A Phase 1, Randomized, Open-Label, Single-Dose, 6-Period Crossover Study to Evaluate the Pharmacokinetics of BIIB091 Formulations and the Effect of Food in Healthy Participants

In this study, researchers will learn how the body processes new tablet forms of BIIB091 when taken with and without food. One new form of BIIB091 is an "extended release" tablet, also known as "ER." This form helps release BIIB091 slowly and consistently, helping to keep steady drug levels in the body for longer. The other new form is a "gastro-retentive" tablet, also known as "GR." This form has a special coating that swells and allows BIIB091 to stay in the stomach longer. For both GR and ER tablets, there are also "slow" and "fast" forms that change how quickly BIIB091 is released into the body. But, eating food with these tablets may affect how much BIIB091 is in the body.
The main objective of this study is to learn how 2 new forms of BIIB091, which are released into the body at different rates, are processed in the body. Researchers also want to learn how these new forms compare to the "immediate release" tablet, also known as "IR". This form delivers BIIB091 immediately into the body.
The main question researchers want to answer in this study is:
* How does the body process different tablet forms of BIIB091 with or without food?
Researchers will also learn more about:
* How the body processes the 2 new tablet forms of BIIB091 with food compared to the IR tablet form with food
* How the body processes the ER tablet form of BIIB091 with food compared to without food
* Any medical problems the participants have during the study
* Any changes in the participants' overall health during the study
This study will be done as follows:
* Participants will be screened to check if they can join the study. The screening period will be up to 22 days, after which eligible participants will check into their study research center.
* Participants will be randomly assigned to 1 of 6 groups. In each group, the participants will take the below tablet forms, but in different orders:
* Immediate-Release (IR)
* Gastro-Retentive slow (GR-slow)
* Gastro-Retentive fast (GR-fast)
* Extended-Release slow (ER-slow)
* Extended-Release fast (ER-fast)
* ER-slow, without food
* Each period includes the participant taking a single dose of what they were assigned to on the first day. There will be 3 days of no dosing in each period. The participant will then move to the next tablet form assigned. This will continue until each participant has taken a single dose of each of the 6 tablet forms.
* Participants will remain at their study research center for 25 days for the treatment periods. Afterwards, there will be follow-up visit 11 to 14 days after each participant's last dose. Each participant will be in the study for up to 57 days.

Start Date16 Oct 2024

Sponsor / Collaborator

Biogen, Inc.

NCT06574828

/ CompletedPhase 1

A Randomized, Double-Blind, Placebo- and Positive-Controlled (Moxifloxacin), Parallel Study With a Nested Crossover to Assess the Effect of Multiple Oral Therapeutic and Supratherapeutic Doses of BIIB091 on Cardiac Repolarization in Healthy Participants

In this study, researchers will learn how the heart reacts to multiple doses of BIIB091 in healthy participants. In previous studies looking at BIIB091, researchers have found that a certain range of doses can cause changes in the electrical activity of the heart. In this study, researchers want to learn more about that activity after participants take BIIB091 at lower and higher doses for 5 days. The main objective of this study is to learn how the heart's electrical activity changes after taking BIIB091. To measure this, researchers will look at something called the QT interval corrected for heartbeat, also known as "QTc". This represents the time it takes for the heart to contract and relax. A QT interval that is too long means that the heart's electrical system is taking longer than normal to recharge between heartbeats. This could increase the risk of abnormal heartbeats that may lead to sudden death.
The main questions researchers want to answer are:
• What is the change in the participants' QTc after taking BIIB091?
Researchers will also learn more about:
* Any changes in other measures of the heart's electrical activity
* How the body processes BIIB091, as well as something called "M23", which is made in the body when BIIB091 is broken down
* Any medical problems the participants have during the study
* Any changes in the participants' overall health during the study
This study will be done as follows:
* Participants will be screened to check if they can join the study. The screening period will be up to 29 days, after which participants will check into their study research center.
* Participants will be randomly assigned to be in 1 of 2 groups:
* Group 1: Participants will take a low dose of BIIB091 for 5 days followed by a high dose of BIIB091 for 5 days.
* Group 2: Participants will take a single dose of moxifloxacin. Moxifloxacin is an antibiotic used to treat bacterial infections. Researchers are using it in this study to compare to BIIB091, because it is known to cause abnormal changes to the heart's electrical activity.
* Participants in both Group 1 and Group 2 will also take a placebo while at the study research center. A placebo looks like the study drug or moxifloxacin, but does not have any real medicine in it.
* Participants will remain at their study research center for 15 days. Afterwards, there will be a follow-up visit 11 to 14 days after each participant's last dose. Each participant will be in the study for up to 57 days.

Start Date29 Aug 2024

Sponsor / Collaborator

Biogen, Inc.

NCT06311786

/ CompletedPhase 1

A Phase 1, Open-Label Study to Investigate the Absorption, Distribution, Metabolism, and Excretion of Single Oral Dose [14C]-BIIB091 in Healthy Male Participants

The main goal of this study is to learn how [14C]-BIIB091 moves through and is processed by the body and to look at how much of BIIB091's metabolites (what is produced when BIIB091 is broken down by the body) appears in the blood, urine, and stool in healthy male participants. The study will also help researchers learn more about the safety of BIIB091 in healthy male participants.

Start Date08 Apr 2024

Sponsor / Collaborator

Biogen, Inc.

100 Clinical Results associated with BIIB-091

100 Translational Medicine associated with BIIB-091

100 Patents (Medical) associated with BIIB-091

Literatures (Medical) associated with BIIB-091

01 Oct 2022·CNS drugs

Bruton’s Tyrosine Kinase Inhibitors in Multiple Sclerosis: Pioneering the Path Towards Treatment of Progression?

Review

Author: Geladaris, Anastasia ; Torke, Sebastian ; Weber, Martin S

In multiple sclerosis (MS) persisting disability can derive from acute relapses or, alternatively, from slow and steady deterioration, termed chronic progression. Emerging data suggest that the latter process occurs largely independent from relapse activity or development of new central nervous system (CNS) inflammatory lesions. Pathophysiologically, acute relapses develop as a consequence of de novo CNS infiltration of immune cells, while MS progression appears to be driven by a CNS-trapped inflammatory circuit between CNS-established hematopoietic cells as well as CNS-resident cells, such as microglia, astrocytes, and oligodendrocytes. Within the last decades, powerful therapies have been developed to control relapse activity in MS. All of these agents were primarily designed to systemically target the peripheral immune system and/or to prevent CNS infiltration of immune cells. Based on the above described dichotomy of MS pathophysiology, it is understandable that these agents only exert minor effects on progression and that novel targets within the CNS have to be utilized to control MS progression independent of relapse activity. In this regard, one promising strategy may be the inhibition of the enzyme Bruton's tyrosine kinase (BTK), which is centrally involved in the activation of B cells as well as myeloid cells, such as macrophages and microglia. In this review, we discuss where and to what extent BTK is involved in the immunological and molecular cascades driving MS progression. We furthermore summarize all mechanistic, preclinical, and clinical data on the various BTK inhibitors (evobrutinib, tolebrutinib, fenebrutinib, remibrutinib, orelabrutinib, BIIB091) that are currently in development for treatment of MS, with a particular focus on the potential ability of either drug to control MS progression.

27 Jan 2022·Journal of medicinal chemistryQ1 · MEDICINE

Discovery and Preclinical Characterization of BIIB091, a Reversible, Selective BTK Inhibitor for the Treatment of Multiple Sclerosis

Q1 · MEDICINE

Article

Author: Bajrami, Bekim ; Otipoby, Kevin L. ; Poreci, Urjana ; Ma, Bin ; Kapadnis, Sudarshan ; Tien, Eric ; Hoemberger, Marc ; Black, Cheryl ; Murugan, Paramasivam ; Hopkins, Brian T. ; Polack, Evelyne ; King, Kris ; Bame, Eris ; Delva, Luisette ; Rowbottom, Chris ; Donaldson, Douglas ; Burdette, Doug ; Mingueneau, Michael ; Metrick, Claire M. ; Prince, Robin ; Santoro, Joseph C. ; Grater, Richard ; Schroeder, Patricia ; Tang, Hao ; Johnson, Josh ; Magee, Tom ; Roach, Allie M. ; Lulla, Mukesh ; Lyssikatos, Joseph ; Bohnert, Tonika ; Meissner, Robert ; Gu, Chungang ; Marx, Isaac ; Boiselle, Carrie ; Burns, Jeremy C. ; Zhang, Fengmei

Multiple Sclerosis is a chronic autoimmune neurodegenerative disorder of the central nervous system (CNS) that is characterized by inflammation, demyelination, and axonal injury leading to permeant disability. In the early stage of MS, inflammation is the primary driver of the disease progression. There remains an unmet need to develop high efficacy therapies with superior safety profiles to prevent the inflammation processes leading to disability. Herein, we describe the discovery of BIIB091, a structurally distinct orthosteric ATP competitive, reversible inhibitor that binds the BTK protein in a DFG-in confirmation designed to sequester Tyr-551, an important phosphorylation site on BTK, into an inactive conformation with excellent affinity. Preclinical studies demonstrated BIB091 to be a high potency molecule with good drug-like properties and a safety/tolerability profile suitable for clinical development as a highly selective, reversible BTKi for treating autoimmune diseases such as MS.

01 Jan 2021·Clinical & translational immunologyQ3 · MEDICINE

Next‐generation Bruton's tyrosine kinase inhibitor BIIB091 selectively and potently inhibits B cell and Fc receptor signaling and downstream functions in B cells and myeloid cells

Q3 · MEDICINE

ArticleOA

Author: Davide Gianni ; Michael Mingueneau ; Klaus Michelsen ; Nathalie Franchimont ; Eris Bame ; Devangi Mehta ; Mike Palte ; Brian T Hopkins ; Joseph Santoro ; Alex Coppell ; Jeremy C Burns ; Hao Tang ; Isaac Marx ; Stephen Rubino ; Thomas M Carlile ; Douglas Donaldson ; Xiaomei Peng ; Matthew Scaramozza ; Katherine Riester ; Patrick Cullen ; Dipen Sangurdekar ; Shibeshih Belachew ; Bin Ma ; Jing Zhu ; Baohong Zhang ; Alex Pellerin ; Allie M Roach ; Fergal Casey ; Patrick Trapa ; Robin Prince ; Bekim Bajrami ; Million Arefayene ; Urjana Poreci ; Param Muragan

Abstract:

Objectives:

Bruton's tyrosine kinase (BTK) plays a non‐redundant signaling role downstream of the B‐cell receptor (BCR) in B cells and the receptors for the Fc region of immunoglobulins (FcR) in myeloid cells. Here, we characterise BIIB091, a novel, potent, selective and reversible small‐molecule inhibitor of BTK.

Methods:

BIIB091 was evaluated in vitro and in vivo in preclinical models and in phase 1 clinical trial.

Results:

In vitro, BIIB091 potently inhibited BTK‐dependent proximal signaling and distal functional responses in both B cells and myeloid cells with IC50s ranging from 3 to 106 nm, including antigen presentation to T cells, a key mechanism of action thought to be underlying the efficacy of B cell‐targeted therapeutics in multiple sclerosis. BIIB091 effectively sequestered tyrosine 551 in the kinase pocket by forming long‐lived complexes with BTK with t1/2 of more than 40 min, thereby preventing its phosphorylation by upstream kinases. As a key differentiating feature of BIIB091, this property explains the very potent whole blood IC50s of 87 and 106 nm observed with stimulated B cells and myeloid cells, respectively. In vivo, BIIB091 blocked B‐cell activation, antibody production and germinal center differentiation. In phase 1 healthy volunteer trial, BIIB091 inhibited naïve and unswitched memory B‐cell activation, with an in vivo IC50 of 55 nm and without significant impact on lymphoid or myeloid cell survival after 14 days of dosing.

Conclusion:

Pharmacodynamic results obtained in preclinical and early clinical settings support the advancement of BIIB091 in phase 2 clinical trials.

News (Medical) associated with BIIB-091

20 Feb 2026

·firstwordpharma.com

Biopharma bites: Blockbuster hopes for Brinsupri, Biogen stops MS study, plus mRNA patent fight heats up

Insmed guides for $1B in Brinsupri salesBiogen bins mid-stage MS studyModerna's mNEXSPIKE faces patent suitInsmed guides for $1B in Brinsupri salesHaving been approved in the US last August, and subsequently authorised in the EU, as the first treatment for non-cystic fibrosis bronchiectasis (NCFB), Insmed now expects Brinsupri (brensocatib) to generate revenue of at least $1 billion in 2026. "Our US commercial launch…continues to exceed our expectations," said CEO Will Lewis.The oral, once-daily DPP1 inhibitor — designed to block the activation of neutrophil serine proteases in neutrophils that are responsible for the underlying inflammation in NCFB — generated sales of $144.6 million in the fourth quarter of 2025 and $172.7 million for the full year.Insmed expects regulatory decisions for Brinsupri for the treatment of NCFB in the UK and Japan in 2026. However, the company cautioned that it "continues to evaluate the potential effect of evolving US policies," which could impact the timing of potential international commercial launches.-Matthew DennisBiogen bins mid-stage MS study Biogen this week terminated the Phase II FUSION study evaluating BIIB091 in patients with relapsing multiple sclerosis (MS), according to an update on ClinicalTrials.gov. The candidate, a reversible, non-covalent BTK inhibitor, was being studied alone or in combination with diroximel fumarate; the trial had enrolled 127 patients. The study discontinuation comes as at least one BTK inhibitor seems to have found its footing in MS. While the drug class has shown tantalising promise in treating the disease, none have yet reached the finish line — though Roche's fenebrutinib may be nearing approval (see – Physician Views Results: Neurologists share cautious optimism for Roche's fenebrutinib in PPMS).However, Sanofi was recently hit with a controversial FDA rejection for its BTK inhibitor, tolebrutinib, to treat non-relapsing secondary progressive MS. For more on how BTK inhibitors may shake up the MS treatment landscape, see KOL Views Q&A: What Sanofi’s PERSEUS, Roche’s FENtrepid divergence says about BTK inhibitors in MS.-Elizabeth EatonModerna's mNEXSPIKE faces patent suit BioNTech has filed a patent infringement lawsuit alleging that Moderna's next-generation COVID-19 vaccine unlawfully infringes on a patent related to the German company's own mRNA shot, Comirnaty. The complaint, filed Thursday in US District Court for the District of Delaware, claims Moderna's mNEXSPIKE infringes US Patent No. 12,133,899, which covers a streamlined mRNA vaccine design that allows for lower dosing. The case intensifies a long-running legal battle between the companies behind two of the world's most successful COVID-19 vaccines. BioNTech developed Comirnaty with Pfizer, while Moderna brought its own shot, Spikevax, to market in late 2020. In 2022, Moderna sued BioNTech and Pfizer, claiming they "unlawfully copied" its mRNA inventions to make Comirnaty; that case remains ongoing. Moderna recently highlighted mNEXSPIKE, which was approved by the FDA in 2025, as a significant growth driver with expected approvals this year in Europe and Japan. According to BioNTech's complaint, mNEXSPIKE accounted for 55% of COVID-19 vaccines sold by Moderna in the 2025-2026 respiratory virus season. A spokesperson for Moderna said Thursday it would defend itself against the new allegations.-Anna Bratulic

Drug ApprovalPhase 2VaccinemRNAPatent Infringement

19 Feb 2026

·www.fiercebiotech.com

Novartis winds down ph. 1 solid tumor program after lacking efficacy

Novartis had previously shared data from the phase 1 study of QEQ278 showing that none of the patients achieved an objective response.\n Novartis has jettisoned an anti-cancer protein from its pipeline after the molecule failed to shrink tumors in 30 patients with advanced disease.The pharma giant halted the phase 1 trial of QEQ278 and has dropped the candidate entirely, a spokesperson confirmed with Fierce Biotech. Novartis had previously shared early data from the trial showing that none of the patients treated with the protein achieved an objective response, with 26 of them halting treatment partway through the trial because their cancer got worse. Patients included in the trial had advanced malignancies and exhausted standard of care treatments.“Following review in 2024, Novartis made the decision to discontinue development of QEQ278 in the phase 1 study,” the spokesperson told Fierce. “This decision was not based on any safety concern and the asset was removed from the Novartis pipeline.”Despite the discontinuation occurring years ago, the trial’s status was only just updated “per protocol” after “the remaining participant recently discontinued study treatment,” the spokesperson added.News of the terminated trial was first reported by ApexOnco. QEQ278 was designed to target a group of proteins that bind to the natural killer group 2D receptor (NKG2D) on the surface of natural killer (NK) cells. Many tumor cells are littered with ligands that bind to NKG2D, which normally, the natural killer cells, could use to identify the cancer and destroy it. As a decoy, these cancers tend to shed some of the ligands into the bloodstream, which distracts the immune cells and allows the tumor to evade detection.With QEQ278, Novartis hoped to both nullify the decoy ligands floating in the body and also attach to the surface of tumor cells and flag them for destruction.Other companies have also tried to target NKG2D ligands, with limited success. For example, Nkarta engineered NK cells to express a boosted NKG2D receptor and saw some early wins in blood cancer, but ultimately dropped the candidate in March 2024 after the response rate plummeted when more patients were treated.Astellas similarly canned an early CAR-T lymphoma candidate using NKG2D in January 2025, which a company spokesperson told Fierce at the time was a “difficult decision” driven by “prioritization efforts.”Novartis’ decision coincides with Biogen discontinuing a combination arm of a phase 2 trial for multiple sclerosis candidate BIIB091. While Biogen is no longer testing the asset in combination with Vumerity (diroximel fumarate) as a “strategic decision,” monotherapy data for BIIB091 is still expected in the second quarter of 2026, a spokesperson told Fierce.

Phase 1PROTACsPhase 2Clinical Trial Termination

19 Feb 2026

·endpoints.news

Biogen stops part of an MS trial; Merck reports more Enflonsia data

Plus, news about Compass Pathways, Starget Pharma and Ten63 Therapeutics: 🛑 Biogen halts combo portion of MS trial: The biotech is not moving forward with the second part of the Phase 2 trial that was testing a BTK inhibitor, named BIIB091, in combination with its oral multiple sclerosis medicine known as Vumerity, a spokesperson confirmed to Endpoints News . It still expects monotherapy data from the first part of the trial in the second quarter. Multiple sclerosis has long been a major part of Biogen’s commercial portfolio: MS product revenues were $4.03 billion in 2025, about a 7% decline over the prior year, according to a full-year earnings report earlier this month. That accounted for 40% of total 2025 revenues. — Kyle LaHucik 📊 Merck heads to regulators in search of expanded RSV monoclonal antibody label: The New Jersey pharma reported findings from the SMART study of Enflonsia for children under 2 years old who remained at increased risk for severe disease through their second RSV season, nearly all of whom had chronic lung disease or congenital heart disease. The results showed there were no drug-related serious adverse events, and monoclonal antibody serum concentrations reached similar levels to those in healthy infants in another study called CLEVER. Merck said it plans to ask regulators for an expanded label for children under 2 who are at elevated risk of severe disease. The FDA began probing the safety of approved RSV antibodies last year, though it wasn’t immediately clear what was being reviewed. Skeptics of the treatments, including those close to CDC advisors, claimed that infants treated with the drugs had a higher risk of seizures. — Lei Lei Wu & Max Bayer 💰 Compass Pathways’ $150M offering: The London and New York biotech will use the offering proceeds to fund multiple Phase 3 trials and fuel the “acceleration” of its commercial prep. Its psilocybin formulation passed the bar in a Phase 3 treatment-resistant depression study earlier this week. — Kyle LaHucik 💰 Starget closes $18M Series A: The biotech, which is researching radiopharmaceuticals, also signed a collaboration with Center for Molecular Imaging and Therapy in Shreveport, LA. The partnership will focus on developing “next-generation peptide radioligand therapies” in oncology. — Max Gelman 💵 Ten63 bolsters runway: The Durham, NC-based AI drug discovery shop has now raised more than $45 million since its December 2018 founding. The Boehringer Ingelheim -partnered biotech previously outlined a $15.9 million Series A in May 2023. Its new backers include Chugai Venture Fund and Gates Foundation. — Kyle LaHucik

Clinical ResultPhase 2Phase 3

100 Deals associated with BIIB-091

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Encephalitis	Phase 2	United States	Biogen, Inc.	25 Jul 2023
Encephalitis	Phase 2	Bulgaria	Biogen, Inc.	25 Jul 2023
Encephalitis	Phase 2	Czechia	Biogen, Inc.	25 Jul 2023
Encephalitis	Phase 2	Germany	Biogen, Inc.	25 Jul 2023
Encephalitis	Phase 2	Italy	Biogen, Inc.	25 Jul 2023
Encephalitis	Phase 2	Poland	Biogen, Inc.	25 Jul 2023
Encephalitis	Phase 2	Romania	Biogen, Inc.	25 Jul 2023
Encephalitis	Phase 2	Spain	Biogen, Inc.	25 Jul 2023
Encephalitis	Phase 2	Switzerland	Biogen, Inc.	25 Jul 2023
Multiple sclerosis relapse	Phase 2	United States	Biogen, Inc.	25 Jul 2023

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