On August 2, 2018 Acceleron Pharma Inc. (Nasdaq:XLRN), a leading biopharmaceutical company in the discovery and development of TGF-beta therapeutics to treat serious and rare diseases, reported financial results for the second quarter ended June 30, 2018.

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"We have had a very successful start to 2018, and we look forward to carrying this momentum forward throughout the rest of the year and beyond. We are extremely pleased that luspatercept, our lead product candidate and first-in-class erythroid maturation agent, achieved positive and highly statistically significant Phase 3 results in both the MEDALIST and BELIEVE trials, confirming our confidence in its clinical profile in myelodysplastic syndromes and beta-thalassemia," said Habib Dable, President and Chief Executive Officer of Acceleron. "We and our collaboration partner, Celgene, look forward to presenting the Phase 3 data at an upcoming medical congress and are focused on the execution of key regulatory activities, including US and EU submission in the first half of 2019. We believe luspatercept is a potential platform treatment to transform the lives of patients suffering from a range of hematologic diseases associated with anemia.
Added Mr. Dable: "Our neuromuscular and pulmonary programs achieved critical milestones, putting us in a position for important Phase 2 readouts for ACE-083 and sotatercept in 2019 and 2020, respectively."

Development Program Highlights

Hematology

Luspatercept:

Myelodysplastic Syndromes (MDS), Beta-Thalassemia, and Myelofibrosis (MF)
Luspatercept is a first-in-class erythroid maturation agent (EMA) designed to treat the late-stage erythroid maturation defect that results in chronic anemia and the need for regular red blood cell transfusions in adults with serious hematologic diseases. Luspatercept is part of the global collaboration between Acceleron and Celgene.

The MEDALIST and BELIEVE Phase 3 trials in patients with lower-risk MDS and transfusion-dependent beta-thalassemia, respectively, met all primary and key secondary endpoints.

Data will be submitted to a future medical meeting for presentation in late 2018.

Acceleron and Celgene plan to submit regulatory filings in the United States and Europe in the first half of 2019.

Updated results from the ongoing Phase 2 trials in MDS and beta-thalassemia were presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in June 2018.

The initiation of the COMMANDS Phase 3 trial in patients with lower-risk MDS who are treatment naïve is planned for the third quarter of 2018.

Enrollment and treatment are ongoing in the BEYOND Phase 2 trial in non-transfusion-dependent beta-thalassemia and the Phase 2 trial in MF.

Neuromuscular Disease

ACE-083:

Facioscapulohumeral Muscular Dystrophy (FSHD) and Charcot-Marie-Tooth (CMT) Disease
ACE-083 is a locally-acting therapeutic designed to have a concentrated effect on muscle mass and strength in target muscles for diseases that cause focal muscle weakness. ACE-083 utilizes the "Myostatin+" approach to inhibit multiple TGF-beta ligands.

Preliminary results from Part 1 of the ACE-083 Phase 2 trial in patients with CMT disease were highlighted in oral and poster presentations at the 2018 Peripheral Nerve Society (PNS) Annual Meeting in July.

Part 2 of the Phase 2 trial in patients with CMT was recently initiated with preliminary results expected by the end of 2019.

The Company plans to present results from all Part 1 dose cohorts in the FSHD Phase 2 trial in October 2018.

Enrollment and treatment are ongoing in Part 2 of the Phase 2 trial in patients with FSHD and preliminary results are expected in the second half of 2019.

ACE-083 received FDA Fast Track status and Orphan Drug designation in FSHD.

ACE-2494:
ACE-2494 is designed to have a systemic effect on muscle mass and strength for diseases that cause muscle weakness throughout the body. ACE-2494 utilizes the "Myostatin+" approach to inhibit multiple TGF-beta ligands.

Enrollment and treatment are ongoing in the Phase 1 healthy volunteer trial with preliminary results expected in the first half of 2019.

Pulmonary Disease
Sotatercept:

Pulmonary Arterial Hypertension (PAH)

Sotatercept acts as a ligand trap for members of the TGF-beta superfamily directly involved in the BMP signaling pathway, which is proven critical for maintaining healthy pulmonary vasculature. In multiple preclinical studies in PAH, sotatercept significantly decreased pulmonary vessel muscularization, improved pulmonary arterial pressures, and decreased indicators of right heart failure.

The Company initiated the PULSAR Phase 2 trial in patients with PAH with preliminary results expected in the first half of 2020.

The Company plans to initiate an exploratory imaging study in Q1 2019 to provide additional understanding of endpoints in anticipation of a potential pivotal trial in the future.

In November 2018, the Company will host a PAH Research and Development Deep Dive event in New York City.

The event will include internal and external expert presentations to discuss disease background, current treatment landscape, key disease pathways including BMP signaling, Acceleron’s clinical development activities, and the latest sotatercept preclinical results.

Corporate Highlights

Robert K. Zeldin, M.D., was appointed Chief Medical Officer (CMO). He brings 20 years of industry experience and joined from Ablynx, where he served as Chief Medical Officer. Prior to Ablynx, Dr. Zeldin served in senior roles at Novartis, Merck, and the U.S. Food & Drug Administration’s Center for Biologics Evaluation and Research.

Janethe Pena, M.D., Ph.D., recently joined us as Vice President of Pulmonary to lead the company’s clinical development efforts in this area. Dr. Pena most recently served as Vice President and Group Head of Pulmonology Clinical Development at Bayer Pharmaceuticals. At Bayer, she was responsible for the pulmonary portfolio, including leading clinical trials with riociguat (Adempas) in different pulmonary hypertension indications and the overall program life cycle management.
Financial Results

Cash position – Cash, cash equivalents and investments as of June 30, 2018 were $332.3 million. As of December 31, 2017, the Company had cash, cash equivalents and investments of $372.9 million. The Company believes that existing cash, cash equivalents and investments will be sufficient to fund projected operating requirements into 2021.

Revenue – Collaboration revenue for the second quarter was $3.7 million. The revenue is all from Acceleron’s partnership with Celgene and is primarily related to expenses incurred by the Company in support of luspatercept.

Costs and expenses – Total costs and expenses for the second quarter were $33.6 million. This includes R&D expenses of $25.9 million and G&A expenses of $7.7 million.

Net loss – The Company’s net loss for the second quarter ended June 30, 2018 was $28.9 million.
Conference Call and Webcast
The Company will host a webcast and conference call to discuss its second quarter financial results for 2018 and provide an update on recent corporate activities on August 2, 2018, at 5:00 p.m. EDT.

The webcast will be accessible under "Events & Presentations" in the Investors/Media page of the Company’s website at www.acceleronpharma.com. Individuals can participate in the conference call by dialing 877-312-5848 (domestic) or 253-237-1155 (international) and referring to the "Acceleron Second Quarter 2018 Earnings Call."

The archived webcast will be available for replay on the Acceleron website approximately two hours after the event.

On August 2, 2018 Xspray Pharma reported that the first clinical trial material from NerPharMa S.r.l., Xspray’s strategic pharmaceutical manufacturing partner in Milan, has been delivered to the HyNap-Dasa clinical trial, the results of which are expected in Q3 2018 (Press release, Xspray, AUG 2, 2018, View Source [SID1234650103]). HyNap-Dasa is one of three product candidates that Xspray currently has in development. The company’s goal is to launch HyNap-Dasa on the US market in 2021.
Xspray has contracted NerPharMa to produce materials for Xspray’s clinical program and finished products for future commercial sale. The material delivered to the HyNap-Dasa study is the first resulting from this collaboration.

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Xspray is developing HyNap-Dasa both as a fully equivalent version of Sprycel to be registered in the US under an Abbreviated New Drug Application (ANDA), or as an improved product under the 505(b)(2) regulatory procedure. NerPharMa is a pharmaceutical contract manufacturer and subsidiary of Nerviano Medical Sciences S.r.l. of Milan, Italy.

NerPharMa’s GMP manufacturing facility has been approved by the Italian Medicines Agency (AIFA), Italy’s national authority responsible for drug regulation, and the US Food and Drug Administration (FDA).

The clinical HyNap-Dasa trial is a pilot study, testing two formulations in healthy volunteers. Study results are expected in the third quarter and will be the base of the planned pivotal study, scheduled to start in 2019.

"Technology transfer in the pharmaceutical industry is complex, but our partnership with Nerpharma over the past half-year has gone very well, and we were able to deliver clinical trial material according to plan," commented Per Andersson, CEO of Xspray Pharma.

"We’ve now proved that we can deliver GMP materials in an FDA-approved manufacturing facility, both clinical. This is critical, partly for our ongoing clinical program, but first and foremost, for our future commercial sales in the US."

"We’re delighted that the transfer of Xspray’s technology has gone well, and that we now have functional equipment at NerPharMa. I’m convinced that we’ll see more widespread uptake of Xspray’s very useful technology soon," responded Angelo Colombo, CEO of NerPharMa.

On August 1, 2018 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, reported that it has initiated a Phase 1/2a clinical study for AGI-134, a novel compound that evokes a direct anti-tumor response, as well as a vaccine effect, via a unique, universally applicable, multi-arm mechanism that targets patient-specific tumor neoantigens (Press release, BioLineRx, AUG 1, 2018, View Source;itemid=617 [SID1234528285]).

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AGI-134 is a synthetic, intratumorally administered glycolipid designed to label cancer cells with alpha-Gal, which then become the target of pre-existing anti-Gal antibodies, effectively triggering an immediate local anti-tumor response, as well as a follow-on systemic anti-tumor response targeting both the primary injected tumor and distal secondary tumors.

The Phase 1/2a study is a multicenter, open-label study that will take place in the UK and Israel, with possible expansion to the US and additional countries in Europe in 2019. The study is primarily designed to evaluate the safety and tolerability of AGI-134, given both as monotherapy and in combination with an immune checkpoint inhibitor, in unresectable metastatic solid tumors. Additional objectives are to perform a wide array of biomarker studies and to demonstrate the mechanism of AGI-134. Furthermore, efficacy will be assessed by clinical and pharmacodynamic parameters.

The study will be comprised of two parts: (i) an accelerated dose-escalation part to assess the safety and tolerability of intratumorally injected AGI-134 as a monotherapy, as well as to determine the maximum tolerated dose and the recommended dose for part 2 of the study; and (ii) a dose expansion part at the recommended dose, comprised of three cohorts and designed to assess the safety, tolerability and anti-tumor activity of AGI-134 as a monotherapy in a basket cohort of multiple solid tumor types, as well as in two additional cohorts in combination with an immune checkpoint inhibitor – in metastatic colorectal cancer and head and neck squamous cell carcinoma.

Prof. Mark Middleton of the University of Oxford, the study’s principal investigator, stated, "We are very excited to be launching a first-in-human clinical trial assessing AGI-134 for the treatment of solid tumors. AGI-134 represents a new mechanistic class of cancer immunotherapies, with a unique and highly differentiated mode of action, harnessing pre-existing immune machinery to trigger a systemic anti-tumor response and create a pro-inflammatory tumor microenvironment. More treatment options are urgently needed for cancer patients and we are optimistic that AGI-134’s encouraging pre-clinical results are going to translate to an efficacious and safe treatment for humans."

"We are pleased to enter the clinic with our second lead oncology project," said Philip Serlin, Chief Executive Officer of BioLineRx. "Numerous pre-clinical studies to date have demonstrated that treatment with AGI-134 leads to regression of established primary tumors, prevents growth of untreated distal secondary tumors, and triggers a vaccine effect that may prevent the development of future metastases. Furthermore, a combination of AGI-134 and an anti-PD-1 immune checkpoint inhibitor has demonstrated synergistic effect in protection from secondary tumor growth. We look forward to the first results of the Phase 1/2a study expected by the end of 2020."

About AGI-134
AGI-134 is a synthetic alpha-Gal glycolipid in development for solid tumors that is highly differentiated from other cancer immunotherapies. AGI-134 is designed to label cancer cells with alpha-Gal via intratumoral administration, thereby targeting the body’s pre-existing, highly abundant anti-alpha-Gal (anti-Gal) antibodies and redirecting them to treated tumors. Binding of anti-Gal antibodies to the treated tumors results in activation of the complement cascade, which destroys the tumor cells and creates a pro-inflammatory tumor microenvironment that also induces a systemic, specific anti-tumor (vaccine) response to the patient’s own tumor neo-antigens.

AGI-134 has completed numerous pre-clinical studies. In a mouse melanoma model, treatment with AGI-134 led to regression of established primary tumors and suppression of secondary tumor (metastases) development. Synergy has also been demonstrated in additional pre-clinical studies when combined with an anti-PD-1 immune checkpoint inhibitor, offering the potential to broaden the utility of such immunotherapies, and improve the rate and duration of responses in multiple cancer types. AGI-134 was obtained by BioLineRx through the acquisition of Agalimmune Ltd.

On August 1, 2018 Clovis Oncology, Inc. (NASDAQ:CLVS) reported financial results for the quarter ended June 30, 2018, and provided an update on the Company’s clinical development programs and regulatory and commercial outlook for the second half of 2018 (Press release, Clovis Oncology, AUG 1, 2018, View Source [SID1234528301]).

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"We are pleased with the launch of Rubraca in the broader maintenance indication in the U.S. and are preparing for the planned launch in the EU early next year," said Patrick J. Mahaffy, CEO and President of Clovis Oncology. "We look forward to the presentation of the initial data for rucaparib in patients with germline or somatic BRCA mutation-positive metastatic castrate-resistant prostate cancer at ESMO (Free ESMO Whitepaper) in October, and we are actively advancing multiple combination studies for each of rucaparib and lucitanib."

Second Quarter 2018 Financial Results

Clovis reported net product revenue for Rubraca of $23.8 million for the second quarter of 2018 following the label expansion to include the earlier-line and all-comers ovarian cancer maintenance treatment indication on April 6. The supply of free drug distributed to eligible patients through the Rubraca patient assistance program for the three months ended June 30, 2018 was an additional approximately 25 percent of the overall commercial supply, or the equivalent of $7.9 million in commercial value. In the six months ended June 30, 2018, the supply of this free drug was an additional approximately 24 percent of the overall commercial supply, or the equivalent of $13.4 million in commercial value. The Company expects the free product percentage to continue in the mid to high 20-percent range for the remainder of 2018. Net product revenue for the first quarter of 2018 was $18.5 million, for a total of $42.3 million for the first six months of 2018. Net product revenue for the quarter and first half ended June 30, 2017 was $14.6 million and $21.7 million, following the initial approval and launch of Rubraca in the treatment setting on December 19, 2016.

Clovis had $682.2 million in cash, cash equivalents and available-for-sale securities as of June 30, 2018. Cash used in operating activities was $110.2 million for the second quarter of 2018 and $210.8 million for the first half of 2018, compared with $69.1 million for the second quarter of 2017 and $149.5 million for the first half of 2017. This includes product supply costs of $44.6 million in the second quarter of 2018 and $76.1 million in the first half of 2018 related to Clovis’ previously-described plan to build additional inventory in advance of the transition to a new manufacturing facility for Rubraca. Product supply costs are expected to be approximately $10 million for the remainder of 2018. The Company also expects to incur final capital costs for the new manufacturing facility of approximately $8 million in late 2018. Additionally, and also as previously described, Clovis made one-time milestone payments to Pfizer of $58 million in the second quarter of 2018 related to U.S. product approvals in December 2016 and April 2018 and European product approval in May 2018.

Clovis reported a net loss for the second quarter of 2018 of $101.2 million, or ($1.94) per share, and $178.9 million, or a net loss of ($3.48) per share for the first half of 2018. Net loss was $175.4 million, or a net loss of ($3.88) per share for the second quarter of 2017, and $233.8 million, or a net loss of ($5.24) per share for the first half of 2017.

During the second quarter of 2018, Clovis recorded a one-time charge of $20.0 million related to an agreement in principle reached with the S.E.C. that, if approved by the S.E.C. and the U.S. District Court where the settlement is to be filed, would resolve the S.E.C.’s investigation related to rociletinib.

Additionally, the net loss for the six months ended June 30, 2018 also includes a charge of $8.0 million in the first quarter related to a legal settlement. The net loss for the quarter and six months ended June 30, 2017 included a charge of $117.0 million related to a legal settlement.

The adjusted net loss excluding these items was $81.2 million, or ($1.55) per share for the second quarter, and $150.9 million, or ($2.93) per share for the first half of 2018, compared to an adjusted net loss of $58.4 million, or ($1.29) per share for the second quarter, and $116.8 million, or ($2.62) per share for the first half of 2017. Net loss for the second quarter and first half of 2018 included share-based compensation expense of $14.9 million and $26.8 million, compared to $10.7 million and $19.6 million for the comparable periods of 2017.

Clovis had approximately 52.6 million shares of common stock outstanding as of June 30, 2018.

Research and development expenses totaled $52.7 million for the second quarter of 2018 and $96.3 million for the first half of 2018, compared to $33.1 million and $65.6 million for the comparable periods in 2017. Research and development expenses will continue to increase compared to last year as planned Rubraca studies progress.

Selling, general and administrative expenses totaled $44.9 million for the second quarter of 2018 and $84.1 million for the first half of 2018, compared to $36.1 million and $65.4 million for the comparable periods in 2017. Selling, general and administrative expenses will continue to increase compared to last year in support of administrative and commercial activities related to Rubraca in the United States and Europe.

Key Milestones and Objectives for Rubraca

U.S. Approval for Ovarian Cancer Maintenance Treatment Indication

On April 6, the U.S. Food and Drug Administration (FDA) approved Rubraca (rucaparib) tablets for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. FDA granted regular approval for Rubraca in this second, broader and earlier-line indication on a priority review timeline based on positive data from the phase 3 ARIEL3 clinical trial. Biomarker testing is not required for patients to be prescribed Rubraca in this maintenance treatment indication. In addition to granting Rubraca approval in this second indication, the FDA converted the approval of the initial treatment indication from an accelerated to a regular approval.

European Union (EU) Authorization Granted for Recurrent Ovarian Cancer Treatment Indication and Maintenance Treatment Variation Under Review

In late May, the Company announced that the European Commission authorized Rubraca as monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Following the receipt of the initial Marketing Authorization for Rubraca, Clovis submitted a variation to include the maintenance indication, which was validated by the European Medicines Agency (EMA) in early July. The review is underway and an opinion for the maintenance indication from the Committee for Medicinal Products for Human Use (CHMP) is anticipated by the end of 2018. Clovis continues to establish its EU organization to support the planned launch of Rubraca in Europe.

Rubraca Clinical Development

Clovis has a robust clinical development program underway in multiple tumor types, including Clovis-sponsored, partner-sponsored and investigator-initiated trials. The following clinical studies are open for enrollment or are anticipated to open during the next several months:

The Clovis-sponsored ARIEL4 confirmatory study in the treatment setting is a Phase 3 multicenter, randomized study of Rubraca versus chemotherapy in relapsed ovarian cancer patients with BRCA mutations who have failed two prior lines of therapy. This study is currently enrolling patients.
The Clovis-sponsored Phase 3 ATHENA study in advanced ovarian cancer in the first-line maintenance treatment setting evaluating Rubraca plus Opdivo (PD-1 inhibitor), Rubraca, Opdivo and placebo in newly-diagnosed patients who have completed platinum-based chemotherapy. This study, as part of a broad clinical collaboration with Bristol-Myers Squibb, is currently open for enrollment.
The Clovis-sponsored TRITON3 study, a Phase 3 comparative study in metastatic castration-resistant prostate cancer (mCRPC) enrolling BRCA mutant and ATM mutant (both inclusive of germline and somatic) patients who have progressed on androgen-receptor (AR)-targeted therapy and who have not yet received chemotherapy in the castrate-resistant setting. TRITON3 compares Rubraca to physician’s choice of AR-targeted therapy or chemotherapy in these patients. This study is currently enrolling patients.
The Clovis-sponsored TRITON2 study in mCRPC, a Phase 2 single-arm study in patients with BRCA mutations (inclusive of germline and somatic) and also enrolling patients with deleterious mutations of other homologous recombination (HR) repair genes, including ATM. All patients will have progressed after receiving one line of taxane-based chemotherapy and one or two lines of AR-targeted therapy. This study is currently enrolling patients. The Company plans to present initial data from the ongoing TRITON2 study in a poster discussion session and host an investor/analyst event at ESMO (Free ESMO Whitepaper) on Sunday, October 21, 2018.
The Clovis-sponsored single-arm Phase 2 open-label monotherapy study of Rubraca in recurrent, metastatic bladder cancer titled ATLAS: A Study of Rucaparib in Patients with Locally Advanced or Metastatic Urothelial Carcinoma. This study is currently enrolling patients.
The Phase 1 RUCA-J study, sponsored by Clovis, is a Phase 1 study to identify the recommended dose of rucaparib in Japanese patients, which will enable development of a bridging strategy and potential inclusion of Japanese sites in planned or ongoing global studies. This study is currently enrolling patients.
The Phase 2, open-label, multi-cohort study evaluating the combination of Rubraca and Opdivo in patients with relapsed, BRCA wild-type ovarian cancer and in patients with locally advanced or metastatic bladder carcinoma. This study is sponsored by Clovis and is expected to begin in the second half of 2018.
The Phase 3 pivotal study in advanced triple-negative breast cancer (TNBC) to evaluate Opdivo and Rubraca in combination. This study is sponsored by Bristol-Myers Squibb.
The Phase 2 combination study of Opdivo with Rubraca for the treatment of mCRPC. This study, sponsored by Bristol-Myers Squibb, is being conducted as an arm of a larger sponsored prostate cancer study. This study is currently enrolling patients.
The Phase 1b combination study of the cancer immunotherapy Tecentriq (atezolizumab; anti-PDL1) and Rubraca for the treatment of ovarian and triple-negative breast cancers. This study is sponsored by Roche and is currently enrolling patients.
Exploratory studies in other tumor types are also underway.

Additionally, in June, the Company announced a planned clinical collaboration with Immunomedics to evaluate the combination of Rubraca and sacituzumab govitecan as a treatment for advanced metastatic triple-negative breast and metastatic urothelial cancers.

Lucitanib Clinical Development

Lucitanib is an oral, potent inhibitor of the tyrosine kinase activity of vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3), platelet-derived growth factor receptors alpha and beta (PDGFRα/β) and fibroblast growth factor receptors 1 through 3 (FGFR1-3), which was previously evaluated in breast and lung cancers in partnership with Servier. Clovis has received notice from Servier that they will return their ex-US rights (excluding China) for lucitanib later in 2018. Clovis therefore will own global rights (excluding China) to lucitanib. There are no payments from Clovis to Servier related to the return of these ex-US rights.

Lucitanib was originally developed by Clovis and Servier with the hypothesis of activity in FGFR driven tumors; data in breast and lung cancer were insufficient to move the program forward. Recent data for a similar drug that inhibits these same three pathways – when combined with a PD-1 inhibitor – are extremely encouraging and represent a validated and alternative hypothesis for the development of lucitanib in combination with a PD-(L)1 inhibitor, and a Clovis-sponsored combination study is now being planned. Clovis also intends to initiate a study of lucitanib in combination with rucaparib, based on encouraging data of VEGF and PARP inhibitors in combination. Each of these studies is expected to initiate before the end of Q1 2019.

Conference Call Details

Clovis will hold a conference call to discuss Q2 2018 results this afternoon, August 1, at 4:30pm ET. The conference call will be simultaneously webcast on the Company’s web site at www.clovisoncology.com, and archived for future review. Dial-in numbers for the conference call are as follows: US participants 866.489.9022, International participants 678.509.7575, conference ID: 9289064.

About Rubraca (rucaparib)

Rubraca is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in ovarian cancer as well as several additional solid tumor indications. Studies open for enrollment or under consideration include ovarian, prostate, breast, gastroesophageal, pancreatic, lung and bladder cancers. Clovis holds worldwide rights for Rubraca.

In the United States, Rubraca is approved for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Rubraca is also approved in the United States for the treatment of adult patients with deleterious BRCA mutation (germline and/or somatic) associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies and selected for therapy based on an FDA-approved companion diagnostic for Rubraca.

Rubraca is an unlicensed medical product outside of the U.S. and EU.

On August 1, 2018 DURECT Corporation (Nasdaq: DRRX) reported financial results for the three months ended June 30, 2018 and provided a corporate update (Press release, DURECT, AUG 1, 2018, View Source [SID1234528347]).

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Total revenues were $3.4 million and net loss was $7.0 million for the three months ended June 30, 2018 as compared to total revenues of $4.3 million and net loss of $9.9 million for the three months ended June 30, 2017.

At June 30, 2018, cash and investments were $42.5 million, compared to cash and investments of $36.9 million at December 31, 2017. Debt at June 30, 2018 was $19.9 million.

"We are pleased that Indivior has received FDA approval for PERSERIS, triggering a $5 million milestone payment to DURECT and future earn-out payments based on U.S. net sales," stated James E. Brown, D.V.M., President and CEO of DURECT. "Enrollment is underway in our DUR-928 Phase 2a trials with PSC and alcoholic hepatitis patients, and we expect to initiate a Phase 2 trial with DUR-928 in psoriasis patients this quarter."

Update on Selected Programs:

Indivior Agreement and PERSERIS. In September 2017, we entered into a patent purchase agreement with an affiliate of Indivior PLC, whereby DURECT 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 DURECT of $12.5 million. Indivior also agreed to make an additional $5 million payment to DURECT 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. On July 27, 2018, Indivior announced that the FDA had approved the NDA for PERSERIS. On July 30, 2018, Indivior stated that they commit to providing the launch timing for PERSERIS as soon as reasonably practicable, but no later than when its Q3 2018 results are announced which is currently scheduled for November 1, 2018. U.S. sales of long acting injectables to treat schizophrenia were in excess of $2 billion in 2017.

Epigenetic Regulator Program. DUR-928, the lead product candidate in our Epigenetic Regulator Program, is an endogenous, first-in-class small molecule, which may have broad applicability in several hepatic and renal diseases such as nonalcoholic steatohepatitis (NASH) and other disorders of the liver including primary sclerosing cholangitis (PSC), in acute organ injuries such as alcoholic hepatitis (AH) and acute kidney injury (AKI), and in inflammatory skin disorders such as psoriasis and atopic dermatitis.

Oral Administration

We are conducting a Phase 2a clinical trial in PSC with orally administered DUR-928. This is a randomized, open label study with two cohorts (a cohort of 10 mg and a cohort of 50 mg), in which patients

(n = 15-20 per cohort) will receive oral dosing of DUR-928 for four weeks with follow-up for an additional four weeks. The objectives of this study include safety, pharmacokinetics (PK), and pharmacodynamic (PD) markers, 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. As this is an open label study, we expect to generate interim data in 2018.

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.

Injectable Administration

We are also conducting a Phase 2a clinical trial with DUR-928 in patients with alcoholic hepatitis (AH). This is an open label, dose escalation study conducted in two parts. Part A is enrolling patients with moderate alcoholic hepatitis (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 will enroll patients with severe alcoholic hepatitis. The study is being conducted using three dose levels (30, 90 and 150 mg) in Part A, with sequential dose escalation following review of safety and PK results of the prior dose level. Patients are receiving DUR-928 by intravenous infusion, and the dose may be adjusted in Part B based on the findings from Part A. The trial will involve multiple clinical sites in the US and the target number of participants to complete the study is 24-36. The objectives of this study include safety, PK and PD signals, as determined by improvement in liver biochemistry, MELD (Model for End-Stage Liver Disease) and Lille scores, 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 NCT03432260. As this is an open label study, we expect to generate interim data in 2018.

Alcoholic hepatitis 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 has not been accurately determined; it 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.

Topical Administration

The promising results we achieved in a previous exploratory Phase 1b trial utilizing intralesional injections of DUR-928 in psoriasis patients led us to develop a topical formulation of DUR-928. We have had pre-IND interactions with the FDA and recently completed the last non-clinical study requested by the FDA prior to submitting the IND for a Phase 2 proof-of-concept study with topically applied DUR-928. We expect to initiate this study in the third quarter of 2018.

REMOXY ER (oxycodone) Extended-Release Capsules CII. Based on our ORADUR technology, the investigational drug REMOXY ER is a unique long-acting formulation of oxycodone designed to discourage common methods of tampering associated with opioid misuse and abuse. The REMOXY ER NDA was resubmitted to the FDA by Pain Therapeutics in February 2018. On June 26, 2018, a joint meeting of the Anesthetic and Analgesic Drug Products Advisory Committee and Drug Safety and Risk Management Advisory Committee of the FDA voted 14 to 3 against the approval of REMOXY ER for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. The PDUFA date for completion of the review is August 7, 2018.

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

In October 2017, we 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, we amended our 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. We continue to evaluate and consider potential next steps with the program.

Earnings Conference Call

A live audio webcast of a conference call to discuss second quarter 2018 results and provide a corporate update will be broadcast live over the internet at 4:30 p.m. Eastern Time on August 1 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.