., departed as Chief Scientific Officer, effective October 4, 2023.

Dolmetsch will serve as a scientific consultant through the end of the year.

In connection with Dr.

Dolmetsch’s transition, the Board of Directors of the Company have appointed Richard Porter, Ph.D., our current Chief Business Officer, to serve as the Company’s Chief Business and Scientific Officer, effective as of October 5, 2023.

Recent Product Candidate Developments

Huntington’s disease program (AMT-130)

AMT-130 is our novel gene therapy candidate for the treatment of Huntington’s disease, which utilizes our proprietary, gene-silencing miQURE platform and incorporates an AAV vector carrying a miRNA specifically designed to silence the huntingtin gene and the potentially highly toxic exon 1 protein fragment.

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

(“US study”) as well as an open-label Phase Ib/II study in Europe with the same early-manifest criteria for Huntington’s disease as the U.S.

study (“European study”).

We completed the enrollment of all 26 patients in the first two cohorts of our US study in March 2022 and the enrollment of 13 patients in the two cohorts of our European study in June 2023.

In November 2023, we initiated patient dosing in a third cohort of up to 12 patients to further investigate both doses of AMT-130 in combination with perioperative immunosuppression.

Patient enrollment is ongoing in this cohort with a focus on evaluating near-term safety and tolerability.

In June 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.

In December 2023, we announced updated interim data, including up to 30-month follow-up from the 26 patients enrolled in the ongoing US study as well as the 13 patients enrolled in the European study.

We plan to initiate interactions with the FDA in the second quarter of 2024.

The goal of these interactions is to define the future clinical and regulatory pathway for AMT-130 and is expected to include discussions of the data from the ongoing Phase I/II trials and the potential to leverage robust natural history comparators and long-term clinical data from the Phase I/II studies.

Temporal lobe epilepsy program (AMT-260)

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AMT-260 comprises an AAV9 vector that locally delivers two engineered micro ribonucleic acids (“miRNAs”) designed to degrade the GRIK2 gene and suppress the aberrant expression of glutamate receptor subtype GLUK2 that is believed to trigger seizures in patients with refractory MTLE.

We acquired AMT-260 as part of our acquisition of uniQure France SAS (formerly Corlieve Therapeutics) in July 2021.

In September 2023, following the IND clearance, we paid EUR 10.0 million ($10.6 million) to the former shareholders of uniQure France SAS (formerly Corlieve Therapeutics SAS), to settle a milestone payment owed in relation to our 2021 acquisition.

Huntington’s disease program (AMT-130)

AMT-130 is our novel gene therapy candidate for the treatment of Huntington’s disease that utilizes our proprietary, gene-silencing miQURE platform and incorporates an AAV vector carrying a miRNA specifically designed to silence the huntingtin gene and the potentially highly toxic exon 1 protein fragment.

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

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 seven patients in the high-dose cohort.

All 13 patients enrolled in the EU study received AMT-130.

Two remaining patients initially scheduled for the EU open-label study will now be enrolled in Cohort 3, which is expected to start enrolling in the fourth quarter of 2023 and will be comprised of up to 12 patients.

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 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 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 interim 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 demonstrated 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 demonstrated 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 demonstrated 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.

Exploratory Biomarkers

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 CSF 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 CSF 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 did not appear to be significantly different from each other or from the natural history.

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 IND application for APB-102 and has granted Orphan Drug and Fast Track designation.

We expect to initiate patient screening in the fourth quarter of 2023 with the first patient dosing occurring in the first quarter of 2024.

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 in February 2023 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.

We are initiating a Phase I/IIa clinical trial that will be conducted in the United States and consist of two parts.

The first part is a multicenter, open-label trial with two dosing cohorts of six patients each to assess safety, tolerability, and first signs for efficacy of AMT-260 in patients with refractory MTLE.

The second part is expected to be a randomized, controlled trial to generate proof of concept (“POC”) data.

Fabry disease program (AMT-191)

AMT-191 is our novel gene therapy candidate for the treatment of Fabry disease.

AMT-191 is our gene therapy candidate for the treatment of Fabry disease.

AMT-191 comprises of an AAV5 capsid that incorporates the α-galactosidase A (“GLA”) transgene and a proprietary, highly potent, liver-specific promoter.

We expect to submit an IND in the fourth quarter of 2023 and to begin patient dosing in 2024.

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 $1.3 billion, under the terms of the CSL Behring Agreement.

Hercules Amendment

On May 12, 2023 we and Hercules Capital, Inc.

(“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.

Investment in debt securities

In July and September 2023, we invested $272.0 million and EUR 87.0 million (or a total of $366.4 million as of the investment dates) of our cash and cash equivalents into short-term U.S.

and European government bonds that are U.S.

dollar and euro denominated, respectively.

Our investment policy requires us to invest in bonds with the highest investment grade credit rating.

As of September 30, 2023, the bonds have remaining maturities ranging from one to ten months.

We classify these bonds as held-to-maturity.

In November 2023 we announced that the FDA had cleared the IND application for AMT-191.

We are initiating a first-in-human Phase I/IIa clinical trial that will be conducted in the United States.

The multicenter, open-label clinical trial consists of two dose-escalating cohorts of up to three adult male patients each to assess safety, tolerability, and early signs of efficacy of AMT-191 in patients with Fabry disease.

Three patients will be dosed in the initial dose.

If no dose-limiting toxicology is identified, the dose will be escalated.

If dose-limiting toxicology occurs in one of the three initial patients, three additional patients will be enrolled at the same dose level.

If no additional patients in the cohort experience a dose-limiting toxicology, the dose will be escalated.

Assessments will be made at three- and six-months post-treatment.

Amyotrophic Lateral Sclerosis (AMT-162)

AMT-162 is our gene therapy candidate 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.

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

AMT-162 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.

The FDA has cleared the IND application for AMT-162 and has granted Orphan Drug and Fast Track designation.

We are initiating a first-in-human Phase I/II clinical trial that will be a U.S.-based, multi-center, open-label trial consisting of three cohorts with up to four patients each receiving a one-time intrathecal infusion with immunosuppression.

Safety, tolerability and early signs of efficacy will be evaluated in the study.

Financial Overview

Key components of our results of operations include the following:

Three months ended September 30,

Nine months ended September 30,

(in thousands)

Three months ended March 31,

(in thousands)

Total revenues

Cost of license revenues

Cost of contract manufacturing revenues

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Selling, general and administrative expenses

As of September 30, 2023 and December 31, 2022, we had cash and cash equivalents and investment securities of $658.9 million and $392.8 million, respectively.

We had a net loss of $89.6 million and $235.3 million in the three and nine months ended September 30, 2023, respectively, compared to net loss of $47.9 million and $133.6 million for the same period in 2022.

As of September 30, 2023 and December 31, 2022, we had accumulated deficits of $817.2 million and $581.9 million, respectively.

Compared to the current period, we expect that our expenses will decline following the Reorganization, until which time we decide to advance one of our gene therapy product candidates into late stage clinical development.

As of March 31, 2024 and December 31, 2023, we had cash and cash equivalents and investment securities of $555.7 million and $617.9 million, respectively.

We had a net loss of $65.6 million in the three months ended March 31, 2024, compared to net loss of $77.2 million for the same period in 2023.

As of March 31, 2024 and December 31, 2023, we had accumulated deficits of $956.0 million and $890.4 million, respectively.

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 nine months ended September 30, 2023 or reasonably possible changes of our critical accounting estimates as of September 30, 2023 that could have had a material impact on our results of operations for the three and nine months ended September 30, 2023.

There were no material changes to our critical accounting policies during the three months ended March 31, 2024 or reasonably possible changes of our critical accounting estimates as of March 31, 2024 that could have had a material impact on our results of operations for the three ended March 31, 2024.

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 the cost to manufacture HEMGENIX® under such agreement as cost of contract manufacturing.

We recognize the cost to manufacture HEMGENIX® under such agreement as cost of contract manufacturing.

Research and development expenses

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

● payments to our licensors for milestones that have been achieved related to our product candidates, including approval of the marketing authorization application (“MAA”);

● payments to our licensors for milestones that have been achieved related to our product candidates;

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

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● the timing of regulatory approvals.

A change in the outcome of any of these variables with respect to the product candidates that we may develop could mean a significant change in the expenses and timing associated with the development of such product candidate.

A change in the outcome of any of these variables with respect to our product candidates that we may develop could mean a significant change in the expenses and timing associated with the development of such product candidate.

Selling, general and administrative expenses

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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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Results of Operations

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

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

Three months ended September 30,

Comparison of the three months ended March 31, 2024 and 2023

The following table presents a comparison of our results of operations for the three months ended March 31, 2024 and 2023.

Three months ended March 31,

(in thousands)

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Operating expenses:

Cost of license revenues

Cost of contract manufacturing

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Other non-operating items, net

Net loss before income tax benefit

Income tax benefit

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

Three months ended September 30,

Net loss before income tax (expense) / benefit

Income tax (expense) / benefit

Our revenues for the three months ended March 31, 2024 and 2023 were as follows:

Three months ended March 31,

(in thousands)

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

For the three months ended September 30, 2023, we recognized $0.5 million of license revenues (nil for the same period in 2022).

For the three months ended March 31, 2024, we recognized $1.2 million of license revenues (nil for the same period in 2023).

Contract manufacturing revenues

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Contract manufacturing revenues is realized when earned upon sales of HEMGENIX® drug product to CSL Behring.

We recognized $0.3 million contract manufacturing revenues in the three months ended September 30, 2023, compared to nil for the same period in 2022.

We did not recognize such revenues in the three months ended September 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 .

We recognized $4.0 million contract manufacturing revenues in the three months ended March 31, 2024 , compared to $4.9 million for the same period in 2023.

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 September 30, 2023, we recognized $0.6 million of collaboration revenue for CSL Behring.

For the three months ended September 30, 2022, we recognized $1.5 million of collaboration revenue for CSL Behring and BMS.

For the three months ended March 31, 2024 and 2023 we recognized $3.3 million and $0.4 million of collaboration revenue for CSL Behring, respectively.

Cost of contract manufacturing

We incurred $1.0 million of cost of contract manufacturing related to the manufacture of HEMGENIX® in the three months ended September 30, 2023, compared to $0.9 million cost of contract manufacturing in the three months ended September 30, 2022.

R&D expenses for the three months ended September 30, 2023 were $65.4 million, compared to $48.1 million for the same period in 2022.

We incurred $9.1 million of cost of contract manufacturing related to the manufacture of HEMGENIX® in the three months ended March 31, 2024, compared to $2.4 million cost of contract manufacturing in the three months ended March 31, 2023.

The increase in cost of $6.7 million in 2024 is primarily related to expensing costs previously capitalized as work in progress, including a write-down to lower net realizable value.

R&D expenses for the three months ended March 31, 2024 were $40.7 million, compared to $60.8 million for the same period in 2023.

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 September 30,

Three months ended March 31,

(in thousands)

Temporal lobe epilepsy (AMT-260)

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

Etranacogene dezaparvovec (AMT-060/061)

Total direct research and development expenses

Employee and contractor-related expenses

Fair value changes related to contingent consideration

Facility expenses

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Other expenses

Fair value changes related to contingent consideration

Total other research and development expenses

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Direct research and development expenses

Temporal lobe epilepsy (AMT-260)

In the three months ended September 30, 2023 and September 30, 2022, we incurred costs of $4.7 million and $2.5 million respectively, for the preclinical development of AMT-260.

Huntington’s disease (AMT-130)

In the three months ended September 30, 2023 and September 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.

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 September 30, 2023, we incurred $2.4 million of costs (nil in the prior period), related to our preclinical activities for AMT-162.

Fabry disease (AMT-191)

In the three months ended September 30, 2023 and September 30, 2022, we incurred costs of $0.4 million and $0.5 million, respectively, related to our preclinical development of AMT-191.

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.

Prior to the transition of these activities to CSL Behring in December 2022, we managed the trials and incurred related expenses.

Direct research and development expenses related to clinical development and other regulatory activities and commercialization expenses incurred in the three months ended September 30, 2023 and September 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 September 30, 2023, and September 30, 2022, we incurred $3.1 million and $0.9 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 $19.4 million in personnel and contractor-related expenses in the three months ended September 30, 2023, compared to $15.6 million for the same period in 2022.

The increase was primarily related to the hiring of personnel and contractors to support our clinical-stage programs and manufacturing operations, as well as an increase in severance costs;

● We incurred $14.2 million of expenses in the three months ended September 30, 2023 related to an increase in the fair value of contingent consideration associated with the acquisition of uniQure France SAS, compared to $5.5 million an increase in fair value for the same period in 2022.

The change was primarily due to the increase in the probability of making a future milestone payment related to the first patient dosed in the Phase I/II clinical trial of AMT-260;

● We incurred $6.7 million in operating expenses and depreciation expenses related to our rented facilities in Amsterdam and Lexington, Massachusetts in the three months ended September 30, 2023, compared to $6.5 million in the same period in 2022;

● We incurred $5.6 million in share-based compensation expenses in the three months ended September 30, 2023, compared to $3.7 million for the same period in 2022.

The increase was primarily a result of recognizing compensation cost related to performance share units granted in December 2021, for which achievement of related performance conditions was deemed probable in the three months ended September 30, 2023.

Compensation cost was not recognized in the three months ended September 30, 2022 as achievement of related performance conditions was not deemed probable at this time;

● We incurred $4.7 million in disposable costs in the three months ended September 30, 2023, compared to $6.0 million for the same period in 2022;

● We incurred $1.1 million of other expenses for the three months ended September 30, 2023, compared to $2.2 million for the same period in 2022.

Selling, general and administrative expenses

Selling, general and administrative expenses for the three months ended September 30, 2023 were $18.1 million, compared to $13.3 million for the same period in 2022.

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

● We incurred $5.1 million in share-based compensation expenses in the three months ended September 30, 2023, compared to $3.8 million in the same period in 2022.

The increase was primarily a result of an increase in expense related to performance share units granted in 2021;

● We incurred $2.8 million in professional fees in the three months ended September 30, 2023, compared to $1.6 million in the same period in 2022.

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

● We incurred $2.

8 million in other operating expenses in the three months ended September 30, 2023, compared to $2.0 million in the same period in 2022.

Other items, net

We recognized $1.4 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 September 30, 2023, compared to $1.3 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 September 30, 2023 and 2022 were as follows:

Three months ended September 30,

(in thousands)

Interest income

Interest expense

Foreign currency gains, net

Total non-operating (expense) / income, net

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

We recognized $7.5 million in interest income in the three months ended September 30, 2023, compared to $0.0 million in the same period in the prior year.

Our interest income increased by $7.5 million due to the interest income earned on investment securities as well as cash on hand during the three months ended September 30, 2023.

We recognized $15.4 million in interest expense for the three months ended September 30, 2023 and $3.1 million for the three months ended September 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 $11.8 million of interest expense related to the Royalty Financing Agreement that we entered into in May 2023.

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 $0.2 million during the three months ended September 30, 2023, compared to a net gain of $14.4 million during the same period in 2022.

Income tax benefit

We recognized $0.1 million of deferred tax benefit in the three months ended September 30, 2023, and $0.3 million of deferred tax benefit for the same period in 2022.

Comparison of the nine months ended September 30, 2023 and 2022

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

Nine months ended September 30,

(in thousands)

Total revenues

Operating expenses:

Cost of contract manufacturing revenues

Research and development expenses

Selling, general and administrative expenses

Total operating expenses

Other expense

Loss from operations

Non-operating items, net

Loss before income tax benefit

Income tax benefit

Our revenue for the nine months ended September 30, 2023 and 2022 was as follows:

Nine months ended September 30,

(in thousands)

License revenues

Contract manufacturing revenues

Collaboration revenues

Total revenues

License revenue

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

For the nine months ended September 30, 2023, we recognized $1.3 million of license revenue (nil for the same period in 2022).

Contract manufacturing revenues

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

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

We recognized $6.6 million contract manufacturing revenues in the nine months ended September 30, 2023, compared to nil for the same period in 2022.

We did not recognize such revenues in the nine months ended September 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 BMS in 2015 which were terminated on February 21, 2023.

For the nine months ended September 30, 2023, we recognized $1.3 million of collaboration revenue for CSL Behring.

For the nine months ended September 30, 2022, we recognized $3.7 million of collaboration revenue for CSL Behring and BMS.

Cost of contract manufacturing

We incurred $4.8 million of cost of contract manufacturing related to the manufacture of HEMGENIX® in the nine months ended September 30, 2023, compared to $1.7 million cost of contract manufacturing in the nine months ended September 30, 2022.

R&D expenses for the nine months ended September 30, 2023 were $172.2 million, compared to $139.3 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.

Nine months ended September 30,

(in thousands)

Amyotrophic lateral sclerosis (AMT-162)

In the three months ended March 31, 2024 and March 31, 2023, we incurred costs of $2.4 million and $3.7 million respectively.

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.

In the prior year, we had enrollment for the European clinical trial.

Temporal lobe epilepsy (AMT-260)

Huntington's disease (AMT-130)

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

Fair value changes related to contingent consideration

Other expenses

Total other research and development expenses

Total research and development expenses

Direct research and development expenses

In the three months ended March 31, 2024 and March 31, 2023, we incurred costs of $2.3 million and $4.3 million respectively, for the development of AMT-260.

In August 2023, the FDA cleared our IND application, and we started incurring costs for the preparation of a Phase I clinical trial.

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.

We have incurred $13.0 million expenses recorded to research and development expense related to the acquisition, as well as for preclinical activities of AMT-162 during the nine-month period ended September 30, 2023.

Temporal lobe epilepsy (AMT-260)

In the nine months ended September 30, 2023 and September 30, 2022, we incurred costs of $12.0 million and $11.4 million, respectively, for the preclinical development of AMT-260.

Huntington’s disease (AMT-130)

In the nine months ended September 30, 2023 and September 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.

In the three months ended March 31, 2024, we incurred $2.0 million of costs to initiate a Phase I/II clinical trial in 2024.

In the three months ended March 31, 2023 we incurred $10.0 million of expenses related to the transaction.

Fabry disease (AMT-191)

In the nine months ended September 30, 2023 and September 30, 2022, we incurred costs of $1.8 million and $1.7 million, respectively, related to our preclinical development of AMT-191.

Etranacogene dezaparvovec (AMT-060/061)

Prior to the transition of these activities to CSL Behring in December 2022, we managed the trials and incurred related expenses.

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

In the three months ended March 31, 2024 and March 31, 2023, we incurred costs of $1.3 million and $1.1 million, respectively, related to our development of AMT-191.

In November 2023, the FDA cleared the IND application, and we started incurring additional costs for the Phase I/II clinical trial preparation.

Preclinical programs & platform development

In the nine months ended September 30, 2023, and September 30, 2022, we incurred costs of $7.2 million and $3.9 million, respectively, primarily related to our preclinical activities associated with product candidates for various other research programs and technology innovation projects.

In the three months ended March 31, 2024 and March 31, 2023, we incurred $0.4 million and $1.9 million of costs, respectively, primarily related to our preclinical activities associated with product candidates for various other research programs and technology innovation projects.

Etranacogene dezaparvovec (AMT-060/061)

We transitioned activities related to the clinical trial and long-term follow-up of patients 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, 2024 and March 31, 2023 are presented net of reimbursements due from CSL Behring and include settlement amounts from the transition.

Other research & development expenses

● We incurred $55.9 million in personnel and contractor-related expenses in the nine months ended September 30, 2023, compared to $46.8 million for the same period in 2022.

The increase was primarily related to the hiring of personnel and contractors to support our clinical-stage programs and manufacturing operations, as well as an increase in severance costs;

● We incurred $21.1 million in operating expenses and depreciation expenses related to our rented facilities in Amsterdam and Lexington, Massachusetts in the nine months ended September 30, 2023, compared to $17.2 million in the same period in 2022.

The increase primarily related to operating expenses and depreciation expense incurred from additional sites in Lexington which commenced in May and November 2022;

● We incurred $15.4 million of expenses in the nine months ended September 30, 2023 related to an increase in the fair value of contingent consideration associated with the acquisition of uniQure France SAS, compared to $7.5 million for the same period in 2022.

The change was primarily due to the increase in the probability of making a future milestone payment related to the first patient dosed in the Phase I/II clinical trial of AMT-260;

● We incurred $14.7 million in share-based compensation expenses in the nine months ended September 30, 2023, compared to $12.1 million for the same period in 2022.

The increase was primarily a result of an increase in awards granted as well as from recognizing compensation cost related to performance share units granted in December 2021, for which achievement of related performance conditions was deemed probable in the nine months ended September 30, 2023.

Compensation cost was not recognized in the nine months ended September 30, 2022 as achievement of related performance conditions was not deemed probable at this time;

● We incurred $14.5 million in disposable costs in the nine months ended September 30, 2023, compared to $15.1 million for the same period in 2022;

● We incurred $6.8 million of other expenses for the nine months ended September 30, 2023, compared to $6.9 million for the same period in 2022.

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

● We incurred $16.9 million in personnel and contractor-related expenses in the three months ended March 31, 2024 , compared to $18.7 million for the same period in 2023.

The decrease was primarily related to the reduction in personnel and contractors as a result of the restructuring that occurred in October 2023;

● We incurred $7.1 million in operating expenses and depreciation expenses related to our rented facilities in Amsterdam and Lexington, Massachusetts in the three months ended March 31, 2024 , compared to $6.8 million in the same period in 2023;

● We incurred $3.4 million in share-based compensation expenses in the three months ended March 31, 2024 , compared to $4.3 million for the same period in 2023.

The decrease was primarily a result of the reduction in expense from the restructuring that occurred in October 2023;

● We incurred $2.7 million of other expenses for the three months ended March 31, 2024 , compared to $4.4 million for the same period in 2023;

● We incurred $1.9 million in disposable costs in the three months ended March 31, 2024 , compared to $3.9 million for the same period in 2023.

The decrease was primarily a result of the reduction in expense from the restructuring that occurred in October 2023;

● We incurred $0.2 million of expenses in the three months ended March 31, 2024 related to an increase in the fair value of contingent consideration associated with the acquisition of uniQure France SAS, compared to $1.0 million increase in fair value for the same period in 2023.

Selling, general and administrative expenses

Selling, general and administrative expenses for the nine months ended September 30, 2023 were $57.1 million, compared to $36.8 million for the same period in 2022.

● We incurred $18.8 million in personnel and contractor-related expenses in the nine months ended September 30, 2023, compared to $14.8 million in the same period in 2022.

The increase was primarily related to the hiring of personnel and contractors to support our business operations;

● We incurred $12.9 million in share-based compensation expenses in the nine months ended September 30, 2023, compared to $9.9 million in the same period in 2022.

The increase was primarily a result of an increase in awards grants and from recognizing compensation cost for performance share units granted in December 2021 that were deemed probable in the nine months ended September 30, 2023;

● We incurred $8.5 million in professional fees in the nine months ended September 30, 2023, compared to $4.3 million in the same period in 2022.

Selling, general and administrative expenses for the three months ended March 31, 2024 were $13.9 million, compared to $17.8 million for the same period in 2023.

● We incurred $6.2 million in personnel and contractor-related expenses in the three months ended March 31, 2024 , compared to $5.9 million in the same period in 2023;

● We incurred $3.4 million in share-based compensation expenses in the three months ended March 31, 2024 , compared to $3.7 million in the same period in 2023;

● We incurred $2.0 million in professional fees in the three months ended March 31, 2024 , compared to $3.2 million in the same period in 2023.

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

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

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

● We incurred $3.3 million in intellectual property fees including registration and professional fees in the nine months ended September 30, 2023 compared to $1.2 million in the same period in 2022.

The increase mainly related to an increase in professional fees;

● We incurred $9.0 million in other operating expenses in the nine months ended September 30, 2023, compared to $6.0 million in the same period in 2022.

The increase was primarily a result of an increase in information technology expenses.

In the prior period, we incurred professional fees related to our global licensing agreement with Apic Bio;

● We incurred $2.0 million in other expenses in the three months ended March 31, 2024, compared to $4.0 million in the same period in 2023.

The $2.0 million decrease was primarily related to a decrease in intellectual property fees as well as a reduction of expenses for information technology.

Other items, net

We recognized $3.9 million in other income from payments received from European authorities to subsidize our research and development efforts in the Netherlands in the nine months ended September 30, 2023, compared to $3.9 million for the same period in 2022.

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, 2024, compared to $1.3 million for the same period in 2023.

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 nine months ended September 30, 2023 and 2022 were as follows:

Nine months ended September 30,

Our other non-operating items, net, for the three months ended March 31, 2024 and 2023 were as follows:

Three months ended March 31,

(in thousands)

1 unchanged sentence

Interest expense

Foreign currency (losses) / gains, net

Other non-operating gains

Total non-operating (expense) / income, net

Foreign currency losses, net

Total non-operating expense, net

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

We recognized $12.4 million in interest income in the nine months ended September 30, 2023, compared to $0.1 million in the same period in the prior year.

Our interest income increased by $12.3 million due to the interest income earned on investment securities as well as cash on hand during the nine months ended September 30, 2023.

We recognized $25.8 million in interest expense for the nine months ended September 30, 2023 and $8.3 million for the nine months ended September 30, 2022.

We recognized $6.5 million in interest income in the three months ended March 31, 2024, compared to $1.7 million in the same period in the prior year.

Our interest income increased by $4.8 million due to the interest income earned on investment securities as well as cash on hand during the three months ended March 31, 2024.

We recognized $16.1 million in interest expense for the three months ended March 31, 2024 and $3.6 million for the three months ended March 31, 2023.

Our interest expense in 2024 increased due to an increase in market interest rates related to the Hercules debt as well as the recognition of $12.4 million of interest expense related to the Royalty Financing Agreement that we entered into in May 2023.

1 unchanged sentence

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, the Royalty Financing Agreement and our cash and cash equivalents and investment securities as well as loans between entities within the uniQure group, of $1.8 million during the nine months ended September 30, 2023, compared to a net gain of $42.3 million during the same period in 2022.

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 $1.1 million during the three months ended March 31, 2024, compared to a net loss of $2.4 million during the same period in 2023.

Income tax benefit

We recognized $1.1 million of deferred tax benefit in the nine months ended September 30, 2023, and $1.3 million of deferred tax benefit for the same period in 2022.

We recognized $0.7 million of deferred tax expense in the three months ended March 31, 2024 , and $1.2 million of deferred tax benefit for the same period in 2023.

Financial Position, Liquidity and Capital Resources

As of September 30, 2023, we had cash and cash equivalents, restricted cash, and investment securities of $662.1 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.

Based on our current operating plan, research and development plans and our timing expectations related to the progress of our programs and following the Reorganization, we believe that our cash and cash equivalents and investment securities will fund our operations into the second quarter of 2027.

As of March 31, 2024, we had cash and cash equivalents, restricted cash and investment securities of $558.9 million.

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

We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect.

1 unchanged sentence

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

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

As of March 31, 2024, we had an outstanding loan amount owed to Hercules Capital, Inc.

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

1 unchanged sentence

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 September 30, 2023, we had fixed lease payment obligations of $54.8 million, with $8.3 million payable within 12 months.

As of March 31, 2024, we had fixed lease payment obligations of $50.7 million, with $8.4 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.

In relation to our acquisition of uniQure France SAS in 2021, 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.

In September 2023, we made a payment of EUR 10.0 million ($10.6 million) to the former shareholders of uniQure France SAS following the FDA’s clearance of the IND application for AMT-260.

As of September 30, 2023, our remaining commitment amounts include a EUR 30.0 million ($31.7 million) milestone payment due upon treating the first patient in Phase I/II clinical trial and EUR 160.0 million ($169.2 million) in potential milestone payments associated with Phase III development and the approvals of AMT-260 in the U.S.

As of March 31, 2024, our remaining commitment amounts include a EUR 30.0 million ($32.4 million) milestone payment due upon treating the first patient in a Phase I/II clinical trial for AMT-260 and EUR 160.0 million ($172.7 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 September 30, 2023, of $1.06/€1.00.

As of September 30, 2023, we expect these obligations will become payable between early 2024 and 2031.

These payments are owed in euro and have been translated at the foreign exchange rate as of March 31, 2024, of $1.08/€1.00.

As of March 31, 2024, we expect these obligations will become payable between 2024 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 because of collecting payments related to our sale of the exclusive global rights to the Product to CSL Behring.

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 of HEMGENIX® 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 nine months ended:

Nine months ended September 30,

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

Three months ended March 31,

(in thousands)

1 unchanged sentence

Net cash used in operating activities

Net cash used in investing activities

Net cash generated from investing activities

Net cash generated from financing activities

2 unchanged sentences

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.

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

We continue to incur losses in the current period.

We recorded a net loss of $89.6 million and $235.3 million in the three and nine months ended September 30, 2023, respectively, compared to a net loss of $47.9 million and $133.6 million during the same period in 2022.

As of September 30, 2023, we had an accumulated deficit of $817.2 million.

We recorded a net loss of $65.6 million in the three months ended March 31, 2024, compared to a net loss of $77.2 million during the same period in 2023.

As of March 31, 2024, we had an accumulated deficit of $956.0 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, 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 have collected $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®.

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

1 unchanged sentence

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% or (ii) 7.95% plus the prime rate less 3.25% per annum.

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.

7 unchanged sentences

Net cash used in operating activities

Net cash used in operating activities was $96.4 million for the nine months ended September 30, 2023 and consisted of net loss of $235.3 million adjusted for non-cash items, including depreciation and amortization expense of $7.7 million, amortization of the premium/discount on investment securities of $6.5 million, share-based compensation expense of $28.1 million, changes in the fair value of contingent consideration of $15.4 million, unrealized foreign exchange losses of $3.1 million, $14.9 million of interest expense related to the royalty financing and a change in deferred taxes of $1.1 million.

Net cash used in operating activities also included favorable changes in operating assets and liabilities of $77.0 million.

There was a net decrease in accounts receivable, prepaid expenses, and other current assets and receivables of $96.6 million, primarily related to the collection of the $100.0 million milestone due from CSL Behring in July 2023 .

There was an increase in inventory balances of $8.7 million.

There was a net decrease in accounts payable, accrued expenses, other liabilities, and operating leases of $10.8 million, primarily related to a decrease of $4.8 million in accounts payable and a decrease of $6.0 million related to various accruals.

Net cash used in operating activities also includes a payment for a contingent consideration milestone of $1.9 million.

Net cash used in operating activities was $90.4 million for the nine months ended September 30, 2022 and consisted of a net loss of $133.6 million adjusted for non-cash items, including depreciation and amortization expense of $6.2 million, share-based compensation expense of $22.3 million, changes in the fair value of contingent consideration and the derivative financial liability of $6.9 million, unrealized foreign exchange gains of $36.4 million and a change in deferred taxes of $1.3 million.

Net cash generated from operating activities also included favorable changes in operating assets and liabilities of $46.1 million.

There was a net decrease in accounts receivable and contract asset, prepaid expenses, and other current assets and receivables of $42.0 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.

There was an increase in inventories of $4.1 million related to the production of etranacogene dezaparvovec under the CSL Behring Agreement.

These changes also relate to a net increase in accounts payable, accrued expenses, other liabilities, and operating leases of $8.2 million, primarily related to increase in accounts payable.

Net cash used in investing activities

In the nine months ended September 30, 2023, we used $265.2 million in our investing activities compared to using $14.5 million for the same period in 2022.

Nine months ended September 30,

Net cash used in operating activities was $60.6 million for the three months ended March 31, 2024 and consisted of net loss of $65.6 million adjusted for non-cash items, including depreciation and amortization expense of $2.6 million, amortization of the discount on investment securities of $3.7 million, share-based compensation expense of $7.2 million, changes in the fair value of contingent consideration of $0.2 million, unrealized foreign exchange losses of $1.4 million, $12.4 million of interest expense related to the royalty financing and a change in deferred taxes of $0.7 million.

Net cash used in operating activities also included unfavorable changes in operating assets and liabilities of $18.4 million.

There was a net increase in accounts receivable, prepaid expenses, and other current assets and receivables of $10.4 million.

There was a decrease in inventory balances of $2.2 million.

There was a net decrease in accounts payable, accrued expenses, other liabilities, and operating leases of $10.3 million, primarily related to a decrease of $6.7 million from personnel related accruals.

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, amortization of the discount on investment securities of $0.9 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 generated from operating activities also included unfavorable changes in operating assets and liabilities of $12.2 million.

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

These changes also relate to a net decrease in accounts payable, accrued expenses, other liabilities, and operating leases of $10.7 million, primarily related to a decrease of $7.9 million from personnel related accruals.

Net cash generated from investing activities

In the three months ended March 31, 2024, we generated $64.4 million in our investing activities compared to generating $3.0 million for the same period in 2023.

Three months ended March 31,

(in thousands)

Investment in investment securities

Proceeds from maturity of investment securities

Investment in investment securities

Build out of Amsterdam site

Build out of Lexington site

Acquisition of uniQure France SAS, net of cash acquired

Net cash used in investing activities

During the nine months ended September 30, 2023, we invested $366.4 million of our cash on hand into euro and U.S.

dollar denominated government bonds (nil for the nine months ended September 30, 2022).

During the nine months ended September 30, 2023, we received $106.3 million from the repayment of previous investments into euro and U.S.

dollar denominated government bonds (nil for nine months ended September 30, 2022).

We invested $2.2 million and $3.0 million, respectively, into our Amsterdam, Netherlands and Lexington, Massachusetts sites consumed during the nine months ended September 30, 2023, compared to $8.3 million and $4.4 million for the same period in 2022.

Net cash generated from investing activities

During the three months ended March 31, 2024, we received $150.1 million from the repayment of previous investments into euro and U.S.

dollar denominated government bonds ($5.3 million for three months ended March 31, 2023).

During the three months ended March 31, 2024, we invested $83.8 million of our cash on hand into euro denominated government bonds (nil for the three months ended March 31, 2023).

We invested $1.1 million and $1.3 million, respectively, into our Amsterdam, Netherlands and Lexington, Massachusetts sites during the three months ended March 31, 2024, compared to $0.7 million and $1.7 million for the same period in 2023.

Net cash generated from financing activities

In the nine months ended September 30, 2023, we generated $362.7 million from financing activities compared to $0.8 million for the same period in 2022.

Nine months ended September 30,

In the three months ended March 31, 2024, we generated nil from financing activities compared to $0.1 million for the same period in 2023.

Three months ended March 31,

(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

Contingent consideration milestone payment

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

Net cash generated from financing activities

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

During the nine months ended September 30, 2023, we received $0.3 million from the exercise of options to purchase ordinary shares in relation to our 2014 Plans compared to $0.8 million for the same period in 2022.

In September 2023, following the FDA’s clearance of the IND application for AMT-260, we made a payment of $9.5 million to the former shareholders of uniQure France SAS to settle a portion of the contingent consideration based on contractually defined milestones, of which $7.6 million was classified as cash flows from financing activities and $1.9 million was classified as a net cash flow used in operating activities.

During the three months ended March 31, 2024, we received nil from the exercise of options to purchase ordinary shares in relation to our 2014 Plans, compared to $0.1 million for the same period in 2023.

Funding requirements

13 unchanged sentences

● the costs associated with maintaining quality compliance and optimizing our manufacturing processes, including the operating costs associated with our Lexington, Massachusetts manufacturing facility.

● the financial impact of the Reorganization;

● the costs associated with increasing the scale and capacity of our manufacturing capabilities.

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