On November 3, 2021 Horizon Therapeutics plc (Nasdaq: HZNP) reported record third-quarter 2021 financial results and increased both its full-year 2021 net sales and adjusted EBITDA guidance (Press release, Horizon Therapeutics, NOV 3, 2021, View Source [SID1234594270]).

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"We generated record results in the third quarter and made significant progress executing our R&D strategy, further expanding our pipeline with five new programs," said Tim Walbert, chairman, president and chief executive officer, Horizon. "In addition to our strong commercial execution with TEPEZZA and KRYSTEXXA, our expanded pipeline positions us to drive future growth and diversification, as well as address the unmet medical needs of many people living with rare, autoimmune and severe inflammatory diseases around the world."

Third Quarter and Recent Company Highlights

Announced Five New R&D Programs and Highlighted Expanded Pipeline at Inaugural R&D Day: In September, the Company announced four new programs for its development-stage candidate daxdilimab (HZN-7734) in alopecia areata, discoid lupus erythematosus, dermatomyositis and lupus nephritis and one new program for its development-stage candidate dazodalibep (HZN-4920) in focal segmental glomerulosclerosis. The Company expects to initiate Phase 2 trials in each of these indications in 2022. The new programs, in addition to the Company’s R&D strategy and other key programs, were highlighted at the Company’s inaugural R&D Day in September.

Announced Positive Topline Data from KRYSTEXXA MIRROR Trial: In October, the Company announced positive topline results from the MIRROR Phase 4 randomized, placebo-controlled trial evaluating the use of KRYSTEXXA plus methotrexate. The MIRROR trial results demonstrated that 71 percent of patients who were randomized to receive KRYSTEXXA plus methotrexate achieved a complete response rate at Month 6 (p<0.001), a significant improvement from the 40 percent response rate in patients who were randomized to receive KRYSTEXXA plus placebo. In the Phase 3 clinical program, which evaluated KRYSTEXXA alone compared to placebo, 42 percent of patients receiving KRYSTEXXA achieved a complete response. The Company plans to submit a sBLA to the U.S. FDA in the first quarter of 2022. Full data from the trial is expected to be presented at future medical meetings. KRYSTEXXA plus immunomodulation is a core element of the Company’s strategy to maximize the value of KRYSTEXXA and enable more patients with uncontrolled gout to benefit from the medicine.

Initiated Enrollment in TEPEZZA Chronic TED Trial: In September, the first patient was enrolled in a Phase 4 randomized, placebo-controlled clinical trial to evaluate the safety and efficacy of TEPEZZA for the treatment of chronic TED. TED is a serious, progressive and potentially vision-threatening rare autoimmune disease. It begins with an acute phase where inflammatory signs and symptoms, such as eye pain, swelling, proptosis (eye bulging) and diplopia (double vision), progress over time. The acute stage is followed by a chronic phase in which inflammation is no longer present or has markedly diminished; however, significant signs and symptoms may remain and continue to impact the quality of life. The objective of the trial is to generate clinical data to better inform physicians and payers about the safety and efficacy of TEPEZZA in patients with chronic TED. Results are expected in the second half of 2022.

Presented New UPLIZNA (inebilizumab-cdon) Data at Key Medical Meetings: New UPLIZNA data were presented at the 15th World Congress on Controversies in Neurology (CONy Virtual), including end-of-study data from the open-label extension period of the Phase 3 trial in patients with neuromyelitis optica spectrum disorder (NMOSD). The data indicated that UPLIZNA may provide durable efficacy and a favorable safety profile for African Americans with NMOSD. Multiple new data were also presented at the virtual 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in October. Additionally, a new analysis of data from the Phase 3 trial was published in the Multiple Sclerosis Journal that highlighted a sustained effect on attack risk in people with NMOSD who were treated with UPLIZNA for four or more years.

Acquired Biologics Manufacturing Facility in Waterford, Ireland: In July, the Company completed the acquisition of a biologics drug product manufacturing facility in Waterford, Ireland. The Company intends to use the manufacturing facility to support the growth of the Company’s on-market medicines, including TEPEZZA, KRYSTEXXA and UPLIZNA, as well as development-stage biologics.

Continued to Demonstrate Gender and Ethnicity Pay Equity: A second study conducted by Aon, a leading compensation consulting firm, showed that Horizon continues to demonstrate both gender and ethnicity pay equity. This study was a follow-on study to the gender and pay ethnicity study Aon conducted in 2019. The Company maintained its gender and ethnicity pay equity despite having grown significantly in the two years since the first study, as well as having completed the acquisition of Viela Bio, which included the addition of a significant number of employees.

Multiple Additional Recognitions as a Best Workplace: In September, the Company was named one of the "2021 Best Workplaces for Women" by Fortune and Great Place to Work for the first time. In addition, the Company was also recognized as one of PEOPLE’s "100 Companies That Care" for the third year. In July, Fortune and Great Place to Work named the Company to the "Best Workplaces for Millennials" list for the second consecutive year and the Company was the highest ranked biotechnology company on the list. In addition, in October the Company was named one of the Top 100 Adoption-Friendly Workplaces by the Dave Thomas Foundation for Adoption for the third consecutive year. Most recently, Horizon was named to Newsweek’s inaugural "Most Loved Workplaces" list, ranking among the top 100 companies recognized for employee happiness and satisfaction at work and was the highest-ranked company in the biotechnology and pharmaceutical category. To date in 2021, the Company has received 11 workplace-related recognitions, reflecting the high level of engagement of its employees.
Key Clinical Development Programs

Daxdilimab (HZN-7734), an anti-ILT7 human monoclonal antibody that depletes certain dendritic cells. Depleting these cells may interrupt the cycle of inflammation that causes tissue damage in diseases such as lupus, and a variety of other autoimmune conditions.

Systemic Lupus Erythematosus (SLE) Trial: Phase 2 randomized, placebo-controlled trial underway to evaluate daxdilimab in patients with SLE, a disease in which the body’s immune system attacks its own tissues and organs.

Alopecia Areata Trial: Phase 2 trial to evaluate daxdilimab in patients with alopecia areata, an autoimmune disorder characterized by nonscarring hair loss, expected to initiate in the first half of 2022.

Discoid Lupus Erythematosus (DLE) Trial:Phase 2 trial to evaluate daxdilimab in patients with DLE, a rare, chronic, inflammatory skin condition characterized by lesions that result in scarring, expected to initiate in the first half of 2022.

Lupus Nephritis Trial: Phase 2 trial to evaluate daxdilimab in patients with lupus nephritis, a rare, autoimmune disorder characterized by rashes, debilitating muscle weakness and interstitial lung disease, expected to initiate in the second half of 2022.

Dermatomyositis Trial: Phase 2 trial to evaluate daxdilimab in patients with dermatomyositis, a rare, autoimmune and inflammatory condition of the kidney, expected to initiate in the second half of 2022.

Dazodalibep (HZN-4920), a CD40 ligand antagonist that blocks T cell interaction with the CD40-expressing B cells, disrupting the overactivation of the CD40 ligand co-stimulatory pathway. Several autoimmune diseases are associated with the overactivation of this pathway.

Sjögren’s Syndrome Trial: Phase 2b randomized, placebo-controlled trial underway to evaluate dazodalibep in patients with Sjögren’s syndrome, a chronic, systemic autoimmune condition that impacts exocrine glands, including the salivary and tear glands.

Rheumatoid Arthritis Trial: Phase 2 randomized, placebo-controlled trial underway to evaluate dazodalibep in patients with rheumatoid arthritis.

Kidney Transplant Rejection Trial: Phase 2 open-label trial underway to evaluate dazodalibep in kidney transplant rejection patients.

Focal Segmental Glomerulosclerosis (FSGS) Trial: Phase 2 trial to evaluate dazodalibep in patients with FSGS, a rare kidney disorder characterized by scarring of glomeruli, expected to initiate in the second half of 2022.

HZN-825, an oral lysophosphatidic acid receptor 1 (LPAR1) antagonist that prevents gene activation.

Diffuse Cutaneous Systemic Sclerosis Trial: Pivotal Phase 2b trial to evaluate HZN-825 in diffuse cutaneous systemic sclerosis, expected to initiate in the fourth quarter of 2021.

Interstitial Lung Disease Trial: Pivotal Phase 2b trial to evaluate HZN-825 in idiopathic pulmonary fibrosis, the most common form of interstitial lung disease, expected to initiate in the fourth quarter of 2021.

UPLIZNA, an anti-CD19 humanized monoclonal antibody that depletes B cells, including the pathogenic cells that produce autoantibodies.

Myasthenia Gravis Trial:Phase 3 randomized, placebo-controlled trial underway to evaluate UPLIZNA in patients with myasthenia gravis, a chronic, rare, autoimmune neuromuscular disease that affects voluntary muscles, especially those that control the eyes, mouth, throat and limbs.

IgG4-Related Disease Trial: Phase 3 randomized, placebo-controlled trial underway to evaluate UPLIZNA in patients with IgG4-related disease, which is a group of disorders marked by tumor-like swelling and fibrosis of affected organs, such as the pancreas, salivary glands and kidneys.

Kidney Transplant Desensitization Trial: Phase 2 open-label trial underway to evaluate UPLIZNA, dazodalibep or both in highly sensitized patients waiting for a kidney transplant.

TEPEZZA, an insulin-like growth factor type 1 receptor (IGF-1R) antagonist monoclonal antibody.

Chronic TED Trial: Phase 4 randomized, placebo-controlled trial initiated in September 2021 to evaluate TEPEZZA in chronic TED.

Subcutaneous (SC) Administration Trial:Phase 1 pharmacokinetic trial underway to explore SC administration of TEPEZZA.

Diffuse Cutaneous Systemic Sclerosis Exploratory Trial: Phase 1 exploratory trial to evaluate TEPEZZA in diffuse cutaneous systemic sclerosis expected to initiate in the fourth quarter of 2021.

KRYSTEXXA, a recombinant uricase enzyme that converts urate into a water-soluble liquid, allantoin, that can be easily excreted from the body.

MIRROR Trial: Phase 4 randomized, placebo-controlled trial to evaluate KRYSTEXXA plus methotrexate to increase the complete response rate in patients with uncontrolled gout. Topline results were announced on Oct. 25, 2021. The results demonstrated that 71 percent of patients who were randomized to receive KRYSTEXXA plus methotrexate achieved a complete response rate at Month 6 (p<0.001), a significant improvement from the 40 percent response rate in patients who were randomized to receive KRYSTEXXA plus placebo.

PROTECT Trial: Phase 4 open-label trial to evaluate KRYSTEXXA to improve management of uncontrolled gout in kidney transplant patients. This trial is completed, and final results will be presented at American Society of Nephrology (ASN) Kidney Week 2021 later this week.

Shorter Infusion Duration Trial: Phase 4 open-label trial underway to evaluate the impact of administering KRYSTEXXA plus methotrexate over a shorter infusion duration in patients with uncontrolled gout.

Monthly Dosing Trial:Phase 4 open-label trial underway to evaluate monthly dosing of KRYSTEXXA plus methotrexate in patients with uncontrolled gout.

Retreatment Trial: Phase 4 open-label trial underway to evaluate KRYSTEXXA plus methotrexate in patients who were not complete responders to KRYSTEXXA monotherapy.

HZN-1116 Autoimmune Disease Trial: Phase 1 trial initiated in July 2021 to evaluate HZN-1116, a monoclonal antibody, in patients with autoimmune diseases.
Third-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: Third-quarter 2021 net sales were $1.037 billion, an increase of 63 percent compared to the third quarter of 2020.

Gross Profit: Under U.S. GAAP, the third-quarter 2021 gross profit ratio was 75.7 percent compared to 76.2 percent in the third quarter of 2020. The non-GAAP gross profit ratio in the third quarter of 2021 was 85.4 percent compared to 86.7 percent in the third quarter of 2020.

Operating Expenses: R&D expenses were 9.0 percent of net sales and SG&A expenses were 34.7 percent of net sales. Non-GAAP R&D expenses were 7.2 percent of net sales and non-GAAP SG&A expenses were 29.0 percent of net sales.

Income Tax Expense (Benefit): On a GAAP basis in the third quarter of 2021, income tax benefit was $19.3 million. Third-quarter non-GAAP income tax expense was $73.8 million.

Net Income: In the third-quarter of 2021, net income on a GAAP and non-GAAP basis was $326.5 million and $413.8 million, respectively.

Adjusted EBITDA: Third-quarter 2021 adjusted EBITDA was $509.0 million.

Earnings per Share: On a GAAP basis, diluted earnings per share in the third quarter of 2021 and 2020 were $1.38 and $1.31, respectively. Non-GAAP diluted earnings per share in the third quarter of 2021 and 2020 were $1.75 and $1.74, respectively. Weighted average shares outstanding used for calculating GAAP and non-GAAP diluted earnings per share in the third quarter of 2021 were 236.2 million.
Third-Quarter Segment Results

Management uses net sales and segment operating income to evaluate the performance of the Company’s two segments, the orphan segment and the inflammation segment. 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.

Third-quarter 2021 net sales of the orphan segment, the Company’s strategic growth segment, were $951.0 million, an increase of 78 percent over the prior year’s quarter, driven by the strong performance of TEPEZZA, KRYSTEXXA, RAVICTI, PROCYSBI and ACTIMMUNE. The orphan segment represented 92 percent of total company third-quarter net sales.

KRYSTEXXA third-quarter 2021 net sales increased 46 percent year-over-year driven by increased adoption of KRYSTEXXA plus immunomodulation, which now exceeds 45 percent. In addition, the Company continues to see strong uptake of KRYSTEXXA from both rheumatologists and nephrologists.

Third-quarter 2021 orphan segment operating income was $476.2 million, which includes additional investment associated with TEPEZZA, UPLIZNA and the Company’s pipeline programs.
Third-quarter 2021 net sales of the inflammation segment were $86.0 million, and segment operating income was $34.1 million.
Cash Flow Statement and Balance Sheet Highlights

On a GAAP basis, operating cash flow in the third quarter of 2021 was $411.0 million. Non-GAAP operating cash flow was $432.3 million.
As of Sept. 30, 2021, the Company had cash and cash equivalents of $1.069 billion.
As of Sept. 30, 2021, the total principal amount of debt outstanding was $2.610 billion, and the gross-debt-to-last-12-months adjusted EBITDA leverage ratio was 2.0 times.
2021 Guidance

The Company now expects full‐year 2021 net sales to range between $3.16 billion and $3.21 billion, representing 45 percent growth at the midpoint and an increase from the previous range of $3.025 billion to $3.125 billion. The company now expects TEPEZZA full-year 2021 net sales of greater than $1.625 billion with year-over-year growth of more than 60 percent in the fourth quarter, compared to the previous guidance of greater than $1.550 billion with year-over-year growth of more than 50 percent in the fourth quarter. The Company now expects KRYSTEXXA full-year 2021 net sales of greater than $550 million, compared to the previous guidance of greater than $500 million. Full-year 2021 adjusted EBITDA is now expected to range between $1.315 billion and $1.345 billion, representing 33 percent growth at the midpoint and an increase from the previous guidance range of $1.26 billion to $1.30 billion.

Webcast

At 8 a.m. EST / 12 p.m. GMT 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.

On November 3, 2021 ITM Isotope Technologies Munich SE reported the presentation of the design of its new phase III trial, COMPOSE, with the radiopharmaceutical candidate n.c.a. 177Lu-edotreotide in patients with well‐differentiated aggressive grade 2 and grade 3 somatostatin receptor-positive gastro-enteropancreatic neuroendocrine tumors (GEP-NETs) at the North American Neuroendocrine Society (NANETS) annual symposium 2021, held virtually from November 3 – 6, 2021 (Press release, ITM Isotopen Technologien Munchen, NOV 3, 2021, View Source [SID1234594269]). COMPOSE is ITM’s second phase III trial with its lead candidate n.c.a. 177Lu-edotreotide, a Targeted Radionuclide Therapy consisting of the high-quality radioisotope no-carrier-added lutetium-177 fused with an innovative somatostatin analogue to specifically target GEP-NETs. N.c.a. 177Lu-edotreotide is also currently being investigated in an ongoing phase III study, COMPETE, in patients with grade 1 and 2 GEP-NETs.

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"The most common form of NETs is gastroenteropancreatic and often develops metastatic disease, limiting treatment options. N.c.a. 177Lu-edotreotide has previously shown a favorable safety and efficacy profile in GEP-NETs and with COMPOSE we aim to also make it available to late-stage patients suffering from this hard-to-treat cancer indication," stated Steffen Schuster, CEO of ITM. "We look forward to the opportunity of introducing our phase III COMPOSE trial to the global scientific community at the NANETS symposium, a key oncology event that features leading research, education, and emerging practices on NETs."

COMPOSE (NCT04919226) is an international, prospective, randomized, controlled, open-label, multi-center phase III study to evaluate the efficacy, safety, and patient-reported outcomes of first or second-line treatment with n.c.a. 177Lu-edotreotide PRRT compared to best standard of care in patients with well-differentiated aggressive grade 2 and grade 3 (Ki-67 index 15-55), somatostatin receptor-positive (SSTR+), GEP-NETs. The study aims to randomize 202 patients 1:1 to n.c.a. 177Lu-edotreotide or to an active comparator — either chemotherapy (CAPTEM or FOLFOX) or everolimus — according to the investigator’s choice. The primary endpoint of the study is progression-free survival (PFS), which will be assessed every 12 weeks from randomization onwards. Secondary outcome measures include overall survival (OS) up to two years after disease progression.

Presentation information

Title: COMPOSE: Pivotal phase III trial of 177Lu-edotreotide versus best standard of care in well-differentiated aggressive grade 2 and grade 3 gastroenteropancreatic neuroendocrine tumors
Abstract No: 136
Poster No: 410
Session: Phase III Clinical Trials in Progress
Presenter: Prof. Thorvardur Halfdanarson, Mayo Clinic, Rochester, MN, USA

For more information on COMPOSE and ITM, visit the ITM virtual booth at the NANETS virtual industry exhibition.

– End –

About Targeted Radionuclide Therapy

Targeted Radionuclide Therapy is an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing radiation exposure to normal tissue. Targeted radiopharmaceuticals are created by linking a therapeutic radioisotope to a targeting molecule (e.g., peptide, antibody, small molecule) that can precisely recognize tumor cells and bind to tumor-specific characteristics, like receptors on the tumor cell surface. As a result, the radioisotope accumulates at the tumor site and decays, releasing a small amount of ionizing radiation, thereby destroying the tumor. The highly precise localization enables targeted treatment with minimal impact to healthy surrounding tissue.

About n.c.a. 177Lu-edotreotide

N.c.a. 177Lu-edotreotide is ITM’s therapeutic radiopharmaceutical candidate being investigated in the phase III clinical studies COMPETE and COMPOSE and consists of two components: the medical radioisotope no-carrier-added lutetium-177 (n.c.a. 177Lu) and the targeting molecule edotreotide, a synthetic form of the peptide hormone somatostatin that targets neuroendocrine tumor-specific receptors. Edotreotide binds to these receptors and places the medical radioisotope n.c.a. lutetium-177 directly onto the diseased neuroendocrine cells so that it accumulates at the tumor site. N.c.a. lutetium-177 is internalized into the tumor cells and decays, releasing medical radiation (ionizing β-radiation) with a maximum radius of 1.7 mm and destroying the tumor. The highly precise localization can result in the healthy tissue surrounding the targeted tumor being minimally affected.

On November 3, 2021 Memgen, Inc. reported that the U.S. Food and Drug Administration (FDA) has accepted its investigational new drug (IND) application for MEM-288, the company’s wholly-owned cancer immunotherapy candidate for the treatment of multiple solid tumors (Press release, Memgen, NOV 3, 2021, View Source [SID1234594268]). Memgen intends to initiate screening of patients by year-end in a Phase 1 first-in-human study.

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"The FDA’s acceptance of our IND for MEM-288 is an important milestone in our pursuit of developing life-saving cancer immunotherapies in collaboration with leading cancer centers including the Moffitt Cancer Center and the Duke Cancer Institute," said Mark Cantwell, Ph.D., Chief Scientific Officer of Memgen. "We expect to initiate this first-in-human study in patients with non-small cell lung cancer, as well as those with other types of cancer, by year-end."

Memgen’s Phase 1 trial is an open-label, dose escalation study designed to evaluate the safety, tolerability, biologic activity and anti-tumor effects of MEM-288. In addition to non-small cell lung cancer (NSCLC), the trial may enroll patients with triple-negative breast cancer, pancreatic cancer, head and neck cancer, melanoma, cutaneous squamous-cell carcinoma, and Merkel cell carcinoma. Except for patients with pancreatic cancer, these are patients whose disease has progressed following treatment with anti-PD-1/PD-L1 therapy, and who have tumor lesions accessible for injection.

Duke Cancer Institute and the H. Lee Moffitt Cancer will be the initial clinical trial sites. Memgen expects patient recruitment to begin by December 31, 2021. Additional information about the study, including patient inclusion and exclusion criteria, can be found at ClinicalTrials.gov under study identifier NCT05076760.

The study will evaluate the oncolytic effect of MEM-288 as well as the activation of the patients’ immune system including T-cells. While the focus of the initial Phase 1 study will be patients with NSCLC, MEM-288 has shown robust anti-tumor effects in 13 different types of cancer. Once safety and tolerability have been evaluated in this trial, Memgen plans to expand clinical development of MEM-288 across multiple cancers and in combination with an immune checkpoint inhibitor.

About MEM-288
MEM-288 is an oncolytic adenovirus encoding transgenes for human interferon beta (IFNß) and the company’s proprietary recombinant chimeric CD40 ligand. MEM-288, armed with Memgen’s proprietary CD40 ligand, leverages a validated target that powerfully activates the patient’s immune system. The company’s proprietary CD40 ligand has been evaluated in earlier clinical studies and demonstrated significant immune activation without the toxicity that had previously prevented development of safe CD40-based therapeutics. Because the CD40 system works as a master "on switch" for the immune system upstream from the immune checkpoint inhibitors, it holds promise in those patients whose disease has progressed despite treatment with immune checkpoint inhibitors.

On November 3, 2021 NOXXON Pharma N.V. (Euronext Growth Paris: ALNOX), a biotechnology company focused on improving cancer treatments by targeting the tumor microenvironment (TME), reported that due to supply-chain issues affecting its drug-supply manufacturer, the start date of its two upcoming NOX-A12 clinical trials will be delayed by up to 3 months until Q3 2022 (Press release, NOXXON, NOV 3, 2021, View Source [SID1234594267]). The affected trials are the Phase 2 trial (OPTIMUS) with NOX-A12 in combination with MSD’s (Merck & Co., Inc., Kenilworth, N.J. USA) anti-PD-1 therapy Keytruda (pembrolizumab) as second-line therapy in pancreatic cancer, and the planned pivotal Phase 2/3 trial of NOX-A12 in combination with radiotherapy in first-line brain cancer (glioblastoma) patients.

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Due to a shortage in the US of dichloroacetic acid, a key chemical reagent necessary to synthesize NOX-A12, NOXXON has been informed by its contract active ingredient manufacturer that the NOX-A12 batches needed to initiate these two studies will only be available in Q2 2022 with first patients therefore expected to be dosed in early August 2022. These delays have impacted the overall approval timelines of NOX-A12 in glioblastoma, pushing it into early 2026, while market approval in pancreatic cancer remains unchanged and is planned in 2027.

Aram Mangasarian, CEO of NOXXON commented: "The effects of the COVID-19 pandemic continue to impact the healthcare industry in many areas, including the most essential ones like manufacturing supply chains. The NOX-A12 studies in pancreatic and brain cancer are our key clinical programs; the pancreas cancer trial is our second collaboration with MSD, a global leader in the immuno-oncology space, and the pivotal brain cancer trial is expected to deliver the data base for our first marketing authorization. We have worked with our contract manufacturer to overcome the unexpected shortages of what are usually easily sourced chemical reagents affecting these batches of NOX-A12 and are doing everything to ensure these batches will be released as soon as possible with the usual high standards of quality. We look forward to getting the trials underway and examining the potential clinical benefits of NOX-A12 in combination with Keytruda or radiotherapy for patients suffering from highly aggressive cancers."

With €13.7 million in cash and cash equivalents on June 30, 2021 and available secured financing of €10.45 million (nominal) drawable at the company’s discretion as reported on October 22, 2021 with the Half-Year Financial Report 2021, updated timing of commitments for manufacturing and clinical trials extends NOXXON’s financial visibility into July 2022.

On November 3, 2021 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that the European Medicines Agency (EMA) has validated the Type II Variation Application for trastuzumab deruxtecan, a HER2 directed antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN), for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior anti-HER2-based regimen (Press release, Daiichi Sankyo, NOV 3, 2021, View Source [SID1234594266]).

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Validation confirms that the application is complete and commences the scientific review process by the EMA’s Committee for Medicinal Products for Human Use (CHMP). This application is based on the positive results from the DESTINY-Gastric01 pivotal phase 2 trial published in The New England Journal of Medicine and the DESTINY-Gastric02 phase 2 trial recently presented at the 2021 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress.

"After progression on initial therapy, patients with HER2 positive advanced gastric cancer are faced with limited options in Europe, so there is a significant unmet need for new therapeutic options," said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. "We look forward to working with the EMA on its review of this application and to potentially bring trastuzumab deruxtecan to physicians and patients in Europe, as it offers the potential to provide an important new treatment option to patients with locally advanced or metastatic HER2 positive gastric or GEJ adenocarcinoma who have received a prior anti-HER2-based regimen."

About HER2 Positive Gastric Cancer

Gastric (stomach) cancer is the fifth most common cancer worldwide and the fourth highest leading cause of cancer mortality, with a five-year global survival rate of 5% to 10% for advanced or metastatic disease.1,2,3 There were approximately one million new cases of gastric cancer and 768,000 deaths reported worldwide in 2020.4 In Europe, approximately 136,000 cases of gastric cancer are diagnosed annually, and Eastern Europe has the second highest incidence of gastric cancer worldwide after Eastern Asia.3,4 Gastric cancer is the sixth leading cause of cancer death in Europe, and is typically diagnosed in the advanced stage but even when diagnosed in earlier stages of the disease the survival rate remains modest.3,5,6,7

Approximately one in five gastric cancers are HER2 positive.8,9 HER2 is a tyrosine kinase receptor growth promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers.9 HER2 overexpression may be associated with a specific HER2 gene alteration known as HER2 amplification.9

Recommended first-line treatment for HER2 positive advanced or metastatic gastric cancer is combination chemotherapy plus trastuzumab, an anti-HER2 medicine, which has been shown to improve survival outcomes when added to chemotherapy.10 For patients with metastatic gastric cancer that progress following initial treatment with a trastuzumab-based regimen, treatment options are limited, and in many regions in the world there are no additional HER2 directed medicines available.1,5,11

About DESTINY-Gastric01

DESTINY-Gastric01 is a pivotal, randomized, open-label, multi-center phase 2 trial assessing the safety and efficacy of trastuzumab deruxtecan (6.4 mg/kg) in patients from Japan and South Korea with HER2 positive (defined as IHC3+ or IHC2+/ISH+) advanced gastric cancer or gastroesophageal junction adenocarcinoma who have progressed on two or more prior treatment regimens including fluoropyrimidine (5-FU), platinum chemotherapy and trastuzumab. Patients were randomized 2:1 to receive trastuzumab deruxtecan or physician’s choice of chemotherapy (paclitaxel or irinotecan monotherapy). The primary endpoint of DESTINY-Gastric01 is objective response rate (ORR). Secondary endpoints include overall survival (OS), progression-free survival (PFS), duration of response (DoR), disease control rate and time to treatment failure as well as pharmacokinetic and safety endpoints. DESTINY-Gastric01 enrolled 189 patients at multiple sites in Japan and South Korea. For more information about the trial, visit ClinicalTrials.gov.

About DESTINY-Gastric02

DESTINY-Gastric02 is an open-label, single-arm, phase 2 trial in Western patients evaluating the safety and efficacy of trastuzumab deruxtecan (6.4 mg/kg) in patients with HER2 positive metastatic and/or unresectable gastric or GEJ adenocarcinoma with disease progression on or after a trastuzumab-containing regimen. The primary endpoint of DESTINY-Gastric02 is confirmed ORR based on independent central review. Secondary endpoints include PFS, OS, DoR and safety. DESTINY-Gastric02 enrolled 79 patients at multiple sites in North America and Europe. For more information about the trial, visit ClinicalTrials.gov.

About Trastuzumab Deruxtecan

Trastuzumab deruxtecan (fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, trastuzumab deruxtecan is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. Trastuzumab deruxtecan consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Trastuzumab deruxtecan (5.4 mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 based regimens based on the results from the DESTINY-Breast01 trial.

Trastuzumab deruxtecan (6.4 mg/kg) is approved in Israel, Japan, Singapore, and U.S. for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

About the Trastuzumab Deruxtecan Clinical Development Program

A comprehensive global development program is underway evaluating the efficacy and safety of trastuzumab deruxtecan monotherapy across multiple HER2 targetable cancers including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Trastuzumab deruxtecan was highlighted in the Clinical Cancer Advances 2021 report as one of two significant advancements in the "ASCO Clinical Advance of the Year: Molecular Profiling Driving Progress in GI Cancers," based on data from both the DESTINY-Gastric01 and DESTINY-CRC01 trials, as well as one of the targeted therapy advances of the year in non-small cell lung cancer (NSCLC) based on the interim results of the HER2 mutated cohort of the DESTINY-Lung01 trial.

Trastuzumab deruxtecan recently received its fourth Breakthrough Therapy Designation (BTD) in the U.S., which was for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received one or more prior anti-HER2-based regimens.

About the Daiichi Sankyo and AstraZeneca Collaboration

Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize trastuzumab deruxtecan in March 2019 and datopotamab deruxtecan (Dato-DXd) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of trastuzumab deruxtecan and datopotamab deruxtecan.

About Daiichi Sankyo in Oncology

The oncology portfolio of Daiichi Sankyo is powered by our team of world-class scientists that push beyond traditional thinking to create transformative medicines for people with cancer. Anchored by our DXd antibody drug conjugate (ADC) technology, our research engines include biologics, medicinal chemistry, modality and other research laboratories in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in the U.S. We also work alongside leading academic and business collaborators to further advance the understanding of cancer as Daiichi Sankyo builds towards our ambitious goal of becoming a global leader in oncology by 2025.