On December 20, 2018 Immatics Biotechnologie reported The prospect of an actively personalized approach to the treatment of cancer has moved a step closer with the recent publication in Nature of data from the phase 1 study GAPVAC-101, testing a novel therapeutic concept tailored to specific characteristics of patients’ individual tumors and immune systems (Press release, Immatics Biotechnologies, DEC 20, 2018, View Source [SID1234569548]). For the first time, the feasibility of such a highly personalized form of immunotherapy has been exemplified in a multi-center, multi-national clinical setting.

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To date, glioblastoma, an aggressive form of brain cancer with poor prognosis, and other tumor types have not sufficiently benefited from recent breakthroughs with checkpoint inhibitors due to lack of high mutational load which is thought to be essential for the mode of action of this therapeutic class. Indeed, many tumor types are characterized by a low mutational load and thus only few neoantigens are targetable by the immune system. Such cancers exhibit a high unmet medical need and require additional therapeutic strategies tailored to the features of the patient’s individual tumor and appreciating the entire breadth of the cancer target repertoire.

The Glioma Actively Personalized Vaccine Consortium (GAPVAC) approach is a highly personalized method being progressed through the GAPVAC-101 first-in-human clinical trial by a European Union-funded consortium, led by Immatics Biotechnologies GmbH (Tuebingen, Germany) and BioNTech AG (Mainz, Germany).

Fifteen newly diagnosed glioblastoma patients treated at six European centers received two immunotherapies in succession; APVAC1 targeted at non-mutated antigens, followed by APVAC2 preferentially targeted at neo-antigens. Immunotherapy compositions were personalized for each patient based on analysis of the transcriptome, immunopeptidome and mutanome of the individuals’ tumors and, for APVAC1, also based on the capability of each patient to mount an immune response. Both immunotherapy types displayed favorable safety and immunogenicity. Non-mutated APVAC1 antigens induced sustained central memory CD8+ T-cell responses, whilst APVAC2 induced T helper cell type 1 (TH1) CD4+ as well as CD8+ T-cell responses against predicted neo-epitopes.

The GAPVAC-101 trial served as a blueprint for the ACTolog IMA101-101 trial sponsored by Immatics. ACTolog is the first adoptive cell therapy trial applying the concept of active personalization.

Dr. Harpreet Singh, Chief Scientific Officer of Immatics and President & CEO of Immatics US, said: "We are at a very exciting stage in the evolution of tailor-made cancer treatments based on the diseases of individual cancer patients. The ability to exploit the full repertoire of tumor antigens, including non-mutated and neoantigens, may offer more effective immunotherapies, especially for tumors with low mutational load. And there is more to come. The next step is to translate the concept of active personalization, successfully demonstrated in this study, into adoptive cell therapies ‒ which we have achieved with the ACTolog IMA101 clinical trial Immatics is currently running at MD Anderson Cancer Center."

Prof. Hans-Georg Rammensee, Head of the Department of Immunology at the University of Tuebingen, Germany, and Co-Founder of Immatics added: "I am very pleased to see that the concept of active personalization proposed by us more than a decade ago has been applied for the treatment of glioblastoma patients. GAPVAC constitutes the first clinical trial using a combination of personalized mass spectrometry, next-generation sequencing, mRNA microarray, immune repertoire analysis and peptide GMP manufacturing for every patient and delivering these complex logistics in a multi-center multi-national clinical trial."

The approach of personalization of immunotherapies was first proposed by Prof. Hans-Georg Rammensee in 2000. His department was also responsible for the APVAC "on-demand" GMP manufacturing, led by Prof. Stefan Stevanovic, in the GAPVAC trial. The University of Tuebingen also served as one of the six European clinical trial centers treating glioblastoma patients.

On December 20, 2018 GT Biopharma, Inc. (OTCQB: GTBP and Euronext Paris GTBP.PA) ("GT Biopharma" or the "Company"), an immuno-oncology biotechnology company focused on innovative treatments based on the Company’s proprietary NK-engager and Bispecific Antibody Drug Conjugate platforms, reported that Raymond W Urbanski, M.D., Ph.D., Chief Executive Officer and Chairman, will present at Biotech Showcase 2019 on Tuesday, January 8, 2019 at 11:30 AM PST in San Francisco, CA (Press release, GT Biopharma , DEC 20, 2018, View Source [SID1234539517]).

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As part of his presentation, Dr. Urbanski will provide a corporate update and discuss GT Biopharma’s pipeline of immuno-oncology products based off the Company’s proprietary Tri-specific Killer Engager (TriKE), Tetra-specific Killer Engager (TetraKE) and bi-specific Antibody Drug Conjugate (ADC) technology platforms.

The Company’s most advanced bi-specific ADC in development, GTB-1550, targets CD19+ and/or CD22+ hematological malignancies and is currently in the Phase 2 component of a Phase 1/2 Non-Hodgkin’s Lymphoma (NHL)/Acute Lymphocytic Leukemia (ALL) trial which is an open-label, investigator-led study. GT Biopharma expects to announce topline results from the Phase 2a trial of GTB-1550 in the first quarter of 2019.

Additionally, the Company recently announced its Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) is now open and it is authorized to initiate a first-in-human Phase 1 study with GTB-3550 (formerly OXS-3550), its first-in-class (TriKE), for the treatment of acute myelogenous leukemia (AML), myelodysplatic syndrome (MDS) and mastocytosis. The study, which is expected to commence in the first half of 2019, will be led by Principal Investigator, Sarah A. Cooley, MD, MS, Associate Professor, Division of Hematology, Oncology and Transplantation at Masonic Cancer Center, University of Minnesota. The Company believes that GTB-3550 could serve as a relatively safe, cost-effective, and easy-to-use therapy for refractory/relapsed AML, high-risk MDS and advanced systemic mastocytosis and could also be combined with chemotherapy and/or other agents as frontline therapy thus targeting a much larger patient population.

In addition to the presentation, Dr. Urbanski will also be available to participate in one-on-one meetings with qualified members of the investor community who are registered to attend the conference. For more information about the conference, please click here to visit the conference website.

A live audio webcast of the presentation will be available on the Events page of the Investors section of the Company’s website (www.gtbiopharma.com). A webcast replay will be accessible for 90 days following the live presentation.

On December 20, 2018 Ayala Pharmaceuticals, Inc., a clinical-stage company developing medicines for cancers that are genetically identified, reported that it entered into an option to license agreement with Novartis for its investigational agent AL102 in multiple myeloma (Press release, Ayala Pharmaceuticals, DEC 20, 2018, View Source [SID1234532198]). Under the terms of the deal, Ayala will receive a $10 million equity investment from Novartis and is eligible to receive development, clinical, regulatory and commercial milestones along with tiered royalties on net sales of AL102.

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Novartis will conduct certain studies to evaluate AL102 in combination with its B-cell maturation antigen (BCMA) therapies in multiple myeloma. Ayala will provide the drug supply. All development costs associated with the above studies will be fully born by Novartis. Ayala retains worldwide license rights for AL102 for all other indications.

"We are extremely pleased to enter this agreement with Novartis on AL102. Novartis has a strong commitment and expertise in oncology, and a proven record of success in drug development, making them an ideal strategic partner for AL102 in multiple myeloma," said Roni Mamluk, PhD, chief executive officer at Ayala. "This collaboration is important to Ayala as it immediately strengthens our balance sheet, further validates our technology and accelerates the clinical development of AL102 as a combination therapy in hematologic cancers."

AL102 is an oral small-molecule that inhibits gamma secretase, an enzyme which may be targeted to increase levels of BCMA, which is expressed in most multiple myeloma patients. BCMA is actively shed from multiple myeloma cells by gamma secretase, hence its inhibition by AL102 may increase BCMA levels on multiple myeloma cells. Therefore, AL102 is being studied to evaluate its clinical role in enhancing anti-BCMA therapies.

Ayala is committed to developing new targeted therapies for genomically-defined cancers in patient populations with high unmet medical need. In addition to investigating AL102 as an anti-BMCA therapy in multiple myeloma, Ayala is evaluating AL102 as an inhibitor of the Notch pathway in other hematologic cancers.

Multiple myeloma is a rare and aggressive blood cancer that accounts for approximately one percent of all cancers. In the U.S., there are nearly 90,000 people living with, or in remission from, multiple myeloma. Approximately, 26,850 Americans are diagnosed with multiple myeloma each year and 11,240 patient deaths are reported on an annual basis.

On December 20, 2018 Novartis reported an offer to acquire CellforCure from LFB. CellforCure, a French company, is one of the first and largest contract development and manufacturing organizations (CDMO) producing cell and gene therapies in Europe (Press release, Novartis, DEC 20, 2018, View Source [SID1234532214]).

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Under the proposed agreement, Novartis would acquire the share capital of CellforCure from LFB including the cell and gene manufacturing facility located in Les Ulis and the related adjacent land. If the offer is accepted, CellforCure would become a wholly owned Novartis manufacturing site, joining the network of cell and gene therapy sites including Morris Plains, New Jersey, USA and Stein, Switzerland, where construction continues to progress as planned.

In July 2018, Novartis announced that it had signed an agreement with CellforCure to produce CAR-T cell therapies including Kymriah (tisagenlecleucel), the first CAR-T cell therapy approved by the United States Food and Drug Administration (FDA) and indicated for two distinct, difficult-to-treat cancers in the United States, European Union, Switzerland, Canada and Australia. Novartis and CellforCure have successfully completed technology transfer and Kymriah clinical supply production is expected to begin by mid-2019. The proposed acquisition of CellforCure is another example of continued commitment by Novartis to investing in cell and gene therapies as well as in France.

Novartis has made several steps recently to strengthen and expand its cell and gene manufacturing, including signing a strategic licensing, collaboration and share purchase agreement with Cellular Biomedicine Group (CBMG) to manufacture and supply Kymriah in China; expanding an alliance with the Fraunhofer Institute in Germany to support manufacturing for clinical trials and post approval manufacturing; and a contract manufacturing collaboration in Japan.

Novartis Global Head of Technical Operations Steffen Lang said, "The proposed acquisition of CellforCure is another strategic step in our pursuit of additional manufacturing capacity to make our transformational CAR-T cell therapy Kymriah available to more patients in need around the world. If completed, this acquisition also would potentially increase manufacturing capacity for other cell and gene therapies in the Novartis pipeline. We are excited about the possibility of adding the significant experience of CellforCure to our existing leadership in pioneering research, development and supply of cell and gene therapies."

The transaction is subject to usual and customary closing conditions, including employee consultation process and necessary regulatory approvals. If approved, the transaction is expected to be funded through available cash and close in the first half of 2019.

CellforCure is an LFB group company specializing in innovative therapy drugs. CellforCure`s industrial platform located in Les Ulis, near Paris is one of the first and largest in Europe for the production of cell and gene therapy drugs. Established as a pharmaceutical company since 2013, CellforCure operates a Contract Development and Manufacturing Organization. The company obtained two Good Manufacturing Practice (GMP) certificates from the French Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM) in 2016 for the production of innovative experimental and commercial therapy drugs.

On December 19, 2018 Eli Lilly and Company (NYSE: LLY) reported its 2019 financial guidance, updated certain elements of its 2018 guidance and 2020 minimum financial expectations, reviewed the performance of recently launched medicines and highlighted numerous potential new medicines in its clinical pipeline (Press release, Eli Lilly, DEC 19, 2018, View Source [SID1234532147]).

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David A. Ricks, Lilly’s chairman and chief executive officer, confirmed that the company is executing well against the company’s priorities to launch with excellence, replenish the pipeline, improve productivity and develop talent.

"Over the past five years, Lilly has successfully launched 10 new medicines, bolstered our pipeline with new candidate medicines from our own labs and from external partners, reshaped the company to be more productive, and attracted world-class scientific talent to our labs," said Ricks. "Our actions over the past several years have positioned Lilly to deliver significant value to our key stakeholders. Most importantly, they have benefited patients, many of whose lives are better because of new Lilly medicines."

Ricks acknowledged Lilly’s current strong performance, and expressed optimism for the company’s future growth. "We are proud of what we have achieved at Lilly over the past several years, but we are determined to raise the bar higher. We see incredible scientific opportunities to address some of the most significant health challenges of an aging society. We aim to create new medicines over the next decade that will transform the care of serious illnesses, and provide valuable new treatment options for doctors and patients."

R&D Transformation is Leading to Impressive Pipeline Productivity
At today’s meeting, Daniel Skovronsky, M.D., Ph.D., Lilly’s Chief Scientific Officer and President of Lilly Research Laboratories, highlighted recent advancements that the company has made to improve R&D productivity and create new medicines that are either first-in-class or best-in-class.

The company is reshaping its drug discovery engine, with the dual goal of decreasing the time from target identification to clinical testing to approximately three years, while also increasing the use of externally-derived innovation to access novel targets, modalities and discovery tools.
Lilly has significantly improved the speed of its development activities and reduced the average time from first human dose of a potential new medicine to commercial launch by over two years.
There has been a steady improvement in the success rate of Phase 3 molecules in Lilly’s clinical pipeline due to a greater emphasis on target validation, patient population, molecule optimization, more robust Phase 2 data, and better Phase 3 design.
Skovronsky discussed the development plans and therapeutic potential for a number of promising late-stage pipeline opportunities and new indications for approved medicines in the company’s five therapeutic areas of focus:

Oncology – Verzenio, pegilodecakin
Pain – Emgality, lasmiditan, tanezumab
Neurodegeneration – N3pG antibody, tau antibody, D1PAM
Immunology – Olumiant, mirikizumab
Diabetes – Insulins and Connected Care, Trulicity, tirzepatide
"Lilly has created an industry-leading late-stage development organization and now we are focused on transforming our drug discovery engine," said Skovronsky. "With an attractive clinical pipeline, two new molecules achieving regulatory submissions and three entering Phase 3 in 2018, we are continuing an impressive period of productivity for Lilly Research Labs, and are on pace to deliver on the company’s goal to launch 20 new medicines in 10 years."

New Medicines Are Driving Volume-Based Revenue Growth and Positive Financial Outlook
Joshua Smiley, Lilly senior vice president and chief financial officer, highlighted the performance of several recently launched medicines and reviewed the company’s 2018 and 2019 financial guidance, as well as certain minimum financial expectations for 2020.

"Lilly has dramatically upgraded the quality of its revenue base over the past five years through the launch and uptake of 10 new medicines, which together are expected to account for over 45 percent of human pharmaceutical sales in 2019," noted Smiley. "These 10 medicines are launching in some of the fastest growing categories and continue to deliver growth through increased volume, not price, meaning more and more people around the world are benefitting from Lilly medicines."

At today’s meeting, Mr. Smiley highlighted the strong U.S. performance and market share gains of several of these medicines, including Trulicity, Jardiance, Taltz and Verzenio, as well as the early progress for Emgality and international growth opportunities across the portfolio.

"We are encouraged by the commercial execution across our new launches, and are excited about their prospects for future growth," added Smiley. "The success of these medicines gives us confidence that we will continue to deliver strong results and generate significant cash balances in 2019 and beyond. Based on these growth prospects, we are pleased to today announce a 15 percent increase in our dividend."

2018 Financial Guidance
The company has revised certain elements of its 2018 financial guidance on a reported basis. Earnings per share on a reported basis are now expected to be in the range of $2.80 to $2.85, while non-GAAP earnings per share for 2018 are still expected to be in the range of $5.55 to $5.60.

Numbers may not add due to rounding

* 2018 Expectations are pending finalization of estimates, accounting policy elections, and guidance issued for tax reform.

(a) Relates to adjustments to the 2017 Toll Tax for U.S. tax reform proposed regulations and tax expenses associated with the separation of the Elanco animal health business.

* Certain elements of 2018 guidance are pending finalization of estimates, accounting policy elections, and guidance issued for tax reform.

Non-GAAP adjustments are consistent with the earnings per share table above.

2019 Financial Guidance
Lilly today issued its 2019 financial guidance. The individual elements of the 2019 financial guidance outlined below include fully consolidated financial expectations for both the company’s human pharmaceutical business and Elanco Animal Health, with the exception of earnings per share, which excludes approximately $0.08 per share for the non-controlling interest in Elanco. Lilly expects to divest its remaining ownership in Elanco through a tax-efficient transaction within one year of Elanco’s initial public offering, and will restate 2019 financial guidance at that time to reflect Elanco as discontinued operations.

Earnings per share for 2019 are expected to be in the range of $5.52 to $5.62 on a reported basis and $5.90 to $6.00 on a non-GAAP basis.

Numbers may not add due to rounding

* 2019 Expectations are pending finalization of estimates, accounting policy elections, and guidance issued for tax reform.

The company anticipates 2019 revenue between $25.3 billion and $25.8 billion. Revenue growth is expected to be driven by volume from newer medicines including Trulicity, Taltz, Basaglar, Jardiance, Verzenio, Cyramza, Olumiant and Lartruvo. Revenue growth is also expected to benefit from the recent launch of Emgality, and could benefit from the potential approval and launch of nasal glucagon and lasmiditan. Revenue growth is expected to be partially offset by lower revenue for Cialis and other products that have lost patent exclusivity. Revenue growth is also expected to be partially offset by the negative impact of foreign exchange rates, as well as continued price pressures in the U.S and some international markets.

Gross margin as a percent of revenue rate is expected to be approximately 75.0 percent on a reported basis and 76.5 percent on a non-GAAP basis.

Marketing, selling and administrative expenses are expected to be in the range of $6.4 billion to $6.7 billion. Research and development expenses are expected to be in the range of $5.6 billion to $5.8 billion.

Other income (expense) is expected to be expense between $75 million and $225 million.

The 2019 effective tax rate is expected to be approximately 16 percent on both a reported basis and on a non-GAAP basis, pending finalization of estimates, accounting policy elections, and guidance issued for tax reform.

* Certain elements of 2019 guidance are pending finalization of estimates, accounting policy elections, and guidance issued for tax reform.

Non-GAAP adjustments are consistent with the earnings per share table above.

2020 Minimum Financial Expectations
The company has revised its 2020 minimum financial expectations and now expects at least 6 percent compound annual revenue growth from 2015 to 2020 for the full company, and at least 7 percent compound annual revenue growth for the human pharmaceutical business.

Certain financial guidance information for 2019 and 2018 is presented on both a reported and a non-GAAP basis. Some numbers in this press release may not add due to rounding. Reported results are prepared in accordance with U.S. generally accepted accounting principles (GAAP) and include all revenue and expenses recognized during the periods. Non-GAAP measures exclude the items described in the reconciliation tables contained in this press release. The non-GAAP measures are presented to provide additional insights into the underlying trends in the company’s business. This press release does not constitute an offer of any securities for sale.

Webcast of Conference Call and Investor Materials
As previously announced, investors and the general public can access a live webcast of the 2018 investment community meeting conference call and investor materials through a link on Lilly’s website at www.investor.lilly.com. The conference call will be held today beginning at 9:00 a.m. Eastern time (ET) and will be available for replay via the website.