On November 7, 2018 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported business and financial highlights for the third quarter ended September 30, 2018 (Press release, Celldex Therapeutics, NOV 7, 2018, View Source [SID1234530915]).

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"We made considerable progress in the third quarter, particularly in the development program for CDX-1140, our promising antibody targeted to CD40," said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex Therapeutics. "We have completed four of the potential eight monotherapy dose levels in the ongoing Phase 1 study and remain encouraged by the safety and biological profile we have observed to date. We look forward to sharing interim data at the SITC (Free SITC Whitepaper) Annual Meeting later this week. During the third quarter, we also began enrolling patients in a combination cohort of CDX-1140 with our dendritic cell mobilizer, CDX-301. We are very interested to explore the potential of CDX-1140 in the presence of greater dendritic cell activity."

"Additionally, we are nearing completion of enrollment to the first stage of the Phase 2 study of CDX-3379 in advanced head and neck squamous cell cancer and anticipate data from this portion of the study in the first quarter of 2019," continued Marucci. "We are also advancing several preclinical programs that we believe can play an important role in enhancing the immune system’s response to cancer, including CDX-0159, our TAM program targeting Tyro3, AXL and MerTK, and our growing bispecific antibody program."

Recent Highlights:

Enrollment continues in the Phase 1 dose-escalation study of CDX-1140 in solid tumors. Interim data from the ongoing study have been accepted for presentation on Friday, November 9, 2018 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting. This study is designed to enroll up to 150 patients with recurrent, locally advanced or metastatic solid tumors and was recently amended to also include B-cell lymphomas. CD40 has long been an important target for immunotherapy, as it plays a critical role in the activation of innate and adaptive immune responses; however, effectively balancing systemic dosing and safety has proven challenging to date for CD40-activating therapeutics. CDX-1140 is a unique, potent CD40 agonist that Celldex believes has the potential to successfully balance systemic doses for good tissue and tumor penetration with an acceptable safety profile. Data to date from the four completed dosing cohorts (0.01, 0.03, 0.09 and 0.18 mg/kg) suggest that CDX-1140 is exhibiting a desirable safety profile and demonstrating early signs of biological activity based on biomarker analysis. The fifth monotherapy cohort at 0.36 mg/kg is currently being enrolled, along with the combination therapy cohort of CDX-1140 (0.09 mg/kg) with CDX-301 which was initiated in late August. CDX-301 is a dendritic cell growth factor that will be used as a priming agent to potentially increase the number of cells available to respond to CDX-1140. In addition, Celldex is evaluating the potential for combination with varlilumab, especially in lymphomas which co-express CD40 and CD27 receptors.

Enrollment is nearing completion in the first stage of the Phase 2 study (n=13) of CDX-3379 in advanced head and neck squamous cell cancer in combination with Erbitux in Erbitux-resistant patients who have been previously treated with or are ineligible for checkpoint therapy. According to the study’s Simon two-stage design, if at least one patient achieves an objective response in the first stage, enrollment may progress to the second stage. While a confirmed partial response has been documented, Celldex will wait to review the full data set before making decisions on future development, as a number of patients are still undergoing treatment and are not yet eligible for response evaluation.

Data from the glioblastoma cohort in the Phase 1/2 study of varlilumab and Opdivo have been accepted for presentation on Saturday, November 17, 2018 at the Society for Neuro-oncology (SNO) Annual Meeting.

As previously disclosed, on May 29, 2018, Celldex received written notice from the Listing Qualifications department of the Nasdaq Stock Market indicating that the Company was not in compliance with the $1.00 minimum bid price requirement for continued listing on the Nasdaq Global Market. As is standard, the Company was afforded 180 days to regain compliance. Unless Celldex regains compliance with the minimum bid requirement by November 26, 2018 (the 180th day), the Company plans to apply to transfer to the Nasdaq Capital Market. Assuming Celldex’s application is accepted, the proposed transition should be seamless for Celldex shareholders and should allow the company an additional 180-day period in which to regain compliance. If Celldex is unable to regain compliance with the minimum bid price requirement, the Company may implement a reverse stock split to maintain its listing, a measure that was approved by shareholders at the Company’s 2018 Annual Meeting.
Third Quarter 2018 and First Nine Months 2018 Financial Highlights and 2018 Guidance

Cash Position: Cash, cash equivalents and marketable securities as of September 30, 2018 were $105.6 million compared to $114.0 million as of June 30, 2018. The decrease was primarily driven by third quarter cash used in operating activities of approximately $14.4 million, of which $3.2 million were glembatumumab vedotin-related payments, partially offset by the receipt of $5.5 million from sales of common stock under the Cantor agreement. Celldex expects that it will make an additional $2.0 million in glembatumumab vedotin-related payments related to the discontinuation of that program. At September 30, 2018, Celldex had 168.6 million shares outstanding.

Revenues: Total revenue was $0.9 million in the third quarter of 2018 and $7.8 million for the nine months ended September 30, 2018, compared to $3.9 million and $9.3 million for the comparable periods in 2017. The decrease in revenue was primarily due to lower contract revenue from the International AIDS Vaccine Initiative.

R&D Expenses: Research and development (R&D) expenses were $11.9 million in the third quarter of 2018 and $55.2 million for the nine months ended September 30, 2018, compared to $21.9 million and $72.7 million for the comparable periods in 2017. The decrease in R&D expense was primarily due to lower clinical trial, contract manufacturing and personnel expenses.

G&A Expenses: General and administrative (G&A) expenses were $3.7 million in the third quarter of 2018 and $14.9 million for the nine months ended September 30, 2018, compared to $5.3 million and $19.1 million for the comparable periods in 2017. The decrease in G&A expenses was primarily due to lower personnel and marketing expenses.

Changes in Fair Value Remeasurement of Contingent Consideration: Gain on the fair value remeasurement of contingent consideration related to the Kolltan acquisition was $6.9 million in the third quarter of 2018 and $28.0 million for the nine months ended September 30, 2018, primarily due to discontinuation of the glembatumumab vedotin and CDX-014 programs and updated assumptions for the varlilumab and anti-KIT programs.

Net Loss: Net loss was $7.2 million, or ($0.04) per share, for the third quarter of 2018, and $141.8 million, or ($0.94) per share, for the nine months ended September 30, 2018, compared to a net loss of $26.4 million, or ($0.20) per share, for the third quarter of 2017 and $89.2 million, or ($0.71) per share, for the nine months ended September 30, 2017.

Financial Guidance: Celldex believes that the cash, cash equivalents and marketable securities at September 30, 2018, combined with the anticipated proceeds from future sales of common stock under the Cantor agreement, are sufficient to meet estimated working capital requirements and fund planned operations through 2020. This could be impacted if Celldex elects to pay Kolltan contingent milestones, if any, in cash.

Opdivo is a registered trademark of Bristol-Myers Squibb. Erbitux is a registered trademark of Eli Lilly & Co.

On November 7, 2018 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development and commercialization of innovative therapeutics for the treatment of cancer, reported upcoming presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 33rd Annual Meeting and participation in an analyst-moderated Q&A panel at Cowen’s 2nd Annual IO NEXT Summit (Press release, Curis, NOV 7, 2018, View Source [SID1234530914]). Curis’ poster presentations will take place on Friday, Nov. 9, with a poster from collaborator Aurigene on Saturday, Nov. 10, at Hall E of the Walter E. Washington Convention Center in Washington, D.C. The Cowen 2nd Annual IO NEXT Summit will take place at the Marriott Marquis in Washington, D.C. featuring a discussion with Jim Dentzer, President and CEO, and Dr. Robert Martell, Head of Research and Development, in an analyst-hosted fireside chat.

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In three posters at the SITC (Free SITC Whitepaper) conference, Curis will present evidence supporting the presence of high VISTA expression on tumor cells, preclinical data supporting VISTA’s ability to independently suppress T cell responses, and Phase 1 clinical trial data of CA-170 in patients with advanced tumors and lymphomas. In addition, Curis collaborator Aurigene will present a poster detailing key findings from its ongoing Phase 2 trial of CA-170 in patients with advanced solid tumors and Hodgkin lymphoma who are immunotherapy treatment-naïve.

Details of these presentations are as follows:

Cowen IO NEXT Summit

Date/Time:

Friday, Nov. 09, 11:50 AM – 12:10 PM EST

Presenters:

Jim Dentzer, President and Chief Executive Officer

Robert Martell, M.D., Ph.D., Head of Research and Development

Location:

Marriot Marquis Washington, DC

Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 33rd Annual Meeting

CA-170 Poster Presentations from Curis:

Date/Time:

Friday, Nov. 9, 12:45 PM – 2:15 PM, 6:30 PM – 8:00 PM EST

Location:

Hall E, Walter E. Washington Convention Center

Abstract Number:

P135

Presentation Title:

Integrative genomic and proteomic analysis identifies cancer subtypes and signaling networks associated with aberrant tumor expression of VISTA

Abstract Number:

P139

Presentation Title:

Pharmacodynamic effects of CA-170, a first-in-class small molecule oral immune checkpoint inhibitor (ICI) dually targeting V-domain Ig suppressor of T-cell activation (VISTA) and PDL1

Abstract Number:

P341

Presentation Title:

Phase 1 study of CA-170, a first-in-class, orally available, small molecule immune checkpoint inhibitor (ICI) dually targeting VISTA and PDL1, in patients with advanced solid tumors or lymphomas

CA-170 Poster Presentation from Aurigene:

Date/Time:

Saturday, Nov. 10, 12:20 PM – 1:50 PM, 7:00 PM – 8:30 PM EST

Location:

Hall E, Walter E. Washington Convention Center

Abstract Number:

P714

Presentation Title:

Phase 2 trial of CA-170, a novel oral small molecule dual inhibitor of immune checkpoints VISTA and PD-1, in patients with advanced solid tumor and Hodgkin lymphoma

On November 7, 2018 Endocyte, Inc. (Nasdaq:ECYT), a biopharmaceutical company developing targeted therapeutics for personalized cancer treatment, reported financial results for the third quarter ended Sept. 30, 2018 and provided an operational update (Press release, Endocyte, NOV 7, 2018, View Source [SID1234530913]).

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"177Lu-PSMA-617’s value as a potential treatment for patients with mCRPC has been reinforced in both our regulatory interactions and our entry into a merger agreement with Novartis AG, along with our longstanding interactions with patients and physicians in the prostate cancer community," said Mike Sherman, president and CEO of Endocyte. "The team at Endocyte has always been passionate about developing innovative therapies to help change the treatment landscape for cancer patients, and we look forward to being able to leverage Novartis’ global expertise and commitment to help realize this mission."

Third Quarter and Recent Highlights

Announced on October 18, 2018, our entry into an agreement and plan of merger with Novartis AG (Novartis), subject to the terms and conditions of which Novartis will acquire Endocyte for $24 per share, or a total equity value of approximately $2.1 billion, in cash. The merger price represents a premium of 54% to Endocyte’s closing price of $15.56 on October 17, 2018.
Announced FDA acceptance of radiographic progression free survival (rPFS) as an alternative primary endpoint of the ongoing phase 3 VISION trial to support the submission of a New Drug Application (NDA) for full approval of 177Lu-PSMA-617 for the treatment of metastatic castration-resistant prostate cancer (mCRPC).
Completed an underwritten registered public offering of 10,878,379 shares of its common stock, including full exercise of the underwriters’ option to purchase additional shares of common stock, raising aggregate net proceeds from the offering of $188.9 million.
Presented pre-clinical data from the company’s chimeric antigen receptor T-cell (CAR T) adaptor molecule (CAM) platform at CAR-TCR Summit 2018.
Expected Upcoming Milestones

Submission of an Investigational New Drug (IND) application for a phase 1 trial of EC17/CAR T-cell therapy in patients with osteosarcoma (4Q 2018).
Completion of the proposed transaction between Endocyte and Novartis expected in 1H 2019, subject to approval by Endocyte stockholders, antitrust and regulatory approvals, and other customary closing conditions.
Analysis of rPFS in VISION trial (late 2019).
Third Quarter 2018 Financial Results

Endocyte reported a net loss of $12.6 million, or $0.17 per basic and diluted share, for the third quarter of 2018, compared to a net loss of $23.3 million, or $0.55 per basic and diluted share, for the same period in 2017.

Research and development expenses were $8.9 million for the third quarter of 2018, compared to $4.1 million for the same period in 2017. The increase was primarily attributable to: an increase of $4.5 million in expenses related to development of PSMA-617, including expenses related to the phase 3 VISION trial; an increase of $1.2 million in compensation expense, of which $0.4 million related to stock-based compensation charges; and an increase of $0.1 million related to the company’s EC17/CAR T-cell therapy program. These increases were partially offset by a decrease of $0.8 million in EC1169 trial expenses and a decrease of $0.2 million for general research.

General and administrative expenses were $4.8 million for the third quarter of 2018, compared to $3.0 million for the same period in 2017. The increase was primarily attributable to: an increase of $0.8 million in compensation expense, of which $0.5 million related to stock-based compensation charges; an increase of $0.6 million in legal and professional fees; and an increase of $0.4 million in other general and administrative fees.

In September 2017, the company recorded $16.5 million of acquired in-process research and development ("IPR&D") expenses related to a development and license agreement with ABX GmbH that granted the company exclusive worldwide rights to develop and commercialize PSMA-617, including the product candidate known as 177Lu-PSMA-617. The company did not incur any IPR&D expenses in the third quarter of 2018.

Cash, cash equivalents and investments were $344.2 million at September 30, 2018, compared to $103.1 million at September 30, 2017, and $97.5 million at Dec. 31, 2017. Cash, cash equivalents and investments of $344.2 million at September 30, 2018 included $188.9 million of net proceeds from the public offering of 10,878,379 shares of the company’s common stock that closed in September 2018.

Financial Expectations

The company anticipates its cash, cash equivalents and investments balance at the end of 2018 to exceed $310 million. Based on current operational assumptions, Endocyte believes it has sufficient cash to fund its activities through the expected end of the VISION trial and potential proof of concept of its EC17/CAR T-cell therapy.

Website Information

Endocyte routinely posts important information for investors on its website, www.endocyte.com, in the "Investors & News" section. Endocyte uses this website as a means of disclosing material information in compliance with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the "Investors & News" section of Endocyte’s website, in addition to following its press releases, SEC filings, public conference calls, presentations and webcasts. The information contained on, or that may be accessed through, Endocyte’s website is not incorporated by reference into, and is not a part of, this document.

On November 7, 2018 Savara Inc. (Nasdaq: SVRA), an orphan lung disease company, reported financial results for the third quarter ending September 30, 2018 and provided a business update (Press release, Savara, NOV 7, 2018, View Source [SID1234530912]).

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"We are creating a differentiated orphan lung disease company through a portfolio of investigational programs addressing significant unmet need in rare respiratory diseases," said Rob Neville, Chief Executive Officer, Savara. "This past quarter’s achievements demonstrate considerable progress with our lead candidate, Molgradex, and in the coming year we look forward to numerous important data read-outs from our three clinical studies, two of which are pivotal. Additionally, we expect Savara’s pipeline, buoyed by indication expansion and product acquisitions, to facilitate sustainable growth now and in the future."

Recent Developments and Upcoming Highlights

Molgradex for autoimmune pulmonary alveolar proteinosis (aPAP)

Completed enrollment of 139 patients in the IMPALA study, a global, pivotal Phase 3 clinical study evaluating Molgradex, an inhaled formulation of granulocyte-macrophage colony-stimulating factory (GM-CSF) for the treatment of aPAP.
Expect top line results from the IMPALA study in Q2 2019. Positive results would facilitate the submission of a Biologic License Application in the first half of 2020, with an anticipated commercial launch in the U.S. and EU in 2020 or early 2021.
Continue active enrollment in IMPALA-X, an open-label, multicenter extension study to determine the long-term safety and utilization of Molgradex in patients with aPAP.
Announced a partnership with the PAP Foundation to support their efforts to unite, educate and assist the PAP patient community, including work to further expand the PAP patient registry.
Molgradex for nontuberculous mycobacterial (NTM) lung infection

Completed enrollment of 32 patients in the OPTIMA study, a Phase 2a clinical study evaluating Molgradex for the treatment of NTM lung infection.
Expect interim results from the OPTIMA study in Q4 2018.
Anticipate top line results from the OPTIMA study in Q2 2019.
The Investigational New Drug application for Molgradex in cystic fibrosis (CF)-affected individuals with chronic NTM lung infection has been accepted by the U.S. Food and Drug Administration. Savara expects to initiate a Phase 2a study of Molgradex in CF subjects with NTM lung infection in Q1 2019.
Completed license agreement with Mayo Clinic, enabling inclusion of Mayo clinical data in Savara’s patent applications related to NTM.
AeroVanc

Continue patient enrollment in the AVAIL study, a pivotal, global Phase 3 clinical study of AeroVanc, an inhaled vancomycin hydrochloride powder for the treatment of persistent methicillin resistant staphylococcus aureus, or MRSA, lung infection in CF. At the end of Q3, patient enrollment was at 126 out of a target of 200.
Continue to target completion of patient enrollment in the AVAIL study in Q1 2019, with top line data in H2 2019.
Exploratory Pipeline

Expect to announce the initial indication for the Phase 2-ready aerosolized amikacin/fosfomycin proprietary combination antibiotic early in 2019, with an anticipated study-start later in 2019.
Financials

Successfully closed a public offering at the end of July with net proceeds to Savara of approximately $45.8 million.
Third Quarter Financial Results
Savara’s net loss attributable to common stockholders for the three months ended September 30, 2018 was $12.6 million, or $(0.37) per share, compared with a net loss attributable to common stockholders of $6.8 million, or $(0.28) per share, for the three months ended September 30, 2017.

Research and development expenses were $9.5 million for the three months ended September 30, 2018, compared with $5.0 million for the three months ended September 30, 2017. This increase was primarily due $2.5 million in additional expenses associated with AeroVanc Phase 3 study activities and $2.5 million in development costs of Molgradex, including the expansion of the aPAP study in the U.S. and costs associated with the Phase 2 NTM study. Conversely, the total research and development costs for the three months ended September 30, 2017 included approximately $0.4 million related to the Aironite program, which was assumed in the merger with Mast Therapeutics, Inc. in April 2017 and subsequently terminated in the first quarter of 2018.

General and administrative expenses for the three months ended September 30, 2018 were $3.1 million, compared with $1.5 million for the three months ended September 30, 2017. This increase was primarily due to $1.5 million additional costs related to personnel. The remaining increase in expense was associated with continued legal and accounting requirements for a public company.

Other income of $0.1 million was recognized for the three months ended September 30, 2018 as compared to other expense of $0.4 million for the three months ended September 30, 2017. The change was primarily due to additional interest income attributable to an increased balance maintained in our short-term investments for the three months ended September 30, 2018, as compared to that for the three months ended September 30, 2017.

As of September 30, 2018, Savara had a debt balance of approximately $15.0 million and had cash, cash equivalents and short-term investments of approximately $112.0 million.

Conference Call and Webcast
Savara will hold a conference call today beginning at 5:30 PM Eastern Time/4:30 PM Central Time to provide a business update. Shareholders and other interested parties may access the conference call by dialing (855) 239-3120 from the U.S., (855) 669-9657 from Canada, and (412) 542-4127 from elsewhere outside the U.S. and request the "Savara Inc." call. A live webcast of the conference call will be available online in the Investors section of Savara’s website at View Source A replay of the webcast will be available on Savara’s website for 30 days, and a telephone replay will be available through November 12, 2018 by dialing (877) 344-7529 from the U.S., (855) 669-9658 from Canada and (412) 317-0088 from elsewhere outside the U.S. and entering the replay access code 10125683

On November 7, 2018 DURECT Corporation (Nasdaq: DRRX) reported financial results for the three months ended September 30, 2018 and provided a corporate update (Press release, DURECT, NOV 7, 2018, http://investors.durect.com/phoenix.zhtml?c=121590&p=irol-newsArticle&ID=2375965 [SID1234530911]).

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Total revenues were $8.0 million and net loss was $2.7 million for the three months ended September 30, 2018 as compared to total revenues of $20.7 million and net income of $6.1 million for the three months ended September 30, 2017. The third quarter of 2018 included a $5 million milestone payment from Indivior related to the FDA approval of PERSERIS (risperidone). The third quarter of 2017 included $12.5 million in revenues from the upfront payment related to a patent purchase agreement with Indivior.
At September 30, 2018, cash and investments were $41.5 million, compared to cash and investments of $36.9 million at December 31, 2017. Debt at September 30, 2018 was $19.9 million.
"During the third quarter, we benefited from two product approvals through corporate relationships, most notably U.S. FDA approval of Indivior’s PERSERIS to treat adults with schizophrenia, as well as the Taiwan Ministry of Health and Welfare’s approval of Orient Pharma’s Methydur Sustained Release Capsules to treat patients with ADHD," stated James E. Brown, D.V.M., President and CEO of DURECT. "We expect anticipated earn-outs and royalties from these approvals to begin providing cash flow, starting next year, that will help finance the development of our proprietary pipeline, including DUR-928, which we are currently evaluating in two Phase 2a clinical trials in alcoholic hepatitis (AH) and primary sclerosing cholangitis (PSC). We are planning to accelerate enrollment in the AH trial by enrolling both moderate and severe AH patients simultaneously going forward. In addition, we plan to initiate a Phase 2a clinical trial of topical DUR-928 in patients suffering from psoriasis in the first quarter of 2019, and a trial in nonalcoholic steatohepatitis (NASH) patients in the first half of 2019."

Update on Selected Programs:

Epigenetic Regulator Program. DUR-928, the lead product candidate in the Company’s Epigenetic Regulator Program, is an endogenous, first-in-class small molecule, which may have broad applicability in several hepatic and renal diseases such as NASH and PSC, in acute organ injuries such as AH and acute kidney injury (AKI), and in inflammatory skin disorders such as psoriasis and atopic dermatitis.

Ongoing Clinical Trials

Alcoholic Hepatitis (AH)

DURECT is conducting a Phase 2a clinical trial with intravenously administered DUR-928 in patients with AH. This is an open label, dose escalation, multi-center U.S. study, originally designed to be conducted in two sequential parts. Part A includes patients with moderate AH (as determined by the Model of End-Stage Liver Disease (MELD) scores, a common scoring system to assess the severity and prognosis of AH patients), and Part B includes patients with severe AH. Three dose levels (30, 90 and 150 mg) are planned for testing in Part A. Dose escalation occurs following review of safety and pharmacokinetic (PK) results of the prior dose level by a Dose Escalation Committee (DEC). The target number of patients for the study is 4-6 per dose group. The objectives of this study include safety, PK and pharmacodynamic (PD) signals, including liver biochemistry and biomarkers. Additional information on the trial design, including eligibility criteria and site locations, can be found at www.clinicaltrials.gov using the NCT Identifier NCT03432260.
The Company recently completed dosing for the low-dose 30 mg cohort (n=4) of Part A (moderate AH patients). After completing the safety and PK review by the DEC, DURECT plans to commence the 90 mg cohort in Part A.
The Company has amended the protocol so that after the DEC completes its review, DURECT can begin enrolling Part B (severe AH patients), starting with the low dose, while it simultaneously continues enrolling Part A (moderate AH patients). The Company believes enrolling Part A and B simultaneously will accelerate the overall timeline for the trial. Over the course of the trial, the clinical sites have encountered many severe AH patients who may have qualified for Part B but were deemed screen failures due to their MELD scores being too high for Part A.
AH is a syndrome of progressive inflammatory liver injury associated with long-term heavy intake of alcohol, and encompasses a spectrum that ranges from mild injury to severe, life threatening liver damage. The prevalence of AH is estimated to occur in 10-35% of heavy drinkers. According to an article in the Journal of Clinical Gastroenterology (2015 July; 49(6): 506-511), there were over 320,000 hospitalizations related to alcoholic hepatitis in 2010, resulting in hospitalization costs of nearly $50,000 per patient.
Primary Sclerosing Cholangitis (PSC)

The Company is currently conducting a Phase 2a clinical trial in PSC with orally administered DUR-928. This is a randomized, open label, multi-center study with two cohorts (10 mg and 50 mg), in which patients (n = 15-20 per cohort) receive daily oral dosing of DUR-928 for four weeks with follow-up for an additional four weeks. The objectives of this study include safety, PK and PD signals, including the percent change from baseline of serum alkaline phosphatase (ALP) and other biomarkers. Additional information on the trial design, including eligibility criteria and site locations, can be found at www.clinicaltrials.gov using the NCT Identifier NCT03394781. To date, five PSC patients have been dosed, and as such the Company is not able to provide meaningful interim data at this time. The Company plans to continue enrolling patients and will provide an update when enrollment has reached a critical mass for data analysis.
PSC is a chronic liver disease characterized by a progression of cholestasis (decrease in bile flow) with inflammation and fibrosis of bile ducts. DUR-928 has been awarded orphan drug designation for the PSC indication.
Planned Clinical Trials

Psoriasis

The Company is planning to conduct a Phase 2a proof-of-concept trial with topical DUR-928 in patients with mild to moderate plaque psoriasis beginning in the first quarter of 2019. This will be a multicenter, randomized, double-blind, vehicle-controlled clinical trial conducted in the U.S. Approximately 20 subjects will be enrolled to obtain about 15 evaluable subjects in the study. DUR-928 will be applied topically once-daily for four weeks. Patients will serve as their own controls, as each patient will have similar contralateral plaques. DUR-928 will be applied to one plaque and the vehicle control will be applied to the contralateral plaque daily for four weeks. Patients will be followed for an additional four weeks and the primary efficacy endpoint will be improvement in local psoriasis scores in the DUR-928-treated plaque compared to the vehicle-treated plaque.
The Company observed activity of DUR-928 in a previous exploratory Phase 1b trial utilizing intralesional injections of DUR-928 in psoriasis patients. In support of the upcoming study, it has completed multiple non-clinical safety studies for topically applied DUR-928.
Skin inflammatory disorders, such as psoriasis and atopic dermatitis, affect approximately 7.5 million and 32 million Americans, respectively. Most currently available topical treatments, typically as first line therapy, either slow down excessive skin cell proliferation or reduce inflammation. Steroids are the most commonly used topical anti-inflammatory agents because they reduce the swelling and redness of lesions.
Non-Alcoholic Steatohepatitis (NASH)

DURECT is planning to conduct a clinical trial in NASH patients with orally-administered DUR-928 beginning in the first half of 2019. Further details on study design and timing will be provided as the Company gets closer to initiation. In the Company’s previous Phase 1b NASH study, reported at the European Association for the Study of the Liver (EASL) in April 2017, a reduction of certain biomarkers after a single oral dose of DUR-928 was observed. Exploratory biomarker analysis indicated that a single oral dose of DUR-928 in NASH patients resulted in statistically significant reductions from baseline of both full-length and cleaved cytokeratin-18 (CK-18), bilirubin, hsCRP and IL-18.
Indivior Agreement and PERSERIS. In September 2017, the Company entered into a patent purchase agreement with an affiliate of Indivior PLC, whereby the Company assigned certain of its U.S. patent rights to Indivior. This assignment may provide further intellectual property protection for PERSERIS (risperidone) extended-release injectable suspension for the treatment of schizophrenia in adults.

Under the terms of the agreement, Indivior made an upfront non-refundable payment to the Company of $12.5 million. Indivior also agreed to make an additional $5 million payment to the Company based on NDA approval of PERSERIS, as well as quarterly earn-out payments that are based on a single digit percentage of U.S. net sales for certain products covered by the patent rights, including PERSERIS. The patent rights include granted patents extending through at least 2026. In July 2018, the FDA approved the NDA for PERSERIS and the Company received the $5 million milestone payment in August 2018. On November 1, 2018, Indivior stated that they are preparing a full promotional launch of PERSERIS with a field force of 40 to 60 representatives, contingent upon the preliminary injunction against Dr. Reddy’s Laboratories being upheld by the U.S. Court of Appeals for the Federal Circuit. Indivior further stated that they will be making PERSERIS available in the U.S. in Q4 2018 to begin generating product awareness and trial. For more information on PERSERIS, please see Indivior’s earnings press release dated November 1, 2018. U.S. sales of long acting injectables to treat schizophrenia were in excess of $3 billion in 2017.

POSIMIR (SABER-Bupivacaine) Post-Operative Pain Relief Depot. POSIMIR is the Company’s investigational post-operative pain relief depot that utilizes the Company’s patented SABER technology and is designed to deliver bupivacaine to provide up to 3 days of pain relief after surgery.

In October 2017, the Company reported that PERSIST, a Phase 3 clinical trial for POSIMIR did not meet its primary efficacy endpoint of reduction in pain on movement as compared to standard bupivacaine HCl over the first 48 hours after surgery. While the efficacy results trended in favor of POSIMIR versus the comparator, they did not achieve statistical significance. In May 2018, the Company amended its U.S. licensing agreement with Sandoz, pursuant to which DURECT is now eligible for up to $30 million in milestone payments based on NDA approval, and remains eligible for up to an additional $230 million in sales-based milestones. Each party, pursuant to the Amendment, is also permitted to develop or commercialize competing products. The Amendment also includes modifications to DURECT’s development obligations and to both parties’ termination provisions, including a right for DURECT to terminate for convenience prior to NDA approval. There is also a new termination fee payable to DURECT in the event that Sandoz terminates the agreement for convenience. The agreement between the two companies remains in full force and effect, except as expressly covered in the Amendment. DURECT continues to evaluate and consider potential next steps with the program.

Methydur Sustained Release Capsules (ORADUR-methylphenidate ER Capsules). In September 2018, Orient Pharma informed DURECT that it had obtained marketing authorization from the Ministry of Health and Welfare in Taiwan for Methydur Sustained Release Capsules. This product is indicated for the treatment of attention deficit hyperactivity disorder (ADHD) and will be available in three strengths (22 mg, 33 mg and 44 mg) in Taiwan. Orient Pharma also has stated that it expects to make Methydur Sustained Release Capsules commercially available in Taiwan in 2019, while seeking a partner in China and pursuing regulatory approvals in selected other countries where it has commercialization rights and a commercial presence.

In August 2009, DURECT entered into a development and license agreement with Orient Pharma Co., Ltd., a diversified multinational pharmaceutical, healthcare and consumer products company with headquarters in Taiwan. In this agreement, DURECT granted to Orient Pharma the development and commercialization rights to ORADUR-Methylphenidate ER Capsules (Methydur Sustained Released Capsules) in certain defined Asian and South Pacific countries. DURECT retains rights to North America, Europe, Japan and all other countries not specifically licensed to Orient Pharma. DURECT is entitled to receive a royalty on sales of Methydur Sustained Release Capsules by Orient Pharma. Orient Pharma has also committed to supply a portion of the commercial requirements in territories other than the United States for Methydur Sustained Release Capsules.

Debt amendment. In November 2018, the Company amended its existing $20 million term loan with Oxford Finance such that principal payments now commence 18 months later than previously scheduled (i.e., commencing June 1, 2020 rather than December 1, 2018) and the final maturity date is moved back by 30 months (i.e., from August 1, 2020 to November 1, 2022). The interest rate and final payment remain unchanged, and the Company paid Oxford Finance an amendment fee of $900,000.

Upcoming investor conference. DURECT will be presenting at the Stifel 2018 Healthcare Conference at 11:45 am Eastern time on Wednesday, November 14. The conference is being held at the Lotte New York Palace Hotel. A live audio webcast of the presentation will be available by accessing View Source . A live audio webcast of these presentations will also be available by accessing DURECT’s homepage at www.durect.com and clicking "Investor Relations." If you are unable to participate during the live webcast, the call will be archived on DURECT’s website under Audio Archive in the "Investor Relations" section.

Earnings Conference Call
A live audio webcast of a conference call to discuss third quarter 2018 results and provide a corporate update will be broadcast live over the internet at 4:30 p.m. Eastern Time on November 7 and will be available by accessing DURECT’s homepage at www.durect.com and clicking "Investor Relations." If you are unable to participate in the live webcast, the call will be archived on DURECT’s website under Audio Archive in the "Investor Relations" section.