Overview
We are a clinical-stage biopharmaceutical company pioneering differentiated therapies for the treatment of NI&I indications with significant unmet need. We target biological pathways associated with specific clinical impairments that we believe, once modulated, will demonstrably alter the course of disease.
We have focused our efforts on developing selective compounds targeting challenging molecular pathways and have built a portfolio of small molecule drug candidates. We believe our two clinical stage, internally-discovered drug candidates, PIPE-791 and PIPE-307, will have broad applicability across multiple NI&I indications. We are developing PIPE-307 in collaboration with J&J.
Our wholly-owned lead asset, PIPE-791, is a novel, brain penetrant, small molecule inhibitor of the lysophosphatidic acid 1 receptor (“LPA1R”) in development for idiopathic pulmonary fibrosis (“IPF”), progressive multiple sclerosis (“PrMS”), and chronic pain. LPA1R antagonism is a clinically validated mechanism in IPF, and we believe that our preclinical studies and Phase 1 healthy volunteer data support the development of PIPE-791 for IPF, as well as PrMS and chronic pain. Specifically, based on its high bioavailability, low plasma protein binding, and long receptor residence time in our preclinical studies compared to the preclinical data of other LPA1R antagonists, we believe PIPE-791 has the potential to be a differentiated LPA1R therapy. We have completed a Phase 1 clinical trial of PIPE-791 in healthy volunteers in support of clinical development in IPF, PrMS and chronic pain. In December 2024, we commenced a Phase 1b open-label trial to measure the relationship of pharmacokinetics (“PK”) to lung and brain receptor occupancy by positron emission tomography (“PET”) imaging. We expect the top-line data from this trial will be available in the second quarter of 2025. This Phase 1b PET trial will inform dose selection for our planned Phase 2 trials of PIPE-791 in IPF and PrMS. In November 2024, the FDA authorized our Investigational New Drug application (“IND”) for the treatment of chronic pain associated with two separate indications, osteoarthritis (“OA”) and low back pain (“LBP”). On March 4, 2025, we announced the initiation of patient dosing in an exploratory PIPE-791 Phase 1b, randomized, double-blind, placebo-controlled, crossover, chronic pain trial. We expect to enroll approximately 40 patients at up to five sites in the U.S., and a treatment duration of 28 days. We anticipate top-line data from this trial in early 2026.
Our second drug candidate, PIPE-307, is a novel, small molecule selective inhibitor of the muscarinic type 1 receptor (“M1R”), in development for depression and relapse-remitting multiple sclerosis (“RRMS”). We have completed two Phase 1 trials of PIPE-307 in healthy volunteers. In 2023, we initiated a Phase 2 VISTA trial of PIPE-307 for the potential treatment of RRMS. In January 2025, we announced that we have fully enrolled our Phase 2 VISTA trial. We expect the top-line data from this trial will be available in the second half of 2025. In December 2024, J&J began recruiting participants for a Phase 2 trial of PIPE-307 (also referred to as JNJ-5120) for the potential treatment of major depressive disorder (“MDD”). We believe PIPE-307 is the most advanced selective M1R antagonist in clinical development.
In addition, we are leveraging our drug discovery capabilities to expand our clinical portfolio. In January 2024, we nominated and commenced preclinical studies for CTX-343, a peripherally-restricted (unable to access the central nervous system (“CNS”)) LPA1R antagonist. In parallel, we are actively conducting preclinical and discovery-phase experiments targeting other NI&I indications where our internally-discovered molecules may have therapeutic potential.
Our Clinical Pipeline
We have a portfolio of novel and proprietary small molecule programs that we believe can modulate innate pathways to restore function in NI&I indications. We retain worldwide rights to our LPA1R programs and discovery portfolio, and we have partnered with J&J for the development and potential commercialization efforts of PIPE-307.
Our Competitive Strengths
We have a strong, complementary relationship between our medicinal chemistry and biology teams, which allows us to develop drug candidates for historically difficult targets. We believe that our competitive strengths include:
Our Strategy
Our mission is to significantly impact the clinical disability associated with NI&I diseases with small molecules designed to modulate innate pathways to restore function. We aim to accomplish our goal by implementing the following strategies:
Execute a balanced development strategy in which we assess both external clinical validation and novel therapeutic approaches for our targets. We have built our current pipeline with the goal of minimizing clinical risk. We leverage external validation for our wholly-owned programs such as PIPE-791 for IPF, PrMS and chronic pain and our partnered program PIPE-307 for both depression and RRMS. Based on scientific rationale, we are also progressing programs in additional disease areas, where we believe there is potential to create significant clinical benefit and address unmet need.
Pursue clinical development of PIPE-791, an LPA1R antagonist, for the treatment of IPF, a sizeable patient population market with significant unmet need. There are approximately 130,000 patients in the United States with IPF, of which the average life span after diagnosis is three to five years. Currently, there are only two FDA-approved treatments in IPF, nintedanib and pirfenidone, which are limited by issues associated with safety, tolerability and compliance. LPA1R antagonism is a clinically validated mechanism, and we believe that our preclinical studies and Phase 1 healthy volunteer data support the continued development of PIPE-791 for IPF.
Pursue clinical development of PIPE-791 in PrMS to address the significant unmet need for a therapy that has the potential to reduce neuroinflammation and support remyelination. We believe PIPE-791 has strong biological rationale to be a potentially novel treatment for PrMS.
Seek to maximize the value of PIPE-791 by investigating its applicability in a broad range of NI&I disorders beyond IPF, PrMS, and chronic pain. We believe PIPE-791 has the potential for broad indication expansion due to the central role of LPA1 in multiple NI&I diseases and we are actively conducting preclinical experiments across those areas. Our future development strategy will be guided by data from our ongoing preclinical studies, observed external validation, and our focus on therapeutic potential in areas of high unmet need.
Support the advancement of PIPE-307 through a broad clinical development strategy in partnership with J&J. J&J is an experienced innovator with a strong commitment to neuroscience, reporting $7.1 billion of neuroscience sales in 2024. Our collaboration provides a foundation for the development of PIPE-307 with access to J&J's robust R&D and commercialization capabilities, which we believe will allow us to achieve the full potential of PIPE-307.
Leverage our drug discovery capabilities to build out a franchise with deliberate focus on developing therapeutics that are synergistic with our existing portfolio, including our peripherally-restricted LPA1R antagonist, CTX-343. We believe that the development of a peripherally-restricted LPA1R antagonist drug candidate will provide us with critical optionality for our portfolio. We will continue to leverage the capabilities and expertise of our team to identify and develop drug candidates with the highest likelihood of clinical and commercial success in NI&I.
Evaluate and selectively engage in strategic collaborations to maximize the potential of our pipeline. We recognize that partnerships may provide a more prudent development path in certain cases to reduce costs and accelerate the delivery of effective therapies to market, as exemplified by our partnership with J&J. Our collective expertise and strategic approach will guide us in selecting not only drug candidates with therapeutic potential but also ideal partners that can meaningfully contribute to the development and commercialization of our therapeutic portfolio.
LPA1 Franchise
Our lead asset, PIPE-791, is a novel, high affinity, brain penetrant, small molecule LPA1R antagonist. We are initially developing PIPE-791 for the treatment of IPF, PrMS and chronic pain. We are also exploring in preclinical studies the potential utility of PIPE-791 in additional disorders where the LPA1R pathway has been implicated. We completed a Phase 1 trial to evaluate the safety, tolerability, and PK of single and multiple doses of PIPE-791 in healthy volunteers. In 2024, we commenced a Phase 1b open-label trial to measure the relationship of PK to lung and brain receptor occupancy by PET imaging. We expect the top-line data from this trial will be available in the second quarter of 2025. This Phase 1b trial will inform dose selection for planned future Phase 2 trials of PIPE-791. In addition, we are advancing CTX-343, a peripherally-restricted LPA1R antagonist. In November 2024, the FDA authorized our IND for the treatment of chronic pain associated with two separate indications, OA and LBP. On March 4, 2025, we announced the initiation of patient dosing in an exploratory PIPE-791 Phase 1b, randomized, double-blind, placebo-controlled, crossover, chronic pain trial. We expect to enroll approximately 40 patients at up to five sites in the U.S., and a treatment duration of 28 days. We anticipate top-line data from this trial in early 2026.
PIPE-791 for the Potential Treatment of IPF
We are developing PIPE-791 for the potential treatment of IPF. Based on the results of external and internal preclinical studies and emerging third-party clinical trials involving LPA1R antagonism, we believe there is a strong rationale for PIPE-791 to be disease modifying in IPF.
The LPA/LPA1R pathway is a key mediator of fibrosis. LPA is a bioactive lipid that is elevated in response to lung injury and activates LPA1R. Activation of LPA1R drives several cellular cascades, including fibroblast recruitment and vascular leakage, that lead to fibrosis. Inhibition of LPA1 can reduce these detrimental processes and may be a beneficial treatment for IPF. We have demonstrated this by our evaluation of PIPE-791 to reduce fibrosis in response to injury in a key in vivo rodent model for IPF. In addition, this rationale is supported by third-party LPA1R antagonist programs, which have demonstrated clinical proof-of-concept in multiple Phase 2 clinical trials in IPF patients. Based on the dosing profile from our preclinical studies and the PK data from our Phase 1 healthy volunteer trial, we believe PIPE-791, pending further clinical development and FDA approval, has the potential to treat IPF with once-daily dosing. In contrast, currently approved IPF therapies require multiple-daily dosing regimens.
Disease Background
IPF is a chronic idiopathic interstitial lung disease characterized by progressive fibrosis of the lung tissue leading to severe loss of respiratory function. As the fibrosis progresses, the lung’s ability to function and transfer oxygen into the bloodstream becomes increasingly impaired. Although the disease course is variable, the prognosis for overall survival is worse than many forms of cancer, with approximately 60% to 80% of patients dying from respiratory failure within five years of diagnosis.
IPF is a rare disease with approximately 130,000 patients in the United States and, as of 2017, 30,000 to 40,000 new cases diagnosed annually. As of 2023, worldwide prevalence is estimated to be three million cases. Although the mechanisms of fibrosis in IPF remain poorly understood, generally accepted concepts of disease pathogenesis involve recurrent subclinical injuries to alveoli (lung tissue) and failure of normal lung tissue repair. Injured cells within the alveoli release multiple cytokines and growth factors that promote the recruitment, proliferation, and differentiation of lung fibroblasts into myofibroblasts, leading to excessive collagen deposition, progressive scarring of the lung parenchyma, and irreversible loss of function. Although IPF is considered the prototypic progressive fibrosing interstitial lung disease (“ILD”), a number of other ILDs display a progressive pathophysiology and clinical course similar to IPF.
IPF only affects the lungs and patients generally present with non-specific symptoms such as shortness of breath on exertion, chronic cough, fatigue, and/or rapid weight loss. The diagnosis is most common in men ages 65 years and older. The major environmental factors that can lead to lung damage in IPF include cigarette smoking (current or ex-smokers), chronic viral infections, abnormal acid reflux and environmental exposures. Genetic factors may also contribute to the development or worsen the prognosis of IPF. The physical, psychologic and socio-economic consequences of IPF are burdensome on patients and healthcare providers, and are significantly exacerbated by an aging population.
Current Approved Therapies
While there is no pharmacological cure for IPF, there are two FDA-approved therapies to treat the disease: pirfenidone (Esbriet, marketed by Genentech/Roche) and nintedanib (Ofev, marketed by Boehringer Ingelheim). Both drugs were approved in 2014 and are recommended by the most recent treatment guidelines from 2015. Neither drug stops the progression of IPF and both are limited by issues associated with safety, tolerability and compliance with multi-daily dosing regimens. Lung transplant is currently the only cure for patients with IPF, but, due to age and comorbidities, this is a limited treatment option for most patients. We believe that PIPE-791 has the potential to address the limitations of current therapies and serve a large unmet need for IPF patients.
Pirfenidone is an orally available, synthetic compound that exerts anti-fibrotic, anti-inflammatory and antioxidant properties through down-regulation of key pro-fibrotic growth factors including TGF-b, inhibition of inflammatory cytokines (e.g., tumor necrosis factor-a) production and release, and reduction of lipid peroxidation and oxidative stress. Four registrational trials have evaluated the efficacy of pirfenidone in patients with IPF, with three showing that pirfenidone slows down disease progression as measured by rate of deterioration in forced vital capacity (“FVC”). Pirfenidone is prescribed in a dose-escalating pattern three times daily (“TID”) over a 14-day period to a target dose of 801 mg TID (total daily dose of 2,403 mg administered by nine 267 mg capsules). Common side effects of pirfenidone include gastrointestinal intolerance characterized by nausea, vomiting, dyspepsia, and diarrhea. Dose modification or discontinuation may be necessary in the case of severe side effects, with 19% of patients requiring dose reductions or interruptions due to gastrointestinal events in the clinical trials. Pirfenidone also carries the risk of skin reactions involving photosensitivity and rashes, with patients instructed to take sun exposure precautions.
Nintedanib is an intracellular inhibitor of vascular endothelial growth factor receptor 1–3, fibroblast growth factor receptor 1–3, and platelet-derived growth factor receptor a and b. By inhibiting these tyrosine kinase receptors, nintedanib interferes with a number of processes that have been implicated in the pathogenesis of IPF. Treatment with nintedanib in multiple clinical trials demonstrated a reduction in the one-year rate of decline in FVC by approximately 50%. The recommended dosage of nintedanib is 150 mg twice daily (“BID”) approximately 12 hours apart. The most frequent side effects associated with nintedanib are diarrhea (reported by approximately 60% of patients within the first 3 months of treatment, with over 10% of patients requiring permanent dose reduction), nausea, and vomiting. In addition to these gastrointestinal side effects, data from clinical trials with nintedanib noted a risk of arterial thromboembolic events, bleeding disorders, and gastrointestinal perforation.
In addition to the side effects noted above, which are associated with discontinuation of therapy, both pirfenidone and nintedanib have demonstrated risk for transaminitis, or elevation in liver enzymes. Both drugs require routine monitoring of liver function that can prompt dose reductions or treatment discontinuations, and each drug’s label includes a warning relating to elevated liver enzymes and gastrointestinal disorders. Specifically, both pirfenidone and nintedanib have the additional warning of drug-induced liver injury and severe liver injury with fatal outcomes. Due to these issues associated with safety and tolerability, it has been estimated that approximately 40% to 50% of patients discontinued treatment on either drug within one year of initiation.
Despite the limitations highlighted above, pirfenidone and nintedanib generated more than $4 billion in combined total sales globally in 2022. Patent expiration for pirfenidone is 2022 (U.S.) and 2026 (EU and Japan), and the patent covering the active pharmaceutical ingredients (“APIs”) for nintedanib is 2025 (U.S., EU, Japan), respectively. In summary, IPF remains an indication with significant unmet need for effective therapies that can address some of these challenges.
Scientific Rationale for LPA1R Antagonism in IPF
LPA is a bioactive lysophospholipid that regulates numerous aspects of cellular function, such as proliferation, migration and cytoskeletal reorganization, and has been recognized as a novel mediator of wound healing and tissue fibrosis. LPA mediates its effects by signaling through a family of six G protein-coupled receptors, LPA1 to LPA6.
The link between the LPA/LPA1R pathway and IPF was first identified by Tager et al., 2008, following an observation that LPA, elevated in bronchoalveolar lavage fluid, promoted fibroblast migration. Using genetic knockout animals, studies demonstrated that this response was driven by activation of the LPA1R. In further studies, rodents lacking the LPA1R were protected from bleomycin-induced pulmonary fibrosis, one of the key animal models for IPF, by reducing fibroblast recruitment and vascular leak. Subsequent studies have replicated these findings using small molecule LPA1R selective antagonists.
The following figure shows LPA1’s mechanism in pulmonary fibrosis.
LPA1R antagonism has also demonstrated clinical proof-of-concept in third-party, randomized, double blind, placebo-controlled Phase 2 trials of LPA1R antagonists (BMS-986020 and BMS-986278) in patients with IPF.
The results of a Phase 2 parallel-arm, multi-center, randomized, double-blind, placebo-controlled trial in 143 adults with IPF treated with BMS-986020 were published in 2018. BMS-986020 is a high-affinity small molecule antagonist of the LPA1R. Patients in the 600mg BID cohort exhibited significantly slower rates of FVC decline from baseline to 26 weeks versus placebo. However, dose-related hepatobiliary toxicity led to early termination of the trial. After conducting additional toxicology investigations, BMS reported that hepatobiliary toxicity was likely caused by off-target inhibition of bile acids efflux transporters such as bile salt export pump (“BSEP”).
BMS-986278 is a second generation LPA1R antagonist that is biased away from BSEP, and the results of a Phase 2 trial in 276 IPF patients with this compound were recently released at the 2023 American Thoracic Society annual meeting. The outcome of the Phase 2 trial showed a statistically significant reduction in the decline in FVC following a 26-week administration of 60mg BID dose of BMS-986278 versus placebo with or without the use of background antifibrotic therapy. A global Phase 3 trial of BMS-986278 for IPF is currently enrolling.
With regard to its high bioavailability, low plasma protein binding, and long receptor residence time in our preclinical studies, compared to the preclinical data of other LPA1R antagonists that we know are currently in development, we believe PIPE-791 has the potential to be a differentiated LPA1R therapy. We are developing PIPE-791 as a once daily (“QD”) therapy at low doses (≤ 10 mg), compared to other LPA1R antagonists, including BMS-986278, which are being studied at significantly higher dose ranges (60-120 mg) all with BID administration.
PIPE-791 for the Potential Treatment of Progressive MS
MS is a chronic, immune-mediated disease of the CNS characterized by neuroinflammation and demyelination. The three main clinical categories of MS include RRMS, Secondary Progressive MS (“SPMS”), and Primary Progressive MS (“PPMS”). We are developing PIPE-791 for the potential treatment of SPMS and PPMS, which are collectively referred to as PrMS. We believe that PIPE-791 has the potential to be a disease-modifying treatment (“DMT”) by impacting the neurodegeneration secondary to chronic demyelination and neuroinflammation, the two leading pathological contributors to clinical disability in PrMS. The development of a brain penetrant small molecule therapy that prevents worsening, reverses damage, and restores function would potentially address the major therapeutic unmet need in PrMS.
The three main clinical forms of MS have differences in prevalence and presentation. RRMS comprises 85% of newly diagnosed MS patients, and the clinical course is marked by relapses and remissions, defined as disease flare-ups followed by periods of partial recovery. Many RRMS patients eventually progress to worsening disease, and it is estimated that roughly 50% to 70% of diagnosed RRMS patients progress to SPMS within 10 to 15 years. PPMS is estimated to include approximately 10% to 15% of newly diagnosed MS patients, which is marked by a steady course of clinical progression from the time of presentation. In 2020, the global prevalence of MS was estimated to be 2.8 million patients, and we believe that more than 750,000 of this global population have PrMS (i.e., the collective population of SPMS and PPMS patients). Although substantial progress has been made in the development of effective immune-modulating treatments for RRMS, many of these approved drugs have been tested in PrMS with limited results. The relative lack of effective therapies for PrMS has further justified the exploration of novel treatment approaches. The LPA/LPA1R axis has been proposed as a potential active pathway contributing to the pathophysiology of MS. Specifically, LPA is a pro-inflammatory lipid that has been shown to be elevated in the plasma and cerebrospinal fluid (“CSF”) of MS patients and that may promote neuroinflammation and limit remyelination through the activation of the LPA1R.
We have demonstrated in our preclinical studies that blocking LPA1R with PIPE-791 reduces neuroinflammation and promotes remyelination. We further demonstrated that the biological mechanism leading to remyelination involves PIPE-791-induced oligodendrocyte formation and survival. We confirmed this remyelination was functional via observed improvements in visual evoked potential (“VEP”) latency, a clinically translatable functional biomarker of remyelination.