Prometheus Biosciences Announces FDA Acceptance of IND Application for PRA023 and Commences Dosing in Phase 1a Clinical Study

 – PRA023 is a TL1A antibody targeting both inflammation and fibrosis in patients with ulcerative colitis and Crohn’s disease –

 – PRA023 is being developed to be used in combination with a companion diagnostic to identify responders in novel precision medicine approach –

SAN DIEGO, December 15, 2020 /PRNewswire/ —  Prometheus Biosciences, Inc. (“Prometheus”), a biotechnology company pioneering a precision medicine approach for the discovery, development, and commercialization of novel therapeutic and companion diagnostic products for the diagnosis and treatment of inflammatory bowel disease (IBD), today announced FDA acceptance of its Investigational New Drug Application (IND) for PRA023 and that dosing has commenced in a Phase 1a clinical study in normal healthy volunteers. PRA023, the company’s lead product candidate, is a humanized IgG1 monoclonal antibody (mAb) that has been shown to block tumor necrosis factor (TNF)-like ligand 1A (TL1A).  TL1A is a validated clinical target that is being developed for the treatment of the two most common forms of IBD, ulcerative colitis (UC) and Crohn’s disease (CD).  Prometheus recently completed a $130M financing to advance novel precision medicine approaches in IBD. 

“PRA023 is a novel precision therapy approach for the treatment of IBD and we are pleased to initiate dosing in this clinical study,” said Mark McKenna, President and CEO of Prometheus.  “Importantly, TL1A is the only therapeutic target in development that targets both inflammation and fibrosis, which represents the biggest unmet medical need in IBD.” 

“Anti-TL1A therapy is a very promising mechanism for the treatment of IBD, and everyone has been waiting for companion diagnostic directed therapy that will allow us to treat the right patient with the right drug,” remarked Dr. William Sandborn, MD, Chief of Gastroenterology and Director of the IBD Center at the University of California San Diego.     

Study PR200-101 is a Phase 1a, single and multi-dose, randomized, double-blind, placebo-controlled study to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of PRA023 in healthy volunteers.

About PRA023, an Anti-TL1A mAb

PRA023 is an IgG1 humanized mAb that has been shown to block TL1A. Third-party antibody programs against TL1A have been shown to reduce both intestinal inflammation and fibrosis in preclinical studies, and this target has been clinically-validated in a third-party Phase 2a clinical trial in UC. PRA023 binds both soluble and membrane-associated human TL1A with high affinity and specificity and has the potential to substantially improve outcomes for moderate-to-severe IBD patients.   Prometheus is developing PRA023 for the two most common forms of IBD, ulcerative colitis (UC) and Crohn’s disease (CD).

About Inflammatory Bowel Disease (IBD)

IBD is a complex disease with many contributing factors, including genetic, environmental and immunologic, and is estimated to affect over 2,000,000 people in the United States and over 5,000,000 people globally. UC and CD are two of the most common forms of IBD. Both UC and CD are chronic, relapsing, remitting, inflammatory conditions of the GI tract that begin most commonly during adolescence and young adulthood. UC involves the innermost lining of the large intestine, and symptoms include abdominal pain and diarrhea, frequently with blood and mucus. CD can affect the entire thickness of the bowel wall and all parts of the GI tract from mouth to anus. CD symptoms include abdominal pain, diarrhea, and other more systemic symptoms such as weight loss, nutritional deficiencies, and fever.

The current standard of care for the treatment of patients with moderate-to-severe IBD is typically anti-inflammatory agents; however, none of these therapies address fibrosis, or scarring, in IBD. Since the approval of the first anti-TNF agent for the treatment of CD in 1998, the availability of JAK inhibitors and newer biological agents, including anti-integrin and anti-IL12/23, has improved the care of moderate-to-severe IBD (JAK inhibitors in UC only). However, these subsequently approved therapies have generally failed to demonstrate a clinical remission effect size of more than 15% relative to placebo. Moreover, among those patients who do respond to therapy, up to 45% will lose response over time. Current therapies used for the treatment of UC and CD apply a one-size-fits-all approach without regard to biologic variations amongst patients, and substantial unmet need remains. 

About Prometheus Biosciences, Inc.

Prometheus Biosciences, Inc. is a privately held biotechnology company pioneering a precision medicine approach for the discovery, development, and commercialization of novel therapeutic and companion diagnostic products for the treatment and diagnosis of IBD. The company’s precision medicine platform, Prometheus360, combines proprietary bioinformatics discovery methods with one of the world’s largest gastrointestinal bioinformatics databases to identify novel therapeutic targets and develop therapeutic candidates to engage those targets. Prometheus is guided by its board of directors, led by Chairman Tachi Yamada, M.D., and a scientific advisory board composed of key opinion leaders in IBD, including Stephan Targan, M.D., William Sandborn, M.D. and Dermot P. McGovern, M.D., Ph.D.  In addition, Prometheus has entered into collaborations to develop targeted therapies for IBD.

Prometheus maintains its headquarters in San Diego, CA.  For more information about Prometheus, please visit  www.prometheusbiosciences.com.

Contacts:

Investor Relations and Media Contact
Juniper Point
Amy Conrad, (858) 914-1962
IR@prometheusbiosciences.com

FIBROSpect® NASH

Non-invasively aids in the detection, staging, and monitoring of liver fibrosis for nonalcoholic steatohepatitus (NASH) patients.

Introduction to NASH

Nonalcoholic steatohepatitis (NASH) affects approximately 25 million people in the US1 and it is projected that by 2020, NASH will overtake hepatitis C as the leading cause of liver transplants2. Currently, biopsy is the gold standard for the diagnosis of NASH. However, biopsy may be subject to sampling problems that can confound the results, in addition to surgical costs, risk, and inconvenience for the patient.

Identifying High-Risk NASH Patients is Imperative

  • F3-F4 stage of liver fibrosis has been identified as the most significant independent risk factor for mortality in NASH patients3,4
  • NASH-related cirrhosis is becoming a more common indication for liver transplantation3
  • Progression of NASH-related liver fibrosis is 2 times faster than nonalcoholic fatty liver disease5

PROMETHEUS® FIBROSpect® NASH

PROMETHEUS FIBROSpect NASH is a laboratory-developed test that aids in in the detection, staging, and monitoring of liver fibrosis in nonalcoholic steatohepatitis patients. The simple blood test is noninvasive and provides a quantitative fibrosis score to help physicians risk stratify and monitor patients based on 3 clinically relevant biomarkers.

New proprietary NASH-specific algorithm

  • Differentiated F0-F2 from F3-F4 liver fibrosis in clinically diagnosed NASH patients9
  • Validated with samples from 396 biopsy-confirmed NASH patients9
  • Provides quantitative liver fibrosis test results

FIBROSpect NASH benefits:

  • Easy-to-read and interpret test result
  • Noninvasive and non-fasting
  • Can be repeated frequently, easily, and safely
  • May reduce the need for biopsy

Resources:

References:

  1. National Institute of Diabetes and Digestive and Kidney Diseases Web site. Definition & facts of NAFLD & NASH. https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash/definition-facts. Accessed August 7, 2017
  2. Canbay A, Sowa JP, Syn WK, Treckman J. NASH cirrhosis – the new burden in liver transplantation: how should it be managed? Visc Med. 2016;32(4):234-238.
  3. Angulo P, Kleiner DE, Dam-Larsen S, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149(2):389-397.
  4. Ekstedt M, Hagström H, Nasr P, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61(5):1547-1554.
  5. Jayakumar S, Harrison SA, Loomba R. Noninvasive markers of fibrosis and inflammation in nonalcoholic fatty liver disease. Curr Hepatol Rep. 2016;15(2):86-95.
  6. Boeker KH, Haberkorn CI, Michels D, Flemming P, Manns MP, Lichtinghagen R. Diagnostic potential of circulating TIMP-1 and MMP-2 as markers of liver fibrosis in patients with chronic hepatitis C. Clin Chim Acta. 2002;316(1-2):71-81.
  7. Halfon P, Bourlière M, Pénaranda G, et al. Accuracy of hyaluronic acid level for predicting liver fibrosis stages in patients with hepatitis C virus. Comp Hepatol. 2005;4:6.
  8. Ho AS, Cheng CC, Lee SC, et al. Novel biomarkers predict liver fibrosis in hepatitis C patients: alpha 2 macroglobulin, vitamin D binding protein and apolipoprotein AI. J Biomed Sci. 2010;17(58):1-7.
  9. Data on file. Prometheus Laboratories Inc.
  10. When and in whom to initiate HCV therapy. American Association for the Study of Liver Diseases and the Infectious Diseases Society of America Web site. http://www.hcvguidelines.org/evaluate/when-whom. Last updated July 6, 2016. Accessed July 24, 2017.

The FibroSPECT tests are laboratory-developed tests that were developed and validated under Federal CLIA laboratory guidelines, and are performed exclusively by Prometheus Laboratories Inc.

FIBROSpect® HCV

Non-invasively aids in the detection, staging, and monitoring of the severity of liver fibrosis for hepatitis C virus (HCV) patients.

PROMETHEUS® FIBROSpect® HCV

For hepatitis C (HCV) patients, we offer the PROMETHEUS FIBROSpect HCV test, which is a laboratory-developed test that aids in in the detection, staging, and monitoring of liver fibrosis. The simple blood test is noninvasive and provides a quantitative fibrosis score to help physicians risk stratify and monitor patients

  • Differentiates between F0-F1 and F2-F4 liver fibrosis9
  • Validated with samples from 348 biopsy-confirmed HCV patients9

Staging of Liver Fibrosis in HCV Patients is Critical

American Association for Study of Liver Disease (AASLD) and Infectious Disease Society of America (IDSA) 2017 guidelines highlight the benefits of initiating therapy in HCV patients with lower-stage liver fibrosis10:

  • “Initiating therapy in patients with lower-stage fibrosis augments the benefits of SVR [sustained virologic response]”
  • “Treatment delay may decrease the benefit of SVR”

Resources:

References:

  1. National Institute of Diabetes and Digestive and Kidney Diseases Web site. Definition & facts of NAFLD & NASH. https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash/definition-facts. Accessed August 7, 2017
  2. Canbay A, Sowa JP, Syn WK, Treckman J. NASH cirrhosis – the new burden in liver transplantation: how should it be managed? Visc Med. 2016;32(4):234-238.
  3. Angulo P, Kleiner DE, Dam-Larsen S, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149(2):389-397.
  4. Ekstedt M, Hagström H, Nasr P, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61(5):1547-1554.
  5. Jayakumar S, Harrison SA, Loomba R. Noninvasive markers of fibrosis and inflammation in nonalcoholic fatty liver disease. Curr Hepatol Rep. 2016;15(2):86-95.
  6. Boeker KH, Haberkorn CI, Michels D, Flemming P, Manns MP, Lichtinghagen R. Diagnostic potential of circulating TIMP-1 and MMP-2 as markers of liver fibrosis in patients with chronic hepatitis C. Clin Chim Acta. 2002;316(1-2):71-81.
  7. Halfon P, Bourlière M, Pénaranda G, et al. Accuracy of hyaluronic acid level for predicting liver fibrosis stages in patients with hepatitis C virus. Comp Hepatol. 2005;4:6.
  8. Ho AS, Cheng CC, Lee SC, et al. Novel biomarkers predict liver fibrosis in hepatitis C patients: alpha 2 macroglobulin, vitamin D binding protein and apolipoprotein AI. J Biomed Sci. 2010;17(58):1-7.
  9. Data on file. Prometheus Laboratories Inc.
  10. When and in whom to initiate HCV therapy. American Association for the Study of Liver Diseases and the Infectious Diseases Society of America Web site. http://www.hcvguidelines.org/evaluate/when-whom. Last updated July 6, 2016. Accessed July 24, 2017.

The FibroSPECT tests are laboratory-developed tests that were developed and validated under Federal CLIA laboratory guidelines, and are performed exclusively by Prometheus Laboratories Inc.

Celiac Genetics

  • Analyzes a patient’s genetic profile for disease risk stratification
  • Only Prometheus genetic testing quantifies the relative risk of disease for every patient
  • A negative predictive value (NPV) of 95% to 100% allows for ruling out celiac disease for life1

Now You Can Asses Your Patients’ Risk

Category NumberDQ Genotype CategoryIncreased Risk Over General Population2,3Relative Risk
8DQ2 homozygous31xExtremely High
7DQ2/other high-risk gene16xVery High
6DQ2/DQ810xVery High
5DQ8 homozygous10xHigh
4DQ2 heterozygous10xHigh
3DQ8 heterozygous2xModerate
2DQ2/other low-risk gene<1xLow
1DQ2-, DQ8-<0.1xExtremely Low


Most celiac patients carry either the DQ2 haplotype (about 95% of celiacs) or the DQ8 haplotype (about 5% of celiacs). There are two DQ2 haplotypes, but only one DQ8 haplotype—specific combinations may confer different risks for the development of celiac disease, as shown above.

Research advises ordering full HLA-DQA1 and DQB1 typing and should also have other clinical correlates including positive serology (gluten challenged) with or without abnormal duodenal biopsy.

References:
1.Kaukinen K, Partanen J, Mäki M, Collin P. HLA-DQ typing in the diagnosis of celiac disease. Am J Gastroenterol. 2002;97(3):695-699.
2. Pietzak M, Schofield T. HLA-DQ2 homozygotes are associated with a 31-fold increased risk of EMA positivity in a large sample of sera (n = 4152) from patients at risk for celiac disease [DDW abstract]. Gastroenterology. 2007;132(7):2585.
3. Fasano A, Berti I, Gerarduzzi T, et al. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med. 2003;163(3):286-292.

Sample insurance correspondence for PROMETHEUS® Celiac Genetics