• BREAKOUT Study is Palatin's third clinical program for the potential treatment of inflammatory diseases with melanocortin agonists
• Primary endpoint of the BREAKOUT Study is a 50% reduction in urine protein/creatinine (UP/Cr) ratio after six months of combined therapy (RAAS inhibition therapy plus bremelanotide)

CRANBURY, N.J., Jan. 19, 2023 /PRNewswire/ -- Palatin Technologies, Inc. (NYSE American: PTN), a biopharmaceutical company developing first-in-class medicines based on molecules that modulate the activity of the melanocortin receptor system, today announced the initiation of a Phase 2b clinical trial with the melanocortin agonist, bremelanotide. The BREAKOUT Study, entitled "A Phase 2b, Multicenter, Open-Label, Prospective Study of BREmelanotide in DiAbetic Kidney Disease to Assess the Efficacy in Reducing Urinary PrOtein and Maintaining Podocyte Density and FUncTion" initiated patient screening/enrollment in December 2022, and currently expects to initiate patient dosing in January 2023.

The BREAKOUT Study (BMT-701) is designed to enroll up to 45 subjects, with biopsy-proven type II diabetic kidney disease and >1000 mg/gm UP/Cr ratio. Patients will administer bremelanotide therapy twice a day (BID), in addition to their maximum tolerated RAAS inhibition therapy, for six months, followed by a 12-month follow-up period. The primary endpoint of the study is a 50% reduction in their urine protein/creatinine (UP/Cr) ratio after six months of combined therapy (RAAS inhibition therapy plus bremelanotide). Secondary endpoints include analyses of partial remission, clinical remission and change in eGFR.

"We are pleased to initiate the Phase 2 BREAKOUT study which utilizes our robust melanocortin anti-inflammation/pro-resolution platform," said Carl Spana, Ph.D., President and CEO of Palatin. "We continue to execute on our strategy that the melanocortin system is an important mechanism for the resolution of inflammation and promotion of tissue repair. With the BREAKOUT Study, we now have three active melanocortin-based clinical programs: our MELODY-1 Phase 3 dry eye disease trial, a Phase 2 ulcerative colitis trial and a Phase 2 diabetic kidney disease trial, all with data readouts throughout calendar year 2023."

The open label BREAKOUT Study will enroll patients at up to seven U.S. sites. Completed patient data will be reviewed and assessed throughout the Study. Based on current enrollment estimates, the BREAKOUT Study is expected to complete enrollment in the third quarter of calendar year 2023, with final topline data by end of the first quarter of calendar year 2024.

"Diabetic nephropathy is one of the leading causes of end-stage renal disease across the world. It is characterized by progressive loss of kidney function over a 10-to-15-year period," said James A. Tumlin MD, CEO and Founder of NephroNet Clinical Trials Consortium. "This exciting new development of using bremelanotide as a first in class activator for a new treatment pathway in diabetic kidney disease, could potentially offer kidney doctors new and powerful tools to treat this very common disease."

About Diabetic (Nephropathy) Kidney Disease

Diabetic nephropathy is the most common cause of end-stage renal disease in the United States and other developed countries. Approximately 30 million U.S. patients have chronic kidney disease  secondary to the combination of hypertension and Type II diabetes mellitus. Despite this remarkable prevalence, clinicians have little consensus on what comprises optimal therapy. While the widespread use of RAAS blockade utilizing angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers and other maneuvers have slowed disease progression, approximately one-third of patients with Type II diabetic nephropathy will progress to end-stage renal disease. As a result, much effort has been devoted to understanding the mechanisms by which the diabetic condition leads to the typical histopathologic changes, including mesangial expansion, thickened basement membranes, and loss of podocyte density and functionality. 

There is evidence that injury to the glomerular podocyte is central to the pathogenesis of diabetic nephropathy and that clinical treatments should be directed toward maintaining podocyte viability. Podocytes are highly differentiated neuron-like cells with limited cell division and replacement capacity. They are central to the support and maintenance of glomerular capillary networks and function as the final barrier in glomerular filtration. Evidence from pre-clinical animal model studies suggests that podocyte losses precede and contributes to progressive diabetic glomerulopathy. Hyperglycemia leading to increased intracellular calcium and oxidant load contributes to accelerated podocyte apoptosis, autophagy, and cellular detachment.

About Melanocortins and Kidney Disease

Melanocortin receptors ("MCr") comprise a complex system of five different receptors with broad and varying physiologic functions. One of these receptors, MC1r, signals through a G-protein coupled pathway that leads to activation of adenylate cyclase and ultimately, stimulation of the serine-threonine kinase activity of protein kinase A. A growing body of work in cell signaling and function of the glomerular podocyte suggests that protein kinase A regulates the formation of footplate processes, cell attachment, and apoptosis. MC1r activation may stabilize podocyte function and survival in diabetes and other conditions of glomerular diseases.

About Melanocortin Receptor Agonists and Inflammation

The melanocortin receptor  system has effects on inflammation, immune system responses, metabolism, food intake, and sexual function. Modulation of the five melanocortin receptors, MC1r through MC5r, using receptor-specific agonists, which activate receptor function, or receptor-specific antagonists, which block receptor function, can have medically significant pharmacological effects. Many tissues and immune cells located throughout the body, including the gut, kidney and eye, express melanocortin receptors, empowering our opportunity to directly activate natural pathways to resolve disease inflammation.

About Palatin

Palatin is a biopharmaceutical company developing first-in-class medicines based on molecules that modulate the activity of the melanocortin receptor systems, with targeted, receptor-specific product candidates for the treatment of diseases with significant unmet medical need and commercial potential. Palatin's strategy is to develop products and then form marketing collaborations with industry leaders to maximize their commercial potential. For additional information regarding Palatin, please visit Palatin's website at www.Palatin.com and follow Palatin on Twitter at @PalatinTech.

Forward-looking Statements

Statements in this press release that are not historical facts, including statements about future expectations of Palatin, such as statements about clinical trials and results, are "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and as that term is defined in the Private Securities Litigation Reform Act of 1995. Palatin intends that such forward-looking statements be subject to the safe harbors created thereby. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that could cause Palatin's actual results to be materially different from its historical results or from any results expressed or implied by such forward-looking statements. Palatin's actual results may differ materially from those discussed in the forward-looking statements for reasons including, but not limited to, results of clinical trials, regulatory actions by the FDA and other regulatory and the need for regulatory approvals, Palatin's ability to fund development of its technology and establish and successfully complete clinical trials, the length of time and cost required to complete clinical trials and submit applications for regulatory approvals, products developed by competing pharmaceutical, biopharmaceutical and biotechnology companies, commercial acceptance of Palatin's products, and other factors discussed in Palatin's periodic filings with the Securities and Exchange Commission. Palatin is not responsible for updating for events that occur after the date of this press release.

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