What changed in this filing

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Item 1A. Risk Factors

2022-08-08 compared with 2022-05-02 · 28 added, 23 removed, 813 unchanged (6% of the section changed)

62 unchanged sentences

We cannot guarantee that any preclinical tests or clinical trials will be completed as planned or completed on schedule, if at all.

In July 2022, we learned that three patients of the 14 patients that were treated with the higher dose of AMT-130 in our Phase Ib/II clinical trial for Huntington’s disease had experienced certain serious adverse reactions that were potentially attributable to AMT-130.

The reactions in these three patients each have been classified as suspected unexpected serious adverse reactions (“SUSARs”).

Based on the recommendation of the independent Data Safety Monitoring Board for the clinical trial (“DSMB”) after review of these SUSARs, we have postponed further enrollment and dosing of high dose patients until we conduct a comprehensive safety review with the DSMB.

We do not currently know what the outcome of this safety review will be.

Moreover, in accordance with regulatory requirements, we have reported these adverse reactions, the DSMB’s recommendations, and our implementation of the recommendations to the applicable regulatory authorities.

We do not currently know whether the regulatory authorities will require or recommend that we take further actions.

A failure of one or more preclinical tests or clinical trials can occur at any stage of testing.

146 unchanged sentences

In the event of an accident or failure to comply with environmental, occupational health and safety and export control laws and regulations, we could be held liable for damages that result, and any such liability could exceed our assets and resources, and could result in material harm to our business, financial condition, and results of operations.

Our resources might be adversely affected if we are unable to validate our manufacturing processes or develop new processes to meet our product supply needs and obligations.

Our resources might be adversely affected if we are unable to validate our manufacturing processes and methods, or develop new processes and methods to meet our product supply needs and obligations.

The manufacture of our AAV gene therapies, including etranacogene dezaparvovec, is complex and requires significant expertise.

2 unchanged sentences

In the past, we have manufactured certain batches of product candidates, intended for nonclinical, clinical and process validation purposes that have not met all of our pre-specified quality parameters.

To meet our expected future production needs and our regulatory filing timelines for gene therapy product candidates we will need to complete the validation of our manufacturing processes, and we may need to develop and validate new or larger scale manufacturing processes.

If we are unable to consistently manufacture our gene therapy product candidates or any approved products in accordance with our pre-specified quality parameters and applicable regulatory standards, it could adversely impact our ability to validate our manufacturing processes, to meet our production needs, to file a BLA or other regulatory submissions, to develop our other proprietary programs, to conserve our cash, or to receive financial payments pursuant to our agreements with third parties.

To meet our expected future production needs and our regulatory filing timelines for gene therapy product candidates we will need to complete the validation of our manufacturing processes and methods, and we may need to develop and validate new or larger scale manufacturing processes and methods.

If we are unable to consistently manufacture our gene therapy product candidates or any approved products in accordance with our pre-specified quality parameters and applicable regulatory standards, it could adversely impact our ability to validate our manufacturing processes and methods, to meet our production needs, to file a BLA or other regulatory submissions, to develop our other proprietary programs, to conserve our cash, or to receive financial payments pursuant to our agreements with third parties.

Risks Related to Regulatory Approval of Our Products

85 unchanged sentences

Risks Related to Commercialization

If we are unable to successfully commercialize our product candidates or experience significant delays in doing so, our business could be materially harmed.

If we, or our commercial partner, are unable to successfully commercialize our product candidates or experience significant delays in doing so, our business could be materially harmed.

Our ability to generate product revenues will depend on the successful development and eventual commercialization of our product candidates.

89 unchanged sentences

Any of these scenarios could decrease demand for any products for which we obtain marketing approval.

If we obtain approval to commercialize any of our product candidates outside of the United States, a variety of risks associated with international operations could materially adversely affect our business.

If we, or our commercial partner, obtain approval to commercialize any of our product candidates outside of the United States, a variety of risks associated with international operations could materially adversely affect our business.

We expect that we will be subject to additional risks in commercializing any of our product candidates outside the United States, including:

170 unchanged sentences

If any of our trade secrets were to be lawfully obtained or independently developed by a competitor, we would have no right to prevent them, or those with whom they communicate, from using that technology or information to compete with us.

Risks Related to Acquisitions

Our acquisition strategy may not produce the cash flows expected or could result in additional costs and challenges.

Any acquisition, including the recent acquisition of Corlieve Therapeutics SAS (“Corlieve”), could expose us to unknown liabilities and risks, and we may incur additional costs and expenses necessary to address an acquired company’s failure to comply with laws and governmental rules and regulations.

Risks Related to Business Development

Our business development strategy may not produce the cash flows expected or could result in additional costs and challenges.

Any business development transaction, including the recent acquisition of Corlieve Therapeutics SAS (“Corlieve”), could expose us to unknown liabilities and risks, and we may incur additional costs and expenses necessary to address an acquired company’s failure to comply with laws and governmental rules and regulations.

We could incur additional costs related to resources to align our business practices and operations.

38 unchanged sentences

Risks Related to Our Financial Position and Need for Additional Capital

We had a gain in the year ended December 31, 2021, but incurred significant losses in previous prior years and expect to incur losses over the next several years and may never achieve or maintain profitability.

We had a net loss of $46.7 million in the three months ended March 31, 2022, and a net gain of $329.6 million in the full year 2021.

As of March 31, 2022, we had an accumulated deficit of $501.8 million.

We had a gain in the year ended December 31, 2021, but incurred significant losses in previous years and expect to incur losses over the next several years and may never achieve or maintain profitability.

We had a net loss of $85.7 million in the six months ended June 30, 2022, and a net gain of $329.6 million in the full year 2021.

As of June 30, 2022, we had an accumulated deficit of $540.9 million.

In the past, we have financed our operations primarily through the sale of equity securities and convertible debt, venture loans, upfront payments from our collaboration partners and, to a lesser extent, subsidies and grants from governmental agencies and fees for services.

2 unchanged sentences

We expect to continue to incur significant expenses and losses over the next several years, and our net losses may fluctuate significantly from quarter to quarter and year to year.

We anticipate that our expenses will increase substantially as we:

● advance the clinical development of AMT-130 for our Huntington’s disease gene therapy program;

● advance multiple research programs related to gene therapy candidates targeting liver-directed and central nervous system (“CNS”) diseases;

● continue to expand our employee base to support research and development, as well as general and administrative functions;

● acquire or in-license rights to new therapeutic targets or product candidates;

● continue to expand, enhance, and optimize our technology platform, including our manufacturing capabilities, next-generation viral vectors and promoters, and other enabling technologies;

● maintain, expand, and protect our intellectual property portfolio, including in-licensing additional intellectual property rights from third parties;

● make potential future milestone payments related to the acquisition of Corlieve, if any.

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

● advancing AMT-130 for our Huntington’s disease gene therapy program into phase III clinical study;

● advancing our gene therapy programs for temporal lobe epilepsy and Fabry into Phase I/II clinical studies;

● advancing preclinical research and development for gene therapy product candidates targeting other diseases;

● 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;

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

● making potential future milestone payments related to the acquisition of Corlieve, if any.

We may never succeed in these activities and, even if we do, may never generate revenues that are sufficient to achieve or sustain profitability.

10 unchanged sentences

Our existing and any future indebtedness could adversely affect our ability to operate our business.

As of March 31, 2022, we had $100.0 million of outstanding principal of borrowings under the 2021 Restated Facility, which we are required to repay in equal installments between December 2024 and December 2025 or in full in December 2025 if, prior to June 30, 2024, either (a) the BLA for AMT-061 is approved by the FDA or (b) AMT-130 is advanced into a pivotal trial.

As of June 30, 2022, we had $100.0 million of outstanding principal of borrowings under the 2021 Restated Facility, which we are required to repay in equal installments between December 2024 and December 2025 or in full in December 2025 if, prior to June 30, 2024, either (a) the BLA for AMT-061 is approved by the FDA or (b) AMT-130 is advanced into a pivotal trial.

We could in the future incur additional debt obligations beyond our borrowings from Hercules.

96 unchanged sentences

Our share price has been and may in the future be volatile.

From the start of trading of our ordinary shares on the Nasdaq Global Select Market on February 4, 2014 through April 27, 2022, the sale price of our ordinary shares ranged from a high of $82.49 to a low of $4.72.

The closing price on April 27, 2022, was $15.15 per ordinary share.

From the start of trading of our ordinary shares on the Nasdaq Global Select Market on February 4, 2014 through August 3, 2022, the sale price of our ordinary shares ranged from a high of $82.49 to a low of $4.72.

The closing price on August 3, 2022, was $24.59 per ordinary share.

The stock market in general and the market for smaller biopharmaceutical companies in particular, have experienced extreme volatility that has often been unrelated to the operating performance of particular companies.

16 unchanged sentences

Our directors, executive officers, and major shareholders, if they choose to act together, will continue to have a significant degree of control with respect to matters submitted to shareholders for approval.

Our directors, executive officers and major shareholders holding more than 5% of our outstanding ordinary shares, in the aggregate, beneficially own approximately 50.3% of our issued shares (including such shares to be issued in relation to exercisable options to purchase ordinary shares) as of March 31, 2022.

Our directors, executive officers and major shareholders holding more than 5% of our outstanding ordinary shares, in the aggregate, beneficially own approximately 54.3% of our issued shares (including such shares to be issued in relation to exercisable options to purchase ordinary shares) as of June 30, 2022.

As a result, if these shareholders were to choose to act together, they may be able, as a practical matter, to control many matters submitted to our shareholders for approval, as well as our management and affairs.

75 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 1A. Risk Factors