Ocera Therapeutics, Inc.
Ocera Therapeutics, Inc. (Form: 8-K, Received: 03/08/2017 08:55:03)


UNITED STATES SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
 
FORM 8-K
 
CURRENT REPORT
 
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
 
Date of Report (Date of Earliest Event Reported): March 8, 2017
 
OCERA THERAPEUTICS, INC.
(Exact name of registrant as specified in its charter)
 
 
 
 
 
 
 
DELAWARE
 
001-35119
 
63-1192270
(State or other jurisdiction
 
(Commission File Number)
 
(I.R.S. Employer
of
 
 
 
Identification No.)
incorporation)
 
 
 
 
 
 
 
 
 
525 University Avenue, Suite 610
 
 
Palo Alto, CA
 
94301
(Address of principal executive offices)
 
(Zip Code)
 
Registrant’s telephone number, including area code (650) 475-0158
 
Not applicable
(Former name or former address, if changed since last report)
 
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
 
o             Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
 
o             Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
 
o             Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
 
o             Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))





  Item 7.01.  Regulation FD Disclosure.
Linda Grais, M.D., Chief Executive Officer of Ocera Therapeutics, Inc. (the “Company”), will present at the Cowen and Company 37 th  Annual Healthcare Conference on March 8, 2017 at 11:20 a.m. Eastern Time in Boston, Massachusetts. A live audio webcast of the presentation will be available in the “Investors” section of the Company's website, www.ocerainc.com. A replay of the presentation will be available for 60 days following the conference for those unable to listen live. A copy of the presentation slide deck is being furnished as Exhibit 99.1 to this Report on Form 8-K.
The information in Exhibit 99.1 and attached hereto is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing. 
Item 8.01 Other Events.
On March 8, 2017, the Company issued a press release announcing additional data from its Phase 2b “STOP-HE” clinical trial of OCR-002 in patients with hepatic encephalopathy. The full text of the press release is filed as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.
Item 9.01 Financial Statements and Exhibits.
  (d)          Exhibits
 
 
 
 
Exhibit No.
 
Description

 
99.1
 
Presentation Slide Deck, furnished hereto.
99.2
 
Press release of Ocera Therapeutics, Inc. dated March 8, 2017.








SIGNATURES
 
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
 
 
 
 
 
 
March 8, 2017
 
Ocera Therapeutics, Inc.
 
 
 
 
 
By:
/s/ Linda S. Grais, M.D.
 
 
Name: Linda S. Grais, M.D.
 
 
Title: President and Chief Executive Officer
 

 
 
 


NASDAQ: OCRX M A R C H 2 0 1 7 37th Annual Cowen Healthcare Conference The Boston Marriott Copley Place March 6-8, 2017 A Liver Disease Medicines Company


 
2 Forward-Looking Statements Certain statements in this presentation constitute “forward-looking statements” within the meaning of the Securities Act of 1933, as amended (the “Securities Act”), and Securities Exchange Act of 1934, as amended (“Exchange Act”), including, without limitation, all statements related to the OCR-002 clinical development program, the timing of our planned meeting with the FDA, our ability to identify a path forward for OCR-002, whether any future studies of OCR-002 will demonstrate similar results to our Phase 2b study, and the size of the potential market opportunity for OCR-002, and we intend these forward- looking statements to be covered by the safe harbor provisions for forward-looking statements contained in the Securities Act and the Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a variety of risks and factors that are beyond our control, including our ability to raise sufficient capital or consummate a strategic transaction to enable the continued development of OCR-002, as well as those risks and uncertainties discussed under “Risk Factors” in our Annual Report on form 10-K for the year ended December 31, 2015, and other risks detailed in our subsequent filings with the SEC. All information in this presentation is as of the date of this presentation, and we undertake no duty to update this information unless required by law.


 
3 Addressing a Serious Unmet Need Alcohol Use NASH / Fatty Liver Hepatitis Drug Exposure Autoimmune Diseases Diabetes Obesity Multiple Causes of Liver Disease (U.S.) CHRONIC LIVER DISEASE 30-35M1 LIVER CIRRHOSIS 5.5M Million2 ~200K Patients Hospitalized with OHE3 1 American Liver Foundation, Clinical Gastroenterology and Hepatology, 2011;9:524-530 Zobair et al 2 Clin Liver Dis (2012) 73-89 Khungar et al 3 HCUP, Company estimate OHE = Overt Hepatic Encephalopathy Chronic HE Patients2 AT RISK OF OHE 5.5M Million2


 
4 Disorientation Impaired Motor Skills Personality Changes Stupor Coma Death 0 1 2 3 4 Hepatic Encephalopathy (HE): Neurocognitive Disorder in Serious Liver Disease Blood Stream Ammonia Gut Note: 0 to 4 as measured by West Haven Scale Covert (CHE) Overt (OHE) Elevated Ammonia Levels Drive HE


 
5 1 HCUP Database 2 Clinical Gastroenterology and Hepatology 2012;10:1034–1041 HE: Large and Growing Healthcare Burden Rising Hospitalizations1 (000s) • Total national charges related to HE: $7 Billion2 • HE hospitalizations continue to grow despite Rifaximin launch in 20101 • Rifaximin 2016 revenue: $932 Million • HE patient demographics show increase in severity of illness, elderly population, and obesity as comorbidities2 Rifaximin approved for Prevention of HE April 2010 2006 2007 2008 2009 2010 2011 2012 2013 2014 105 107 106 110 120 133 141 148 156 83 104 180 196 252 275 331 380 436 Hepatic Coma Encephalopathy


 
6 OCR-002 is the ONLY Direct IV and Oral Ammonia Scavenger in Development for HE Treatment and Prevention


 
7 Significant Commercial Opportunity for IV and Oral OCR-002 1 HCUP Database (includes ICD-9 codes 572.2/hepatic coma and 348.3/ encephalopathy NOS)


 
8 Valuable Commercial Estate BROAD PATENTS Composition of Matter to 2030 (not including Hatch-Waxman extension) ORPHAN STATUS in US for hyperammonemia and HE* WORLDWIDE RIGHTS *Orphan Status also granted in EU for Acute Liver Failure (ALF)


 
9 OCR-002 Dual Mechanism of Action: Note: Simplification of MOA


 
10 OCR-002 (Ornithine Phenylacetate) Validated Ammonia Scavenger Designed to Treat HE • IV easy to administer in hospitalized patients ▪ Peripheral IV line, low infusion volume and neutral pH ▪ Rapid onset ▪ No sodium load or electrolyte disturbances • Oral formulation for chronic care patients ▪ Prevention of HE via ammonia-scavenging has been clinically established ▪ Provides continuity of care for patients at home


 
STOP-HE Phase 2b Study OCR-002 IV for Overt HE


 
12 STOP-HE Phase 2b: OCR-002 IV for Overt HE *As scored by a modified version of the West Haven Scale 20g 15g 10g


 
13 Primary Endpoint: Time to meaningful clinical improvement in HE symptoms Secondary Endpoints: Time to complete resolution of HE symptoms, % responders, length of hospital stay Exploratory endpoints: Ammonia interrelationships, hospital discharge destination Meaningful Clinical Improvement As Scored by Hepatic Encephalopathy Scoring Tool (HEST) Modified Version of West Haven Scale Stage / Symptoms Meaningful Clinical Improvement 4 to 2 or lower 3 to 2 or lower 2 to 1 or lower --- Hospi tali za tion -- -Comatose Stuporous Disoriented Difficult to Arouse Asterixis Mild Confusion Normal Mode ra te Mil d Se ve re 0 1 2 3 4


 
14 • Level of HE severity correlated with ammonia levels, p=0.032 • OCR-002 is a potent ammonia scavenger, achieving statistically significant ammonia reduction, p=0.017 • Primary endpoint: median time to meaningful clinical improvement was 47 hours (OCR-002) and 64 hours (PBO). The 17-hour difference corresponds to p=0.129, hazard ratio 1.25 • Higher doses (15g, 20g) consistently show strong evidence of benefit across multiple endpoints • Clinical improvement dose trend observed: responder rate increased as dose increased and was superior to PBO at all doses • OCR-002 was safe and well-tolerated. Higher doses had a lower percentage of deaths and life threatening AEs compared to placebo STOP-HE Top-line Data Overview (January 30)


 
15 STOP-HE Primary Endpoint: Median Time to Clinical Improvement in HE Symptoms


 
16 Dose Proportional Responder Rate: Clinical Improvement at 3 hours Post-End-of-Infusion*


 
17 OCR-002 is Safe and Well-Tolerated


 
STOP-HE Phase 2b Study Subsequent Analysis


 
19 Summary of Subsequent Analyses • Ammonia reduction correlates with clinical improvement (p=0.0006) • Dose proportional response and PK data indicate some patients were under- dosed • Earlier timing of drug administration and efficacy assessment is important: ▪ Patients who improve within 48 hours are discharged earlier than patients who do not improve within 48 hours ▪ Patients on OCR-002 more likely to respond within 48 hours compared to placebo (p=0.026) • Pre-defined measures of improvement were statistically significant: ammonia reduction (p=0.017), Physician overall evaluation (p= 0.026) • OCR-002 appears to have an equal or better benefit-risk ratio than rifaximin, which is not indicated for overt HE but widely used in the hospital


 
20 Ammonia Reduction Correlates with Clinical Improvement (change in ammonia from baseline) Clinical Improvement Positively Correlated with Ammonia Reduction, p=0.0006* *ANCOVA, 2 sided Ammonia l ev el µ g/m L Clinical Outcome No Improvement Improvement


 
21 OCR-002 Has a Dose-Proportional Reduction in Ammonia and Does So Faster than Placebo p=0.028 hazard ratio: 1.69 p=0.017 OCR-002 Superior to PBO in Both Ammonia Parameters, p=0.017 and p=0.028


 
22 Not all Patients Achieved Target Exposure Target Range Possible Change to Dosing Regimen Under Evaluation


 
23 Timing of Outcome Measurement: OCR-002 was Statistically Significantly Better than PBO at 48 Hours • Most HE patients eventually respond to SOC; goal of study was to shorten time to response • Patients received SOC immediately; OCR-002 patients waited >12 hours • OCR-002 superior to PBO at 48 hours, p=0.026 • Patients on OCR-002 had a higher response rate at 48 hours vs PBO (51% and 37%, respectively) and responders left hospital ~1.5 days earlier • We believe future studies should begin OCR-002 administration earlier in admission and measure efficacy at an earlier timepoint


 
24 Measure Description p-Value Ammonia Time to ammonia below normal is earlier for OCR-002 than Placebo (median difference of 40 hours) 0.028 Physician Overall Treatment Evaluation Proportion of subjects demonstrating improvement 0.026 Choice of Endpoint: HEST (novel tool) Used for Primary Endpoint Considerations for Phase 3 • HEST validation is currently underway • Discussions with FDA encouraged use of more objective measure of clinical benefit rather than PD marker • STOP-HE data demonstrate strong correlation of ammonia with clinical improvement and level of symptom severity • Consider a composite primary endpoint that may include more objective measures of pharmacodynamics that include ammonia Other Predefined Endpoints Reached Statistical Significance (to be Discussed with FDA)


 
25 Role of Rifaximin was Explored OCR-002 without rifaximin vs. PBO without rifaximin OCR-002 vs. PBO irrespective of rifaximin 147 patients (78 OCR-002, 69 Placebo) received rifaximin during therapy or entered hospital on rifaximin 31% of patients were on rifaximin at admission STOP-HE Without Rifaximin Would Have Met Primary Endpoint with High Statistical Significance, p=0.004


 
26 OCR-002 vs. Rifaximin Shows Positive Drug Effect for Acute Care OHE Patients were given SOC (with many also receiving rifaximin) right away; patients on OCR-002 waited >12 hours to receive study drug Though Study Not Powered to Show OCR-002 vs. Rifaximin Difference, OCR-002 Shows Positive Effect vs. Rifaximin


 
27 OCR-002 May Be More Appropriate than Rifaximin in Treating Acute Episodes of Overt HE • Rifaximin, an antibiotic to reduce the recurrence of acute HE episodes, is not indicated for overt HE, but is widely used in acute care settings • Rifaximin label cautions use in severe liver impairment and cites potential for 21-fold increase in systemic exposure in Child-Pugh C patients (70% in the study) • Serious treatment-emergent infections were disproportionately observed in the rifaximin group • Safety and efficacy profile observed to date of OCR-002 IV make it well-suited for acute treatment of overt HE patients, especially those with severe liver impairment


 
28 Clinical Effects - Data Suggest Patients Benefit from OCR-002 as it Addresses “Ammonia Toxicity Syndrome” *MELD = Model for End-Stage Liver Disease, an estimate of life-expectancy ^BUN = Blood Urea Nitrogen, a measure of kidney function # HSPE = Hepatic Synthetic Portal Elements, a measure of liver impairment


 
29 Data Suggest OCR-002 has Potential Broad Application 1. Hospital-based Acute Care for HE ◦ Acute therapy, rapidly reduce ammonia; effect seen early ◦ Dose without rifaxamin as patients presenting in hospital have moderate to severe liver disease, in whom rifaxamin must be used with caution, nor is it indicated for acute episodes of overt HE 2. Step Down Therapy ◦ Continued administration following initial ammonia reduction to allow “inflammatory cascade”* from ammonia to reduce (Child- Pugh B and/or Child-Pugh C patients) 3. Chronic Care Outpatient Use ◦ Maintain remission of HE for patients at home and/or rescue therapy for patients at risk of developing therapy ◦ May allow for reduction of lactulose use IV infusion Oral *Wright, et al “Brain cytokine flux in acute liver failure and its relationship with intracranial hypertension” Metabolic Brain Disorder 2007 Dec:22(3-4):375-88


 
30 Wealth of Data Supports Promise of OCR-002


 
31 Next Steps


 
OCERALOGO1.JPG

Exhibit 99.2
PRESS RELEASE

Ocera to Announce Additional Encouraging Results from its Phase 2b STOP-HE
Study of IV OCR-002 in Patients with Hepatic Encephalopathy
IV OCR-002 statistically significantly normalized ammonia faster than standard of care
Ammonia reduction statistically significantly correlated with clinical improvement in
HE symptoms
Ocera plans to meet with FDA in Q3 2017 to inform development paths forward for
IV OCR-002
Company presentation scheduled for today, March 8, 2017 at 11:20 AM ET
PALO ALTO, Calif. and RESEARCH TRIANGLE PARK, N.C., March 8, 2017 – Ocera Therapeutics, Inc. (NASDAQ:OCRX), a clinical stage biopharmaceutical company focused on acute and chronic orphan liver diseases, today announced it will report additional encouraging results from its Phase 2b STOP-HE study of intravenous (IV) OCR-002 in hospitalized patients with Hepatic Encephalopathy (HE) at the Cowen and Company 37 th Annual Healthcare Conference at 11:20 AM Eastern Time today.
"Further analysis of the data from our STOP-HE trial confirms that OCR-002 rapidly and safely lowered ammonia and, importantly, the ammonia reduction correlated statistically with clinical improvement," said Linda Grais, M.D., Chief Executive Officer of Ocera. "With greater confidence, we believe the most relevant efficacy considerations likely include earlier timing of drug administration, measuring efficacy sooner after drug administration, and administering the appropriate and tolerable dose regimen of OCR-002. We look forward to discussing these data as well as Phase 3 development with FDA later this year."
“We are very encouraged by the additional study data indicating IV OCR-002 provided clinical benefit over placebo in other parameters as well, such as the Physician Overall Evaluation, Model for End-Stage Liver Disease (MELD) scores, and in renal function as measured by the change from baseline in Blood Urea Nitrogen (BUN) levels,” said Stan Bukofzer, M.D., Chief Medical Officer of Ocera.
Initial STOP-HE results reported in January 2017 included:
OCR-002 demonstrated a highly statistically significant reduction in ammonia levels over placebo, p=0.028;
Higher doses (15g, 20g) showed strong evidence of benefit across multiple endpoints;
Clinical improvement dose trend observed; responder rate increased as dose increased and was superior to placebo at all doses; and
OCR-002 was safe and well-tolerated; higher doses had a lower percentage of deaths and life threatening adverse events compared to placebo

Additional results to be presented today include:
Ammonia reduction correlates with clinical improvement, p=0.0006;





Dose proportional response and pharmacokinetic data indicate some patients were under-dosed;
Earlier timing of drug administration and efficacy assessment is important:
o
Patients who improve within 48 hours are discharged earlier than patients who do not improve within 48 hours;
o
Patients on OCR-002 are more likely to respond within 48 hours compared to placebo, p=0.026;
Pre-defined measures of improvement were statistically significant: ammonia reduction, p=0.017 and Physician overall evaluation, p= 0.026;
OCR-002 demonstrated improvement in the Model for End-Stage Liver Disease (MELD) scores, p=0.051; and
OCR-002 showed improvement in renal function as measured by the change from baseline in Blood Urea Nitrogen (BUN) levels, p=0.04
A live webcast of the presentation will be available in the "Investors" section of Ocera's website, www.ocerainc.com. A replay of the presentation will be available for 60 days following the conference for those unable to listen live.
STOP-HE Study Design
STOP-HE was a placebo-controlled, randomized, double-blind clinical trial designed to evaluate the safety, pharmacokinetics and efficacy of intravenously-administered OCR-002 in resolving neurocognitive symptoms of acute HE in 231 hospitalized patients with liver cirrhosis and elevated serum ammonia (hyperammonemia). Either OCR-002 or placebo was administered to patients intravenously as a continuous infusion for up to five days along with standard of care. The OCR-002 arm was dosed with 10, 15 or 20 grams over 24 hours based on the patient's degree of liver impairment and modeling of OCR-002 metabolism, in addition to safety considerations in this high-risk patient population.
About Hepatic Encephalopathy
Hepatic encephalopathy (HE) is a debilitating and progressive complication of liver cirrhosis or liver failure, marked by increasing ammonia levels, mental changes including confusion, impaired motor skills, disorientation, and in its more severe form, stupor, coma and even death. HE is categorized as either covert or overt depending on the degree of neurocognitive impairment, with overt HE (OHE) typically precipitating the need for hospitalization. Patients frequently cycle from remission to recurrence following an initial overt episode. The number of OHE episodes appears to be directly linked to persistent neurological impairment and seems to be cumulative; thus the need to manage HE patients is vital. It is estimated that HE-related hospitalization costs exceed $7 billion 1  annually in the U.S. alone.
1  Clinical Gastroenterology and Hepatology 2012; 10:1034-1041
About Ocera
Ocera Therapeutics, Inc. is a clinical stage biopharmaceutical company focused on the development and commercialization of OCR-002 (ornithine phenylacetate) in both intravenous and oral formulations. OCR-002 is an ammonia scavenger and has been granted orphan drug designation and Fast Track status by the U.S. Food and Drug Administration (FDA) for the





treatment of hyperammonemia and resultant hepatic encephalopathy in patients with acute liver failure and acute-on-chronic liver disease.
Ocera's HE clinical development efforts also include a recently completed Phase 1 clinical trial of an oral formulation of OCR-002 in patients with cirrhosis as a potential chronic use option to maintain remission of HE. The Company expects to initiate a multi-dose Phase 2a study of oral OCR-002, also in cirrhotic patients, in the first half of 2017. For additional information, please see www.ocerainc.com.
Forward-Looking Statements
This press release contains "forward-looking" statements, including, without limitation, all statements related to the OCR-002 clinical development program, including but not limited to the potential benefits of OCR-002 to help patients with hepatic encephalopathy, the timing of our planned meeting with the FDA, our ability to identify a development path forward for OCR-002, whether any future studies of OCR-002 we may conduct will demonstrate similar results to our Phase 2b study, the timing of our planned Phase 2a study of the oral formulation of OCR-002 in cirrhotic patients, and the timing and nature of our future clinical development plans. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believe," "expected," "hope," "plan," "potential," "will" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Ocera's current expectations. Forward-looking statements involve risks and uncertainties and Ocera's actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, including the risk that we may need to conduct one or more additional studies in light of the fact our Phase 2b trial did not meet its clinical endpoints, including related cost and timing issues associated with future studies, if any, our ability to raise sufficient capital or consummate other strategic transactions to enable the continued development of OCR-002, as well as those risks and uncertainties discussed under the heading "Risk Factors" in Ocera's Annual Report on Form 10-K for the year ended December 31, 2015 and subsequent filings with the SEC. All information in this press release is as of the date of the release, and Ocera undertakes no duty to update this information unless required by law.

###

Source: Ocera Therapeutics, Inc.
OCRX-G

Susan Sharpe
Ocera Therapeutics, Inc.
contact@ocerainc.com 
919-328-1109