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Deciphera Pharmaceuticals, Inc. Announces Fourth Quarter and Year-end 2018 Financial Results

On March 14, 2019 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, reported financial results for the fourth quarter and year ended December 31, 2018 and provided an update on clinical and corporate developments (Press release, Deciphera Pharmaceuticals, MAR 14, 2019, View Source [SID1234534334]).

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"2018 was punctuated by significant progress in advancing our diverse pipeline of targeted drug candidates," said Michael D. Taylor, Ph.D. President and Chief Executive Officer. "We continued to add to the growing body of data that we believe supports ripretinib’s potential to provide improved, durable clinical benefit for GIST patients across multiple lines of therapy. Notably, we initiated two pivotal Phase 3 studies in 2018, INVICTUS and INTRIGUE, in fourth-line and fourth-line plus and second-line GIST, respectively."

Dr. Taylor continued, "As we near the reporting of top-line data from the INVICTUS study, expected in mid-2019, we are actively working to build out our commercial capabilities for ripretinib’s potential launch in the United States. In parallel, we continue to advance our earlier stage pipeline candidates, DCC-3014 and rebastinib, and expect to announce one new clinical candidate and commence IND-enabling studies during 2019."

Recent Clinical Updates

Ripretinib (DCC-2618)
Deciphera announced completion of enrollment in the INVICTUS pivotal Phase 3 clinical study evaluating the safety and efficacy of ripretinib (DCC-2618), the Company’s investigational broad-spectrum KIT and PDGFRα inhibitor, in fourth-line and fourth-line plus gastrointestinal stromal tumor (GIST) patients. The Company expects to report top-line data from this study in mid-2019 and is building commercial capabilities to support the planned launch of ripretinib in the United States, if approved.
Deciphera announced the initiation of its INTRIGUE pivotal Phase 3 clinical study evaluating the efficacy and tolerability of ripretinib compared to sunitinib in second-line GIST patients.
At the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress in October, Deciphera presented updated preliminary Phase 1 clinical study results of ripretinib in patients with GIST that the Company believes demonstrate the potential of ripretinib to provide improved, durable clinical benefit for GIST patients from second-line through fourth-line-plus. These data were also presented at the Annual Meeting of the Connective Tissue Oncology Society (CTOS) in November 2018.
Deciphera expanded the ongoing Phase 1 study of ripretinib to include additional cohorts for patients with various solid tumors, including melanoma, non-small cell lung cancer, germ cell cancer, penile cancer, soft tissue sarcoma, and GIST or other solid tumor patients with renal impairment.
During a poster session at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium in November 2018, Deciphera presented preclinical data on the effects of the combination of ripretinib and MAPK pathway inhibitors on cell death and apoptosis in cellular assays of GIST and mastocytosis.
Rebastinib
Deciphera recently announced the initiation of two open-label, multicenter, Phase 1b/2 combination studies of rebastinib, the Company’s investigational small molecule switch control inhibitor of TIE2 kinase:
Phase 1b/2 study in combination with carboplatin in patients with advanced or metastatic solid tumors.
Phase 1b/2 study in combination with paclitaxel in patients with advanced or metastatic solid tumors. The Company expects to report initial data from this study in 2019.
DCC-3014
Deciphera announced positive, preliminary, top-line data from the ongoing dose escalation portion of the Phase 1 clinical study of DCC-3014, the Company’s investigational small molecule switch control inhibitor of CSF1R, in patients with advanced malignancies. A review of further data from this Phase 1 study is planned to be presented at a medical meeting in 2019.
The Company also announced a plan to expand the Phase 1 study to evaluate DCC-3014 in patients diagnosed with Tenosynovial Giant Cell Tumors (TGCT).
Corporate Update

Earlier this month, Deciphera announced the appointment of Steve Hoerter as President & Chief Executive Officer, effective March 18, 2019. Mr. Hoerter, who currently serves as a member of the Deciphera Board of Directors, joins the Company from Agios, where he was Chief Commercial Officer. He will succeed Dr. Taylor, who will retire as President & Chief Executive Officer of the Company. Dr. Taylor will be available to support the transition and will remain as a member of the Company’s Board of Directors.
Fourth Quarter 2018 Financial Results

Cash Position: As of December 31, 2018, cash and cash equivalents were $293.8 million, compared to cash and cash equivalents of $196.8 million as of December 31, 2017. This increase was primarily related to proceeds obtained from the Company’s June 2018 underwritten public offering, offset by cash used in operating activities. We expect our current cash and cash equivalents will enable us to fund our operating and capital expenditures and debt service payments into the second half of 2020.
R&D Expenses: Research and development expenses for the fourth quarter of 2018 were $27.4 million, compared to $15.7 million for the same period in 2017. The increase was primarily due to an increase in spending on the ripretinib (DCC-2618) program of $5.8 million as a result of clinical trial start-up activities related to the Phase 3 INTRIGUE study in second-line GIST, which the Company initiated in December 2018. Expenses related to the rebastinib program increased $1.8 million, primarily due to the Phase 1b/2 study of rebastinib in combination with paclitaxel, which the Company initiated in October 2018, and start-up activities related to the second Phase 1b/2 clinical trial of rebastinib in combination with carboplatin, which the Company initiated in January 2019. Personnel-related costs increased $2.5 million due primarily to increased headcount in our research and development functions. Personnel-related costs for the fourth quarters of 2018 and 2017 included non-cash stock-based compensation expense of $1.0 million and $0.5 million, respectively. Facility-related and other costs included in unallocated expenses increased $2.0 million primarily due to increased costs incurred in connection with our early-stage drug discovery programs.
G&A Expenses: General and administrative expenses for the fourth quarter of 2018 were $6.5 million, compared to $4.7 million for the same period in 2017. The increase was primarily due to an increase in legal and professional fees as a result of various advisory fees related to ongoing operations as a public company. Facility-related and other costs increased due to insurance costs and higher rent expense related to the Company’s new lease. Non-cash stock-based compensation was $1.8 million and $2.3 million for the fourth quarters of 2018 and 2017, respectively.
Net Loss: For the fourth quarter of 2018, Deciphera reported a net loss of $32.3 million, or $0.86 per share, compared with a net loss of $19.9 million, or $0.62 per share, for the same period in 2017.

Agenus Reports Fourth Quarter and Full Year 2018 Financial Results and Provides Corporate Update

On March 14, 2019 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology (I-O) company with a pipeline of immune checkpoint antibodies, cancer vaccines and adoptive cell therapies1, reported and update and reported financial results for the fourth quarter and full year of 2018 (Press release, Agenus, MAR 14, 2019, View Source [SID1234534331]).

Agenus Logo

"We are rapidly advancing with the discovery and clinical development of our innovative I-O agents," said Garo H. Armen, Ph.D., Chairman and CEO of Agenus. "In the past year, we entered into an important partnership with Gilead, delivered 6 INDs, and confirmed benefit in the majority of patients treated with our lead CTLA-4 and PD-1 antibodies. Our next steps will target submission and commercial launch readiness for our first two antibodies."

Achievements
Strengthened balance sheet with the Gilead collaboration and payments from milestones achieved with Incyte and Merck
$150M payment from Gilead
$21.5M additional milestones for advancing LAG-3 (INCAGN02385), TIM-3 (INCAGN02390), ILT4 (MK-4830) and FDA acceptance of the IND for AGEN1423, licensed to Gilead
Advanced lead programs and reported clinical benefit in majority of patients across multiple solid tumors, including cervical cancer
Ongoing trials in cervical cancer are designed to support BLA via accelerated pathway
We plan to expand PD-1 development in additional indications
Advanced new discoveries, which will enter the clinic this year
Next-Gen CTLA-4, AGEN1181
First-in-class bispecific, AGEN1223 (a Gilead option program)
Revenues of GSK’s Shingrix, containing our QS-21 Stimulon, exceed $1Bn (USD)
Bill & Melinda Gates Foundation award Agenus ~$1M to develop novel technology for QS-21
AgenTus Cell Therapy Business:
2019 INDs are on track
Partnership and private financing discussions are underway
Fourth Quarter and Full Year 2018 Financial Results

We ended 2018 with a cash balance of $53 million followed by the $150 million received from Gilead in 2019.

For the fourth quarter ended December 31, 2018, we reported a net loss of $49 million or $0.40 per share compared to a net loss for same period in 2017 of $35 million, or $0.35 per share. In the fourth quarter, we recognized revenue of $6.5 million which includes non-cash royalties earned.

For the year ended December 31, 2018, we reported a net loss of $162 million or $1.44 per share compared to a net loss for the year ended 2017 of $121 million or $1.23 per share. The increased net loss reflects reduced revenue during 2018 due to an accelerated milestone received during 2017 from Incyte, the 2018 loss on early extinguishment of debt and increased non-cash interest on our liability related to the sale of future royalties.

Conference Call, Webcast and Prepared Statement Information

Date: Thursday, March 14, 2019

Time: 8:30 a.m. ET

Domestic Dial-in Number: 1-844-492-3727

International Dial-in Number: 1-412-317-5118

Conference ID: Agenus

Live Webcast: accessible from the Company’s website at View Source or with this link View Source

A replay will be available on the Company’s website approximately two hours after the call and will remain available for 90 days.

AVEO Reports Full Year 2018 Financial Results and Provides Business Update

On March 14, 2019 AVEO Oncology (NASDAQ: AVEO) reported financial results for the full year ended December 31, 2018 and provided a business update (Press release, AVEO, MAR 14, 2019, View Source [SID1234534330]).

"The results of TIVO-3, presented in February at the 2019 ASCO (Free ASCO Whitepaper) GU Symposium, underscore a unique activity and tolerability profile among VEGF TKIs in the treatment of kidney cancer"

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"The results of TIVO-3, presented in February at the 2019 ASCO (Free ASCO Whitepaper) GU Symposium, underscore a unique activity and tolerability profile among VEGF TKIs in the treatment of kidney cancer," said Michael Bailey, president and chief executive officer of AVEO. "We continue to believe that there is a significant potential commercial opportunity for an active and well tolerated therapy within the third plus line of therapy, particularly one that demonstrated activity in a highly refractory patient population that has received prior PD-1 treatment. We are hopeful that the positive PFS outcomes from TIVO-3 translate into an improved overall survival hazard ratio and look forward to reporting a more mature interim OS outcome in the fourth quarter of 2019."

Recent Highlights

Presented Topline Results from TIVO-3 During an Oral Presentation at the 2019 ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium. In February 2019, AVEO presented topline results from the TIVO-3 trial, AVEO’s Phase 3 randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in 350 subjects with refractory advanced or metastatic renal cell carcinoma (RCC) at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (GU) Cancers Symposium held February 14-16, 2019 in San Francisco. The results were presented during an oral presentation titled "TIVO-3: A Phase 3, Randomized, Controlled, Multi-Center, Open-Label Study to Compare Tivozanib to Sorafenib in Subjects with Refractory Advanced Renal Cell Carcinoma (RCC)." A copy of the presentation is currently available in the Publications & Presentation section of AVEO’s website.

The presentation noted that the TIVO-3 trial met its primary endpoint of demonstrating a statistically significant benefit in median progression-free survival (PFS). Median PFS for tivozanib was also longer than sorafenib both in patients who received prior PD-1 therapy and those who received two prior VEGF TKI therapies. The secondary endpoint of overall response rate also demonstrated a statistically significant improvement for patients receiving tivozanib compared to sorafenib.

The analysis of the secondary endpoint of overall survival (OS) was not mature at the time of the final PFS analysis. As presented, the preliminary OS analysis conducted at an October 4, 2018 data cutoff date, which included additional patients previously lost to follow-up, showed a non-statistically significant difference in OS favoring sorafenib (hazard ratio: 1.12, p-value: 0.44).

Tivozanib was generally well-tolerated relative to sorafenib, with reported grade 3 or higher adverse events consistent with those observed in previous tivozanib trials. The improved tolerability of tivozanib was evident in the lower rates of dose reductions and interruptions for toxicity in patients receiving tivozanib compared to those receiving sorafenib. The most common adverse event in patients receiving tivozanib was hypertension, an adverse event known to reflect effective VEGF pathway inhibition.
Announced NDA Timing Update. In January 2019, the U.S. Food and Drug Administration (FDA) recommended that AVEO not submit a New Drug Application (NDA) for tivozanib at this time using the preliminary OS results from the TIVO-3 trial. The FDA indicated that these preliminary OS results do not allay their concerns about the potential detriment in OS outlined in the Complete Response Letter dated June 6, 2013. AVEO now plans to make an NDA filing decision following the availability of more mature OS results. AVEO intends to conduct an additional interim OS analysis in August 2019, the results of which are expected to be reported in the fourth quarter of 2019.
Data from Phase 1b Expansion Cohort of Ficlatuzumab and Cytarabine in Relapsed and Refractory AML to be Presented at 2019 AACR (Free AACR Whitepaper) Annual Meeting. Data from the investigator-sponsored Phase 1b expansion cohort evaluating the safety and tolerability of ficlatuzumab, AVEO’s potent hepatocyte growth factor (HGF) inhibitory antibody, in combination with cytarabine in patients with relapsed and refractory acute myeloid leukemia (AML) will be presented during a poster session at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. The presentation, titled, "Cyfi: Results from a Phase 1b expansion cohort of anti-hepatocyte growth factor and cytarabine in relapsed and refractory AML" (abstract CT078 / 2) will be featured during a poster session (Session PO.CT03) on Monday, April 1, 2019 from 1:00-5:00pm Eastern Time.
Entered Immuno-Oncology Clinical Supply Agreement with AstraZeneca. In December 2018, AVEO entered into a clinical supply agreement with AstraZeneca to evaluate the safety and efficacy of AstraZeneca’s IMFINZI (durvalumab), a human monoclonal antibody directed against programmed death-ligand 1 (PD-L1), in combination with tivozanib in first-line hepatocellular carcinoma, or liver cancer, in a Phase 1/2 study. AVEO will serve as the study sponsor; each party will contribute the clinical supply of its study drug and study costs will be otherwise shared equally. The Phase 1 portion of the study is expected to commence this year.
Earned $2 Million Milestone Payment from EUSA Pharma. In November 2018, AVEO announced the triggering of a $2 million milestone payment from EUSA Pharma related to the reimbursement in Germany for FOTIVDA as a first line treatment of adult patients with advanced RCC.
Extended Debt Facility Interest-Only Period. In December 2018, AVEO announced a six-month extension to the interest-only period under its existing amended and restated loan and security agreement with Hercules Capital, Inc. The extension was granted as a result of achieving certain predefined requirements under the agreement, including successfully meeting the primary endpoint of the TIVO-3 trial.
Raised $7.5 Million Under the Sales Agreement with SVB Leerink, Extending Financial Runway. In February 2019, AVEO raised $7.5 million through its sales agreement with SVB Leerink. Approximately $32 million of shares remain available for future issuance and sale pursuant to the sales agreement, which was originally entered into in February 2018. AVEO believes that the proceeds generated in February 2019 through the sales agreement, together with its available cash, cash equivalents, and marketable securities at December 31, 2018, and together with the extension of the interest-only period under the Hercules loan agreement, which results in deferment of principal payments, will allow it to fund planned operations into the first quarter of 2020.
Full Year 2018 Financial Highlights

AVEO ended 2018 with $24.4 million in cash, cash equivalents and marketable securities as compared with $33.5 million at December 31, 2017.
Total revenue for 2018 was approximately $5.4 million compared with $7.6 million for 2017.
Research and development expense for 2018 was $20.7 million compared with $25.2 million for 2017.
General and administrative expense for 2018 was $10.8 million compared with $9.1 million for 2017.
Net loss for 2018 was $5.3 million, or a loss of $0.04 and $0.19 per basic and diluted share, respectively, compared with a net loss of $65.0 million for 2017, or a loss of $0.61 per basic and diluted share.
The 2018 net loss was partially offset by an approximate $19.9 million non-cash gain attributable to the decrease in the fair value of the 2016 private placement warrant liability that principally resulted from the decrease in the stock price that occurred within the fiscal year. In 2017, the non-cash loss attributable to the increase in the fair value of such warrant liability was $33.7 million.
Financial Guidance

AVEO believes that its $24.4 million in cash, cash equivalents, and marketable securities at the end of 2018, together with the additional $7.5 million raised from sales under its sales agreement with SVB Leerink in February 2019 and together with the extension of the interest-only period under the Hercules loan agreement, which results in deferment of principal payments, would allow it to fund planned operations into the first quarter of 2020. This estimate assumes no receipt of additional milestones from AVEO’s partners, no additional funding from new partnership agreements, no additional equity or debt financings, and no sales of equity through the exercise of outstanding warrants issued in connection with the 2016 private placement or outstanding warrants issued in connection with the recent settlement of the securities class action litigation.

About Tivozanib (FOTIVDA)

Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) discovered by Kyowa Hakko Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway and Iceland. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications.1,2 Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models3 and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC. Tivozanib has been investigated in several tumor types, including renal cell, hepatocellular, colorectal and breast cancers. In addition, a new formulation of tivozanib is in pre-clinical development for the treatment of age-related macular degeneration.

Novelion Therapeutics Reports Fourth Quarter and Full Year 2018 Financial Results

On March 14, 2019 Novelion Therapeutics Inc. (NASDAQ: NVLN), a biopharmaceutical company dedicated to developing and commercializing therapies for individuals living with rare diseases ("Novelion" or the "Company"), today reported financial results for the fourth quarter and year ended December 31, 2018 (Press release, QLT, MAR 14, 2019, View Source [SID1234534329]).

Novelion’s Interim Chief Executive Officer Ben Harshbarger commented, "We are pleased with our fourth quarter results which reflect strong revenue performance and show meaningful impact from the cost reduction initiatives executed throughout 2018. We remain focused on undertaking a comprehensive capital restructuring and also on delivering our two very important rare disease therapies to indicated patients in need."

Business Update

Following marketing authorization of MYALEPTA (metreleptin) for generalized lipodystrophy (GL) and partial lipodystrophy (PL) by the EMA in July, our subsidiary Aegerion Pharmaceuticals commenced the pricing and reimbursement processes in key EU markets. Reimbursement decisions in many of the key EU markets are anticipated throughout 2019. MYALEPTA sales growth in 2018 was supported by named patient sales programs, which allow for sales on an unsolicited basis prior to regulatory approval and/or pricing and reimbursement decisions, as well as the launch of MYALEPTA in Germany in the fourth quarter.

In February 2019, Aegerion entered into an exclusive licensing agreement with Recordati Rare Diseases Inc. ("Recordati") for the commercialization of JUXTAPID (lomitapide) in Japan. The agreement includes exclusive rights in Japan for Recordati to commercialize JUXTAPID for the current approved indication, homozygous familial hypercholesterolemia (HoFH). The terms of, and use of proceeds from, the Recordati licensing agreement are described more fully in Novelion’s Form 8-K filed on February 6, 2019.

In January 2019, Aegerion held a meeting with the U.S. Food and Drug Administration (FDA) to obtain feedback on the design of the placebo-controlled study that will be required in order to pursue the PL indication for MYALEPT in the U.S. The Company is assessing feedback on the study design and integrating it into the Phase 3 study protocol.

Aegerion plans to file for regulatory approvals for metreleptin in GL and PL in certain key markets outside the U.S. and EU, including Brazil, in 2019.

As previously announced, Novelion and Aegerion have each engaged advisors to independently explore and advise them on all available strategic alternatives regarding the Company’s capital structure, such as a restructuring of Aegerion’s Convertible Notes due August 2019 (including a restructuring that would likely involve a debt for equity swap), a sale or merger of Novelion or Aegerion, or the sale or other disposition of certain businesses or assets. The implementation of one or more of such transactions (or the failure to complete any such transaction or transactions) will likely require Aegerion, and could require Novelion, to seek the protections of applicable bankruptcy laws allowing for corporations to seek to restructure their debts and other affairs under a reorganization.
Fourth Quarter 2018 Financial Results

JUXTAPID: Novelion reported net revenues of JUXTAPID of $15.2 million in the fourth quarter of 2018, compared to $20.1 million for the same period in 2017, $8.2 million, or 53.9%, of which was from prescriptions written in the U.S. and $0.8 million of which was royalty revenue from sales of JUXTAPID in the EMEA region. The JUXTAPID revenue decline in the fourth quarter of 2018 compared to the same period in 2017 was primarily due to product competition for JUXTAPID, restrictions on reimbursement, and patient discontinuation from therapy.

MYALEPT: Novelion reported net revenues of MYALEPT of $25.5 million in the fourth quarter of 2018, compared to $18.8 million for the same period in 2017, $13.4 million, or 52.5%, of which was from prescriptions written in the U.S. MYALEPT revenue growth in the fourth quarter was driven by increased sales in all key markets.

GAAP total net revenues for the fourth quarter of 2018 were $40.7 million compared to $38.9 million for the same period in 2017.

Cost of product sales for the fourth quarter of 2018 was $18.0 million compared to $17.0 million for the same period in 2017, resulting in stable year-over-year fourth quarter gross margins.

GAAP total operating expenses for the fourth quarter of 2018 were $21.7 million compared to total operating expenses of $35.9 million, a 39.6% reduction compared to the same period in 2017. GAAP SG&A expenses were $14.1 million in the fourth quarter of 2018 compared to $24.1 million for the same period in 2017. GAAP R&D expenses were $7.7 million in the fourth quarter of 2018 compared to $11.8 million for the same period in 2017.

On a non-GAAP basis, during the fourth quarter of 2018, SG&A expenses were $13.0 million compared to $22.5 million for the same period in 2017. The 42.2% decrease in non-GAAP SG&A expenses in the fourth quarter of 2018 compared with the same period in 2017 was primarily related to cost reduction initiatives executed throughout 2018.

On a non-GAAP basis, during the fourth quarter of 2018, R&D expenses decreased 33.6% to $7.7 million compared to $11.6 million for the same period in 2017, reflecting cost reduction initiatives executed throughout 2018.

GAAP net loss in the fourth quarter of 2018 was $19.4 million, an improvement of approximately 21.1% compared to GAAP net loss of $24.6 million during the same period in 2017.

On a non-GAAP basis, net income was $2.9 million in the fourth quarter of 2018 compared to a net loss of $3.3 million for the same period in 2017.

A full reconciliation of the GAAP financial results to non-GAAP financial results is included in the financial information tables below.

Full Year 2018 Financial Results

JUXTAPID: Novelion reported net revenues of JUXTAPID of $59.1 million for the year ended December 31, 2018, compared to $72.1 million for 2017. The decline in sales resulted from product competition for JUXTAPID, restrictions on reimbursement, and patient discontinuation from therapy. Named patient sales of JUXTAPID in Brazil totaled $0.4 million in 2018, compared to $6.7 million of JUXTAPID named patient sales in Brazil in 2017. Revenue growth in Japan in 2018 helped offset the sales decline in the U.S. and Brazil.

MYALEPT: Novelion reported net revenues of MYALEPT of $71.4 million for the year ended December 31, 2018, compared to $66.3 million for 2017. The increase was primarily attributable to revenues in France, Germany and Turkey. In addition, 2017 MYALEPT sales benefited from $2.3 million of one-time deferred revenue recognition in the U.S.

GAAP total net revenues for the year ended December 31, 2018 were $130.4 million compared to $138.4 million for 2017.

Cost of product sales for the year ended December 31, 2018 was $59.7 million compared to $77.2 million for 2017, resulting in improved gross margin. The improvement in 2018 was primarily a result of higher reserves in 2017 for excess and obsolete inventory which were charged to cost of product sales, partially offset by a higher royalty rate on U.S. sales of metreleptin in 2018.

GAAP total operating expenses for the year ended December 31, 2018 were $120.8 million compared to total operating expenses of $148.0 million for 2017. GAAP SG&A expenses were $79.8 million for the year ended December 31, 2018 compared to $96.5 million for 2017. GAAP R&D expenses were $38.8 million for the year ended December 31, 2018 compared to $49.0 million for 2017.

On a non-GAAP basis, for the year ended December 31, 2018, SG&A expenses decreased 20.0% to $72.6 million compared to $90.7 million for 2017, primarily as a result of cost reduction initiatives executed throughout 2018. Restructuring charges for 2018 were $2.2 million, compared with restructuring charges of $2.5 million for 2017.

On a non-GAAP basis, for the year ended December 31, 2018, R&D expenses decreased 20.5% to $38.3 million compared to $48.2 million for 2017 due primarily to cost reduction initiatives executed throughout 2018.

GAAP net loss for the year ended December 31, 2018 was $108.3 million compared to GAAP net loss of $126.7 million for 2017.

Net loss on a non-GAAP basis for the year ended December 31, 2018 was $25.3 million, compared to $30.0 million for 2017.

As of December 31, 2018, the Company’s consolidated unrestricted cash balance was $45.2 million, compared to $55.4 million at December 31, 2017. Novelion’s consolidated cash as of December 31, 2018 includes $13.3 million at Novelion and $31.9 million at the Aegerion subsidiary level.

Debt and Government Settlement Payments

As of December 31, 2018, Aegerion’s debt liabilities and government settlement payments included $302.5 million in outstanding principal under Aegerion’s Convertible Notes due August 15, 2019, $75.9 million in outstanding principal (including paid in kind fees and interest) under Aegerion’s secured term loans having a maturity date of June 30, 2019, $37.1 million outstanding under Aegerion’s secured intercompany term loan with Novelion, as lender, which has a maturity date of July 1, 2019 (which term loan amounts were subsequently reduced by repayments received from the Recordati license transaction described above), as well as $31.1 million owed under Aegerion’s settlements with the Department of Justice and the U.S. Securities and Exchange Commission (the "Commission"), payable in prescribed installments until the first quarter of 2021.

Financial Guidance

Novelion expects total net revenues in 2019 to be between $160.0 and $175.0 million, including $30.0 million of licensing revenues, in the form of the $25.0 million upfront licensing payment and $5.0 payment upon transfer of the marketing authorization to Recordati, resulting from the Recordati transaction.

AstraZeneca showcases next-generation Oncology pipeline addressing unmet patient needs at AACR Annual Meeting

On March 14, 2019 AstraZeneca will share pioneering research and development across its successful Oncology portfolio and extensive next-generation pipeline at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Atlanta, USA, 29 March to 3 April 2019 (Press release, AstraZeneca, MAR 14, 2019, View Source [SID1234534328]).

The new research will showcase AstraZeneca’s potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor, taking the DNA Damage Response (DDR) pipeline beyond PARP inhibition. Additional highlights include new insights from the MYSTIC and TATTON trials for Imfinzi (durvalumab) and Tagrisso (osimertinib) in predicting response and addressing treatment resistance in lung cancer.

In total, data from 84 presentations will illustrate the progress of AstraZeneca’s Oncology pipeline, with 28 abstracts reporting new Immuno-Oncology (IO) data, 33 focused on complementary biological pathways exploring the DDR mechanism, and 20 on tumour drivers and resistance mechanisms.

José Baselga, Executive Vice President, Research & Development, Oncology, said: "AstraZeneca is continuing to strengthen its portfolio of innovative cancer medicines by exploring new indications and developing a pioneering next-generation pipeline. We will be sharing some of our latest research at the 2019 AACR (Free AACR Whitepaper) Annual Meeting, including 28 new molecular entities and six combinations, highlighting an exciting new phase of scientific discovery from our Oncology R&D."

IO pipeline explores new pathways to enhance immune response

Key data from AstraZeneca’s early-stage clinical and preclinical IO pipeline include potential new medicines targeting multiple pathways, providing insight into novel mechanisms to boost current immune response and modify the tumour microenvironment both alone and in combination with checkpoint inhibition.

Presentations will highlight AstraZeneca’s growing portfolio in small molecules and antisense oligonucleotides (ASOs) targeting immunosuppressive mechanisms in cancer, and the Company’s exploration of the adenosine pathway, which is increasingly recognised as critical to tumour suppression and represents a new frontier within IO.

Phase I and preclinical data demonstrating AZD4635, a small molecule A2AR antagonist, prevents adenosine-mediated immunosuppression. Early clinical activity has been observed with AZD4635 monotherapy or in combination with Imfinzi in patients with metastatic castration-resistant prostate cancer (Abstracts #LB-192/10, #CT026/21)
Preclinical research on the activity of ASO AZD8701 (ION-AZ7), showing that inhibiting FOXP3 may limit immunosuppressive functions and induce tumour regression (Abstract #2713)
Preclinical pharmacodynamic and mechanistic data illustrating how danvatirsen (AZD9150), a STAT3 ASO reverses immunosuppression to produce significant anti-tumour effects, both as monotherapy and in combination with anti-PDL1 (Abstract #3215/25)
Preclinical data for MEDI5083, a novel fusion protein which activates the CD40 pathway, indicating robust immune activation and anti-tumour activity (Abstract #1534/3)
Preclinical data for MEDI1191, a novel IL12-based treatment designed for injection directly into tumours, showing potential to drive anti-tumour response for patients with solid tumours both as monotherapy and in combination with anti-PDL1 (Abstract #5017/11)
Next wave of DDR targets

New research will showcase AstraZeneca’s DDR pipeline beyond PARP inhibition, including on the discovery and first structural disclosure of AZD7648, a potent and selective DNA-PK inhibitor (Abstract #DDT01-02). DNA-PK is critical in repairing DNA double strand breaks through the non-homologous end joining (NHEJ) pathway and has also been linked to the replication stress response (RSR), a type of DDR.

Additional new data will be shared on reversing PARP inhibitor resistance by targeting alternative DDR dependencies, like the RSR (Abstract #932).

Predicting response and addressing treatment resistance in lung cancer: new insights from MYSTIC and TATTON trials for Imfinzi and Tagrisso

Exploratory analyses of blood and tissue tumour mutational burden (TMB) from the Phase III MYSTIC trial assess TMB as a potential biomarker of survival in 1st-line use of Imfinzi with or without tremelimumab vs. chemotherapy in metastatic non-small cell lung cancer (NSCLC) (Abstract #CT074). The trial did not meet the primary endpoints, but Imfinzi monotherapy demonstrated clinical activity in the primary analysis. The MYSTIC trial provides the most comprehensive data set to date evaluating blood TMB and is the only Phase III randomised, controlled trial to demonstrate an association between high TMB and overall survival benefit with immunotherapy treatment. This new analysis will further evaluate the use of TMB as a potential biomarker predictive of survival benefit with IO treatment.

In addition, several abstracts will be presented from the TATTON Phase Ib trial testing the combination of Tagrisso with potential new medicines savolitinib or selumetinib in NSCLC patients who have progressed on prior epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment (Abstracts #CT032, #CT033, #CT034). The TATTON trial supports SAVANNAH, an ongoing Phase II clinical trial exploring the combination of Tagrisso and savolitinib to overcome MET-driven EGFR-TKI resistance following treatment with Tagrisso in EGFR-mutated (EGFRm) NSCLC. Characterisation of detection methods for identifying MET-driven EGFR-TKI resistance will be presented (Abstract #4897/20). TATTON will also inform the trial design of ORCHARD, a Phase II platform trial exploring potential new treatment options to address resistance mechanisms in patients with EGFRm NSCLC who have experienced disease progression following 1st-line treatment with Tagrisso.

Key AstraZeneca presentations at AACR (Free AACR Whitepaper) 2019

Lead author

Abstract title

Presentation details

Immuno-Oncology

Peters, S

Tumour mutational burden (TMB) as a biomarker of survival in metastatic non-small cell lung cancer (mNSCLC): blood and tissue TMB analysis from MYSTIC, a Phase 3 study of first-line durvalumab ± tremelimumab vs chemotherapy

Abstract #CT074

Session CTPL03 – Optimizing PD-1/PD-L1 Immune Checkpoint Inhibitor Therapy: Dedicated to the Memory of Waun Ki Hong

Monday 1 April

10:30am-12:45pm

Marcus Auditorium- Bldg A-GWCC

Srinivasan, S

STAT3 ASO reverses immunosuppression and enhances cytotoxic cell function to enhance PDL1 blockade

Abstract #3215/25

Session PO.IM02.01 – Combination Immunotherapies 2

Tuesday 2 April

8:00am-12:00pm

Section 23

Barbon, CM

The A2AR antagonist AZD4635 prevents adenosine-mediated immunosuppression of CD103+ dendritic cells

Abstract #LB-192/10

Session LBPO.IM02 – Late-Breaking Research:
Immunology 2

Tuesday 2 April

8:00am-12:00pm

Section 42

Merchant, MS

Evidence of Immune Activation in the first-in-human Phase 1a dose escalation study of the Adenosine 2a Receptor Antagonist, AZD4635, in patients with advanced solid tumors

Abstract #CT026/21

Session PO.CT01 – Phase I Clinical Trials: Part 1

Sunday 31 March

1:00pm-5:00pm

Section 16

Sinclair, C

Discovery and characterization of AZD8701, a high affinity antisense oligonucleotide targeting FOXP3 to relieve immunosuppression in cancer

Abstract #2713

Session MS.IM02.01 – Rational Combinations of Immunotherapy

Monday 1 April

4:35pm-4:50pm

Room A411-Georgia World CC

Wang, Y

MEDI5083, a novel CD40L-Fc fusion protein, activates the CD40 pathway on antigen presenting cells and promotes a robust anti-tumor immune response in a B16F10 murine tumor model

Abstract #1534/3

Session PO.IM02.17 – Therapeutic Antibodies 2

Monday 1 April

8:00am-12:00pm

Section 25

Luheshi, N

MEDI1191, a novel IL-12 mRNA therapy for intratumoral injection to promote TH1 transformation of the patient tumor microenvironment

Abstract #5017/11

Session PO.IM02.10 – Tumor Immune Microenvironment

Wednesday 3 April

8:00am-12:00pm

Section 25

DNA damage response

Goldberg, FW

Discovery and first structural disclosure of AZD7648, a potent and selective DNA-PK inhibitor

Abstract #DDT01-02

Session DDT01 – New Drugs on the Horizon: Part 1

Sunday 31 March

1:24pm-1:48pm

Room A305 – Georgia World CC

Cadogan, EB

AZD7648: A potent and selective inhibitor of DNA-PK with pharmacodynamic and monotherapy anti-tumour activity

Abstract #3505/16

Session PO.MCB07.03 – DNA Damage and Repair 3

Tuesday 2 April

8:00am-12:00pm

Section 35

Fok, J

AZD7648, a potent and selective inhibitor of DNA-PK, potentiates the activity of ionising radiation and doxorubicin in vitro and causes tumour regression in xenograft models

Abstract #3512/23

Session PO.MCB07.03 – DNA Damage and Repair 3

Tuesday 2 April

8:00am-12:00pm

Section 35

O’Connor, M

Reversing PARP inhibitor resistance by targeting the replication stress response

Abstract #932

Session MS.ET03.01 – Drug Resistance

Sunday 31 March

4:35pm-4:50pm

Room B304 – Georgia World CC

Tumour drivers and resistance

Yu, H

TATTON Phase Ib expansion cohort: osimertinib plus savolitinib for patients (pts) with EGFR-mutant, MET amplified NSCLC after progression on prior first/second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)

Abstract #CT032

Session CTPL02 – Can the Challenge of NSCLC Resistance be MET or Will We Not MEK It?

Sunday 31 March

3:00pm-5:15pm

Marcus Auditorium- Bldg A-GWCC

Sequist, L

TATTON Phase Ib expansion cohort: osimertinib plus savolitinib for patients (pts) with EGFR-mutant, MET-amplified NSCLC after progression on prior third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)

Abstract #CT033

Session Clinical Trials Plenary, Can the Challenge of NSCLC Resistance be MET or Will We Not MEK it?

Sunday 31 March

3:00pm-5:15pm

Marcus Auditorium- Bldg A-GWCC

Ramalingam, S

Osimertinib plus selumetinib for patients (pts) with EGFR-mutant (EGFRm) NSCLC following disease progression on an EGFR-TKI: results from the Phase Ib TATTON study

Abstract #CT034

Session Clinical Trials Plenary, Can the Challenge of NSCLC Resistance be MET or Will We Not MEK it?

Sunday 31 March

3:00pm-5:15pm

Marcus Auditorium- Bldg A-GWCC

Hartmaier, RJ

Detection of MET-mediated EGFR tyrosine kinase inhibitor (TKI) resistance in advanced non-small cell lung cancer (NSCLC): biomarker analysis of the TATTON study

Abstract #4897/20

Session PO.CL11.07 – Novel Strategies for Biomarker Identification and Use in Cancer 3

Wednesday 3 April

8:00am-12:00pm

Section 19

Liquid biopsies

Barrett, JC

Regulatory Considerations for Utilizing Liquid Biopsies in Drug and Diagnostic Development

Major Symposium: Regulatory Science and Policy

Session SYPOL07 – Regulatory Considerations for Utilizing Liquid Biopsies in Drug and Diagnostic Development

Tuesday 2 April

3:00pm-5:00pm

Room A402 – Georgia World CC

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance Oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.