LPAR1

Johnson & Johnson is a partner on Contineum Therapeutics’ most advanced program, which is currently in mid-stage clinical testing for multiple sclerosis. As that research continues and Contineum plans to advance the development of its wholly owned assets, the biotech is moving forward with plans for an IPO. Contineum, which traces its origins to a startup creation engine of venture capital firm Versant Ventures, filed its IPO paperwork with the Securities and Exchange Commission late Friday. The company has not yet set any financial terms for its planned stock market debut, but IPO research firm Renaissance Capital said the offering could reach up to $150 million. The San Diego-based biotech has applied for a Nasdaq listing under the stock symbol “CTNM.” Contineum’s most advanced program is PIPE-307, a small molecule designed to selectively block the M1R receptor. This approach has potential applications in the treatment of multiple sclerosis and depression. Contineum has reported Phase 1 results showed the drug candidate was well tolerated across all doses and showed no dose-related effects on cognitive function. Nearly a year ago, J&J licensed global rights to PIPE-307 for all potential indications. However, the deal still permits Contineum to develop this molecule for relapsing and remitting forms of MS by conducting a Phase 2 study. That clinical trial is ongoing. A Phase 1 test of this molecule in depression is also underway as part of the J&J collaboration. The lead wholly owned Contineum asset is PIPE-791, a program currently in Phase 1 testing. This small molecule is designed to block LPA1, a receptor whose activation is associated with the development of organ scarring called fibrosis. The company believes the molecule’s ability to block LPA1 could treat idiopathic pulmonary fibrosis (IPF), a chronic lung disorder with few available treatments. MS is another potential application for PIPE-791. Levels of LPA, a pro-inflammatory protein, are elevated in the blood and cerebrospinal fluid of MS patients, which may contribute to the progression of this disease, Contineum said in the filing. One key feature of this molecule is its ability to penetrate the brain. In preclinical research, the company said blocking the LPA1 receptor reduces neuroinflammation and promotes remyelination, the formation of new myelin sheaths on axons that have lost this protective layer. Contineum plans to submit an application this year seeking permission in the U.K. for an open-label Phase 1b test of PIPE-791 to assess the molecule’s ability to bind to receptors in the lungs and brain as measured by PET imaging. This study will inform dose selection for planned future Phase 2 tests of the molecule in IPF and progressive MS. The pipeline also includes CTX-343, an LPA1 receptor-blocking molecule that does not cross the blood brain barrier. This capability could provide Contineum more options for its drug portfolio, the company said. CTX-343 is currently preclinical. Contineum traces its roots to Inception Sciences, one of the drug discovery engine of Versant Ventures. Inception and Roche had collaborated to discover and develop small molecules that promote remyelination of nerve fibers damaged as MS progresses. After Roche acquired this neuroscience program for an undisclosed sum in 2018, Versant launched Pipeline Therapeutics, a startup led by the same team that worked on the program that Roche acquired. Versant said Pipeline would focus on developing “next-generation neurodegenerative therapies.” In late 2023, Pipeline changed its name to Contineum Therapeutics. Contineum has raised about $194 million in financing, according to the filing. The J&J alliance paid $50 million upfront and could pay out up to $1 billion tied to the achievement of milestones. Versant is Contineum’s largest shareholder with a 32.2% pre-IPO stake; Johnson & Johnson’s stake is 10.1%. The company’s most recent financing was a 2021 Series C round that raised $80 million. As of the end of 2023, Contineum reported a $15.5 million cash position along with $109.6 million in marketable securities. That capital, combined with the IPO proceeds, will go toward continued clinical development of the LPA1 receptor antagonist, including the completion of Phase 1b testing. An unspecified amount of additional cash will go toward planned Phase 2 tests in IPF and progressive MS. Contineum also plans to use the IPO proceeds to complete Phase 2 testing of its J&J-partnered molecule in relapsing and remitting forms of MS. Image: Getty Images

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.

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.