Amylyx Pharmaceuticals, Inc.

Previous wording

LUCIDITY (NCT06747468) is a 78-participant, multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating the efficacy and safety of avexitide in participants with PBH following RYGB surgery. The Phase 3 trial is being conducted at 21 sites in the U.S. Participants were randomized 3:2 to receive either 90 mg of avexitide subcutaneously once daily or placebo. The trial includes an up to six-week screening period, including a three-week run-in period, a 16-week double-blind treatment period, and an open-label extension (OLE) period with a duration of 32 weeks. The primary efficacy objective of LUCIDITY is to evaluate the FDA-agreed upon primary outcome of reduction in the composite of Level 2 and Level 3 hypoglycemic events through Week 16. Safety and tolerability will also be evaluated. Enrollment for LUCIDITY was completed in March 2026. We continue to expect to announce topline data in the third quarter of 2026, and if approved, a commercial launch in 2027.

Current wording

LUCIDITY (NCT06747468) is a 78-participant, multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating the efficacy and safety of avexitide in participants with PBH following RYGB surgery. The Phase 3 trial is being conducted at 21 sites in the U.S. Participants were randomized 3:2 to receive either 90 mg of avexitide subcutaneously once daily or placebo. The trial includes an up to six-week screening period, including a three-week run-in period, a 16-week double-blind treatment period, and an open-label extension (OLE) period with a duration of 32 weeks. The last participant completed the final trial visit in the 16-week double-blind period of the LUCIDITY trial of avexitide. The primary efficacy objective of LUCIDITY is to evaluate the FDA-agreed-upon primary outcome of reduction in the composite of Level 2 and Level 3 hypoglycemic events through Week 16. Safety and tolerability will also be evaluated. We continue to expect to announce topline data in the third quarter of 2026, and, if approved, a commercial launch in 2027.

Previous wording

In the Phase 2 (PREVENT), 28-day, randomized, placebo-controlled crossover trial (n=18), results showed a significant reduction in rates of Level 2 and 3 hypoglycemic events in participants with PBH after RYGB surgery following treatment with 30 mg twice daily and 60 mg once daily of avexitide compared with placebo. PREVENT’s primary endpoint was met with statistical significance, showing both avexitide dosing regimens improved the lowest glucose level (nadir) after a meal as measured during formal mixed meal tolerance testing, or MMTT. Mean plasma glucose nadir was increased by 21% (p=0.001) and 26% (p=0.0002) following avexitide 30 mg twice daily and 60 mg once daily dosing, respectively, compared to placebo. Avexitide was generally well-tolerated. The most common adverse events, or AEs, were injection site bruising, headache, and nausea; these occurred more often with placebo than either avexitide dose. No participants withdrew due to AEs.

Current wording

(nadir) after a meal as measured during formal mixed meal tolerance testing, or MMTT. Mean plasma glucose nadir was increased by 21% (p=0.001) and 26% (p=0.0002) following avexitide 30 mg twice daily and 60 mg once daily dosing, respectively, compared to placebo. Avexitide was generally well-tolerated. The most common adverse events, or AEs, were injection site bruising, headache, and nausea; these occurred more often with placebo than either avexitide dose. No participants withdrew due to AEs.

Previous wording

In the Phase 2b, 28-day, open-label, investigator-initiated, crossover trial (n=16), 90 mg once daily and 45 mg twice daily of avexitide met its primary endpoint and significantly reduced rates of hypoglycemic events in participants following a variety of upper gastrointestinal surgeries, including RYGB, sleeve gastrectomy, esophagectomy, Nissen fundoplication, and gastrectomy. Participants in the Phase 2b trial receiving 90 mg once daily of avexitide, the dose Amylyx is evaluating in LUCIDITY, saw a statistically significant 53% reduction in Level 2 hypoglycemic events (p=0.004) and a statistically significant 66% reduction in Level 3 hypoglycemic events (p=0.0003). There were no reported serious AEs, and AEs were mostly mild to moderate and resolved without medical treatment. The most common AEs included diarrhea, headache, bloating, and injection site reaction/bruising. No participant withdrew due to AEs. In the Phase 2b trial, 90 mg once daily of avexitide has also demonstrated a favorable pharmacokinetic profile maintaining exposure in the therapeutic range through 24 hours, supporting once daily dosing.

Current wording

In the Phase 2b, 28-day, open-label, investigator-initiated, crossover trial (n=16), 90 mg once daily and 45 mg twice daily of avexitide met its primary endpoint and significantly reduced rates of hypoglycemic events in participants following a variety of upper gastrointestinal surgeries, including RYGB, sleeve gastrectomy, esophagectomy, Nissen fundoplication, and gastrectomy. Participants in the Phase 2b trial receiving 90 mg once daily of avexitide, the dose we are evaluating in LUCIDITY, saw a statistically significant 53% reduction in Level 2 hypoglycemic events (p=0.004) and a statistically significant 66% reduction in Level 3 hypoglycemic events (p=0.0003). There were no reported serious AEs, and AEs were mostly mild to moderate and resolved without medical treatment. The most common AEs included diarrhea, headache, bloating, and injection site reaction/bruising. No participant withdrew due to AEs. In the Phase 2b trial, 90 mg once daily of avexitide has also demonstrated a favorable pharmacokinetic profile maintaining exposure in the therapeutic range through 24 hours, supporting once daily dosing.

Previous wording

In May 2025, we announced positive data from HELIOS at Week 48. Consistent with the HELIOS trial’s previously presented primary efficacy outcome of improvement in pancreatic function (as described above), treatment with AMX0035 through Week 48 demonstrated continued and sustained improvement in pancreatic beta cell function. Treatment with AMX0035 from Week 24 to Week 48 also showed sustained improvements or stabilization in glycemic control, as measured by hemoglobin A1c, or HbA1c, and time in target glucose range assessed by continuous glucose monitoring, as well as visual acuity. All participants with available measurements met the responder criteria, defined as either improvement or no change, on both the Patient Global Impression of Change and Clinician Global Impression of Change at Weeks 24 and 48, indicating stability or improvement in their Wolfram syndrome-related symptoms. Results from qualitative on-study interviews further supported the potential positive impact of AMX0035 on symptom burden.

Current wording

In May 2025, we announced positive data from HELIOS at Week 48. Consistent with the HELIOS trial’s previously presented primary efficacy outcome of improvement in pancreatic function (as described above), treatment with AMX0035 through Week 48 demonstrated continued and sustained improvement in pancreatic beta cell function. Treatment with AMX0035 from Week 24 to Week 48 also showed sustained improvements or stabilization in glycemic control, as measured by hemoglobin A1c, or HbA1c, and time in target glucose range assessed by continuous glucose monitoring, as well as visual acuity. All participants with available measurements met the responder criteria, defined as either improvement or no change, on both the Patient Global Impression of Change and Clinician Global Impression of Change at Weeks 24 and 48, indicating stability or improvement in their Wolfram syndrome-related symptoms. Results from qualitative on-study interviews further supported the potential positive impact of AMX0035 on symptom burden. In June 2026, we presented longer-term Week 96 (n=9) data from HELIOS. At Week 96, measures of pancreatic function and glycemic control were stable or improved relative to baseline in most participants. Visual acuity and patient- and clinician-reported outcomes showed patterns consistent with disease stabilization with interpretation limited by the open-label, single-arm design and small sample size.

Previous wording

The safety profile of AMX0035 in HELIOS data at Week 48 and Week 24 were consistent with prior safety data from the studies of AMX0035. All AEs were mild or moderate, and there were no serious AEs related to AMX0035 treatment. We anticipate presenting longer-term Week 96 data from HELIOS at an upcoming scientific meeting. We continue to work with the FDA on a Phase 3 trial in Wolfram syndrome. In addition, Amylyx is committed to supporting medically and scientifically sound research, including externally-sponsored research conducted with an institution or organization. Breakthrough T1D has provided funding to University of Washington and Amsterdam University Medical Center for a trial investigating AMX0035 as adjunctive therapy for treatment of insulin resistance in type 1 diabetes. Amylyx will provide clinical trial supply of AMX0035.

Current wording

In addition, we are committed to supporting medically and scientifically sound research, including externally-sponsored research conducted with an institution or organization. Breakthrough T1D has provided funding to University of Washington and Amsterdam University Medical Center for a trial investigating AMX0035 as adjunctive therapy for treatment of insulin resistance in type 1 diabetes. We will provide clinical trial supply of AMX0035.

Previous wording

The Phase 1 LUMINA clinical trial (NCT06665165) is a multinational, randomized, double-blind, placebo-controlled, multiple ascending dose trial evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMX0114 in people living with ALS. LUMINA will also assess change from baseline in calpain-2 levels, NfL levels, and other pharmacodynamic biomarkers of ALS. LUMINA is anticipated to enroll approximately 48 adult participants. Participants will be randomized 3:1 to receive AMX0114 or placebo by intrathecal administration once every four weeks for a total of up to four doses. We completed enrollment of Cohort 1 (n=12) of LUMINA in September 2025 and completed enrollment of Cohort 2 (n=12) in March 2026.

Current wording

The Phase 1 LUMINA clinical trial (NCT06665165) is a multinational, randomized, double-blind, placebo-controlled, multiple ascending dose trial evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMX0114 in people living with ALS. LUMINA will also assess change from baseline in calpain-2 levels, NfL levels, and other pharmacodynamic biomarkers of ALS. LUMINA is anticipated to enroll approximately 48 adult participants. Participants will be randomized 3:1 to receive AMX0114 or placebo by intrathecal administration once every four weeks for a total of up to four doses.

Previous wording

AMX0318 is a novel GLP-1 receptor antagonist for long-acting administration selected as a development candidate for PBH and other rare diseases in January 2026. AMX0318 was selected as a development candidate after demonstrating robust preclinical and chemical properties, including a favorable pharmacokinetic profile that may support long-acting administration, a robust chemical stability profile, strongin vitro potency, evidence ofin vivo activity and tolerability, and high solubility. AMX0318 was identified through a research collaboration with Gubra A/S, a company specializing in peptide-based drug discovery and preclinical contract research services. IND-enabling studies for AMX0318 are underway with an IND targeted for 2027.

Current wording

AMX0318 is a novel GLP-1 receptor antagonist for long-acting administration selected as a development candidate for PBH and other rare diseases in January 2026. AMX0318 was selected as a development candidate after demonstrating robust preclinical and chemical properties, including a favorable pharmacokinetic profile that may support long-acting administration, a robust chemical stability profile, strongin vitro potency, evidence ofin vivo activity and tolerability, and high solubility. AMX0318 was identified through a research collaboration with Gubra, a company specializing in peptide-based drug discovery and preclinical contract research services. IND-enabling studies for AMX0318 are underway with an IND submission targeted for 2027.

Previous wording

As of March 31, 2026, we had cash, cash equivalents and marketable securities of $279.8 million and an accumulated deficit of $792.7 million. We believe our existing cash, cash equivalents and marketable securities as of March 31, 2026 will be sufficient to fund our operations into 2028. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. See “Liquidity and Capital Resources” below.

Current wording

As of June 30, 2026, we had cash, cash equivalents and marketable securities of $250.8 million and an accumulated deficit of $836.1 million. We believe our existing cash, cash equivalents and marketable securities as of June 30, 2026 will be sufficient to fund our operations into 2028. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. See “Liquidity and Capital Resources” below.

Previous wording

Selling, general and administrative expenses were $16.2 million for the three months ended March 31, 2026 compared to $15.7 million for the three months ended March 31, 2025. The increase was primarily due to an increase of $0.7 million in consulting and professional services, partially offset by a decrease of $0.2 million in other expenses. The increase in consulting and professional services is primarily due to an increase in commercial and marketing activity as we prepare for a potential commercial launch of avexitide, if approved, as well as increased spend for general legal services. The decrease in other expenses is primarily due to lower facilities and IT-related expenses.

Current wording

Selling, general and administrative expenses were $21.9 million for the three months ended June 30, 2026 compared to $15.6 million for the three months ended June 30, 2025. The increase was primarily due to increases of $5.6 million in consulting and professional services and $1.0 million in payroll and personnel-related costs, including stock-based compensation, partially offset by a decrease of $0.3 million in other expenses. The increase in consulting and professional services was primarily due to increased spend for legal expenses related to the settlement of the February 2024 Shih Complaint, as well as an increase in commercial and marketing activity as we prepare for a potential commercial launch of avexitide, if approved. The increase in payroll and personnel-related costs was primarily due to hiring additional personnel to support our pre-commercialization activities.

Previous wording

Research and development expenses were $27.6 million for the three months ended March 31, 2026, compared to $22.1 million for the three months ended March 31, 2025. The increase was primarily due to a $4.6 million increase in expenses related to the pivotal Phase 3 LUCIDITY clinical trial in PBH and other costs related to avexitide, and a $4.2 million increase in expenses related to other programs. Other programs includes milestone payments totaling $4.0 million made to Gubra following the selection and handover of AMX0318 as a development candidate for PBH and other rare diseases during the three months ended March 31, 2026. The increase was offset by a $3.9 million decrease in expenses related to AMX0035 for the treatment of PSP after its discontinuation.

Current wording

Research and development expenses were $51.4 million for the six months ended June 30, 2026, compared to $49.3 million for the six months ended June 30, 2025. The increase was primarily due to a $6.8 million increase in expenses related to the pivotal Phase 3 LUCIDITY clinical trial in PBH and other costs related to avexitide, and a $4.1 million increase in expenses related to other programs, including milestone payments totaling $4.0 million made to Gubra following the selection and handover of AMX0318 as a development candidate for PBH and other rare diseases during the six months ended June 30, 2026. The increase was partially offset by a $11.0 million decrease in expenses related to AMX0035 for the treatment of PSP after its discontinuation.

Previous wording

As of March 31, 2026, we had cash, cash equivalents and marketable securities of $279.8 million and an accumulated deficit of $792.7 million. We believe our existing cash, cash equivalents and marketable securities as of March 31, 2026 will be sufficient to fund our operations into 2028. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect.

Current wording

As of June 30, 2026, we had cash, cash equivalents and marketable securities of $250.8 million and an accumulated deficit of $836.1 million. We believe our existing cash, cash equivalents and marketable securities as of June 30, 2026 will be sufficient to fund our operations into 2028. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect.

Previous wording

Despite the decline in research and development and general administrative expenses in 2025 as compared to 2024, we expect our expenses to increase in connection with our ongoing activities, particularly as we advance the preclinical activities, manufacturing and clinical trials of avexitide, AMX0035, AMX0114, AMX0318 and any other current or future product candidates or acquire or in-license additional product candidates or products. We may also incur expenses related to business development activities, such as in-licensing or acquisition of product candidates. In addition, we expect to incur additional costs associated with operating as a public company, including significant legal, accounting, investor relations and other expenses. We expect to incur significant expenses as we:

Current wording

We expect our expenses to increase in connection with our ongoing activities, particularly as we advance the preclinical activities, manufacturing and clinical trials of avexitide, AMX0035, AMX0114, AMX0318 and any other current or future product candidates or acquire or in-license additional product candidates or products. We may also incur expenses related to business development activities, such as in-licensing or acquisition of product candidates. In addition, we expect to incur additional costs associated with operating as a public company, including significant legal, accounting, investor relations and other expenses. We expect to incur significant expenses as we:

Previous wording

seek to identify and develop, acquire or in-license additional product candidates or other assets;

Current wording

seek to identify and develop, acquire or in-license additional product candidates or other assets, including through our recent collaboration agreement with Gubra;

Previous wording

During the three months ended March 31, 2026, operating activities used $36.9 million of cash, primarily resulting from our net loss of $41.3 million, $0.6 million net accretion of discounts on investments, and $5.3 million of net cash used by changes in our operating assets and liabilities, offset by $6.1 million of non-cash stock-based compensation expense and a $4.0 million charge for in-process research and development, or IPR&D, milestones related to the Gubra collaboration.

Current wording

During the six months ended June 30, 2026, operating activities used $68.3 million of cash, primarily resulting from our net loss of $84.7 million, $1.8 million net accretion of discounts on investments, and $0.4 million of net cash used by changes in our operating assets and liabilities, offset by $14.4 million of non-cash stock-based compensation expense and a $4.0 million charge for IPR&D milestones related to the Gubra collaboration.

Previous wording

Net cash used by changes in our operating assets and liabilities primarily consisted of a $0.7 million decrease in prepaid expenses and other current assets, a $1.9 million increase in accounts payable, offset by a $11.9 million decrease in accrued expenses.

Current wording

Net cash used by changes in our operating assets and liabilities primarily consisted of a $3.5 million decrease in accrued expenses and a $0.7 million decrease in operating lease liabilities, offset by a $1.1 million decrease in prepaid expenses and other current assets and a $2.0 million increase in accounts payable.

Previous wording

During the three months ended March 31, 2025, operating activities used $39.8 million of cash, primarily resulting from our net loss of $35.9 million, $9.2 million of net cash used by changes in our operating assets and liabilities and $1.7 million net accretion of discounts on investments, offset by $6.8 million of non-cash stock-based compensation expense.

Current wording

During the six months ended June 30, 2025, operating activities used $65.1 million of cash, primarily resulting from our net loss of $77.4 million and $3.2 million net accretion of discounts on investments, offset by $14.2 million of non-cash stock-based compensation expense and $0.8 million of net cash provided by changes in our operating assets and liabilities.

Previous wording

Net cash used by changes in our operating assets and liabilities primarily consisted of a $6.7 million decrease in accrued expenses and a $0.3 million decrease in operating lease liabilities, offset by a $1.4 million decrease in prepaid expenses and other current assets and a $0.3 million decrease in operating right-of-use assets.

Current wording

Net cash provided by changes in our operating assets and liabilities primarily consisted of a $6.5 million decrease in prepaid expenses and other current assets, and a $1.1 million decrease in operating ROU assets, offset by a $6.5 million decrease in accrued expenses and a $1.2 million decrease in operating lease liabilities.

Previous wording

During the three months ended March 31, 2026, net cash provided by investing activities was $36.3 million, resulting primarily from $60.0 million of investments that matured, offset by $19.7 million of purchases of marketable securities and $4.0 million in IPR&D milestone payments related to the Gubra collaboration.

Current wording

During the six months ended June 30, 2026, net cash used in investing activities was $113.5 million, resulting primarily from $200.5 million of purchases of marketable securities and $4.0 million in IPR&D milestone payments related to the Gubra collaboration, offset by $91.0 million of investments that matured.

Previous wording

During the three months ended March 31, 2025, net cash used in investing activities was $43.7 million, resulting primarily from $103.6 million of purchases of marketable securities, offset by $60.0 million of investments that matured.

Current wording

During the six months ended June 30, 2025, net cash used in investing activities was $20.7 million, resulting primarily from $142.6 million of purchases of marketable securities, offset by $122.0 million of investments that matured.

Previous wording

During the three months ended March 31, 2026, net cash provided by financing activities was $3.2 million. This amount consisted of $3.2 million of proceeds from exercises of stock options and vesting of stock awards, net of withholding taxes paid on stock-based awards.

Current wording

During the six months ended June 30, 2026, net cash provided by financing activities was $4.7 million. This amount consisted of $4.7 million of proceeds from exercises of stock options and vesting of stock awards, net of withholding taxes paid on stock-based awards.

Previous wording

During the three months ended March 31, 2025, net cash provided by financing activities was $65.7 million. This amount consisted primarily of $65.6 million in proceeds from the January 2025 Offering, net of offering costs paid.

Current wording

During the six months ended June 30, 2025, net cash provided by financing activities was $65.6 million. This amount consisted primarily of $65.6 million in proceeds from the January 2025 Offering, net of offering costs.