Amylyx (NASDAQ: AMLX) halts AMX0035 PSP program after Phase 2b shows no benefit

Rhea-AI Filing Summary

Amylyx Pharmaceuticals reported a key setback in its neurology pipeline. The company is discontinuing the ORION program of AMX0035 (sodium phenylbutyrate and taurursodiol) in adults living with progressive supranuclear palsy after the treatment did not show differences compared to placebo on primary or secondary outcomes at Week 24.

As a result, Amylyx will stop the ongoing Phase 2b trial and its open-label extension and will not start the planned Phase 3 portion of the program. The company noted that safety data in this study were consistent with safety data from prior AMX0035 studies, indicating no new safety concerns despite the lack of efficacy in this indication.

Positive

• None.

Negative

• AMX0035 fails to outperform placebo in PSP, leading Amylyx to discontinue the ORION Phase 2b trial, stop the open-label extension, and cancel the planned Phase 3 portion for this indication.

Insights

Biotech clinical-stage analyst

Amylyx halts AMX0035 PSP program after lack of efficacy, removing a development opportunity while confirming a stable safety profile.

The company states that AMX0035 did not show differences versus placebo on primary or secondary outcomes at Week 24 in adults with progressive supranuclear palsy. That outcome leads Amylyx to discontinue the Phase 2b trial, close the open-label extension, and forego the planned Phase 3 segment of the ORION program, effectively ending development of AMX0035 in this specific indication.

Clinically, this removes a potential new use for AMX0035, narrowing the asset’s development footprint. At the same time, safety data were described as consistent with prior AMX0035 studies, which supports the existing understanding of the drug’s tolerability profile. The financial and strategic impact will depend on how resources previously allocated to ORION are redeployed across other programs in future disclosures.

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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): August 27, 2025

AMYLYX PHARMACEUTICALS, INC.

(Exact name of Registrant as Specified in Its Charter)

Delaware		001-41199		46-4600503
(State or Other Jurisdiction of Incorporation)		(Commission File Number)		(IRS Employer Identification No.)

43 Thorndike St.,
Cambridge, MA		02141
(Address of Principal Executive Offices)		(Zip Code)

Registrant’s Telephone Number, Including Area Code: (617) 682-0917

Not Applicable

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class		Trading Symbol(s)		Name of each exchange on which registered
Common Stock, $0.0001 par value per share		AMLX		Nasdaq Global Select Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Item 8.01 Other Events

On August 27, 2025, Amylyx Pharmaceuticals, Inc. (the “Company”) announced it is discontinuing the ORION program of AMX0035 (sodium phenylbutyrate [PB] and taurursodiol [TURSO, also known as ursodoxicoltaurine]) in adults living with progressive supranuclear palsy.

AMX0035 did not show differences compared to placebo on primary or secondary outcomes at Week 24. Based on these results, the Company will discontinue the Phase 2b trial and open-label extension and will not initiate the Phase 3 portion of the program. Safety data were consistent with safety data from prior studies of AMX0035.

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

				AMYLYX PHARMACEUTICALS, INC.
Date: August 27, 2025				By:		/s/ James M. Frates
						James M. Frates
						Chief Financial Officer

FAQ

What did Amylyx Pharmaceuticals (AMLX) announce about the ORION program?

Amylyx Pharmaceuticals announced it is discontinuing the ORION program of AMX0035 in adults living with progressive supranuclear palsy after the drug did not show differences compared to placebo on primary or secondary outcomes at Week 24.

What happens to the AMX0035 Phase 2b trial in progressive supranuclear palsy?

The company will discontinue the Phase 2b trial of AMX0035 in progressive supranuclear palsy and will also stop the associated open-label extension.

Will Amylyx Pharmaceuticals run a Phase 3 trial of AMX0035 in progressive supranuclear palsy?

No. Based on the ORION Phase 2b results, Amylyx Pharmaceuticals will not initiate the Phase 3 portion of the AMX0035 program in progressive supranuclear palsy.

How did AMX0035 perform versus placebo in the ORION study?

AMX0035 did not show differences compared to placebo on primary or secondary outcomes at Week 24 in adults with progressive supranuclear palsy.

Were there any new safety concerns for AMX0035 in the ORION program?

Safety data from the ORION program were described as consistent with safety data from prior studies of AMX0035, indicating no new safety findings in this trial.

What indication was being studied in the ORION program for Amylyx’s AMX0035?

The ORION program was evaluating AMX0035 in adults living with progressive supranuclear palsy, a neurodegenerative movement disorder.