On September 6, 2016 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported positive top-line results from its Phase 2b STORM study evaluating the activity of selinexor (KPT-330) in multiple myeloma (MM) (Press release, Karyopharm, SEP 6, 2016, View Source [SID:1234514955]). Selinexor, the Company’s lead, novel, oral Selective Inhibitor of Nuclear Export / SINE compound, is being developed for the treatment of a variety of malignancies, including MM. Karyopharm also provided an overview of the planned development path for selinexor in MM.

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The Phase 2b STORM study is a single-arm clinical trial evaluating selinexor in combination with low-dose dexamethasone in heavily pretreated MM patients, meaning patients with quad-refractory disease or penta-refractory disease. Patients with quad-refractory disease have previously received two proteasome inhibitors (PIs) (bortezomib (Velcade) and carfilzomib (Kyprolis)) and two immunomodulatory agents (IMiDs) (lenalidomide (Revlimid) and pomalidomide (Pomalyst)), and their disease is refractory to at least one PI, at least one IMiD, and has progressed following their most recent therapy. Patients with penta-refractory myeloma have quad-refractory disease that is also refractory to an anti-CD38 monoclonal antibody, such as daratumumab (Darzalex) or isatuximab.

Among the 78 evaluable patients (median seven prior treatment regimens), the overall response rate (ORR) was 20.5% based on Independent Review Committee adjudication, including very good partial responses (VGPR) and partial responses (PR). Among the 48 patients in the quad-refractory group, the ORR was 20.8%. For comparison, in a similar quad-refractory patient population, Darzalex had an ORR of 21% and isatuximab had an ORR of 20%. Among the 30 patients in the penta-refractory group, the ORR was 20.0%. Several patients remain on study, including those with VGPRs, PRs and minor responses. To the Company’s knowledge, no agent has previously shown activity in this penta-refractory population. The side effect profile for selinexor was consistent with previous trials, and no new safety signals were identified. Additional data will be presented later this year.

Keith Stewart, MB. ChB., Anna Maria and Vasek Polack Professor of Cancer Research at the Mayo Clinic and lead investigator of the STORM study, said, "Although treatment of multiple myeloma has improved dramatically, eventually many patients will develop refractory disease, no longer responding to any of the immunomodulatory agents and proteasome inhibitors commonly used (quad-refractory). These patients will also eventually progress on anti-CD38 monoclonal antibodies, which we refer to as penta-refractory disease. These are clearly the patients with the highest unmet need, as they have no remaining viable treatment options. The STORM data are compelling because they demonstrate that oral selinexor achieves a 20.8% response rate in the quad-refractory group, similar to recently reported intravenous anti-CD38 therapy results in the same patient population. Selinexor also achieves an equally notable 20.0% response rate in the penta-refractory group, with the significant advantage of oral administration. We are currently unaware of any other therapy, oral or intravenous, reporting such activity in these difficult-to-treat patients who have exhausted all available therapies."

In addition to the STORM study, Karyopharm initiated the Phase 1b/2 STOMP (Selinexor and Backbone Treatments of Multiple Myeloma Patients) study to evaluate selinexor in combination with existing therapies across the broader population in MM. In the arm evaluating the combination of selinexor, bortezomib and dexamethasone, dose escalation has been completed and the recommended dose has been determined, providing a basis for the randomized Phase 3 "BOSTON" study described below.

Sagar Lonial, MD, Professor and Chair, Department of Hematology and Medical Oncology, Emory University School of Medicine and Chief Medical Officer, Winship Cancer Institute of Emory University, commented, "Myeloma continues to be an incurable blood cancer in most patients and our main goal in treating refractory disease is to induce responses and maintain them as long as possible. In addition to these new data with oral selinexor and low-dose dexamethasone, the emerging clinical data from selinexor in combination with bortezomib, including in proteasome-inhibitor refractory disease, suggests a synergistic effect and favorable safety profile. These data are quite exciting and will form the basis for future studies."

Selinexor: Multiple Myeloma Clinical Development Plans and Timelines

Based on these positive top-line STORM data and existing unmet medical need, Karyopharm plans to implement the following clinical development initiatives focusing on obtaining regulatory approval of selinexor in MM:

Karyopharm is expanding the STORM study to include approximately 120 additional patients with penta-refractory MM. To the Company’s knowledge, this will be the largest study ever undertaken in this patient population. Assuming a positive outcome and remaining unmet medical need, Karyopharm intends to use the data from the expanded STORM study to support a request that the FDA consider granting accelerated approval for selinexor in MM. The Company anticipates reporting top-line data from the expanded cohort in early 2018.

The FDA instituted its Accelerated Approval Program to allow for expedited approval of drugs that treat serious conditions and that fill an unmet medical need based on a surrogate endpoint or an intermediate clinical endpoint thought to predict clinical benefit, like ORR. Accelerated approval is available only for drugs that provide a meaningful therapeutic benefit over existing treatments at the time of consideration of the application for accelerated approval, which the FDA has reiterated in its feedback to the Company. Particularly in disease areas with multiple available and potential new therapies, such as MM, accelerated approval carries a high regulatory threshold. Drugs approved under the Accelerated Approval Program are also typically required to be studied in randomized confirmatory trials on a post-approval basis to confirm clinical benefit. Given the number of approved and experimental therapies in development to treat MM, and consistent with its standard guidance, the FDA has recommended that the Company conduct a randomized study geared towards full approval, which the Company is planning with the BOSTON study discussed below. In addition, to the Company’s knowledge, no other studies are currently being conducted in the penta-refractory patient population and no agents have shown activity in these patients. In light of this unmet medical need, the Company believes that positive data in this patient population could support accelerated approval. The FDA has stated to the Company that other therapies in MM may receive full approval prior to the potential action date on any accelerated approval request for selinexor that the Company may submit, which may prevent accelerated approval for selinexor if the FDA deems that such therapies constitute earlier lines of therapy in MM that were not administered to patients in the STORM study. Also, while the FDA has previously indicated its preference for studies that isolate the effects of individual drugs, steroids like dexamethasone are part of nearly every myeloma treatment regimen, and low-dose dexamethasone is not a single-agent treatment for MM. Other available therapies for MM, such as pomalidomide (Pomalyst), have received accelerated approval based on studies that were conducted in combination with dexamethasone or a similar steroid. Based on these factors, the Company believes that the STORM study design and the planned expansion in the penta-refractory patient group present an opportunity for the Company to request that the FDA grant accelerated approval if data from the expansion confirm the data presented today.

The Company also plans to initiate a pivotal randomized Phase 3 study, known as the BOSTON (Bortezomib, Selinexor and dexamethasone) study, which will evaluate selinexor in combination with bortezomib (Velcade) and low-dose dexamethasone (SVd) compared to bortezomib and low-dose dexamethasone (Vd) in patients with MM who have had one to three prior lines of therapy. Based on data from the Phase 1b portion of the STOMP study, which was most recently presented at the 2016 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting, the Company has identified the combination dose to be used in the BOSTON study. Karyopharm expects that the study will enroll approximately 360 patients. The Company intends to seek additional FDA input on the protocol for the BOSTON study prior to commencing the trial in early 2017.

Based in part on its plans to conduct the pivotal randomized BOSTON study to support full regulatory approval of selinexor for patients with previously-treated MM and the Company’s planned expansion of STORM to support potential accelerated approval, Karyopharm will not pursue the SCORE study at this time. The SCORE study was designed to assess the combination of selinexor with carfilzomib (Kyprolis) and low-dose dexamethasone. The ongoing Phase 1/2 investigator sponsored study evaluating selinexor in combination with carfilzomib and dexamethasone in refractory MM, including carfilzomib-refractory MM, continues to enroll patients, and updated data from this study is expected to be presented later this year.
"Our updated clinical development plan for selinexor in myeloma reflects the strong foundation of clinical data from both the STORM and STOMP studies," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. Dr. Kauffman was instrumental in the clinical development and regulatory approvals of Velcade and Kyprolis in MM. "We believe this development plan provides a path to potential FDA and EMA filings for oral selinexor in MM, with the potential to support accelerated or conditional approval if the FDA or EMA, respectively, agree. We look forward to sharing the additional data from both STORM and STOMP later this year. We believe selinexor has the potential to be a much-needed oral treatment option for patients suffering with this incurable disease."

More About the Phase 2b STORM Study

The Phase 2b STORM (Selinexor Treatment of Refractory Myeloma) (NCT02336815) study is a multi-center, single-arm clinical trial evaluating selinexor in combination with low-dose dexamethasone in patients with heavily-pretreated multiple myeloma (MM), which the Company refers to as having at least quad-refractory MM. These are patients who have received bortezomib (Velcade) and carfilzomib (Kyprolis), each of which is a proteasome inhibitor (PI), and lenalidomide (Revlimid) and pomalidomide (Pomalyst), each of which is an immunomodulatory agent (IMiD), and whose disease is refractory to at least one PI, at least one IMiD, and is refractory to their most recent therapy. Prior treatment regimens must have also included an alkylating agent and a glucocorticoid. In the original version of the protocol, at least 25% of patients in this study must have had MM that is also refractory to an anti-CD38 monoclonal antibody, such as daratumumab (DarzalexTM), which the Company refers to as having penta-refractory MM. Of the 79 patients enrolled in the first cohort, 78 had measurable disease at baseline, with 48 (62%) patients classified as having quad-refractory and 30 (38%) patients classified as having penta-refractory MM.

The primary endpoint of the STORM study is overall response rate (ORR). The original trial had several secondary endpoints, including ORR in patients whose disease is relapsed/refractory to an anti-CD38 monoclonal antibody, duration of response (DOR) and clinical benefit rate (CBR). Karyopharm is now expanding the STORM study to include additional sites in the United States and Europe to enroll approximately 120 additional patients with penta-refractory MM to further evaluate the safety and efficacy of selinexor as a basis for potential regulatory submission requesting accelerated (FDA) or conditional (EMA) approval, based on ORR.

More About the Phase 1b/2 STOMP Study

The Phase 1b/2 STOMP (NCT02343042) study is a multi-arm clinical trial evaluating selinexor and low-dose dexamethasone in combination with backbone therapies bortezomib (Velcade), pomalidomide (Pomalyst) or lenalidomide (Revlimid) in patients with heavily pretreated relapsed/refractory MM. Each combination is evaluated on a separate arm of the STOMP study and, within each combination, each of two treatment cohorts will receive either once weekly or twice weekly dosing of selinexor.

Data from the STOMP study was initially reported at the European Hematology Association (EHA) (Free EHA Whitepaper) 2016 annual meeting. As of June 8, 2016, of the 16 patients treated in the SVd combination arm, all of whom are evaluable, 11 responded (1 patient with a complete response (CR), 3 with VGPRs and 7 with PRs for an ORR of 69%). An additional three patients achieved a minor response (MR), for a CBR of 88%. Several of the patients on this selinexor, Velcade and low-dose dexamethasone (SVd) combination arm had high-risk haplotypes, including deletion of chromosome 17p, and 10 of the 16 evaluable patients had MM previously refractory to a proteasome inhibitor. Seven of these 10 patients responded (1 CR, 1 VGPR, and 5 PRs) for an ORR of 70%. An additional patient achieved an MR for a CBR of 80% in this subgroup. Overall, side effects reported in the SVd arm were similar to, or less severe than, those observed with single-agent selinexor. Karyopharm plans to submit updated data from the STOMP study for presentation at a medical conference later this year. The Company is also planning to add two additional arms to the STOMP study — one to evaluate selinexor in combination with daratumumab (Darzalex) and the other to evaluate selinexor in combination with Pomalyst, Velcade and low-dose dexamethasone.

About Selinexor

Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export / SINE compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. Over 1,600 patients have been treated with selinexor in company- and investigator-sponsored Phase 1 and Phase 2 clinical trials in advanced hematologic malignancies and solid tumors. Selinexor is currently being evaluated in several mid- and later-stage clinical trials, including a Phase 2b single-arm trial of selinexor and low-dose dexamethasone in multiple myeloma (STORM), a Phase 1b/2 trial in combination with backbone therapies in multiple myeloma (STOMP), a Phase 2 trial in older patients with acute myeloid leukemia (SOPRA), a Phase 2b trial in diffuse large B-cell lymphoma (SADAL), and a Phase 2/3 trial in liposarcoma (SEAL), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types to further inform the Company’s clinical development priorities for selinexor. The latest clinical trial information for selinexor is available at www.clinicaltrials.gov.

About Multiple Myeloma

Multiple myeloma (MM) is form of blood cancer that develops in the bone marrow. In multiple myeloma, normal plasma cells transform into malignant myeloma cells and produce large quantities of an abnormal immunoglobulin called monoclonal protein or M protein. The monoclonal protein produced by myeloma cells interferes with normal blood cell production. In addition, the levels of functional immunoglobulins are depressed in individuals with multiple myeloma. Although the process is not completely understood, it appears that the functional immunoglobulins made by existing, healthy plasma cells breaks down more quickly in patients with multiple myeloma than in healthy individuals. MM is the second most commonly diagnosed blood cancer after Non-Hodgkin’s Lymphoma (NHL). According to SEER data from the National Cancer Institute, in the United States in 2016 approximately 30,000 new cases of MM will be diagnosed, and approximately 12,500 patients will die from the disease. Approximately 100,000 people in the United States were living with MM in 2013. According to GlobalData, the 2015 MM market was valued at approximately $11 billion and the size of the myeloma market is projected to increase to over $22 billion by 2023.

On September 6, 2016 Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a biopharmaceutical company committed to improving patient lives by manufacturing high quality products for biotechnology and pharmaceutical companies and advancing its proprietary R&D pipeline, reported that the National Comprehensive Cancer Network (NCCN) Oncology Research Program (ORP) has awarded three grants to investigators to support research of bavituximab in combination with other therapeutics for the treatment of glioblastoma, head and neck cancer, and hepatocellular carcinoma (Press release, Peregrine Pharmaceuticals, SEP 6, 2016, View Source [SID:1234514951]).

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NCCN, a not-for-profit alliance of 27 of the world’s leading cancer centers devoted to patient care, research, and education, is dedicated to improving the quality, effectiveness, and efficiency of cancer care so that patients can live better lives. Funding for the three investigator-initiated clinical studies will take place through a $2 million research grant made by Peregrine to NCCN’s ORP. NCCN will be responsible for oversight and monitoring of the clinical studies through the research grant. It is expected that the selected trials will be initiated in early 2017.
"NCCN is excited to initiate three studies by accomplished investigators at NCCN Member Institutions that will explore the effect of this novel immunotherapy in three different cancers with significant unmet need," said Robert C. Young, MD, Interim Vice President, NCCN ORP.
The following NCCN-affiliated researchers were recipients of the grant awards:
Jessica Frakes, MD, Moffitt Cancer Center, "A Phase I Trial of Sorafenib and Bavituximab Plus Stereotactic Body Radiation Therapy (SBRT) for Unresectable Hepatitis C Associated Hepatocellular Carcinoma"

Elizabeth Gerstner, MD, Massachusetts General Hospital Cancer Center, "Phase I/II Clinical Trial of Bavituximab with Radiation and Temozolomide for Patients with Newly Diagnosed Glioblastoma"

Ranee Mehra, MD, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, "Phase II Study of Pembrolizumab and Bavituximab for Progressive Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck"
"Our collaboration with NCCN provides the unique opportunity to support the group’s highly-regarded research institutions and advance our understanding of the potential role of bavituximab in the treatment of various cancers. With this in mind, we were very pleased by the level of interest shown in bavituximab from the NCCN community and are grateful to all those who submitted their projects for rigorous evaluation by the ORP scientific review committee," said Joseph Shan, MPH, vice president, clinical and regulatory affairs of Peregrine. "We’d like to extend our congratulations to the three investigators who were selected for their unique and innovative concepts. These studies align with our development strategy for bavituximab which is currently focused on small, early stage clinical trials evaluating the drug in combination with other cancer treatments. Collaborators such as NCCN play a central role in this strategy and we look forward to integrating the valuable clinical data generated by these investigators to expand our knowledge regarding bavituximab-focused cancer treatment combinations."
Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab is believed to override PS mediated immunosuppressive signaling by blocking the engagement of PS with its receptors as well as by sending an alternate immune activating signal. PS targeting antibodies have been shown to shift the functions of immune cells in tumors, resulting in multiple signs of immune activation and anti-tumor immune responses.

O September 5, 2016 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) reported that the first patient has been dosed in the safety evaluation phase of a phase 2/3 combination trial of MOR208 with bendamustine (Press release, MorphoSys, SEP 5, 2016, View Source [SID:1234514927]). The B-MIND trial (Bendamustine-MOR208 IN DLBCL) will evaluate the safety and efficacy of MOR208 combined with the chemotherapeutic agent bendamustine in comparison to rituximab plus bendamustine. The randomized international study will enroll adult patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplantation. DLBCL is the most common form of non-Hodgkin’s lymphoma (NHL). Following the phase 2 safety evaluation part, the study is expected to be transitioned into a pivotal phase 3 part in 2017. The investigational drug MOR208 is an Fc-enhanced monoclonal antibody targeting CD19, and is being developed for the treatment of patients with B cell malignancies.

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"We are truly excited to begin the phase 2/3 B-MIND trial with MOR208 in DLBCL, which we aim to transition into MorphoSys’s first pivotal study with an antibody from our proprietary pipeline next year. CD19 is a potential target in B cell malignancies and, coupled with MOR208’s proprietary antibody design, we aim at developing MOR208 as a new treatment option for patients with a high unmet medical need," said Dr. Arndt Schottelius, Chief Development Officer of MorphoSys. "With the start of the B-MIND clinical trial, we now have two combination studies ongoing with MOR208 in relapsed/refractory DLBCL. We are encouraged by the results we have seen so far in patients treated with MOR208 as a single agent in our earlier clinical trials and we look forward to more data coming from our combination trials."

The randomized, double-arm, open-label, multicenter phase 2/3 B-MIND study is expected to enroll approximately 330 patients in about 180 centers in Europe, Asia Pacific (APAC) and the USA. At the time of study entry, patients must present with relapsed or refractory DLBCL, which has previously been treated with at least one and not more than three prior lines of therapy, including one anti-CD20 targeting therapy (e.g. rituximab). Patients must not be eligible for high-dose chemotherapy and autologous stem cell transplantation.

The phase 2 safety evaluation part of the study will assess the safety and tolerability of MOR208 plus bendamustine vs. the rituximab plus bendamustine combination, enrolling approximately 10 patients in each treatment arm.

Following the safety evaluation part, the trial is intended to be transitioned into the pivotal phase 3 part, expected to start in 2017. The primary endpoint of the study is progression-free survival (PFS). Secondary outcome measures will include objective response rate (ORR), duration of response (DoR), overall survival (OS), disease control rate (DCR), time to progression (TTP) as well as an evaluation of patients’ quality of life (QoL).

Detailed information on the trial can be found at clinicaltrials.gov.

About CD19
CD19 is broadly and homogeneously expressed across different B cell malignancies including DLBCL and CLL. CD19 enhances B cell receptor (BCR) signaling, which is important for B cell survival, making CD19 a potential target in B cell malignancies.

About MOR208
MOR208 (previously Xmab5574) is an Fc-enhanced monoclonal antibody targeting CD19. Fc-modification of MOR208 is intended to lead to a significant potentiation of antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), thus possibly improving a key mechanism of tumor cell killing. Furthermore, MOR208 induces direct apoptosis by binding to CD19, which is a crucial component for B cell receptor (BCR) signaling.
MorphoSys AG is investigating MOR208 as an immunotherapeutic option in B cell malignancies.
Updated data, presented at the 2016 annual meetings of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and European Hematology Association (EHA) (Free EHA Whitepaper), presented the safety and efficacy results of an open-label study of MOR208 as monotherapy in 92 heavily pre-treated NHL patients (non-Hodgkin’s lymphoma). The overall response rate (ORR) in evaluable patients was 36% in the diffuse large B cell lymphoma (DLBCL) and 33% in indolent NHL (iNHL) patients. At the time of the analysis, the median duration of response (DoR) (Kaplan-Meier estimates) in DLBCL was 20 months with three ongoing responses. Median DoR was not reached in iNHL patients with 72% of responders without disease progression at 16 months. The 12-months PFS rate in DLBCL was 40% with similar PFS in both rituximab-sensitive and -refractory patients. The incidence of grade 3 or higher hematologic treatment-emergent adverse events was 26% in DLBCL and 9% in iNHL. Infusion-related reactions were seen in 9% of patients with DLBCL and iNHL, respectively. No treatment-related deaths were reported.

On September 5, 2016 Fresenius Helios reported that it has acquired IDC Salud Holding S.L.U. ("Quirónsalud"), Spain’s largest private hospital operator, for a purchase price of €5.76 billion2. Quirónsalud’s network is comprised of 43 hospitals, 39 outpatient centers and around 300 Occupational Risk Prevention ("ORP") centers located in all economically important areas in Spain (Press release, Fresenius, SEP 5, 2016, View Source [SID:1234514925]). The company has about 35,000 employees and offers the full spectrum of inpatient and outpatient care. Quirónsalud was created by the merger of IDC Salud ("IDC") and Grupo Hospitalario Quirón ("GHQ") in 2014.

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Quirónsalud has posted organic sales growth of more than 5% p.a. in recent years. Growth is driven by an above-market increase of patient admissions due to excellent quality of care combined with consistently short waiting times.

Quirónsalud is also a pioneer in public-private partnership ("PPP") models, operating five hospitals (four in Madrid and one in Barcelona) that are integrated within the public healthcare network. Under the PPP agreements, Quirónsalud is assigned responsibility for the publicly insured inhabitants of certain coverage areas and receives remuneration based on capitation or activity performed.

Greenfield hospital projects and acquisitions have also contributed to Quirónsalud’s overall strong sales growth. Going forward, cross-selling between the recently acquired ORPs and Quirónsalud’s hospitals are expected to be yet another growth driver.
For 2016, Quirónsalud expects sales of approximately €2.5 billion and EBITDA of €460 to €480 million. In 2017, EBITDA is expected to be in the range of €520 to €550 million. The purchase price corresponds to approximately 10.8x at the mid-point of the 2017 EBITDA range.

Key drivers of the anticipated EBITDA growth are already implemented synergy projects related to the 2014 merger of IDC and GHQ, recent acquisitions, well-advanced efficiency projects as well as operating leverage. Neither greenfield projects, further acquisitions nor synergies with HELIOS are included in the 2017 projections. In the medium-term, the merger of HELIOS and Quirónsalud is expected to lead to incremental pre-tax synergies of approximately €50 million p.a. without meaningful implementation expenses.

Stephan Sturm, CEO of Fresenius, said: "This acquisition combines two leaders in terms of quality and size. Our patients will benefit from the exchange of knowledge and ideas. For Fresenius, this acquisition is another strategic step towards offering quality and yet affordable care for patients worldwide."

Francesco De Meo, CEO of Fresenius Helios, said: "We are acquiring the largest private hospital operator in Spain, Europe’s number four. Quirónsalud has shown an impressive development and stands for best-in-class quality in patient care. Quirónsalud and HELIOS perfectly fit together as we can leverage on each other’s experience and knowledge. The new group will preserve both brands, Quirónsalud in Spain and Helios in Germany. I am particularly delighted that Víctor Madera will, beyond his ongoing role as CEO of Quirónsalud, play a very active role in our combined group. We aim to achieve the best for our patients in Germany and Spain, and, together with our Spanish partners, intend to leave a mark in the European health care system."

Víctor Madera, founder and CEO of Quirónsalud, said: "I am extremely pleased to join such a splendid organization as HELIOS and very much look forward to a fruitful cooperation with Francesco De Meo. I am firmly convinced that HELIOS and Quirónsalud are ideal partners to achieve the best care for our patients in both Germany and Spain."

Fresenius Helios acquires 100% of the share capital in Quirónsalud. Sellers are the private equity group CVC Capital Partners, Víctor Madera and other members of Quirónsalud’s management board.

Fresenius will issue 6,108,176 shares valued at €400 million to Víctor Madera who has agreed to a two year lock-up period. The balance of the purchase price will be debt-financed.

Group net debt/EBITDA will temporarily increase to approximately 3.1. Already in mid-2017, the leverage ratio is expected to return to the 2.5 to 3.0 target range.

The transaction is subject to regulatory approval by the relevant antitrust authorities and is expected to close in Q4/2016 or Q1/2017.

The transaction is expected to be highly accretive to Group net income3 and EPS3 already in 2017.

Given the expected meaningful accretion to Group sales and earnings, Fresenius will publish new mid-term targets as part of its full-year 2016 reporting.