Contineum Therapeutics Announces Encouraging Topline Results from Exploratory Phase 1b Study of PIPE-791 in Chronic Pain
Contineum Therapeutics, Inc. (NASDAQ: CTNM), a clinical-stage biopharmaceutical company focused on advancing differentiated therapies across neuroscience, inflammation, and immunology (NI&I) indications, has announced encouraging topline results from its exploratory Phase 1b clinical trial evaluating PIPE-791. The investigational therapy, a selective antagonist of the lysophosphatidic acid 1 (LPA1) receptor, is being developed as a potential non-opioid treatment for chronic pain conditions, specifically chronic osteoarthritis pain (COAP) and chronic low back pain (CLBP).
The newly released data represent an important milestone for Contineum as it continues to build a clinical profile for PIPE-791, which the company believes could emerge as a best-in-class therapy within its category. Chronic pain remains one of the most challenging therapeutic areas, with millions of patients worldwide seeking effective alternatives to opioid-based treatments due to concerns around safety, dependence, and long-term use.
According to Timothy Watkins, M.D., M.Sc., Chief Medical Officer and Head of Development at Contineum Therapeutics, the findings from this study reinforce confidence in PIPE-791’s tolerability and therapeutic potential. Administered as a once-daily 10 mg oral dose, the drug was generally well tolerated across the study population, which represents the largest group of patients and longest duration of treatment evaluated with PIPE-791 to date. Watkins emphasized that the observed trends across multiple exploratory efficacy endpoints—while preliminary—consistently favored PIPE-791 over placebo, suggesting meaningful potential for further development.
The Phase 1b trial was designed as a randomized, double-blind, placebo-controlled crossover study conducted over four weeks, followed by a second four-week treatment period. A total of 43 patients were enrolled, including 23 individuals with chronic osteoarthritis pain and 20 with chronic low back pain. Prior to initiating treatment, participants underwent a washout period to eliminate the influence of prior therapies. Patients were then assigned to receive either PIPE-791 or placebo during the first treatment period (TP1), after which they crossed over directly into the second treatment period (TP2) without an additional washout phase for PIPE-791.
The primary objective of the study was to evaluate safety and tolerability. In this regard, PIPE-791 met expectations, demonstrating an adverse event profile consistent with earlier clinical experience. Most treatment-emergent adverse events were mild to moderate in severity, and importantly, no serious adverse events were reported during the study. The most commonly observed side effects included headache and fatigue, each affecting a small number of participants. Additionally, there were no clinically meaningful changes in blood pressure—either systolic or diastolic—and no notable orthostatic events, supporting a favorable cardiovascular safety profile.
Beyond safety, the study also explored multiple efficacy endpoints related to pain reduction. Pain intensity was measured using the widely accepted 11-point Pain-Intensity Numerical Rating Scale (PI-NRS), which captures both average daily pain and the worst daily pain experienced by patients. Across both COAP and CLBP cohorts, patients receiving PIPE-791 demonstrated improvements from baseline that were generally greater than those observed in the placebo group.
In the COAP subgroup during the first treatment period, patients treated with PIPE-791 showed a mean reduction in average daily pain scores of -1.60 compared to -1.27 in the placebo arm. This trend continued into the second treatment period, where the reduction in pain scores remained numerically greater for PIPE-791 (-1.42) versus placebo (-0.74). Similar patterns were observed in the CLBP cohort, particularly during the first treatment period, where PIPE-791 demonstrated a greater reduction in pain compared to placebo.
Although the study was not powered to achieve statistical significance on efficacy endpoints, the consistency of these trends across multiple measures provides an encouraging signal. Notably, improvements were also observed in assessments of worst daily pain, further supporting the potential analgesic effect of PIPE-791.
Additional exploratory endpoints included the proportion of patients achieving a clinically meaningful response—defined as a reduction of at least 30% in pain from baseline—as well as patient-reported outcomes measured by the Modified Knee Injury and Osteoarthritis Outcome Score (KOOS). Results from these analyses aligned with the PI-NRS findings, with a greater proportion of responders observed in the PIPE-791 group compared to placebo, particularly among patients with osteoarthritis-related pain.
Experts in the field have highlighted the significance of these early findings. Dr. Robert H. Dworkin, Professor of Anesthesiology and Perioperative Medicine and of Neurology at the University of Rochester Medicine, noted that chronic pain remains a major unmet medical need, especially for patients seeking non-opioid therapeutic options. He pointed out that the improvements in pain measures and responder rates seen with PIPE-791 are promising, particularly given the drug’s novel mechanism of action targeting LPA1 signaling pathways.
The scientific rationale for PIPE-791 is rooted in the role of LPA1 in the development and persistence of neuropathic pain. Preclinical studies have demonstrated that activation of the LPA1 receptor contributes to pathological changes in the central nervous system, including demyelination of nerve fibers, increased neuronal excitability, and neuroinflammation. These processes are believed to drive chronic pain and hypersensitivity. By selectively antagonizing LPA1, PIPE-791 aims to interrupt these maladaptive pathways, potentially offering a disease-modifying approach rather than simply masking symptoms.
Contineum Therapeutics believes that these findings, particularly the signals observed in the osteoarthritis pain cohort, provide sufficient justification to advance PIPE-791 into further clinical development. The company is currently evaluating next steps, which may include larger and more definitive trials designed to confirm efficacy and further characterize the drug’s safety profile over longer durations.
In addition to its development in chronic pain, PIPE-791 is also being investigated in other indications, including idiopathic pulmonary fibrosis (IPF), through the ongoing PROPEL-IPF trial. The favorable tolerability observed in the Phase 1b study further supports its broader clinical utility and potential application across multiple disease areas driven by LPA1-mediated pathways.
In summary, while still in early-stage development, PIPE-791 has demonstrated a compelling combination of safety, tolerability, and preliminary efficacy signals in patients with chronic osteoarthritis pain and chronic low back pain. These results position the therapy as a promising candidate in the ongoing effort to develop effective, non-opioid treatments for chronic pain—a field that continues to demand innovative solutions.
About Contineum Therapeutics
Contineum Therapeutics (Nasdaq: CTNM) is a clinical-stage biopharmaceutical company pioneering novel, oral small molecule therapies for NI&I indications with significant unmet need. Contineum is advancing a pipeline of internally-developed programs with multiple drug candidates now in clinical trials. PIPE-791 is an LPA1 receptor antagonist in clinical development for idiopathic pulmonary fibrosis and chronic pain. PIPE-307 is a selective inhibitor of the M1 receptor in clinical development for relapsing-remitting multiple sclerosis and major depressive disorder.
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