On November 9, 2015 Curis, Inc. (NASDAQ:CRIS), a biotechnology company focused on the development and commercialization of innovative drug candidates for the treatment of cancers, reported its financial results for the third quarter ended September 30, 2015 (Press release, Curis, NOV 9, 2015, View Source [SID:1234508131]).

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"We are excited to have recently exercised two options under our collaboration with Aurigene to obtain exclusive licenses to the PD-L1/VISTA and IRAK4 programs," said Ali Fattaey, Ph.D., Curis’ President and CEO. "Aurigene scientists presented compelling preclinical data for each program this weekend at the AACR (Free AACR Whitepaper)-NCI-EORTC International Conference, and our internal team is working diligently with Aurigene to advance both programs into clinical development. During the first half of 2016, we expect to file an IND and initiate Phase 1 clinical testing of the PD-L1/VISTA inhibitor, CA-170, and also expect to file an IND for development of the IRAK4 inhibitor."

Dr. Fattaey continued, "We have also been working to advance CUDC-907 into the next stage of clinical development. We expect to provide additional data from the ongoing Phase 1 trial, as well as details of the planned Phase 2 study at the ASH (Free ASH Whitepaper) annual meeting later this year."

Third Quarter and Nine Months ended September 30, 2015 Financial Results

Curis reported a net loss of $5.5 million, or ($0.04) per share on both a basic and fully diluted basis for the third quarter of 2015, as compared to a net loss of $5.6 million, or ($0.06) per share on both a basic and fully diluted basis for the third quarter of 2014. Curis reported a net loss of $45.5 million, or ($0.37) per share on both a basic and fully diluted basis for the nine months ended September 30, 2015, as compared to a net loss of $13.0 million, or ($0.15) per share on both a basic and fully diluted basis for the nine months ended September 30, 2014. The net loss for the first nine months of 2015 includes an in-process research and development charge of $24.3 million related to Curis’ collaboration agreement with Aurigene.

Revenues for the third quarter of 2015 were $2.0 million, as compared to $1.8 million for the same period in 2014. The increase in revenues was primarily due to an increase in royalty revenues recorded on Genentech/Roche’s net sales of Erivedge, which increased to $2.3 million during the third quarter of 2015, as compared to $1.8 million during the same period in 2014.

Revenues for the nine months ended September 30, 2015, were $5.8 million, as compared to $7.9 million for the same period in 2014. The decrease was primarily related to a $3.0 million milestone payment that Curis received in 2014 related to its Genentech collaboration. Curis did not receive any such payments from Genentech during the nine months ended September 30, 2015. Offsetting this decrease, royalty revenues recognized from Genentech and Roche’s net sales of Erivedge increased $1.1 million to $6.0 million during the nine months ended September 30, 2015 as compared to $4.9 million during the same period in 2014, a 23% increase over the prior year period.

Operating expenses for the third quarter of 2015 were $6.9 million, as compared to $6.5 million for the same period in 2014. Operating expenses for the nine months ended September 30, 2015 were $49.0 million, as compared to $18.9 million for the same period in 2014 and were comprised of the following:

Costs of royalty revenues. Costs of royalty revenues, which are comprised of amounts due to third-party university patent licensors in connection with Genentech/Roche’s Erivedge net sales, were $116,000 and $89,000 during the third quarters of 2015 and 2014, respectively. Costs of royalty revenues for the nine months ended September 30, 2015 were $303,000, as compared to $246,000 for the same period in 2014.

In-process research and development expenses. The Company recorded a one-time charge for in-process research and development expense of $24.3 million during the nine months ended September 30, 2015 associated with the issuance of 17,120,131 shares of Curis common stock to Aurigene as partial consideration for the rights granted under the terms of the parties’ January 2015 collaboration agreement.

Research and development expenses. Research and development expenses were $4.0 million for the third quarter of 2015, as compared to $3.7 million for the same period in 2014. The increase in research and development expenses was primarily due to increased spending on CUDC-907 and preclinical programs under the Company’s collaboration with Aurigene. The Company incurred expenses of $2.8 million and $2.1 million on CUDC-907 for the quarters ended September 30, 2015 and 2014, respectively, related to its ongoing Phase 1 studies of this molecule. The Company recorded costs of $700,000 on the Company’s preclinical research programs under the Aurigene collaboration for the three months ended September 30, 2015. Offsetting these increases, spending on CUDC-427 and other programs decreased by $1 million during the three months ended September 30, 2015 as compared to the prior year period. Research and development expenses were $14.7 million for the nine months ended September 30, 2015 as compared to $10.2 million for the same period in 2014.

General and administrative expenses. General and administrative expenses were $2.8 million for the third quarter of 2015, as compared to $2.7 million for the same period in 2014. Increased spending on consulting and professional services and stock-based compensation were offset by decreases in legal spending. General and administrative expenses were $9.7 million for the nine months ended September 30, 2015 as compared to $8.5 million for the same period in 2014.

Other expense was $699,000 for the third quarter of 2015, as compared to $827,000 for the same period in 2014. Other expense primarily consisted of $827,000 and $934,000 in interest expense for the quarters ended September 30, 2015 and 2014, respectively, related to the loan made by BioPharma-II to Curis Royalty, a wholly-owned subsidiary of Curis. Other expense was $2.3 million and $2.0 million for the nine month periods ended September 30, 2015 and 2014, respectively.

As of September 30, 2015, Curis’ cash, cash equivalents, marketable securities and investments totaled $93.5 million, and there were approximately 128.4 million shares of common stock outstanding.

Recent Operational Highlights

Aurigene Collaboration:

In October 2015, Curis exercised its option to exclusively license a first-in-class oral, small molecule antagonist designated as CA-170 that targets PD-L1 and VISTA, two negative checkpoint regulators of immune activation. CA-170 was selected from the broad PD-L1 antagonist program that the companies have been engaged in since the collaboration was established in January 2015. Curis also exercised its option to exclusively license a program of orally available small molecule inhibitors of IRAK4 kinase, a serine/threonine kinase involved in innate immune responses as well as in certain hematologic cancers.
Curis selected another preclinical program within the immuno-oncology collaboration with Aurigene that is focused on evaluating small molecule antagonists with dual PD-L1 and T-cell immunoglobulin and mucin domain containing protein-3 (TIM-3) targeting properties.

In November, Curis presented data at the 2015 AACR (Free AACR Whitepaper)-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference in Boston, Massachusetts for the PD-L1/VISTA and IRAK4 programs.

Erivedge:

In November, Roche disclosed its intent to initiate a clinical study to examine the effectiveness of Erivedge in combination with ruxolitinib in participants with intermediate- or high-risk myelofibrosis. Myelofibrosis is a serious bone marrow disorder that disrupts the body’s normal production of blood cells. The result is extensive scarring in bone marrow, leading to anemia, weakness, fatigue, and often, an enlarged spleen and liver.
A Phase 1b portion of the study will assess the safety of Erivedge plus ruxolitinib combined therapy. After getting confirmation about the safety and toxicity of this combination, a randomized, controlled portion of the study may begin. The primary endpoints relate to reduction in spleen volume and overall response rate. Details of the study have been posted on clinicaltrials.gov.

Upcoming Activities

Curis expects to present at the following conferences through February 2016:

American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando, Florida: December 5-8, 2015
Oppenheimer 26th Annual Healthcare Conference in New York City: December 8-9, 2015
BIO CEO Investor Conference 2016: February 8-9, 2016
2016 RBC Capital Markets’ Healthcare Conference in New York City: February 23-24, 2016

On November 9, 2015 BioTime, Inc. (NYSE MKT and TASE:BTX) reported financial results for the third quarter ended September 30, 2015 and provided an update on its recent accomplishments (Press release, BioTime, NOV 9, 2015, View Source;p=RssLanding&cat=news&id=2110377 [SID:1234508130]).

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"During the third quarter, BioTime and its family of companies achieved significant progress on multiple fronts," said Adi Mohanty, BioTime’s co-Chief Executive Officer. "We are delivering on our commitment to reduce the complexity of our operations while progressively unlocking the value of our subsidiaries for BioTime shareholders. An important step forward in this effort was the announcement that OncoCyte Corporation, our cancer diagnostics subsidiary, had filed a Form 10 Registration Statement with the Securities and Exchange Commission for our planned distribution of OncoCyte common stock to our shareholders. On the financial front, we strengthened our capital position through the sale of $34.0 million of BioTime common shares to institutional investors in September and early October. At the same time, we continued to advance the clinical development of our products that are aimed at addressing large unmet patient needs. We also announced several collaborations with leading medical and academic institutions, as well as a major corporate partnership to develop bone grafting products. All the while, we’ve continued to evolve the management of the company toward an organization that is structured to support later-stage clinical trials and commercial products."

"BioTime continues to strengthen its leadership position in regenerative medicine on many fronts," said Dr. Michael D. West, BioTime’s co-Chief Executive Officer. "During the third quarter, BioTime’s ESI-BIO division launched its new technology platform that provides a more complete and accurate model to study the effects of drugs and therapeutic compounds on vascular network formation. The recently announced formation of Ascendance Biotechnology, Inc. by combining ESI-BIO with Hepregen Corporation has the potential to offer an enhanced, broad portfolio of products and services to the rapidly growing and largest segment of the research product market. Our proprietary PureStem technology for the production of industrial-scale pure stem cells is the basis for the collaboration between our subsidiary OrthoCyte Corporation and Heraeus Medical GmbH for the development of bone grafting therapies. This collaboration represents validation for our human embryonic progenitor cell technology as we continue to develop other products based on PureStem."

Third Quarter and Recent Highlights

Corporate Developments

On November 5, 2015, BioTime and Hepregen Corporation formed Ascendance Biotechnology, Inc., a new self-funding company that combines Hepregen’s cellular micro-patterning drug and chemical screening technologies with BioTime’s ESI-BIO research products and proprietary stem cell technologies.

BioTime’s Board of Directors appointed Adi Mohanty to serve with Michael D. West as co-Chief Executive Officer. Dr. West will lead BioTime’s science, technology development, and intellectual property activities with a particular focus on growing the Company’s discovery and pre-clinical product development programs. Mr. Mohanty will lead the Company’s advanced clinical development programs and commercialization strategies, as well as assume leadership of its corporate and administrative activities. Mr. Mohanty has served as BioTime’s Chief Operating Officer since December 2014.

BioTime raised approximately $34.0 million during the third quarter and early October through sales of common shares to a select group of U.S. investors, and certain investment funds in Israel that hold shares of companies that are included within Tel Aviv Stock Exchange indexes.

BioTime’s subsidiary OncoCyte Corporation filed a Form 10 Registration Statement with the Securities and Exchange Commission for BioTime’s planned distribution of OncoCyte common stock to BioTime common shareholders. BioTime expects that the distribution will provide OncoCyte with greater access to capital markets in order to obtain its own financing for its operations, separately from BioTime financings. The distribution will also allow BioTime and OncoCyte to each focus on its own strategic priorities relating to its own management, capital structure, business model, and financial goals. BioTime’s plan is to effect the distribution to BioTime shareholders in late 2015, subject to certain conditions. BioTime expects to continue to own a majority of the outstanding common stock in OncoCyte immediately after the distribution.

OncoCyte Corporation appointed Cavan Redmond, former CEO of WebMD Health Corp. and Group President of Pfizer, as an independent member of its Board of Directors. Mr. Redmond is a seasoned healthcare strategist who has held a number of global leadership positions and has over 25 years of corporate strategy experience.

On November 2, 2015, BioTime’s subsidiary Asterias Biotherapeutics, Inc. (NYSE MKT: AST) announced the appointment of Georgia Erbez as Chief Financial Officer, effective November 9, 2015. Ms. Erbez is a seasoned financial executive with experience in the areas of capital resource development and business development. Previously, Ms. Erbez served as a financial consultant to numerous biotechnology companies. Prior to that, she served as Chief Financial Officer, Secretary, and Treasurer of Raptor Pharmaceutical Corp.

BioTime’s common shares began trading on the Tel Aviv Stock Exchange (TASE) under the ticker symbol BTX on September 8, 2015. BioTime’s shares were included in six major TASE equity indexes: TA-75, TA-100, TA-BlueTech, TA-Composite, TA-Tech-Elite, and TA-Biomed. BioTime’s shares will continue to be listed on the NYSE MKT, subject to the rules and regulations of the NYSE MKT applicable to listed companies.

Cell Therapies

Cell Cure Neurosciences Ltd. received Fast Track designation from the U.S. Food and Drug Administration (FDA) for OpRegen for the treatment of the dry form of age-related macular degeneration (AMD), a leading cause of blindness in an aging population. The Fast Track designation confers benefits to a drug sponsor, including more frequent communication with FDA on the drug development plan, clinical trial design, potential eligibility for Accelerated Approval and Priority Review, and a rolling regulatory review. OpRegen is a cell-based therapeutic product consisting of retinal pigment epithelial (RPE) cells.
In August, Asterias Biotherapeutics, Inc. concluded recruitment of the initial safety cohort of the SCiStar Phase 1/2a dose-escalation clinical trial of AST-OPC1 (oligodendrocyte progenitor cells) for complete cervical spinal cord injury (SCI), in which three patients were administered a low dose of 2 million AST-OPC1 cells. The results of the study continue to support a robust safety profile for AST-OPC1, with no serious adverse events observed in any of the three treated patients to date.

In October, following review of the 30-day post-injection safety data from the initial safety cohort, the Data Monitoring Committee recommended dose escalation of AST-OPC1 to the second cohort in the Phase 1/2a clinical trial. Recruitment for the second cohort has commenced, with a planned enrollment of five patients who will each receive 10 million cells of AST-OPC1.
Asterias announced the publication of preclinical data in Regenerative Medicine that supports the safety and use of AST-OPC1 as a treatment for SCI. The preclinical results showed that AST-OPC1 cells did not cause any adverse clinical observations, toxicities, allodynia, or tumors. AST-OPC1 exhibited robust persistence and limited migration within the thoracic and cervical spinal cord. In addition, AST-OPC1 demonstrated nerve growth-stimulating properties and remyelinating properties that supported restoration of function in animal models.

Asterias announced a collaboration with the UK-based Cell Therapy Catapult to advance the development of large-scale manufacturing processes for AST-VAC2, Asterias’ allogeneic dendritic cell immunotherapy. Under the agreement, the Cell Therapy Catapult will streamline and scale manufacturing processes for AST-VAC2 to support advanced clinical trials and eventual commercialization of AST-VAC2. Asterias has an ongoing partnership with Cancer Research UK to execute the first stage of AST-VAC2 clinical development, under which Cancer Research UK will sponsor and manage a Phase 1/2a clinical trial of AST-VAC2 in non-small cell lung carcinoma.

BioTime’s subsidiary OrthoCyte Corporation and Heraeus Medical entered into exclusive development and worldwide licensing agreements for the development of innovative bone grafting therapies to address orthopedic unmet needs based on the use of BioTime’s proprietary PureStem human embryonic progenitor cell technology.

Cell Delivery Technology

Patient enrollment is ongoing in BioTime’s pivotal clinical trial in Europe of Renevia for HIV-associated lipoatrophy. As planned, an additional clinical trial site in Barcelona was recently opened. BioTime currently expects completion of trial enrollment in the first half of 2016. There have been no serious adverse events observed in any of the treated patients to date.

Cancer Diagnostics Platform

The Wistar Institute and BioTime subsidiary OncoCyte Corporation expanded their collaboration to continue to develop a simple, non-invasive, highly sensitive and specific, blood-based diagnostic test designed to aid physicians in the early detection of lung cancer. The expanded collaboration follows the presentation at the American Thoracic Society International Conference in May 2015 of interim results from a large clinical trial, which showed that OncoCyte’s blood-based diagnostic test for non-invasive detection of lung cancer demonstrated a high level of observed sensitivity and specificity. Dependent on achieving successful scientific and technical results at this stage of development, OncoCyte and Wistar will conduct final validation of the diagnostic test with the goal of completing that work in 2016 to enable OncoCyte to commercially launch the lung diagnostic test.

Other Products

ESI-BIO, the stem cell products division of BioTime, Inc., launched its new technology platform, VascuNet Pericyte Co-Culture Assay, designed to give pharmaceutical drug screeners and researchers new standardized in vitro assays that provide a stable, clinically relevant angiogenesis model with greater physiological relevance and accuracy not currently obtainable by other vascular network systems.

The Icahn School of Medicine at Mount Sinai and LifeMap Solutions, a digital-health subsidiary of BioTime, Inc., announced initial results and new features to enhance clinical impact for their free Asthma Health app. The app enables individuals with asthma to participate in a large-scale medical research study by simply using their Apple iPhones. The app’s newest features will help enable Asthma Health study participants to use the app with their physicians.

LifeMap Sciences, Inc. announced that its next-generation sequencing (NGS) analysis and interpretation tools, VarElect, the NGS phenotyper, and GeneAnalytics, a novel gene set analysis tool, have been licensed by SciLifeLab. The LifeMap NGS tools will be used by SciLifeLab, a leading provider of molecular biosciences services to leading biomedical research institutions and companies, to enhance the bioinformatics analysis services that it provides across Sweden.

Financial Results

Revenue

BioTime’s operating revenues are currently generated from the following sources: research grants, licensing fees, and royalties from the sale of Hextend; advertising from the marketing of the LifeMap Sciences online database products; and from the sale of hydrogels and stem cell products for research.

Total consolidated revenues for the third quarter were $2.3 million, up $1.1 million from $1.2 million for the same period one year ago. Total consolidated revenues for the nine months ended September 30, 2015 were $5.6 million, up $2.2 million from $3.4 million for the same period one year ago. The increase in revenues is primarily attributable to increases in grant income primarily from Israel’s Office of the Chief Scientist and the California Institute for Regenerative Medicine, and from sales of research products and services.

Expenses

Consolidated operating expenses for the third quarter were $19.0 million, compared to $13.1 million for the same period in 2014. Research and development expenses for the third quarter were $11.4 million, compared to $8.8 million in the third quarter a year ago. The increase is in part a result of increased expense primarily related to regulatory and clinical trials of Asterias’ AST-OPC1, and OncoCyte’s cancer diagnostic tests. General and administrative expenses for the third quarter were $7.5 million, compared to $4.3 million in the third quarter a year ago. The increase is in part a result of increased staffing at BioTime, OncoCyte, and LifeMap Sciences’ subsidiary LifeMap Solutions.

Operating expenses for the nine months ended September 30, 2015 were $48.7 million, compared to expenses of $39.0 million for the same period of 2014. Excluding Asterias’ operating expense of $17.0 million, the expenses of BioTime and its other subsidiaries, including OncoCyte and the ESI-BIO operations that are now part of Ascendance, totaled $31.7 million. The increase in operating expenses is primarily attributable to increases in staffing and increased expenditures for the Asterias, OncoCyte, and LifeMap Solutions product development programs, offset in part by a reduction in development expenses for BioTime’s HyStem hydrogel and the OrthoCyte and ReCyte Therapeutics product development programs.

Net Loss

Net loss attributable to BioTime for the three months ended September 30, 2015 was $13.6 million, including deferred income tax benefits of $948,000. For the same period in 2014, net loss was $8.3 million, including deferred income tax benefits of $2.3 million. On a per share basis, net loss for the third quarter in 2015 was $0.18 per share, compared to a net loss of $0.12 per share for the same period in 2014.

Net loss attributable to BioTime common shareholders for the nine months ended September 30, 2015 was $33.6 million or $0.43 per share, compared to a net loss of $25.8 million or $0.41 per share for the same period in 2014. The increase in net loss is primarily attributed to increased expenditures for the Asterias, OncoCyte, and LifeMap Solutions product development programs, offset in part by a reduction in development expenses for BioTime’s HyStem hydrogel and the OrthoCyte and ReCyte Therapeutics product development programs. This increase in net loss is also to some extent offset by the $3.4 million income tax benefit recorded as of September 30, 2015 and $5.2 million in the same period in 2014.

Net losses attributable to BioTime include losses from BioTime majority-owned subsidiaries based upon BioTime’s percentage ownership of those subsidiaries.

Balance Sheet

Cash and cash equivalents totaled $29.4 million as of September 30, 2015, compared to $29.5 million as of December 31, 2014. The cash on hand as of September 30, 2015 includes $24.8 million held by Asterias, OncoCyte, and other subsidiaries.

During October 2015, BioTime raised an additional $25.5 million and BioTime’s subsidiary OncoCyte raised an additional $771,000 of equity capital through the sale of 8.4 million BioTime common shares, combined, to certain investors. As a result, BioTime had approximately $52.0 million in cash and cash equivalents as of October 31, 2015.

On November 09, 2015 Advaxis, Inc. (NASDAQ:ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, reported it presented a poster featuring clinical development advances with its Lm Technology at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2015 Annual Meeting in National Harbor, Md (Press release, Advaxis, NOV 9, 2015, View Source [SID:1234508128]). The purpose of this study was to evaluate whether axalimogene filolisbac could be dosed at higher levels than previous studies conducted by Advaxis in patients with persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC).

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While previous clinical studies of axalimogene filolisbac were evaluated at 1 x 109 CFU, data from this Phase 1 dose escalation study showed axalimogene filolisbac may be safely administered with prophylactic antibiotics up to 1 x 1010 CFU, a tenfold increase. Higher doses of axalimogene filolisbac have been shown pre-clinically to correlate with increased antigen presentation and greater targeted anti-tumor activity.

Clinical data from the ongoing Phase 1/2 clinical trial reported the first evidence for the safety and tolerability of axalimogene filolisbac at higher doses in patients with PRmCC. In the study, a total of 27 cycles of therapy were delivered at the 5 x 109 CFU dose level and to date, 5 cycles at the high dose of 1 x 1010 CFU, which will now constitute the randomized Phase 2 dose (RP2D). The adverse events observed at the high dose are consistent with previous experience.

"I’m extremely excited about this study because we have evaluated doses of axalimogene filolisbac at 5 and 10 times the level currently administered in the clinical trial program to date, with the goal of evaluating whether the increased dose and protein expression may lead to greater clinical benefit," said principal investigator Sharad Ghamande, M.D., Director of Gynecology Oncology at GRU Cancer Center, Georgia Regents University in Augusta, Ga. "Importantly, even at higher doses, the adverse event profile continues to be predominantly grade 1 grade 2, transient events, self-resolving within hours or resolving promptly with the introduction of anti-inflammatory medications."

The RP2D will now be explored further in an expansion cohort in subjects with PRmCC.

About Cervical Cancer

Cervical cancer is the fourth most common cancer and the most common cause of mortality in women worldwide. In the United States, nearly 13,000 new cases are diagnosed and approximately 4,100 deaths are reported because of cervical cancer. According to the WHO/ICO Information Centre on HPV and Cervical Cancer, about 3.9 percent of women in the U.S. are estimated to harbor high-risk cervical HPV infection at a given time, and 71.7 percent of invasive cervical cancers are attributed to high-risk HPV strains.

About Axalimogene Filolisbac

Axalimogene filolisbac (ADXS-HPV) is Advaxis’s lead Lm Technology immunotherapy candidate for the treatment of HPV-associated cancers and is in clinical trials for three potential indications: invasive cervical cancer, head and neck cancer, and anal cancer. In a completed randomized Phase 2 study in recurrent/refractory cervical cancer, axalimogene filolisbac showed apparent prolonged survival, objective tumor responses, and a manageable safety profile alone or in combination with chemotherapy, supporting further development of the company’s Lm Technology.

On November 09, 2015 Aduro Biotech, Inc. (Nasdaq:ADRO) reported five posters highlighting ongoing clinical trials and pre-clinical programs investigating its novel immunotherapies in development for the treatment of cancer were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting held in National Harbor, Maryland last week (Press release, Aduro BioTech, NOV 9, 2015, View Source;p=RssLanding&cat=news&id=2110402 [SID:1234508127]).

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In a poster presented on Saturday, November 7, 2015 by Nitya Nair, Ph.D., scientist at Aduro, updated safety and efficacy data were shared from the Phase 2a clinical trial of Aduro’s novel immunotherapy CRS-207 in combination with GVAX Pancreas in patients with metastatic pancreatic cancer. Seven patients treated with this regimen survived for over three years, with one patient continuing to receive the combination regimen. In addition, the poster highlighted key biomarker findings in 38 patients from the 93-patient trial which demonstrated a statistically significant correlation between levels of certain immune cells in the peripheral blood and overall survival. Specifically, the data showed elevated subsets of CD8+ immune T cells at baseline and at seven weeks after treatment initiation resulted in better performance outcomes. Conversely, an increase in subsets of certain myeloid cells (CD14+) at the same time points was associated with worse outcomes.

In another poster presented by Jeremy Foote, Ph.D. D.V.M., at Johns Hopkins University School of Medicine, encouraging preclinical results demonstrated that direct intratumoral injection of Aduro’s human STING-activating CDN immunotherapy in a model of HER2+ breast cancer resulted in complete eradication of the injected tumor as well as distant untreated tumors. In addition, the responses observed were durable, showing long lasting immunologic memory and anti-tumor protection when CDN-treated mice were re-challenged with HER2+ breast cancer tumor cells. In a much more challenging tumor model that is profoundly tolerant for the HER2 tumor antigen and with greater similarity to advanced cancer patients, treatment combining a single intratumoral injection of CDN with cyclophosphamide and anti-PD-L1 immune checkpoint antibodies resulted in pronounced inhibition of tumor growth. Together, these results demonstrate that activation of the STING pathway in the tumor microenvironment by the direct injection of Aduro’s proprietary CDNs results in the development of tumor antigen-specific immunity and tumor regression.

Separately, three additional posters were presented at the SITC (Free SITC Whitepaper) meeting that provide details on the ongoing trials, namely the Phase 2b STELLAR trial in pancreatic cancer, an expanded cohort in a Phase 1b trial in mesothelioma and a Phase 1 trial in grade 3/4 gliomas, including glioblastoma multiforme.

The STELLAR (Safety and Therapeutic Efficacy of Live-attenuated Listeria/GVAX with Anti-PD1 Regimen) poster highlighted the randomized, controlled trial that now has an increased enrollment target of 102 adult patients with metastatic pancreatic cancer who have failed one prior chemotherapy regimen for metastatic disease. Patients are randomized equally to one of two arms: Arm A with CRS-207/GVAX Pancreas vaccine and nivolumab or Arm B with CRS-207/GVAX Pancreas vaccine. The primary objective of this study is to compare the overall survival of patients in Arm A and Arm B. Secondary endpoints include evaluation of clinical and immune response and safety. For more information, please visit ClinicalTrials.gov (Identifier: NCT02243371). With the increased enrollment target, Aduro now expects enrollment to be completed in the second half of 2016 and continues to expect interim data in the second half of 2016.

A separate poster highlighted an expansion cohort in the Phase 1b clinical trial of CRS-207 in combination with chemotherapy. In this second cohort, eligible patients will first receive low-dose cyclophosphamide (Cy) one day prior to receiving two prime vaccinations with CRS-207 two weeks apart, followed by up to six cycles of standard-of-care pemetrexed and cisplatin chemotherapy three weeks apart and two CRS-207 boost vaccinations three weeks apart. Cy has been added to the regimen for the second cohort of patients to evaluate whether the triplet regimen improves tumor responses by reducing regulatory T-cells with Cy. Clinically stable patients will continue to receive Cy/CRS-207 maintenance vaccinations every eight weeks and are followed every eight weeks until disease progression. Objectives of the study are safety, immunogenicity, objective tumor responses and tumor marker kinetics.

Another poster provided an overview of the investigator-sponsored Phase 1 trial to evaluate the safety and immunogenicity of Aduro’s ADU-623 in grade 3/4 gliomas (including anaplastic astrocytomas and glioblastoma brain cancers). This is a dose-escalation trial enrolling up to 18 patients. The primary objective of the trial is to identify the maximum tolerated dose and characterize the safety profile of the ADU-623 vaccine in patients with treated and recurrent grade 3/4 astrocytomas. For more information, please visit ClinicalTrials.gov (Identifier: NCT01967758).

About CRS-207
CRS-207 is one of a family of product candidates based on Aduro’s live-attenuated, double-deleted (LADD) Listeria monocytogenes immunotherapy platform that induces a potent innate and T cell-mediated adaptive immune response. CRS-207 has been engineered to express the tumor-associated antigen mesothelin, which is over-expressed in many cancers including mesothelioma and pancreatic, non-small cell lung, ovarian, endometrial and gastric cancers.

About Cyclic Dinucleotide (CDN)
Aduro’s proprietary CDN product candidates are synthetic small molecule immune modulators that are designed to target and activate a receptor known as the Stimulator of Interferon Genes, or STING. The STING receptor is generally expressed at high levels in immune cells, including dendritic cells. Once activated, the STING receptor initiates a profound innate immune response through multiple pathways, inducing the expression of a broad profile of cytokines, including interferons and chemokines. This subsequently leads to the development of an effective tumor antigen-specific T cell adaptive immune response.

About LADD and ADU-623

LADD is Aduro’s proprietary platform of live-attenuated double-deleted Listeria monocytogenes strains that have been engineered to induce a potent innate immune response and to express tumor-associated antigens to induce tumor-specific T cell-mediated immunity. ADU-623 is engineered to express EGFRvIII and NY-ESO-1, which are expressed in glioblastoma and other cancers.

About Aduro

On November 9, 2015 RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) ("RedHill" or the "Company"), an Israeli biopharmaceutical company primarily focused on late clinical-stage, proprietary, orally-administered, small molecule drugs for inflammatory and gastrointestinal diseases, including cancer, reported its financial results for the quarter ended September 30, 2015 (Press release, RedHill Biopharma, NOV 9, 2015, View Source [SID:1234508126]).

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Financial highlights for the third quarter and for the nine months ended September 30, 2015:

Revenues for the nine months ended September 30, 2015 were immaterial compared to revenues of approximately $7.0 million for the nine months ended September 30, 2014, which resulted mainly from an upfront payment of $7.0 million received from Salix Pharmaceuticals, Inc. ("Salix") for the out-licensing of RedHill’s RHB-106 encapsulated bowel preparation and related rights received in 2014.

Cost of Revenues for the nine months ended September 30, 2015 was immaterial compared to approximately $1.0 million for the nine months ended September 30, 2014, which resulted from a payment of $1.0 million to Giaconda Limited, triggered by the Salix licensing transaction in 2014.

Research and Development Expenses, net for the quarter ended September 30, 2015 were approximately $3.9 million, compared to approximately $4.1 million in the quarter ended September 30, 2014. Research and Development Expenses, net for the nine months ended September 30, 2015 were approximately $12.8 million, compared to approximately $9.0 million for the nine months ended September 30, 2014. The increase in the nine months ended September 30, 2015 was mainly due to an increase in expenses related to the ongoing Phase III studies with RHB-104 (Crohn’s disease), RHB-105 (H. pylori) and BEKINDA (gastroenteritis and gastritis).

General and Administrative Expenses for the quarter ended September 30, 2015 were approximately $0.7 million, compared to approximately $0.9 million in the quarter ended September 30, 2014. The decrease was mainly due to a reduction in share-based compensation. General and Administrative Expenses for the nine months ended September 30, 2015 were approximately $2.4 million, compared to approximately $2.9 million for the nine months ended September 30, 2014. Thehigher expenses during the comparable period in 2014 were mainly due to professional fees associated with the January 2014 private placement.

Operating Loss for the quarter ended September 30, 2015 was approximately $4.6 million, compared to approximately $5.0 million in the quarter ended September 30, 2014. Operating Loss for the nine months ended September 30, 2015 was approximately $15.2 million, compared to approximately $5.8 million in the nine months ended September 30, 2014. The increase was mainly due to higher Research and Development Expenses and to immaterial revenues during the current period compared to the $7.0 million revenues during the comparable period in 2014..

Financing Income, net for the quarter ended September 30, 2015 were approximately $1.3 million, compared to approximately $0.8 million in the quarter ended September 30, 2014. The increase was mainly due to non-cash financing income of $1.3 million that resulted from the revaluation of warrants to investors presented at fair value under the Company’s derivative financial instruments.

Net Cash Used in Operating Activities for the quarter ended September 30, 2015 was approximately $3.7 million, compared to approximately $3.8 million in the quarter ended September 30, 2014. Net Cash Used in Operating Activities for the nine months ended September 30, 2015 was approximately $11.8 million, compared to approximately $6.3 million in the nine months ended September 30, 2014. The increase was mainly due to a higher Operating Loss.

Net Cash Used by Investment Activities for the nine months ended September 30, 2015 was approximately $1.1 million, compared to approximately $17.8 million in the nine months ended September 30, 2014. The decrease was mainly due to investments of cash in bank deposits in the amount of $17 million during the nine months ended September 30, 2014.

Net Cash Provided by Financing Activities for the quarter ended September 30, 2015 was approximately $41.5 million, mainly due to the July 2015 public offerings, compared to immaterial Net Cash Provided by Financing Activities in the quarter ended September 30, 2014. Net Cash Provided by Financing Activities for the nine months ended September 30, 2015 was approximately $54.8 million, mainly due to the February and July 2015 public offerings, compared to approximately $24.4 million for the nine months ended September 30, 2014, mainly from two private placements and the exercise of warrants during the first quarter of 2014.

Cash Balance1 as of September 30, 2015 was approximately $64.2 million,compared to $26.6 million as of June 30, 2015. The increase was due to the July 2015 public offering.

Ori Shilo, Deputy CEO, Finance and Operations, said: "We are very pleased with our financial and operational results for the third quarter of 2015. Following our recent public offering, we strengthened our cash position to approximately $64 million at the end of the quarter. Our solid cash position allows us to continue the development of our advanced development pipeline, including the ongoing Phase III studies with BEKINDA for gastroenteritis and with RHB-104 for Crohn’s disease, and to conduct a confirmatory Phase III study with RHB-105 for H. pylori eradication. During the quarter we generated more data from the successful RHB-105 first Phase III study for H. pylori, further supporting the potential superior efficacy of RHB-105 over standard-of-care therapies and we intend to hold a meeting with the FDA to present the Phase III data and to discuss the path to approval. Earlier today, we announced that we have received the first marketing approval for RIZAPORT for the treatment of acute migraines in Europe. This is a very significant milestone for RedHill and we are continuing our discussions with potential commercialization partners for Europe, the U.S. and additional territories. We are also advancing the development program for our promising novel oncology drug candidate YELIVA, with recently announced positive results from the Phase I study for advanced solid tumors and the recent initiation of a Phase I/II for diffuse large B-cell lymphoma. The YELIVA development program is supported by various grants from the National Cancer Institute, including a $2 million grant supporting a Phase I/II study for multiple myeloma, planned to be initiated by early 2016."

Recent operational highlights:

On November 9, 2015, the Company, together with IntelGenx Corp. ("IntelGenx"), announced that the Federal Institute for Drugs and Medical Devices of Germany (BfArM) granted marketing authorization of RIZAPORT (RHB-103) 5mg and 10mg, an oral thin film formulation of rizatriptan benzoate for the treatment of acute migraines. The national approval of RIZAPORT in Germany was granted under the European Decentralized Procedure (DCP), in which Germany served as the Reference Member State. This authorization is the first national marketing approval of RIZAPORT. Marketing authorization in Luxemburg, the Concerned Member State, is expected to follow. RedHill and IntelGenx intend to continue to work together to obtain national phase approvals in other European DCP territories.

On October 26, 2015, the Company announced positive top-line results from the Phase I study with YELIVA (ABC294640) in patients with advanced solid cancers. The study successfully met its primary and secondary endpoints, providing key information about the drug’s safety, toxicities, pharmacokinetics (PK) and pharmacodynamics (PD), supporting the ongoing and planned Phase II studies with YELIVA (ABC294640), a proprietary, first-in-class, orally-administered sphingosine kinase-2 (SK2) selective inhibitor. The results demonstrated that YELIVA (ABC294640) can be safely administered to cancer patients at doses that provide circulating drug levels that are predicted to have therapeutic activity, based on levels required in preclinical models. The first-in-human Phase I study treated 21 patients with advanced solid tumors, the majority of which were gastrointestinal cancer patients, including pancreatic, colorectal and cholangiocarcinoma cancers.

On October 22, 2015, the Company announced that the U.S. National Cancer Institute (NCI) has awarded Apogee Biotechnology Corporation ("Apogee") a $225,000 Small Business Innovation Research Program (SBIR) grant to support a pre-clinical study with YELIVA (ABC294640) for the treatment of prostate cancer. RedHill acquired from Apogee the exclusive worldwide rights to YELIVA (ABC294640) in March 2015. The NCI grant is intended to support additional studies with YELIVA (ABC294640) to determine its therapeutic efficacy in in vitro and in vivo models of prostate cancer in combination with radiotherapy.
On October 14, 2015, the Company announced that, following a meeting with the U.S. FDA regarding the development path for BEKINDA, the Company filed a protocol amendment to the BEKINDA Phase III gastroenteritis study’s approved IND to increase data collection and to conduct, among other things, additional safety tests. RedHill also reported that it expects to receive top-line results from the Phase III study in mid-late 2016 and believes that, subject to achieving highly significant positive results, the expanded Phase III study for gastroenteritis and gastritis may be sufficient as a single study to support the filing of a marketing application for BEKINDA for this indication in both the U.S. and Europe. RedHill further announced that it is initiating a new gastrointestinal development program with a new formulation of BEKINDA for the treatment of irritable bowel syndrome with diarrhea (IBS-D), with a Phase II study planned to be initiated by early 2016, subject to fulfillment of all regulatory requirements. The Company also announced that the FDA’s feedback from the recent meeting also indicated that additional clinical data is required to support a U.S. New Drug Application (NDA) with BEKINDA for oncology support indications under the 505(b)(2) regulatory path. Further development for oncology support indications will be decided as data from the ongoing and planned efficacy studies with BEKINDA for gastroenteritis and IBS-D becomes available, and once RedHill receives additional regulatory feedback from the MHRA with regard to the European Marketing Authorization Application (MAA) that was filed in December 2014 for oncology support indications.

On September 9, 2015, the Company announced that the NCI awarded a $2 million SBIR grant to Apogee to support the planned Phase II study with YELIVA (ABC294640) for the treatment of refractory or relapsed multiple myeloma. The grant covers a three year period and was awarded to Apogee in conjunction with Duke University. A Phase I/II study with YELIVA (ABC294640) for the treatment of refractory or relapsed multiple myeloma is planned to be initiated by early 2016. The study will be conducted at Duke University Medical Center and has received Institutional Review Board (IRB) approval from Duke University Health Sciences (DUHS IRB).

On September 8, 2015, the Company announced additional supportive data from the first Phase III study with RHB-105 for the eradication of H. pylori. Results from the subsequent open-label treatment of patients in the placebo arm with standard-of-care (SoC) therapy for persistent H. pylori infection demonstrated a 63% eradication rate with SoC. These results further support the potential superior efficacy of RHB-105 over SoC and validate the use of the historical SoC efficacy threshold of 70% implemented in the Phase III study as the control for the study’s primary endpoint. RedHill announced in June 2015 positive top-line results from the ERADICATE Hp Phase III study demonstrating 89.4% efficacy in eradicating H. pylori infection with RHB-105 meeting its primary endpoint with high statistical significance (p < 0.001).

On July 27, 2015, the Company announced that it had received confirmation from Salix Pharmaceuticals Ltd., recently acquired by Valeant Pharmaceuticals International, Inc., (NYSE/TSX: VRX), that it is continuing the development of RedHill’s RHB-106 tasteless solid oral formulation bowel preparation development program. RedHill and Salix entered into an exclusive license agreement in February 2014, under which Salix acquired the worldwide exclusive rights to RedHill’s RHB-106 encapsulated formulation for bowel preparation and rights to other purgative developments.

On July 22, 2015, the Company closed an underwritten public offering, which included an over-allotment option exercised by the underwriters of 277,143 American Depository Shares ("ADSs"), for a total of 2,739,143 ADSs, each representing 10 of its ordinary shares, at an offering price of $16.25 per ADS. Gross proceeds from the public offering were approximately $44.5 million, before underwriting discounts and commissions and other offering expenses. Investors in the offering included Broadfin Capital LLC, Visium Asset Management, Special Situations Funds, funds managed by Sabby Management LLC, Longwood Capital Partners LLC, Menora Mivtachim and others. Nomura and Roth Capital Partners actedas joint book-running managers. MLV & Co. and H.C. Wainwright & Co. acted as co-managers for the offering.

On July 6, 2015, the Company announced that it had received regulatory authorization to commence patient enrollment in Australia and New Zealand for its ongoing Phase III study with RHB-104 for Crohn’s disease (the MAP US study), and had commenced patient screening in New Zealand. The MAP US first Phase III study is currently ongoing in the U.S. and additional countries, with interim analysis of the study expected in the second half of 2016, after half of the 270 patients expected to be enrolled in the study will have completed 26 weeks of treatment. RedHill also announced in July 2015 that it had received two notices of allowance from the United States Patent and Trademark Office (USPTO) regarding two patent applications covering RHB-104, which are expected to be valid through 2029.