What changed in this filing

/stocks — the workspaceLOADING

Item 2. Management’s Discussion and Analysis

2024-08-08 compared with 2024-05-09 · 61 added, 34 removed, 161 unchanged (37% of the section changed)

18 unchanged sentences

Food and Drug Administration (“FDA”) placed a clinical hold on the our nomlabofusp clinical program after we notified the FDA of mortalities at the highest dose levels of a 26-week non-human primate toxicology study that was designed to support extended dosing of patients with nomlabofusp.

In August 2022, we submitted a complete response to the clinical hold following a Type C Meeting with the FDA, and proposed as nomlabofusp's next clinical trial a Phase 2, four-week, dose exploration study in FA patients starting at the lower dose levels tested in our Phase 1 multiple-ascending dose clinical trial.

In September 2022, the FDA lifted its full clinical hold on the nomlabofusp program and imposed a partial clinical hold.

3 unchanged sentences

In July 2023, following the FDA’s review of our complete response to the partial clinical hold, the FDA cleared initiation of a second cohort at 50 mg of our four-week, placebo-controlled, Phase 2 dose exploration trial and initiation of an OLE study with daily dosing of 25 mg.

In May 2024 the FDA removed the partial clinical hold.

In February 2024, we reported positive top-line data and successful completion of their four-week, placebo-controlled Phase 2 dose exploration study of nomlabofusp in participants with FA.

Nomlabofusp was generally well tolerated throughout the four-week treatment periods, had a predictable pharmacokinetic profile and let to dose dependent increases in FXN levels in all evaluated tissues (skin and buccal cells) after daily dosing of 14 days followed by every other day dosing until day 28 in the 25 mg and 50 mg cohorts.

Nomlabofusp was generally well tolerated throughout the four-week treatment periods, had a predictable pharmacokinetic profile and led to dose dependent increases in FXN levels in all evaluated tissues (skin and buccal cells) after daily dosing of 14 days followed by every other day dosing until day 28 in the 25 mg and 50 mg cohorts.

Participants in the 25 mg (n=13) and 50 mg (n=15) cohorts were randomized 2:1 to receive subcutaneous injections of nomlabofusp or placebo.

The initiation of additional U.S.

clinical trials evaluating nomlabofusp are contingent on FDA review of data under the partial clinical hold.

In January 2024, we initiated the OLE trial, discussed above, evaluating daily subcutaneous injections of 25 mg of nomlabofusp self-administered or administered by a caregiver, with the first patient dosed in March 2024.

Additional patients continue to be enrolled and dosed and additional clinical sites added.

In May 2024 the FDA removed the partial clinical hold on the development of nomlabofusp.

In March 2024, the first patient was dosed in the OLE trial, discussed above, evaluating daily subcutaneous injections of 25 mg of nomlabofusp self-administered or administered by a caregiver.

This study is ongoing with all 7 sites activated and additional patients continue to be enrolled.

Participants who completed treatment in the Phase 2 dose exploration study, or who previously completed a prior clinical trial of nomlabofusp, are potentially eligible to screen for the OLE study.

The OLE study will evaluate the safety and tolerability, pharmacokinetics, and frataxin levels in peripheral tissues as well as other exploratory pharmacodynamic markers (lipid profiles and gene expression data) following long-term subcutaneous administration of nomlabofusp.

Dose escalation in the OLE study is contingent on the FDA’s review of data from the 50 mg cohort of the Phase 2 study and available data from the OLE study, due to the continued partial clinical hold.

Interim data is expected in the fourth quarter of 2024.

In addition, clinical assessments collected during the study will be compared to data from a matched control arm derived from participants in the Friedreich’s Ataxia Clinical Outcome Measures Study (FACOMS) database.

Recently, we had discussions with the FDA regarding the use of tissue FXN levels as a novel surrogate endpoint.

The FDA has acknowledged that frataxin deficiency appears to be critical to the pathogenic mechanism of FA, and that there continues to be an unmet need for treatments for FA patients that address the underlying disease pathophysiology.

Dose escalation to the 50 mg dose in the OLE study is currently planned following further characterization of the frataxin pharmacodynamics (PD) at the 25 mg dose.

Interim data is expected in the fourth quarter of 2024.

We also had separate discussions with the FDA regarding the use of tissue FXN levels as a novel surrogate endpoint.

The FDA acknowledged that frataxin deficiency appears to be critical to the pathogenic mechanism of FA, and that there continues to be an unmet need for treatments for FA patients that address the underlying disease pathophysiology.

We intend to pursue an accelerated approval using FXN levels, supportive PD and clinical information, and safety data from the OLE study, along with additional non-clinical pharmacology information needed to support the novel surrogate endpoint approach.

We are beginning to plan for a confirmatory study and are targeting a BLA submission in the second half of 2025.

We plan to expand the nomlabofusp clinical program into adolescent (12-17 years old) and pediatric (2-11 years old) patients with FA.

The Company expects to initiate a pharmacokinetics (PK)run-in study in adolescents by the end of this year and expects to transition these study participants into the ongoing OLE study upon completion of the PK study.

The run-in-study will enroll 12-15 adolescent patients who will be randomized 2:1 to receive either nomlabofusp or placebo daily.

The Company is also planning the initiation of a global confirmatory study by mid-2025 with potential sites in the U.S., Europe, the U.K., Canada and Australia.

The Biologics License Application (BLA) filing is targeted in the second half of 2025 to support accelerated approval.

On May 30, 2024, we announced that the FDA's Center for Drug Evaluation and Research ("CDER") had selected nomlabofusp as one of a few programs for participation in the Support for Clinical Trials Advancing Rare Disease Therapeutics ("Start") Pilot Program.

The objective of the START Pilot Program is to accelerate the development of drugs for rare diseases that lead to significant disability or death by facilitating frequent advise and regular communication with the FDA staff to expedite the review process for biologics and drugs.

Nomlabofusp has been granted Orphan Drug (U.S.

8 unchanged sentences

We received net proceeds of approximately $161.8 million after deducting underwriting discounts, commissions and other offering expenses.

In May 2024, we entered into a Sales Agreement (the "ATM Agreement") with Guggenheim Securities, LLC in connection with the establishment of an “at-the-market” offering program providing for the sale of up to an aggregate of $100.0 million of shares of our common stock from time to time.

To date, we have made no sales under this ATM agreement.

Critical Accounting Policies and Significant Judgments and Estimates

63 unchanged sentences

Results of Operations

Comparison of three months ended March 31, 2024 and 2023

The following table summarizes our results of operations for the three months ended March 31, 2024 and 2023:

Three Months Ended March 31,

Comparison of three months ended June 30, 2024 and 2023

The following table summarizes our results of operations for the three months ended June 30, 2024 and 2023:

Three Months Ended June 30,

(in thousands)

7 unchanged sentences

Research and development expenses

Research and development expenses for the three months ended March 31, 2024 increased $8.4 million compared to the three months ended March 31, 2023.

The increase in research and development expenses was primarily driven by an increase of $5.7 million in nomlabofusp manufacturing costs, an increase of $1.0 million in clinical costs primarily associated with the OLE study which began dosing patients in the first quarter of 2024, an increase of $1.0 million in personnel expense due to increased headcount, an increase of $0.3 million in consulting fees and an increase of $0.2 million in stock compensation expense associated with grants made in the first quarter of 2024.

Research and development expenses for the three months ended June 30, 2024 increased $13.8 million compared to the three months ended June 30, 2023.

The increase in research and development expenses was primarily driven by an increase of $10.6 million in nomlabofusp manufacturing costs, an increase of $2.1 million in clinical costs primarily associated with the OLE study which began dosing patients in the first quarter of 2024 and initial costs related to the Company's participation in the Friedreich's Ataxia Research Alliances (FARA) Track-FA program, an increase of $1.1 million in personnel expense due to increased headcount.

General and administrative expenses

General and administrative expenses for the three months ended March 31, 2024 increased $0.7 million compared to the three months ended March 31, 2023.

The increase in general and administrative expenses was primarily driven by an increase of $0.2 million in personnel expense, an increase of $0.2 million in legal fees, an increase of $0.1 million in stock compensation expense associated with grants made in the first quarter of 2024.

General and administrative expenses for the three months ended June 30, 2024 increased $1.2 million compared to the three months ended June 30, 2023.

The increase in general and administrative expenses was primarily driven by an increase of $0.6 million in professional fees primarily related to legal fees, consulting costs and other public company related expenses, an increase of $0.4 million in personnel expense and an increase of $0.1 million in higher stock compensation expense associated with grants made in the first quarter of 2024.

Other income (expense), net

Other income (expense), net was $2.1 million income in the first quarter of 2024 compared to $1.1 million income in the first quarter of 2023.

The first quarter of 2024 primarily relates to interest income which increased as compared to the first quarter of 2023 due to a higher investment base and higher interest rates on that base.

Other income (expense), net was $3.0 million income in the three months ended June 30, 2024 compared to $1.3 million income in the three months ended June 30, 2023.

The increase primarily relates to interest income earned on a higher investment base and with higher interest rates on that base.

Comparison of six months ended June 30, 2024 and 2023

The following table summarizes our results of operations for the six months ended June 30, 2024 and 2023:

Six Months Ended June 30,

(in thousands)

Statement of Operations Data:

Operating expenses:

Research and development

General and administrative

Total operating expenses

Loss from operations

Other income (expense), net

Research and development expenses

Research and development expenses for the six months ended June 30, 2024 increased $22.2 million compared to the six months ended June 30, 2023.

The increase in research and development expenses was primarily driven by an increase of $16.3 million in nomlabofusp manufacturing costs, an increase of $3.1 million in clinical costs primarily associated with the OLE study which began dosing patients in the first quarter of 2024 and the Track FA program discussed above, an increase of $2.0 million in personnel expense due to increased headcount, an increase of $0.3 million of internal laboratory costs and an increase of $0.3 million in stock compensation expense associated with grants made in the first quarter of 2024.

General and administrative expenses

General and administrative expenses for the six months ended June 30, 2024 increased $1.9 million compared to the six months ended June 30, 2023.

The increase in general and administrative expenses was primarily driven by an increase of $0.8 million in professional fees primarily related to legal fees, consulting costs and other public company related expenses, an increase of $0.6 million in personnel expense, an increase of $0.3 million in stock compensation expense associated with grants made in the first quarter of 2024.

Other income (expense), net

Other income (expense), net was $5.1 million income in the six months ended June 30, 2024 compared to $2.4 million income in the six months ended June 30, 2023.

The increase primarily relates to interest income earned on a higher investment base and with higher interest rates on that base.

Liquidity and Capital Resources

2 unchanged sentences

The following table summarizes our sources and uses of cash for each of the periods presented below:

Three Months Ended March 31,

Six Months Ended June 30,

(in thousands)

4 unchanged sentences

Net cash used in operating activities

During the three months ended March 31, 2024, operating activities used $10.4 million of cash, resulting from our net loss of $14.7 million, adjusted for noncash expenses of $1.6 million and changes in our operating assets and liabilities resulting in a source of cash of $2.7 million.

During the six months ended June 30, 2024, operating activities used $24.4 million of cash, resulting from our net loss of $36.3 million, adjusted for noncash expenses of $2.1 million and changes in our operating assets and liabilities resulting in a source of cash of $9.7 million.

Our net loss was primarily attributed to research and development activities related to our nomlabofusp program and our general and administrative expenses as described above.

Noncash expenses are primarily stock-based compensation expenses.

The change in operating assets and liabilities was primarily due to an increase in accounts payable and accrued expenses.

During the three months ended March 31, 2023, operating activities used $7.6 million of cash, resulting from our net loss of $6.5 million, adjusted for noncash expenses of $1.3 million and changes in our operating assets and liabilities resulting in a source of cash of $2.3 million.

Noncash expenses primarily relate to stock-based compensation expenses.

The change in operating assets and liabilities was primarily due to an increase in accrued expenses and accounts payable driven primarily by the increase in R&D activities discussed as well as an increase in prepaid expense.

During the six months ended June 30, 2023, operating activities used $14.9 million of cash, resulting from our net loss of $14.9 million, adjusted for noncash expenses of $3.3 million and changes in our operating assets and liabilities resulting in a source of cash of $3.4 million.

Our net loss was primarily attributed to research and development activities related to our nomlabofusp program and our general and administrative expenses as described above.

Noncash expenses are primarily stock-based compensation expenses.

The change in operating assets and liabilities was primarily due to a decrease in accounts payable and accrued expenses.

Noncash expenses primarily relate to stock-based compensation expenses.

The change in operating assets and liabilities was primarily due to a decrease in accrued expenses and offset by an increase in accounts payable.

Net cash provided by (used in) investing activities

During the three months ended March 31, 2024, investing activities used $68.4 million of cash to purchase $84.9 million of marketable securities, partially offset by $16.5 million of cash provided by maturities of marketable securities.

During the three months ended March 31, 2023, investing activities provided $92.3 million of cash from maturities of marketable securities.

During the six months ended June 30, 2024, investing activities used $131.9 million of cash to purchase $166.6 million of marketable securities, partially offset by $35 million of cash provided by maturities of marketable securities.

During the six months ended June 30, 2023, investing activities provided $82.4 million of cash, including $92.3 million from maturities of marketable securities and partially offset by $9.8 million in purchases of marketable securities.

Net cash provided by financing activities

During the three months ended March 31, 2024, financing activities provided $162.2 million of cash flows primarily from an offering of common stock.

During the three months ended March 31, 2023, there were no financing activities.

During the six months ended June 30, 2024, financing activities provided $161.8 million of cash flows primarily from an offering of common stock.

During the six months ended June 30, 2023, there were no financing activities.

Operating Capital Requirements

1 unchanged sentence

We have to date incurred net losses.

We incurred net losses of approximately $14.7 million and $6.5 million for the three months ended March 31, 2024 and 2023, respectively.

As of March 31, 2024, we had an accumulated deficit of $203.2 million and cash and cash equivalents of $239.0 million, excluding restricted cash of $1.3 million.

We incurred net losses of approximately $36.3 million and $14.9 million for the six months ended June 30, 2024 and 2023, respectively.

As of June 30, 2024, we had an accumulated deficit of $224.8 million and cash and cash equivalents of $226.1 million, excluding restricted cash of $1.3 million.

Losses have resulted principally from costs incurred in connection with research and development activities, and general and administrative costs associated with the development of nomlabofusp and our operations.

15 unchanged sentences

We could also be required to seek funds through arrangements with collaborative partners, strategic alliances or otherwise at an earlier stage than otherwise would be desirable and we may be required to relinquish rights to some of our technologies or product candidates or otherwise agree to terms unfavorable to us, any of which may have a material adverse effect on our business, operating results and prospects.

In addition, geopolitical tensions, volatility of capital markets, and other adverse macroeconomic events, including those due to inflationary pressures, rising interest rates, bank instability and the ability of the U.S.

government to manage federal debt limits, as well as the potential impact of health crises on the global financial markets may reduce our ability to access capital, which could negatively affect our liquidity and ability to continue as a going concern.

10 unchanged sentences

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

What changed 10-Q

Item 2. Management’s Discussion and Analysis