On February 20, 2019 Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of cancer, autoimmune diseases, asthma and allergic diseases, reported that the U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on its Phase 1 study of XmAb14045, a CD123 x CD3 bispecific antibody molecule being evaluated in patients with relapsed or refractory acute myeloid leukemia and other CD123-expressing hematologic malignancies (Press release, Xencor, FEB 20, 2019, View Source [SID1234533491]). Patients currently on treatment and benefiting from treatment may continue treatment on the study. No new patients will be allowed to enroll in the study until the partial clinical hold is lifted by the FDA.

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The partial clinical hold was initiated following recent safety reports Xencor submitted to the FDA on two patient deaths that were considered at least possibly related to XmAb14045. One patient experienced cytokine release syndrome (CRS) after their first dose, the treatment of which was complicated by the patient’s decision to withdraw care. One patient developed acute pulmonary edema following several doses of XmAb14045. The FDA has placed the trial on partial clinical hold pending review of additional details regarding these events, safety and efficacy information across the study, and satisfactory review of amendments to the study protocol and related documents. Xencor will be working closely with the FDA to review these events and resolve the partial clinical hold.

"Patient safety is Xencor’s highest concern," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "We are working with the investigators and the FDA and will provide an update when more information about resuming enrollment can be shared. Our ongoing Phase 1 studies evaluating our other CD3 bispecific antibodies, XmAb13676 and XmAb18087, are not affected."

About XmAb14045

XmAb14045 is a tumor-targeted antibody that contains both a CD123 binding domain and a cytotoxic T-cell binding domain (CD3) in a Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and other CD123-expressing hematologic malignancies. An XmAb Bispecific Fc domain serves as the scaffold for these two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on XmAb14045. CD123 is highly expressed on AML cells and leukemic stem cells, and it is associated with poorer prognosis in AML patients. Engagement of CD3 by XmAb14045 activates T cells for highly potent and targeted killing of CD123-expressing tumor cells.

On February 20, 2019 The Melanoma Research Alliance (MRA), the largest non-profit funder of melanoma research worldwide, reported the U.S. Food & Drug Administration (FDA) approval of Merck’s pembrolizumab (Keytruda) in the adjuvant setting for melanoma patients with lymph node involvement following complete lymph node resection (Press release, Melanoma Research Alliance, FEB 20, 2019, View Source [SID1234533510]).

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Melanoma, the deadliest skin cancer, is the fifth most common cancer in the U.S. An estimated 9% of new cases have spread to lymph nodes or nearby sites around the tumor— referred to as Stage III disease—with correspondingly high risk of recurrence and death. Reducing the risk of recurrence after surgery represents a major opportunity to eliminate melanoma suffering and death.

"Over the last year we have seen a flurry of drug approvals that help reduce the risk of recurrence for high-risk Stage III melanoma following surgery while reducing treatment-related side effects," said Chief Science Officer Marc Hurlbert, Ph.D. "This is important because it makes more treatment options available to patients and assists in making the decision to start adjuvant therapy that much easier for patients and their doctors."

Pembrolizumab, an anti-PD-1 antibody, works by stimulating the patient’s immune system to attack melanoma by promoting the tumor-killing effectiveness of T cells. It was first approved for the treatment of unresectable or metastatic melanoma in 2014 and has since gained FDA approval to treat multiple cancers, including certain cancers of the lung, bladder and blood.

"Giving patients access to more, better tolerated, treatments to choose from at an earlier stage of disease is critical to achieving our mission of ending suffering and death due to melanoma," said MRA President & CEO Michael Kaplan.

Without adjuvant therapy, about 60% of Stage III melanoma patients will relapse within three years of surgical resection. While adjuvant therapy works to reduce this risk, it does have its own range of side effects. Doctors and patients must work together to weigh the relative benefits of adjuvant therapy.

FDA approval of pembrolizumab in the adjuvant setting is based on results from the KEYNOTE-054 trial. In this phase-three study, pembrolizumab significantly reduced melanoma recurrence/death (26%) compared with patients receiving placebo (43%). The safety of pembrolizumab has been evaluated in 4,948 patients with various cancers and the most commonly reported adverse reactions were fatigue, rash, and nausea.

On February 20, 2019 ICON plc (NASDAQ: ICLR), a global provider of drug development solutions and services to the pharmaceutical, biotechnology and medical device industries, reported its financial results for the fourth quarter and full year ended December 31, 2018 (Press release, ICON, FEB 20, 2019, View Source [SID1234533511]).

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CEO Dr. Steve Cutler commented, "During 2018, ICON’s operational excellence and market leading service offerings resulted in net business bookings of over $2.4 billion and the expansion of our backlog by 10% to $5.4 billion. Our revenues grew by 8% year over year and our continued focus on pro-active cost saving efficiencies enabled us to grow EPS by over 14% to $6.16.

Today we are delighted to announce the acquisition of MolecularMD. MolecularMD enhances our laboratory offering in molecular diagnostic testing, a key area in oncology research, and also brings to ICON expanded testing platforms, including next generation sequencing and immunohistochemistry. MolecularMD’s services also include companion diagnostic development which will further enhance the competitiveness of our overall lab offering.

We are also delighted to announce the extension of ICON’s master services agreement with Pfizer. The extension of the agreement reflects our strong working relationship with Pfizer and we look forward to continuing to help Pfizer advance its development pipeline rapidly and efficiently.

As we look forward, we expect 2019 to be another year of robust revenue and earnings growth and we reaffirm our outlook with revenue guidance in the range of $2,735 – $2,835 million and earnings per share guidance in the range of $6.69 – $6.89, a year over year increase of 10% – 13%."

Fourth Quarter 2018 Results

Excluding the impact of ASC 606, gross business wins in the fourth quarter were $722 million and cancellations were $115 million. This resulted in net business wins of $607 million, a book to bill of 1.25.

Reported revenue for quarter 4 was $679.0 million. Excluding the impact of ASC 606, quarter 4 revenue increased to $484.7 million from $455.1 million in the same quarter last year, an increase of 6.5%.

Reported income from operations in the quarter was $101.8 million or 15.0% of revenue. Excluding the impact of ASC 606, income from operations increased by 14.2% to $102.4 million, or 21.1% of revenue, compared to $89.7 million or 19.7% for the same quarter last year.

Reported net income for the quarter was $88.2 million or 13.0% of revenue. Excluding the impact of ASC 606, net income increased by 13.0% to $88.7 million, compared with $78.5 million in the same quarter last year.

Reported earnings per share on a diluted basis was $1.62. Excluding the impact of ASC 606, diluted earnings per share increased by 13.8% to $1.63, compared to $1.43 per share for the same quarter last year.

Days sales outstanding on a 605 basis, comprising accounts receivable and unbilled revenue less payments on account, were 57 days at December 31, 2018, compared with 49 days at the end of December 2017.

Cash generated from operating activities for the quarter was $60.9 million. During the quarter, capital expenditure was $20.0 million and $72 million worth of stock was repurchased at an average price of $137.66. As a result, at December 31, 2018, the company had net cash of $106.5 million, compared to net cash of $142.3 million at September 30, 2018 and net cash of $11.6 million at the end of December 2017.

Full Year 2018 Results

Excluding the impact of ASC 606, full year gross business wins were $2,860 million and cancellations were $459 million. This resulted in net business wins of $2,401 million, a book to bill of 1.27.

Full year reported revenue was $2,595.8 million. Excluding the impact of ASC 606, full year revenue increased to $1,897.6 million from $1,758.4 million in 2017, an increase of 7.9%.

Full year reported income from operations before non-recurring charges was $385.8 million or 14.9% of revenue. Excluding the impact of ASC 606, income from operations before non-recurring charges increased by 12.7% to $390.0 million, or 20.6% of revenue, compared to $346.1 million or 19.7% of revenue in the previous year.

Full year reported net income before non-recurring charges was $333.7 million or 12.9% of revenue. Excluding the impact of ASC 606, net income before non-recurring charges increased by 14.1% to $337.4 million, compared with $295.7 million last year.

Full year reported earnings per share on a diluted basis before non-recurring charges was $6.09. Excluding the impact of ASC 606, diluted earnings per share before non-recurring charges increased by 14.2% to $6.16, compared to $5.39 per share last year.

Pfizer Master Services Agreement extension

The extension extends the term of the agreement signed in June 2016 from a 3 year term with Pfizer having the right to extend the term by a further 2 years, to a term of 4 years with Pfizer retaining the right to extend the term by a further 2 years.

On February 20, 2019 Sunstar, a multi-national healthcare company based on oral care reported the acquisition from BMG Pharma S.p.A. of the innovative cancer supportive care product, GelX (Press release, SUNSTAR Americas, FEB 20, 2019, View Source [SID1234553908]). Through this acquisition Sunstar gains global distribution of this product line, expanding its position as a global leader in the development and commercialisation of oral healthcare products, mainly marketed under the GUM brand.

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BMG Pharma S.p.A, an innovative specialty pharmaceutical company, will invest the proceeds from this transaction into the rapid development completion of a number of new patent protected products with topical, subcutaneous dermatology, osteoarthritis and oral care applications, which it will be able to offer to its network of global marketing partners.

Takeshi Kamigouchi, CEO of Sunstar Suisse SA, commented– "We are proud and excited to distribute the superior product GelX to make the difference in cancer patients’ oral conditions globally. Our purpose is to develop and provide products and services that promote mouth & body concept to extend people’s healthy lifespan and improve their quality of life. GelX is truly expected as a product that plays a key role that demonstrates we are the purpose driven company."

Marco Mastrodonato, CEO of BMG Pharma S.p.A., commented– "I have been partnering with Sunstar since 2002 with a win-win partnership in the oral care segment and at BMG are very proud to be the development and provider partner to a global oral care market leader. This is an important step for the company, bringing a strategic investment which represents a significant growth opportunity by allowing focus on the rapid completion of a number of products in our pipeline with unique propositions.

On February 20, 2019 Five Prime Therapeutics, Inc. (NASDAQ: FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that it initiated patient dosing in the Phase 1b dose expansion portion of the Phase 1a/1b clinical trial of FPA150 (FPA150-001; NCT03514121), a first-in-class immuno-oncology antibody that targets B7-H4 (Press release, Five Prime Therapeutics, FEB 20, 2019, View Source [SID1234533512]).

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"We are very pleased with the progress of our FPA150 clinical program that began with a dose escalation study in solid tumors and rapidly proceeded to an exploratory basket cohort of tumors that over-express B7-H4," said Helen Collins, Senior Vice President and Chief Medical Officer. "We have now dosed the first patient in the Phase 1b dose expansion portion of the trial. FPA150 specifically targets B7-H4, which is in the same family of checkpoint inhibitors as PD-L1 and is over-expressed in breast and gynecological cancers that are not well served by immunotherapy. We are hopeful that a targeted immunotherapy like FPA150 will provide clinical benefit to these patients who have limited treatment options."

The objective of the Phase 1b dose expansion is to evaluate the safety, tolerability, pharmacokinetics (PK) and potential preliminary clinical benefit of FPA150 monotherapy in patients with breast, ovarian and endometrial cancers that over-express B7-H4. A subgroup of patients in the Phase 1b portion will undergo pre- and on-treatment biopsies to assess the pharmacodynamic effects of FPA150 on the tumor and the tumor microenvironment, including changes in markers of tumor immune infiltrates and cytokine levels. Endpoints for the Phase 1b portion include objective response rate (ORR), duration of response and progression-free survival (PFS).

About FPA150

FPA150 is a novel, fully human, afucosylated monoclonal antibody targeting B7-H4. B7-H4 expression is observed in multiple solid tumors, including breast and gynecologic cancers. FPA150 is designed with a dual mechanism of action: blocking the T cell checkpoint activity of B7-H4 as well as delivering ADCC against tumor cells expressing B7-H4.