Phase III trial of darolutamide in patients with non-metastatic castration-resistant prostate cancer meets primary endpoint (for specialized target groups only)

On October 24, 2018 The Phase III ARAMIS (Androgen Receptor inhibiting Agent for MetastatIc-free Survival) trial that investigated darolutamide in men with non-metastatic castration-resistant prostate cancer (nmCRPC), met its primary endpoint (Press release, Bayer, OCT 24, 2018, View Source [SID1234530182]). Darolutamide significantly extended metastasis-free survival (MFS) compared to placebo. The safety profile and the tolerability of darolutamide observed in the ARAMIS trial were consistent with previously published data on darolutamide. ARAMIS is a randomized, multi-center, double-blind, placebo-controlled trial in patients with nmCRPC. Darolutamide is an investigational, oral androgen receptor (AR) antagonist developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company.

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"Despite recent advances in nmCRPC, there remains a high unmet need for additional treatment options that delay the time to metastases," said Scott Fields, MD, senior vice president and head of Oncology Development at Bayer’s Pharmaceutical Division. "We are encouraged by the results of the ARAMIS trial and look forward to presenting the full data at an upcoming scientific meeting."

Bayer plans to discuss the data from the ARAMIS trial with health authorities regarding the submission of a new drug application. Bayer has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for darolutamide in men with nmCRPC.

About the ARAMIS Trial
The ARAMIS trial is a randomized, Phase III, multi-center, double-blind, placebo-controlled trial evaluating the safety and efficacy of oral darolutamide in patients with nmCRPC who are currently being treated with androgen deprivation therapy (ADT) and are at risk for developing metastatic disease. More than 1,500 patients were randomized in a 2:1 ratio to receive 600 mg of darolutamide twice a day or matching placebo.

The primary endpoint of this trial is metastasis-free survival (MFS), defined as time between randomization and evidence of metastasis or death from any cause. The secondary objectives of this trial are overall survival (OS), time to first symptomatic skeletal event (SSE), time to initiation of first cytotoxic chemotherapy, time to pain progression and characterization of the safety and tolerability of darolutamide.

About Castration-Resistant Prostate Cancer (CRPC)
Prostate cancer is the second most commonly diagnosed malignancy in men worldwide. In 2018, an estimated 1.2 million men will be diagnosed with prostate cancer, and about 358,000 will die from the disease worldwide. Prostate cancer is the fifth leading cause of death from cancer in men.

Prostate cancer results from the abnormal proliferation of cells within the prostate gland, which is part of a man’s reproductive system. It mainly affects men over the age of 50, and the risk increases with age.

Treatment options range from surgery to radiation treatment to therapy using hormone-receptor antagonists, i.e. substances that stop the formation of testosterone or prevent its effect at the target location. However, in nearly all cases, the cancer will become resistant to conventional hormone therapy1.

CRPC is an advanced form of the disease where the cancer keeps progressing even when the amount of testosterone is reduced to very low levels in the body. The field of treatment options for castration-resistant patients is evolving rapidly, but until recently, there have been no approved treatment options for CRPC patients who have rising Prostate-Specific Antigen (PSA) levels during ADT and no detectable metastases. In men with progressive nmCRPC, a short PSA doubling time has been consistently associated with reduced time to first metastasis and death2.

About Darolutamide
Darolutamide is an investigational, non-steroidal androgen receptor antagonist with a chemical structure that binds to the receptor and exhibits antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. Darolutamide has also completed Phase 1/2 studies in patients with mCRPC. A Phase 3 study in metastatic hormone-sensitive prostate cancer (ARASENS) is ongoing. Information about these trials can be found at www.clinicaltrials.gov.

Darolutamide is not approved by the U.S. FDA, the European Medicines Agency or any other health authority.

LabCorp Announces 2018 Third Quarter Results and Updates 2018 Guidance

On October 24, 2018 LabCorp (or the Company) (NYSE: LH) reported results for the third quarter ended September 30, 2018, and updated its 2018 guidance (Press release, LabCorp, OCT 24, 2018, View Source;p=RssLanding&cat=news&id=2373135 [SID1234530177]).

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"We are pleased with our performance in the quarter, highlighted by excellent results in our Covance Drug Development business and solid results in LabCorp Diagnostics," said David P. King, chairman and chief executive officer. "Covance delivered growth in net orders, a strong book to bill and significant margin expansion, while Diagnostics continued its consistent organic revenue and volume growth. In addition, we made progress on our three strategic objectives, and initiated LaunchPad Phase II in Diagnostics to continue streamlining the business and reducing the fixed cost base. Despite the dynamically changing market, we have two strong businesses, outstanding cash flow and a strong balance sheet, positioning us well to deliver growth for the balance of this year and in the years ahead."

Effective January 1, 2018, the Company adopted the FASB-issued converged standard on revenue recognition (ASC 606), using the full retrospective method. Unless otherwise indicated, all financial results in 2017 and comparisons to financial results in 2017 have been restated in this press release as if the Company had adopted ASC 606 on January 1, 2017.

Consolidated Results

Third Quarter Results

Revenue for the quarter was $2.83 billion, an increase of 8.0% compared to $2.62 billion in the third quarter of 2017. The increase in revenue was primarily due to growth from acquisitions of 6.5% and organic growth of 2.8%, partially offset by the negative impact from the disposition of businesses of 1.1% and foreign currency translation of approximately 30 basis points. Revenue growth was negatively impacted by approximately 50 basis points due to the ransomware attack and Hurricane Florence (hereinafter "Business Disruptions") during the quarter.

Operating income for the quarter was $343.4 million, or 12.1% of revenue, compared to $326.7 million, or 12.5%, in the third quarter of 2017. The increase in operating income was primarily due to acquisitions, organic revenue growth, the Company’s LaunchPad business process improvement initiative, and fewer restructuring charges and special items. These drivers were partially offset by lower Medicare pricing as a result of the implementation of PAMA, costs related to the ransomware attack, the disposition of businesses, and personnel costs. The Company recorded restructuring charges, special items, and amortization which together totaled $85.8 million in the quarter, compared to $105.2 million during the same period in 2017. Adjusted operating income (excluding amortization, restructuring charges, and special items) for the quarter was $429.2 million, or 15.2% of revenue, compared to $431.9 million, or 16.5%, in the third quarter of 2017. The decline in adjusted operating margin was primarily due to the implementation of PAMA, the negative impact from the Business Disruptions, as well as the mix impact from the acquisition of Chiltern.

Net earnings in the quarter were $318.8 million, compared to $171.6 million in the third quarter of 2017. Diluted EPS were $3.10 in the quarter, an increase of 187.9% compared to $1.65 in the same period in 2017. Net earnings and diluted EPS in the quarter benefitted from the net gain on disposition of businesses of $125.3 million and $1.22 per share, respectively. Adjusted EPS (excluding amortization, restructuring charges, special items, and the net gain on disposition of businesses) were $2.74 in the quarter, an increase of 15.6% compared to $2.37 in the third quarter of 2017. The Company’s adjusted earnings in the quarter were reduced by approximately $0.10 per diluted share due to the impact from the Business Disruptions, primarily due to lower volume.

Operating cash flow for the quarter was $251.9 million, down from $350.5 million in the third quarter of 2017, as the benefit of higher cash earnings was more than offset by an increase in working capital, a discretionary pension contribution, and the impact from the Business Disruptions. Capital expenditures totaled $97.9 million, compared to $75.3 million a year ago. As a result, free cash flow (operating cash flow less capital expenditures) was $154.0 million, compared to $275.2 million in the third quarter of 2017.

At the end of the quarter, the Company’s cash balance and total debt were $892.6 million and $6.5 billion, respectively. During the quarter, the Company repurchased $150.0 million of stock representing approximately 0.8 million shares. The Company had $843.5 million of authorization remaining under its share repurchase program at the end of the quarter.

Year-To-Date Results

Revenue was $8.55 billion, an increase of 13.0% over last year’s $7.56 billion. The increase in revenue was due to growth from acquisitions of 10.0%, organic growth of 2.7%, and the benefit from foreign currency translation of approximately 60 basis points, partially offset by the impact from the disposition of businesses of 0.4%.

Operating income was $1,018.0 million, or 11.9% of revenue, compared to $974.7 million, or 12.9%, in the first nine months of 2017. The increase in operating income was primarily due to acquisitions, organic revenue growth, and the Company’s LaunchPad initiative, partially offset by the implementation of PAMA, costs related to the ransomware attack, and personnel costs. The decline in operating margin was primarily due to the implementation of PAMA, the negative impact from the Business Disruptions, as well as the mix impact from the acquisition of Chiltern. The Company recorded restructuring charges, special items, and amortization which together totaled $310.4 million in the first nine months of the year, compared to $265.1 million during the same period in 2017. This increase was primarily due to higher amortization expense, and the payment of a one-time bonus to non-bonus-eligible employees following the implementation of the Tax Cuts and Jobs Act of 2017. Adjusted operating income (excluding amortization, restructuring charges, and special items) was $1.33 billion, or 15.5% of revenue, compared to $1.24 billion, or 16.4%, in the first nine months of 2017.

Net earnings in the first nine months of 2018 were $725.8 million, or $7.04 per diluted share, compared to $539.4 million, or $5.19 per diluted share, last year. Net earnings and diluted EPS in the first nine months of 2018 benefitted from the net gain on disposition of businesses of $125.3 million and $1.22 per share, respectively. Adjusted EPS (excluding amortization, restructuring, special items, and the net gain on disposition of businesses) were $8.50, an increase of 22.7% compared to $6.93 in the first nine months of 2017.

Operating cash flow was $819.0 million, compared to $933.1 million in the first nine months of 2017, as the benefit of higher cash earnings was more than offset by an increase in working capital, a discretionary pension contribution, and the impact from the Business Disruptions. Capital expenditures totaled $257.6 million, compared to $216.8 million during the same period in 2017. As a result, free cash flow (operating cash flow less capital expenditures) was $561.4 million, compared to $716.3 million in the first nine months of 2017.

***

The following segment results reflect the Company’s retrospective adoption of ASC 606 on January 1, 2017, and exclude amortization, restructuring charges, special items and unallocated corporate expenses.

Third Quarter Segment Results

LabCorp Diagnostics

Revenue for the quarter was $1.75 billion, a decrease of 0.2% from $1.75 billion in the third quarter of 2017. Revenue benefitted from acquisitions and organic volume (measured by requisitions), offset by the negative impact from the disposition of businesses (described below) and the implementation of PAMA. In addition, foreign currency translation reduced revenue by approximately 20 basis points.

The Company’s Food Solutions business was divested on August 1, 2018, and the Company’s UK-based forensic laboratory testing business was divested on August 7, 2018. These divested businesses contributed $14.6 million in revenue in the quarter, compared to $43.0 million during the third quarter of 2017. Excluding the disposition of businesses, revenue for the quarter would have been $1.74 billion, an increase of 1.4% over $1.71 billion last year.

Excluding the disposition of businesses, revenue per requisition decreased by 0.4% and total volume (measured by requisitions) increased by 2.0%, of which organic volume was 1.3% and acquisition volume was 0.8%. Volume growth was negatively impacted by 0.6% due to the Business Disruptions.

Adjusted operating income (excluding amortization, restructuring charges and special items) for the quarter was $331.5 million, or 18.9% of revenue, compared to $374.3 million, or 21.3%, in the third quarter of 2017. Operating income and margin declined primarily due to the negative impact from PAMA, the ransomware attack, the disposition of businesses, and personnel costs, partially offset by acquisitions and organic volume growth.

Covance Drug Development

Revenue for the quarter was $1.08 billion, an increase of 24.7% over $867 million in the third quarter of 2017. The increase in revenue was primarily due to growth from acquisitions of 17.9%, and organic growth of 7.3%, partially offset by the impact from foreign currency translation of approximately 50 basis points.

Adjusted operating income (excluding amortization, restructuring charges and special items) for the quarter was $131.3 million, or 12.1% of revenue, compared to $93.8 million, or 10.8%, in the third quarter of 2017. The increase in operating income and margin were primarily due to organic demand, LaunchPad savings and acquisitions, partially offset by personnel costs. The Company expects to deliver $150 million of net savings from LaunchPad by the end of 2020, and $30 million of cost synergies from the integration of Chiltern by the end of 2019.

Net orders and net book-to-bill during the trailing twelve months were $5.26 billion and 1.25, respectively. Backlog at the end of the quarter was $9.40 billion compared to $8.97 billion last quarter, and the Company expects approximately $3.8 billion of its backlog to convert into revenue in the next twelve months.

Outlook for 2018

In the following guidance, all financial results in 2017 and comparisons to financial results in 2017 have been restated in this press release as if the Company had adopted ASC 606 on January 1, 2017. The guidance assumes foreign exchange rates effective as of September 30, 2018 for the remainder of the year, and includes capital allocation.

Revenue growth of 10.5% to 11.0% over 2017 revenue of $10.31 billion, which includes the benefit of approximately 40 basis points of foreign currency translation. This is a narrowing of the range from the prior guidance of 10.5% to 11.5%, and includes the impact from Business Disruptions of 10 basis points, as well as the 10 basis point unfavorable change in currency translation.
Revenue growth in LabCorp Diagnostics of 3.0% to 3.5% over 2017 revenue of $6.86 billion, which includes the negative impact of PAMA as well as the benefit of approximately 10 basis points of foreign currency translation. This is a narrowing of the range from the prior guidance of 3.0% to 4.5%, and now includes the impact from the Business Disruptions of 20 basis points, and the 10 basis point unfavorable change in currency translation.
Revenue growth in Covance Drug Development of 24.0% to 26.0% over 2017 revenue of $3.45 billion, which includes the benefit of approximately 110 basis points of foreign currency translation. This is a narrowing of the range from the prior guidance of 23.0% to 26.0%.
Adjusted EPS of $11.25 to $11.45, which is an increase of approximately 22.3% to 24.4% over 2017 adjusted EPS of $9.20. This is lower than the prior guidance of $11.35 to $11.65 primarily due to the negative impact from the Business Disruptions of $0.10 per share as well as third quarter performance.
Free cash flow (operating cash flow less capital expenditures) of $975 million to $1,025 million, compared to $1.1 billion in 2017. This is lower than the prior guidance of $1.1 billion to $1.2 billion primarily due to the upcoming tax payment of approximately $125 million related to the disposition of the Food Solutions business, which was not included in the prior guidance.
Use of Adjusted Measures

The Company has provided in this press release and accompanying tables "adjusted" financial information that has not been prepared in accordance with GAAP, including adjusted EPS, adjusted operating income, free cash flow, and certain segment information. The Company believes these adjusted measures are useful to investors as a supplement to, but not as a substitute for, GAAP measures, in evaluating the Company’s operational performance. The Company further believes that the use of these non-GAAP financial measures provides an additional tool for investors in evaluating operating results and trends, and growth and shareholder returns, as well as in comparing the Company’s financial results with the financial results of other companies. However, the Company notes that these adjusted measures may be different from and not directly comparable to the measures presented by other companies. Reconciliations of these non-GAAP measures to the most comparable GAAP measures are included in the tables accompanying this press release.

The Company today is furnishing a Current Report on Form 8-K that will include additional information on its business and operations. This information will also be available in the investor relations section of the Company’s website at View Source." target="_blank" title="View Source." rel="nofollow">View Source Analysts and investors are directed to the Current Report on Form 8-K and the website to review this supplemental information.

A conference call discussing LabCorp’s quarterly results will be held today at 9:00 a.m. EDT and is available by dialing 844-634-1444 (615-247-0253 for international callers). The access code is 7398818. A telephone replay of the call will be available through November 7, 2018, and can be heard by dialing 855-859-2056 (404-537-3406 for international callers). The access code for the replay is 7398818. A live online broadcast of LabCorp’s quarterly conference call on October 24, 2018, will be available at View Source or at View Source beginning at 9:00 a.m. EDT. This webcast will be archived and accessible through October 18, 2019.

Myovant Sciences Announces Completion of Enrollment in Phase 3 HERO Trial of Relugolix in Men with Advanced Prostate Cancer

On October 24, 2018 Myovant Sciences (NYSE: MYOV) reported it has completed patient enrollment in its pivotal Phase 3 clinical trial, HERO, which is evaluating the safety and efficacy of relugolix for the treatment of men with advanced prostate cancer (Press release, Myovant Sciences, OCT 24, 2018, http://investors.myovant.com/news-releases/2018/10-24-2018-133055538 [SID1234530139]). The HERO study is designed to support approval by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the Japanese Pharmaceuticals and Medical Devices Agency.

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"Completion of enrollment in HERO is a critical milestone for our prostate cancer program," said Lynn Seely, M.D., President and CEO of Myovant. "We look forward to reporting top-line efficacy and safety data for HERO in the fourth quarter of 2019. Relugolix is the only oral gonadotropin-releasing hormone, or GnRH, receptor antagonist in development to lower testosterone and prostate-specific antigen, or PSA, in men with prostate cancer."

Pending positive Phase 3 results, Myovant expects to submit a New Drug Application for relugolix with the FDA in early 2020. If approved, relugolix has the potential to be the first oral GnRH receptor antagonist approved for the treatment of advanced prostate cancer. Relugolix is administered as one pill once-daily and has been shown to decrease testosterone and PSA levels within days in Phase 1 and 2 clinical studies.

About the HERO Study
This randomized, open-label, parallel-group, international Phase 3 clinical trial is evaluating the safety and efficacy of relugolix in men with androgen-sensitive advanced prostate cancer who require at least one year of continuous androgen deprivation therapy. Patients enrolled in the study were randomized 2:1 to receive a single loading dose of relugolix 360 mg followed by relugolix 120 mg once daily or to treatment with leuprolide acetate 3-month depot injection, respectively. The primary efficacy outcome of the study is the ability of relugolix to achieve and maintain serum testosterone suppression to castrate levels (≤50 ng/dL [1.7 nmol/L]) for 48 weeks. A total of 934 patients have been enrolled in the HERO study in North and South America, Europe and the Asia-Pacific region.

About Advanced Prostate Cancer
Prostate cancer is the second most prevalent form of cancer in men and the second leading cause of death due to cancer in men in the United States. According to the National Cancer Institute, approximately 2.9 million men in the United States are currently living with prostate cancer, and approximately 165,000 men are estimated to be newly diagnosed in 2018. Treatment for advanced prostate cancer typically involves treatment with androgen deprivation therapy, which reduces testosterone to very low levels, commonly referred to as castration levels. GnRH agonists, such as leuprolide depot, or slow-release injections are the current standard of care for medical castration. However, GnRH agonists may be associated with mechanism-of-action limitations, including the potentially detrimental initial rise in testosterone levels that can exacerbate clinical symptoms, which is known as clinical or hormonal flare, and delayed testosterone recovery if the drug is discontinued.

OncoSec Announces Publication of Data in Nature Gene Therapy Demonstrating the Ability of its Newly Optimized Intratumoral IL-12 Immunotherapy Platform to Increase Systemic Anti-tumor Responses in both Treated and Untreated Lesions

On October 24, 2018 OncoSec Medical Incorporated (OncoSec) (NASDAQ:ONCS), a company developing intratumoral cancer immunotherapies, reported the publication of a study in the peer-reviewed journal, Nature Gene Therapy (an open access article; View Source), demonstrating that the newly optimized intratumoral IL-12 immunotherapy platform (electroporation-mediated intratumoral IL-12 gene therapy) induces immunological changes in both locally-treated and distant, untreated tumors (Press release, OncoSec Medical, OCT 24, 2018, View Source [SID1234530143]). The publication provides new mechanistic insights into this systemic anti-tumor immunity including the observation that IL-12 primed effector T cells diminished expression of PD-1, which is particularly relevant to Oncosec’s ongoing KEYNOTE-695 clinical study.

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The paper, titled "Characterization of abscopal effects of intratumoral electroporation-mediated IL-12 gene therapy," by Mukhopadhyay et al., reported results from a pre-clinical study of OncoSec’s optimized plasmid IL-12 (TAVO) therapeutic platform on both locally-treated and distant, untreated lesions, with a particular emphasis on understanding "abscopal" effects in distant non-electroporated tumors. Results from the study indicated that intratumoral IL-12 treatment led to an induction of IL-12-regulated genes, other cytokines and chemokines pathways, as well as genes for enhanced antigen processing and presentation in the treated tumor. These localized IL-12-mediated effects then led to the generation of systemic anti-tumor immune responses, including a surge of CD8+ T cells in the spleen and in non-treated tumors and when coupled with PD-1 modulation, suggests an orchestrated "armoring" of these effector T cells against T-cell checkpoints when primed in the presence of IL-12 in situ.

"Data from previously completed clinical and pre-clinical studies of our TAVO platform in multiple cancer settings has clearly demonstrated that our intratumoral electroporation-mediated IL-12 gene therapy is safe and produces systemic anti-tumor effects from a local delivery of this potent cytokine," said Christopher G. Twitty, PhD, Chief Scientific Officer of OncoSec. "Based on these outcomes, OncoSec is advancing an optimized version of TAVO that is designed to increase transgene expression and efficacy. The study published in Gene Therapy indicates that tumors treated directly with the optimized TAVO therapy rapidly engage IL-12/IFN-g regulated pathways, altering the tumor microenvironment’s immunogenicity and effectively creating an in situ vaccine that ultimately drives an increase of tumor infiltrating lymphocytes and immune-specific gene expression in both treated and distant untreated tumors, indicative of a de novo immune response. These results confirm that OncoSec’s TAVO platform may represent a mechanism by which local intratumoral IL-12 gene therapy can deliver a safe and effective abscopal response."

Orion and Bayer have completed the phase III trial of darolutamide in patients with non-metastatic castration-resistant prostate cancer – The primary endpoint was met

On October 24, 2018 Orion and Bayer reported that they have completed the phase III clinical trial (ARAMIS) of darolutamide, the novel oral androgen receptor antagonist for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) (Press release, Orion Pharma, OCT 24, 2018, View Source;the-primary-endpoint-was-met/ [SID1234530144]). The primary endpoint of the trial was met: Darolutamide significantly extended metastasis-free survival compared to placebo.The safety profile and the tolerability of darolutamide observed in the ARAMIS trial were consistent with previously published data on darolutamide.

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The full data will be presented at an upcoming scientific meeting. Bayer plans to discuss the data from the ARAMIS trial with health authorities regarding the submission for marketing authorization application. As a rule, Orion will provide information on the progress of the marketing authorization application process in a press release or in its financial reports. Darolutamide has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment in men with nmCRPC.

The ARAMIS trial

Commenced in 2014, the ARAMIS trial evaluated the efficacy and safety of darolutamide in patients with non-metastatic castration-resistant prostate cancer who are currently being treated with androgen deprivation therapy (ADT) as standard of care and are at risk of developing metastatic disease. In the double-blind, placebo-controlled trial, more than 1,500 patients were randomized to receive 600 mg of darolutamide or matching placebo twice a day. The primary endpoint was metastasis-free survival, defined as time between randomization and evidence of metastasis or death from any cause.

Financial terms

Darolutamide was developed jointly by Orion and Bayer, and the partnership was announced in a stock exchange release on 2 June 2014. Bayer has covered the majority of the darolutamide development costs. According to the agreement, Bayer has the right to commercialize darolutamide globally while Orion has the option of co-promoting the product in Europe. In addition, Orion will manufacture the product for global markets.

Orion is eligible to receive milestone payments from Bayer upon first commercial sale of darolutamide as follows:

EUR 45 million upon first commercial sale in the United States
EUR 20 million upon first commercial sale in the EU
EUR 8 million upon first commercial sale in Japan

Besides milestone payments, Orion will also receive tiered royalties on the product sales, which will be approximately 20 percent, including production revenue. With sales increase, royalties may increase slightly. Orion also has the possibility to receive one-off payments from Bayer if certain sales targets are met.

In addition to the completed ARAMIS trial, Orion and Bayer have an ongoing phase III clinical trial (ARASENS) which evaluates the safety and efficacy of darolutamide in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Expected to be completed in 2022, there are no separate milestone payments related to the ARASENS trial.

"Prostate cancer is the second most commonly diagnosed malignancy in men in worldwide, and approximately 70 percent of patients have the non-metastatic form of the disease. While conventional hormone therapy is effective in the treatment of non-metastatic cancer, the efficacy is often eventually lost as the sole form of treatment. Additional treatment options in the early stages of the cancer that delay the time to metastases with a manageable safety profile are long awaited. They are significant for the patient’s overall well-being," says Christer Nordstedt, Senior Vice President, Research and Development at Orion.