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Genmab Announces Submission of Supplemental Biologics License Application to FDA for Daratumumab in Combination with Bortezomib, Thalidomide and Dexamethasone in Frontline Multiple Myeloma

On March 26, 2019 Genmab A/S (Nasdaq Copenhagen: GEN) reported that its licensing partner, Janssen Biotech, Inc., has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (U.S. FDA) for the use of daratumumab (DARZALEX) in combination with bortezomib, thalidomide and dexamethasone (VTD) as treatment for newly diagnosed patients with multiple myeloma who are candidates for autologous stem cell transplant (ASCT) (Press release, Genmab, MAR 26, 2019, View Source [SID1234534637]). In August 2012, Genmab granted Janssen an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

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"This application is an important step in potentially providing a new group of multiple myeloma patients access to DARZALEX. We look forward to the U.S. FDA’s feedback regarding this proposed front line indication," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The submission is based on data from the Phase III CASSIOPEIA study of daratumumab in combination with VTD as frontline treatment for patients with multiple myeloma who are candidates for ASCT. The study is sponsored by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen R&D, LLC. The topline results of the data were announced in October 2018 and Janssen expects to publish detailed data from the study during 2019.

About the CASSIOPEIA (MMY3006) study
This Phase III study is a randomized, open-label, multicenter study, run by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen R&D, LLC, including 1,085 newly diagnosed subjects with previously untreated symptomatic multiple myeloma who are eligible for high dose chemotherapy and stem cell transplant. In the first part of the study, patients were randomized to receive induction and consolidation treatment with daratumumab combined with bortezomib, thalidomide (an immunomodulatory agent) and dexamethasone (a corticosteroid) or bortezomib, thalidomide and dexamethasone alone. The primary endpoint is the proportion of patients that achieve a stringent Complete Response (sCR). In the second part of the study, patients that achieved a response will undergo a second randomization to either receive maintenance treatment of daratumumab 16 mg/kg every 8 weeks for up to 2 years versus no further treatment (observation). The primary endpoint of this part of the study is progression free survival (PFS).

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 26,000 new patients were expected to be diagnosed with multiple myeloma and approximately 13,650 people were expected to die from the disease in the U.S. in 2018.3 Globally, it was estimated that 160,000 people were diagnosed and 106,000 died from the disease in 2018.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5

About DARZALEX(daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.6 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).6,7,8,9,10

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and frontline multiple myeloma settings and in amyloidosis. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases, such as NKT-cell lymphoma B and T-ALL. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.

Moleculin Announces Positive Interim Results in First Cohort of Phase 1/2 Clinical Studies of Annamycin in Acute Myeloid Leukemia in the US and in Poland

On March 26, 2019 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors, reported positive interim safety and efficacy data from two ongoing open label, single arm Phase 1/2 studies of Annamycin. In the first study, being conducted in the US, four patients have completed treatment at 100 mg/m2 with no significant adverse events related to Annamycin, and the study will now proceed to the next higher dose of 120 mg/m2 (Press release, Moleculin, MAR 26, 2019, https://www.prnewswire.com/news-releases/moleculin-announces-positive-interim-results-in-first-cohort-of-phase-12-clinical-studies-of-annamycin-in-acute-myeloid-leukemia-in-the-us-and-in-poland-300818195.html [SID1234534636]). The second trial, taking place in Poland, started at a 120 mg/m2 dose of Annamycin and has treated three patients. The first patient treated in that trial received a single course of Annamycin and his bone marrow blasts have reduced from 60% to 11%. Our principal investigator considers this response sufficient for the patient to proceed to consolidation therapy, with the goal of receiving a potentially curative bone marrow transplant. To date in Poland, one patient experienced grade 2 mucositis (which resolved to grade 1 within 2 days) and no other adverse events related to Annamycin have been reported. Trial results for the other two patients treated in Poland will not be known until the second quarter of this year.

"We are very pleased to have completed the treatment of patients in cohort 1 of the US trial and move to the next higher dose," commented Walter Klemp, Moleculin’s Chairman and CEO. "In Poland, we are pleased to have such a positive response at the starting dose level in this trial. Of course the response of a single patient doesn’t necessarily predict the outcome of the trial, but this is a great way to begin and it’s consistent with our expectations for Annamycin."

Mr. Klemp continued: "One of the advantages we believe Annamycin will offer is a lack of cardiotoxicity. We have seen no evidence of cardiotoxicity in any of the patients treated thus far. We intend to advance the clinical study of Annamycin with the goal of ultimately demonstrating the drug’s safety and effectiveness to support regulatory approval in the US and European Union."

Dr. Robert Shepard, Moleculin’s Chief Medical Officer for Annamycin added: "A prior clinical trial for Annamycin in acute leukemia demonstrated activity at its Maximum Tolerable Dose of 150 mg/m2, so we are pleased for the US trial to move to the next higher dose in cohort 2 of 120 mg/m2. In Poland, we consider reducing bone marrow blasts for Patient 1 down to 11% with a single course of Annamycin to be very encouraging. Of course, significant additional study is necessary to definitively demonstrate causality."

"We have begun a second course of Annamycin as a consolidation phase for Patient 1," commented Dr. Lidia Gil, Principal Investigator in the Polish Annamycin clinical trial. "Considering that this patient was refractory to standard of care induction therapy, I am very pleased to see that Annamycin appears to be showing activity. While this is considered a ‘Partial Response,’ I believe it’s enough of a reduction to serve as a ‘bridge to transplant’ for this patient. Importantly, with the first course of Annamycin, no toxicities have been observed that would limit continued dosing with Annamycin."

Study Design

The Company is studying Annamycin in both the US and Poland in open label, single arm clinical trials to assess the safety and efficacy of Annamycin for the treatment of adults with relapsed or refractory acute myeloid leukemia. Both the US and Polish trials have the same study design, providing for a Phase 1 intended to establish a "Recommended Phase 2 Dose," ("RP2D") with cohorts of 3 patients each where the first cohort starts at a low beginning dose and each successive cohort receives the next higher dose level until "dose limiting toxicities" prevent further increases. In the case of cohort 1 in the US, one patient did not complete the evaluation protocol, so a fourth patient was added to complete that cohort.

A key difference in the US is that the starting dose was 100 mg/m2, whereas, in Poland, the starting dose was 120 mg/m2. Having completed the first cohort in the US, the Company is seeking patients for the second cohort at a dose level of 120 mg/m2. Once 3 patients have completed the safety evaluation period of the first cohort in Poland, the second cohort will begin there at a dose level of 150 mg/m2. Once the Company establishes an RP2D, the intent is for each trial to advance to a Phase 2 arm planned to assess the safety and efficacy of Annamycin in 21 additional patients.

The US trial also differs from the Polish trial in that the FDA would like to review safety data relating to cardiotoxicity from patients treated prior to advancing beyond 120 mg/m2. The Company believes that the additional patient safety data gained from the Polish trial may also assist in the FDA’s review of cardiac safety.

Onconova Therapeutics, Inc. Reports Business Highlights And Full Year 2018 Financial Results

On March 26, 2019 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a Phase 3 stage biopharmaceutical company focused on discovering and developing novel small molecule drug candidates to treat cancer, with a primary focus on Myelodysplastic Syndromes (MDS), reported financial results for the fourth quarter and fiscal year ended December 31, 2018 (Press release, Onconova, MAR 26, 2019, View Source [SID1234534635]).

"This year was a period of important progress for Onconova, as we advanced our clinical pipeline, strengthened our balance sheet and senior leadership team, advanced our business development activities and expanded our intellectual property estate," said Steven M. Fruchtman, M.D., President and Chief Executive Officer. "As we move through 2019, we anticipate continued progress across the Company, including recruiting for our Phase 3 IV rigosertib trial in second-line higher-risk MDS (HR-MDS) patients and advancing oral rigosertib in combination with azacitidine toward a pivotal phase 3 trial in first-line HR-MDS patients. In addition, we have surpassed the 75% accrual figure and anticipate completion of recruitment to the pivotal Phase 3 INSPIRE trial in the second half of 2019. We anticipate reporting top-line data following full enrollment and reaching 288 death events."

2018 and Recent Highlights

Executed succession plan by promoting Steven M. Fruchtman, M.D., who previously served as Chief Medical Officer, to President and Chief Executive Officer upon the transition of Ramesh Kumar, Ph.D., to an advisory role
Strengthened the senior leadership team with the appointment of Richard Woodman, M.D., as Chief Medical Officer and Senior Vice President of Research and Development; and Avi Oler, J.D., M.B.A., as Vice President, Corporate Development and General Counsel
Achieved greater than 75% enrollment in the INSPIRE study, and enrollment is expected to be completed in 2019
Opening of new geographical areas to expedite completion of enrollment in the INSPIRE study
A new patent was issued covering oral and IV formulations of rigosertib by the U.S. Patent and Trademark Office extending the Company’s patent for rigosertib to 2037
Hosted a well-attended Key Opinion Leader Breakfast on February 7, 2019, focused on rigosertib development and earlier-stage programs
Oral Rigosertib in Combination with Azacitidine for First-Line HR MDS Trial Progress and Near-Term Milestones

Reported promising efficacy and acceptable safety profile from the Phase 2 study of a higher dose of oral rigosertib in combination with azacitidine (Vidaza) in patients with HR-MDS at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2018
Overall response rate of 90% reported in Onconova’s multi-institutional Phase 2 study in hypomethylating agent (HMA) naïve patients demonstrating a complete remission rate of 34%
Submitted a Special Protocol Assessment (SPA) to the FDA for a Phase 3 Trial of oral rigosertib in combination with azacitidine (Vidaza) for treatment of first-line HR-MDS, and are in discussions with the FDA to finalize the protocol
Business Development Progress for Rigosertib and Pipeline Products

Entered into a license agreement with Pint Pharma to commercialize rigosertib in Latin America including an up to $2.5 million investment by Pint Pharma and up to $42.75 million in regulatory and sales milestones
ON 123300, a first-in-class dual inhibitor of CDK4/6 + ARK5 with the potential to treat a variety of cancers, is advancing toward clinical development in partnership with HanX Biopharmaceuticals, Onconova’s greater China collaborator. HanX has begun manufacturing the compound and initiated toxicology studies to support an IND filing in the U.S., anticipated in the first half of 2019
Collaboration ongoing with preclinical studies of rigosertib for pediatric cancer associated RASopathies
Scheduled scientific presentations on rigosertib development and clinical trials at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, MDS Symposium in Copenhagen, European Hematology Association (EHA) (Free EHA Whitepaper) Congress, and American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting
Discussions with potential partners are ongoing
Year End 2018 Financial Results

Cash and cash equivalents as of December 31, 2018, totaled $17.0 million, compared to $4.0 million as of December 31, 2017. Based on current projections, the Company expects that cash and cash equivalents will be sufficient to fund ongoing trials and operations into the fourth quarter of 2019.

Net loss was $20.4 million for the year ended December 31, 2018, compared to $24.1 million for the year ended December 31, 2017, primarily due to cost controls resulting in lower operating expenses and improved revenue in 2018 from collaboration agreements executed during the first half of 2018. Research and development expenses were $16.9 million for the year ended December 31, 2018, and $19.1 million for the comparable period in 2017. General and administrative expenses were $7.6 million for the year ended December 31, 2018, and $7.4 million for the comparable period in 2017.

Conference Call and Webcast Information

The Company will host a conference call today, March 26, at 9 a.m. Eastern Time, to provide a corporate update and discuss year-end 2018 financial results. Interested parties may access the call by dialing toll-free (855) 428-5741 from the U.S., or internationally (210) 229-8823 and using conference ID: 1878978. The call will also be webcast live. Please click here to access the webcast. A replay will be available following the live webcast.

About Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are conditions that can occur when the blood-forming cells in the bone marrow become dysfunctional and thus produce an inadequate number of circulating blood cells. It is frequently associated with the presence of blasts or leukemic cells in the marrow. This leads to low numbers of one or more types of circulating blood cells, and to the need for blood transfusions. In MDS, some of the cells in the bone marrow are abnormal (dysplastic) and may have genetic abnormalities associated with them. Different cell types can be affected, although the most common finding in MDS is a shortage of red blood cells (anemia). Patients with higher-risk MDS may progress to the development of acute leukemia.

Can-Fite Announces Phase II Advanced Liver Cancer Top-Line Results for its Orphan/Fast Track Drug Namodenoson

On March 26, 2019 Can-Fite BioPharma Ltd. (NYSE MKT: CANF) (TASE:CFBI), a biotechnology company with a pipeline of proprietary small molecule drugs that address cancer, liver and inflammatory diseases, reported that the Phase II advanced liver cancer study did not achieve its primary end point of overall survival in the whole population (n=78) (Press release, Can-Fite BioPharma, MAR 26, 2019, View Source [SID1234534634]). At the same time, superiority in overall survival was found in the largest study subpopulation of CPB7 (n=56) and in secondary end points in the whole population, including objective response measured by CT or MRI. These data strongly support the progression into Phase III.

Advanced liver cancer in patients with underlying cirrhosis is categorized into three subclasses based on the severity of cirrhosis, starting with Child Pugh A (CPA), mostly treated with Nexavar and progressing to Child Pugh B (CPB) and Child Pugh C (CPC), for which there are no drugs on market with proven efficacy.

In the study, the Company enrolled only patients with CPB stage liver cancer with CBP stage patients being further divided into three categories of increasing severity, namely CPB7, CPB8, and CPB9. These patients already failed first line Nexavar and were treated with Namodenoson (25mg), or placebo, as a second line treatment, twice daily, using a 2:1 randomization. The primary endpoint of the study was defined as the length of time the patients lived after receiving treatment or median overall survival (OS). Secondary endpoints included safety, the length of time tumors did not grow after treatment, or progression free survival (PFS), the percent of patients whose tumors partially shrank after treatment, or partial response (PR), and the percent of patients who were PR or stable, or disease control rate (DCR).

Findings from the study include the following:

1.For the whole population (n=78), median OS was 4.1 months for Namodenoson vs. 4.3 months for placebo (HR: 0.82).

2Pre-planned subpopulation analysis of the CPB7 patients (n=56), revealed that the Namodenoson treated group (n=34) showed median overall survival of 6.8 months vs 4.3 months in placebo (n=22) [HR: 0.77 (95% CI 0.49-1.40)]. Similarly, for this subgroup of patients, PFS was 3.5 months for the Namodenoson treated group vs 1.9 (HR: 0.87) in the placebo group.

3.Objective response in the whole patient population measured by CT or MRI, demonstrated that 9% treated by Namodenoson achieved PR vs 0% in the placebo group.
4.Consistent with safety results from previously completed clinical trials, Namodenoson was generally well-tolerated, with no treated patients being withdrawn for toxicity and no cases of treatment-related deaths.
5.DCR was 18.0% in the Namodenoson group vs 7.1% in the placebo group (p=0.013) after four months of treatment.
6.32.0% of patients treated with Namodenoson completed at least 12 months of treatment vs 14.3% who were treated with placebo (p=0.058).
7.As of today, two patients in the Namodenoson group are ongoing after 19 and 28 months of treatment, respectively. These patients will continue to receive Namodenoson.
8.All nine patients with CBP9 cirrhosis, the most severe grade allowed into the trial, were randomly assigned to the Namodenoson treatment group (OS=3.5 months), a fact which has distorted the results in the whole population.

Dr. Llovet, a Founder and Director of the Liver Cancer Program and Full Professor of Medicine at the Mount Sinai School of Medicine, New York University, and Professor of Research-ICREA in the BCLC Group, Liver Unit, IDIBAPS-Hospital Clínic, University of Barcelona, stated, "The global incidence of liver cancer continues to increase and has more than tripled in the United States over the last three decades, and currently there are no recommended systemic treatment options for patients with advanced HCC and severe liver dysfunction (Child Pugh B)." Dr. Llovet added, "Considering that patients with advanced HCC and severe liver dysfunction do not have any accepted standard of care, the current data from this Phase II trial suggest a signal of efficacy that supports continuing the development of Namodenoson with a Phase III study in this population. I will be happy to help with the design of the Phase III and serve as the principal investigator of the trial."

Dr. Salomon M Stemmer, Institute of Oncology, Davidoff Center, Rabin Medical Center, Petah Tikva/Sackler Faculty of Medicine, Tel Aviv University, Israel and the study principal investigator, added, "Given the evidence of Namodenoson’s clinical benefit, I plan on offering it to selected HCC CPB patients in the compassionate use setting."

"We are encouraged by the advantage shown by Namodenoson in the CPB7 HCC population, a group for which there are no drugs with proven effectiveness," stated Pnina Fishman, Chief Executive Officer of Can-Fite. "Since Namodenoson has a favorable safety profile and shows no evidence of hepatotoxicity, it may possess a unique therapeutic index in this high-need population. Given that Namodenoson has been granted Fast Track status by the FDA, we look forward to engaging regulatory authorities in a dialog at the earliest opportunity."

An abstract for the late-breaking session has been submitted to The American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, to take place May, 2019 in Chicago, IL, USA.

Conference Call

The Company’s management will host a conference call today at 8:30 a.m. Eastern time to discuss the results of the Phase II advanced liver cancer trial. To participate in the conference call, please dial 877-705-6003 (domestic) or 201-493-6725 (international) or 1 809 406 247 in Israel, five minutes prior to the start of the call and provide the Conference ID: 13689112. Investors may also listen via webcast at: View Source A replay of the webcast will be available shortly after the conclusion of the call and archived on the Company’s website for 90 days following the call.

About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson is being evaluated in Phase II trials for two indications, as a second line treatment for hepatocellular carcinoma, and as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug.

Curis Reports Fourth Quarter and Year-End 2018 Financial Results

On March 26, 2019 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported its financial results for the fourth quarter and year ended December 31, 2018 (Press release, Curis, MAR 26, 2019, View Source [SID1234534631]).

"2018 was a pivotal year for Curis as we transitioned from a company broadly engaged in discovery research and pipeline expansion into a company singularly focused on clinical execution," said James Dentzer, President and Chief Executive Officer of Curis. "We now have three novel programs in the clinic, all potential blockbusters and all with significant data catalysts expected in 2019."

Dentzer continued, "With our recently announced agreement with Oberland Capital, we secured the financial flexibility needed to ensure we can continue to move forward aggressively in our clinical execution on all three programs and produce the data readouts everyone is so excited to see.

"As we move through 2019, we are focused on the development of first-in-class and best-in-class precision medicines that we hope will transform the lives of patients," he concluded.

Full Year and Fourth Quarter 2018 Financial Results

For the year ended December 31, 2018, Curis reported a net loss of $32.6 million, or $0.98 per share on both a basic and diluted basis, as compared to a net loss of $53.3 million, or $1.79 per share on both a basic and diluted basis in 2017. For the fourth quarter of 2018, Curis reported a net loss of $5.9 million or $0.18 per share on both a basic and diluted basis, as compared to a net loss of $8.0 million, or $0.24 per share on both a basic and diluted basis for the same period in 2017.

Revenues for the year ended December 31, 2018, were $10.4 million as compared to $9.9 million for the same period in 2017. Revenues for both periods comprise primarily royalty revenues recorded on Genentech and Roche’s net sales of Erivedge. Revenues for the fourth quarters of 2018 and 2017 were $2.8 million and $3.3 million, respectively.

Operating expenses for the year ended December 31, 2018 were $39.8 million as compared to $59.7 million for the same period in 2017. Operating expenses for the fourth quarter of 2018 were $7.9 million, as compared to $10.4 million for the same period in 2017, and comprised the following:

Costs of Royalty Revenues. Costs of royalty revenues, primarily amounts due to third-party university patent licensors in connection with Genentech and Roche’s Erivedge net sales, were $0.6 million for the year ended December 31, 2018 as compared to $0.5 million for the same period in 2017. Cost of royalty revenues were $0.1 million for the fourth quarter of 2018, as compared to $0.2 million for the same period in 2017.

Research and Development Expenses. Research and development expenses were $24.4 million for the year ended December 31, 2018, as compared to $45.1 million for the same period in 2017. The decrease was primarily due to aggregate payments to Aurigene of $7.5 million, for an exclusivity option that was paid in 2017 as well as decreased costs related to ongoing clinical activities for CA-170. These costs included decreased clinical site, patient, clinical research organization, formulation and manufacturing and consulting costs for our ongoing Phase 1 clinical trial. Employee-related expenses decreased over the prior year period primarily due to a reduction in headcount that occurred in the fourth quarter of 2018. Research and development expenses were $4.7 million for the fourth quarter of 2018 as compared to $6.9 million for the same period in 2017.

General and Administrative Expenses. General and administrative expenses were $14.8 million for the year ended December 31, 2018 as compared to $14.1 million for the same period in 2017. The increase in general and administrative expenses was driven primarily by higher legal, professional and consulting services and other administrative expenses, partially offset by lower stock-based compensation for the period. General and administrative expenses were $3.0 million for the fourth quarter of 2018, as compared to $3.3 million for the same period in prior 2017.

Other expense, net, was $3.2 million for the year ended December 31, 2018, as compared to $3.6 million for the same period in 2017. Other expense, net primarily consisted of interest expense related to the debt obligations of Curis Royalty (a wholly owned subsidiary of Curis). The decrease in interest expense in the current year was related to a lower principal balance on Curis Royalty’s outstanding debt with HealthCare Royalty, which was refinanced in the first quarter of 2017. Other expense, net was $0.8 million and $0.9 million for the fourth quarter of 2018 and 2017, respectively.

As of December 31, 2018, Curis’ cash, cash equivalents, marketable securities and investments totaled $24.3 million and there were approximately 33.2 million shares of common stock outstanding. The previously announced sale of a portion of Erivedge royalties to Oberland Capital Management will provide net proceeds of approximately $30 million before closing costs and transaction fees.

Full Year 2018 and Recent Operational Highlights

Precision oncology, fimepinostat (HDAC/PI3K inhibitor):

Curis initiated its study of fimepinostat (a MYC inhibitor) with venetoclax (a BCL-2 inhibitor) combination regimen in diffuse large B-cell lymphoma (DLBCL), including patients with Double-Hit/Double-Expressor Lymphoma. In preclinical models, fimepinostat administered in combination with venetoclax resulted in an enhanced benefit relative to each agent alone.
In December 2018 at the American Society of Hematology (ASH) (Free ASH Whitepaper)’s (ASH) (Free ASH Whitepaper) annual meeting, Curis presented a pooled analysis of patients with relapsed/refractory DLBCL treated with fimepinostat, including individuals with MYC-alterations that demonstrated the treatment’s safety and durable benefit in this patient population.
Precision oncology, CA-4948 (IRAK4 Inhibitor; Aurigene collaboration):

In 2018, Curis initiated and continued to enroll patients with relapsed or refractory non-Hodgkin lymphoma in a Phase 1 dose escalation study. CA-4948 is designed to target cancers with MYD88 mutations present in various tumor cell lines including DLBCL, Waldenström’s macroglobulinemia (WM), and acute myeloid leukemia.
In December 2018, at the ASH (Free ASH Whitepaper) annual meeting, Curis presented preclinical results showing potent anti-tumor in vivo activity for CA-4948 as a single agent as well as an enhanced effect when combined with other agents supporting the potential for IRAK4-based combination regimens.
Immuno-oncology, CA-170 (VISTA / PDL1 antagonist; Aurigene collaboration):

In November 2018, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s Annual Meeting, Curis presented three posters providing an update to the ongoing CA-170 Phase 1 trial and preclinical support of VISTA’s role as an oncology target of interest. At the same conference, collaborator Aurigene presented 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.
In January 2019, Curis announced the first mesothelioma patient dosed in its ongoing Phase 1 CA-170 trial, which recently started to enroll patients with mesothelioma, following evidence supporting high levels of VISTA expression in mesothelioma tumor samples. Recent publications have identified VISTA as a possible resistance mechanism to treatment with anti-PD1 antibodies in several cancer indications.
Full Year 2018 and Recent Corporate Highlights

Curis announced a 1-for-5 reverse stock split that came into effect on May 29, 2018.
In May 2018, Curis appointed Robert Martell, M.D., Ph.D., a practicing oncologist, experienced drug developer and former CMO of Tesaro, as Head of Research and Development.
In September 2018, Curis announced the appointment of James Dentzer to the position of President and Chief Executive Officer.
In October 2018, Curis implemented a 27% reduction in headcount and a re-allocation of pre-clinical resources to strengthen focus on clinical development. The result of these changes reduced the forecasted cash burn from approximately $11 million to $8 million per quarter going forward.
In March 2019, Curis announced that it sold a portion of its Erivedge royalties to Oberland Capital for up to $135.7 million, including $65 million upfront and $70.7 million in future milestones.
2019 Data Catalysts

Curis expects to report initial data on the combination of fimepinostat and venetoclax regimen in patients with R/R DLBCL, including patients with DH/DE Lymphoma, in the second half of 2019.
Curis expects to report initial efficacy data from its CA-4948 dose escalation study in patients with D/DE DLBCL in mid-year 2019.
Curis expects to report initial efficacy data from its CA-170 Phase 1 trial in patients with mesothelioma (high VISTA expressors) in the second half of 2019.
Conference Call Information

Curis management will host a conference call today, March 26, 2019, at 4:30 p.m. ET, to discuss these financial results, as well as provide a corporate update.

To access the live conference call, please dial 1-888-346-6389 (from the United States) or 1-412-317-5252 from other locations, shortly before 4:30 p.m. ET. The conference call can also be accessed in the Investors section on the Curis website at www.curis.com.