On February 28, 2019 Novocure (NASDAQ: NVCR) reported financial results for the quarter and year ended December 31, 2018, highlighting continued revenue growth, anticipated clinical and regulatory milestones and a strong cash position (Press release, NovoCure, FEB 28, 2019, View Source [SID1234533831]). Novocure is a global oncology company working to extend survival in some of the most aggressive forms of cancer through the development and commercialization of its innovative therapy, Tumor Treating Fields.

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An "active patient" is a patient who is on Optune under a commercial prescription order as of the measurement date, including patients who may be on a temporary break from treatment and who plan to resume treatment in less than 60 days.

A "prescription received" is a commercial order for Optune that is received from a physician certified to treat patients with Optune for a patient not previously on Optune. Orders to renew or extend treatment are not included in this total.

"2018 was an extremely productive year for Novocure," said William Doyle, Novocure’s Executive Chairman. "Highlights included annual revenue growth of 40 percent, the presentation of our STELLAR data in mesothelioma, the first patient enrollment in our PANOVA-3 phase 3 trial for pancreatic cancer and our collaboration agreement with Zai Labs in China. We continued to grow our glioblastoma business globally and invested more than $50 million in research and development in 2018."

"At Novocure, we are working to extend survival in some of the most aggressive forms of cancer by developing and commercializing Tumor Treating Fields," continued Mr. Doyle. "With 2018 revenues approaching $250 million, four indications in our late stage pipeline and significant cash on hand, we believe we enter 2019 well-positioned to deliver both continued near-term growth and significant long-term value."

Fourth quarter 2018 operating statistics and financial update

There were 2,383 active patients on Optune at December 31, 2018, representing 30 percent growth compared to December 31, 2017, and 6 percent growth compared to September 30, 2018. The increase in active patients was driven by increased commercial adoption and by continued growth in prescriptions for patients with newly diagnosed GBM, who typically have a longer duration of treatment with Optune.

In the United States, there were 1,637 active patients on Optune at December 31, 2018, representing 24 percent growth compared to December 31, 2017.
In Germany and other EMEA markets, there were 654 active patients on Optune at December 31, 2018, representing 28 percent growth compared to December 31, 2017.
In Japan, there were 92 active patients on Optune at December 31, 2018, representing significant growth in the first year with reimbursement approval for Optune in Japan.
There were 1,315 prescriptions received in the quarter ended December 31, 2018, representing 21 percent growth compared to the same period in 2017, and 6 percent growth compared to the quarter ended September 30, 2018. Prescriptions for newly diagnosed GBM continued to grow, with approximately 950 Optune prescriptions in the fourth quarter written for patients with newly diagnosed GBM.

In the United States, 941 prescriptions were received in the quarter ended December 31, 2018, representing 16 percent growth compared to the same period in 2017.
In Germany and other EMEA markets, 322 prescriptions were received in the quarter ended December 31, 2018, representing 15 percent growth compared to the same period in 2017.
In Japan, 52 prescriptions were received in the quarter ended December 31, 2018, representing significant growth in the first year with reimbursement approval for Optune in Japan.
For the three months ended December 31, 2018, net revenues were $69.7 million, representing 30 percent growth versus the same period in 2017 and 8 percent growth versus the three months ended September 30, 2018. This growth was primarily driven by an increase in active patients.

For the three months ended December 31, 2018, cost of revenues was $23.0 million compared to $15.6 million for the same period in 2017, representing an increase of 47 percent. The increase was primarily driven by the cost of shipping transducer arrays to a higher volume of commercial patients and a one-time increase of $2.7 million in non-recoverable indirect taxes.

Research, development and clinical trials expenses for the three months ended December 31, 2018, were $15.0 million compared to $10.0 million for the same period in 2017, representing an increase of 50 percent. This was primarily due to an increase in clinical trial and personnel expenses for our METIS, LUNAR, and PANOVA-3 trials and an increase in personnel costs associated with regulatory and medical affairs.

Sales and marketing expenses for the three months ended December 31, 2018, were $21.2 million compared to $16.0 million for the same period in 2017, representing an increase of 32 percent. This was primarily due to increased marketing expenses, increases in personnel costs associated with a larger sales force globally and increased share-based compensation expense.

General and administrative expenses for the three months ended December 31, 2018, were $19.1 million compared to $16.5 million for the same period in 2017, representing an increase of 16 percent. This was primarily due to an increase in share-based compensation and an increase in professional services.

Personnel costs for the three months ended December 31, 2018, included $10.6 million in non-cash share-based compensation expenses, comprised of $0.4 million in cost of revenues; $1.3 million in research, development and clinical trials; $2.1 million in sales and marketing; and $6.9 million in general and administrative expenses. Total non-cash share-based compensation expenses for the fourth quarter 2017 were $6.4 million.

Net loss for the three months ended December 31, 2018, was $15.6 million compared to net loss of $10.9 million for the same period in 2017.

At December 31, 2018, we had $140.6 million in cash and cash equivalents and $105.3 million in short-term investments, for a total balance of $245.9 million in cash, cash equivalents and short-term investments. This represents an increase of $18.2 million in cash and investments since September 30, 2018.

Anticipated clinical and regulatory milestones

FDA approval for unresectable malignant pleural mesothelioma (2019)
Initiation of phase 3 pivotal trial in recurrent ovarian cancer (2019)
Zai Labs initiation of phase 2 pilot trial in gastric cancer (2019)
Data from phase 2 pilot HEPANOVA trial in advanced liver cancer (2020)
Interim analysis of phase 3 pivotal LUNAR trial in non-small cell lung cancer (2020)
Data from phase 3 pivotal METIS trial in brain metastases (2021)
Interim analysis of phase 3 pivotal PANOVA-3 trial in locally advanced pancreatic cancer (2021)
Final data from phase 3 pivotal LUNAR trial in non-small cell lung cancer (2021)
Interim analysis of phase 3 pivotal INNOVATE-3 trial in recurrent ovarian cancer (2022)
Conference call details

Novocure will host a conference call and webcast to discuss fourth quarter and full year 2018 financial results today, Thursday, Feb. 28, 2019 at 8 a.m. EDT. Analysts and investors can participate in the conference call by dialing 855-442-6895 for domestic callers and 509-960-9037 for international callers, using the conference ID 3956899.

The webcast, earnings slides presented during the webcast and the corporate presentation can be accessed live from the Investor Relations page of Novocure’s website, www.novocure.com/investor-relations, and will be available for at least 14 days following the call.

Contractor advisory committee meeting details

The durable medical equipment Medicare administrative contractors (DME MACs) plan to host a contractor advisory committee on March 6, 2019 from 9 a.m. to 4 p.m. EDT to discuss the scientific evidence underlying Novocure’s local coverage decision reconsideration request.

The meeting agenda is available on the DME MAC web sites. Morning and afternoon sessions of the contractor advisory committee meeting can be viewed live on the Centers for Medicare and Medicaid Services YouTube channel. A recording of the meeting will also be posted on the DME MAC web sites following the meeting.

On February 28, 2019 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, and through our license to Santen Pharmaceutical Co. Ltd., wet age‐related macular degeneration, reported financial results for the fourth quarter and year ended December 31, 2018 (Press release, Tracon Pharmaceuticals, FEB 28, 2019, View Source [SID1234533871]).

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Fourth Quarter 2018 and Recent Corporate Highlights

In February, we began preparation of data tables for the interim analysis by the Independent Data Monitoring Committee (DMC), following enrollment of the 120th patient into the TAPPAS Phase 3 trial. We expect the DMC to meet and provide the final sample size of the trial in April. The sample size needed to complete the trial will be a total of 190 patients if the interim results lie in the favorable or unfavorable zone and will be a total of 340 patients if in the promising zone. If the interim results lie in the enrichment zone, the trial will enroll a total of 220 patients with cutaneous disease. In the unfavorable scenario, the DMC could elect to terminate the trial early for futility.

In February, our partner Santen announced that they increased the sample size of the ongoing AVANTE Phase 2 randomized trial assessing the efficacy of DE-122, the ophthalmic formulation of TRC105, in combination with Lucentis in patients with wet AMD. The primary endpoint of the trial is unchanged and measures best corrected visual acuity. Top-line data from the study is expected in the first half of 2020. Santen is responsible for global development of DE-122 in eye disease and TRACON is entitled to receive up to $145M in additional developmental, regulatory and commercial milestones, as well as royalties on net sales ranging from the high single digits to low teen double digits.

In February, Dr. Francisco Robert of the University of Alabama, Birmingham updated positive top-line data reported in December 2018 from the Phase 1 trial of TRC105 and Opdivo in patients with non-small cell lung cancer at the International Association for the Study of Lung Cancer Targeted Therapies for Lung Cancer conference. The combination of TRC105 and Opdivo was well-tolerated without the development of dose limiting toxicity in six patients who were treated as part of dose escalation. One of these six patients, whose archival tumor did not express PD-L1 and who had not received prior PD-1/PD-L1 checkpoint inhibitor treatment, developed a confirmed partial response by RECIST and remains on study for more than 12 months. Two of the other five patients, one of whom progressed following prior Opdivo treatment, remain on trial with stable disease. Patients are currently enrolling into two parallel 12 patient expansion cohorts, one that includes patients who have progressed following prior PD-1/PD-L1 checkpoint inhibitor treatment and one that includes patients who have not received prior PD-1/PD-L1 checkpoint inhibitor treatment. Top-line data from these cohorts is expected to be reported in late 2019.

In February, we reacquired rights to develop TRC105 in Greater China from Ambrx. We had licensed rights to develop and commercialize TRC105 in Greater China to Ambrx for terms that included an upfront fee of $3.0M that was received in December 2017. Following discussions with Ambrx regarding their progress towards initiating a Phase 1 clinical trial of TRC105 in China, Ambrx notified us that it had elected to terminate the license agreement, resulting in all rights to TRC105 in Greater China reverting to TRACON. We now expect to engage a partner with substantial clinical development experience in China to lead TRC105 development, especially in hepatocellular cancer.

In February, following completion of pre-clinical development of TRC694, we determined the compound did not warrant further development and returned all rights to Janssen. TRC694 was licensed from Janssen in 2016 as part of a two compound agreement, one that included the license of TRC253 and an equity investment from Johnson & Johnson Innovation – JJDC, Inc. We continue to develop TRC253, which is in Phase 2 testing.

In January, we reported updated data from the ongoing Phase 1/2 trial of TRC105 and Nexavar in patients with hepatocellular carcinoma (HCC) at the Gastrointestinal Cancers Symposia of ASCO (Free ASCO Whitepaper). Three of 15 evaluable patients had confirmed partial responses by RECIST (20%). Since that time, one additional patient achieved a partial response, such that four of seventeen evaluable patients (24%) have now achieved partial responses by RECIST to date. For comparison, in separate Phase 3 trials, the confirmed partial response rate by RECIST in HCC patients treated with single agent Nexavar was 2% and 3%.

In December 2018, we submitted an IND for the CD73 antibody TJ4309 after executing a licensing agreement with I-Mab Biopharma (I-Mab) in November 2018. In January, the FDA cleared the IND and we expect to dose TJ4309 in a Phase 1 trial of cancer patients beginning in the first half of 2019.

In December 2018, we reported the Phase 2 TRAXAR trial of TRC105 and Inlyta in patients with advanced or metastatic renal cell carcinoma did not meet the primary endpoint of improving progression free survival when compared to single agent Inlyta. We expect to present data from this study at a scientific conference in the second half of 2019.

In November 2018, we announced a strategic partnership for up to five immuno-oncology programs with I-Mab to be nominated over a five year period. TRACON and I-Mab entered into a cost-sharing product development and commercialization collaboration whereby TRACON will be responsible for the regulatory and clinical development of TJ4309 and up to five bispecific antibodies in North America, with the majority of development expected to occur in the US. TRACON will bear the costs of early phases of clinical trials and I-Mab will share the costs for more advanced development stages and commercialization. TRACON will also share the North America rights of any selected bispecific antibodies with I-Mab for each collaborative program, with opt-in rights to in-license the bispecific antibodies from I-Mab in certain territories.

In November 2018, we reported top-line data from the Phase 2 trial of TRC102 and Temodar in patients with recurrent glioblastoma at the Society for Neuro-Oncology annual meeting. The combination of TRC102 and Temodar was tolerable, but did not meet the primary efficacy endpoint of demonstrating objective responses by Response Assessment in Neuro-Oncology criteria in the initial 19 enrolled patients. Two patients (10.5%) demonstrated evidence of clinical benefit and met the secondary endpoint of progression free survival (PFS) beyond 6 months. Both patients who demonstrated PFS for more than 11 months expressed methyl purine glycosylase, a biomarker associated with TRC102 activity in preclinical models.
"We continue to be encouraged by the rate of accrual into the TAPPAS Phase 3 trial and are excited to complete the interim analysis and implement the DMC’s decision with respect to the final sample size of the trial." said Charles Theuer, M.D., Ph.D., President and CEO of TRACON. "We expect the DMC decision in April, at which time we will provide further details in a conference call."

Expected Upcoming Milestones

Announcement of the results of the interim analysis to determine the final sample size of the Phase 3 pivotal TAPPAS trial of TRC105 in angiosarcoma is expected in April.

Announcement of first in human dosing of TJ4309 is expected in the first half of 2019.

Presentation of preclinical data by Leiden University researchers on the activity of TRC105 in combination with checkpoint inhibitors at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in Philadelphia, PA is expected in March.

Presentation of expanded cohort data by the National Cancer Institute from the Phase 1 trial of TRC102 and Temodar in patients with colorectal, lung and ovarian cancer at the AACR (Free AACR Whitepaper) annual meeting in Philadelphia, PA is expected in April.

Presentation of TRC253 Phase 1 data in patients with metastatic castrate resistant prostate cancer is expected in the first half of 2019.
Fourth Quarter 2018 Financial Results

Cash, cash equivalents and short-term investments were $39.1 million at December 31, 2018, compared to $34.5 million at December 31, 2017. We expect our current cash, cash equivalents and short-term investments to fund operations late into the first quarter of 2020.

Research and development expenses for the fourth quarter of 2018 were $5.9 million compared to $4.6 million for the fourth quarter of 2017. The increase was primarily attributable to manufacturing expenses for TRC105 in the fourth quarter of 2018 as compared to the 2017 period.

General and administrative expenses for the fourth quarter of 2018 were $1.8 million compared to $1.7 million for the fourth quarter of 2017.

Net loss for the fourth quarter of 2018 was $7.8 million compared to a net loss of $6.6 million for the fourth quarter of 2017.
Investor Conference Call

The Company will hold a conference call today at 4:30 p.m. EST / 1:30 p.m. PST to provide an update on corporate activities and to discuss the financial results of its fourth quarter and full year of 2018. The dial-in numbers are (855) 779‑9066 for domestic callers and (631) 485-4859 for international callers. Please use passcode 7886794. A live webcast of the conference call will be available online from the Investor/Events and Presentation page of the Company’s website at www.traconpharma.com.

After the live webcast, a replay will remain available on TRACON’s website for 60 days.

About TRC105 (carotuximab)

TRC105, the oncology formulation of carotuximab, is a novel, clinical stage antibody to endoglin, a protein overexpressed on proliferating endothelial cells that is essential for angiogenesis, the process of new blood vessel formation. TRC105 is currently being studied in the pivotal Phase 3 TAPPAS trial in patients with angiosarcoma as well as multiple Phase 1 and Phase 2 clinical trials in other tumor types. TRC105 has received orphan designation for the treatment of soft tissue sarcoma in both the US and EU. The ophthalmic formulation of TRC105, DE-122, is currently being studied in the randomized Phase 2 AVANTE trial in patients with wet AMD. For more information about the clinical trials, please visit TRACON’s website at www.traconpharma.com/clinical_trials.php.

About DE-122 (carotuximab)

DE-122, a novel ophthalmic formulation of carotuximab, is active in preclinical choroidal neovascularization (CNV) models and expected to enhance the effect of approved VEGF inhibitors used to treat wet AMD. DE-122 is being investigated in the Phase 2 randomized AVANTE trial assessing the efficacy and safety of intravitreal injections in combination with Lucentis (ranibizumab) compared to Lucentis monotherapy in patients with wet AMD.

About TRC102

TRC102 (methoxyamine) is a novel, clinical-stage small molecule inhibitor of the DNA base excision repair pathway, which is a pathway that causes resistance to alkylating and antimetabolite chemotherapeutics. TRC102 is currently being studied in multiple Phase 1 and Phase 2 clinical trials sponsored by the National Cancer Institute or Case Comprehensive Cancer Center. For more information about the clinical trials, please visit TRACON’s website at www.traconpharma.com/clinical_trials.php.

About TRC253

TRC253 is a novel, orally bioavailable small molecule that is a potent, high affinity competitive inhibitor of the androgen receptor (AR) and AR mutations, including the F877L mutation. The AR F877L mutation results in an alteration in the AR ligand binding domain that confers resistance to therapies for prostate cancer. Therapies targeting the AR have demonstrated clinical efficacy by extending time to disease progression, and in some cases, the survival of patients with metastatic castration-resistant prostate cancer. However, resistance to these agents is often observed and several molecular mechanisms of resistance have been identified, including gene amplification, overexpression, alternative splicing, and point mutation of the AR. TRC253 is currently being studied in a Phase 1/2 clinical trial in prostate cancer. For more information about the clinical trial, please visit TRACON’s website at www.traconpharma.com/clinical_trials.php

About TJ4309

TJ4309 is a novel, humanized antibody against CD73, an ecto-enzyme expressed on stromal cells and tumors that converts extracellular adenosine monophosphate (AMP) to adenosine, which is highly immunosuppressive. TJ4309 is expected to begin clinical testing in the U.S. in the first half of 2019 in a trial to assess safety and preliminary efficacy as a single agent and when combined with a PD-1/PD-L1 checkpoint inhibitor in patients with advanced solid tumors.

On February 27, 2019 Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) reported financial results for the fourth quarter and full year 2018 and reviewed highlights of its successful year (Press release, Ionis Pharmaceuticals, FEB 27, 2019, View Source [SID1234533727]).

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"We begin 2019 in the strongest position in our 30-year history. Building on this foundation, we believe we are positioned for continued growth," said Stanley T. Crooke, M.D., Ph.D., chairman of the board and chief executive officer of Ionis. "In 2018, we launched TEGSEDI globally through our affiliate, Akcea, adding revenue from TEGSEDI sales to our substantial commercial revenue from SPINRAZA. We also achieved many important milestones in our pipeline, particularly among the medicines within our late-stage pipeline. This week, Novartis exercised its option to license AKCEA-APO(a)-LRx for which we earned $150 million. Novartis plans to initiate a Phase 3 cardiovascular outcomes study and initiation activities are already underway. We and Akcea are finalizing Phase 3 study designs for the AKCEA-TTR-LRx pivotal program that we plan to initiate in the second half of this year. In addition, our late-stage neurological disease programs recently achieved important milestones. Roche is now enrolling patients in the Phase 3 study of IONIS-HTTRx for Huntington’s disease and Biogen is planning to add an additional cohort to the ongoing study of IONIS-SOD1Rx for patients with SOD1-related ALS that has the potential to support marketing approval. We achieved these successes while growing revenues, investing in the commercialization of TEGSEDI, advancing our broad and diverse pipeline, and consistently leading our industry in innovation – demonstrating the success of our business model and robust technology platform."

2018 Financial Results and Highlights

Revenues increased by 17 percent compared to 2017

Total revenue was $600 million compared to $514 million in 2017.

Commercial revenue from SPINRAZA for 2018 was $238 million, more than double compared to 2017.

TEGSEDI sales were $2.2 million in the fourth quarter of 2018, with commercial sales commencing in the EU in October and in the U.S. in December.

Commercial revenue was over 40 percent of total revenue in 2018 compared to less than 25 percent in 2017, reflecting Ionis’ transition to a commercial-stage company.

Achieved third consecutive year of non-GAAP operating profitability

GAAP operating income was $11 million for the fourth quarter and an operating loss of $61 million for the full year 2018, compared to an operating loss of $6 million and operating income of $31 million for the same periods in 2017.

Non-GAAP operating income was $45 million for the fourth quarter and $70 million for the full year 2018, compared to operating income of $16 million and $117 million for the same periods in 2017

Operating expenses increased in 2018 primarily due to investment in the commercialization of TEGSEDI.

Strong financial results trigger the recognition of a significant tax benefit

In 2018, Ionis reported GAAP net income attributable to Ionis common stockholders of $274 million, primarily driven by a $291 million one-time non-cash income tax benefit Ionis recorded in 2018 related to its income tax assets.

Because of Ionis’ strong financial performance over the past few years and its outlook regarding the continued growth of its business, the Company believes it is more likely than not that it will be able to use the significant amount of income tax assets it has accumulated to offset future taxable income.

Substantial cash position of over $2 billion enables continued investment in commercial products and pipeline

2019 Financial Guidance

"Building upon our success in 2018, we expect to continue our momentum this year and beyond. We anticipate both commercial and R&D revenues to contribute to our overall earnings growth this year, potentially making 2019 our fourth consecutive year of non-GAAP operating profitability. And for the first time, due to our strong financial performance in recent years and strong confidence in our future, we are projecting to be profitable on the bottom line on a non-GAAP basis in 2019. We believe our ability to be profitable while investing in commercial activities, fully exploiting our pipeline and advancing our technology, clearly sets us apart from our peers," said Elizabeth L. Hougen, chief financial officer of Ionis.

All non-GAAP amounts referred to in this press release exclude non-cash compensation expense related to equity awards. Please refer to the reconciliation of non-GAAP and GAAP measures, which is provided later in this release. In prior financial results releases, Ionis referred to amounts that excluded non-cash compensation expense related to equity awards as "pro forma". Additionally, Ionis has labeled its prior period financial statements "as revised" to reflect the revenue recognition accounting standard the Company adopted on January 1, 2018.

Business Highlights

·
SPINRAZA – the worldwide standard-of-care for the treatment of all people with spinal muscular atrophy

o
In 2018, SPINRAZA sales nearly doubled to $1.7 billion compared to 2017, driven by growth in the U.S. and outside the U.S., as reported by Biogen.

o
As of the fourth quarter of 2018, more than 6,600 SMA patients from over 40 countries were on SPINRAZA, including commercial patients and patients in the expanded access program and clinical trials.

o
In the fourth quarter of 2018, the number of adult patients on therapy in the U.S. grew by over 20 percent compared to the third quarter, accounting for more than 50 percent of new patient starts in the U.S.

·
TEGSEDI (inotersen) – launch underway in multiple markets for the treatment of polyneuropathy of hereditary transthyretin amyloidosis (hATTR) in adult patients

o
TEGSEDI generated $2.2 million in sales from the U.S. and EU in its first quarter of launch.

o
PTC Therapeutics, Ionis and Akcea’s commercialization partner in Latin America, filed for marketing authorization for TEGSEDI in Brazil and was granted priority review.

Key Upcoming Events

·
Roche plans to present data from the OLE study of IONIS-HTTRx in patients with Huntington’s disease in 2019.
·
Biogen plans to present data from the completed portions of the Phase 1/2 study of IONIS-SOD1Rx in 2019.
·
Ongoing regulatory discussions on WAYLIVRA in the EU, and if approved, launch.
·
Ionis and its partners plan to report data from numerous Phase 2 studies including IONIS-FXIRx, IONIS-HBVRx and IONIS-GHR-LRx.

Revenue

Ionis’ revenue in the three months and year ended December 31, 2018 was $192 million and $600 million, respectively, compared to $168 million and $514 million for the same periods in 2017 and was comprised of the following (amounts in millions):

The increase in revenue in 2018 compared to 2017 was primarily due to increasing commercial revenue from SPINRAZA royalties, which more than doubled. Additionally, Ionis earned more than $2 million from TEGSEDI product sales in the fourth quarter of 2018.

Ionis’ R&D revenue demonstrates the Company’s ability to generate sustainable revenue from its numerous partnerships. R&D revenue from the amortization of upfront payments increased over $25 million in 2018 compared to 2017. The increase in amortization was primarily due to Ionis’ 2018 strategic neurology collaboration with Biogen. Also, in 2018, Ionis added amortization revenue from its new collaboration with Roche to develop IONIS-FB-LRx. Ionis’ R&D revenue from milestone payments, license fees and other services for 2018 continued to make a significant contribution to Ionis’ financial results.

Already in the first quarter of 2019, Ionis has earned $185 million. The Company earned $150 million from Novartis when it licensed AKCEA-APO(a)-LRx and $35 million from Roche when it enrolled the first patient in the Phase 3 study of IONIS-HTTRx in patients with Huntington’s disease.

Operating Expenses

Operating expenses for the three months and year ended December 31, 2018 on a GAAP basis were $181 million and $661 million, respectively, and on a non-GAAP basis were $147 million and $530 million, respectively. These amounts compare to GAAP operating expenses for the three months and year ended December 31, 2017 of $174 million and $483 million, respectively, and non-GAAP operating expenses of $152 million and $397 million, respectively. The full year increase in operating expenses in 2018 compared to 2017 was principally due to Ionis’ investments in the global launch of TEGSEDI. The Company’s SG&A expenses also increased due to an increase in fees the Company owed under its in-licensing agreements related to SPINRAZA, due to increased SPINRAZA product sales.

Income Tax Benefit

Ionis reported an income tax benefit of $292 million and $291 million for the three months and year ended December 31, 2018, respectively, compared to $7 million and $6 million for the same periods in 2017. Ionis’ tax benefit increased significantly in 2018 primarily due to a one-time non-cash tax benefit related to its deferred income tax assets. In the fourth quarter of 2018, the Company released a large portion of the valuation allowance associated with its deferred tax assets. Because of Ionis’ strong financial performance over the past few years and its outlook regarding the continued growth of its business, the Company determined that it is more likely than not that it will be able to utilize most of the deferred income tax assets it has accumulated to offset future taxable income.

Net Loss Attributable to Noncontrolling Interest in Akcea

At December 31, 2018, Ionis owned approximately 75 percent of Akcea. The shares of Akcea third parties own represent an interest in Akcea’s equity that Ionis does not control. However, because Ionis continues to maintain overall control of Akcea through its voting interest, Ionis reflects the assets, liabilities and results of operations of Akcea in Ionis’ consolidated financial statements. Ionis reflects the noncontrolling interest attributable to other owners of Akcea’s common stock in a separate line called "Net loss attributable to noncontrolling interest in Akcea" on Ionis’ statement of operations. Ionis’ net loss attributable to noncontrolling interest in Akcea for the three months and year ended December 31, 2018, was $17 million and $59 million, respectively. Ionis’ net loss attributable to noncontrolling interest in Akcea for the three months and year ended December 31, 2017, was $6 million and $11 million, respectively.

Net Income (Loss) Attributable to Ionis Common Stockholders

Ionis reported net income attributable to Ionis’ common stockholders of $320 million and $274 million for the three months and year ended December 31, 2018, respectively, compared to a net loss of $3 million and net income of $0.3 million for the same periods in 2017, all on a GAAP basis. On a non-GAAP basis, Ionis reported net income attributable to Ionis’ common stockholders of $351 million and $394 million for the three months and year ended December 31, 2018, respectively, compared to $18 million and $85 million for the same periods in 2017. The increase in 2018 net income attributable to Ionis’ common stockholders was primarily due to increases in revenue and the income tax benefit Ionis recognized in the fourth quarter of 2018.

For the three months ended December 31, 2018, basic and diluted net income per share were $2.32 and $2.21, respectively. For the year ended December 31, 2018, basic and diluted net income per share were $2.09 and $2.07, respectively. For the three months ended December 31, 2017, basic and diluted net loss per share were each $0.03. For the year ended December 31, 2017, basic and diluted net income per share were each $0.15. All amounts are on a GAAP basis.

Balance Sheet

As of December 31, 2018, Ionis had cash, cash equivalents and short-term investments of $2.1 billion compared to $1.0 billion at December 31, 2017. The increase in Ionis’ cash, cash equivalents and short-term investments was primarily due to the $1 billion Ionis received from Biogen for the 2018 strategic neurology collaboration.

Webcast and Conference Call

Today, at 11:30 a.m. Eastern Time, Ionis will conduct a live webcast conference call to discuss this earnings release and related activities. Interested parties may listen to the call by dialing 877-443-5662 or access the webcast at www.ionispharma.com. A webcast replay will be available for a limited time.

On February 27, 2019 Molecular Templates, Inc., (Nasdaq: MTEM) a clinical stage biopharmaceutical company focused on the discovery and development of Engineered Toxin Bodies (ETBs), a new class of targeted biologic therapies that possess unique mechanisms of action in oncology, reported that new data on its pipeline programs and technology platform will be presented in four posters at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019, to be held March 29 – Apr 3, 2019 at the Georgia World Congress Center in Atlanta, Georgia (Press release, Molecular Templates, FEB 27, 2019, View Source [SID1234533763]).

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Preclinical data on TAK-169, the company’s CD38-targeted ETB (partnered with Takeda Pharmaceutical Company Limited), will be presented for the first time at the AACR (Free AACR Whitepaper) meeting. This molecule is the most potent ETB that Molecular Templates has developed against any target to date. Importantly, in preclinical models, TAK-169 is active in the presence of daratumumab and active against daratumumab resistant cells.

"We are excited to be presenting new data on multiple pipeline programs as well as potential new applications of our ETB technology platform," said Eric Poma, Ph.D., CEO and CSO of Molecular Templates. "We believe that TAK-169 could be an important new therapy for multiple myeloma patients and these new preclinical data support our rationale for the partnership we announced with Takeda in September 2018. We look forward to the start of clinical development for TAK-169 this year. We believe that data on our CD20 and PD-L1 ETBs support our clinical development plans for those programs. Furthermore, the data on bispecific ETBs highlight the breadth of potential application of our technology, which we expect to drive continued pipeline expansion and partnership opportunities."

Date: Monday, April 1
Time: 1:00pm – 5:00pm Eastern Time
Session: Immunology: Therapeutic Antibodies 3
Abstract #: 2384
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 25, Poster Board Number 8
Poster Title: TAK-169, an Exceptionally Potent CD38 Targeted Engineered Toxin Body, as a Novel Direct Cell Kill Approach for the Treatment of Multiple Myeloma
Authors: Erin K. Willert1, Garrett L. Robinson1, Jack P. Higgins1, Jensing Liu1, Janice Lee2, Sakeena Syed2, Yuhong Zhang2, Dan Tavares2, Anya Lublinsky2, Nibedita Chattopadhyay2, Haiqing Wang2, Laura Packer2, Pu Shi2, Carole Harbison2, Sanjay Patel2, John Newcomb2
1Molecular Templates Inc., Austin, TX; 2Takeda, Cambridge, MA
Molecular Templates will present on its CD38-targeted ETB, TAK-169. Although CD38 is a poorly internalizing receptor, TAK-169 is able to efficiently internalize and directly kill CD38-expressing cells. This novel mechanism of action may be relevant in patients who have progressed after or are unlikely to respond to CD38-targeted antibody therapy. TAK-169 has demonstrated potent cytotoxicity across a range of myeloma cell lines with a range of CD38 expression in vitro as well as in patient-derived samples including those with previous exposure to daratumumab. Furthermore, TAK-169 retains activity in the presence of excess approved, CD38 targeted therapeutic daratumumab. In xenograft models, complete regressions were observed using both a once-weekly and bi-weekly schedule of TAK-169. Tolerability studies in non-human primates demonstrate that repeat administration is tolerated at doses that are expected to be efficacious. TAK-169 is expected to enter the clinic in 2019.

Date: Monday, April 1
Time: 1:00pm – 5:00pm Eastern Time
Session: Experimental and Molecular Therapeutics: Apoptosis, Necrosis, and Cancer Cell Survival
Abstract #: 2060
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 9, Poster Board Number 12
Poster Title: Combination of CD20 targeted Engineered Toxin Body, MT-3724, with chemotherapy or IMiDs for the treatment of Non Hodgkin’s Lymphoma
Authors: Jack P. Higgins, Aimee Iberg, Caleigh Howard & Erin K. Willert
MT-3724 is a CD20-targeted ETB that has demonstrated single agent anti-tumor activity in heavily pre-treated relapsed/refractory (R/R) Non-Hodgkin’s lymphoma (NHL) patients in a Phase I clinical study. The combination of MT-3724 with chemotherapeutic agents (doxorubicin, gemcitabine, bendamustine, and vincristine) or an immunomodulatory (IMiD) agent (lenalidomide) all demonstrated additive or synergistic cytotoxicity of NHL cell lines. Additional clinical studies to evaluate MT-3724 as single agent and in combination with gemcitabine and oxaliplatin (GEMOX) or lenalidomide are underway and expected to generate data in 2019.

Date: Tuesday, April 2
Time: 1:00pm – 5:00pm Eastern Time
Session: Experimental and Molecular Therapeutics: Pharmacokinetics and Pharmacodynamics / Preclinical Toxicology
Abstract #: 3900
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 13, Poster Board Number 20
Poster Title: The Safety and efficacy Profile of a PD-L1 Directed, Engineered Toxin Body, as a Novel Targeted Direct-Cell Kill Approach for the Treatment of PD-L1 Expressing Cancers
Authors: Hilario J. Ramos, Asis K. Sarkar, Sara Le Mar, Brigitte Brieschke, Joseph D. Dekker, Veronica R. Partridge, Pablo A. Maceda, Michaela M. Sousares, Garrett L. Robinson, Aimee Iberg, Shaoyou Chu, Jensing Liu, Jack P. Higgins, Erin K. Willert.
Molecular Templates has developed PD-L1-targeting ETBs as an approach to directly target tumor cells and overcome resistance mechanisms against PD-1 and PD-L1 antibodies. The cytotoxicity delivered by PD-L1-specific ETBs is engineered to be independent of a requirement for tumor infiltrating lymphocytes, high tumor mutational burden, or modulatory effects of the tumor microenvironment. Further, the activity is not dependent on blockade of the PD-1/PD-L1 checkpoint axis. Thus, PD-L1-targeting ETBs represent a distinct class of therapeutics with direct cell-kill mechanism of action and ability for activity in patients who have progressed on current standard of care or checkpoint therapy. In this presentation, we highlight the efficacy and safety profile of MT-6020, a human and cynomolgus cross-reactive, PD-L1 targeted, ETB. MT-6020 binds to cell lines expressing non-human primate PD-L1 and elicits cytotoxic responses comparable to those observed on human tumor target cells. Molecular Templates’ PD-L1 ETB, MT-6035, is built upon the MT-6020 scaffold and can also deliver a viral peptide for cell surface presentation and targeting by a specific antiviral CTL population for a second and complementary mechanism for tumor cell destruction, referred to as antigen seeding. MT-6020 and MT-6035 represent a novel approach to targeting and destroying tumors expressing PD-L1 that is unlikely to be inhibited by resistance mechanisms to current checkpoint inhibitors, is well tolerated in relevant toxicity models, and has the capacity for activity in indications where standard of care has failed. Molecular Templates expects to initiate clinical development of the PD-L1-targeted-ETB (with antigen seeding) in 2H19.

Date: Tuesday, April 2
Time: 8:00am – 12:00pm Eastern Time
Session: Experimental and Molecular Therapeutics: Diagnostics, Biomarkers, and the Tumor Microenvironment
Abstract #: 2984
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 11, Poster Board Number 6
Poster Title: Design and Characterization of Bispecific Engineered Toxin Bodies for Targeted Cancer Therapy
Authors: Aimee Iberg, Garrett L. Cornelison, Caleigh Howard, Paul Amador, Steven Rivera, Michael Jamaleddine, Garrett L. Robinson, Erin K. Willert
To further expand the therapeutic benefit of its ETB platform, Molecular Templates is characterizing ETBs that are targeted through multiple binding domains. Bispecific ETBs that target two epitopes on the same receptor, or two distinct cell surface molecules both expressed on cancer cells, may allow for enhanced activity profiles. These possibilities include: (i) activity in the presence of a competitive binding protein (ii) sustained activity when one target molecule is shed or downregulated, (iii) synergistic binding events to increase overall potency, and (iv) increased specificity towards cancer over normal tissue. Bispecific ETBs have been generated to engage a variety of target combinations, relevant to both solid and hematologic cancer treatment. MTEM is exploring therapeutically relevant target combinations to facilitate the development of a bispecific clinical lead. By pairing the biology and potency of ETB-mediated killing with the expanded targeting possibilities afforded by bispecific molecules, Molecular Templates aims to develop a new class of therapeutics to benefit cancer patients.

On February 27, 2019 Oncopeptides AB (Nasdaq Stockholm: ONCO) reported that data from its Phase II HORIZON study and Phase I/II ANCHOR study evaluating the company’s novel candidate melflufen, a peptide-conjugated alkylator belonging to the novel class of peptidase enhanced compounds, have been selected as poster presentations at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on 29 March – 3 April 2019 in Atlanta, Georgia, USA (Press release, Oncopeptides, FEB 27, 2019, View Source [SID1234533791]).

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– Data demonstrate tolerability and high level of activity associated with melflufen in relapsed/refractory multiple myeloma (RRMM) patients –

– Early signs of high efficacy are encouraging; studies are ongoing –

"Our rigorous clinical development program is initially focused on our first-in-class candidate melflufen, which is currently being studied in global Phase II studies and the Phase III OCEAN study," said Jakob Lindberg, CEO of Oncopeptides. "We are extremely pleased that these data have been selected for poster presentation at AACR (Free AACR Whitepaper), following their initial presentation at the ASH (Free ASH Whitepaper) 2018 Annual Meeting, and believe that this further validates the promise that melflufen holds for the treatment of patients with advanced multiple myeloma whose treatment options are limited."

Melflufen’s novel mechanism of action works by eliciting increased cytotoxicity in target multiple myeloma (MM) cells and substantially reduced off-target cell toxicity. Melflufen is in a pivotal Phase III study, OCEAN, for its initial indication in RRMM under a Special Protocol Assessment from the US Food and Drug Administration (FDA). Based on ongoing preclinical studies, Oncopeptides is also exploring the potential for the use of melflufen, or other peptide-conjugated drugs, to treat various cancers beyond MM.

The full AACR (Free AACR Whitepaper) 2019 Annual Meeting abstract book can be viewed at www.aacr.org.

The posters we present are found under the title:
HORIZON: Melflufen in patients (pts) with relapsed/refractory multiple myeloma (RRMM) refractory to daratumumab (dara) and/or pomalidomide (pom) (OP-106)

ANCHOR: Melflufen and dexamethasone (dex) plus bortezomib (BTZ) or daratumumab (dara) in patients (pts) with relapsed/refractory multiple myeloma (RRMM) (OP-104)

For more information, please contact:
Jakob Lindberg, CEO of Oncopeptides
Telephone: +46 (0)8 615 20 40
E-mail: [email protected]

Rein Piir, Head of Investor Relations at Oncopeptides
Cell phone: +46 70 853 72 92
E-mail: [email protected]

This information was submitted for publication at 22.30 CET, 27 February 2019