Multiple Sclerosis, Chronic Progressive

Boundless Bio and now Contineum Therapeutics have kept the IPO market ticking over in March. The biotech IPO class of 2024 could be getting another member. Contineum Therapeutics is the latest company to test the waters, filing paperwork to raise money for phase 2 clinical trials of its lead prospect and a Johnson & Johnson-partnered molecule. Contineum, a biotech previously called Pipeline Therapeutics, wants the money to fund phase 1b and 2 trials of its lead drug candidate in idiopathic pulmonary fibrosis (IPF) and progressive multiple sclerosis (MS). The molecule, PIPE-791, is designed to inhibit LPA1, a receptor that studies suggest may drive scarring in IPF and promote neuroinflammation and limit remyelination in MS. Based on preclinical studies and tests in healthy volunteers, Contineum believes once-daily doses of the molecule could treat IPF. The schedule would set PIPE-791 apart from existing IPF therapies. Boehringer Ingelheim’s Ofev and Roche’s Esbriet are, respectively, taken two and three times a day. Other drug developers have hit on the idea of targeting LPA1 to treat IPF. Bristol Myers Squibb picked up a LPA1 candidate in 2011 through its $325 million acquisition of Amira Pharmaceuticals, a biotech at which Contineum founder and chief scientific officer Daniel Lorrain, Ph.D., worked. BMS posted phase 2 data on the LPA1 antagonist BMS-986278 last year. Amgen acquired a phase 2 LPA1 drug, now called AMG 670, as part of the Horizon Therapeutics buyout. AbbVie entered the LPA1 space in 2022 by paying $255 million for DJS Antibodies. Structure Therapeutics has also discovered inhibitors of the receptor. The progressive MS space is less competitive. Contineum contends PIPE-791 is the only brain-penetrant LPA1 receptor antagonist in clinical development in the indication. Progressive MS has proven a tougher nut to crack than other forms of the disease, with Contineum noting that studies of would-be rivals have generated “almost uniformly disappointing results.” But the mechanism of PIPE-791 suggests it may be able to improve outcomes by addressing chronic neuroinflammation and demyelination. Contineum has earmarked another chunk of the anticipated IPO haul for a phase 2 trial of PIPE-307, the drug candidate covered by the J&J agreement, in relapsing-remitting MS. The terms of the J&J deal require Contineum to run a phase 2 trial in the indication. Enrollment in the study began in November.  Interest in developing PIPE-307 in relapsing-remitting MS, a setting where effective immune-modulating treatments exist, is underpinned by evidence that the M1R inhibitor may be the molecule that finally achieves direct promotion of remyelination. Decades of failed programs have made remyelination the holy grail of MS drug development.  Contineum had run up an accumulated deficit of $75 million pursuing remyelination and other projects by the end of last year. The spending left the biotech with $125 million in cash, cash equivalents and marketable securities from its private financing rounds, which include an $80 million series C it closed in 2021. The biotech’s identification of public investors as the people to bankroll the next steps in its evolution keeps the IPO stream trickling along. While the pace of new listings slowed after a flurry early in the year, Boundless Bio and now Contineum have kept the IPO market ticking over in March.

Contineum Therapeutics has thrown its hat into the ring for a spring public debut. The neurology and inflammation-focused company filed for an IPO last week to fund clinical trials of its two lead programmes, including a multiple sclerosis (MS) and depression candidate that’s partnered with Johnson & Johnson. Formerly Pipeline Therapeutics, Contineum joins Boundless Bio in the IPO queue, which was the first biotech in March to signal its public interest following the rapid-fire offerings of late January and early February. The mid-stage oncology company has yet to set terms for its offering.Also in line for public offerings are several biotechs seeking sub-$30 million debuts: Aprinoia Therapeutics, Lirum Therapeutics, and Jyong Biotech.  MS, depression in the pipelineContineum’s clinical pipeline comprises two oral small molecules: LPA1R antagonist PIPE-791, and M1 muscarinic receptor antagonist PIPE-307.The former is a brain penetrant compound that’s completed Phase I studies for idiopathic pulmonary fibrosis (IPF) and progressive multiple sclerosis (MS). With the IPO proceeds, Contineum expects to start this year a Phase Ib PET imaging trial to measure the relationship of pharmacokinetics to lung and brain receptor occupancy, which will help inform dosing for Phase II trials for each indication.Johnson & Johnson has an exclusive, worldwide licence to the latter candidate, which is in development for relapsing/remitting MS and depression.Last year Contineum received $50 million upfront for rights to PIPE-307 and is eligible for up to $1 billion in milestones, plus low-double digit to high-teen tiered royalties. The company also received a $25 million equity investment from the US pharma’s venture capital arm, JJDC. Muscarinic receptor modulators have gained steam as of late for their potential in mood disorders, particularly schizophrenia. For more, see KOL Views Q&A: Leading psychiatrist sees a muscarinic revolution coming in schizophrenia and beyond.“To our knowledge, PIPE-307 is the most clinically advanced selective M1R antagonist in development,” the company said in the filing.  Contineum is in charge of a Phase II trial of PIPE-307 in relapsing/remitting MS; IPO proceeds are expected to help the biotech wrap up the study. Johnson & Johnson plans to start a Phase II trial this year of the candidate to treat depression.

PRESS RELEASE NEW RESEARCH SHOWS THAT MASITINIB LIMITS NEURONAL DAMAGE IN A MODEL OF NEUROIMMUNE-DRIVEN NEURODEGENERATIVE DISEASE THIS IS THE FIRST DEMONSTRATION THAT MASITINIB CAN LOWER SERUM NEUROFILAMENT LIGHT CHAIN, AN IMPORTANT BIOMARKER FOR NEURODEGENERATIVE DISORDERS Paris, March 13, 2024, 12.45pm CET AB Science SA (Euronext - FR0010557264 - AB) today announced the publication of new preclinical results for masitinib in neurodegenerative diseases (NDD). Findings have been published on the bioRxiv preprint service as an article entitled, ‘Masitinib limits neuronal damage, as measured by serum neurofilament light chain concentration, in a model of neuroimmune-driven neurodegenerative disease’. This article is freely accessible online from the bioRxiv site [1]. The neuroprotective action of masitinib was studied in an animal model of experimental autoimmune encephalitis (EAE). EAE is a model of neuroimmune-driven chronic neuroinflammation and importantly, neuronal damage, or prevention thereof, can be rapidly assessed by measuring serum neurofilament light chain (NfL) concentration in EAE-induced mice. Results showed that masitinib can significantly lower serum NfL levels, and by extension therefore, neuronal damage, in a neuroimmune-driven neurodegenerative disease model, with concomitant reduction in pro-inflammatory cytokines and slowing of clinical symptoms. Patrick Vermersch, MD, Professor of Neurology at the University of Lille, France, and co-author of this article commented: “Using a model that is highly relevant to masitinib's mechanism of action in neurodegenerative diseases, this research has shown for the first time that masitinib can lower serum NfL levels, as well as pro-inflammatory cytokines, and by extension therefore, reduce the rate of neuronal damage. Because chronic neuroinflammation is a common pathological characteristic of most neurodegenerative diseases, the observed NfL treatment response indicates that masitinib has a plausible disease-modifying activity in diseases such as progressive multiple sclerosis, amyotrophic lateral sclerosis (ALS) and Alzheimer's disease.” Alain Moussy, co-founder and CEO of AB Science said: “The ability of masitinib to impact NFL in an animal model might be important because biomarkers are at the forefront not only of research in neurodegenerative disorders to predict clinical outcome but also reglementary guidelines to accelerate registration. FDA has recognized recently NFL from patients as a potential biomarker for ALS registration and has issued a recent guideline in Alzheimer’s Disease encouraging the use of biomarker for accelerated approval. AB Science is not only working on disease biomarkers such an NFL but also on mechanistic biomarkers of the response of masitinib.” Key points from this research article include: Masitinib treatment significantly limited NfL production in EAE mice with respect to the control group, at various timepoints during the 15-day treatment period and in a dose dependent manner.Masitinib significantly lowered several well-established pro-inflammatory cytokine biomarker concentrations in EAE mice.A beneficial effect of masitinib on functional performance was also observed, with significantly less relative deterioration in grip strength as compared with the control group. The measurement of NfL in biological fluids has been proposed for monitoring the therapeutic effect of drugs aimed at reducing axonal damage in various NDDs, including amyotrophic lateral sclerosis, multiple sclerosis, and Alzheimer’s disease.EAE is a model of neuroimmune-driven chronic neuroinflammation and therefore highly relevant to masitinib's mechanism of action in NDDs.Data was derived after disease onset (i.e., in a therapeutic setting as opposed to an asymptomatic preventative setting), which is of greater relevance because such models more closely simulate the clinical condition of NDD patients and therefore better represent their therapeutic needs. [1] Hermine O, Vermersch P, et al. Masitinib limits neuronal damage, as measured by serum neurofilament light chain concentration, in a model of neuroimmune-driven neurodegenerative disease. Preprint. bioRxiv 2024.03.07.583695; doi: https://doi.org/10.1101/2024.03.07.583695https://www.biorxiv.org/content/10.1101/2024.03.07.583695v1.full.pdf+html About the neurofilament light chain (NfL) biomarkerThe measurement of neurofilament light chain (NfL) in biological fluids has been proposed for monitoring the therapeutic effect of drugs aimed at reducing axonal damage. NfL are cytoskeletal proteins that are highly specific for neurons in both the central nervous system (CNS) and the peripheral nervous system. NfL in cerebrospinal fluid or the bloodstream is therefore indicative of axonal lesions and/or degeneration and elevated NfL levels are associated with traumatic brain injuries or neurodegenerative diseases (NDD), including amyotrophic lateral sclerosis, multiple sclerosis, and Alzheimer’s disease. A growing body of literature shows that because the level of free NfL in serum/plasma directly reflects neuronal damage within the CNS, it can be used as a reliable and easily accessible marker of disease intensity and/or activity across a variety of neurological disorders. About bioRxivbioRxiv (pronounced "bio-archive") is a free online archive and distribution service for unpublished preprints in the life sciences. It is operated by Cold Spring Harbor Laboratory, a not-for-profit research and educational institution. By posting preprints on bioRxiv, authors are able to make their findings immediately available to the scientific community and receive feedback on draft manuscripts before they are submitted to journals. About masitinibMasitinib is a orally administered tyrosine kinase inhibitor that targets mast cells and macrophages, important cells for immunity, through inhibiting a limited number of kinases. Based on its unique mechanism of action, masitinib can be developed in a large number of conditions in oncology, in inflammatory diseases, and in certain diseases of the central nervous system. In oncology due to its immunotherapy effect, masitinib can have an effect on survival, alone or in combination with chemotherapy. Through its activity on mast cells and microglia and consequently the inhibition of the activation of the inflammatory process, masitinib can have an effect on the symptoms associated with some inflammatory and central nervous system diseases and the degeneration of these diseases. About AB ScienceFounded in 2001, AB Science is a pharmaceutical company specializing in the research, development and commercialization of protein kinase inhibitors (PKIs), a class of targeted proteins whose action are key in signaling pathways within cells. Our programs target only diseases with high unmet medical needs, often lethal with short term survival or rare or refractory to previous line of treatment. AB Science has developed a proprietary portfolio of molecules and the Company’s lead compound, masitinib, has already been registered for veterinary medicine and is developed in human medicine in oncology, neurological diseases, inflammatory diseases and viral diseases. The company is headquartered in Paris, France, and listed on Euronext Paris (ticker: AB). Further information is available on AB Science’s website: www.ab-science.com. Forward-looking Statements - AB ScienceThis press release contains forward-looking statements. These statements are not historical facts. These statements include projections and estimates as well as the assumptions on which they are based, statements based on projects, objectives, intentions and expectations regarding financial results, events, operations, future services, product development and their potential or future performance. These forward-looking statements can often be identified by the words "expect", "anticipate", "believe", "intend", "estimate" or "plan" as well as other similar terms. While AB Science believes these forward-looking statements are reasonable, investors are cautioned that these forward-looking statements are subject to numerous risks and uncertainties that are difficult to predict and generally beyond the control of AB Science and which may imply that results and actual events significantly differ from those expressed, induced or anticipated in the forward-looking information and statements. These risks and uncertainties include the uncertainties related to product development of the Company which may not be successful or to the marketing authorizations granted by competent authorities or, more generally, any factors that may affect marketing capacity of the products developed by AB Science, as well as those developed or identified in the public documents published by AB Science. AB Science disclaims any obligation or undertaking to update the forward-looking information and statements, subject to the applicable regulations, in particular articles 223-1 et seq. of the AMF General Regulations. For additional information, please contact: AB ScienceFinancial Communication & Media Relations investors@ab-science.com Attachment Masitinib NfL BioRxiv vENG VF