38 unchanged sentences
We have incurred net losses since our inception in 2017.
−Removed: We incurred net losses of $34.3 million and $42.8 million for the three months ended March 31, 2023, and 2022, respectively.
−Removed: As of March 31, 2023, we had an accumulated deficit of $526.7 million.
+Added: We incurred net losses of $58.2 million and $82.4 million for the six months ended June 30, 2023 and 2022, respectively.
+Added: As of June 30, 2023, we had an accumulated deficit of $550.6 million.
Substantially all of our operating losses have resulted from expenses incurred in connection with our research and development programs, acquiring the rights to our product candidates, and from general and administrative expenses associated with our operations.
25 unchanged sentences
We will require substantial future capital in order to complete planned and future preclinical and clinical development for our portfolio of product candidates and potentially commercialize these product candidates, if approved.
−Removed: If our product portfolio progresses into later stage clinical trials, or our current preclinical product candidates progress into the clinical trial stage, we expect our spending levels to significantly increase in connection with our continued clinical trial activites and production of our clinical product candidates supply.
+Added: If our product portfolio progresses into later stage clinical trials, or our current preclinical product candidates progress into the clinical trial stage, we expect our spending levels to significantly increase in connection with our continued clinical trial activities and production of our clinical product candidates supply.
In addition, if we obtain marketing approval for any of our product candidates, we expect to incur significant expenses related to product sales, medical affairs, marketing, manufacturing and distribution.
4 unchanged sentences
Our operations have consumed significant amounts of cash since inception.
−Removed: As of March 31, 2023, our cash, cash equivalents and marketable securities were $167.8 million.
−Removed: We expect that our existing cash, cash equivalents and marketable securities will enable us to fund our operating expenses and capital expenditure requirements into the first half of 2025.
+Added: As of June 30, 2023, our cash, cash equivalents and marketable securities were $151.5 million.
+Added: We expect that our existing cash, cash equivalents and marketable securities will enable us to fund our operating expenses and capital expenditure requirements into the fourth quarter of 2025.
However, we have based this estimate on assumptions that may prove to be wrong, and our operating plan may change as a result of factors currently unknown to us.
145 unchanged sentences
Other recent clinical trials involving high doses of AAV vectors have also resulted in liver damage and death.
−Removed: Further, following administration of any AAV vector, patients are likely to develop NAbs specific to the vector administered.
+Added: Further, following administration of any AAV vector, patients are likely to develop neutralizing antibodies specific to the vector administered.
Other preclinical studies have suggested that high dosages of AAV administration may result in toxicity due to degeneration of the dorsal root ganglia.
152 unchanged sentences
In addition, the discovery program, under which we have rights to new technologies for our product candidates is currently also set to expire in
−Removed: The term of the exploratory research program in large indications, initially TLE, expires in August 2024.
+Added: The term of the exploratory research program in large indications expires in August 2024.
If we seek to extend or alter the terms of our collaboration, we will need to negotiate a new or amended agreement, which may not be available to us on equally favorable terms, if at all.
22 unchanged sentences
We cannot assure you that, upon inspection, the FDA will determine that any of our future clinical trials will comply with cGCPs.
−Removed: In addition, our clinical trials must be conducted with product candidates produced in accordance with the requirements in cGMP regulations.
+Added: In addition, our clinical trials must be conducted with product candidates produced in accordance with the requirements in the current Good Manufacturing Practices, or cGMP regulations.
Our failure or the failure of our CROs to comply with these regulations may require us to repeat clinical trials, which would delay the regulatory approval process and could also subject us to enforcement action.
Although we currently design and intend to continue designing our planned clinical trials for our product candidates, for the foreseeable future CROs will conduct all of our planned clinical trials.
−Removed: As a result, many important aspects of our development programs, including their conduct and timing, will be outside of our direct control.
−Removed: Our reliance on third
−Removed: parties to conduct future preclinical studies and clinical trials will also result in less day-to-day control over the management of data developed through preclinical studies and clinical trials than would be the case if we were relying entirely upon our own staff.
+Added: As a result, many important aspects of our
+Added: development programs, including their conduct and timing, will be outside of our direct control.
+Added: Our reliance on third parties to conduct future preclinical studies and clinical trials will also result in less day-to-day control over the management of data developed through preclinical studies and clinical trials than would be the case if we were relying entirely upon our own staff.
If any of our relationships with these third-party CROs terminate, we may not be able to enter into arrangements with alternative CROs.
177 unchanged sentences
(partnered with GlaxoSmithKline), which is enrolling a Phase 3 clinical trial with a humanized anti-human sortilin monoclonal antibody for FTD-GRN, and Prevail Therapeutics Inc.
−Removed: (now part of Eli Lilly & Co), which has initiated a Phase 1/2 clinical trial for a gene therapy treatment for FTD-GRN, and is expected to continue enrolling through 2023.
−Removed: Several other companies, including Applied Genetic Technologies Corporation (acquired by Syncona in November 2022), Orchard Therapeutics plc, Sinfonia Biotherapeutics, QurAlis and AviadoBio Therapeutics, are conducting preclinical research using gene therapy approaches to treat FTD-GRN patients.
+Added: (now part of Eli Lilly & Co), which is conducting a Phase 1/2 clinical trial for a gene therapy treatment for FTD-GRN, and is expected to continue enrolling through 2023.
+Added: Several other companies, including Orchard Therapeutics plc, Sinfonia Biotherapeutics, QurAlis and AviadoBio Therapeutics, are conducting preclinical research using gene therapy approaches to treat FTD-GRN patients.
AviadoBio Ltd has reported the planned initiation of a phase 1/2 trial in 2023.
57 unchanged sentences
The in-licensed patent applications are directed to certain new AAV capsids, to recombinant AAV viruses, or rAAV, capable of delivering certain genes into human cells to treat monogenic disorders of the CNS, to methods of treating those monogenic diseases with rAAV, as well as to certain aspects of our manufacturing capabilities and related technologies.
−Removed: Our intellectual property further includes a patent application that we solely own that covers processes for manufacturing rAAV.
+Added: Our intellectual property further includes patent applications that we solely own that cover processes for manufacturing rAAV.
We also have options under the Penn Agreement to add additional intellectual property to our existing license.
443 unchanged sentences
Failure to succeed in clinical trials may make it more challenging to recruit and retain qualified scientific personnel.
−Removed: Further, the reductions in workforce announced in March 2022 and November 2022 may also make retention of our current personnel both more important and more challenging.
+Added: Further, the reductions in workforce announced in March 2022, November 2022 and July 2023 may also make retention of our current personnel both more important and more challenging.
These workforce reductions resulted in the loss of longer-term employees, the loss of institutional knowledge and expertise and the reallocation and combination of certain roles and responsibilities across the organization, all of which could adversely affect our operations.
−Removed: Given the complexity of
−Removed: our business, we must continue to implement and improve our managerial, operational and financial systems, manage our facilities and continue to recruit and retain qualified personnel.
+Added: complexity of our business, we must continue to implement and improve our managerial, operational and financial systems, manage our facilities and continue to recruit and retain qualified personnel.
Given the complexity of our business, we must continue to implement and improve our managerial, operational and financial systems, manage our facilities and continue to recruit and retain qualified personnel.
37 unchanged sentences
Changes in tax laws and regulations in federal, state, local, and foreign jurisdictions could have material adverse impacts on our business, cash flows, operating results, or financial condition, and could materially affect our tax obligations and effective tax rate.
−Removed: For example, U.S.
−Removed: tax legislation enacted on December 22, 2017, informally titled the Tax Cuts and Jobs Act, or the Tax Cuts and Jobs Act, significantly reformed the Internal Revenue Code of 1986, as amended, or the Code.
+Added: For example, the Tax Cuts and Jobs Act significantly reformed the Internal Revenue Code of 1986, as amended, or the Code.
This legislation, among other things, included changes to U.S.
federal tax rates, imposed significant additional limitations on the deductibility of interest and the use of net operating losses generated in tax years beginning after December 31, 2017 and allowed for the expensing of capital expenditures.
−Removed: The Tax Cuts and Jobs Act is unclear in many respects and could be subject to potential amendments and technical corrections, as well as interpretations and implementing regulations by the Treasury and the Internal Revenue Service, or IRS, any of which could lessen or increase certain adverse impacts of the legislation.
+Added: The Tax Cuts and Jobs Act is unclear in many respects and could be subject to potential amendments and technical corrections, as well as interpretations and implementing regulations by the U.S.
+Added: Treasury and the Internal Revenue Service, or IRS, any of which could lessen or increase certain adverse impacts of the legislation.
In addition, in response to the COVID-19 pandemic, the Coronavirus Aid, Relief, and Economic Security Act, or the CARES Act, was signed into law in March 2020, and subsequently in December 2020, the Continued Assistance for Unemployed Workers Act of 2020, or CARES Act II, was signed into law.
3 unchanged sentences
In addition, it is uncertain if and to what extent various states will conform to the Tax Cuts and Jobs Act, as amended by the CARES Act and CARES Act II, or any newly enacted federal tax legislation.
−Removed: Changes in tax laws or regulations in the
−Removed: various tax jurisdictions we are subject to that are applied adversely to us or our clients could increase the costs of our products and harm our business.
+Added: Changes in tax laws or regulations in the various tax jurisdictions we are subject to that are applied adversely to us or our clients could increase the costs of our products and harm our business.
Additionally, we use our best judgment in attempting to quantify and reserve for our tax obligations.
67 unchanged sentences
● our cash position or the announcement or expectation of additional financing efforts;
−Removed: ● the ongoing COVID-19 pandemic could adversely impact our business, including our clinical trials and clinical trial operations;
+Added: ● health pandemics could adversely impact our business, including our clinical trials and clinical trial operations;
● general economic, industry and market conditions, including rising interest rates, market volatility, and inflation;
2 unchanged sentences
Our executive officers, directors, principal stockholders and their affiliates exercise significant influence over our company, which will limit your ability to influence corporate matters and could delay or prevent a change in corporate control.
−Removed: As of March 31, 2023, our executive officers, directors, beneficial owners of 5% or more of our capital stock and their respective affiliates beneficially owned shares representing a substantial portion of our capital stock.
+Added: As of June 30, 2023, our executive officers, directors, beneficial owners of 5% or more of our capital stock and their respective affiliates beneficially owned shares representing a substantial portion of our capital stock.
This group of stockholders has the ability to control us through this ownership position and may be able to determine all matters requiring stockholder approval.
12 unchanged sentences
Ensuring that we have adequate internal financial and accounting controls and procedures in place so that we can produce accurate financial statements on a timely basis is a costly and time-consuming effort that will need to be frequently evaluated.
−Removed: Our failure to maintain the effectiveness of our internal controls in accordance with the requirements of the Sarbanes-Oxley Act could have a material adverse effect on our business.If we identify one or more material weaknesses, it could result in an adverse reaction in the financial markets due to a loss of confidence in the reliability of our financial statements.
+Added: Our failure to maintain the effectiveness of our internal controls in accordance with the requirements of the Sarbanes-Oxley Act could have a material adverse effect on our business.
+Added: If we identify one or more material weaknesses, it could result in an adverse reaction in the financial markets due to a loss of confidence in the reliability of our financial statements.
In addition, if we are not able to continue to meet these requirements, we may not be able to remain listed on The Nasdaq Stock Market LLC, or Nasdaq.
123 unchanged sentences
For example, the global financial crisis caused extreme volatility and disruptions in the capital and credit markets, and, in recent months, the global economy has been impacted by increasing interest rates and inflation.
−Removed: Likewise, the capital and credit markets may be adversely affected by the recent conflict between Russia and Ukraine, and the possibility of a wider European or global conflict, and global sanctions imposed in response thereto.
+Added: Likewise, the capital and credit markets may be adversely affected by the ongoing conflict between Russia and Ukraine, and the possibility of a wider European or global conflict, and global sanctions imposed in response thereto.
Moreover, there has been recent turmoil in the global banking system.
For example, in March 2023, Sillicon Valley Bank was closed by the California Department of Financial Protection and Innovation, which appointed the FDIC as receiver.
−Removed: While we did not hold any cash directly at SVB, we regularly maintain cash balances at third-party financial institutions in excess of the FDIC insurance limit and there is no guarantee that the federal government would guarantee all depositors if such financial instutitions were to fail, as they did with SVB depositors, in the event of further bank closures and continued instability in the global banking system.
+Added: While we did not hold any cash directly at SVB or other banking institutions that have since failed, we regularly maintain cash balances at third-party financial institutions in excess of the FDIC insurance limit and there is no guarantee that the federal government would guarantee all depositors if such financial instutitions were to fail, as they did with SVB depositors, in the event of further bank closures and continued instability in the global banking system.
A severe or prolonged economic downturn, such as the global financial crisis, could result in a variety of risks to our business, including, weakened demand for our product candidates and our ability to raise additional capital when needed on acceptable terms, if at all.
13 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.