Milestone Pharmaceuticals Inc.

Previous wording

We are also developing etripamil nasal spray for a subsequent indication to treat patients with AFib-RVR. Similar to our approach for PSVT, we believe that etripamil has the potential to help the person experiencing a symptomatic episode of AFib-RVR to self-treat themselves and to conveniently, reliably, and quickly, reduce their elevated heart rate, with the goal of reducing the need for emergency department utilization. We completed a successful Phase 2 study in patients presenting urgently with AFib-RVR, i.e., to an emergency department. We publicly presented these positive Phase 2 data in November 2023, which demonstrated that patients receiving etripamil nasal spray experienced rapid and statistically superior ventricular rate reduction and improved symptom-relief compared to placebo, with safety and tolerability findings generally consistent with those observed in our PSVT program. These data support the continued development of etripamil, self-administered in the medically unmonitored setting, for the treatment of AFib-RVR. Following dialogue with FDA, we have finalized a Phase 3, potentially registrational study.

Current wording

We are also developing etripamil nasal spray for a subsequent indication to treat patients with AFib-RVR. Similar to our approach for PSVT, we believe that etripamil has the potential to help the person experiencing a symptomatic episode of AFib-RVR to self-treat themselves and to conveniently, reliably, and quickly, reduce their elevated heart rate, with the goal of reducing the need for emergency department utilization. We completed a successful Phase 2 study in patients presenting urgently with AFib-RVR, i.e., to an emergency department. We publicly presented these positive Phase 2 data in November 2023, which demonstrated that patients receiving etripamil nasal spray experienced rapid and statistically superior ventricular rate reduction and improved symptom-relief compared to placebo, with safety and tolerability findings generally consistent with those observed in our PSVT program. These data support the continued development of etripamil, self-administered in the medically unmonitored setting, for the treatment of AFib-RVR.

Previous wording

PSVT is a condition that causes a patient’s heart to suddenly start beating faster than normal. It can be life-altering as PSVT is highly symptomatic, characterized by unpredictable attacks of a racing heart, often exceeding 150 beats per minute. Symptoms of PSVT arise suddenly and may include palpitations, sweating, chest pressure or pain, shortness of breath, sudden onset of fatigue, lightheadedness or dizziness, fainting, and anxiety, causing many patients to interrupt their daily activities at the time of symptom-onset. The impact and morbidity from an episode of PSVT can be especially detrimental in patients with underlying cardiovascular or medical conditions, such as heart failure, obstructive coronary disease, or dehydration. The uncertainty of when such an attack of PSVT will strike or how long it will persist is often anxiety-provoking, reducing patients’ quality of life and preventing participation in many desired activities. Drugs approved for the treatment of attacks of PSVT include adenosine, verapamil, and diltiazem, with all being administered intravenously under medical supervision, usually in the emergency department. Other oral drugs are sometimes used to treat attacks in a concept called “pill in the pocket.” However, those drugs have never been proven effective or safe and are not approved for this use. Doctors are often frustrated by the lack of effective treatment options besides a prolonged,

Current wording

disease, or dehydration. The uncertainty of when such an attack of PSVT will strike or how long it will persist is often anxiety-provoking, reducing patients’ quality of life and preventing participation in many desired activities. Drugs approved for the treatment of attacks of PSVT include adenosine, verapamil, and diltiazem, with all being administered intravenously under medical supervision, usually in the emergency department. Other oral drugs are sometimes used to treat attacks in a concept called “pill in the pocket.” However, those drugs have never been proven effective or safe and are not approved for this use. Doctors are often frustrated by the lack of effective treatment options besides a prolonged, unpleasant, and costly trip to the emergency department or, for some patients, an invasive ablation procedure. PSVT can be traumatic for patients, frustrating for healthcare providers, and costly for payors. With no pharmaceutical innovation in the treatment of PSVT for more than 30 years and a movement in the healthcare system to enable patient-centered care, we believe there is an opportunity to help patients living with PSVT to take greater control over their PSVT.

Previous wording

We believe that PSVT is a large and under-recognized market which we estimate affects more than two million Americans. From this diagnosed population, we define the immediate target addressable market for CARDAMYST as approximately 60% of patients who are actively managed by clinical cardiologists, interventional cardiologists and electrophysiologists. The remaining patients with PSVT can become addressable over time, as they are inconsistently managed (cycling in and out of the healthcare system) and/or being managed less frequently by primary care healthcare providers. Furthermore, PSVT is expected to increase in diagnosed prevalence in coming years as wearable electrocardiogram, or “ECG,” technology (e.g., smartphone, watches) becomes both more adept at diagnosing PSVT and more widely used by patients and clinical practitioners, in turn shortening the time to diagnosis.

Current wording

We believe that PSVT is a large and under-recognized market which we estimate affects more than two million Americans. From this diagnosed population, we define the immediate target addressable market for CARDAMYST as approximately 70% of patients who are actively managed by clinical cardiologists, interventional cardiologists and electrophysiologists. The remaining patients with PSVT can become addressable over time, as they are inconsistently managed (cycling in and out of the healthcare system) and/or being managed less frequently by primary care healthcare providers. Furthermore, PSVT is expected to increase in diagnosed prevalence in coming years as wearable electrocardiogram, or “ECG,” technology (e.g., smartphone, watches) becomes both more adept at diagnosing PSVT and more widely used by patients and clinical practitioners, in turn shortening the time to diagnosis.

Previous wording

Current treatment for PSVT also consumes significant healthcare resources. Research published in the American Journal of Cardiology in 2020 shows that total healthcare expenditures in the year following a diagnosis of PSVT ranged from $20,000 to $30,000 per patient which were significantly higher than the expenditures observed for patients without PSVT. These significant increases included increased emergency department visits and hospitalization costs. Of note, catheter ablations following diagnosis represented only 23% of this increased spend, meaning most costs were unrelated to ablations. Recent data from the Healthcare Cost and Utilization Project (HCUP) database indicate that in 2019 there were approximately 140,000 emergency department, or “ED,” visits for PSVT when coded in the primary diagnostic position, and a total of approximately 525,000 ED visits when PSVT was coded in any diagnostic position. Of these, approximately 25% of ED admissions for PSVT resulted in a hospital admission. HCUP estimates a total of approximately 40,000 to approximately 120,000 inpatient admissions for PSVT in 2019 (based again if PSVT were found in the primary v. any diagnostic position). Despite the effectiveness of catheter ablation, claims data suggests that only approximately 15% of patients with PSVT are ablated over a three-year period, leading to a total of approximately 100,000 catheter ablations annually. In total, at least $5 billion is spent annually in the United States on the management of PSVT.

Current wording

Current treatment for PSVT also consumes significant healthcare resources. Research published in the American Journal of Cardiology in 2020 shows that total healthcare expenditures in the year following a diagnosis of PSVT ranged from $20,000 to $30,000 per patient which were significantly higher than the expenditures observed for patients without PSVT. These significant increases included increased emergency department visits and hospitalization costs. Of note, catheter ablations following diagnosis represented only 23% of this increased spend, meaning most costs were unrelated to ablations. Recent data from the Healthcare Cost and Utilization Project (HCUP) database indicate that in 2019 there were approximately 140,000 emergency department, or “ED,” visits for PSVT when coded (for billing) in the primary diagnostic position, and a total of approximately 525,000 ED visits when PSVT was coded in any diagnostic position. Of these, approximately 25% of ED admissions for PSVT resulted in a hospital admission. HCUP estimates a total of approximately 40,000 to approximately 120,000 inpatient admissions for PSVT in 2019 (based again if a PSVT billing code was found in the primary v. any diagnostic position). Despite the effectiveness of catheter ablation, claims data suggests that only approximately 15% of patients with PSVT are ablated over a three-year period, leading to a total of approximately 100,000 catheter ablations annually. In total, at least $5 billion is spent annually in the United States on the management of PSVT.

Previous wording

Atrial Fibrillation, or “AFib,” is a common cardiac arrhythmia with an irregular and often rapid heart rate that is often markedly symptomatic and, without proper treatment, can increase the risk of stroke, heart failure, and other cardiovascular complications. A common complication of AFib is a rapid heart rate, also referred to as AFib-RVR, which is frequently defined as a heart rate ≥ 110 beats per minute. The occurrence of a rapid ventricular rate, or “RVR,” in patients with atrial fibrillation increases the likelihood of marked symptoms including heart palpitations, shortness of breath and weakness. There are two commonly used pharmacological approaches to chronically manage AFib, rhythm control and rate control. Regardless of the chronic approach, break-through episodes of rapid heart rate occur frequently; and when faced with a sudden episode of AFib-RVR, acute rate control is needed, with most treatments being AV-nodal targeted drugs such as a beta blocker or calcium channel blocker. These treatments can be given intravenously; however, this requires a burdensome trip to an emergency department which may lead to a hospital admission. Acute treatment can be attempted by administration of an oral rate control drug; however, such drugs do not adequately provide immediate or adequate ventricular rate control due to a 30- to 90-minute delayed onset of action, and, as a result, many patients need faster and more certain rate-reduction and symptom-resolution and so seek acute-medical care by going to the emergency department for treatment utilizing intravenous rate control and/or electrical cardioversion of their atrial fibrillation. Furthermore, the

Current wording

Atrial Fibrillation, or “AFib,” is a common cardiac arrhythmia with an irregular and often rapid heart rate that is often markedly symptomatic and, without proper treatment, can increase the risk of stroke, heart failure, and other cardiovascular complications. A common complication of AFib is a rapid heart rate, also referred to as AFib-RVR, which is frequently defined as a heart rate ≥ 110 beats per minute. The occurrence of a rapid ventricular rate, or “RVR,” in patients with atrial fibrillation increases the likelihood of marked symptoms including heart palpitations, shortness of breath and weakness. There are two commonly used pharmacological approaches to chronically manage AFib, rhythm control and rate control. Regardless of the chronic approach, break-through episodes of rapid heart rate occur frequently; and when faced with a sudden episode of AFib-RVR, acute rate control is needed, with most treatments being AV-nodal targeted drugs such as a

Previous wording

chronic administration of oral rate-control drugs does not broadly prevent episodes of AFib-RVR. Similar to PSVT, patients may feel a loss of control by needing to visit the emergency department for overcoming their AFib-RVR episode and the unpredictable nature of these episodes, which can occur anytime and anywhere. Doctors have expressed frustration at the lack of options for patients to self-manage these acute rate attacks; and payor organizations would prefer to treat the AFib-RVR attacks in a more cost effective and time-efficient manner.

Current wording

beta blocker or calcium channel blocker. These treatments can be given intravenously; however, this requires a burdensome trip to an emergency department which may lead to a hospital admission. Acute treatment can be attempted by administration of an oral rate control drug; however, such drugs do not adequately provide immediate or adequate ventricular rate control due to a 30- to 90-minute delayed onset of action, and, as a result, many patients need faster and more certain rate-reduction and symptom-resolution and so seek acute-medical care by going to the emergency department for treatment utilizing intravenous rate control and/or electrical cardioversion of their atrial fibrillation. Furthermore, the chronic administration of oral rate-control drugs does not broadly prevent episodes of AFib-RVR. Similar to PSVT, patients may feel a loss of control by needing to visit the emergency department for overcoming their AFib-RVR episode and the unpredictable nature of these episodes, which can occur anytime and anywhere. Doctors have expressed frustration at the lack of options for patients to self-manage these acute rate attacks; and payor organizations would prefer to treat the AFib-RVR attacks in a more cost effective and time-efficient manner.

Previous wording

In March 2025, we announced that we received a CRL regarding our NDA for CARDAMYST (etripamil) nasal spray for the treatment of PSVT. Within the CRL, the FDA did not raise any concerns regarding clinical safety or efficacy. The FDA highlighted two key Chemistry, Manufacturing and Controls, or “CMC,” issues to be addressed. The FDA requested that we submit additional information on nitrosamine impurities based on new draft guidance issued after the NDA submission. Secondly, the FDA stated that an inspection is required at a facility listed in the NDA, to ensure it is in compliance with Current Good Manufacturing Practices. The facility mentioned previously performed a portion of the testing required to release etripamil final product, but changed ownership during the review of the NDA. On June 13, 2025, we submitted our response to the FDA’s CRL regarding the NDA for CARDAMYST (etripamil) nasal spray. Further, on July 11, 2025, we announced that the FDA accepted for review our response to issues raised in the CRL. The FDA has assigned a new PDUFA target date of December 13, 2025.

Current wording

In March 2025, we announced that we received a CRL regarding our NDA for CARDAMYST (etripamil) nasal spray for the treatment of PSVT. Within the CRL, the FDA did not raise any concerns regarding clinical safety or efficacy. The FDA highlighted two key Chemistry, Manufacturing and Controls, or “CMC,” issues to be addressed. The FDA requested that we submit additional information on nitrosamine impurities based on new draft guidance issued after the NDA submission. Secondly, the FDA stated that an inspection is required at a facility listed in the NDA, to ensure it is in compliance with Current Good Manufacturing Practices. The facility mentioned previously performed a portion of the testing required to release etripamil final product, but changed ownership during the review of the NDA. On June 13,

Previous wording

On July 11, 2025, we announced that the FDA accepted for review our response to issues raised in the CRL for CARDAMYST™ (etripamil) nasal spray, an investigational, novel therapy for the treatment of patients with paroxysmal supraventricular tachycardia. In conjunction with the acceptance, the FDA has assigned a new PDUFA target action date of December 13, 2025.

Current wording

2025, we submitted our response to the FDA’s CRL regarding the NDA for CARDAMYST (etripamil) nasal spray. Further, on July 11, 2025, we announced that the FDA accepted for review our response to issues raised in the CRL. The FDA has assigned a new PDUFA target date of December 13, 2025.

Previous wording

During 2024, we met with the FDA on the ReVeRA study, during which the FDA confirmed its guidance from our Pre-IND meeting (2023) regarding the availability of a supplemental new drug application, or “sNDA,” pathway for the marketing approval for etripamil for the indication of AFib-RVR. The sNDA pathway potentially permits a single pivotal efficacy study to be sufficient for filing for marketing approval if etripamil is already approved for PSVT. FDA further concurred with respect to key proposed study elements including powering, inclusion criteria, patient population, and statistical analyses, and offered clarification with respect to the endpoints to guide the design of the Phase 3 study. In our mid-2023 Pre-IND meeting, the FDA provided guidance that our primary endpoint can be the reduction of ventricular rate, and the primary analysis would be performed on the intent to treat, or “ITT,” population. In addition, the study would have to show statistical significance (p<0.05) on the key secondary endpoint of symptom relief as a patient benefit, also in the ITT population. The secondary endpoint could use a PRO measure, and the application of a seven-point anchored scale was discussed with the FDA. We have finalized the Phase 3 study protocol following FDA’s review and obtained concurrence with the FDA to proceed; however, we are delaying enrollment of the study due to the CRL received on the NDA for etripamil in PSVT.

Current wording

During 2024, we met with the FDA on the ReVeRA study, during which the FDA confirmed its guidance from our Pre-IND meeting (2023) regarding the availability of a supplemental new drug application, or “sNDA,” pathway for the marketing approval for etripamil for the indication of AFib-RVR. The sNDA pathway potentially permits a single pivotal efficacy study to be sufficient for filing for marketing approval if etripamil is already approved for PSVT. FDA further concurred with respect to key proposed study elements including powering, inclusion criteria, patient population, and statistical analyses, and offered clarification with respect to the endpoints to guide the design of the Phase 3 study. In our mid-2023 Pre-IND meeting, the FDA provided guidance that our primary endpoint can be the reduction of ventricular rate, and the primary analysis would be performed on the intent to treat, or “ITT,” population. In addition, the study would have to show statistical significance (p<0.05) on the key secondary endpoint of symptom relief as a patient benefit, also in the

Previous wording

The Phase 3 study will be conducted in a medically unmonitored setting (e.g., at-home) in a manner very similar to the conduct of our Phase 3 development program for PSVT. The Phase 3 AFib-RVR study will enroll patients with a history of symptomatic AFib episodes, and will use a self-administered, repeat-dose regimen of 70 mg per dose (the dose and dosing approach that was studied in the RAPID trial in patients with PSVT). The Phase 3 study’s target population will be patients with verified history of AFib-RVR, and the ITT population will be all patients self-administering the study drug for perceived AFib-RVR. The primary endpoint is the mean change from baseline ventricular rate to nadir ventricular rate

Current wording

The Phase 3 study will be conducted in a medically unmonitored setting (e.g., at-home) in a manner very similar to the conduct of our Phase 3 development program for PSVT. The Phase 3 AFib-RVR study will enroll patients with a history of symptomatic AFib episodes, and will use a self-administered, repeat-dose regimen of 70 mg per dose (the dose and dosing approach that was studied in the RAPID trial in patients with PSVT). The Phase 3 study’s target population will be patients with verified history of AFib-RVR, and the ITT population will be all patients self-administering the study drug for perceived AFib-RVR. The primary endpoint is the mean change from baseline ventricular rate to nadir ventricular rate for patients treated with etripamil versus placebo, as was studied in the ReVeRA trial in AFib-RVR. The key secondary endpoint will be based on a PRO of symptomatic improvement, discussed with the FDA, which is similar to the PRO questions utilized in our PSVT and AFib-RVR programs. The study has been powered and sized based upon approximately 150 events from 150 unique patients with a history of symptomatic episodes of AFib-RVR.

Previous wording

Since inception, we have incurred significant operating losses. For the three months ended June 30, 2025 and 2024, we recorded net losses of $13.0 million and $9.4 million, respectively. For the six months ended June 30, 2025 and 2024, we recorded net losses of $33.7 million and $19.7 million, respectively. As of June 30, 2025, we had an accumulated deficit of $401.3 million. We expect to continue to incur significant losses for the foreseeable future. We anticipate that a substantial portion of our capital resources and efforts in the foreseeable future will be focused on completing the necessary development activities required for obtaining regulatory approval and preparing for potential commercialization of our product candidates. We had $42.5 million of cash and cash equivalents and $0.9 million of short-term investments at June 30, 2025.

Current wording

Since inception, we have incurred significant operating losses. For the three months ended September 30, 2025 and 2024, we recorded net losses of $11.9 million and $9.4 million, respectively. For the nine months ended September 30, 2025 and 2024, we recorded net losses of $45.6 million and $29.2 million, respectively. As of September 30, 2025, we had an accumulated deficit of $413.2 million. We expect to continue to incur significant losses for the foreseeable future. We anticipate that a substantial portion of our capital resources and efforts in the foreseeable future will be focused on completing the necessary development activities required for obtaining regulatory approval and preparing for potential commercialization of our product candidates. We had $46.7 million of cash and cash equivalents and $35.9 million of short-term investments at September 30, 2025.

Previous wording

Inflation rates may materially adversely affect our business and corresponding financial position and cash flows. Inflationary factors, changes to interest rates and overhead costs may adversely affect our operating results. Interest and inflation rates also present a recent challenge impacting the U.S. economy and could make it more difficult for us to obtain traditional financing on acceptable terms, if at all, in the future. Additionally, geopolitical events such as the Russia-Ukraine war and unrest and/or further escalation in Israel and Gaza, banking instabilities, ongoing changes to U.S. and international tariffs and other trade restrictions and trade barriers, renegotiation of international trade agreements or further escalations of trade tensions, and other U.S. geopolitical issues affecting other territories and employee availability and wage increases, and economic markets all of which may result in additional stress on our working capital resources.

Current wording

Inflation rates may materially adversely affect our business and corresponding financial position and cash flows. Inflationary factors, changes to interest rates and overhead costs may adversely affect our operating results. Interest and inflation rates also present a recent challenge impacting the U.S. economy and could make it more difficult for us to obtain traditional financing on acceptable terms, if at all, in the future. Additionally, geopolitical events such as the Russia-Ukraine war and unrest and/or further escalation in the Middle East, banking instabilities, ongoing changes to U.S. and international tariffs and other trade restrictions and trade barriers, renegotiation of international trade agreements or further escalations of trade tensions, and other U.S. geopolitical issues affecting other territories and employee availability and wage increases, and economic markets all of which may result in additional stress on our working capital resources. The ongoing trade tensions between the U.S. and other jurisdictions have resulted in multiple rounds of tariffs and anticipated tariffs affecting pharmaceuticals and pharmaceutical ingredients, including finished drug products, manufacturing equipment, and related supplies. In any event, the dynamic and unpredictable tariff and trade landscape may create substantial uncertainty and [significant] planning challenges for our operations.

Previous wording

We record license revenue when milestones are reached pursuant to our License and Collaboration Agreement, dated May 15, 2021, with Corxel Pharmaceuticals, or “Corxel,” formerly known as Ji Xing Pharmaceuticals Limited (such party “Ji Xing” and, such agreement, the “Ji Xing License Agreement”). During the three and six months ended June 30, 2025 and 2024, no milestones were achieved, and no revenue was recorded under this agreement.

Current wording

We record license revenue when milestones are reached pursuant to our License and Collaboration Agreement, dated May 15, 2021, with Corxel Pharmaceuticals, or “Corxel,” formerly known as Ji Xing Pharmaceuticals Limited (such party “Ji Xing” and, such agreement, the “Ji Xing License Agreement”). During the three and nine months ended September 30, 2025 and 2024, no milestones were achieved, and no revenue was recorded under this agreement.

Previous wording

To date, substantially all of our research and development expenses have been related to the preclinical and clinical development of etripamil. As we advance etripamil or other product candidates for other indications, we expect to allocate our direct external research and development costs across each of the indications or product candidates. Further, we expect our research and development costs to increase for the development of etripamil in atrial fibrillation with rapid ventricular rate, and we expect our research and development expenses related to the development of etripamil for PSVT decrease as a percentage of our total research and development expenses.

Current wording

To date, substantially all of our research and development expenses have been related to the preclinical and clinical development of etripamil. As we advance etripamil or other product candidates for other indications, we expect to allocate our direct external research and development costs across each of the indications or product candidates. Further, we expect

Previous wording

General and administrative expenses include personnel and related compensation costs, expenses for outside professional services, lease expense, insurance expense and other general administrative expenses. Personnel costs consist of salaries,

Current wording

General and administrative expenses include personnel and related compensation costs, expenses for outside professional services, lease expense, insurance expense and other general administrative expenses. Personnel costs consist of salaries, bonuses, benefits, related payroll taxes and share-based compensation. Outside professional services consist of legal, accounting and audit services and other consulting fees.

Previous wording

Comparison of the Three and Six Months Ended June 30, 2025 and 2024

Current wording

Comparison of the Three and Nine Months Ended September 30, 2025 and 2024

Previous wording

We recorded no revenue for the three or six months ended June 30, 2025 and 2024.

Current wording

We recorded no revenue for the three or nine months ended September 30, 2025 and 2024.

Previous wording

The following table shows our research and development expenses by type of activity for the three and six months ended June 30, 2025 and 2024, respectively.

Current wording

The following table shows our research and development expenses by type of activity for the three and nine months ended September 30, 2025 and 2024, respectively.

Previous wording

General and administrative expenses remained consistent for the six months ended June 30, 2025, compared to the six months ended June 30, 2024.

Current wording

Research and development expenses, net of tax credits, remained consistent for the three months ended September 30, 2025, compared to the three months ended September 30, 2024.

Previous wording

Research and development expenses, net of tax credits, increased by $2.2 million, or 34.0%, for the six months ended June 30, 2025, compared to the six months ended June 30, 2024. The increase was primarily due to higher consulting and outside service costs. These higher costs were partially offset by lower personnel-related costs.

Current wording

Research and development expenses, net of tax credits, increased by $2.2 million, or 20.8%, for the nine months ended September 30, 2025, compared to the nine months ended September 30, 2024. The increase was primarily due to higher consulting and outside service costs. These higher costs were partially offset by lower personnel-related costs.

Previous wording

General and administrative expenses decreased by $1.3 million, or 25.5%, for the three months ended June 30, 2025, compared to the three months ended June 30, 2024, primarily due to a decrease in legal, professional fees and personnel costs.

Current wording

General and administrative expenses decreased by $0.5 million, or 12.8%, for the three months ended September 30, 2025, compared to the three months ended September 30, 2024, primarily due to a decrease in professional costs and personnel costs.

Previous wording

Commercial expenses increased by $3.3 million, or 183.3%, for the three months ended June 30, 2025, compared to the same period in 2024. This increase is primarily a result of additional personnel costs, professional costs and other operational expenses related to preparation for the launch of CARDAMYST.

Current wording

Commercial expenses increased by $2.7 million, or 142.1%, for the three months ended September 30, 2025, compared to the same period in 2024. This increase is primarily a result of additional personnel costs, professional costs and other operational expenses related to preparation for the launch of CARDAMYST.

Previous wording

Commercial expenses increased by $10.8 million, or 230.4%, for the six months ended June 30, 2025, compared to the same period in 2024. This increase is primarily a result of additional personnel costs, professional costs and other operational expenses related to preparation for the launch of CARDAMYST.

Current wording

Commercial expenses increased by $13.5 million, or 204.8%, for the nine months ended September 30, 2025, compared to the same period in 2024. This increase is primarily a result of additional personnel costs, professional costs and other operational expenses related to preparation for the launch of CARDAMYST.

Previous wording

As a result of the CRL, Milestone temporarily paused the ramping up of operational expenditures related to launch. During this period, Milestone has focused on compliantly engaging healthcare providers and payers in profiling and disease state discussions with the goal of optimizing the launch plan for CARDAMYST. Milestone continues to maintain the capability of launching quickly following the potential approval of CARDAMYST by the FDA.

Current wording

As a result of the CRL, Milestone temporarily paused the ramping up of operational expenditures related to launch. During this period, Milestone has focused on compliantly engaging healthcare providers and payors in profiling and disease state discussions with the goal of optimizing the launch plan for CARDAMYST. Milestone continues to maintain the capability of launching quickly following the potential approval of CARDAMYST by the FDA.

Previous wording

Interest income was $0.5 million and $1.2 million for the three months ended June 30, 2025 and 2024, respectively. Interest income was $1.2 million and $2.2 million for the six months ended June 30, 2025 and 2024, respectively. The decrease in interest income was due to decreasing interest rates and less assets invested in 2025 when compared to 2024.

Current wording

Interest income was $0.9 million and $1.1 million for the three months ended September 30, 2025 and 2024, respectively. Interest income was $2.1 million and $3.3 million for the nine months ended September 30, 2025 and 2024, respectively. The decrease in interest income was due to decreasing interest rates and less assets invested in 2025 when compared to 2024.

Previous wording

Interest expense remained consistent for the three and six months ended June 30, 2025, compared to the same periods in 2024.

Current wording

Interest expense remained consistent for the three and nine months ended September 30, 2025, compared to the same periods in 2024.

Previous wording

We have incurred operating losses and experienced negative operating cash flows since our inception, and we anticipate continuing to incur losses for at least the next several years. As of June 30, 2025, we had cash, cash equivalents and short-term investments of $43.4 million and an accumulated deficit of $401.3 million.

Current wording

We have incurred operating losses and experienced negative operating cash flows since our inception, and we anticipate continuing to incur losses for at least the next several years. As of September 30, 2025, we had cash, cash equivalents and short-term investments of $82.6 million and an accumulated deficit of $413.2 million.

Previous wording

On July 11, 2025, we entered into an underwriting agreement, or the “Underwriting Agreement,” related to an underwritten public offering, or the “Offering,” of (i) 31,500,000 of our common shares, without par value, accompanying Series A common warrants, or the “Series A Common Warrants,” to purchase an aggregate of 31,500,000 common shares and accompanying Series B common warrants, or the “Series B Common Warrants,” to purchase an aggregate of 31,500,000 common shares, at a combined public offering price of $1.50 per share and accompanying Series A Common Warrant and Series B Common Warrant and (ii) in lieu of common shares to certain investors that so choose, pre-funded warrants or the “2025 Pre-Funded Warrants” and, together with the Series A Common Warrants and the Series B Common Warrants, the “Warrants,” to purchase 3,502,335 common shares, accompanying Series A Common Warrants to purchase an aggregate of 3,502,335 common shares and accompanying Series B Common Warrants to purchase an aggregate of 3,502,335 common shares, at a combined public offering price of $1.499 per Pre-Funded Warrant and accompanying Series A Common Warrant and Series B Common Warrant, which represented the combined public offering price for the Shares and accompanying common warrants less the $0.001 per share exercise price for each such Pre-Funded Warrant.

Current wording

On July 11, 2025, we entered into an underwriting agreement, or the “Underwriting Agreement,” related to an underwritten public offering, or the “2025 Offering,” of (i) 31,500,000 of our common shares, without par value, accompanying Series A common warrants, or the “Series A Common Warrants,” to purchase an aggregate of 31,500,000 common shares and accompanying Series B common warrants, or the “Series B Common Warrants,” to purchase an aggregate of 31,500,000 common shares, at a combined public offering price of $1.50 per share and accompanying Series A Common Warrant and Series B Common Warrant and (ii) in lieu of common shares to certain investors that so choose, pre-funded warrants or the “2025 Pre-Funded Warrants” and, together with the Series A Common Warrants and the Series B Common Warrants, the “Warrants,” to purchase 3,502,335 common shares, accompanying Series A Common Warrants to purchase an aggregate of 3,502,335 common shares and accompanying Series B Common Warrants to purchase an aggregate of 3,502,335 common shares, at a combined public offering price of $1.499 per Pre-Funded Warrant and accompanying Series A Common Warrant and Series B Common Warrant, which represented the combined public offering price for the Shares and accompanying common warrants less the $0.001 per share exercise price for each such Pre-Funded Warrant.

Previous wording

The net proceeds to the Company from the Offering were approximately $48.7 million after deducting underwriting commissions and estimated offering expenses payable by the Company.

Current wording

The net proceeds to the Company from the 2025 Offering were $48.6 million after deducting underwriting commissions and estimated offering expenses payable by the Company.

Previous wording

On July 29, 2020, we entered into an Open Market Sale Agreement SM, or the “Original Sale Agreement,” with respect to an at-the-market offering program, or the “ATM Program,” under which the Company could issue and sell its common shares having an aggregate offering price of up to $50.0 million through Jefferies LLC, or “Jefferies,” as its sales. On March 18, 2025, we entered into an Amended and Restated Open Market Sale Agreement SM, or the “Amended Agreement,” with Jefferies. The Amended Agreement amends and restates, in its entirety, the Original Sale Agreement. Under the Amended Agreement, the Company may issue and sell its common shares, no par value per share, for an aggregate offering price of up to $77.8 million (which includes the approximately $2.8 million of sales previously made pursuant to the Original Sale Agreement through the date the Amended Agreement was entered into), or the “ATM Shares.” The ATM Shares will be sold pursuant to the Company’s shelf registration statement on Form S-3 (File No. 333-283162). We previously issued 361,236 common shares under the Original Sale Agreement, resulting in net proceeds of approximately $2.7 million (net of issuance costs of approximately $0.1 million). No common shares were sold under the Amended Agreement during the three and six months ended June 30, 2025.

Current wording

Under the Amended Agreement, the Company may issue and sell its common shares, no par value per share, for an aggregate offering price of up to $77.8 million (which includes the approximately $2.8 million of sales previously made pursuant to the Original Sale Agreement through the date the Amended Agreement was entered into), or the “ATM Shares.” The ATM Shares will be sold pursuant to the Company’s shelf registration statement on Form S-3 (File No. 333-283162). We previously issued 361,236 common shares under the Original Sale Agreement, resulting in net proceeds of approximately $2.7 million (net of issuance costs of approximately $0.1 million). No common shares were sold under the Amended Agreement during the three and nine months ended September 30, 2025.

Previous wording

We expect that our operating plan, existing cash and cash equivalents and short-term investments, including the proceeds from the July 11, 2025 offering discussed below, to be sufficient to fund our operations for at least the next 12 months from the date of issuance of this Form 10-Q for the quarter ending June 30, 2025 and that there are no events or conditions that may cast substantial doubt on our ability to continue as a going concern for at least the next 12 months from the date of this filing.

Current wording

We expect that our operating plan, existing cash and cash equivalents and short-term investments to be sufficient to fund our operations for at least the next 12 months from the date of issuance of this Form 10-Q for the quarter ending September 30, 2025 and that there are no events or conditions that may cast substantial doubt on our ability to continue as a going concern for at least the next 12 months from the date of this filing.

Previous wording

On March 27, 2023, we entered into a purchase and sale agreement, as amended, or the “Royalty Purchase Agreement.” Pursuant to the Royalty Purchase Agreement, as amended in July 2025, as described further in “─Recent Developments─Royalty Purchase Agreement Amendment,” RTW has agreed to purchase, following the FDA approval of etripamil on or prior to December 31, 2025 (subject to certain conditions), in exchange for a purchase price of $75.0 million, the right to receive a tiered quarterly royalty payments, or “royalty interest,” on the annual net product sales of etripamil in the United States.

Current wording

On March 27, 2023, we entered into a purchase and sale agreement, as amended, or the “Royalty Purchase Agreement.” Pursuant to the Royalty Purchase Agreement, as amended in July 2025 to extend the marketing approval deadline for etripamil to December 31, 2025, following the FDA approval of etripamil on or prior to December 31, 2025 (subject to certain conditions), in exchange for a purchase price of $75.0 million, the right to receive a tiered quarterly royalty payments, or “royalty interest,” on the annual net product sales of etripamil in the United States.

Previous wording

In addition, we have exclusive development and commercialization rights for etripamil for all indications that we may pursue and as such have the potential to license development and or commercialization rights for etripamil to a potential partner in regions outside of Greater China. We plan to establish commercialization and marketing capabilities using a

Current wording

In addition, we have exclusive development and commercialization rights for etripamil for all indications that we may pursue and as such have the potential to license development and or commercialization rights for etripamil to a potential partner in regions outside of Greater China. We plan to establish commercialization and marketing capabilities using a direct sales force to commercialize etripamil in the United States. Outside of the United States, we are considering commercialization strategies that may include collaborations with other companies.

Previous wording

Net cash used in operating activities during the six months ended June 30, 2025 was $26.5 million, which consisted primarily of a net loss of $33.7 million, offset by a net cash increase of $2.7 million related to the change in assets and liabilities, non-cash charges of $2.7 million related to share-based compensation, and non-cash interest charges of $1.7 million related to the 2029 convertible notes.

Current wording

Net cash used in operating activities during the nine months ended September 30, 2025 was $36.3 million, which consisted primarily of a net loss of $45.6 million, offset by a net cash increase of $2.6 million related to the change in assets and liabilities, non-cash charges of $3.9 million related to share-based compensation, and non-cash interest charges and debt costs of $2.9 million related to the 2029 Convertible Notes.

Previous wording

Net cash used in operating activities during the six months ended June 30, 2024 was $15.0 million, which consisted primarily of a net loss of $19.7 million and a net cash increase of $0.2 million related to the change in assets and liabilities. These decreases were offset by non-cash charges of $2.9 million related to share-based compensation and non-cash interest charges of $1.6 million related to the convertible notes.

Current wording

Net cash used in operating activities during the nine months ended September 30, 2024 was $22.0 million, which consisted primarily of a net loss of $29.2 million. The net loss was partially offset by a net cash increase of $0.4 million related to the change in assets and liabilities, non-cash charges of $4.3 million related to share based compensation, and non-cash interest charges of $2.4 million related to the convertible notes.

Previous wording

In the six months ended June 30, 2025, we acquired $0.9 million of short-term investments, and we redeemed $44.5 million in short-term investments. In the six months ended June 30, 2024, we acquired $69.8 million of short-term investments, and we redeemed $52.3 million in short-term investments.

Current wording

In the nine months ended September 30, 2025, we acquired $35.9 million of short-term investments, and we redeemed $44.5 million in short-term investments. In the nine months ended September 30, 2024, we acquired $99.6 million of short-term investments, and we redeemed $88.5 million in short-term investments.

Previous wording

In the six months ended June 30, 2024, our financing activities provided cash proceeds of $32.0 million. These proceeds were primarily a result of the $31.9 million received from the issuance of common shares and pre-funded warrants, net of $2.6 million in issuance costs paid.

Current wording

In the nine months ended September 30, 2024, our financing activities provided cash proceeds of $32.1 million. These proceeds were primarily a result of the $31.9 million received from the issuance of common shares and pre-funded warrants, net of $2.6 million in issuance costs paid under the 2024 underwriting agreement.

Previous wording

During the six months ended June 30, 2025, there were no material changes to our contractual obligations and commitments described under Management’s Discussion and Analysis of Financial Condition and Results of Operations in our Annual Report on Form 10-K, filed with the SEC on March 13, 2025.

Current wording

During the nine months ended September 30, 2025, there were no material changes to our contractual obligations and commitments described under Management’s Discussion and Analysis of Financial Condition and Results of Operations in our Annual Report on Form 10-K, filed with the SEC on March 13, 2025.