Multiple Sclerosis, Relapsing-Remitting

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.

Pictured: Nasdaq Stock Exchange building in New York City/iStock, JHVEPhoto Contineum Therapeutics on Friday filed for an initial public offering, hoping to drum up additional support to advance its pipeline of small molecule drugs for multiple sclerosis and other neuroscience, inflammation and immunology indications. The California-based biotech did not specify a fundraising target in its SEC document, but several media reports indicate that Contineum is aiming to raise $150 million. At this stage in the initial public offering (IPO) process, it’s customary for companies to put $100 million as a maximum value placeholder in their S-1 forms. Contineum also did not reveal when it expects to close its IPO, only noting that it hopes to wrap the offering up within the year. Once completed, Contineum will trade on the Nasdaq Global Select Market Under the ticker symbol CNTM. The biotech will use the IPO proceeds to complete the Phase II trial for its most mature candidate PIPE-307, which is currently being developed in partnership with Johnson & Johnson for the treatment of relapse remitting multiple sclerosis (RRMS), according to its SEC filing. The companies signed their global license and development deal in April 2023, with J&J dropping $50 million upfront and pledging up to $1 billion in potential milestone payments. PIPE-307 is a brain-penetrant small molecule inhibitor of the muscarinic type 1 M1 receptor (M1R), which plays a key role in various brain functions such as attention, memory and sleep regulation. According to a 2021 study published in ACS Medicinal Chemistry Letters, and conducted by company scientists, blocking M1R in the brain could promote the remyelination of neurons while repairing nerve function in RRMS. Contineum is currently running a Phase II study for PIPE-307 as an adjunctive treatment for RRMS. The company is also assessing the potential of the candidate in depression, for which J&J is planning to launch a Phase II study this year. In addition to PIPE-307, Contineum will also use the IPO proceeds to advance its lead asset PIPE-791, which is being developed for idiopathic pulmonary fibrosis (IPF) and progressive MS. In IPF, PIPE-781 works by targeting the lysophosphatidic acid 1 receptor (LPA1R), which drives cellular cascades for vascular leakage and fibroblast recruitment while reducing fibrosis. In progressive MS, PIPE-781’s mechanism of action targets neuroinflammation and promotes remyelination, both of which are prominent disease pathways. According to Contineum’s SEC document, PIPE-781 is currently the “only brain-penetrant LPA1R antagonist in clinical development for progressive MS.” Contineum maintains the 2024 IPO spree as the industry tries to bounce back from a record low last year. This year’s class includes CG Oncology, ArriVent BioPharma, Kyverna Therapeutics and Metagenomi. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.