Treatment with PBI-4050 for 12 weeks positively affected biomarkers known to have antifibrotic activity
New clinical data presented at the American Thoracic Society 2018 International Conference
Overview of Data for PBI-4050 for Idiopathic Pulmonary Fibrosis
LAVAL, QUEBEC, CANADA – May 22, 2018 – Prometic Life Sciences Inc. (TSX: PLI) (OTCQX: PFSCF) (Prometic) today announced an oral presentation of new clinical data assessing the effect of its lead small molecule candidate, PBI-4050, on blood biomarkers for the treatment of idiopathic pulmonary fibrosis (IPF) at the American Thoracic Society (ATS) 2018 International Conference. Four additional poster presentations on PBI-4050 and the Company’s lead plasma-derived product candidate, Ryplazim™(plasminogen), were also delivered at the conference.
“Our evaluation of the effect of PBI-4050 on blood biomarkers linked to the fibrotic process in IPF patients has shown the positive impact the drug candidate has on antifibrotic pathways,” said Lyne Gagnon, Ph.D., Prometic’s vice president of R&D preclinical. “These most recent data demonstrated that PBI-4050 was well-tolerated when given alone or in combination with nintedanib or pirfenidone, two marketed IPF treatments. In addition, PBI-4050 given alone, as well as in combination with nintedanib, showed promise in stopping the decline in lung function, something that current treatments have been unable to achieve.”
Pierre Laurin, president and chief executive officer of Prometic, added, “The data generated to date have demonstrated the potential of PBI-4050 in addressing debilitating fibrotic diseases, such as IPF. The data presented at this year’s ATS conference further enhance our confidence that PBI-4050 and Ryplazim™ are well-positioned to treat the full spectrum of the IPF condition. We look forward to continuing our clinical development of these two promising drug candidates to address the significant unmet needs of patients suffering from IPF.”
The Oral Presentation on the New Clinical Data
The oral presentation entitled, “Evaluation of the effect of PBI-4050 Alone or in Combination with Pirfenidone or Nintedanib on Blood Biomarkers Linked to the Fibrotic Process in IPF Patients,” was presented by Dr. Gagnon. The data presented included:
- PBI-4050 significantly increased levels of biomarkers known to have antifibrotic effects. Following 12 weeks of treatment, PBI-4050 increased the levels of IL-9, known to have antifibrotic activity, by 35% (p < 0.05); IL-7, which acts as a counter-regulator to the pro-fibrotic cytokine TGF-β, by 14% (p < 0.05); and MIP-1β, of which an increase may reflect a change in the balance between a pro-fibrotic and an inflammatory, wound-healing environment, by 11% (p < 0.05).
- PBI-4050 positively affected IL-1Ra, which could have a protective role in fibrotic diseases, by 98% (p = 0.08).
- PBI-4050 in combination with nintedanib significantly decreased CCL-18 levels by 10% (p < 0.01). CCL-18 is a recognized marker of disease severity and elevated levels in serum are associated with a high-risk of disease progression.
- Patients who responded to PBI-4050 treatment had significantly higher serum plasminogen levels, indicating the importance of plasminogen in IPF.
Key Data Presented in Four Additional Posters
Key data presented in four additional poster presentations entitled, “PBI-4050, a Novel First-in-Class Agent, Improves Hypoxia/Sugen Induced Pulmonary Arterial Hypertension in Rats,” “PBI-4050 Therapy Selectively Improves Pulmonary Hypertension, Lung Remodeling and Right Ventricular Function in Heart Failure with Reduced Ejection Fraction,” “PBI-4050, a Novel First-in-Class Antifibrotic Agent, Improves Pulmonary Hypertension and Fibrosis, as Well as Right Ventricular Hypertrophy and Fibrosis in Monocrotaline-Treated Rats,” and “Plasminogen Reduces Lung Fibrosis in the Bleomycin-Induced Lung Fibrosis Model,” included:
- In a rat model of pulmonary arterial hypertension (PAH), PBI-4050 demonstrated strong efficacy in improving the severity of PAH. PBI-4050 showed a different efficacy profile when compared to standard of care, sildenafil, supporting the possible benefit of combination therapy;
- In a rat model of pulmonary hypertension (PH), PBI-4050 showed promise as a potential treatment for group II PH by reducing lung fibrosis and remodeling;
- In a different rat model of PH, PBI-4050 demonstrated superior efficacy on PH, right ventricular hypertrophy, right ventricle fibrosis and interstitial pulmonary fibrosis, as compared to sildenafil;
- In a mouse model of pulmonary fibrosis, plasminogen reduced fibrosis and fibrotic markers, demonstrating its potential as a treatment for IPF.
About Idiopathic Pulmonary Fibrosis (IPF) and Acute Exacerbation
Idiopathic pulmonary fibrosis (IPF) is a chronic, devastating, and ultimately fatal disease characterized by a progressive decline in lung function. It is a specific type of interstitial lung disease in which the small air sacs of the lung, the “alveoli,” gradually become replaced by fibrotic (scar) tissue and is the cause of worsening dyspnea (shortness of breath). IPF is usually associated with a poor prognosis. The term “idiopathic” is used because the cause of pulmonary fibrosis is still unknown. IPF usually occurs in adult individuals of between 50 and 70 years of age, particularly those with a history of cigarette smoking, and affects men more often than women. IPF affects approximately 130,000 people in the United States, with about 48,000 new cases diagnosed annually. Nearly 40,000 people with IPF die each year, a mortality rate similar to breast cancer. The five-year mortality rate for patients with IPF is estimated to range from 50% to 70%. Acute exacerbation of IPF (AE-IPF) is defined as a sudden acceleration of the disease or an idiopathic acute injury superimposed on diseased lung tissue that leads to a significant decline in lung function. An AE-IPF is associated with a mortality rate as high as 85%, with mean survival periods between 3 to 13 days.
About Fibrotic Process
Fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) in damaged or inflamed tissues and is the common pathological outcome of many inflammatory and metabolic diseases. Numerous clinical conditions can lead to organ fibrosis and functional failure; in many disorders, acute or persistent inflammation is crucial to trigger the fibrotic response. The production of various profibrotic cytokines and growth factors by innate inflammatory cells results in the recruitment and activation of ECM-producing myofibroblasts. There is currently a great need for therapies that could effectively target pathophysiological pathways involved in fibrosis. PBI-4050, a synthetic ligand of GPR40 and GPR84, acts on cells involved in the fibrotic pathway: macrophages, fibroblasts and epithelial cells. Moreover, PBI-4050 reduces fibrosis in animal models of kidney, lung, heart, liver, pancreas and skin fibrosis. GPR40 and GPR84 are both modulated in models of fibrotic diseases and mice with a deletion in GPR40 have increased renal interstitial fibrosis in response to ischemia, unilateral ureteral obstruction (UUO), and adenine-induced nephropathy models, while GPR84 knockout mice have reduced kidney fibrosis in a model of adenine-induced nephropathy.
PBI-4050 is an orally active lead drug candidate with excellent safety and efficacy profiles demonstrated in a large number of animal models of fibrosis affecting different organs, including the lung, liver, heart, kidney, and pancreas. The effects of PBI-4050 demonstrated in animal models have been replicated in Phase 2 studies in IPF, in metabolic syndrome with type 2 diabetes and in Alström syndrome. PBI-4050 is entering pivotal placebo-controlled phase 3 clinical trials for the treatment of IPF and has already started placebo-controlled phase 2 trials in metabolic syndrome and type 2 diabetes patients.
Plasminogen is a naturally occurring protein that is synthesized by the liver and circulates in the blood. Activated plasminogen, plasmin, is a fundamental component of the fibrinolytic system and is the main enzyme involved in the lysis of blood clots and clearance of extravasated fibrin. Plasminogen therefore is vital in wound healing, cell migration, tissue remodeling, angiogenesis and embryogenesis
Prometic (www.prometic.com) is a biopharmaceutical corporation with two drug discovery platforms focusing on unmet medical needs. The first platform (small molecule therapeutics) stems from the discovery of two receptors which we believe are at the core of how the body heals: namely, promoting tissue regeneration and scar resolution as opposed to fibrosis. One of the lead drug candidates emerging from this platform, PBI-4050, is expected to enter pivotal phase 3 clinical trials for the treatment of Idiopathic Pulmonary Fibrosis (IPF). The second drug discovery and development platform (plasma-derived therapeutics) leverages Prometic’s experience in bioseparation technologies used to isolate and purify biopharmaceuticals from human plasma. The Corporation’s primary goal with respect to this second platform is to address unmet medical needs with therapeutic proteins not currently commercially available, such as Ryplazim™ (plasminogen). We are also leveraging this platform’s higher recovery yield potential to advance established plasma-derived therapeutics such as Intravenous Immunoglobulin (IVIG). Furthermore, the Corporation is continuing to secure its plasma supply through the execution of third party contracts and expansion of its own collection activities for its plasma processing needs. The Corporation also provides access to its proprietary bioseparation technologies to enable pharmaceutical companies in their production of non-competing biopharmaceuticals. Recognized as a bioseparations expert, the Corporation derives revenue from this activity through sales of affinity chromatography media which contributes to offset the costs of its own R&D investments.
We are headquartered in Laval, Quebec (Canada) and have R&D facilities in Canada, the United Kingdom (“UK”) and the United States (“USA”), manufacturing facilities in Canada and the Isle of Man and corporate and business development activities in Canada, the USA, Europe and Asia.
Forward Looking Statements
This press release contains forward-looking statements about Prometic’s objectives, strategies and businesses that involve risks and uncertainties. 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. Such risks and assumptions include, but are not limited to, Prometic’s ability to develop, manufacture, and successfully commercialize value-added pharmaceutical products, the availability of funds and resources to pursue R&D projects, the successful and timely completion of clinical studies, the ability of Prometic to take advantage of business opportunities in the pharmaceutical industry, uncertainties related to the regulatory process and general changes in economic conditions. You will find a more detailed assessment of the risks that could cause actual events or results to materially differ from our current expectations in Prometic’s Annual Information Form for the year ended December 31, 2017, under the heading “Risk and Uncertainties related to Prometic’s business”. As a result, we cannot guarantee that any forward-looking statement will materialize. We assume no obligation to update any forward-looking statement 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. All amounts are in Canadian dollars unless indicated otherwise