On February 27, 2019 Idera Pharmaceuticals, Inc. (NASDAQ: IDRA) reported completion of enrollment into the ongoing phase 2 expansion of the ILLUMINATE-204 trial investigating tilsotolimod, Idera’s intratumorally-delivered toll-like receptor 9 (TLR9) agonist, in combination with ipilimumab (Yervoy*) in patients with unresectable or metastatic melanoma following failure of PD-1 inhibitor treatment (Press release, Idera Pharmaceuticals, FEB 27, 2019, View Source [SID1234533745]).

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52 patients have been dosed in the trial which included two separate patient groups. The company completed the targeted enrollment of 40 patients in the primary enrollment population, constituting patients who are naïve to prior ipilimumab treatment in the metastatic setting. This patient population mirrors the enrollment for the ILLUMINATE-301 phase 3 pivotal trial. The secondary exploratory enrollment population targeted up to 20 patients who had prior ipilimumab treatment in the metastatic setting.

The ILLUMINATE-204 trial is a multi-center trial being conducted at 10 sites throughout the United States.

The company is currently enrolling ILLUMINATE-301, a global, multi-center, randomized Phase 3 trial that compares effectiveness and safety between two treatment groups: tilsotolimod combined with ipilimumab versus ipilimumab given alone. This trial is being conducted at up to 100 centers with a target enrollment of 308 patients. Enrollment remains on track and is expected to be completed in the 4th quarter of 2019.

The company also recently received notice from the U.S. Food and Drug Administration that the company can proceed to implement the ILLUMINATE-206 clinical trial under a new Investigational New Drug (IND) Application. The ILLUMINATE-206 trial will test the safety and effectiveness of tilsotolimod in combination with ipilimumab and nivolumab in treating patients with Squamous Cell Carcinoma of the Head and Neck (SCCHN) and Microsatellite Stable Colorectal Cancer (MSS-CRC). The ILLUMINATE-206 trial is expected to initiate in the second quarter of 2019.

"We made tremendous progress with the clinical development of tilsotolimod in the second half of 2018, and enrollment in the phase 3 study in patients with melanoma progressing on PD-1 therapy is tracking to complete by the end of 2019." stated Joanna Horobin, M.B. Ch.B, Idera’s Chief Medical Officer. "Oncologists are enthusiastic to extend the use of tilsotolimod to potentially improve the outcome of immuno-therapy for other patient populations, such as head and neck cancer, and in microsatellite stable CRC where so far immunotherapy outcomes have not been optimal."

As a reminder, the company provided an interim data update from the ILLUMINATE-204 trial in December 2018.

Summary of ILLUMINATE-204 Key Findings from the December 2018 Update:

37 patients dosed with 8 mg of tilsotolimod in combination with ipilimumab were evaluated for the December 2018 update;
All 37 patients were evaluable for safety;
The combination regimen continues to be generally well tolerated. 9/37 subjects (24.3%) had immune-related toxicities indicating that tilsotolimod + ipilimumab does not appear to add immune-related toxicity versus ipilimumab alone;
Injection-related toxicities were grade 1-2 transient fever and flu-like symptoms lasting <48 hours;
34 patients were evaluable for efficacy;
Responses, including 3 Complete Responses (CR), were observed in 11 of the 34 evaluable patients (32.4%);
Duration of response ranges from > 1 month to > 30 months, with 36% of responses ongoing at the time of the report;
Per RECIST v1.1, the Overall Response Rate (ORR) is 29.4%; one patient with an unconfirmed Partial Response (uPR) at the end of treatment assessment progressed due to a new lesion at the 3-month follow-up disease assessment;
Overall, 26 patients out of 34 evaluable for efficacy (76.5%) experienced disease control (CR, PR, or Stable Disease [SD]);
Analysis of spider plots show tumor shrinkage in both injected and uninjected lesions, indicating an abscopal effect;
Responding subjects include one patient with mucosal melanoma and one patient with acral melanoma, two forms of melanoma that are particularly difficult to treat; and
Importantly, 2 of 5 patients with prior ipilimumab experience achieved responses, further demonstrating a signal that tilsotolimod has the potential to help overcome prior ipilimumab resistance.
Additionally:

A RECIST v1.1 PR of > 2.5 years is ongoing in 1 patient treated with tilsotolimod 4 mg in combination with ipilimumab; and
A RECIST v1.1 CR of > 1 year is ongoing in 1 patient treated with tilsotolimod 16 mg in combination with pembrolizumab.
About Tilsotolimod (IMO-2125)
Tilsotolimod is a TLR 9 agonist that received Fast Track Designation from the US Food and Drug Administration (FDA) in 2017 for the treatment of anti-PD-1 refractory melanoma, in combination with ipilimumab as well as orphan drug designation from the FDA for the treatment of melanoma Stages IIb to IV. It signals the immune system to create and activate cancer-fighting cells (T-cells) to target solid tumors. Currently approved immuno-oncology treatments, specifically check-point inhibitors, work for some but not all, as many patients’ immune response is missing or weak and thus they do not benefit from the checkpoint therapy. Intratumoral injections with tilsotolimod are designed to selectively enable the tumor-specific T-cells to recognize and attack cancers that remained elusive and unrecognized by the immune system exposed to checkpoint inhibitors alone, while limiting toxicity or impact on healthy cells in the body.

About ILLUMINATE-301
The ILLUMINATE-301 study (2125-MEL-301) is for patients who have metastatic melanoma for whom treatment with an anti-PD-1 drug like Keytruda (pembrolizumab) or Opdivo (nivolumab) has failed. ILLUMINATE-301 is a global, multi-center, randomized Phase 3 study that compares the effectiveness and safety between two treatment groups: IMO-2125 combined with ipilimumab (Yervoy) versus ipilimumab given alone.

For additional details about ILLUMINATE-301, please go to clinicaltrials.gov and search for study identifier NCT03445533.

About ILLUMINATE-204
The ILLUMINATE-204 study (2125-204) is for patients who have metastatic melanoma for whom treatment with an anti-PD-1 drug like Keytruda** (pembrolizumab) or Opdivo* (nivolumab) has failed. ILLUMINATE-204 is a multi-center, two-arm Phase 1/2 study that tests the safety and effectiveness of tilsotolimod in combination with either ipilimumab (Yervoy) or pembrolizumab (Keytruda) for the treatment of patients with anti-PD-1 refractory metastatic melanoma.

For additional details about ILLUMINATE-204, please go to clinicaltrials.gov and search for study identifier NCT02644967.

About ILLUMINATE-206
The ILLUMINATE-206 study (2125-206) is a Phase 2 multi-center, multi-cohort study of intratumoral tilsotolimod in combination with nivolumab and ipilimumab in patients with Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are either immunotherapy naïve and immunotherapy refractory and immunotherapy naïve patients with Microsatellite Stable Colorectal Cancer (MSS-CRC). The trial is expected to open for enrollment in the second quarter of 2019.

About Metastatic Melanoma
Although melanoma is a rare form of skin cancer, it comprises over 75% of skin cancer deaths. The American Cancer Society estimates that there were approximately 76,000 new invasive melanoma cases and 10,000 deaths from the disease in the USA in 2016. Additionally, according to the World Health Organization, about 132,000 new cases of melanoma are diagnosed around the world every year.

On February 27, 2019 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a clinical-stage oncology-focused biopharmaceutical company pioneering a novel class of investigational antibody therapeutics based on its Probody therapeutic technology platform, reported full-year 2018 financial results (Press release, CytomX Therapeutics, FEB 27, 2019, View Source/news-releases/news-release-details/cytomx-therapeutics-announces-full-year-2018-financial-results" target="_blank" title="View Source/news-releases/news-release-details/cytomx-therapeutics-announces-full-year-2018-financial-results" rel="nofollow">View Source [SID1234533793]). As part of its 2019 Research and Development Day held yesterday in New York, CytomX provided an operational update on the company.

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As of December 31, 2018, CytomX had cash, cash equivalents and short-term investments of $436.1 million, sufficient capital to fund its operating expenses and capital requirement into 2021.

"Over the last year, we have generated meaningful clinical proof of concept data for the Probody platform across both of our lead, wholly-owned programs," said Sean McCarthy, D.Phil., president, chief executive officer and chairman of CytomX Therapeutics. "As we showed at our inaugural Research and Development Day yesterday, our PD-L1 Probody therapeutic, CX-072, is active across a wide range of tumors and has a potentially differentiated safety profile as monotherapy and in combination. CX-2009, our first-in-class CD166 Probody Drug Conjugate, is well tolerated and has demonstrated anti-tumor activity across multiple tumor types. In 2019, we will continue to explore the full potential of these innovative product candidates as we maintain our intense focus on discovery, development and ultimate commercialization of a new generation of differentiated cancer therapeutics."

2018 Business Highlights and Recent Developments

PROCLAIM-CX-072 (PD-L1 Probody Therapeutic) Clinical Program

CX-072 is a Probody therapeutic targeting PD-L1, a clinically- and commercially-validated anti-cancer target.
Enrollment began in January 2017 in PROCLAIM-CX-072, a Phase 1/2 clinical trial evaluating CX-072 as monotherapy and in combination with YERVOY (ipilimumab) or Zelboraf (vemurafenib) in patients with cancer.
Enrollment is complete with follow-up continuing in the monotherapy dose escalation arm evaluating CX-072 in patients with advanced unresectable solid tumors or lymphomas (Part A) and in the monotherapy dose escalation arm in patients with PD-L1-positive tumors (Part A2).
Enrollment and follow-up are ongoing in the monotherapy expansion cohorts of CX-072 at 10 mg/kg in multiple indications (Part D).
Data from Parts A, A2 and D was presented most recently at CytomX’s 2019 Research and Development Day.
Additional data from Part D is expected in 2019.
Enrollment of the dose escalation arm combining CX-072 plus Yervoy (ipilimumab) in patients with advanced unresectable solid tumors or lymphomas (Part B) is complete and was presented most recently at CytomX’s 2019 Research and Development Day.
Enrollment is ongoing in the dose escalation combination arm of CX-072 plus Zelboraf (vemurafenib) in patients with V600E BRAF-positive melanoma (Part C).
PROCLAIM-CX-2009 (CD166 Probody Drug Conjugate) Clinical Program

CX-2009 is a Probody drug conjugate (PDC) that targets CD166, an antigen that is broadly and highly expressed in many types of cancer, and is conjugated with DM4, a clinically-validated toxin licensed from ImmunoGen.
Enrollment began in June 2017 in PROCLAIM-CX-2009, a Phase 1/2 clinical trial, evaluating CX-2009 as monotherapy in a subset of seven cancer types (Part A) and in patients selected for high level of CD166 expression (Part A2).
Preliminary data from Parts A and A2 was presented at CytomX’s 2019 Research and Development Day.
BMS-986249 (CTLA-4 Probody Therapeutic) Clinical Program

Bristol-Myers Squibb (BMS), continues enrollment in a Phase 1/2 clinical trial evaluating BMS-986249 alone and in combination with OPDIVO (nivolumab) in solid tumors that are advanced and have spread.
BMS has stated that they anticipate preliminary data from this trial in 2019.
CX-2029 (CD71 Probody Drug Conjugate) Clinical Program

CytomX, in collaboration with AbbVie, is advancing CX-2029, a CD71-directed Probody Drug Conjugate.
CD71, also known as the transferrin receptor 1 (TfR1), is highly expressed in a number of solid and hematologic cancers and has particularly attractive molecular properties for efficient delivery of cytotoxic payloads to tumor cells.
Enrollment began in late June 2018 in PROCLAIM-CX-2029, a Phase 1/2 clinical trial evaluating CX-2029 as monotherapy in patients with solid tumors or lymphomas and is ongoing.
CX-188 (PD-1 Probody Therapeutic) Program

CX-188 is a PD-1-directed Probody therapeutic.
PD-1 is the receptor for the PD-L1 ligand responsible for inhibiting T-cell activation in a variety of cancers and is a clinically- and commercially-validated anti-cancer target.
In October 2018, CytomX filed an Investigational New Drug Application (IND) with the Food and Drug Administration (FDA) on CX-188. The CX-188 IND was cleared by the FDA in November 2018. Due to a recent program and portfolio prioritization, the company has decided to indefinitely postpone the CX-188 clinical trials. The company may elect to initiate clinical trials of CX-188 in the future.
CytomX Technology Acquisition from Agensys, Inc.

In January 2019, CytomX announced the acquisition of drug conjugate linker-toxin and CD3-based bispecific technologies from Agensys, Inc., an affiliate of Astellas Pharma Inc.
CytomX Therapeutics 2019 Research and Development Day

CytomX hosted a Research and Development Day on Tuesday, February 26, 2019. A replay of the webcasted event is available under the "Investors & News" section of www.CytomX.com.

Full Year Financial Results

Cash, cash equivalents and short-term investments totaled $436.1 million as of December 31, 2018, compared to $374.1 million as of December 31, 2017.

Revenue was $59.5 million for the year ended December 31, 2018, compared to $71.6 million for the year ended December 31, 2017. The $12.1 million decrease is largely attributable to the recognition of $14.0 million in milestone revenue in 2017 from AbbVie (net of a $1.0 million license fee paid to SGEN) as a result of completion of certain milestones under the CD71 Agreement, the recognition of a $10 million milestone in 2017 from BMS related to the IND filing for BMS-986249, the recognition of $6.5 million in revenue in 2017 related to the delivery of the ImmunoGen 2017 License to ImmunoGen in connection with the ImmunoGen Research Agreement, a decrease of $4.5 million in the amortization of deferred revenue under the ImmunoGen Research Agreement which concluded on June 30, 2018, and a decrease of $0.5 million in revenues from Pfizer as a result of Pfizer terminating our Research Collaboration, Option and License Agreement in March 2018. These decreases were partially offset by the recognition of $11.7 million of revenue in 2018 related to the milestone payment of $21.0 million from AbbVie (net of the associated $4.0 million sublicense fee to SGEN) for the achievement of the IND filing success criteria under the CD71 Agreement, an increase of $7.9 million in amortization of deferred revenue in 2018 related to the $200.0 million upfront payment received in the second quarter of 2017 as a result of the extension of the BMS collaboration, and an increase of $3.6 million of revenue from Amgen under the Amgen Agreement entered into in September 2017.

Research and development expenses increased by $11.6 million during the year ended December 31, 2018 compared to the corresponding period in 2017. The increase was primarily attributed to an increase in lab services of $10.0 million and $12.3 million in clinical trial expenses related to CX-072, CX-2009 and CX-2029 Phase 1/2 clinical development. There was also an increase of $10.5 million in personnel related expenses; $1.2 million increase in allocation of information technology and facilities related expenses; $0.9 million in lab supplies and $0.7 in consulting expenses. These amounts were largely offset by the recognition, during the third quarter of 2017, of $10.7 million of non-cash in-process research and development expense; $12.1 million of sublicense fees payable to the University of California, Santa Barbara, as a result of both the $200 million upfront payment made by BMS in connection with the expanded collaboration and the Amgen Agreement and a $1.0 million sublicense fee to ImmunoGen upon commencement of enrollment of Phase 1/2 and first patient dosing in the clinical trial for CX-2009 in the second quarter of 2017.

General and administrative expenses increased by $7.9 million during the year ended December 31, 2018 compared to the corresponding period in 2017. This increase was largely attributed to an increase of $5.6 million in personnel related expenses due to increases in headcount, and $2.3 million for various consulting and other services.

Teleconference Scheduled Today at 5:00 p.m. ET
Conference Call/Webcast Information

CytomX management will host a conference call today at 5:00 p.m. ET. Interested parties may access the live audio webcast of the teleconference through the "Investor & News" section of CytomX’s website at View Source or by dialing 1-877-809-6037 (U.S. and Canada) or 1-615-247-0221 (International) and using the passcode 3748238. An archive of the webcast will be available on the CytomX website from February 27, 2019, until March 6, 2019.

On February 27, 2019 Tocagen Inc. (Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy company, reported financial results and business highlights for the fourth quarter and full year ended December 31, 2018 (Press release, Tocagen, FEB 27, 2019, View Source [SID1234533808]).

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"We had a very strong close to the year, accomplishing all of our 2018 business goals. In particular, NRG Oncology’s selection of Toca 511 & Toca FC for a Phase 2/3 trial in newly diagnosed glioblastoma was a major accomplishment for our team and we look forward to initiating this trial in late 2019. Expansion of our late-stage cancer-selective gene therapy program regimen into the front-line indication could pave the way to having a greater impact on more patients in the years ahead," said Marty Duvall, chief executive officer of Tocagen. "Furthermore, having ended the year with approximately $96 million in cash, we have a favorable financial position as we look towards the results in 2019 from our Phase 3 Toca 5 trial in recurrent high grade glioma and build for success going into 2020."

Fourth Quarter 2018 Highlights

NRG Oncology, a member of the National Cancer Institute’s National Clinical Trial Network, announced in November 2018 plans to conduct and sponsor a clinical trial to evaluate Toca 511 & Toca FC for the treatment of patients with newly diagnosed glioblastoma (GBM). The proposed NRG-BN006 Phase 2/3 trial will be the first clinical trial of the Toca 511 & Toca FC regimen in the newly diagnosed GBM setting, and is expected to commence in late 2019. NRG Oncology conducts practice-defining, multi-institutional trials funded primarily by the NCI.

Under Tocagen’s PRIME (PRIority MEdicines) designation for Toca 511 & Toca FC, the European Medicines Agency indicated that the statistical analyses, seamless design and use of overall survival as the primary endpoint in the ongoing Phase 3 Toca 5 clinical trial are appropriate for a potential marketing authorization applications for Toca 511 & Toca FC in Europe.

Tocagen presented clinical and preclinical data at congresses hosted by the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) and Society for Neuro-Oncology (SNO). We identified immunologic biomarkers in our clinical trials that may help predict patient outcomes following treatment with Toca 511 & Toca FC, and preclinical studies demonstrated the additive benefits of combining Toca 511 & Toca FC with chemotherapy.

In December 2018, Tocagen raised $30.0 million of gross proceeds in an underwritten public offering of its common stock.

2019 Milestones

Toca 5 second interim analysis expected in the second quarter of 2019

Toca 5 final analysis planned for the fourth quarter of 2019

Prepare to initiate a rolling biologics license application (BLA) for Toca 511 & Toca FC in recurrent high grade glioma

Build U.S. commercial team for potential launch of Toca 511 & Toca FC

NRG Oncology to initiate NRG-BN006 clinical trial evaluating Toca 511 & Toca FC in newly diagnosed GBM in late 2019

Report updated Toca 6 safety and immune activity data in advanced solid tumors

Fourth Quarter 2018 Financial Results

Research and Development (R&D) Expenses: R&D expenses were $15.6 million for the quarter ended December 31, 2018, compared to $8.3 million for the quarter ended December 31, 2017. The R&D expenses in both periods were primarily driven by costs to support the Toca 5 trial and to support the manufacturing of drug product. The increase in 2018 reflects primarily higher manufacturing spend as compared to the same period in 2017.

General and Administrative (G&A) Expenses: G&A expenses were $3.5 million for the quarter ended December 31, 2018, compared to $2.4 million for the quarter ended December 31, 2017. The increase in G&A expenses was primarily due to higher costs to support increased operations activity.

Net Loss: Net loss was $19.6 million, or $0.96 per common share (basic and diluted), for the quarter ended December 31, 2018, compared to a net loss of $10.8 million, or $0.55 per common share (basic and diluted), for the quarter ended December 31, 2017. The 2018 calculation is based on 20.5 million average common shares outstanding for the fourth quarter of 2018, compared to 19.8 million average common shares outstanding for the fourth quarter of 2017.

2018 Twelve-Month Results

License Revenue: License revenue was $18.0 million for the 12 months ended December 31, 2018, compared to less than $0.1 million for the 12 months ended December 31, 2017. The 2018 revenue was associated with a $16.0 million upfront payment and a $2.0 million development milestone earned upon completion of enrollment in the Toca 5 clinical study, both recognized under Tocagen’s license agreement with ApolloBio.

R&D Expenses: R&D expenses were $51.1 million for the 12 months ended December 31, 2018, compared to $29.1 million for the 12 months ended December 31, 2017. The increase in R&D expenses primarily reflects increased costs in manufacturing and our Toca 5 clinical trial.

G&A Expenses: G&A expenses were $12.8 million for the 12 months ended December 31, 2018, compared to $8.6 million for the 12 months ended December 31, 2017, with the increase primarily driven by higher personnel costs and costs to support increased operations activity.

Net Loss: Net loss was $49.0 million, or $2.44 per common share (basic and diluted), for the 12 months ended December 31, 2018, compared to a net loss of $38.9 million, or $2.66 per common share (basic and diluted), for the 12 months ended December 31, 2017. The 2018 calculation is based on 20.1 million average common shares outstanding for the 12 months ended December 31, 2018, compared to 14.6 million average common shares outstanding for the prior year.

Cash Position and Guidance

Cash, cash equivalents and marketable securities were $96.1 million at December 31, 2018 compared to $88.7 million at December 31, 2017. Total gross cash burn to support operations was $51.3 million for the year ended December 31, 2018. Based on current operating plans, Tocagen estimates the total cash used in 2019 to fund operations and capital expenditures will be approximately $65 million.

About Toca 511 & Toca FC

Tocagen’s lead product candidate is a two-part cancer-selective immunotherapy comprising an investigational biologic, Toca 511 (vocimagene amiretrorepvec), and an investigational small molecule, Toca FC (flucytosine, extended-release). Toca 511 is a retroviral replicating vector (RRV) that selectively infects cancer cells and delivers a gene for the enzyme, cytosine deaminase (CD). Through this targeted delivery, infected cancer cells carry the CD gene and produce CD. Toca FC is an orally administered prodrug, 5-fluorocytosine (5-FC), which is converted into an anti-cancer drug, 5-fluorouracil (5-FU), when it encounters CD. 5-FU kills cancer cells and immune-suppressive myeloid cells resulting in anti-cancer immune activation and subsequent tumor killing.

On February 27, 2019 Nordic Nanovector ASA (OSE: NANO) reported its results for the fourth quarter and full year 2018 (Press release, Nordic Nanovector, FEB 27, 2019, View Source;results-for-the-fourth-quarter-and-full-year-2018-300802989.html [SID1234533702]). A presentation by the company’s senior management team will take place today in Oslo at 08:30 CET, see details below.

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Eduardo Bravo, CEO, commented:

"We believe we have made solid progress during 2018 advancing the key clinical development programmes for Betalutin as a single agent and in combination with rituximab in non-Hodgkin’s lymphoma patients. The latest results from the LYMRIT 37-01 trial, presented at ASH (Free ASH Whitepaper) in December, continue to highlight strong clinical profiles of two dosing regimens that we are now testing in the pivotal PARADIGME trial. Furthermore, the recent financing enables us to expand our preparatory activities for the future commercialisation of our exciting lead asset, pending completion of PARADIGME and successful regulatory review. Our clear priority for the coming year is on recruiting patients into PARADIGME to ensure we can achieve our goal of data read-out in the first half of 2020."

Q4’18 Highlights

• Updated results from Phase 1/2 LYMRIT 37-01 demonstrating that single-administration Betalutin is effective and well-tolerated in relapsed/refractory indolent non-Hodgkin’s lymphoma (R/R iNHL) patients reported at ASH (Free ASH Whitepaper) (December)

• Pivotal Phase 2b PARADIGME trial progressing with 69 (of 80-85) sites in 23 countries open for enrolment, as of 26 February 2019, including the first site in the US

• Promising Innovative Medicine (PIM) designation (October) in the UK granted for the treatment of advanced R/R FL, adding to US Fast Track designation (granted in June)

• First patient dosed in Phase 1b Archer-1 trial of Betalutin in combination with rituximab in second-line (2L) FL patients (November)

• Promising results from an R&D collaboration to develop a CD37-targeted alpha therapy published at ASH (Free ASH Whitepaper)

Events after Q4’18

• Approximately NOK 222 million (USD 26m) (gross) raised in an oversubscribed private placement which provides funds to support manufacturing and other activities in preparation for the commercialisation of Betalutin

• Jan H. Egberts, M.D. elected new Chairman, succeeding Ludvik Sandnes who stepped down from the board of directors

• Dr Mark Wright appointed as Head of Manufacturing to lead production of Betalutin for clinical trials and future commercialisation, and of CD37-targeting candidates emerging from the company’s pipeline

Financial Highlights Q4 and FY’18

(Figures in brackets = same period 2017 unless otherwise stated)

• Revenues for the fourth quarter amounted to NOK 0.0 million (NOK 0.05 million). Revenues for the full year 2018 were NOK 0.0 million (NOK 0.3 million).

• Total operating expenses for the fourth quarter were NOK 96.3 million (NOK 102.0 million). Total operating expenses for the full year 2018 amounted to NOK 340.0 million (NOK 316.8 million).

• Comprehensive loss for the fourth quarter amounted to NOK 87.7 million (loss of NOK 87.6 million). Comprehensive loss for the full year 2017 was NOK 336.8 million (NOK 295.6 million).

• Cash and cash equivalents amounted to NOK 440.1 million at the end of December 2018 (NOK 756.6 million).

Outlook

Nordic Nanovector aspires to become a leader in the field of targeted therapies for haematological cancers by developing, manufacturing and commercialising innovative therapies to address major unmet medical needs and advance cancer care.

Betalutin, the company’s most advanced product candidate, has a highly differentiated, competitive, clinical profile for R/R FL, based on the promising results from the LYMRIT 37-01 Phase 1/2 clinical study. The company’s pivotal Phase 2b PARADIGME trial with a once-only administration of Betalutin in 3L R/R FL is underway with the initial clinical data read-out targeted for 1H 2020 and subsequent filing in 2020 for marketing approval.

Nordic Nanovector intends to maximize the value of Betalutin and other CD37-targeting opportunities across other stages of FL, NHL and other haematological cancer indications.

The company is confident that Betalutin could become an attractive and convenient therapeutic option, which, based on detailed market research, has the potential to be commercially successful.

Current cash resources are expected to be sufficient to reach data read-out from PARADIGME in the first half of 2020.

Presentation and webcast – Q4 and Full Year 2018 results

A presentation by Nordic Nanovector’s senior management team will take place today at 8:30 am CET at:

Thon Hotel Vika Atrium, Munkedamsveien 45, 0250 Oslo

Meeting Room: AKER

The presentation will be recorded as a webcast and will be available at www.nordicnanovector.com in the section: Investors & Media

The results report and the presentation is available at www.nordicnanovector.com in the section: Investors & Media/Reports and Presentation/Interim Reports/2018.

For further information, please contact:

IR enquiries

Malene Brondberg, VP Investor Relations and Corporate Communications

Cell: +44-7561-431-62

Email: [email protected]

Media Enquiries

Mark Swallow/David Dible (Citigate Dewe Rogerson)

Tel: +44-207-638-9571

Email: [email protected]

on February 27, 2019 Horizon Pharma plc (Nasdaq: HZNP) reported its fourth-quarter and full-year 2018 financial results and provided its full-year 2019 net sales and adjusted EBITDA guidance (Press release, Horizon Pharma, FEB 27, 2019, View Source [SID1234533746]).

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"2018 was a year of exceptional progress – in addition to generating total company net sales growth of 14 percent, we executed on our strategic objectives – advancing our pipeline and driving net sales growth of KRYSTEXXA, which increased 65 percent," said Timothy P. Walbert, chairman, president and chief executive officer, Horizon Pharma plc. "We enrolled the Phase 3 trial of our biologic candidate teprotumumab well ahead of schedule and are now expecting top-line data by the end of the first quarter.

"We are building on the momentum we established in 2018 and expect continued strong commercial execution across our operating segments," continued Walbert. "We plan to submit our biologics license application for teprotumumab in mid-2019 if the clinical data is positive and expect to initiate two important clinical trials for KRYSTEXXA, with the MIRROR trial initiating in the second quarter and a new study in kidney transplant patients with uncontrolled gout beginning in the second half of 2019."

Fourth-Quarter and Recent Company Highlights

Accelerated Teprotumumab Phase 3 Top-Line Data Read-Out Timeline: The Company announced in January that it expects top-line data results for its pivotal teprotumumab Phase 3 confirmatory trial, OPTIC (Treatment of Graves’ Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study), by the end of first quarter of 2019. This is accelerated from the initial second quarter of 2019 timeline, and the Company is tracking to a mid-2019 biologics license application (BLA) submission.

Teprotumumab is a fully human monoclonal antibody insulin-like growth factor-1 receptor (IGF-1R) inhibitor in Phase 3 development for the treatment of thyroid eye disease (TED), in which the muscles and fatty tissue behind the eye expand and become inflamed, which can lead to proptosis (eye bulging) and diplopia (double vision) as well as quality-of-life issues.
Phase 2 Teprotumumab Data Presented at American Thyroid Association (ATA)and American Academy of Ophthalmology (AAO) Meetings: Additional data for the pivotal Phase 2 teprotumumab trial presented at ATA and AAO demonstrated durability of the Phase 2 trial 48 weeks following the end of the treatment period (Week 24) and nearly a year off therapy. At Week 24, 71.4 percent (30 of 42) of patients responded with reductions of ≥2mm in proptosis and 61.9 percent of patients (26 of 42) responded with improvement of at least one grade in diplopia, both of which are considered a clinically meaningful change. At Week 72, 48 weeks following the study completion and nearly a year off therapy, 53.3 percent of the Week 24 proptosis responders maintained the reductions and 69.2 percent of patients with diplopia improvement maintained the benefit. These results demonstrate that teprotumumab has the potential to be the first and only disease-modifying therapy for thyroid eye disease.
New KRYSTEXXA Study in Kidney Transplant Patients with Uncontrolled Gout: The Company is announcing today that it plans to initiate a clinical trial in the second half of 2019 evaluating the effect of KRYSTEXXA, the Company’s medicine for uncontrolled gout, on serum uric acid levels in kidney transplant patients with uncontrolled gout (uncontrolled gout is chronic gout that is refractory to conventional therapies). Kidney transplant patients have more than a tenfold increase in the prevalence of gout when compared to the general population, and literature suggests that high serum uric acid levels are associated with organ rejection. Managing uncontrolled gout is one of the most common and significant unmet needs of kidney transplant patients.
New KRYSTEXXA Immunomodulation Data Presented at American College of Rheumatology/ Association of Rheumatology Health Professionals (ACR) Meeting: At the October 2018 ACR meeting, external investigators shared results from a case series of nine sequential patients with uncontrolled gout, evaluating the administration of KRYSTEXXA with the immunomodulator methotrexate to improve the durability of KRYSTEXXA response. The study stated that of the nine patients followed out to five months, all nine were responders as defined by >80 percent of serum uric acid levels being maintained at goal <6.0 mg/dL during the observation period.
Expanded Indication for RAVICTI: The Company received U.S. Food and Drug Administration (FDA) approval in December to expand the age range for chronic management of urea cycle disorders to birth and older from the previous age range of two months of age and older.
Recent Business Development Initiatives: On Dec. 28, 2018, the Company sold the rights to RAVICTI and AMMONAPS outside of North America and Japan to Medical Need Europe AB for $35 million. In addition, effective Jan. 1, 2019, the RAYOS and LODOTRA license and supply agreements were amended, including the transfer of LODOTRA to Vectura Group plc, the current third-party supplier. Beginning in 2019, the Company will no longer recognize revenue from RAVICTI and AMMONAPS sales outside of North America and Japan, or from sales of LODOTRA. AMMONAPS is known as BUPHENYL and LODOTRA is known as RAYOS in the United States.
Research and Development Programs

Orphan Candidate and Program:

Teprotumumab: The pivotal Phase 3 confirmatory study, OPTIC, is evaluating teprotumumab for the treatment of TED, which has no FDA-approved treatments. OPTIC completed enrollment September of 2018, ahead of the year-end target, and top-line results are expected by the end of first-quarter 2019. OPTIC-X, a 48-week extension study in which participants may receive up to eight additional infusions of teprotumumab, continues to enroll patients. The objective of OPTIC-X is to evaluate the potential for retreatment as well as longer duration of treatment with teprotumumab.
Rheumatology Pipeline Candidates and Programs:

KRYSTEXXA Study in Kidney Transplant Patients: The Company plans to initiate a clinical trial in the second half of 2019 evaluating the effect of KRYSTEXXA on serum uric acid levels in kidney transplant patients with uncontrolled gout. Kidney transplant patients have more than a tenfold increase in the prevalence of gout when compared to the general population, and literature suggests that high serum uric acid levels are associated with organ rejection. Managing uncontrolled gout is one of the most common and significant unmet needs of kidney transplant patients.
KRYSTEXXA Immunomodulation Study: The Company is evaluating the use of methotrexate to enhance the response rate to KRYSTEXXA through its MIRROR (Methotrexate to Increase Response Rates in Patients with UncontrolledGOut Receiving KRYSTEXXA) open-label study. Methotrexate, the immunomodulator most commonly used by rheumatologists, has been shown to reduce anti-drug antibodies when combined with other biologics. The Company is adapting MIRROR’s trial design to support the potential for registration, with enrollment expected to begin in the second quarter of 2019.
Next-generation Biologic Programs for Uncontrolled Gout: The Company is pursuing two development programs for next-generation biologics for uncontrolled gout, HZN-003 and PASylated uricase technology, to support and sustain the Company’s market leadership in uncontrolled gout. The programs are exploring the use of optimized uricase technology coupled with optimized PEGylation or PASylation technology, to improve the molecule’s half-life, with the potential for subcutaneous dosing.
Augmented Rheumatology Pipeline with HemoShear Collaboration: The Company is collaborating with HemoShear Therapeutics, LLC, a privately held biotechnology company, to discover and develop novel therapeutics for gout.
Fourth-Quarter Financial Results

Note:For additional detail and reconciliation of non-GAAP financial measures to the most directly comparable GAAP financial measures, please refer to the tables at the end of this release.

Net Sales: Fourth-quarter 2018 net sales were $355.5 million, an increase of 30 percent, driven by continued strong growth of the Company’s orphan and rheumatology segment.
Gross Profit: Under U.S. GAAP, the fourth-quarter 2018 gross profit ratio was 69.2 percent compared to 47.8 percent in the fourth quarter of 2017. The non-GAAP gross profit ratio in the fourth quarter of 2018 was 89.1 percent compared to 89.3 percent in the fourth quarter of 2017.
Operating Expenses: Research and development (R&D) expenses were 5.5 percent of net sales and selling, general and administrative (SG&A) expenses were 49.1 percent of net sales. Non-GAAP R&D expenses were 5.3 percent of net sales and non-GAAP SG&A expenses were 41.4 percent of net sales.
Income Tax Rate: In the fourth quarter of 2018, the income tax benefit rate on a GAAP basis was 114.9 percent and the income tax expense rate on a non-GAAP basis was 8.2 percent.
Net Income: On a GAAP basis in the fourth quarter of 2018, net income was $87.6 million. Fourth-quarter 2018 non-GAAP net income was $116.8 million.
Adjusted EBITDA: Fourth-quarter 2018 adjusted EBITDA was $151.1 million.
Earnings (Loss) per Share: On a GAAP basis in the fourth quarter of 2018, diluted earnings per share were $0.50 versus a diluted loss per share of $0.23 in the fourth quarter of 2017. Non-GAAP diluted earnings per share in the fourth quarter of 2018 and 2017 were $0.67 and $0.29, respectively. Weighted average shares outstanding used for calculating GAAP and non-GAAP diluted earnings per share in the fourth quarter of 2018 were 174.2 million.
Fourth-Quarter Segment Results

Management uses net sales and segment operating income to evaluate the performance of the Company’s two segments. While segment operating income contains certain adjustments to the directly comparable GAAP figures in the Company’s consolidated financial results, it is considered to be prepared in accordance with GAAP for purposes of presenting the Company’s segment operating results.

(1)On Jun. 23, 2017, Horizon Pharma completed the divestiture of a European subsidiary that owned the marketing rights to PROCYSBI and QUINSAIR in Europe, the Middle East and Africa (EMEA) to Chiesi Farmaceutici S.p.A. Horizon Pharma retains marketing rights for the two medicines in the United States, Canada, Latin America and Asia. Horizon Pharma’s 2017 net sales of PROCYSBI and QUINSAIR in EMEA were $9.5 million.

Fourth-quarter 2018 net sales of the orphan and rheumatology segment were $237.6 million, an increase of 33 percent over the prior year’s quarter, driven by continued strong KRYSTEXXA growth as well as growth of RAVICTI, PROCYSBI and RAYOS. Fourth-quarter 2018 orphan and rheumatology segment operating income was $84.8 million, an increase of 39 percent.
For the full-year 2018, KRYSTEXXA net sales of $258.9 million represented a 65 percent year-over-year increase, in line with the Company’s expectation.
On Dec. 28, 2018, the Company sold the rights to RAVICTI and AMMONAPS (AMMONAPS is known as BUPHENYL and LODOTRA is known as RAYOS in the United States) outside of North America and Japan to Medical Need Europe AB for $35.0 million. In addition, effective Jan. 1, 2019, the RAYOS and LODOTRA license and supply agreements were amended, including the transfer of LODOTRA to Vectura Group plc, the current third-party supplier. Beginning in 2019, the Company will no longer recognize revenue from RAVICTI and AMMONAPS sales outside of North America and Japan, or from sales of LODOTRA.

Fourth-quarter 2018 net sales of the primary care segment were $117.9 million and operating income was $66.2 million.
Cash Flow Statement and Balance Sheet Highlights

On a GAAP basis in the fourth quarter of 2018, operating cash flow was $108.7 million. Non-GAAP operating cash flow was $115.1 million.
The Company had cash and cash equivalents of $958.7 million as of Dec. 31, 2018.
As of Dec. 31, 2018, the total principal amount of debt outstanding was $1.993 billion, which consisted of $818 million in senior secured term loans due 2024; $300 million senior notes due 2024; $475 million senior notes due 2023 and $400 million exchangeable senior notes due 2022. As of Dec. 31, 2018, net debt was $1.034 billion and our net-debt-to-last-12-months adjusted EBITDA leverage ratio was 2.3 times.
2019 Guidance

The Company expects full‐year 2019 net sales to range between $1.23 billion and $1.25 billion and full‐year 2019 adjusted EBITDA is expected to range between $440 million and $455 million, reflecting investment in preparation for the potential U.S. launch of teprotumumab and continued R&D pipeline programs to drive long-term growth.

Webcast

At 8 a.m. EST / 1 p.m. IST today, the Company will host a live webcast to review its financial and operating results and provide a general business update. The live webcast and a replay may be accessed at View Source Please connect to the Company’s website at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast. A replay of the webcast will be available approximately two hours after the live webcast.