PCS12852

A Safer Solution for Postoperative GI Dysfunction and Opioid-induced Constipation

PCS12852 Targets GI Motility Disorders

PCS12852 is a novel, potent, and highly selective 5-HT4 receptor agonist for treating Gastrointestinal (GI) motility disorder, also called gastrointestinal dysfunction (POGD). These GI disorders take many forms, including chronic constipation, constipation-predominant irritable bowel syndrome, functional dyspepsia, and gastroparesis. GI mobility disorders that develop following GI surgery are the most common cause of prolonged hospital stays, leading to increased healthcare costs.

Other 5-HT receptor antagonists have been successful in treating GI motility disorders. However, these often have less 5-HT4 selectivity and are associated with cardiovascular side effects due to the drugs binding to other receptors. In contrast, PCS12852 has been shown in clinical trials to increase GI function with no serious adverse effects.

License Agreement

On August 19, 2020, we acquired an exclusive license from Yuhan Corporation to develop, manufacture, and commercialize PCS12852 globally except for South Korea.

An Investigational New Drug Now in Development

Clinical Development

Previous History

Previous History

Yuhan Corporation previously conducted two clinical studies with PCS12852 to assess its initial safety and tolerability. In the first trial, PCS12852 was shown to increase stool frequency with faster onset than those who received prucalopride (an FDA-approved drug for chronic idiopathic constipation). When compared to the prucalopride group, the PCS12852 dose group showed higher stool frequency and had increased spontaneous bowel movements for 24 hours following their first dose. During this 7-day multiple dosing study, all doses of PCS12852 administered to patients were safe and well-tolerated with no serious adverse events.

The second study conducted was a Phase 1/2A. The purpose of this trial was to evaluate the safety, tolerability, and dosing regimen of PCS12852 in immediate- and delayed-release formulations after multiple oral dosing. Following single and multiple administrations, PCS12852 was safe and well-tolerated. The most frequent adverse effects (headache, nausea, and diarrhea, which are commonly observed with other 5-HT4 agonists) were comparable with those of the prucalopride 2 mg group.

Extensive toxicological studies for PCS12852, also previously conducted by Yuhan, demonstrated the product’s safety, allowing for a quick transition into Phase 2 studies.

Current Status & Clinical Trials

Current Status & Clinical Trials

With guidance from the FDA, we are planning a Phase 2A trial for PCS12852. The trial's purpose will be to establish a dosage regimen for PCS12852 in treating GI motility disorders, including POGD. We will use the data collected from this study to identify a safe and effective dosage regimen of PCS12852 for use in a larger pivotal study.

Benefits of PCS12852

PCS12852 is a more potent and selective alternative to existing 5HT4 agonists and carries a lower risk of cardiovascular side effects.

  • 5HT4 receptor agonist.
  • More potent and selective to 5HT4 than other 5HT4 drugs.
  • Lower cardiovascular toxicity risk.
  • Wider safety margin against cardiovascular side effects than other 5HT4 drugs.
  • Increases gastric emptying rate.
  • No serious side effects in clinical studies to date.

Market Landscape

Decreasing Patient Suffering and Cost of Care

Gastroparesis is a gastric mobility disorder that affects the nerves and muscles of the stomach, leading to postprandial fullness, nausea, vomiting, and bloating. It is the most common cause of prolonged hospital stays following GI surgery, leading to increased healthcare costs. Current treatments for gastroparesis carry an increased risk of severe side effects such as heart attacks, neurological toxicity, and suicidal ideation. Having shown no serious adverse effects in clinical studies, PCS12852 may be a promising new treatment for POGD.

$1 Billion

Market1

More than 4,000,000

Patients in the U.S.2

1. Source: Gastroparesisclinic.org; Swinburne University of Technology

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  • Pharmacokinetics and Efficacy
    • Lee HA, Moon SJ, Yoo H, Kim MK, Jang SB, Lee S, Kim S, Lee YH12852, a Potent and Selective Receptor Agonist of 5- hydroxytryptamine, Increased Gastrointestinal Motility in Healthy Volunteers and Patients With Functional Constipation. Clin Transl Sci. 2020 Nov 17. doi: 10.1111/cts.12924. Epub ahead of print. PMID: 33202093.
    • Kim S, Lee HA, Jang SB, Lee H. A population pharmacokinetic-pharmacodynamic model of YH12852, a highly selective 5-hydroxytryptamine 4 receptor agonist, in healthy subjects and patients with functional constipation. CPT Pharmacometrics Syst Pharmacol. 2021;00:1–12. https://doi.org/10.1002/psp4.12664

Gastroparesis

  • Epidemiology
    • Jung HK, Choung RS, Locke GR 3rd, Schleck CD, Zinsmeister AR, Szarka LA, Mullan B, Talley NJ. The incidence, prevalence, and outcomes of patients with gastroparesis in Olmsted County, Minnesota, from 1996 to 2006. 2009 Apr;136(4):1225-33. doi: 10.1053/j.gastro.2008.12.047. Epub 2008 Dec 24. PMID: 19249393; PMCID: PMC2705939.
  • Syed AR, Wolfe MM, Calles-Escandon Epidemiology and Diagnosis of Gastroparesis in the United States: A Population-based Study. J Clin Gastroenterol. 2020 Jan;54(1):50-54. doi: 10.1097/MCG.0000000000001231. PMID: 31135630; PMCID: PMC6903337.
  • Overview
    • Camilleri, M Gastroparesis: Etiology, clinical manifestations, and diagnosis. UpToDate Sep 2020.
    • Krishnasamy S, Abell Diabetic Gastroparesis: Principles and Current Trends in Management. Diabetes Ther. 2018 Jul;9(Suppl 1):1-42. doi: 10.1007/s13300-018-0454-9. Epub 2018 Jun 22. PMID: 29934758; PMCID: PMC6028327.
    • Parkman Idiopathic gastroparesis. Gastroenterol Clin North Am. 2015 Mar;44(1):59-68. doi: 10.1016/j.gtc.2014.11.015. Epub 2014 Dec 24. PMID: 25667023; PMCID: PMC4324534.
  • Pharmacology
    • Tack J, Camilleri M, Chang L, Chey WD, Galligan JJ, Lacy BE, Müller- Lissner S, Quigley EM, Schuurkes J, De Maeyer JH, Stanghellini Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders. Aliment Pharmacol Ther. 2012 Apr;35(7):745-67. doi: 10.1111/j.1365-2036.2012.05011.x. Epub 2012 Feb 22. PMID: 22356640; PMCID: PMC3491670. 
  • Treatment
    • Camilleri Treatment of gastroparesis. UpToDate Apr 2020.
    • Lee A, Kuo Metoclopramide in the treatment of diabetic gastroparesis. Expert Rev Endocrinol Metab. 2010;5(5):653-662. doi: 10.1586/eem.10.41. PMID: 21278804; PMCID: PMC3027056.