Amylyx Pharmaceuticals Inc.

08/07/2025 | Press release | Distributed by Public on 08/07/2025 05:15

Quarterly Report for Quarter Ending June 30, 2025 (Form 10-Q)

Management's Discussion and Analysis of Financial Condition and Results of Operations.

The following information should be read in conjunction with the condensed consolidated financial information and the notes thereto appearing elsewhere in this Quarterly Report.

This discussion and other parts of this Quarterly Report contain forward-looking statements that involve risks and uncertainties, such as statements of our plans, objectives, expectations and intentions. As a result of many factors, including those risk factors set forth in our most recent Annual Report on Form 10-K, or 2024 Annual Report, and in our subsequent Quarterly Reports, our actual results could differ materially from the results described in or implied by the forward-looking statements contained in the following discussion and analysis.

Overview

We are a clinical-stage pharmaceutical company with a mission to develop novel therapies for communities with high unmet medical needs. We have preclinical and clinical development programs underway in neurodegenerative diseases and endocrine conditions. We are advancing a pipeline in which we have matched investigational therapies with diseases where we believe they can make the greatest impact, based on well-defined mechanistic rationale, clear clinical outcomes and biomarkers, and rigorous preclinical data, agnostic of modality. We are currently developing three investigational therapies for potential impact across several diseases: avexitide in PBH, AMX0035 in Wolfram syndrome and PSP, and AMX0114 in ALS.

Our lead investigational asset is avexitide, a first-in-class glucagon-like peptide-1, or GLP-1 receptor antagonist. Avexitide has been evaluated as a treatment for PBH and congenital hyperinsulinism, or HI, two indications characterized by hyperinsulinemic hypoglycemia. The U.S. Food and Drug Administration, or the FDA, has granted avexitide Breakthrough Therapy Designation for both PBH and congenital HI, Rare Pediatric Disease Designation in congenital HI, and Orphan Drug Designation for the treatment of hyperinsulinemic hypoglycemia (which includes PBH and congenital HI).

PBH is a condition that affects about 160,000 people in the U.S., or approximately 8% of those in the U.S. who have undergone the two most common types of bariatric surgery: sleeve gastrectomy and Roux-en-Y gastric bypass, or RYGB surgery. Currently, there are no FDA-approved therapies for PBH. PBH is thought to be caused by an excessive GLP-1 response, leading to hypoglycemia and impaired quality of life. Clinical manifestations can include impaired cognition, loss of consciousness, and seizures. Avexitide is designed to bind to the GLP-1 receptor on pancreatic islet beta cells and inhibit the effects of excessive GLP-1 in PBH, mitigating hypoglycemia by decreasing insulin secretion and stabilizing blood glucose levels.

In April 2025, we dosed the first participant for the pivotal Phase 3 LUCIDITY clinical trial for avexitide in PBH following RYGB surgery. LUCIDITY (NCT06747468) is a multicenter, randomized, double-blind, placebo-controlled, 16-week clinical trial evaluating the efficacy and safety of avexitide in participants with PBH following RYGB surgery. The Phase 3 trial is being conducted at approximately 20 sites in the U.S. Approximately 75 participants will be randomized 3:2 to receive either 90 mg of avexitide subcutaneously once daily or placebo. Participants who complete the 16-week double-blind period of the ongoing study will be eligible to enter an open-label extension, or OLE, period with a duration of 32 weeks. The primary efficacy objective of LUCIDITY is to evaluate the FDA-agreed primary endpoint of reduction in the composite of Level 2 and Level 3 hypoglycemic events through Week 16. Safety and tolerability will also be evaluated. Completion of recruitment is expected in 2025, with topline data anticipated in the first half of 2026 and, if approved, commercial launch is anticipated in 2027.

LUCIDITY was informed by data from five clinical trials of avexitide in people with PBH showing consistent, dose-dependent effects across studies. The five clinical trials include a Phase 1 trial, a single ascending dose trial, a multiple ascending dose trial, and two Phase 2 trials:

In the Phase 2 (PREVENT), 28-day, randomized, blinded, 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.
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
RYGB surgery and other upper-gastrointestinal surgeries. 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, or PK, profile maintaining exposure in the therapeutic range through 24 hours, supporting once daily dosing.
In addition, new exploratory analyses from the Phase 2 PREVENT and Phase 2b clinical trials of avexitide were presented at the Endocrine Society's annual meeting in July 2025. In the Phase 2b trial, avexitide 90 mg once daily, the dose being evaluated in the pivotal Phase 3 LUCIDITY trial, led to a 64% least-squares mean reduction (p=0.0031) vs. baseline in the composite rate of Level 2 and Level 3 hypoglycemic events in PBH, with more than half of the participants experiencing no events during the treatment period. Consistent reductions in composite rate of Level 2 and Level 3 hypoglycemic events also were seen with avexitide 45 mg twice daily studied in the Phase 2b trial and avexitide 30 mg twice daily and 60 mg once daily studied in the Phase 2 PREVENT trial. New PK and pharmacodynamic, or PD, data were also presented, demonstrating continuous pharmacologic activity of the 90 mg once daily dose regimen for a 24-hour period.

Avexitide was generally well-tolerated, with a favorable safety profile replicated across five clinical trials in people with PBH. In healthy volunteers, avexitide demonstrated a clear GLP-1 antagonist PD effect, including lowering insulin and raising the glucose nadir.

In congenital HI, we are actively engaging in discussions with the broader congenital HI community to develop a path forward.

In December 2024, we announced a collaboration with Gubra A/S for the development of a potential novel long-acting GLP-1 receptor antagonist. As part of this collaboration, we anticipate identifying a lead development candidate to enter Investigational New Drug, or IND-enabling studies.

In addition to avexitide, we are investigating AMX0035, an oral, fixed-dose combination of sodium phenylbutyrate and taurursodiol in Wolfram syndrome and PSP, and AMX0114, an antisense oligonucleotide targeting calpain-2 in ALS.

AMX0035 is designed to slow or mitigate neurodegeneration by targeting endoplasmic reticulum, or ER stress, and mitochondrial dysfunction, two connected central pathways that lead to cell death and neurodegeneration. We are investigating AMX0035 in neurodegenerative diseases and endocrine conditions where ER stress and mitochondrial dysfunction are implicated, including Wolfram syndrome and PSP.

Wolfram syndrome is a rare, monogenic, progressive neurodegenerative disorder that progressively impacts multiple organs and systems. Wolfram syndrome is characterized by childhood-onset diabetes mellitus, optic nerve atrophy, and neurodegeneration. Common manifestations of Wolfram syndrome include diabetes mellitus and diabetes insipidus, gradual vision loss leading to blindness, hearing loss, neurogenic bladder, difficulties with balance and coordination, and difficulty breathing that can lead to respiratory failure. There are currently no approved therapies for the approximately 3,000 people in the U.S., and more around the world, living with Wolfram syndrome.

The majority of people with Wolfram syndrome carry mutations in the WFS1 gene, which encodes a protein called wolframin that spans the membrane of the ER. Loss of wolframin function leads to ER stress and impaired mitochondrial dynamics, which lead to multi-organ cell dysfunction and death - starting with beta cells in the pancreas, then neurons in the visual system, auditory system, and throughout the body. Because of the clear link between WFS1 mutations and ER stress, Wolfram syndrome is considered a prototypical ER stress disorder. AMX0035 is hypothesized to mitigate cell death in Wolfram syndrome by reducing ER stress and mitochondrial dysfunction. In preclinical models, treatment with AMX0035 improved WFS1 protein expression, increased insulin secretion, and inhibited beta cell death in cells derived from people with Wolfram syndrome. AMX0035 also prevented cell death in neuronal cells derived from people with Wolfram syndrome and significantly delayed progression of the diabetes phenotype in a WFS1-knock-out preclinical model.

In October 2024, we announced positive topline data, including the primary efficacy outcome of the trial, from the Phase 2 open-label HELIOS clinical trial of AMX0035 in 12 adults living with Wolfram syndrome, and in May 2025, we announced positive long-term data from the HELIOS trial of AMX0035 in Wolfram syndrome through Week 48. HELIOS (NCT05676034) is a single-site, single-arm, open-label, Phase 2 trial designed to evaluate the safety and tolerability of AMX0035, as well as its effects on various measures of endocrinological, neurological, and ophthalmologic function in adult participants living with Wolfram syndrome. Consistent with the HELIOS trial's previously presented primary efficacy outcome of improvement in pancreatic function, as

measured by C-peptide response to a mixed-meal tolerance test at Week 24, treatment with AMX0035 through Week 48 demonstrated continued and sustained improvement in pancreatic beta cell function, in contrast to the expected decrease in pancreatic function with disease progression.

Treatment with AMX0035 at Week 24 and at Week 48 also showed sustained improvements or stabilization in glycemic control, as measured by hemoglobin A1c (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. Safety data were consistent with safety data from prior studies of AMX0035. All AEs were mild or moderate, and there were no serious AEs related to AMX0035 treatment. The analysis performed at Week 24 included 11 participants in the Per Protocol population with genetically confirmed Wolfram syndrome (one participant was excluded from the Per Protocol population due to not meeting the study inclusion criteria of genetically confirmed Wolfram syndrome) and 12 participants in the Intent-to-Treat population. Long-term data at Week 48 included 10 participants in the Per Protocol population with genetically confirmed Wolfram syndrome and 11 participants in the Intent-to-Treat population. One participant discontinued between Week 24 and Week 48 for reasons unrelated to safety. These data and discussions with the FDA will inform the design of a Phase 3 trial of AMX0035 in Wolfram syndrome.

PSP is a rare, progressive, and fatal neurodegenerative disease that can affect movement, gait, balance, cognition, eye movements, swallowing, and speech and is estimated to affect 23,000 people in the U.S. People living with PSP have a life expectancy of six to eight years after symptom onset. There are no approved therapies for PSP. PSP is a tauopathy, which is defined by the buildup of tau protein in the brain. Based on its prior effect from a Phase 2 trial of AMX0035 in reducing tau in cerebrospinal fluid, or CSF, in people with Alzheimer's disease, we believe AM00X35 is the first brain- and cell-penetrant agent that has demonstrated a significant tau reduction in CSF to be tested in PSP.

In December 2023, we initiated the Phase 2b/3 ORION (NCT06122662) clinical trial, a global, randomized, double-blind, placebo-controlled trial of AMX0035 for the treatment of PSP. ORION is a Phase 2b/3 clinical trial designed to assess the efficacy and safety of AMX0035 compared to placebo. The primary objective of the ORION trial is to assess the impact of AMX0035 compared to placebo on disease progression rate as measured by the Progressive Supranuclear Palsy Rating Scale, an established and validated endpoint in PSP clinical trials. Safety and tolerability will also be evaluated. We completed enrollment in the Phase 2b portion of the ORION trial in January 2025, with a total of 139 participants randomized. Efficacy and safety data from an unblinded interim analysis of the Phase 2b portion of the Phase 2b/3 ORION trial of AMX0035 in PSP is anticipated in the third quarter of 2025, which will be used to inform a go/no-go decision on the Phase 3 portion of the trial.

AMX0114 is an investigational antisense oligonucleotide designed to target calpain-2, a calcium-activated protease. The FDA has granted AMX0114 Fast Track designation for the treatment of ALS. Peer-reviewed research has demonstrated that overactive calpain-2 activity may be an important driver of disease progression in ALS and other neurodegenerative diseases by executing the degeneration of axons, the long tubular neuronal segments which carry signals from neurons to the muscle or other neurons. ALS is a relentlessly progressive and fatal neurodegenerative disorder caused by motor neuron death in the brain and spinal cord. Motor neuron loss in ALS leads to deteriorating muscle function, the inability to move and speak, respiratory paralysis, and eventually, death. ALS is defined as a rare disease, but it affects as many as 30,000 adults in the U.S. and 3,000 in Canada. The most common form of the disease is sporadic ALS, with more than 90% of people with ALS showing no clear family history.

In preclinical studies, treatment with AMX0114 resulted in potent, dose-dependent, and durable reduction in CAPN2mRNA and calpain-2 protein levels in disease-relevant cell models of axonal degeneration. This translated to improved neuronal survival and reductions in extracellular neurofilament light chain, or NfL levels, a broadly researched biomarker for axonal degeneration in ALS, across multiple disease models and paradigms of neuronal injury. AMX0114 was generally well-tolerated in in vivo preclinical safety studies.

In April 2025, we dosed the first participant in Canada for the Phase 1 LUMINA clinical trial (NCT06665165), a multicenter, randomized, double-blind, placebo-controlled, multiple ascending dose trial designed to evaluate the safety and biological activity of AMX0114 in people living with ALS. LUMINA will also assess ALS biomarkers, including change from baseline in NfL levels. In addition to the activated sites in Canada, we are continuing to open U.S. sites for screening, enrollment, and dosing. Approximately 48 participants will be randomized 3:1 to receive AMX0114 or placebo by intrathecal administration once every four weeks, for up to four doses. Early cohort data from LUMINA are expected in 2025.

Components of Our Results of Operations

Operating Expenses

Research and Development Expenses

Research and development expenses consist primarily of costs incurred in connection with the research and development of avexitide, AMX0035, AMX0114 and other potential future product candidates. We expense research and development costs as incurred. These expenses include:

expenses incurred under agreements with CROs, CMOs, as well as investigative sites and consultants that conduct our clinical trials, preclinical studies and other scientific development services;
manufacturing scale-up expenses and the cost of acquiring and manufacturing drug product for our preclinical studies and clinical trials, including manufacturing registration and validation batches, as well as pre-commercial manufacturing activities;
expenses to acquire technologies to be used in research and development;
employee-related expenses, including salaries, payroll taxes, related benefits and stock-based compensation expense for employees engaged in research and development functions; and
costs related to compliance with quality and regulatory requirements.

Advance payments that we make for goods or services to be received in the future for use in research and development activities are recorded as prepaid expenses. Such amounts are recognized as an expense as the goods are delivered or the related services are performed, or until it is no longer expected that the goods will be delivered, or the services rendered.

Certain of our indirect research and development expenses are not tracked on an indication-by-indication basis. We do not allocate employee costs and facilities, including depreciation or other indirect costs, to specific indications because these costs are deployed across multiple indications and, as such, are not separately classified. We use internal resources to oversee the research and discovery as well as to manage our preclinical development, process development, manufacturing and clinical development activities. These employees work across multiple indications and, therefore, we do not track their costs by indication.

Research and development activities are central to our business model. Product candidates such as avexitide and AMX0035 in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development, such as AMX0114, primarily due to the increased size and duration of later-stage clinical trials and related product manufacturing expenses. Despite a decline in research and development expenses in 2024 and in the first quarter of 2025 compared to prior respective periods, research and development expenses increased in the second quarter of 2025 compared to the prior year period and we expect that our research and development expenses will continue to increase in connection with our planned clinical development activities in the near term and in the future. At this time, we cannot accurately estimate or know the nature, timing and costs of the efforts that will be necessary to complete the clinical development of avexitide, AMX0035, AMX0114 and any future product candidates. Our clinical development costs may vary significantly based on factors such as:

per patient trial costs;
the number of trials required for approval;
the number of sites included in the trials;
the countries in which the trials are conducted;
the length of time required to enroll eligible patients;
the number of patients that participate in the trials;
the number of doses that patients receive;
the drop-out or discontinuation rates of patients;
potential additional safety monitoring requested by regulatory agencies;
the duration of patient participation in the trials and follow-up periods;
the cost and timing of manufacturing our current or future product candidates;
the phase of development of our current or future product candidates;
the efficacy and safety profile from clinical trials and preclinical studies of our current or future product candidates; and
the number of product candidates we are developing.

The successful development and commercialization of avexitide, AMX0035 and any other current or future product candidates is highly uncertain, due to the numerous risks and uncertainties associated with product development and commercialization, including the following:

the timing and progress of preclinical and clinical development activities;
the number and scope of preclinical and clinical trials for separate indications we decide to pursue;
raising additional funds, if necessary;
the progress of the development efforts of parties with whom we may enter into collaboration arrangements;
our ability to maintain our current development activities and to establish new ones;
our ability to establish new licensing or collaboration arrangements;
the successful initiation and completion of clinical trials with safety, tolerability and efficacy profiles that are satisfactory to the FDA or any other comparable foreign regulatory authority;
the availability of drug substance and drug product for use in production of avexitide, AMX0035 or other product candidates;
establishing and maintaining agreements with third-party manufacturers for clinical supply for our clinical trials;
our ability to obtain and maintain patents, trade secret protection and regulatory exclusivity, both in the U.S. and internationally;
our ability to protect our rights in our intellectual property portfolio;
obtaining and maintaining third-party insurance coverage and adequate reimbursement in the future for any approved products;
the acceptance of our products and product candidates, if approved, by patients, the medical community and third-party payors;
competition with other products; and
a continued acceptable safety profile of our therapies in pre-approval market access programs or in commercial access following approval.

A change in the outcome of any of these variables with respect to the development of avexitide, AMX0035, AMX0114 or any other current or future product candidates could have a significant impact on the cost and timing associated with the development of our product candidates. We may never succeed in obtaining or maintaining, as applicable, regulatory approval for avexitide, AMX0035, AMX0114 or any other current or future product candidates.

Selling, General and Administrative Expenses

Selling, general and administrative expenses consist primarily of salaries and related costs for personnel in executive, finance, sales, marketing, as well as administrative functions. Selling, general and administrative expenses also include legal fees relating to patent and corporate matters; professional fees for accounting, auditing, tax and administrative consulting services; corporate insurance costs; administrative travel expenses; sales and marketing expenses; information technology; charitable donations to independent charitable foundations; facility-related and other operating costs. In April 2024, we announced a restructuring plan, or the Restructuring Plan, designed to focus our resources on key clinical and preclinical programs. The restructuring included a reduction in force which reduced our workforce by approximately 70% and a decrease in external financial commitments outside our priority areas. As a result, our selling, general and administrative expenses decreased during the three and six months ended June 30, 2025 as compared to the three and six months ended June 30, 2024. However, we expect that general and administrative expenses will increase in future periods as we advance our clinical pipeline.

Income Taxes

We have historically not incurred significant income taxes. We continue to maintain a full valuation allowance against all of our deferred tax assets based on management's evaluation of all available evidence, including our history of incurring significant losses from operations. As a result, we don't expect to incur material income taxes for the foreseeable future.

Results of Operations

Comparison of the three months ended June 30, 2025 and 2024

The following table summarizes our results of operations for the periods presented (in thousands):

Three Months Ended June 30,

2025

2024

$ Change

% Change

Product revenue, net

$

-

$

(1,023

)

$

1,023

(100

)%

Operating expenses:

Cost of sales

-

8

(8

)

(100

)%

Cost of sales - inventory impairment and loss on firm purchase commitments

-

7,410

(7,410

)

(100

)%

Research and development

27,217

23,347

3,870

17

%

Selling, general and administrative

15,640

21,647

(6,007

)

(28

)%

Restructuring expenses

-

22,851

(22,851

)

(100

)%

Total operating expenses

42,857

75,263

(32,406

)

(43

)%

Loss from operations

(42,857

)

(76,286

)

33,429

(44

)%

Other income, net:

Interest income

1,960

4,069

(2,109

)

(52

)%

Other expense, net

(546

)

(483

)

(63

)

13

%

Total other income, net

1,414

3,586

(2,172

)

(61

)%

Loss before income taxes

(41,443

)

(72,700

)

31,257

(43

)%

Provision for income taxes

-

-

-

*NM

Net loss

$

(41,443

)

$

(72,700

)

$

31,257

(43

)%

* NM - not meaningful

Product Revenue, Net and Cost of Sales

As a result of the RELYVRIO®/ALBRIOZA™ Discontinuation, we did not generate revenue from product sales for the three months ended June 30, 2025. For the three months ended June 30, 2024, product revenue, net was primarily related to gross-to-net adjustments reflecting actual rebate and return activity during the period.

As a result of the RELYVRIO®/ALBRIOZA™ Discontinuation, we did not generate cost of sales for the three months ended June 30, 2025. Cost of sales for the three months ended June 30, 2024 consisted of costs to procure, manufacture and distribute our marketed products, RELYVRIO and ALBRIOZA. As a result of the RELYVRIO®/ALBRIOZA™ Discontinuation, we recorded approximately $7.4 million of charges associated with the write-down of inventory and losses on firm purchase commitments for the three months ended June 30, 2024.

Research and Development Expenses

The following table summarizes our research and development expenses for the three months ended June 30, 2025 and 2024 (in thousands):

Three Months Ended June 30,

2025

2024

$ Change

% Change

Direct research and development expenses by program:

Avexitide

$

7,105

$

-

$

7,105

*NM

AMX0035 - PSP

7,146

3,546

3,600

102

%

AMX0035 - ALS

794

9,408

(8,614

)

(92

)%

Other programs

3,965

2,221

1,744

79

%

Total direct research and development expenses by program

19,010

15,175

3,835

25

%

Payroll and personnel-related

8,207

8,172

35

0

%

$

27,217

$

23,347

$

3,870

17

%

* NM - not meaningful

Research and development expenses were $27.2 million for the three months ended June 30, 2025, compared to $23.3 million for the three months ended June 30, 2024. The increase was primarily due to a $7.1 million increase in expenses related to the pivotal Phase 3 LUCIDITY clinical trial for avexitide in PBH, a $3.6 million increase in expenses related to AMX0035 for the treatment of PSP and a $1.7 million increase in expenses related to other research and development activities. The increase was partially offset by a $8.6 million decrease in spending on AMX0035 for the treatment of ALS following the topline data from the PHOENIX trial.

Selling, General and Administrative Expenses

Selling, general and administrative expenses were $15.6 million for the three months ended June 30, 2025 compared to $21.6 million for the three months ended June 30, 2024. The decrease was primarily due to a decrease of $0.8 million in payroll and personnel-related costs, a decrease of $2.0 million in consulting and professional services and a decrease of $3.2 million in other expenses. The decrease in payroll and personnel-related costs was primarily related to a decrease in the number of employees as a result of the Restructuring Plan. The decrease in consulting and professional services is primarily due to a decrease in commercial sales and marketing activity as a result of the RELYVRIO®/ALBRIOZA Discontinuation. The decrease in other expenses is primarily due to a decrease in facilities and IT-related expenses.

Restructuring Expenses

We did not recognize restructuring expenses for the three months ended June 30, 2025. During the three months ended June 30, 2024, restructuring expenses were approximately $22.9 million which includes employee severance and termination benefits of approximately $21.8 million, contract termination costs, impairment of long-lived assets and other costs of $1.0 million. We substantially completed the Restructuring Plan in the second quarter of 2024.

Comparison of the six months ended June 30, 2025 and 2024

The following table summarizes our results of operations for the periods presented (in thousands):

Six Months Ended June 30,

2025

2024

$ Change

% Change

Product revenue, net

$

-

$

87,620

$

(87,620

)

(100

)%

Operating expenses:

Cost of sales

-

5,953

(5,953

)

(100

)%

Cost of sales - inventory impairment and loss on firm purchase commitments

-

117,871

(117,871

)

(100

)%

Research and development

49,336

59,955

(10,619

)

(18

)%

Selling, general and administrative

31,324

79,406

(48,082

)

(61

)%

Restructuring expenses

-

22,851

(22,851

)

(100

)%

Total operating expenses

80,660

286,036

(205,376

)

(72

)%

Loss from operations

(80,660

)

(198,416

)

117,756

(59

)%

Other income, net:

Interest income

4,191

8,395

(4,204

)

(50

)%

Other expense, net

(881

)

(1,230

)

349

(28

)%

Total other income, net

3,310

7,165

(3,855

)

(54

)%

Loss before income taxes

(77,350

)

(191,251

)

113,901

(60

)%

Provision for income taxes

-

242

(242

)

(100

)%

Net loss

$

(77,350

)

$

(191,493

)

$

114,143

(60

)%

Product Revenue, Net and Cost of Sales

As a result of the RELYVRIO®/ALBRIOZA™ Discontinuation, we did not generate revenue from product sales for the six months ended June 30, 2025. For the six months ended June 30, 2024, product revenue, net was primarily related to units of RELYVRIO and ALBRIOZA previously sold in the U.S. and Canada.

As a result of the RELYVRIO®/ALBRIOZA™ Discontinuation, we did not generate cost of sales for the six months ended June 30, 2025. Cost of sales for the six months ended June 30, 2024 consisted of costs to procure, manufacture and distribute our marketed products, RELYVRIO and ALBRIOZA. As a result of the RELYVRIO®/ALBRIOZA™ Discontinuation, we recorded

approximately $117.9 million of charges associated with the write-down of inventory and losses on firm purchase commitments for the six months ended June 30, 2024.

Research and Development Expenses

The following table summarizes our research and development expenses for the six months ended June 30, 2025 and 2024 (in thousands):

Six Months Ended June 30,

2025

2024

$ Change

% Change

Direct research and development expenses by program:

Avexitide

$

12,531

$

-

$

12,531

*NM

AMX0035 - PSP

11,709

7,734

3,975

51

%

AMX0035 - ALS

1,264

23,818

(22,554

)

(95

)%

Other programs

7,267

4,771

2,496

52

%

Total direct research and development expenses by program

32,771

36,323

(3,552

)

(10

)%

Payroll and personnel-related

16,565

23,632

(7,067

)

(30

)%

$

49,336

$

59,955

$

(10,619

)

(18

)%

* NM - not meaningful

Research and development expenses were $49.3 million for the six months ended June 30, 2025, compared to $60.0 million for the six months ended June 30, 2024. The decrease was primarily due to a $22.6 million decrease in spending on AMX0035 for the treatment of ALS following the topline data from the PHOENIX trial, and a $7.1 million decrease in payroll and personnel-related costs primarily related to a decrease in the number of employees as a result of the Restructuring Plan. The decrease was partially offset by a $12.5 million increase in expenses related to the pivotal Phase 3 LUCIDITY clinical trial for avexitide in PBH, a $4.0 million increase in expenses related to AMX0035 for the treatment of PSP and a $2.5 million increase in expenses related to other research and development activities.

Selling, General and Administrative Expenses

Selling, general and administrative expenses were $31.3 million for the six months ended June 30, 2025 compared to $79.4 million for the six months ended June 30, 2024. The decrease was primarily due to a decrease of $16.8 million in payroll and personnel-related costs, a decrease of $14.8 million in consulting and professional services and a decrease of $16.5 million in other expenses. The decrease in payroll and personnel-related costs was primarily related to a decrease in the number of employees as a result of the Restructuring Plan. The decrease in consulting and professional services is primarily due to a decrease in commercial sales and marketing activity as a result of the RELYVRIO®/ALBRIOZA Discontinuation. The decrease in other expenses is primarily due to a decrease in charitable contributions and activity to wind down commercial operations.

Restructuring Expenses

We did not recognize restructuring expenses for the six months ended June 30, 2025. During the six months ended June 30, 2024, restructuring expenses were approximately $22.9 million, which includes employee severance and termination benefits of approximately $21.8 million, contract termination costs, impairment of long-lived assets and other costs of $1.0 million. We substantially completed the Restructuring Plan in the second quarter of 2024.

Liquidity and Capital Resources

Sources of Liquidity

In January 2025, we entered into an underwriting agreement with Leerink Partners LLC relating to the issuance and sale of an aggregate of 19,714,285 shares of our common stock, which includes the exercise in full by the underwriter of its option to purchase an additional 2,571,428 shares, or the January 2025 Offering. The public offering price per share was $3.50. The January 2025 Offering resulted in proceeds of approximately $65.5 million, net of underwriting discounts and offering expenses.

As of June 30, 2025, we had cash, cash equivalents and marketable securities of $180.8 million and an accumulated deficit of $684.0 million. We believe our existing cash, cash equivalents and marketable securities as of June 30, 2025 will be sufficient to meet our anticipated operating and capital expenditure requirements through 2026. 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.

Since inception, we have devoted substantially all of our efforts to research and development, pre-commercialization and commercialization activities, including recruiting management and technical staff, raising capital, producing materials for preclinical studies and clinical trials, and building infrastructure to support such activities. As of June 30, 2025, we have funded our operations primarily through public offerings of our common stock, private sales of preferred stock, convertible notes, and through revenue from sales of RELYVRIO and ALBRIOZA in the U.S. and Canada, respectively, between July 2022 and April 2024.

We expect to finance our near-term operations through our existing cash, cash equivalents and marketable securities and the sale of equity, debt financings or other capital sources, including potential collaborations with other companies, royalty financings, or other strategic transactions. Our inability to raise capital or secure other funding as and when needed could have a negative impact on our financial condition and ability to pursue our business strategies. There can be no assurances that our current operating plan will be achieved or that additional funding, if required, will be available on terms acceptable to us, or at all.

Capital Resources and Uses

Despite the decline in research and development and general administrative expenses in 2024 as compared to 2023, 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 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 will continue 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:

continue our research and development efforts of avexitide in PBH, or any other indications, and conduct clinical trials of avexitide;
continue our research and development efforts of AMX0035, including our ongoing Phase 2b/3 trial of AMX0035 in PSP and our ongoing Phase 2 trial of AMX0035 for the treatment of Wolfram syndrome;
continue our research and development efforts of AMX0114, including our ongoing Phase 1 clinical trial of AMX0114 for the treatment of ALS;
pursue INDs of AMX0035 for additional indications;
conduct preclinical studies and clinical trials for AMX0035 for additional indications and for potential future product candidates;
seek to identify and develop, acquire or in-license additional product candidates;
experience any delays or encounter any issues with any of the above, including but not limited to failed studies, complex results, safety issues, or other regulatory challenges;
develop the necessary processes, controls and manufacturing data to obtain marketing approval for current or future product candidates and to support manufacturing on a commercial scale;
seek regulatory approvals for any current or future product candidates that successfully complete clinical trials, if any;
incur expenses in preparation for commercialization for any approved product candidates related to product sales, marketing, manufacturing, and distribution;
hire and retain additional personnel, such as preclinical, clinical, quality assurance, regulatory affairs, manufacturing, distribution, legal, compliance, finance, general and administrative, commercial and scientific personnel; and
develop, maintain, expand and protect our intellectual property portfolio.

Because of the numerous risks and uncertainties associated with research, development and commercialization of product candidates and programs, we are unable to estimate the exact amount of our working capital requirements. Our future funding requirements will depend on and could increase significantly as a result of many factors, including:

the scope, progress, results and costs of drug discovery, laboratory testing, preclinical and clinical development for avexitide, AMX0035, AMX0114 and any future product candidates;
the costs, timing and outcome of any future commercialization activities, including manufacturing, marketing, sales and distribution costs;
the costs, timing and outcome of regulatory review of avexitide, AMX0035, AMX0114 and any future product candidates;
our ability to establish and maintain collaborations, marketing, distribution and license agreements on favorable terms, if at all;
our ability to enroll clinical trials in a timely manner and to quickly resolve any delays or clinical holds that may be imposed on our development activities;
timing delays with respect to preclinical and clinical development of avexitide, AMX0035, AMX0114 and any future product candidates, including as result of any future outbreak of any highly infectious or contagious diseases;
costs associated with identifying and developing, acquiring or in-licensing additional product candidates or products;
the costs of any future expansion of our facilities to accommodate our potential growth in personnel, and the costs of such additional personnel;
the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims;
the extent to which we acquire technologies or other assets;
the sales price and availability of adequate third-party coverage and reimbursement for any future product candidates, if and when approved;
the costs of current and potential legal proceedings that may not be covered by our insurance; and
the costs of operating as a public company.

Until such time, if ever, that we can generate product revenue sufficient to sustain profitability, we may finance our cash needs through equity offerings, debt financings, government or other third-party funding, marketing and distribution arrangements and other collaborations, strategic alliances and licensing arrangements. To the extent that we raise additional capital through the sale of common stock, convertible securities or other equity securities, current ownership interests will be diluted. If we raise additional funds through collaborations or marketing, distribution or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams or product candidates or grant licenses on terms that may not be favorable to us. In addition, debt financing, if available, may result in fixed payment obligations and may involve agreements that include restrictive covenants that limit our ability to take specific actions, such as incurring additional debt, making capital expenditures, creating liens, redeeming stock or declaring dividends, that could adversely impact our ability to conduct our business. If we are unable to raise additional funds when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

Cash Flows

Comparison of the six months ended June 30, 2025 and 2024

The following table summarizes our sources and uses of cash for the periods presented (in thousands):

Six Months Ended June 30,

2025

2024

$ Change

% Change

Net cash used in operating activities

$

(65,072

)

$

(67,069

)

$

1,997

(3

)%

Net cash used in investing activities

(20,665

)

(28,142

)

7,477

(27

)%

Net cash provided by financing activities

65,631

158

65,473

41,439

%

Effect of exchange rate changes on cash, cash equivalents and restricted cash equivalents

805

(149

)

954

(640

)%

Net decrease in cash, cash equivalents and restricted cash equivalents

$

(19,301

)

$

(95,202

)

$

75,901

(80

)%

Operating Activities

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.

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.

During the six months ended June 30, 2024, operating activities used $67.1 million of cash, primarily resulting from our net loss of $191.5 million, $5.8 million net accretion of discounts on investments and $8.5 million of net cash used by changes in our operating assets and liabilities, offset by $117.9 million of inventory impairment and loss on firm purchase commitments and $19.5 million of non-cash stock-based compensation expense.

Net cash used by changes in our operating assets and liabilities primarily consisted of a $36.0 million decrease in accounts receivable, net, offset by a $9.3 million increase in inventory capitalized during the period, net of inventory written-off, a decrease of $20.3 million in accrued expenses and a $17.1 million decrease in accounts payable.

Investing Activities

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.

During the six months ended June 30, 2024, net cash used in investing activities was $28.1 million, resulting primarily from $232.0 million of purchases of short-term investments during the period, offset by $204.0 million of investments that matured.

Financing Activities

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.

During the six months ended June 30, 2024, net cash provided by financing activities was $0.2 million. This amount consisted primarily of $0.2 million of proceeds from exercises of stock options and vesting of stock awards, net of withholding taxes paid on stock-based awards.

Critical Accounting Policies, Recent Accounting Pronouncements and Significant Judgments and Estimates

Our condensed consolidated financial statements are prepared in accordance with generally accepted accounting principles in the U.S. The preparation of our condensed consolidated financial statements and related disclosures requires us to make estimates and judgments that affect the reported amounts of assets, liabilities, costs and expenses, and the disclosure of contingent assets and liabilities in our condensed consolidated financial statements. We base our estimates on historical experience, known trends and events and various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making

judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. We evaluate our estimates and assumptions on an ongoing basis. Our actual results may differ from these estimates under different assumptions or conditions.

There have been no significant changes to our critical accounting policies from those described in "Management's Discussion and Analysis of Financial Condition and Results of Operations," disclosed in our 2024 Annual Report.

Amylyx Pharmaceuticals Inc. published this content on August 07, 2025, and is solely responsible for the information contained herein. Distributed via SEC EDGAR on August 07, 2025 at 11:16 UTC. If you believe the information included in the content is inaccurate or outdated and requires editing or removal, please contact us at [email protected]