Contineum Therapeutics: PIPE-791's Dual-Threat Potential in Chronic Pain and Fibrosis

Contineum Therapeutics (CNTM) is pushing the boundaries of drug development with its experimental compound, PIPE-791, a first-in-class, brain-penetrant antagonist of the lysophosphatidic acid 1 receptor (LPA1R). The drug is currently in Phase 1b clinical trials for chronic pain (osteoarthritis, low back pain) and fibrotic diseases (idiopathic pulmonary fibrosis, progressive multiple sclerosis), targeting pathways that underpin two of medicine's most intractable challenges. With no approved therapies that directly address LPA1R-mediated mechanisms, PIPE-791's dual-action profile could carve out a unique niche—if its clinical trials deliver.

Clinical Progress: A Dual-Pronged Approach

PIPE-791's journey to commercialization hinges on two parallel tracks: chronic pain and fibrotic diseases.

Chronic Pain: A Non-Opioid Alternative

The Phase 1b trial for chronic pain, initiated in March . 2025, is evaluating safety and efficacy in 40 patients with osteoarthritis or low back pain. The trial's endpoints—reduction in pain intensity and assessment of neuropathic components—are critical because current therapies like opioids, gabapentin, and NSAIDs often fall short in addressing the central nervous system (CNS) changes that perpetuate chronic pain.

PIPE-791's mechanism directly targets LPA1R, which drives neuronal hyperexcitability, demyelination, and neuroinflammation. If successful, this could provide a non-addictive alternative to opioids, a market increasingly sought after by insurers and regulators. Topline data is expected in early 2026, which will determine whether Contineum advances to Phase 2 trials.

Fibrotic Diseases: A High-Risk, High-Reward Market

In fibrosis, Contineum is tackling idiopathic pulmonary fibrosis (IPF) and progressive multiple sclerosis (PrMS), both of which have limited treatment options. The Phase 1b PET trial for IPF, expected to report results in Q2 2025, uses imaging to correlate receptor occupancy with pharmacokinetics—a critical step to set doses for future trials.

The ATX/LPA/LPA1R pathway is a promising target here. Preclinical studies show LPA1R activation drives fibroblast proliferation and extracellular matrix (ECM) deposition. While ATX inhibitors like ziritaxestat (from Roche) failed in Phase 3 trials for IPF, Contineum's approach differs: it directly blocks LPA1R, bypassing the enzymatic step targeted by ziritaxestat. This distinction may offer a better safety profile or efficacy, though only clinical data will confirm this.

Market Differentiation: A Novel Mechanism in Need of Validation

PIPE-791's potential lies in its novel mechanism and dual therapeutic focus.

• Chronic Pain: Competitors include gabapentin, NSAIDs, and opioids, but none target LPA1R. The lack of CNS-penetrant LPA1R inhibitors means Contineum faces no direct competition in this space.
• Fibrosis: Approved therapies like pirfenidone and nintedanib for IPF target different pathways (e.g., anti-fibrotic and anti-inflammatory mechanisms). While newer agents like pamrevlumab (anti-CTGF) have failed, the fibrosis market is still underserved, with a 2025 global IPF drug market estimated at $2.8 billion and growing.

However, the fibrosis space is littered with clinical failures. The recent termination of Roche's ziritaxestat for IPF—a drug targeting the same pathway—raises red flags. Contineum's success will depend on whether its LPA1R antagonism approach avoids the pitfalls of prior agents, such as off-target effects or insufficient receptor occupancy.

Financial and Risk Considerations

Contineum's Q1 2025 financials show a cash balance of $190.7 million, sufficient to fund operations through 2027. However, its net loss of $16 million reflects escalating clinical costs. Key risks include:
1. Clinical Trial Failures: Negative data in either chronic pain or fibrosis trials could derail the program.
2. Regulatory Hurdles: Even positive Phase 2 results may face scrutiny due to the high bar for fibrosis therapies.
3. Partnership Dependency: While PIPE-307 (a partnered M1 receptor antagonist for depression and MS) could diversify the pipeline, its success is tied to Johnson & Johnson's decisions post-Phase 2.

Investment Thesis: Wait for Milestones, but Watch for Catalysts

PIPE-791's dual potential makes Contineum a compelling high-risk, high-reward play. Here's how investors should approach it:
- Near-Term Catalyst: The Q2 2025 PET trial results for IPF will determine whether Contineum can advance to Phase 2. Positive data could trigger a stock surge.
- Long-Term Catalyst: Chronic pain Phase 1b data in early 2026 will validate the drug's CNS-penetrant profile and safety.
- Risk Management: Avoid overexposure until at least one Phase 2 trial starts. The stock's volatility (currently trading at ~$20/share with a 52-week range of $15–$25) reflects its speculative nature.

Conclusion

PIPE-791's first-in-class mechanism offers a rare opportunity to address two major unmet needs with a single drug. However, Contineum's fate hinges on its ability to replicate preclinical promise in humans—a hurdle even the most promising therapies often fail. Investors should treat this as a stage-gated opportunity, entering cautiously and scaling up only after pivotal data readouts. For those willing to bet on innovation, Contineum's stock could be a poster child for biotech's high-reward, high-risk ethos.

Investment Rating: Hold until Q2 2025 data; reevaluate post-catalyst.