Dyne Therapeutics Inc

Previous wording

Our product candidate DYNE-101 is being evaluated in ACHIEVE, an ongoing Phase 1/2 global clinical trial in patients with DM1, consisting of a 24-week multiple ascending dose, or MAD, randomized, placebo-controlled period, a 24-week open-label extension, or OLE, and a 96-week long-term extension. ACHIEVE, which is designed to be registrational, is enrolling adult patients with DM1 who are 18 to 49 years of age. The primary endpoints are safety and tolerability. Additional endpoints include pharmacokinetics, change from baseline in splicing, multiple measures of muscle strength and function as well as patient-reported outcomes, including the Myotonic Dystrophy Type 1 Activity and Participation Scale (DM1-ACTIVc) and the Myotonic Dystrophy Health Index (MDHI). In the MAD portion of the ACHIEVE trial, patients are randomized to receive DYNE-101 or placebo intravenously every four weeks or every eight weeks for 24 weeks, depending on cohort. Patient cohorts will be dosed from 1.8 mg/kg to 10.2 mg/kg (approximate antisense oligonucleotide, or ASO, dose). Following the placebo-controlled period, patients transition to DYNE-101 treatment in the OLE portion of the trial and in the long-term extension.

Current wording

Our product candidate DYNE-101 is being evaluated in ACHIEVE, an ongoing Phase 1/2 global clinical trial in patients with DM1, consisting of a 24-week multiple ascending dose, or MAD, randomized, placebo-controlled period, a 24-week open-label extension, or OLE, and a 96-week long-term extension. ACHIEVE, which is designed to be registrational, is enrolling adult patients with DM1 who are 18 to 49 years of age. The primary endpoints are safety and tolerability. Additional endpoints include pharmacokinetics, change from baseline in splicing, multiple measures of muscle strength and function as well as patient-reported outcomes, including the Myotonic Dystrophy Type 1 Activity and Participation Scale (DM1-ACTIVc) and the Myotonic Dystrophy Health Index (MDHI).

Previous wording

Safety and tolerability data from the assessment of the ACHIEVE trial reported in May 2024 were based on 56 patients enrolled through the 6.8 mg/kg Q8W cohort of the MAD portion of the ACHIEVE trial. As of the safety data cut-off date of May 8, 2024, DYNE-101 demonstrated a favorable safety profile and the majority of treatment emergent adverse events were mild or moderate and no related serious treatment emergent adverse events were identified.

Current wording

Safety and tolerability data from the assessment of the ACHIEVE trial reported in September 2024 were based on 56 patients enrolled through the 6.8 mg/kg Q8W cohort of the MAD portion of the ACHIEVE trial. As of August 20, 2024, the safety profile of DYNE-101 continued to be favorable and included safety data up to the 6.8 mg/kg Q8W cohort.

Previous wording

In May 2024, we announced positive clinical data from the DELIVER trial. The efficacy assessment of the DYNE-251 DELIVER trial reported in May 2024 was based on 6-month data from eight male patients with DMD amenable to exon 51 skipping enrolled in the 10 mg/kg (approximate PMO dose) cohort of the randomized, placebo-controlled MAD portion of the trial. Patients were randomized to receive either DYNE-251 (n=6) or placebo (n=2) once every four weeks for 6 months. In the 10 mg/kg dose cohort, DYNE-251 Q4W demonstrated dose-dependent exon skipping and dystrophin expression. In these data, DYNE-251 reached levels of dystrophin expression that exceeded levels reported in a third-party clinical trial for the current weekly standard of care for DMD exon 51, eteplirsen, at 6 months with a 12-fold lower PMO dose. In these data, DYNE-251 also demonstrated encouraging trends in multiple functional endpoints.

Current wording

In September 2024, we announced positive clinical data from the DELIVER trial. The efficacy assessment of the DYNE-251 DELIVER trial reported in September 2024 was based on 6-month biomarker and functional data from eight male patients with DMD amenable to exon 51 skipping enrolled in the 20 mg/kg (approximate PMO dose) cohort of the randomized, placebo-controlled MAD portion of the trial and 12-month functional data from six male patients enrolled in the 10 mg/kg (approximate PMO dose) cohort. During the open label extension period, all participants in the 10 mg/kg cohort were dose escalated to 20 mg/kg Q4W regimen. DYNE-251 demonstrated dose-dependent exon skipping and dystrophin expression and improvement in multiple functional endpoints in both cohorts. In these data, DYNE-251 reached levels of dystrophin expression that exceeded levels reported in a third-party clinical trial for the current weekly standard of care for DMD exon 51, eteplirsen, at 6 months with a significantly lower PMO dose. In these data, DYNE-251 also demonstrated encouraging trends in multiple functional endpoints.

Previous wording

Safety and tolerability data from the assessment of the DELIVER trial reported in May 2024 were based on 48 patients enrolled through the 40 mg/kg Q8W cohort of the MAD portion of the DELIVER trial. As of the safety data cut-off date of April 30, 2024, DYNE-251 demonstrated a favorable safety profile and the majority of treatment emergent adverse events were mild or moderate and no related serious treatment emergent adverse events were identified.

Current wording

Safety and tolerability data from the assessment of the DELIVER trial reported in September 2024 were based on 54 participants enrolled in the DELIVER trial. As of the safety data cut-off date of August 21, 2024, DYNE-251 demonstrated a favorable safety profile and the majority of treatment emergent adverse events were mild or moderate and no related serious treatment emergent adverse events were identified other than in two participants at the 40 mg/kg dose level which events were potentially related to study drug. One participant experienced symptoms which suggested hemolytic uremic syndrome with potentially caused by an infection. The second participant had a history of unexplained hemolytic anemia and developed fever and tonsillitis after joining the DELIVER trial. Both participants have recovered.

Previous wording

We were incorporated and commenced operations in 2017. Since our incorporation, we have devoted substantially all of our financial resources and efforts to organizing and staffing our company, business planning, raising capital, conducting research and development activities and filing and prosecuting patent applications. We do not have any products for sale and have not generated any revenue from product sales or otherwise. To date, we have principally raised capital through sales of equity securities.

Current wording

We were incorporated and commenced operations in 2017. Since our inception, we have devoted substantially all of our financial resources and efforts to organizing and staffing our company, business planning, raising capital, conducting research and development activities and filing and prosecuting patent applications. We do not have any products for sale and have not generated any revenue from product sales or otherwise. To date, we have principally raised capital through sales of equity securities.

Previous wording

Since our inception, we have incurred significant operating losses. Our ability to generate any product revenue or product revenue sufficient to achieve profitability will depend on the successful development and eventual commercialization of one or more product candidates. For the six months ended June 30, 2024 and 2023, we reported net losses of $130.8 million and $109.1 million, respectively. As of June 30, 2024, we had an accumulated deficit of $763.3 million.

Current wording

Since our inception, we have incurred significant operating losses. Our ability to generate any product revenue or product revenue sufficient to achieve profitability will depend on the successful development and eventual commercialization of one or more product candidates. For the nine months ended September 30, 2024 and 2023, we reported net losses of $227.9 million and $169.3 million, respectively. As of September 30, 2024, we had an accumulated deficit of $860.4 million.

Previous wording

Expenses related to DYNE-101 decreased in the second quarter of 2024 compared to the second quarter of 2023. This was attributable to higher manufacturing activity in the second quarter of 2023. Expenses related to DYNE-251 increased in the second quarter of 2024 compared to the second quarter of 2023. This was attributable to an increase in clinical trial activity for the DELIVER trial.

Current wording

Expenses related to DYNE-101 increased in the third quarter of 2024 compared to the third quarter of 2023. This was attributable to higher manufacturing and clinical trial activity for the ACHIEVE trial in the third quarter of 2024. Expenses related to DYNE-251 increased in the third quarter of 2024 compared to the third quarter of 2023. This was attributable to higher manufacturing and clinical trial activity for the DELIVER trial in the third quarter of 2024.

Previous wording

The increase in platform and external research and development expenses in the second quarter of 2024 compared to the second quarter of 2023 was primarily due to increased external research activity associated with our preclinical programs. The increase in personnel-related expenses and stock-based compensation expense was primarily due to increased headcount in our research and development function. The increase in facility-related and other expenses was primarily due to the increased costs of supporting a larger number of research and development personnel.

Current wording

The increase in platform and external research and development expenses in the third quarter of 2024 compared to the third quarter of 2023 was primarily due to increased external research activity associated with our preclinical programs. The increase in personnel-related expenses and stock-based compensation expense was primarily due to increased headcount in our research and development function. The increase in facility-related and other expenses was primarily due to the increased costs of supporting a larger number of research and development personnel.

Previous wording

The increase in stock-based compensation expense was due to increased headcount in our general and administrative function. The increase in professional and consulting fees was primarily due to higher intellectual property related legal costs associated with our patent portfolio and other professional fees. Personnel-related expenses and facility-related and other expenses remained generally consistent in the second quarter of 2024 compared to the second quarter of 2023.

Current wording

The increase in personnel-related expenses and stock-based compensation expense was due to increased headcount in our general and administrative function and entering into a consulting agreement with our former chief business officer in September 2024, resulting in the modification of previously granted equity awards. The increase in professional and consulting fees was primarily due to higher intellectual property related legal costs associated with our patent portfolio and other professional fees.

Previous wording

Interest income for the three months ended June 30, 2024 and 2023 was $7.1 million and $2.2 million, respectively, due to interest earned on invested cash balances. The increase in interest income was due to an increased cash, cash equivalents and marketable securities balance on which we are earning interest due to the sale of common stock in the first and second quarters of 2024.

Current wording

Interest income for the three months ended September 30, 2024 and 2023 was $9.3 million and $2.2 million, respectively, due to interest earned on invested cash balances. The increase in interest income was due to an increased cash, cash equivalents and marketable securities balance on which we are earning interest due to the sale of common stock in the first and second quarters of 2024.

Previous wording

Other expense for the three months ended June 30, 2024 and 2023 was $0.2 million and $0.4 million, respectively, due to realized foreign currency losses.

Current wording

Other expense for the three months ended September 30, 2024 and 2023 was $0.7 million and $0.1 million, respectively, due to net foreign currency losses, partially offset by realized gains on the sales of marketable securities.

Previous wording

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

Current wording

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

Previous wording

The following table summarizes our research and development expenses for the six months ended June 30, 2024 and 2023:

Current wording

The following table summarizes our research and development expenses for the nine months ended September 30, 2024 and 2023:

Previous wording

Expenses related to DYNE-101 decreased in the six months ended June 30, 2024 compared to the six months ended June 30, 2023. This was attributable to higher manufacturing activity in the six months ended June 30, 2023. Expenses related to DYNE-251 increased in the six months ended June 30, 2024 compared to the six months ended June 30, 2023. This was attributable to an increase in clinical trial activity for the DELIVER trial and higher manufacturing activity in the six months ended June 30, 2024.

Current wording

Expenses related to DYNE-101 increased in the nine months ended September 30, 2024 compared to the nine months ended September 30, 2023. This was attributable to higher manufacturing activity and an increase in clinical trial activity for the ACHIEVE trial in the nine months ended September 30, 2024. Expenses related to DYNE-251 increased in the nine months ended September 30, 2024 compared to the nine months ended September 30, 2023. This was attributable to higher manufacturing activity and an increase in clinical trial activity for the DELIVER trial in the nine months ended September 30, 2024.

Previous wording

The increase in platform and external research and development expenses in the six months ended June 30, 2024 compared to the six months ended June 30, 2023 was primarily due to increased external research activity associated with our preclinical programs. The increase in personnel-related expenses and stock-based compensation expense was primarily due to increased headcount in our research and development function. The increase in facility-related and other expenses was primarily due to the increased costs of supporting a larger number of research and development personnel.

Current wording

The increase in platform and external research and development expenses in the nine months ended September 30, 2024 compared to the nine months ended September 30, 2023 was primarily due to increased external research activity associated with our preclinical programs. The increase in personnel-related expenses and stock-based compensation expense was primarily due to increased headcount in our research and development function. The increase in facility-related and other expenses was primarily due to the increased costs of supporting a larger number of research and development personnel.

Previous wording

The following table summarizes our general and administrative expenses for the six months ended June 30, 2024 and 2023:

Current wording

The following table summarizes our general and administrative expenses for the nine months ended September 30, 2024 and 2023:

Previous wording

The increase in personnel-related expenses in the six months ended June 30, 2024 compared to the six months ended June 30, 2023 was due to increased headcount in our general and administrative function. The increase in stock-based compensation expense was primarily the result of entering into separation and consulting agreements with our former chief executive officer in March 2024, resulting in the acceleration of vesting and modification of previously granted awards. The increase in professional and consulting fees was primarily due to higher intellectual property related legal costs associated with our patent portfolio and other professional fees. Facility-related and other expenses decreased primarily due to decreased general business expenses, including the cost of corporate insurance policies.

Current wording

The increase in personnel-related expenses in the nine months ended September 30, 2024 compared to the nine months ended September 30, 2023 was due to increased headcount in our general and administrative function. The increase in stock-based compensation expense was primarily the result of acceleration of vesting terms and modification of previously granted awards in connection with entering into separation and consulting agreements with our former chief executive officer and former chief business officer. The increase in professional and consulting fees was primarily due to higher intellectual property related legal costs associated with our patent portfolio and other professional fees. Facility-related and other expenses remained generally consistent in the nine months ended September 30, 2024 compared to the nine months ended September 30, 2023.

Previous wording

Interest income for the six months ended June 30, 2024 and 2023 was $10.1 million and $3.7 million, respectively, due to interest earned on invested cash balances. The increase in interest income was due to an increased cash, cash equivalents and marketable securities balance on which we are earning interest due to the sale of common stock in the first and second quarters of 2024.

Current wording

Interest income for the nine months ended September 30, 2024 and 2023 was $19.3 million and $5.9 million, respectively, due to interest earned on invested cash balances. The increase in interest income was due to an increased cash, cash equivalents and marketable securities balance on which we are earning interest due to the public sale of common stock in the first and second quarters of 2024.

Previous wording

Other income for the six months ended June 30, 2024 was $0.3 million due to foreign currency gains. Other expense for the six months ended June 30, 2023 was $0.6 million due to realized losses on the sale of marketable securities and net foreign currency losses.

Current wording

Other income for the nine months ended September 30, 2024 was $0.4 million due to net foreign currency losses, partially offset by realized gains on the sales of marketable securities. Other expense for the nine months ended September 30, 2023 was $0.7 million due to realized losses on the sale of marketable securities and net foreign currency losses.

Previous wording

Since our inception, we have incurred significant operating losses. We expect to incur significant expenses and operating losses for the foreseeable future as we support our continued research activities and development of our product candidates and platform. We have not yet commercialized any product candidates, and we do not expect to generate revenue from sales of any product candidates for several years, if at all. To date, we have funded our operations primarily with proceeds from sales of equity securities. As of June 30, 2024 we had cash, cash equivalents and marketable securities of $778.8 million.

Current wording

Since our inception, we have incurred significant operating losses. We expect to incur significant expenses and operating losses for the foreseeable future as we support our continued research activities and development of our product candidates and platform. We have not yet commercialized any product candidates, and we do not expect to generate revenue from sales of any product candidates for several years, if at all. To date, we have funded our operations primarily with proceeds from sales of equity securities. As of September 30, 2024 we had cash, cash equivalents and marketable securities of $723.7 million.

Previous wording

During the six months ended June 30, 2024, we issued and sold an aggregate of 3,800,465 shares of common stock pursuant to the Sales Agreement for aggregate net proceeds of $97.9 million, after deducting sales agent commissions and offering expenses payable by us. We sold such shares at a weighted average price of $26.86 per share.

Current wording

During the nine months ended September 30, 2024, we issued and sold an aggregate of 3,800,465 shares of common stock pursuant to the Sales Agreement for aggregate net proceeds of $97.9 million, after deducting sales agent commissions and offering expenses payable by us. We sold such shares at a weighted average price of $26.86 per share.

Previous wording

During the six months ended June 30, 2024, operating activities used $133.4 million of cash, due to our net loss of $130.8 million and net cash used by changes in our operating assets and liabilities of $28.6 million, partially offset by non-cash charges of $25.9 million. Net cash used by changes in our operating assets and liabilities consisted of a $21.4 million decrease in accounts payable and other liabilities and a $7.2 million increase in prepaid expenses. During the six months ended June 30, 2023, operating activities used $102.6 million of cash, due to our net loss of $109.1 million and net cash used by changes in our operating assets and liabilities of $3.7 million, partially offset by non-cash charges of $10.3 million. Net cash used by changes in our operating assets and liabilities consisted of a $7.9 million decrease in accounts payable and other liabilities, partially offset by a $4.2 million decrease in prepaid expenses. Changes in our operating assets and liabilities during these periods were generally due to the growth of our business, increased clinical trial activity, increased manufacturing activities, advancement of our product candidates, the timing of vendor invoices and payments and annual bonus payments.

Current wording

During the nine months ended September 30, 2024, operating activities used $208.0 million of cash, due to our net loss of $227.9 million and net cash used by changes in our operating assets and liabilities of $14.4 million, partially offset by non-cash charges of $34.2 million. Net cash used by changes in our operating assets and liabilities consisted of a $8.0 million decrease in accounts payable and other liabilities and a $6.4 million increase in prepaid expenses. During the nine months ended September 30, 2023, operating activities used $153.2 million of cash, due to our net loss of $169.3 million, partially offset by partially offset by non-cash charges of $15.4 million and net cash provided by changes in our operating assets and liabilities of $0.8 million. Net cash provided by changes in our operating assets and liabilities consisted of a $1.6 million increase in accounts payable and other liabilities, partially offset by a $0.8 million increase in prepaid expenses. Changes in our operating assets and liabilities during these periods were generally due to the growth of our business, increased clinical trial activity, increased manufacturing activities, advancement of our product candidates, the timing of vendor invoices and payments and annual bonus payments.

Previous wording

During the six months ended June 30, 2024, net cash used in investing activities was $168.7 million due to purchases of marketable securities of $207.7 and purchases of property and equipment of $1.0 million, partially offset by maturities of marketable securities of $40.1 million. During the six months ended June 30, 2023, net cash provided by investing activities was $44.3 million due to maturities of marketable securities of $77.6 million and sales of marketable securities of $1.8 million, partially offset by purchases of marketable securities of $34.7 million and purchases of property and equipment of $0.5 million.

Current wording

During the nine months ended September 30, 2024, net cash used in investing activities was $188.1 million due to purchases of marketable securities of $264.7 and purchases of property and equipment of $1.3 million, partially offset by maturities of marketable securities of $76.2 million and sales of marketable securities of $1.7 million. During the nine months ended September 30, 2023, net cash provided by investing activities was $57.1 million due to maturities of marketable securities of $100.2 million and sales of marketable securities of $1.8 million, partially offset by purchases of marketable securities of $44.3 million and purchases of property and equipment of $0.6 million.

Previous wording

During the six months ended June 30, 2024, net cash provided by financing activities was $788.3 million, consisting of $675.2 million in aggregate net proceeds from sales of common stock in our January 2024 and May 2024 offerings, $97.9 million in aggregate net proceeds from sales of common stock under our at-the-market offering program and $15.2 million in proceeds received from stock option exercises. During the six months ended June 30, 2023, net cash provided by financing activities was $53.7 million, consisting of $52.4 million in aggregate net proceeds from sales of common stock under our at-the-market offering program and $1.4 million in net proceeds received from stock option exercises.

Current wording

During the nine months ended September 30, 2024, net cash provided by financing activities was $806.3 million, consisting of $675.2 million in aggregate net proceeds from sales of common stock in our January 2024 and May 2024 offerings, $97.9 million in aggregate net proceeds from sales of common stock under our at-the-market offering program and $33.2 million in proceeds received from stock option exercises. During the nine months ended September 30, 2023, net cash provided by financing activities was $54.2 million, consisting of $52.4 million in aggregate net proceeds from sales of common stock under our at-the-market offering program and $1.8 million in net proceeds received from stock option exercises.