On March 28, 2019 ISA Pharmaceuticals B.V., a clinical-stage immuno-oncology company, reported that its Chief Scientific Officer Prof. Dr. Cornelis Melief will give an oral presentation at the upcoming AACR (Free AACR Whitepaper) Annual Meeting 2019 in Atlanta, GA, USA, on March 31, 2019 (Press release, ISA Pharmaceuticals, MAR 28, 2019, View Source [SID1234534689]).

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The presentation titled "A strong HPV-specific T-cell response after chemo-immunotherapy for advanced cervical cancer is associated with prolonged survival"is scheduled for Sunday, March 31, 2019, as part of the session "Predictive Biomarkers for Immunotherapy" (12:45-2:45pm, Marcus Auditorium- Bldg A-GWCC).

The data will outline the effects of vaccination with ISA Pharmaceuticals´ therapeutic vaccine ISA101 during chemotherapy in 77 patients with advanced, recurrent or metastatic cervical cancer in a dose assessment study.

ISA101 is directed against the HPV16 oncoproteins E6/E7 and is the Company´s clinical-stage lead compound. It is being developed to treat HPV16-induced cancers such as cervical cancer and head-and-neck cancer. Clinical efficacy of ISA101 in combination with Regeneron’s PD-1 inhibitor cemiplimab is currently being tested in a randomized controlled Phase 2 trial in platinum refractory, HPV16-positive oropharyngeal cancer patients (NCT03669718). The results to be presented at AACR (Free AACR Whitepaper) form the basis for a planned Phase 3 trial, in which the clinical benefit of the combination of ISA101 plus cemiplimab on top of standard-of-care chemotherapy will be studied in patients with advanced HPV16-positive cervical cancer.

On March 28, 2019 Evotec AG (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) reported financial results and corporate updates for the fiscal year ended 31 December 2018 (Press release, Evotec, MAR 28, 2019, View Source;announcements/press-releases/p/evotec-ag-fiscal-year-2018-results-accelerated-growth-and-strong-long-term-outlook-5795 [SID1234534685]).

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STRONG FINANCIAL PERFORMANCE
Group revenues up 42% to € 375.4 m (2017: € 263.8 m); € 364.0 m Revenues from customer contracts, excluding revenues from recharges according to IFRS 15
Adjusted Group EBITDA up 67% to € 95.5 m (2017: € 57.2 m); € 92.0 m excluding one-off effects from tax credits and receivables
Total R&D expenses of € 35.6 m (2017: € 17.6 m) including € 12.7 m of infectious diseases-related expenses fully reimbursed by Sanofi ("partnered R&D")
Strong strategic liquidity position of € 149.4 m
OPERATIONAL AND SCIENTIFIC EXCELLENCE – "EXCELLENCE SQUARED"
Multiple new and extended drug discovery and development alliances
INDiGO roll-out and integration of high-end CMC offering
Leading application of Artificial Intelligence ("AI") in drug discovery projects
Continued strong performance of high-throughput ADME-tox testing (Cyprotex)
Significant progress in partnered co-owned pipeline; Clinical Phase I & Phase II starts
Multiple important milestone achievements, also in iPSC-based alliances
Continued expansion of iPSC leadership and focus on patient-centric approaches
Initiation of world-leading protein degradation platform
Global roll-out and expansion of Academic BRIDGE model
CORPORATE
Creating important footprint in infectious disease through acquisition of Evotec ID (Lyon)
Conversion into European Company (SE) expected to become effective by end of March 2019
FINANCIAL GUIDANCE 2019 – CONTINUED STRONG LONG-TERM GROWTH
Group revenues expected to increase by approx. 10% (2018: € 364.0 m excluding revenues from recharges according to IFRS 15)
Adjusted Group EBITDA expected to improve by approx. 10% (2018: € 92.0 m excluding one-off effects from tax credits and receivables)
Unpartnered research and development expenses expected to be approximately € 30-40 m (2018: € 22.9 m)

1. STRONG FINANCIAL PERFORMANCE
In 2018, Evotec’s Group revenues increased by 42% to € 375.4 m (2017: € 263.8 m). This increase was driven primarily by the strong performance in the base business, increased milestone payments and a positive first full-year contribution from the acquired business of Aptuit (€ 117.7 m) while contributing only € 46.0 m in 2017 (mid-August to December 2017). Revenues from milestones, upfronts and licences amounted to € 29.5 m, an increase of 6% in comparison to the previous year (€ 27.8 m). Milestones in 2018 resulted mainly from the collaborations with Bayer in endometriosis/chronic cough and kidney diseases, and from Evotec’s iPSC-based collaborations with Celgene in neurodegeneration as well as Sanofi in diabetes.

In 2018, Evotec focused its R&D expenses of € 35.6 m primarily on its iPSC research, projects in metabolic diseases, oncology and R&D platforms (2017: € 17.6 m). Furthermore, Evotec increased its R&D expenses significantly in infectious disease (ID)-related research following the acquisition of Evotec ID (Lyon) from Sanofi. These additional ID-related R&D expenses (€ 12.7 m) are fully reimbursed by Sanofi in context of the five-year agreement and are recognised under other operating income. Thus, they are not detrimental to the operating result and the adjusted EBITDA.

In 2018, the Group’s selling, general and administrative ("SG&A") expenses increased as expected by 35% to € 57.0 m (2017: € 42.4 m). This increase resulted primarily from first full-year SG&A expenses of Aptuit, additional Evotec ID (Lyon) costs as well as M&A-related and increased business development and administrative expenses in response to overall Company growth. However, this increase remained sub-proportional to revenue and adjusted EBITDA growth rates.

Evotec recorded a significant step-up in the adjusted Group EBITDA for 2018 to € 95.5 m (2017: € 57.2 m), yielding an adjusted EBITDA margin of 25.4% (2017: 21.7%). This adjusted EBITDA contains positive one-off effects from receivables and tax credits relating to prior periods in the amount of € 3.5 m. Without this effect, the adjusted EBITDA would amount to € 92.0 m.

Evotec’s operating result amounted to € 77.5 m in 2018 (2017: operating result of € 36.7 m) being positively impacted by the income from bargain purchase and higher R&D tax credits as well as positive one-off effects from receivables and tax credits. In 2018, an income from bargain purchase of € 15.4 m was recorded for the acquisition of Evotec ID (Lyon) as the purchase price was below the net assets acquired. The Company’s net result in 2018 amounted to € 84.1 m (2017: net result of € 23.2 m), being impacted by most recent acquisitions and the strong performance of the base business.

Evotec ended 2018 with a liquidity of € 149.4 m (2017: € 91.2 m), which was composed of cash and cash equivalents (€ 109.0 m) and investments (€ 40.4 m). The strong increase in liquidity in 2018 resulted mainly from the prepayments received from Celgene and the upfront received from Sanofi for Evotec ID (Lyon) (€ 61 m), off-set by net loan repayments (€ 78.2 m).

2. OPERATIONAL AND SCIENTIFIC EXCELLENCE – "EXCELLENCE SQUARED" IN EVT EXECUTE & EVT INNOVATE
The EVT Execute segment demonstrated strong progress in 2018 with new and extended alliances (e.g. CHDI, C4X, Dermira, Ferring, Forge, LEO Pharma, Novo Nordisk). In 2018, Evotec was involved in more than 700 customer alliances and recorded a repeat business of 92%. Following the launch of its INDiGO services in early 2018, Evotec was able to sign multiple new INDiGO agreements with e.g. Ankar, Astex, Carna Biosciences, Inflazome, and Yumanity. The high-throughput ADME-tox testing business of Cyprotex continued its excellent performance.

In EVT Innovate, 2018 was characterised by important progress in its strategic partnerships (iPSC neurodegeneration alliance with Celgene; iPSC diabetes alliance with Sanofi; kidney disease alliance with Bayer) as well as the signing of new partnerships, e.g. two new partnerships with Celgene in oncology as well as a new partnership with Almirall in dermatological diseases. Furthermore, the Company is blending artificial intelligence ("AI") and machine-learning tools into many of its biology- and chemistry-driven platforms to further accelerate and increase effectiveness in the process and continues to place great emphasis on patient-centric approaches to drug discovery. The partnered clinical projects are progressing to plan.

In 2018, Evotec’s academic BRIDGE model continued to attract significant interest from academia and industry partners.

3. CORPORATE
ACQUISITION OF EVOTEC ID (LYON)

Effective 01 July 2018, Evotec acquired 100% of the shares of Evotec ID (Lyon), the former Sanofi infectious disease unit in Lyon. The collaboration resulted in an upfront payment of € 61 m (€ 43 m in cash plus € 18 m cash of the acquired company) to Evotec. Evotec is eligible for significant further long-term funding from Sanofi in order to ensure the support and progression of a world-leading portfolio in this field.

4. FINANCIAL GUIDANCE 2019 – CONTINUED STRONG LONG-TERM GROWTH
Revenues, research and development expenses and adjusted EBITDA remain the financial key performance indicators of the Evotec Group.

For the financial year 2019, the Management Board expects Evotec to show Group revenue growth from contracts with customers without revenues from recharges of approx. 10%. This revenue growth is based on visibility of the current order book, expected new contracts, contract extensions and milestone opportunities. Projections are based on constant 2018 exchange rates.

Evotec’s adjusted Group EBITDA from 2018 includes one-off effects associated to the business years 2016 and 2017 in the amount of € 3.5 m. Without these one-off effects, the adjusted Group EBITDA in 2018 would amount to € 92.0 m. Against this number, Evotec’s adjusted Group EBITDA is expected to improve by approx. 10% in 2019 compared to 2018.

Evotec will continue to significantly invest in its own "unpartnered" research and development (R&D) efforts to create a long-term pipeline of first-in class assets and platforms. In addition, the Company will also continue to invest in its infectious disease-related efforts. ID-related R&D expenses of approx. € 35 m will be completely cost-covered by its partner Sanofi ("partnered R&D"). For better comparison against previous years, Evotec will focus its guidance and reporting during the course of 2019 on the "unpartnered R&D" part, estimated at approx. € 30-40 m.

WEBCAST/CONFERENCE CALL
The Company is going to hold a conference call to discuss the results as well as to provide an update on its performance. Furthermore, the Management Board will present an outlook for fiscal year 2019. The conference call will be held in English.

Conference call details

Date: Thursday, 28 March 2019

Time: 02.00 pm CET (09.00 am EDT, 01.00 pm GMT)

From Germany: +49 69 201 744 220

From France: +33 170 709 502

From Italy: +39 02 3600 6663

From the UK: +44 20 3009 2470

From the USA: +1 877 423 0830

Access Code: 75185877#

A simultaneous slide presentation for participants dialling in via phone is available at View Source

Webcast details

To join the audio webcast and to access the presentation slides you will find a link on our home page www.evotec.com shortly before the event.

A replay of the conference call will be available for 24 hours and can be accessed in Europe by dialling +49 69 20 17 44 222 (Germany) or +44 20 3364 5150 (UK) and in the USA by dialling +1 844 307 9362. The access code is 315534320#. The on-demand version of the webcast will be available on our website: View Source

On March 28, 2019 -Seattle Genetics, Inc. (Nasdaq:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported positive topline results from the first cohort of patients in a pivotal phase 2 single-arm clinical trial known as EV-201 (Press release, Seattle Genetics, MAR 28, 2019, View Source [SID1234534679]). The cohort is evaluating enfortumab vedotin for the treatment of patients with locally advanced or metastatic urothelial cancer who have received previous treatment with both platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor. Results showed a 44 percent objective response rate (ORR) per blinded independent central review. The duration of response was consistent with that recently reported in the previous phase 1 study (EV-101). The most common treatment-related adverse events included fatigue, alopecia, decreased appetite, rash and peripheral neuropathy. The data will be presented at an upcoming medical meeting.

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Enfortumab vedotin is an investigational antibody-drug conjugate (ADC) that targets Nectin-4, a therapeutic target that is highly expressed in multiple solid tumors including urothelial cancers. Based on preliminary results from a phase 1 trial (EV-101), enfortumab vedotin was granted Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for patients with locally advanced or metastatic urothelial cancer whose disease has progressed during or following treatment with a PD-1 or PD-L1 inhibitor.

The companies plan to submit a Biologics License Application (BLA) to the FDA later this year based on the results from the EV-201 trial (cohort 1). A global, randomized phase 3 clinical trial (EV-301) is ongoing and intended to support global registration as well as to serve as the confirmatory randomized trial for enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor.

"Despite recent approvals of multiple checkpoint inhibitors for previously treated locally advanced or metastatic urothelial cancer, there remains a high unmet need for effective treatments upon progression after initial chemotherapy and immunotherapy," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "These results for enfortumab vedotin indicate it may be able to help patients whose urothelial cancer progresses following treatment with standard chemotherapy and a PD-1 or PD-L1 inhibitor."

"After progression on platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor, patients with locally advanced or metastatic urothelial cancer are left with no approved standard of care treatment options," said Steven Benner, M.D., Senior Vice President and Global Therapeutic Area Head, Oncology Development at Astellas. "These data are very encouraging, and we look forward to discussing the data with relevant health authorities."

Urothelial cancer is the most common type of bladder cancer (90 percent of cases).1 In 2018, more than 82,000 people were diagnosed with bladder cancer in the United States.2 Globally, approximately 549,000 people were diagnosed with bladder cancer last year, and there were approximately 200,000 deaths worldwide.3 Approximately 80 percent of people do not respond to PD-1 or PD-L1 inhibitors after a platinum-containing therapy has failed as an initial treatment for advanced disease.4 There are currently no approved therapies for metastatic urothelial cancer once it has progressed after chemotherapy and a PD-1 or PD-L1 inhibitor.5

In addition to the ongoing confirmatory phase 3 study intended to also support global registration, development of enfortumab vedotin is underway in earlier lines of treatment for locally advanced or metastatic urothelial cancer, including in newly diagnosed patients in combination with pembrolizumab and/or platinum chemotherapy.

About The EV-201 Trial

EV-201 is an ongoing single-arm, pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (cohort 1) and those who have not received a platinum-containing chemotherapy and who are ineligible for cisplatin (cohort 2). The EV-201 phase 2 trial continues to enroll patients in cohort 2. In cohort 1, 128 patients were enrolled at multiple centers internationally.6 The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability. More information about enfortumab vedotin clinical trials can be found at clinical trials.gov.

About Enfortumab Vedotin

Enfortumab vedotin is an investigational ADC composed of an anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting agent (MMAE) using Seattle Genetics’ proprietary linker technology. Enfortumab vedotin targets Nectin-4, a cell adhesion molecule identified as an ADC target by Astellas, which is expressed on many solid tumors.

The safety and efficacy of enfortumab vedotin are under investigation and have not been established. There is no guarantee that the agent will receive regulatory approval and become commercially available for the uses being investigated.

Seattle Genetics Conference Call Details

Seattle Genetics’ management will host a conference call and webcast to discuss the announcement of enfortumab vedotin topline data. The event will be held today at 6:00 a.m. Pacific Time (PT); 9:00 a.m. Eastern Time (ET). The live event will be available from the Seattle Genetics website at www.seattlegenetics.com, under the Investors section, or by calling 866-288-0540 (domestic) or 786-460-7199 (international). The conference ID is 3807860. A replay of the live event will be available starting on March 28, 2019 on the Seattle Genetics website or by calling 888-203-1112 (domestic) or 719-457-0820 (international), using conference ID 3807860. The telephone replay will be available until 5:00 p.m. PT on April 1, 2019.

On March 27, 2019 Crown Bioscience, a global drug discovery and development services company, providing translational platforms to advance oncology, inflammation and autoimmune, cardiovascular and metabolic disease research reported that parent company, JSR Corporation, has entered into a strategic partnership with Hubrecht Organoid Technology (HUB) (Press release, JSR, MAR 27, 2019, View Source [SID1234553813]).

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The agreement provides CrownBio, a wholly owned subsidiary of JSR Corporation, with an exclusive license to provide preclinical oncology drug development and validation services using HUB Organoid Technology, including access to HUB’s highly characterized tumor organoid biobank. CrownBio and HUB will also launch a collaborative research & development program to accelerate further development of Organoid Technology, while CrownBio will establish a new operations center in Utrecht, Netherlands.

HUB’s adult stem cell-derived organoids, developed by Prof. Hans Clevers at the Hubrecht Institute in Utrecht, are generated using highly standardized, proprietary culture methods. The Organoids faithfully recapitulate tumors in patients and are extensively characterized by pathology, genomics, and sensitivity to known and experimental drugs.

"This agreement is a pivotal moment in our growth and the evolution of the company," said Dr. Jean-Pierre Wery, CEO of CrownBio. "This partnership positions CrownBio at the forefront of global preclinical research by creating an unparalleled translational platform to accelerate drug development and validation."

Building on a global leadership in Patient-Derived Xenografts (PDX), CrownBio will offer comprehensive pharmacology and translational services based on HUB Organoid Technology, establishing a unique platform that incorporates in vitro screening of Patient-Derived Organoids (PDO) and PDX derived organoids (PDXO), matched to downstream in vivo models.

"We are delighted with the increased access to HUB Organoid Technology for researchers worldwide through CrownBio’s global reach and preclinical service expertise," said Dr. Robert Vries, Executive Director of HUB. "Our partnership with CrownBio equips the drug development community with powerful new translational tools to guide the creation of novel and improved treatments for cancer."

On March 27, 2019 XenTech SAS, a company specialized in the development and sale of preclinical research services to foster the development of oncology drugs, reported a strategic collaboration with Gustave Roussy, Europe’s leading cancer center (Press release, XENTECH, MAR 27, 2019, View Source [SID1234553821]). This co-operation, the first of its kind for XenTech, will focus on the development of a collection of tumor explant models from patients who developed acquired resistance to targeted therapies following initial response. These PDX models will be used in Gustave Roussy’s oncology R&D programs, as well as being added to XenTech’s existing PDX platform for translational oncology research projects for academic and industry customers.

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Patients with tumors that harbor specific driver molecular alterations benefit from targeted therapies, but responses are generally short-lived due to the emergence of adaptive/secondary resistance. Between 2015 and 2020 the MATCH-R trial led by Gustave Roussy (NCT02517892) will have enrolled 600 patients treated with targeted therapies. Biopsies will be used to generate PDX models, obtained from 300 patients who have developed resistance following initial response. The MATCH-R PDX platform will be regularly upgraded with new models, providing a unique resource in unravelling the mechanisms involved in acquired resistance to targeted therapies and testing novel therapeutic strategies to circumvent or delay the emergence of resistance.

"We are delighted to collaborate with Gustave Roussy on this unique and ambitious program," said Jean-Gabriel Judde, CSO and president of XenTech. "These new models will expand XenTech’s bank of PDX models with focus on the advanced drug-resistant setting. The MATCH-R PDX platform will enable a better understanding of acquired resistance to last-generation targeted therapies, providing clinically relevant models to perform preclinical POC studies, translating into increased patient survival. Full clinical and molecular annotation will enable model selection for testing innovative therapies, investigating new and existing pathways, and identifying biomarkers."

"Understanding the mechanisms of acquired resistance to novel targeting agents is crucial in providing optimal care to cancer patients," said Benjamin Besse, head of the department of medical oncology at Gustave Roussy and principal investigator of the MATCH-R clinical trial. "This strategic collaboration with XenTech, a renowned expert in PDX development and in vivo pharmacological studies, is a major asset for Gustave Roussy’s precision medicine program. There is no doubt that these clinically relevant models will speed-up the development of novel therapeutic agents leading to extended clinical benefit for metastatic cancer patients."

XenTech will participate in American Association Cancer Research Annual Meeting, Friday, March 29 – Wednesday, April 3, 2019, in Atlanta, GA.