InFlectis BioScience Announces Promising Results for IFB-088 in a Phase 2a Clinical Study in Bulbar-Onset ALS Patients

Biomarker Evidence Highlights IFB-088 Impact on Integrated Stress Response and Oxidative Pathways

Key Takeaways

Promising results reported for IFB-088 in a Phase 2a clinical study in bulbar-onset ALS Patients.
Biomarker evidence highlights IFB-088 impact on integrated stress response and oxidative pathways.
These findings confirm the hypotheses raised from preclinical studies and strongly support the premise of moving IFB-088 to pivotal study.

Nantes, France – February 6^th, 2025 – InFlectis BioScience SAS, a drug discovery company pioneering development of therapeutics harnessing the Integrated Stress Response (ISR) for a spectrum of neurological diseases, today announced the successful completion of its P288ALS TRIAL study (NCT05508074). This study was designed as a randomized, double-blind, placebo-controlled, parallel-group phase 2a trial comparing its drug candidate IFB-088 (25 mg BID) plus riluzole with placebo plus riluzole, in patients afflicted with bulbar-onset ALS, a particularly severe ALS subtype.

The primary objective was the assessment of safety of IFB-088. The sample size was powered to demonstrate safety with a total of 51 bulbar-onset ALS patients randomized (2:1, treatment:placebo with standard of care), among whom 41 have data available at 6 months. Secondary endpoints included a range of validated efficacy parameters and biomarkers.

Overall, IFB-088 was found to be safe and well-tolerated with non-meaningful observations, meeting the primary objective of the study and confirming the findings of the Phase 1 study in healthy volunteers.

The study also showed promising results for IFB-088 on efficacy parameters although the sample size was not powered to demonstrate efficacy. A trend in favor of a lower functional decline measured with ALSFRS score in IFB-088-treated patients was shown in the Intent-to-Treat population (51 patients). In the per protocol population (40 patients), this difference in functional decline measured with ALSFRS score between the placebo and IFB-088-treated patients was statistically significant with a decline of -0.95 pts ALSFRS/month in IFB-088 treated group versus a -1.42 pts ALSFRS/month in the placebo group over the six months; this difference is also clinically meaningful. The evolution of clinical scores on the ALS-MiToS and King’s College scales, and of respiratory function decline assessed by measurement of slow vital capacity (SVC) in the per protocol population, confirm this trend in favor of IFB-088. Overall, these clinical results confirm previous findings of the ProMISe Phase 2 study with IFB-088 parent drug, guanabenz, in ALS patients, carried out by IRCCS “Carlo Besta” Neurological Institute in Milan, Italy.

The clinical trial also confirmed that both the integrated stress response (ISR) and oxidative stress pathways were engaged in bulbar ALS patients upon IFB-088 treatment. Biomarker measurements demonstrated IFB-088’s activity on these metabolic pathways. Biomarker assessments also substantiated the efficacy of IFB-088 on critical ALS pathological pathways including TDP-43 mis-localization, oxidative stress, neurodegeneration and inflammation. These results validate preclinical findings and support the underlying medical hypotheses.

“These findings confirm the hypotheses raised from preclinical studies and strongly support the premise of moving IFB-088 to pivotal study,” said Dr. Anne Visbecq, InFlectis Chief Medical Officer.

“The positive results, supported by both clinical outcomes and biomarker validation, while confirming our previous work, strengthen the therapeutic potential of targeting the integrated stress response (ISR) and oxidative stress pathways in bulbar onset ALS. These findings provide a strong foundation for further clinical development and bring us one step closer to delivering an innovative and effective treatment to patients,” said Prof. Giuseppe Lauria, Principal Investigator, Professor of Neurology at University of Milan, Scientific Director at IRCCS “Carlo Besta” Neurological Institute.

Pierre Miniou, Chief Executive Officer of InFlectis, declared: “We are very encouraged by the results we observed with IFB-088 and appreciate the financial support of ALS Association and AFM-Téléthon. These compelling findings position IFB-088 for forthcoming pivotal studies and pave the way for new treatment possibilities for ALS. InFlectis BioScience is now seeking global partners to complete the development and registration of IFB-088 in ALS and leverage the company’s assets in a broader pipeline of neurological indications with unmet medical needs, such as Charcot-Marie-Tooth Disease."

About IFB-088 (icerguastat)

InFlectis is developing IFB-088 (also named sephin1), a first-in-class, multi-functional, brain-penetrant, orally administered small molecule that selectively inhibits the dephosphorylation of eIF2α. By doing so, IFB-088 amplifies the integrated stress response (ISR), acting as a formidable shield against various cellular stresses, including endoplasmic reticulum (ER) stress which is a hallmark of neurodegeneration. IFB-088 also selectively antagonizes NMDA receptors containing the NR2B subunit, which are involved in glutamate excitotoxicity that triggers calcium influx, mitochondrial dysfunction, and ROS production, and ultimately contributes to neurodegeneration. IFB-088 also reduces mitochondrial ROS production in an NMDAR-independent manner. Hence, IFB-088 normalizes dysregulated calcium homeostasis and oxidative stress to provide neuroprotection in different diseases context. This approach holds promise for designing disease-modifying therapeutics to fight intractable diseases such as ALS.

About Bulbar-Onset ALS

ALS is increasingly being recognized as a heterogeneous disease. To optimize assessment in a small study, InFlectis has focused IFB-088 development to date on bulbar-onset ALS patients, who account for ~30% of all ALS patients and represent a more homogeneous patient population. Bulbar ALS is a distinct phenotype identified with specific clinical parameters; disease onset primarily affects the brainstem, impacting muscles responsible for speech, swallowing, and limb functions. Patients experience slurred speech (dysarthria) and difficulty swallowing (dysphagia) early in the disease progression. Bulbar-onset ALS usually exhibits a rapid evolution and poor prognosis (~26 months from symptom onset to death). Treatment options remain a high unmet medical need for this patient group.

About the ALS ASSOCIATION

The ALS Association is the largest philanthropic funder of ALS research in the world. The Association funds global research collaborations, assists people with ALS and their families through its nationwide network of care and certified clinical care centers, and advocates for better public policies for people with ALS. The ALS Association is working to make ALS a livable disease while urgently searching for new treatments and a cure. For more information about the ALS Association, visit our website at als.org.

About AFM-Téléthon

The French Muscular Dystrophy Association (AFM) - AFM-Telethon - is a major player in biomedical research for rare diseases in France and worldwide. It currently funds about 350 research programs and 40 clinical trials in different genetic diseases affecting the eye, blood, brain, immune system, motor neurons and muscles... The AFM-Telethon has also created three research and development institutes dedicated to gene therapy, stem cells and myology. To learn more visit www.afm-telethon.fr/en

Key Takeaways

Promising results reported for IFB-088 in a Phase 2a clinical study in bulbar-onset ALS Patients.
Biomarker evidence highlights IFB-088 impact on integrated stress response and oxidative pathways.
These findings confirm the hypotheses raised from preclinical studies and strongly support the premise of moving IFB-088 to pivotal study.

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Media Gallery

Quotes

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These findings confirm the hypotheses raised from preclinical studies and strongly support the premise of moving IFB-088 to pivotal study.

Anne VISBECQ, MD — Chief Medical Officer

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These compelling findings position IFB-088 for forthcoming pivotal studies and pave the way for new treatment possibilities for ALS.

Pierre MINIOU, PhD, MBA — Co-Founder, President & CEO 

“

The positive results, supported by both clinical outcomes and biomarker validation, while confirming our previous work, strengthen the therapeutic ...

Prof. Giuseppe Lauria, M.D. — Scientific Director of the IRCCS Foundation "Carlo Besta" Neurological Institute

“

New treatments are urgently needed to make ALS a livable disease, so we are thrilled to see IFB-088 hit its primary endpoint of safety and tolerabi...

Kuldip Dave, Ph.D. — Senior Vice President for Research at the Association

Related Bios

Pierre MINIOU, PhD, MBA

Co-Founder, President & CEO

Dr Pierre Miniou has over 20 years of international experience in business development and licensing in the biopharmaceutical industry with the signing of many partnering and license agreements. He has experience of senior management having been the head of the patent department of Pierre Fabre Laboratories, a member of the Executive Committee of Vivalis (now Valneva) and Director of Vivalis Toyama (Japan).

Pierre holds a Master’s degree and Engineering degree in Biotechnology from the School of Biotechnology of Strasbourg and a PhD in Molecular and Cellular Biology from the Louis Pasteur University of Strasbourg. He is also graduated from the CEIPI (Centre for International Studies of Industrial Property) in Strasbourg and holds a MBA (Audencia, Nantes).

He worked as a researcher at Transgene (Strasbourg), the Wistar Institute (Philadelphia, PA), the Necker Hospital (Paris) and the IGBMC (Strasbourg). He then left the laboratory activities to join the law firm Cabinet Regimbeau (Paris) prior to join Pierre Fabre Laboratories and in 2003 he moves to Vivalis (today Valneva) as Director of Business Development and Director of Intellectual Property. In 2013, he co-founded InFlectis BioScience with Philippe Guedat.

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Anne VISBECQ, MD

Chief Medical Officer

Anne Visbecq is a Medical Doctor with over 20 years of experience in the pharmaceutical industry. She obtained her medical degree with thesis award (University of Nantes), and then completed her training with university degrees in clinical research and oncopharmacology. She also has Master’s degrees in pharmacology, biostatistics and health management.

Anne joined the pharmaceutical industry in 1997 and worked as medical advisor in infectious diseases and endocrinology. She then became the head of medical group in an international company (Pharmacia & Upjohn), managing 6 therapeutic areas. She also gained marketing and communication experience to broader her knowledge and better understand the global functioning of pharmaceutical industry and the interactions between departments (Pfizer). Her last position was medical director at Keocyt a company specialized in oncology and neurology. She had to deal with clinical trials, relationships with opinion leaders, business development and procedures of Marketing Authorization. In her professional pathway, she has been employed in very small companies as well as big pharma.

Meanwhile, she has been consultant in medical affairs for years. Thanks to this extensive and diversified experience, her expertise ranges from drug development to launch.

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Prof. Giuseppe Lauria, M.D.

Scientific Director of the IRCCS Foundation "Carlo Besta" Neurological Institute

Giuseppe Lauria is Professor of Neurology at the University of Milan and Director of the Department of Clinical Neurosciences at the IRCCS “Carlo Besta” Neurological Institute of Milan, Italy. He received the degree in Medicine at the University of Padova and trained as resident in Neurology at the University of Ferrara and has been fellow at the Department of Neuroscience of the Johns Hopkins University, USA. He leads the Motor Neuron/ALS Centre at the IRCCS "Carlo Besta" Neurological Institute whose research activities include clinical, preclinical, and molecular biology projects. He has pioneered the use of skin biopsy in painful neuropathies and neurodegenerative disorders, and contributed to the discovery of new gene mutations and phenotypes. He received grants from several national and international funding agencies. Prof. Lauria is currently Editor-in-Chief of the Journal of the Peripheral Nervous System.

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Contacts

Pierre Miniou

pierreminiou@inflectisbioscience.com

Co-Founder, President and CEO