• Data From CENTAUR Trial Published in Muscle & Nerve Demonstrates That Administration of AMX0035 Results in Longer Survival for People With ALS
• Early Administration of AMX0035 Reduced the Risk of Death by 44% Over the Duration of Follow-Up
• AMX0035 is the First ALS Therapeutic to Demonstrate Both a Statistically Significant Survival and Functional Benefit in ALS in a Randomized Controlled Trial
• Majority (77%) of Patients Were Receiving One or More Approved ALS Therapies at or Before Study Entry

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Amylyx Pharmaceuticals, Inc., a pharmaceutical company focused on developing new treatments for amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and other neurodegenerative diseases, today announced the publication of an overall survival analysis from the CENTAUR trial evaluating AMX0035 in people with ALS in the neuromuscular disease journal Muscle & Nerve.

The survival analysis followed each CENTAUR participant for up to three years from the start of the trial regardless of whether or not they continued long-term treatment in the open-label extension (OLE) part of CENTAUR. The analysis found that the group of participants who was randomized to AMX0035 at baseline had a 44% lower risk of death compared to the group who originally received placebo over the duration of follow-up (HR, 0.56; 95% CI, 0.34–0.92; P=0.023).

As previously reported in the New England Journal of Medicine, the CENTAUR study also met its primary efficacy end point of slowing ALS as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) versus placebo over a six-month period. AMX0035 was generally well tolerated with a manageable safety profile. These sister publications highlight that administration of AMX0035 resulted in both functional and survival benefits in people with ALS.

“We have many reasons to be encouraged today,” said Sabrina Paganoni, M. (Read more…)D., Ph.D., principal investigator of the CENTAUR trial, investigator at the Sean M. Healey & AMG Center for ALS at Mass General and Assistant Professor of PM&R at Harvard Medical School and Spaulding Rehabilitation Hospital. “In this trial, we have seen promising functional and survival benefits. To add, these results were seen on top of baseline use of approved ALS therapies. I am so excited about the potential of this drug for the people living with ALS.”

AMX0035 is an investigational neuroprotective therapy designed to reduce the death and dysfunction of motor neurons through targeting of mitochondrial and endoplasmic reticulum related cell death pathways. These pathways represent a different approach from currently approved drugs riluzole and edaravone. Most CENTAUR participants (77%) were receiving an approved ALS therapy (riluzole, edaravone, or both) during and/or before trial entry and were allowed to continue these medications during the OLE. Sensitivity analyses accounting for concomitant approved ALS therapies confirmed the published function and survival benefits of AMX0035 were independent of background medication use.

“These results support that AMX0035 has both functional and long-term survival benefits,” commented Dr. Merit Cudkowicz, Director of the Healey & AMG Center for ALS, Chief of Neurology at Mass General, Chief Medical Officer of ALS Finding a Cure®, and the Julieanne Dorn Professor of Neurology at Harvard Medical School. “ALS is a serious disease that progresses rapidly. With these results, we have shown that AMX0035 may provide patients hope and the chance to function better and live longer lives. On behalf of ALS Finding a Cure, our colleagues, and foundations that supported us, I want to thank all participants not only in this study, but also in all previous ALS studies, for their critical role in helping to reach wonderful milestones like this.”

Survival Results

Survival analyses compared time to death (all-cause mortality) between participants originally randomized to AMX0035 and those originally randomized to placebo, with the longest follow-up 35 months after randomization. There was a 44% risk reduction for death over the course of follow-up (HR, 0.56; 95% CI, 0.34–0.92; P=0.023). Survival benefit of AMX0035 was independent of baseline use of riluzole, and/or edaravone, or both together.

“We are thrilled about the long-term overall survival results for AMX0035 as well as the positive data from the landmark CENTAUR trial, which showed that AMX0035 demonstrated a clinically meaningful functional benefit and was generally well-tolerated,” said Josh Cohen, Co-CEO, Chairman and Co-Founder at Amylyx. “These results provide evidence to support the rapid advancement of AMX0035. We will continue to work collaboratively and expeditiously with global regulatory agencies to bring this potential treatment to people living with ALS in accordance with the applicable regulatory approval processes.”

Participants in CENTAUR were given the option after the trial to enroll in an OLE study to receive AMX0035. 92% of participants who completed CENTAUR elected to enroll in the extension study. Long-term functional and safety data from the CENTAUR and OLE studies are also being submitted to a peer reviewed journal and planned for publication in the near future. Interim data from the ongoing extension study will be presented in 2020.

CENTAUR was the recipient of two grants from ALS Finding a Cure®, including the ALS-ACT grant which was a joint partnership between ALS Finding a Cure and The ALS Association. ALS Finding a Cure is a program of The Leandro P. Rizzuto Foundation dedicated to the research and discovery of treatments for ALS.

“We want to thank all of the CENTAUR participants for their involvement in the study,” said Justin Klee, Co-CEO and Co-Founder of Amylyx. “The commitment of so many people with ALS to this research over the course of nearly three years, especially when weighing just how valuable time is for this patient community, has led us to this critical development milestone where we can now reimagine outcomes for ALS. We know there is nothing more valuable than time to these and other patients, so we hope to share updates on our progress with AMX0035 with the ALS community as soon as possible.”

About CENTAUR

CENTAUR was a 24-week, randomized, double-blind, placebo-controlled Phase 2/3 clinical trial that evaluated the safety and tolerability of AMX0035 and assessed the drug’s impact on disease progression as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) when compared to placebo. The trial also assessed the effects of AMX0035 on other measures that are critical to people with ALS, including muscle strength, lung vital capacity, and biomarkers of neuronal degeneration.

CENTAUR was the recipient of the ALS ACT grant, and is supported by The ALS Association, ALS Finding a Cure, a program of The Leandro P. Rizzuto Foundation, the Northeast ALS Consortium, Healey Center for ALS at Mass General, and was funded in part by the ALS Ice Bucket Challenge.

CENTAUR enrolled patients 18-80 years old with definite ALS and within 18 months of symptom onset. The trial did not restrict patients from receiving edaravone or riluzole. Participants who completed CENTAUR were given the option after the trial to enroll in an open-label extension study and receive AMX0035 for up to 30 months (132 weeks). 92% of eligible CENTAUR participants elected to enroll in the extension study. More information on the CENTAUR trial can be found at https://www.amylyx.com/science/ or www.clinicaltrials.gov, NCT03127514 or NCT03488524.

About Amyotrophic Lateral Sclerosis (ALS)

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. The vast majority of patients with ALS (>90%) have sporadic disease, showing no clear family history. Approximately 6000 people are diagnosed with ALS in the United States every year with an approximately similar number of deaths every year.

About AMX0035

AMX0035 is an investigational neuroprotective therapy designed to reduce neuronal death and dysfunction. AMX0035 targets endoplasmic reticulum and mitochondrial dependent neuronal degeneration pathways in ALS and other neurodegenerative diseases.

About Amylyx Pharmaceuticals

Amylyx Pharmaceuticals, Inc. is a pharmaceutical company working on developing a novel therapeutic for amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and other neurodegenerative diseases. For more information, visit www.amylyx.com and follow us on LinkedIn and Twitter.

About ALS Finding a Cure

ALS Finding a Cure® is a research organization dedicated to being a game changer in discovering a cure for this fatal disease. Founded in 2014 by noted philanthropist and Conair Founder and Chairman, Leandro (Lee) Rizzuto, as a tribute to Christie Rizzuto, Lee’s daughter-in-law who was diagnosed with ALS in 2009 at the age of 41, and under the joint leadership of Denis Rizzuto and Peter N. Foss, ALS Finding a Cure® is focused on identifying the gaps in the scientific understanding of ALS that are preventing the development of a cure. The organization, a program of The Leandro P. Rizzuto Foundation, collaborates with a wide range of companies, ALS organizations, other disease non-profits, and ALS patients and families to ensure research efforts are non-duplicative, synergistic, and focused on the ultimate goal: getting to a cure. For more information about ALS Finding a Cure®, visit www.alsfindingacure.org.

Contacts

Merissa Muller

Finn Partners

(617) 778-6633

[email protected]

• Data From CENTAUR Trial Published in Muscle & Nerve Demonstrates That Administration of AMX0035 Results in Longer Survival for People With ALS
• Early Administration of AMX0035 Reduced the Risk of Death by 44% Over the Duration of Follow-Up
• AMX0035 is the First ALS Therapeutic to Demonstrate Both a Statistically Significant Survival and Functional Benefit in ALS in a Randomized Controlled Trial
• Majority (77%) of Patients Were Receiving One or More Approved ALS Therapies at or Before Study Entry

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Amylyx Pharmaceuticals, Inc., a pharmaceutical company focused on developing new treatments for amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and other neurodegenerative diseases, today announced the publication of an overall survival analysis from the CENTAUR trial evaluating AMX0035 in people with ALS in the neuromuscular disease journal Muscle & Nerve.

The survival analysis followed each CENTAUR participant for up to three years from the start of the trial regardless of whether or not they continued long-term treatment in the open-label extension (OLE) part of CENTAUR. The analysis found that the group of participants who was randomized to AMX0035 at baseline had a 44% lower risk of death compared to the group who originally received placebo over the duration of follow-up (HR, 0.56; 95% CI, 0.34–0.92; P=0.023).

As previously reported in the New England Journal of Medicine, the CENTAUR study also met its primary efficacy end point of slowing ALS as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) versus placebo over a six-month period. AMX0035 was generally well tolerated with a manageable safety profile. These sister publications highlight that administration of AMX0035 resulted in both functional and survival benefits in people with ALS.

“We have many reasons to be encouraged today,” said Sabrina Paganoni, M. (Read more…)D., Ph.D., principal investigator of the CENTAUR trial, investigator at the Sean M. Healey & AMG Center for ALS at Mass General and Assistant Professor of PM&R at Harvard Medical School and Spaulding Rehabilitation Hospital. “In this trial, we have seen promising functional and survival benefits. To add, these results were seen on top of baseline use of approved ALS therapies. I am so excited about the potential of this drug for the people living with ALS.”

AMX0035 is an investigational neuroprotective therapy designed to reduce the death and dysfunction of motor neurons through targeting of mitochondrial and endoplasmic reticulum related cell death pathways. These pathways represent a different approach from currently approved drugs riluzole and edaravone. Most CENTAUR participants (77%) were receiving an approved ALS therapy (riluzole, edaravone, or both) during and/or before trial entry and were allowed to continue these medications during the OLE. Sensitivity analyses accounting for concomitant approved ALS therapies confirmed the published function and survival benefits of AMX0035 were independent of background medication use.

“These results support that AMX0035 has both functional and long-term survival benefits,” commented Dr. Merit Cudkowicz, Director of the Healey & AMG Center for ALS, Chief of Neurology at Mass General, Chief Medical Officer of ALS Finding a Cure®, and the Julieanne Dorn Professor of Neurology at Harvard Medical School. “ALS is a serious disease that progresses rapidly. With these results, we have shown that AMX0035 may provide patients hope and the chance to function better and live longer lives. On behalf of ALS Finding a Cure, our colleagues, and foundations that supported us, I want to thank all participants not only in this study, but also in all previous ALS studies, for their critical role in helping to reach wonderful milestones like this.”

Survival Results

Survival analyses compared time to death (all-cause mortality) between participants originally randomized to AMX0035 and those originally randomized to placebo, with the longest follow-up 35 months after randomization. There was a 44% risk reduction for death over the course of follow-up (HR, 0.56; 95% CI, 0.34–0.92; P=0.023). Survival benefit of AMX0035 was independent of baseline use of riluzole, and/or edaravone, or both together.

“We are thrilled about the long-term overall survival results for AMX0035 as well as the positive data from the landmark CENTAUR trial, which showed that AMX0035 demonstrated a clinically meaningful functional benefit and was generally well-tolerated,” said Josh Cohen, Co-CEO, Chairman and Co-Founder at Amylyx. “These results provide evidence to support the rapid advancement of AMX0035. We will continue to work collaboratively and expeditiously with global regulatory agencies to bring this potential treatment to people living with ALS in accordance with the applicable regulatory approval processes.”

Participants in CENTAUR were given the option after the trial to enroll in an OLE study to receive AMX0035. 92% of participants who completed CENTAUR elected to enroll in the extension study. Long-term functional and safety data from the CENTAUR and OLE studies are also being submitted to a peer reviewed journal and planned for publication in the near future. Interim data from the ongoing extension study will be presented in 2020.

CENTAUR was the recipient of two grants from ALS Finding a Cure®, including the ALS-ACT grant which was a joint partnership between ALS Finding a Cure and The ALS Association. ALS Finding a Cure is a program of The Leandro P. Rizzuto Foundation dedicated to the research and discovery of treatments for ALS.

“We want to thank all of the CENTAUR participants for their involvement in the study,” said Justin Klee, Co-CEO and Co-Founder of Amylyx. “The commitment of so many people with ALS to this research over the course of nearly three years, especially when weighing just how valuable time is for this patient community, has led us to this critical development milestone where we can now reimagine outcomes for ALS. We know there is nothing more valuable than time to these and other patients, so we hope to share updates on our progress with AMX0035 with the ALS community as soon as possible.”

About CENTAUR

CENTAUR was a 24-week, randomized, double-blind, placebo-controlled Phase 2/3 clinical trial that evaluated the safety and tolerability of AMX0035 and assessed the drug’s impact on disease progression as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) when compared to placebo. The trial also assessed the effects of AMX0035 on other measures that are critical to people with ALS, including muscle strength, lung vital capacity, and biomarkers of neuronal degeneration.

CENTAUR was the recipient of the ALS ACT grant, and is supported by The ALS Association, ALS Finding a Cure, a program of The Leandro P. Rizzuto Foundation, the Northeast ALS Consortium, Healey Center for ALS at Mass General, and was funded in part by the ALS Ice Bucket Challenge.

CENTAUR enrolled patients 18-80 years old with definite ALS and within 18 months of symptom onset. The trial did not restrict patients from receiving edaravone or riluzole. Participants who completed CENTAUR were given the option after the trial to enroll in an open-label extension study and receive AMX0035 for up to 30 months (132 weeks). 92% of eligible CENTAUR participants elected to enroll in the extension study. More information on the CENTAUR trial can be found at https://www.amylyx.com/science/ or www.clinicaltrials.gov, NCT03127514 or NCT03488524.

About Amyotrophic Lateral Sclerosis (ALS)

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. The vast majority of patients with ALS (>90%) have sporadic disease, showing no clear family history. Approximately 6000 people are diagnosed with ALS in the United States every year with an approximately similar number of deaths every year.

About AMX0035

AMX0035 is an investigational neuroprotective therapy designed to reduce neuronal death and dysfunction. AMX0035 targets endoplasmic reticulum and mitochondrial dependent neuronal degeneration pathways in ALS and other neurodegenerative diseases.

About Amylyx Pharmaceuticals

Amylyx Pharmaceuticals, Inc. is a pharmaceutical company working on developing a novel therapeutic for amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and other neurodegenerative diseases. For more information, visit www.amylyx.com and follow us on LinkedIn and Twitter.

About ALS Finding a Cure

ALS Finding a Cure® is a research organization dedicated to being a game changer in discovering a cure for this fatal disease. Founded in 2014 by noted philanthropist and Conair Founder and Chairman, Leandro (Lee) Rizzuto, as a tribute to Christie Rizzuto, Lee’s daughter-in-law who was diagnosed with ALS in 2009 at the age of 41, and under the joint leadership of Denis Rizzuto and Peter N. Foss, ALS Finding a Cure® is focused on identifying the gaps in the scientific understanding of ALS that are preventing the development of a cure. The organization, a program of The Leandro P. Rizzuto Foundation, collaborates with a wide range of companies, ALS organizations, other disease non-profits, and ALS patients and families to ensure research efforts are non-duplicative, synergistic, and focused on the ultimate goal: getting to a cure. For more information about ALS Finding a Cure®, visit www.alsfindingacure.org.

Contacts

Merissa Muller

Finn Partners

(617) 778-6633

[email protected]