GPR84

In September last year, the South Korean biopharmaceutical company GPCR Therapeutics published a research paper in "Cell Communication and Signaling" about the direct interaction between two different GPCRs (CXCR4 and LPA1). Through various in vitro experiments, the company discovered that the efficacy of LPA1 inhibitors could be enhanced to its maximum potential by inhibiting CXCR4, thereby providing scientific evidence that the combination of CXCR4-LPA1 inhibitors might be a necessary condition for comprehensive antifibrotic activity. Based on this discovery, GPCR Therapeutics filed a provisional patent application for a combined therapeutic method involving CXCR4-LPA1 inhibitors. GPCR Therapeutics will collaborate with Bridge Biotherapeutics to jointly develop and commercialize this combined therapy. Bridge Biotherapeutics is conducting a phase 2a multinational clinical trial for the autonomic sympatho-inhibitor BBT-877, intended for the treatment of idiopathic pulmonary fibrosis (IPF), and is accelerating the development of its proprietary IPF product pipeline. About Idiopathic Pulmonary FibrosisIdiopathic Pulmonary Fibrosis (IPF) is a progressive chronic lung disease that leads to scarring (fibrosis) of the lungs, resulting in stiffening and loss of elasticity of the lung tissues, making breathing increasingly difficult. The efficiency of oxygen transfer in the lungs decreases, thus the process of oxygen passing from the alveoli to the blood during inhalation is compromised in IPF patients. The lung damage caused by IPF is irreversible, and currently, there are no treatment methods available that can stop or reverse the formation of scarring. The prognosis of Idiopathic Pulmonary Fibrosis is generally poor and the progression of the disease is difficult to predict. For some patients, the disease may progress slowly, whereas for others, it may advance more rapidly. On average, the life expectancy of patients is relatively short. Even in the United States, which has some of the world's leading medical conditions, there are approximately 495 cases per 100,000 people, with a median survival estimated at 2-5 years post-diagnosis. According to statistics from the Synapse database, there are a total of 341 R&D pipelines globally in the direction of idiopathic pulmonary fibrosis, with 4 approved drugs on the market, 6 projects in phase III clinical trials, 40 projects in phase II clinical trials, and 45 projects in phase I clinical trials. GPCR-class targets that are popular research targets for this clinical indication include autotaxin, LPAR1, αvβ6, etc. BMS-986278 is a lysophosphatidic acid receptor 1 (LPAR1) antagonist developed originally by BMS Company. Extensive research indicates that idiopathic pulmonary fibrosis (IPF) can be mediated by lysophosphatidic acid (LPA), which acts through several of the six known lysophosphatidic acid receptor-mediated downstream signaling pathways. The first generation LPAR1 antagonist developed by BMS Company, represented by BMS-986020, exhibited hepatobiliary toxicity and increased plasma bile acids in a phase II clinical trial. Subsequently, BMS Company conducted preclinical studies on the mechanism of hepatic toxicity with BMS-986020 and two structurally different LPA1 antagonists (BMS-986234 and BMS-986278), further confirming that the second-generation LPA1 antagonist BMS-986278 did not show hepatobiliary toxicity in preclinical and clinical safety studies. BMS-986278 is currently in phase II clinical development for the treatment of IPF and progressive fibrotic interstitial lung diseases. In addition to BMS, companies including Sanofi, UBE, Novo Nordisk, and DJS Antibodies have also been involved in the development of drugs targeting LPAR1 for the treatment of idiopathic pulmonary fibrosis. VP01 (C-21) is an AT2R agonist developed by Vicore Pharma. The company recently published research data demonstrating that C21 can reduce the content of TGFβ1 and collagen in human IPF lung slices. In a phase 2a clinical trial, C21 showed good safety and efficacy in newly treated IPF patients, maintaining stable forced vital capacity over a 36-week treatment period. Apart from Vicore Pharma, companies including MorphoSys and Emeriti Bio are also strategizing on the development of therapeutics targeting the AT2R for the treatment of idiopathic pulmonary fibrosis. In 2017, a team from Genentech published a research paper in the journal Thorax, discussing CXCL14 as a potential biomarker for Hedgehog signaling in idiopathic pulmonary fibrosis. Compared to the control group, there is a significant increase in the expression of Hedgehog-associated genes in the lung tissue of patients with Idiopathic Pulmonary Fibrosis (IPF). The most upregulated gene in IPF lung biopsy tissues and fibroblasts subjected to SHh stimulation in vitro was CXCL14, a gene that encodes a soluble secreted chemokine whose expression is inhibited in vitro by vismodegib. Overexpression of SHh in the lungs of mice induces the expression of CXCL14. Circulating levels of CXCL14 protein in the plasma of IPF patients are significantly higher than those in the control group. In cancer patients, circulating levels of CXCL14 decreased significantly after treatment with vismodegib. Therefore, the IL-13 inhibitor Lebrikizumab, originally developed by Genentech, is considered to have potential for the treatment of IPF. Treprostinil is a prostacyclin receptor agonist originally developed by United Therapeutics for the treatment of pulmonary arterial hypertension to alleviate exercise-related symptoms. Treprostinil is a stable, synthetic analog of prostacyclin that promotes vasodilation of the pulmonary and systemic arterial beds and inhibits platelet aggregation. It helps reduce symptoms in patients with Pulmonary Arterial Hypertension (PAH) and patients with pulmonary hypertension associated with interstitial lung disease. The FDA approved Treprostinil for the treatment of PAH in 2002. The first drug approved for the treatment of PAH was epoprostenol, an artificially synthesized prostacyclin, which significantly improves the quality of life for patients. However, the use of epoprostenol has been limited due to its short half-life (3-5 minutes) and instability at room temperature. The use of Treprostinil, a more stable alternative drug, has provided PAH patients with more treatment options. In 2021, clinical study data published in The Lancet Respiratory Medicine journal indicated that, for patients with interstitial lung disease and accompanying pulmonary arterial hypertension, inhaled Treprostinil improved patients' forced vital capacity (FVC) after 16 weeks compared to a placebo. This difference was most pronounced in patients with specific types of interstitial pneumonia, particularly those with Idiopathic Pulmonary Fibrosis. Inhaled Treprostinil appears to be a promising therapy for the treatment of Idiopathic Pulmonary Fibrosis. In 2021, multiple teams jointly initiated a phase III clinical trial of Treprostinil for the treatment of idiopathic pulmonary fibrosis. Nalbuphine is a κ-opioid receptor agonist and μ-opioid receptor antagonist that was originally researched and developed by Endo International plc. Currently, this medication is undergoing a Phase II clinical trial for Idiopathic Pulmonary Fibrosis (IPF). Brilaroxazine is a 5-HT1A/5-HT2A partial agonist originally researched and developed by Reviva Pharmaceuticals and is being used for the development of various clinical indications, including schizophrenia, idiopathic pulmonary fibrosis (IPF), and pulmonary arterial hypertension. Brilaroxazine has shown promising results in a Bleomycin-induced IPF rodent model when used alone or in combination with standard therapies. At present, this drug is also undergoing a Phase II clinical trial for IPF. Setogepram (PBI-4050) is a novel orally bioavailable small molecule compound developed by Liminal BioSciences. Its mechanism of action includes being an agonist for GPR40 and an antagonist for GPR84, demonstrating anti-fibrotic activity in various fibrosis models, including pulmonary fibrosis. Data from a 12-week Phase 2 clinical trial published in 2019 evaluated the safety, efficacy, and pharmacokinetics of daily oral administration of 800 mg of PBI-4050 alone or in combination with nintedanib or pirfenidone in patients with mild to moderate idiopathic pulmonary fibrosis (IPF). The 12-week open-label study investigated the effects of PBI-4050 in monotherapy in 9 patients, combined with nintedanib in 16 patients, and combined with nintedanib or pirfenidone in another 16 patients. The pharmacokinetic profiles were similar in both the PBI-4050 monotherapy group and the PBI-4050+nintedanib combination group, whereas the pharmacokinetics were reduced in the PBI-4050+pirfenidone group. There were no significant changes in Forced Vital Capacity (FVC) from baseline to week 12 in either the PBI-4050 monotherapy or the PBI-4050+nintedanib combination group. In contrast, a statistically significant decline in the percentage of predicted FVC was observed after 12 weeks of treatment with PBI-4050+pirfenidone. The stability of FVC between baseline and week 12 when using PBI-4050 alone or in combination with nintedanib was encouraging.

This article will introduce the GPCR targets and pipelines that received attention for Novartis, Bristol Myers Squibb, Amgen, Bayer, and Gilead at the JP Morgan Healthcare Conference 2024. For more details, please follow the link below. GPCR Targets and Pipeline at the JP Morgan Healthcare Conference 2024 (2)GPCR Targets and Pipeline at the JP Morgan Healthcare Conference 2024 (3)GPCR Targets and Pipeline at the JP Morgan Healthcare Conference 2024 (4)GPCR Targets and Pipeline at the JP Morgan Healthcare Conference 2024 (5)Novartis in JPM 2024Novartis's differentiated characteristics provide an extremely attractive opportunity for creating value for shareholders: it is an innovation-driven pharmaceutical company with 4 core therapeutic areas and 2+3 technology platforms. Over the past year, Novartis has signed more than 15 strategic deals totaling over $6 billion in order to bolster our product portfolio within key therapeutic areas and technology platforms. Promoting three breakthrough technologies to unlock significant mid- to long-term growth potential for Novartis. Entresto (Sacubitril/Valsartan) achieved an annualized sales figure of $5.9 billion in the third quarter, with a 31% increase in Q3: Sacubitril is a neprilysin inhibitor, which as a single agent has not yet been approved for marketing; Valsartan is an AT1R receptor antagonist. The combination formulation of Sacubitril and Valsartan, developed by Novartis, is used to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure and reduced ejection fraction. Atrasentan is currently undergoing a phase 3 clinical study with clinically meaningful primary endpoints: Atrasentan is an ETA receptor antagonist, currently in phase 3 clinical trials for the treatment of immunoglobulin A (IgA) nephropathy. Lutathera (Lutetium Dotatate LU-177) ongoing phase 3 (NETTER-2) results show the potential of radioligand therapy in early-stage gastroenteropancreatic neuroendocrine tumors (GEP-NETs): Lutathera is a radiopharmaceutical consisting of 177 Lu-labeled somatostatin analog, with the mechanism of action being an SSTR2 receptor antagonist. Lutathera features a high uptake in tumors with a prolonged retention time; biodistribution-wise, Lutathera has a lower systemic retention, resulting in reduced toxicity and associated risks. Bristol Myers Squibb in JPM 2024Bristol Myers Squibb is writing a new chapter in its history, entering another period of innovation, and will continue to provide patients with innovative medications. In 2023, the company has expanded its product portfolio, which has become more diverse and robust, comprising 11 major brands spanning across four key therapeutic areas. The company has 12 assets at or entering the registration phase, with over 30 assets in early-stage clinical development. In three primary directions, consolidate the company's leading position. In the fields of immunology and neuroscience, influence continues to expand. BMS-986278 is a LPA1 receptor antagonist currently in Phase 3 clinical development for the treatment of idiopathic pulmonary fibrosis or progressive pulmonary fibrosis. In addition, two other LPA1 receptor antagonists from the company, 18F-BMS-986327 and BMS-986337, are in Phase 1 clinical trials. Both GPRC5D CAR-T and dual-target BCMAxGPRC5D CAR-T products target the Class C GPCR member GPRC5D. In August 2023, a dual-target GPRC5DxCD3 bispecific antibody developed by Johnson & Johnson was approved for marketing, making GPRC5D a popular research target. BMS-986340 is a monoclonal antibody against CCR8, intended for the treatment of solid tumors and currently in Phase 1 clinical research. Amgen in JPM 2024Amgen is using a range of novel therapeutics to treat a variety of severe illnesses, including common conditions such as obesity, heart disease, migraines, chronic kidney disease, as well as rare diseases, cancer, and immune disorders. The Four Pillars of Promoting Long-Term Growth. The pipeline projects for which the company is expected to achieve significant milestones in 2024. MariTide (maridebart cafraglutide) is a dual-specificity molecule currently undergoing Phase II clinical trials, which acts as a GIPR antagonist and a GLP-1R agonist. In addition, AMGEN's small molecule candidate drug AMG 786 (target not disclosed) is in Phase I clinical study. AMGEN hopes that the combined use of these two interventions will allow for quicker and more effective weight loss, as well as better weight maintenance. Bayer in JPM 2024Bayer continues to drive the sales of a multitude of medications, maximizing the full commercial value of its existing product portfolio while persistently redirecting resources towards brands and assets with high innovative potential. Focusing on four primary areas, which include oncology, cardiovascular, neurological and rare diseases, as well as immunological disorders. Several pipelines will reach multiple important milestones. Elinzanetant is being explored as a non-hormonal therapeutic option for menopause with significant potential. It is a dual NK1 and NK3 receptor antagonist currently in Phase III clinical trials. The OASIS clinical trial program for Elinzanetant has two pivotal Phase III studies that have met all primary and key secondary endpoints. BAY-3375968 is a monoclonal antibody targeting the CCR8 receptor and is being clinically developed for the treatment of solid tumors. In vitro studies have shown that BAY-3375968 can selectively deplete human CCR8-positive Tregs through antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). BAY-3178275 is an antagonist targeting GPR84 and is undergoing Phase I clinical development as a treatment for diabetic neuropathic pain. Gilead in JPM 2024Gilead's robust execution in 2023 has become a catalyst for 2024, accelerating the development of its oncology business while maintaining sustained growth in its leading portfolio of HIV products. Gradually establishing leadership in cell therapy and CAR-T direction. In 2024, we will see updates across multiple research and development pipelines. GS-1811 is an inhibitor targeting CCR8 and is currently being developed clinically for the treatment of solid tumors. GS-1811 is intended to selectively deplete tumor-infiltrating regulatory T cells, which exert immunosuppressive effects within the tumor microenvironment. It is presently in Phase 1 clinical development. This drug may potentially be used in combination with multiple Gilead medications, such as Trodelvy. GS-6201 is a selective small molecule antagonist targeting the A2bR receptor. It is undergoing Phase 1 clinical trials for conditions including lung cancer.

Provided R&D update on GPCR-targeted pipeline, including nomination of lead candidate for OXER1 antagonist program Closed June 30, 2023 with over CAD 19 million cash on hand, expecting to provide cash runway into December 2023 Net loss from continuing operations of CAD 9 million during the quarter ended June, 2023 compared to CAD 6.4 million during the second quarter of 2022 Entry into Arrangement Agreement with Structured Alpha LP potentially providing minority shareholders US$8.50 in cash per Common Share LAVAL, QC and CAMBRIDGE, England, Aug. 8, 2023 /PRNewswire/ - Liminal BioSciences Inc. (Nasdaq: LMNL) ("Liminal BioSciences" or the "Company"), a development-stage biopharmaceutical company focused on discovering and developing distinctive novel small molecule therapeutics for metabolic, inflammatory, and fibrotic diseases, today reported its financial results for the second quarter ended June 30, 2023. "I am very pleased with the progress we have made in the past quarter, marking a significant leap forward in our mission to develop novel treatments for metabolic, fibrotic and inflammatory conditions," stated Bruce Pritchard, Chief Executive Officer of Liminal BioSciences. "Our dedication to innovation and scientific excellence has led to several key milestones, bringing us closer to clinical studies in which we aim to seek early biological validation of our assets." Recent R&D milestones LMNL6326 was nominated as the lead preclinical candidate for our OXER1 antagonist development program, targeting the treatment of eosinophil-driven diseases. Advancement of clinical trial application (CTA) enabling preclinical studies of LMNL6511 to support CTA filing for Phase 1 clinical trial in H2 2023. Insights gained from In Vivo preclinical studies of LMNL6511 to further refine potential indications' spectrum. GPR40 agonist development program on track and the Company aims to identify potent, low molecular weight GPR40 agonists without significant PPARy activity in 2023. Upcoming R&D Milestones GPR84 antagonist program On-going In-vivo experiments expected to narrow down selection of a lead clinical indication in 2023. Ongoing Clinical Trial Application (CTA)-enabling studies for first-in-human clinical trial in 2023. Expect to file CTA for first in-human Phase 1 clinical trial and to commence clinical trial in H2 2023. OXER1 antagonist program Aim to file CTA/Investigational New Drug (IND) for LMNL6326 first-in-human clinical trial in 2024. GPR40 antagonist program Aim to identify potent, low molecular weight GPR40 agonists without significant PPARγ activity in 2023. Arrangement with SALP On July 11, 2023, we entered into a definitive arrangement agreement (the "Arrangement Agreement") with Structured Alpha LP ("SALP") under which SALP will acquire all of the issued and outstanding common shares of Liminal BioSciences (the "Common Shares") that it does not already own, subject to customary closing conditions. The transaction will be implemented by way of plan of arrangement under the Canada Business Corporations Act. Under the terms of the Arrangement Agreement, Liminal BioSciences shareholders (other than SALP and its affiliates or associates) will receive US$8.50 in cash per Common Share. Liminal BioSciences intends to mail a management information circular to its shareholders in the coming weeks for the special meeting of shareholders anticipated to be held virtually on September 15, 2023 to approve the proposed transaction. The transaction is expected to close no later than September 30, 2023, subject to satisfaction of customary closing conditions. The transaction is not subject to any financing condition. Second Quarter Ended June 30th 2023 Financial Results All figures presented in this section are in Canadian dollars. Cash and cash equivalents were $19.3 million at June 30, 2023 while our working capital, i.e., the current assets net of current liabilities, was $16.4 million. Research and development expenses were $4.3 million during the second quarter of 2023 compared to $3.9 million for the second quarter of 2022. The increase of $0.4 million in R&D expenses during the quarter ended June 30, 2023 compared to the corresponding period in 2022 was mainly attributable to an increase of $0.7 million in preclinical studies expense associated with the advancement of our GPR84 and OXER1 antagonist programs. This increase was partially offset by a $0.3 million decrease in personnel costs due to reductions in our workforce. Administration expenses were $4.8 million for the second quarter of 2023 compared to $4.5 million for the second quarter of 2022. The decrease of $0.3 million in administration expenses during the quarter ended June 30, 2023 compared to the corresponding period in 2022 was mainly attributable to an increase of $0.9 million in professional fees incurred in connection with the non-binding proposal received from SALP, which was partially offset by a $0.6 million decrease in reduced directors' and officers' insurance premiums. Net loss from continuing operations, net of taxes was $9.0 million for the second quarter of 2023 compared to $6.3 million for the second quarter of 2022. This decrease of $2.6 million was mainly driven by the decrease in foreign exchange gains of $1.7 million, a decrease in the gains from the change in fair value of the warrant liability that is measured at FVPL of $1.3 million, an increase in administration expenses of $0.3 million reflecting the increase in professional fees and an increase in R&D expenses of $0.4 million as a result of an increase in preclinical studies expense associated with the advancement of our GPR84 and OXER1 antagonist programs. These increases in expenses were partially offset by a $1.0 million decrease in finance costs. Total loss from discontinued operations Total loss from discontinued operations was $0.2 million during the quarter ended June 30, 2023 compared to a total income from discontinued operations of $0.1 million during the corresponding period in 2022. This variation was mainly attributable to to changes in the underlying assumptions used to value the provision pertaining to the CDMO. Net Loss was $9.1 million for the second quarter of 2023 compared to $6.2 million for the second quarter of 2022. This increase in the net loss was mainly driven by the decrease in foreign exchange gains of $1.7 million, a decrease in the gains from the change in fair value of the warrant liability that is measured at FVPL of $1.3 million, an increase in administration expenses of $0.3 million reflecting the increase in professional fees and an increase in R&D expenses of $0.4 million as a result of an increase in preclinical studies expense associated with the advancement of our GPR84 and OXER1 antagonist programs. These increases in expenses were partially offset by a $1.0 million decrease in finance costs. About Liminal BioSciences Inc. Liminal BioSciences is a development-stage biopharmaceutical company focused on discovering and developing novel and distinctive small molecule therapeutics that modulate G protein-coupled receptor pathways (GPCRs). The Company is designing proprietary novel small molecule therapeutic candidates with the intent of developing best/first in class therapeutics for the treatment of metabolic, inflammatory and fibrotic diseases with significant unmet medical needs, using its integrated drug discovery platform, medicinal chemistry expertise and deep understanding of GPCR biology. The Company's pipeline is currently made up of three programs. LMNL6511, a selective antagonist for the GPR84 receptor, is expected to commence a Phase 1 clinical trial in the second half of 2023. LMNL6326 has been nominated as the preclinical candidate for its OXER1 antagonist program, and the Company is also developing GPR40 agonists. Both the OXER1 antagonist program and GPR40 agonist program are currently in the preclinical stage. In addition to these programs, the Company continues to explore other development opportunities to add to its pipeline. Liminal BioSciences has active business operations in Canada and the United Kingdom. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Some of the forward-looking statements can be identified by the use of forward-looking words. Statements that are not historical in nature, including the words "anticipate," "expect," "suggest," "plan," "believe," "intend," "estimate," "target," "project," "should," "could," "would," "may," "will," "forecast" and other similar expressions are intended to identify forward-looking statements. These statements include those related to Liminal BioSciences' objectives, strategies and businesses that involve risks and uncertainties. Forward–looking information includes statements concerning, among other things: advancement of Liminal Biosciences' candidates or development programs, including the timing and outcome of the potential development of the Company's R&D programs such as the development of LMNL6511, LMNL6326 and our GPR40 agonist discovery program; the timing of initiation or nature of preclinical and clinical trials, including the expected commencement of a Phase 1 clinical trial of LMNL6511 in the second half of 2023; the contemplated potential therapeutic areas, including Eosinophilic mediated diseases and T2D; the potential for our development programs to address significant unmet medical needs; our ability to add new development opportunities to our pipeline; our ability to continue to comply with Nasdaq Listing Rule 5450(a)(1) to remain listed on the Nasdaq Capital Market; the ability to complete and the timing of completion of the transactions contemplated by the arrangement agreement between Liminal BioSciences and SALP, including the parties' ability to satisfy the conditions to the consummation of the transaction and the possibility of any termination of the agreement; our expected cash runway and our ability to actively seek and close on opportunities to monetize non-core assets or commercial opportunities related to our assets. These statements are "forward-looking" because they are based on our current expectations about the markets we operate in and on various estimates and assumptions. Actual events or results may differ materially from those anticipated in these forward-looking statements if known or unknown risks affect our business, or if our estimates or assumptions turn out to be inaccurate. Among the factors that could cause actual results to differ materially from those described or projected herein include, but are not limited to, risks associated with: the Company's ability to develop, manufacture, and successfully commercialize product candidates, if ever; the impact of current global economic conditions and other geopolitical tensions on the Company's workforce, business operations, clinical development, regulatory activities and financial and other corporate impacts; the availability of funds and resources to pursue R&D projects, clinical development, manufacturing operations or commercialization opportunities; the successful and timely initiation or completion of preclinical and clinical trials; the ability to take advantage of financing opportunities or business opportunities in the pharmaceutical industry, uncertainties associated generally with research and development, clinical trials and related regulatory reviews and approvals; our ability to comply with Nasdaq listing rules and remain listed on the Nasdaq Capital Market and general changes in economic conditions, including as a result of increased inflation, bank failures and rising interest rates. You will find a more detailed assessment of these risks, uncertainties and other risks that could cause actual events or results to materially differ from our current expectations in the filings and reports the Company makes with the U.S. Securities and Exchange Commission and Canadian Securities Administrators, including in the Annual Report on Form 20-F for the year ended December 31, 2022, as well as other filings and reports Liminal Biosciences' may make from time to time. As a result, we cannot guarantee that any given forward-looking statement will materialize. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements and estimates, which speak only as of the date hereof. We assume no obligation to update any forward-looking statement contained in this press release even if new information becomes available, as a result of future events or for any other reason, unless required by applicable securities laws and regulations. SOURCE Liminal BioSciences Inc.