On February 25, 2021 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company developing drugs to treat cancers with the greatest medical need for new treatment options, including KRAS-mutated colorectal cancer, pancreatic cancer, castrate-resistant prostate cancer and leukemias, reported recent company highlights and financial results for the fourth quarter and full year ended December 31, 2020 (Press release, Cardiff Oncology, FEB 25, 2021, View Source [SID1234575717]).

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"Over the last several months we achieved key clinical milestones, which provided the momentum for our successful raise of over $100 million. Together, these events have enabled us to accelerate the execution of our clinical programs and expand our pipeline to other relevant cancer indications," said Dr. Mark Erlander, chief executive officer of Cardiff Oncology. "Data from our lead KRAS-mutated metastatic colorectal cancer (mCRC) program show promising and durable efficacy, highlighting the potential of onvansertib in combination with standard-of-care FOLFIRI (irinotecan and 5-FU)/bevacizumab to address the need for a new second-line treatment option. Importantly, we completed enrollment in the Phase 1b portion of this trial in December of 2020 and initiated patient accrual in the Phase 2 segment in January of this year. Based on the mCRC trial results, we are leveraging the known synergy of onvansertib with irinotecan and 5-FU by evaluating this combination (nanoliposoamal irinotecan and 5-FU) in pancreatic ductal adenocarcinoma (PDAC). Approximately 95% of PDAC patients have a KRAS mutation and current second-line treatment for this indication conveys only a 7.7% response rate and 6-month median overall survival benefit. We plan to initiate a Phase 2 trial in this indication in the first half of the year following the receipt of our "study may proceed" notification from the FDA last month. Our goal is to further demonstrate the broad applicability of onvansertib across KRAS-mutated cancers and to address an indication with a significant unmet need for new treatment options."

Dr. Erlander continued, "Onvansertib’s broad applicability extends beyond targeting KRAS-mutated cancers, as shown by the exciting progress of our metastatic castrate-resistant prostate cancer (mCRPC) trial. The addition of onvansertib to daily abiraterone treatment in patients showing initial resistance to abiraterone has resulted in durable disease control. Notably, the most recent data presented at ASCO (Free ASCO Whitepaper)-GU showed a significant increase in disease control rate in patients receiving onvansertib for more days within a treatment cycle. Looking ahead, the progress we’ve made across our clinical programs leaves us poised to achieve a steady cadence of catalysts throughout 2021 and beyond as we continue to advance onvansertib’s development."

Program highlights for the quarter ended December 31, 2020 include:

Corporate Milestones:

Raised gross proceeds of approximately $100 million in an offering of common stock

Cardiff Oncology substantially strengthened its balance sheet in the fourth quarter, closing an underwritten public offering of 6,500,000 shares of its common stock at a public offering price of $13.50 per share, before deducting underwriter discounts and commissions and estimated offering expenses. The underwriters also exercised an option to purchase an additional 975,000 shares at the public offering price (less the underwriting discounts and commissions). The Company intends to use the net proceeds from this offering for clinical development of onvansertib, working capital and for other general corporate purposes.

Appointed Dr. Rodney Markin as Chairman of the Board

Prior to being appointed Chairman, Dr. Markin previously served as a Director on Cardiff’s Board from February 2014 to December 2020. He has extensive medical expertise and experience in institutional healthcare, and is currently the Vice President for Network Development, Nebraska Medicine and Associate Vice Chancellor for Business and Executive Director of the UNeTech Institute at the University of Nebraska Medical Center. In addition to currently holding several other distinguished positions in academia, Dr. Markin also has served on the boards of Perceptimed Inc. since 2014, MikroScan Technologies Inc. since 2015, Afaxys Inc. since 2017 and Paradigm Diagnostics Inc. since 2018.

Metastatic Castrate-Resistant Prostate Cancer (mCRPC) Program:

Identified a biomarker associated with onvansertib-abiraterone synergy that is enriched in mCRPC patients with the clinically defined basal molecular tumor subtype

Collaborative studies with the Massachusetts Institute of Technology and Decipher Biosciences identified a gene signature (biomarker) related to cell division pathways that can be used to predict which cancer cells will show a synergistic anti-tumor response to treatment with onvansertib in combination with abiraterone. This gene signature is correlated with the clinically defined basal molecular subtype of mCRPC, suggesting that patients with this tumor subtype may be more likely to respond to onvansertib-abiraterone combination therapy. These studies were featured in an electronic poster at the 27th Annual Prostate Cancer Foundation Scientific Retreat.

Acute Myeloid Leukemia (AML) Program:

Presented data at ASH (Free ASH Whitepaper) demonstrating the safety and anti-leukemic activity of onvansertib in relapsed/refractory AML

Updated data from a Phase 1b/2 clinical trial evaluating onvansertib in combination with decitabine in relapsed/refractory AML patients were featured in a virtual oral poster presentation at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. These data demonstrated the safety, tolerability and anti-leukemic activity of the onvansertib-decitabine combination and showed an over-representation of splicing factor mutations in patients achieving a complete response. Additional highlights from the presentation included:

9 of 45 (20%) evaluated patients achieved a complete remission with or without hematologic count recovery (CR/CRi – 5 in Phase 1b and 4 in Phase 2)
55% of responders had a mutation in a splicing factor
2 patients proceeded to transplant following CR and 3 patients had ongoing responses as of the ASH (Free ASH Whitepaper) data cutoff
4 patients have achieved a durable response (≥9 months) – as of data cut-off date
Decreases in mutant circulating tumor DNA (ctDNA) within the first treatment cycle appeared to be highly correlated with clinical response; 7 of 7 (100%) patients with CR/CRi showed a decrease in mutant ctDNA after one cycle of treatment, while only 2 of 15 (13%) non-responders showed a similar decrease
Data demonstrated that onvansertib in combination with decitabine is a safe and well-tolerated treatment regimen
Highlights for the period subsequent to the quarter end include:

KRAS-mutated Metastatic Colorectal Cancer (mCRC) Program:

Announced updated data from its Phase 1b/2 trial evaluating onvansertib plus FOLFIRI (irinotecan and 5-FU)/bevacizumab in second line KRAS-mutated mCRC patients and initial findings from its Expanded Access Program (EAP)

In conjunction with the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI), Cardiff Oncology announced updated Phase 1b data demonstrating the clinical benefit of onvansertib in KRAS-mutated mCRC, as well as initial findings from its EAP. Data highlights from the Phase 1b trial, as of January 6, 2021, include:

12 of 14 (86%) evaluable patients achieved a clinical benefit (SD – stable disease plus PR – partial response)
5 of 14 (36%) evaluable patients achieved a PR; 4 patients had a confirmed PR; 1 patient went on to have curative surgery; 1 patient with a non-confirmed PR went off study following PR due to a treatment-unrelated AE
3 patients with SD remain on treatment, including 2 who have yet to have their 16-week (second) scan; time to achieving a PR ranges from 2 to 6 months in trial participants on treatment
Clinical responses were observed across different KRAS variants, including the 3 most common in colorectal cancer
Patients achieving a PR or SD showed the greatest decrease in plasma mutant KRAS after one cycle of therapy
The combination of onvansertib and FOLFIRI/bevacizumab was well tolerated
Enrollment of patients in the Phase 1b segment of the trial is complete and the recommended Phase 2 dose of onvansertib has been confirmed at 15 mg/m2. The Phase 2 segment of the trial is open to full enrollment of approximately 26 patients across 6 trial sites: USC Norris Comprehensive Cancer Center, Mayo Clinic Cancer Centers (Arizona, Rochester, Jacksonville), Kansas University Medical Center and CARTI Cancer Center.

In the EAP, Cardiff Oncology announced that 6 of the initial 9 patients treated showed tumor shrinkage and remained on treatment with durable responses lasting an average of 6 months. Notably, 5 different KRAS mutation subtypes were represented amongst these patients and most patients had received prior treatment with FOLFIRI and progressed before enrolling in the EAP.

Metastatic Castrate-Resistant Prostate Cancer (mCRPC) Program:

Announced updated Phase 2 data showing a two-fold increase in efficacy with an optimized onvansertib dosing schedule

Updated data from a Phase 2 trial evaluating the all-oral combination of onvansertib, abiraterone and prednisone in patients showing initial abiraterone resistance were featured in a virtual oral poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO-GU). These data showed that increasing the number of days of treatment with onvansertib from 5 to 14 in a 21-day cycle was associated with a greater than two-fold increase (29% to 63%) in disease control rate (DCR) at 12 weeks, the trial’s primary efficacy endpoint. Across all cohorts, the DCR at 12 weeks is 35% (13/37), indicating the trial is on track to meet the stated criteria for success on its primary efficacy endpoint (30% DCR at 12 weeks). Additional highlights from the presentation included:

The optimized dosing schedule of cohort C shows a greater than two-fold improvement in disease control rate compared to cohorts A and B
o 63% (5/8) of cohort C patients achieved the primary efficacy endpoint compared to 29% (5/17) and 25% (3/12) of cohort A and B patients, respectively
75% (6/8) of evaluable patients in cohort C had radiographic stable disease (SD) at 12 weeks, compared to 53% (9/17) in cohort A, 42% (5/12) in cohort B and 54% (20/37) across all cohorts
All cohort C patients achieving the primary efficacy endpoint remain on treatment
Data show that the combination of onvansertib and abiraterone is well tolerated across the three different dosing schedules of cohorts A-C:
Cohort A: 24 mg/m2 onvansertib on Days 1-5 of 21-day cycles, plus abiraterone and prednisone beginning on Day 1 and continuing uninterrupted throughout each cycle
Cohort B: 18 mg/m2 onvansertib on Days 1-5 of 14-day cycles, plus abiraterone and prednisone beginning on Day 1 and continuing uninterrupted throughout each cycle
Cohort C: 12 mg/m2 onvansertib on Days 1-14 of 21-day cycles, plus abiraterone and prednisone beginning on Day 1 and continuing uninterrupted throughout each cycle
Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) Program:

Received "Study May Proceed" letter from the U.S. Food and Drug Administration (FDA) to begin a Phase 2 trial of onvansertib in metastatic PDAC

The Phase 2 clinical trial of onvansertib in metastatic PDAC is designed to assess the safety and preliminary efficacy of onvansertib in combination with nanoliposomal irinotecan (Onyvide), leucovorin and fluorouracil (5-FU) as a second-line treatment in patients with metastatic PDAC who have failed first-line gemcitabine-based therapy. Onvansertib’s potential in PDAC, where ~95% of patients have a KRAS mutation, is supported by the promising clinical data seen in the KRAS-mutated mCRC trial evaluating onvansertib in combination with irinotecan and 5-FU (FOLFIRI). Initiation of the Phase 2 trial is expected in the first half of 2021.

Fourth Quarter Financial Results:

As of December 31, 2020, Cardiff Oncology had approximately $131 million in cash and cash equivalents.

Net cash used in operating activities in the fourth quarter of 2020 was $5.1 million, an increase of $1.8 million from $3.3 million for the same period in 2019. The increase is attributed mainly to outside services and professional fees, facilities and other and changes in operating assets and liabilities.

Research and development expenses increased by approximately $0.3 million to $3.2 million for the three months ended December 31, 2020, from $2.9 million for the same period in 2019. The increase in research and development expenses was primarily due to the increased outside service costs and clinical studies for advancing the development of our drug candidate, onvansertib. We expect increases in research and development costs to continue as we advance the onvansertib clinical development programs.

Selling, general and administrative expenses increased by approximately $1.9 million to $3.4 million for the three months ended December 31, 2020, from $1.5 million for the same period in 2019. The increase is primarily due to a one time increase in stock compensation expense, and outside services and professional fees.

On February 25, 2021 Aurinia Pharmaceuticals Inc. (NASDAQ: AUPH / TSX: AUP) ("Aurinia" or the "Company") reported its financial results for the fourth quarter and year ended December 31, 2020 (Press release, Aurinia Pharmaceuticals, FEB 25, 2021, View Source [SID1234575738]). Amounts, unless specified otherwise, are expressed in U.S. dollars.

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"Over the past year, Aurinia matured into a fully-integrated biopharmaceutical company with capabilities spanning R&D, clinical, regulatory, CMC, and commercial. The recent FDA approval and immediate launch of LUPKYNIS underscores the exemplary performance and expertise of the Aurinia team," commented Peter Greenleaf, President and Chief Executive Officer of Aurinia. "During 2020, we made calculated investments following the positive AURORA clinical trial results by building out a world-class commercial team, signing a major ex-US partnership with Otsuka, and ensuring we can meet future market demand for LUPKYNIS by securing our supply chain by expanding our manufacturing agreement with Lonza. After just 30 days, we are pleased by the uptake of LUPKYNIS by the healthcare community and believe we are on track to meet our internal expectations."

"Launching LUPKYNIS within hours of our approval allows us to focus on getting LN patients who need intervention onto therapy as soon as possible," said Max Colao, Chief Commercial Officer at Aurinia. "We look forward to translating years of innovation and development work, and our early preparation and planning for launch, into commercial success for LUPKYNIS."

Recent Highlights

FDA Approval and Commercial Launch of LUPKYNISTM

On January 22, 2021, the FDA approved LUPKYNIS in combination with a background immunosuppressive therapy regimen to treat adult patients with active LN. LUPKYNIS was approved by the FDA under Priority Review and was previously granted Fast Track designation from the Agency in 2016.

Collaboration and Licensing Agreement with Otsuka Pharmaceutical Co., Ltd.

On December 17, 2020, Aurinia announced it had entered into a collaboration and licensing agreement with Otsuka Pharmaceutical Co., Ltd., for the development and commercialization of oral LUPKYNIS for the treatment of LN in the European Union (EU), Japan, as well as the United Kingdom, Russia, Switzerland, Norway, Belarus, Iceland, Liechtenstein, and Ukraine.

As part of the agreement, Aurinia received an upfront cash payment of $50 million for the license agreement, and has the potential to receive up to an additional $50 million in regulatory milestones. Aurinia will receive tiered royalties on future sales ranging from 10 to 20 percent on net sales upon commercialization, along with additional milestone payments based on the attainment of certain annual sales by Otsuka. In addition, Aurinia will provide LUPKYNIS to Otsuka via a supply agreement under a cost plus arrangement.

Agreement for Dedicated LUPKYNIS Manufacturing Capacity

On December 15, 2020, Aurinia entered into a collaborative agreement with Lonza Ltd. (Lonza) to build a dedicated manufacturing capacity within Lonza’s existing small molecule facility in Visp, Switzerland. The dedicated facility (also referred to as "monoplant") will be equipped with state-of-the-art manufacturing equipment to provide cost and production efficiency for the manufacture of LUPKYNIS, while expanding existing capacity and providing supply security to meet future commercial demand. Upon completion of the monoplant, Aurinia will have the right to maintain exclusive use of the monoplant by paying a quarterly fixed facility fee. The first capital expenditure payment was made in February 2021.

Financial Liquidity at December 31, 2020

As of December 31, 2020, Aurinia had cash, cash equivalents and investments of $423 million compared to $306 million at December 31, 2019. Net cash used in operating activities was $69.9 million for the year ended December 31, 2020 compared to $63.6 million for the year ended December 31, 2019.

The Company believes that it has sufficient financial resources to fund its current plans, which include funding commercial launch activities, manufacturing and packaging of commercial drug supply, conducting our planned R&D programs, and operating activities into at least 2023.

Financial Results for the Year Ended December 31, 2020

For the year ended December 31, 2020, Aurinia recorded a consolidated net loss of $102.7 million or $0.87 per common share.

Revenues were $50.1 million and $0.3 million for the years ended December 31, 2020 and 2019, respectively. The increase of $49.8 million in 2020 was due to the upfront license payment received from Otsuka of $50 million, recorded as licensing revenue in the fourth quarter of 2020.

Research and development (R&D) expenses decreased to $50.3 million for the year ended December 31, 2020 compared to $52.9 million for the year ended December 31, 2019. The primary driver for the decrease of $2.5 million in R&D spend in 2020 was a decrease in drug manufacturing and supply costs, lower Contract Research Organization (CRO) expenses and other third party clinical trial expenses, partially offset by an increase in regulatory related costs as Aurinia prepared for FDA approval.

Corporate, administration and business development expenses increased to $96 million for the year ended December 31, 2020 compared to $22.3 million for the year ended December 31, 2019. The primary driver for the increase of $73.6 million was the build out of commercial infrastructure in advance of approval, which included an increase in salaries and employee benefits, share based compensation expense and professional fees incurred during the year.

Financial Results for the Fourth Quarter Ended December 31, 2020

For the three months ended December 31, 2020, Aurinia recorded a consolidated net loss of $8.1 million or $0.05 per common share.

Revenues were $50 million and $0.03 million for the three months ended December 31, 2020 and 2019, respectively. The increase of $50 million in 2020 was due to the upfront payment from Otsuka of $50 million recorded as licensing revenue.

R&D expenses decreased to $13.2 million for the three months ended December 31, 2020 compared to $13.3 million for the three months ended December 31, 2019. The primary drivers for the slight decrease in R&D spend in 2020 was a decrease in drug manufacturing and supply costs, lower CRO expenses and other third party clinical trial expenses, partially offset by an increase in regulatory related costs as Aurinia prepared for FDA approval.

Corporate, administration and business development expenses increased to $38.8 million for the three months ended December 31, 2020 compared to $7.3 million for the three months ended December 31, 2019. The primary driver for the increase of $31.5 million in 2020 was the build out of commercial infrastructure in advance of approval, which included an increase in salaries and employee benefits, share based compensation expense and professional fees incurred during the quarter.

This press release is intended to be read in conjunction with the Company’s audited financial statements and the Management’s Discussion and Analysis for the year ended December 31, 2020 in the Company’s Annual Report on Form 10-K, which is accessible on Aurinia’s website at www.auriniapharma.com, on SEDAR at www.sedar.com or on EDGAR at www.sec.gov/edgar.

Aurinia will host a conference call and webcast to discuss the fourth quarter and year ended December 31, 2020 financial results today, Wednesday, February 24, 2020 at 4:30 p.m. ET. This event can be accessed on the investor section of the Aurinia website at www.auriniapharma.com.

About Lupus Nephritis

LN is a serious progression of systemic lupus erythematosus (SLE), a chronic and complex autoimmune disease. About 200,000-300,000 people live with SLE in the U.S. and approximately one out of three of these individuals have already developed LN at the time of SLE diagnosis. If poorly controlled, LN can lead to permanent and irreversible tissue damage within the kidney, resulting in kidney failure. Black and Asian individuals with SLE are four times more likely to develop LN and individuals with Hispanic ancestry are approximately twice as likely to develop the disease when compared with Caucasian individuals. Black and Hispanic individuals with SLE also tend to develop LN earlier and have poorer outcomes when compared to Caucasian individuals.

On February 25, 2021 Theratechnologies Inc. (Theratechnologies) (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported that Paul Levesque, President and Chief Executive Officer, will present at the H.C. Wainwright Global Life Sciences Conference being held virtually March 9 – 10, 2021 (Press release, Theratechnologies, FEB 25, 2021, View Source [SID1234575636]).

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The presentation will be available on demand beginning Tuesday, March 9, 2021 at 7:00 a.m. ET on the ‘News’ section of the Company’s website or via the virtual conference link, and will be archived for 90 days.

On February 25, 2021 BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) (BioMarin or the Company) reported financial results for the fourth quarter and full year ended December 31, 2020 (Press release, BioMarin, FEB 25, 2021, View Source [SID1234575664]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Net Product Revenues for the fourth quarter of 2020 were essentially flat as compared to the fourth quarter of 2019. The change in Net Product Revenues was primarily attributed to the following:

Kuvan Net Product Revenues decreased by $33.6 million, primarily due to the U.S. loss of market exclusivity in October 2020 resulting from generic competition; and
Aldurazyme Net Product Revenues decreased by $22.7 million due to timing of product fulfillment to Genzyme. Aldurazyme is marketed by Genzyme and BioMarin Aldurazyme revenues are driven by the timing of when the product is released and control is transferred to Genzyme. Revenues for the fourth quarter of 2020 were comparatively lower than 2019 due to such timing. Based on data provided to us by Genzyme, patients receiving commercial Aldurazyme increased by 10% during 2020; partially offset by
Naglazyme and Vimizim Net Product Revenues increased by an aggregate of $35.1 million primarily due to timing of sales in the Middle East and Latin America;
Palynziq Net Product Revenues increased by $17.9 million driven by a combination of revenue from U.S. patients achieving maintenance dosing and new patients initiating therapy; and
Brineura Net Product Revenues increased by $9.8 million driven by growth in the number of patients in all regions.
The increase in GAAP Net Income for the fourth quarter of 2020, compared to the same period in 2019 was primarily due to the following:

decreased research and development (R&D) expense of $16.1 million primarily due to lower clinical activity spend for valoctocogene roxaparvovec gene therapy programs and decreased tralesinidase alfa costs as the program was licensed to a third-party in 2019; and
an increase in the benefit from income taxes of $37.5 million primarily due to the change in the jurisdictional mix of earnings and the related tax impact from the completion of an intra-entity transfer of certain intellectual property rights to an Irish subsidiary where the Company’s ex-US regional headquarters are located during the third quarter of 2020; partially offset by
an increase in Cost of Sales of $30.2 million primarily due to inventory reserves and higher sales volumes of products with lower margins.
Non-GAAP Income for the fourth quarter of 2020 decreased to $39.5 million, compared to Non-GAAP Income of $46.4 million for the same period in 2019. The decrease in Non-GAAP Income for the quarter, compared to the same period in 2019, was primarily attributed to lower gross profits and higher SG&A expenses, partially offset by lower R&D expenses.

As of December 31, 2020, BioMarin had cash, cash equivalents and investments totaling $1.35 billion, which includes net proceeds of $535.8 million from the Company’s May 2020 convertible debt offering, as compared to $1.17 billion as of December 31, 2019. On October 15, 2020, the Company’s 1.50% senior subordinate convertible notes matured and were settled in cash for approximately $375.0 million.

Commenting on full-year 2020 results, Jean-Jacques Bienaimé, Chairman and Chief Executive Officer of BioMarin, said, "Despite the impact in 2020 from the COVID-19 pandemic and a delay in the potential approval of valoctocogene roxaparvovec for severe hemophilia A, demand for our current product portfolio continued to drive steady revenue growth and expansion of our pipeline. Excluding contributions from Kuvan, for which a generic became available during 2020, total revenues grew 13% in 2020, and generated $85 million of positive operating cash flows for the full year, underscoring the essential nature of our medicines."

Mr. Bienaimé continued, "The most recent Phase 3 data updates from our latest-stage development programs in achondroplasia and severe hemophilia A demonstrated significant efficacy. In the largest gene therapy trial ever conducted for the treatment of severe hemophilia A, we were pleased that valoctocogene roxaparvovec was the first in hemophilia A to demonstrate statistically significant evidence of annualized bleed rate superiority over standard of care recombinant FVIII. Based on these results, we are very encouraged that one infusion of valoctocogene roxaparvovec gene therapy may potentially address the high treatment burden for people with severe hemophilia A. We are targeting submission of the one-year Phase 3 results to the European Medicines Agency in the second quarter of 2021 and planning to dialog with the FDA to align on steps to obtain approval in the United States."

"Also in 2021, we look forward to the potential approval of vosoritide, which would be the first pharmacological treatment to address the underlying cause of achondroplasia, the most common form of dwarfism. We announced in the fourth quarter of 2020 that vosoritide demonstrated sustained growth effects for over two years in children with achondroplasia participating in our Phase 3 extension study. In addition to the large, Phase 3 program currently in the extension phase, we have built a multi-pronged dossier of additional studies to support our understanding of the unmet medical need for children with achondroplasia and the effects of vosoritide in this condition. In addition to the highly statistically significant placebo-controlled Phase 3 results, the program includes the long-term clinical results in 5 to 18 year-olds from our Phase 2 study, natural history data, and the ongoing study of newborns through 5 years. Many families are keen to seek early treatment for their children so we are hopeful that, if approved, vosoritide will become available later in 2021 upon potential approvals."

Key Program Highlights

Valoctocogene roxaparvovec gene therapy for severe hemophilia A: On January 10, 2021, the Company announced positive top-line, one-year data results from its ongoing global Phase 3 GENEr8-1 study of valoctocogene roxaparvovec, an investigational gene therapy for the treatment of adults with severe hemophilia A. Data from the study in the pre-specified primary analysis for Annualized Bleeding Rate (ABR) showed that a single dose of valoctocogene roxaparvovec significantly reduced ABR by 84% compared with prior treatment with prophylactic FVIII infusions. These results were from a pre-specified group of participants in a non-interventional prospective baseline observational study (rollover population; N=112) with a median follow-up of 60.1 weeks after dosing with valoctocogene roxaparvovec. 80% of the rollover participants were bleed-free starting at week five after treatment.
Additionally, at the end of the first year post-infusion with valoctocogene roxaparvovec, participants in the modified intent-to-treat (mITT) population (N=132) had a mean endogenous Factor VIII expression level of 42.9 (SD 45.5, median 23.9) IU/dL, as measured by the chromogenic substrate (CS) assay, supporting the marked clinical benefits observed with abrogation of bleeding episodes and Factor VIII infusion treatment rate. Factor VIII expression declined at a slower rate compared to the Phase 1/2 study, and remained in a range to provide hemostatic efficacy. In a subset of the mITT population that had been dosed at least two years prior to the data cut date (N=17), Factor VIII expression declined from a mean of 42.2 (SD 50.9, median 23.9) IU/dL at the end of year one to a mean of 24.4 (SD 29.2, median 14.7) IU/dL at the end of year two with continued hemostatic efficacy demonstrated by a mean ABR of 0.9 (median 0.0) bleeding episodes per year.

Valoctocogene roxaparvovec also significantly reduced the mean annualized Factor VIII usage in the rollover population by 99% from 135.9 (median 128.6) to 2.0 (median 0.0) infusions per year (p-value <0.0001).

In the U.S., the FDA recommended that the Company complete the Phase 3 study and submit two-year follow-up safety and efficacy data on all study participants. The Company plans to meet with FDA to review the two-year data request and share the Phase 3 GENEr8-1 results announced on January 10, 2021. BioMarin is targeting submission of the Marketing Authorization Application (MAA) with these results to the EMA in the second quarter of 2021 pending confirmation in presubmission meetings.

Vosoritide for children with achondroplasia: On December 21, 2020 the Company announced that children in the open-label long-term extension of the Phase 3 study of vosoritide, an investigational, once daily injection analog of C-type Natriuretic Peptide (CNP), maintained an increase in Annual Growth Velocity (AGV) through the second year of continuous treatment. An analysis, comparing all children randomized and treated with vosoritide for two years (n=52) to all children from the run-in study who were randomized to receive placebo with an untreated observation period of two years (n=38), showed improvement in one-year height change in the treated group relative to the untreated group that was similar in the second year of treatment, 1.79 cm, as in the first year of treatment, 1.73 cm. The cumulative height gain over the 2-year treatment period was 3.52 cm more than the untreated children.
In 2020, marketing applications for vosoritide were validated and accepted by EMA and FDA, respectively. The CHMP opinion is expected in Europe in June of 2021. The U.S. New Drug Application (NDA) for vosoritide is under review by the FDA with a Prescription Drug User Fee Act (PDUFA) target action date of August 20, 2021.

In January 2021, the Company received notice from FDA that the NDA for vosoritide had been granted Priority Review Designation. Under this designation, the vosoritide NDA may qualify for a Priority Review Voucher (PRV) upon approval. A PRV confers priority review to a subsequent drug application that would not otherwise qualify for that designation. The rare pediatric disease review voucher program is designed to encourage development of new drugs and biologics for the prevention or treatment of rare pediatric diseases.

Palynziq for PKU: On October 7, 2020 the Company announced that the FDA approved the supplemental Biologics License Application (sBLA) to increase the maximum allowable dose of Palynziq (pegvaliase-pqpz) Injection for treatment of adults with PKU to 60 mg daily. Previously, the maximum dose was 40 mg daily. In the Phase 3 PRISM studies, 19% of study participants required a 60 mg dose to achieve adequate response to Palynziq.
Palynziq is indicated to reduce blood Phe concentrations in adults with PKU, who have uncontrolled blood Phe concentrations greater than 600 μmol/L on existing management. Palynziq, a PEGylated recombinant phenylalanine ammonia lyase enzyme, is the first and only approved enzyme substitution therapy to target the underlying cause of PKU by helping the body to break down Phe.

BMN 307 gene therapy product candidate for PKU: The Company announced that it plans to dose escalate in PHEarless, the Phase 1/2 study of BMN 307 based on encouraging Phe lowering and safety signals observed in study participants who were treated with the lowest dose. Both the FDA and EMA granted BMN 307 Orphan Drug Status. Additionally, the FDA has granted Fast Track status to BMN 307. Product for use in the Phase 1/2 study was made at commercial scale from BioMarin’s award-winning gene therapy manufacturing facility.
BMN 331 gene therapy product candidate for Hereditary Angioedema (HAE): IND-enabling studies are ongoing with BMN 331, BioMarin’s third gene therapy candidate, for the treatment of HAE. BioMarin plans to leverage its broad expertise in developing gene therapies for severe hemophilia A and PKU to improve efficiencies in the development process of BMN 331.
DiNA-001 for MYBPC3 hypertrophic cardiomyopathy (HCM): Pre-clinical studies are underway with DiNA-001 following a collaboration announced in 2020 with DiNAQOR, a gene therapy platform company, to develop novel gene therapies to treat rare genetic cardiomyopathies. DiNAQOR received an undisclosed upfront payment and is eligible to receive development, regulatory and commercial milestones on product sales in addition to tiered royalties on worldwide sales.
BMN 255 for a subset of chronic renal disease: On January 11, 2021 the Company announced that it filed an IND in 2020 for BMN 255, a small molecule for a subset of chronic renal disease. BMN 255 was driven by genetic discoveries for both mechanism and for identifying individuals for treatment.
BMN 351 for Duchenne Muscular Dystrophy (DMD): IND-enabling studies are underway with BMN 351, an oligonucleotide therapy that has demonstrated a high-level of protein expression in experimental animals possessing skippable dystrophic mutations and at doses that are promising in regard to safety. The Company intends to determine timing of a potential IND filing at the end of the year based on results of ongoing IND-enabling studies.
BioMarin will host a conference call and webcast to discuss fourth quarter and full-year 2020 financial results today, Thursday, February 25, 2021 at 4:30 p.m. ET. This event can be accessed on the investor section of the BioMarin website at www.biomarin.com.

On February 25, 2021 Novocure (NASDAQ: NVCR) reported financial results for the quarter and full year ended December 31, 2020, highlighting revenue growth and financial strength as well as the advancement of the company’s clinical and product development programs (Press release, NovoCure, FEB 25, 2021, View Source [SID1234575680]). Novocure is a global oncology company working to extend survival in some of the most aggressive forms of cancer by developing and commercializing its innovative therapy, Tumor Treating Fields.

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(1) Adjusted EBITDA is a non-U.S. GAAP measurement of earnings before interest, taxes, depreciation, amortization and share-based compensation.

(2) An "active patient" is a patient who is receiving treatment 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.

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

"Our track record of execution continued throughout 2020 with notable progress made in advancing our three overarching priorities: to drive commercial adoption; to carry out our clinical trial programs; and to deliver product innovations to optimize Tumor Treating Fields therapy," said William Doyle, Novocure’s Executive Chairman. "Despite the complexities posed by the COVID-19 pandemic, we generated nearly $500 million in net revenues and $20 million in net income in 2020. Our financial strength positions us well to invest strategically in science and technology to unleash the potential of the Tumor Treating Fields platform."

"As proud as we are of treating more than 18,000 patients to-date, we remain focused on extending the reach of Tumor Treating Fields therapy to many more cancer patients," added Asaf Danziger, Novocure’s Chief Executive Officer. "With multiple clinical trials expected to read out over the next few years, we believe we are just beginning to unlock our potential to impact oncology. Acceptance of our therapy continues to build within the global oncology community, which reinforces our commitment to our mission to extend survival in some of the most aggressive forms of cancer."

Fourth quarter 2020 financial update

For the quarter ended December 31, 2020, net revenues were $144.0 million, representing 45% growth compared to the fourth quarter 2019.

In the United States, net revenues totaled $97.7 million in the quarter ended December 31, 2020, representing 48% growth compared to the same period in 2019.
In Germany and other EMEA markets, net revenues totaled $33.8 million in the quarter ended December 31, 2020, representing 31% growth compared to the same period in 2019.
In Japan, net revenues totaled $7.9 million in the quarter ended December 31, 2020, representing 42% growth compared to the same period in 2019.
In Greater China, net revenues totaled $4.5 million in the quarter ended December 31, 2020, representing 132% growth compared to the same period in 2019.
For the three months ended December 31, 2020, the increases primarily resulted from an increase of 502 active patients in our active markets and an increase in the net revenues per active patient per month. The increase in net revenues per active patient per month primarily was driven by improving reimbursement approval rates in the U.S.

In the fourth quarter 2020, we recorded $9 million in revenues from Medicare fee-for-service beneficiaries billed under the coverage policy effective on September 1, 2019. We have gained a good understanding of how to ensure timely processing of Medicare claims and have sufficient experience to recognize approximately two-thirds of the expected contribution from Medicare beneficiaries. In the fourth quarter of 2020, we also recognized approximately $11 million in incremental net revenues compared to the first half of 2020 resulting from the successful appeal of previously denied claims for Medicare fee-for-service beneficiaries billed prior to established coverage.

Cost of revenues for the three months ended December 31, 2020 was $28.1 million compared to $24.8 million for the same period in 2019, representing an increase of 14%. The increase in cost of revenues primarily was due to the cost of shipping arrays to a higher volume of commercial patients. Gross margin was 80% for the three months ended December 31, 2020 compared to 75% for the three months ended December 31, 2019. Gross margin continues to benefit from ongoing efficiency initiatives and increasing scale. Gross margin is also improved with revenue resulting from the successful appeal of previously denied claims for Medicare fee-for-service beneficiaries and tempered by product sales to Zai.

Research, development and clinical trials expenses for the three months ended December 31, 2020 were $44.0 million compared to $23.7 million for the same period in 2019, representing an increase of 85%. The increase primarily was due to increased investments in clinical trials and clinical administration personnel to advance and broaden our clinical development programs, preclinical and basic research to better understand the optimal use of Tumor Treating Fields, product development intended to optimize the delivery of Tumor Treating Fields therapy, and expanded medical affairs efforts to educate the clinical community.

We expect growth in our research and development to continue into 2021 as we work to advance our pipeline programs and increase acceptance of Tumor Treating Fields within the global oncology community. We balance our investments in research and development with our organizational capacity to effectively execute our strategic initiatives.

Sales and marketing expenses for the three months ended December 31, 2020 were $31.4 million compared to $26.8 million for the same period in 2019, representing an increase of 17%. This primarily was due to an increase in personnel and professional services costs to support our growing commercial business and reimbursement efforts and an increase in marketing expenses related to the launch of Optune Lua for MPM.

General and administrative expenses for the three months ended December 31, 2020 were $28.4 million compared to $23.7 million for the same period in 2019, representing an increase of 19%. This primarily was due to an increase in personnel costs, insurance premiums and professional services.

Net income for the three months ended December 31, 2020 was $4.9 million compared to net income of $4.3 million for the same period in 2019.

At December 31, 2020, we had $842.6 million in cash and cash equivalents and short-term investments, an increase of $516.5 million compared to $326.1 million at December 31, 2019. The increase in our cash, cash equivalents and short-term investments primarily was due to convertible notes issued, net cash provided by operating activities and the exercise of options.

Fourth quarter 2020 operating statistics

There were 3,411 active patients at December 31, 2020, representing 17% growth compared to December 31, 2019, and 1% growth compared to September 30, 2020.

In the United States, there were 2,193 active patients at December 31, 2020, representing 12% growth compared to December 31, 2019.
In Germany and other EMEA markets, there were 953 active patients at December 31, 2020, representing 25% growth compared to December 31, 2019.
In Japan, there were 265 active patients at December 31, 2020, representing 38% growth compared to December 31, 2019.
Additionally, 1,411 prescriptions were received in the quarter ended December 31, 2020, representing 2% growth compared to the same period in 2019, and a 3% increase compared to the quarter ended September 30, 2020. In the quarter ended December 31, 2020, 1,160 Optune prescriptions were written for patients with newly diagnosed glioblastoma.

In the United States, 962 prescriptions were received in the quarter ended December 31, 2020, representing a 4% decrease compared to the same period in 2019.
In Germany and other EMEA markets, 349 prescriptions were received in the quarter ended December 31, 2020, representing 22% growth compared to the same period in 2019.
In Japan, 100 prescriptions were received in the quarter ended December 31, 2020, representing 8% growth compared to the same period in 2019.
Fourth quarter 2020 non-U.S. GAAP measures

We also measure our performance based upon a non-U.S. GAAP measurement of earnings before interest, taxes, depreciation, amortization and shared-based compensation ("Adjusted EBITDA"). We believe Adjusted EBITDA is useful to investors in evaluating our operating performance because it helps investors compare the results of our operations from period to period by removing the impact of earnings attributable to our capital structure, tax rate and material non-cash items, specifically share-based compensation.

Adjusted EBITDA was $34.8 million for the three months ended December 31, 2020, an increase of $17.5 million, or 101%, from $17.3 million for the three months ended December 31, 2019. This improvement in fundamental financial performance was driven by net revenue growth coupled with an ongoing commitment to disciplined management of expenses.

Anticipated clinical milestones

Final data from phase 2 pilot HEPANOVA trial in advanced liver cancer (Q2 2021)
Interim analysis of phase 3 pivotal INNOVATE-3 trial in recurrent ovarian cancer (Q3 2021)
Interim analysis of phase 3 pivotal LUNAR trial in non-small cell lung cancer (Q4 2021)
Final data from phase 2 pilot EF-31 trial in gastric cancer (2022)
Interim analysis of phase 3 pivotal PANOVA-3 trial in locally advanced pancreatic cancer (2022)
Final data from phase 3 pivotal METIS trial in brain metastases (2022)
Final data from phase 2 pilot EF-33 trial with high-intensity arrays in recurrent glioblastoma (2022)
Final data from phase 3 pivotal INNOVATE-3 trial in recurrent ovarian cancer (2023)
Final data from phase 3 pivotal LUNAR trial in non-small cell lung cancer (2023)
Final data from phase 3 pivotal PANOVA-3 trial in locally advanced pancreatic cancer (2023)
Conference call details

Novocure will host a conference call and webcast to discuss fourth quarter and full year 2020 financial results at 8 a.m. EST today, Thursday, February 25, 2021. 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 3965899.

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. Novocure has used, and intends to continue to use, its investor relations website, as a means of disclosing material non-public information and for complying with its disclosure obligations under Regulation FD.