On November 14, 2017 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported that it has entered into a global collaboration with Bayer to develop and commercialize larotrectinib and LOXO-195, Loxo Oncology’s franchise of highly selective TRK inhibitors for patients with TRK fusion cancers (Press release, Loxo Oncology, NOV 14, 2017, View Source [SID1234522033]).

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Under the terms of the agreement, Loxo Oncology will receive a $400M upfront payment. Loxo Oncology is eligible for $450M in milestone payments upon larotrectinib regulatory approvals and first commercial sale events in certain major markets and an additional $200M in milestone payments upon LOXO-195 regulatory approvals and first commercial sale events in certain major markets.

"This is a transformational collaboration for the company as we prepare for commercialization," said Jacob Van Naarden, chief business officer of Loxo Oncology. "Bayer has a history of successful co-promotion efforts with emerging biopharmaceutical companies and we are confident that their oncology team has the global reach and expertise, including an existing field force dedicated to cancer, to complement our existing commercial plans. We look forward to working with Bayer and believe that together we can bring our TRK inhibitors to more patients more quickly."

"We see great potential in larotrectinib and moreover the follow-on compound LOXO-195 which may provide additional benefit for patients who might progress on an initial TRK inhibition therapy. These agents have the potential to fulfill the promise of precision medicine, where tumor genetics rather than tumor site of origin define the treatment approach for patients," said Robert LaCaze, executive vice president and head of the Oncology Strategic Business Unit at Bayer.

Loxo Oncology will lead global development activities and United States (U.S.) regulatory activities. Bayer will lead ex-U.S. regulatory activities, and worldwide commercial activities. Globally, Loxo Oncology and Bayer will share development costs on a 50/50 basis. In the U.S., where Loxo Oncology and Bayer will co-promote the products, the parties will share commercial costs and profits on a 50/50 basis. Bayer will pay Loxo Oncology a $25M milestone upon achieving a certain U.S. net sales threshold. Outside of the U.S., where Bayer will commercialize, Bayer will pay Loxo Oncology tiered, double-digit royalties on net sales, and sales milestones totaling $475M. Bayer will book revenues worldwide.

Loxo Oncology was advised by Fenwick and West in the transaction.

Conference Call Information
Loxo Oncology will host a conference call today at 8:00 a.m. ET to discuss this collaboration announcement. To participate in the conference call, please dial (877) 930-8065 (domestic) or (253) 336-8041 (international) and refer to conference ID 8077486. A replay will be available shortly after the conclusion of the call and archived on the company’s website for 30 days following the call.

About Larotrectinib (LOXO-101)
Larotrectinib is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. In an analysis of 55 RECIST-evaluable TRK fusion adult and pediatric patients, larotrectinib demonstrated a 75 percent independently-reviewed confirmed overall response rate (ORR) and an 80 percent investigator-assessed confirmed ORR, across many different types of solid tumors. Larotrectinib has been granted Breakthrough Therapy Designation, Rare Pediatric Disease Designation and Orphan Drug Designation by the U.S. FDA. For additional information about the larotrectinib clinical trials, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123 or visit www.loxooncologytrials.com.

About LOXO-195
LOXO-195 is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that have acquired resistance to initial TRK therapy such as larotrectinib. Though drugs such as larotrectinib can induce durable responses in these patients, the cancer may eventually begin to grow again. This phenomenon is called "acquired resistance," in that the cancer has acquired features conferring resistance to the initial therapy that was once effective. Emerging data in the field of TRK inhibition suggest that acquired resistance may emerge due to TRK kinase point mutations, such as those in the solvent front domain, xDFG domain, or gatekeeper region. LOXO-195 was designed to address these new point mutations and induce a new response in the patient’s cancer. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123 or email [email protected].

About TRK Fusion Cancer
TRK fusions are chromosomal abnormalities that occur when one of the NTRK genes (NTRK1, NTRK2, NTRK3) becomes abnormally connected to another, unrelated gene (e.g. ETV6, LMNA, TPM3). This abnormality results in uncontrolled TRK signaling that can lead to cancer. TRK fusions occur rarely but broadly in various adult and pediatric solid tumors, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, GIST, infantile fibrosarcoma, lung cancer, mammary analogue secretory carcinoma of the salivary gland, melanoma, pancreatic cancer, thyroid cancer, and various sarcomas. TRK fusions can be identified through various diagnostic tests, including targeted next-generation sequencing (NGS), immunohistochemistry (IHC), polymerase chain reaction (PCR), and fluorescent in situ hybridization (FISH). For more information, please visit www.TRKtesting.com.

On November 14, 2017 Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) reported that the company will make a presentation at the following upcoming event (Press release, Arrowhead Research Corporation, NOV 14, 2017, View Source [SID1234522035]):

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29th Annual Piper Jaffray Healthcare Conference – New York, November 28-29, 2017

November 28, 9:30 a.m. EST – Christopher Anzalone Ph.D., Arrowhead president and chief executive officer will participate in a fireside chat presentation.

A webcast of the event may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website.

On November 14, 2017 Pieris Pharmaceuticals, Inc presents Investor Presentation (Presentation, Pieris Pharmaceuticals, NOV 14, 2017, View Source [SID1234522036]).

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On November 14, 2017 Actinium Pharmaceuticals, Inc. (NYSE American:ATNM) ("Actinium" or "the Company"), a clinical-stage biopharmaceutical company focused on developing and commercializing targeted therapies for safer myeloablation and conditioning of the bone marrow prior to a bone marrow transplant and for the targeting and killing of cancer cells, reported that the Company has launched its AWE Program or Actinium Warhead Enabling Program (Press release, Actinium Pharmaceuticals, NOV 14, 2017, View Source [SID1234522039]).

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The AWE Program is designed to provide biopharmaceutical companies with access to the Company’s proprietary AWE technology platform in order to allow development of actinium-225 enabled conjugates wherein targeting agents are labeled with the alpha particle emitting radioisotope, actinium-225. Utilizing the AWE Technology Platform, the cell-killing power of targeting agents such as antibodies, peptides, Fab fragments, nanobodies etc. can potentially be improved via labeling with actinium-225. In addition to increased efficacy, these actinium-225 enhanced targeting agents can offer optimized dosing or administration and in the case of approved targeting agents, provide an opportunity to extend intellectual property protection by the creation of "Biobetters" or improved versions of the approved agent. Actinium is currently conducting a Phase 2 clinical trial for its drug candidate Actimab-A and a Phase 1 clinical trial for its drug candidate Actimab-M, both of which are fruits of the AWE Technology Platform and are comprised of actinium-225 labeled to an antibody that targets the antigen CD33 in patients with acute myeloid leukemia and multiple myeloma, respectively.

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Recently, Actinium announced that it successfully labeled the anti-CD38 monoclonal antibody daratumumab, a blockbuster therapy for patients with multiple myeloma, with actinium-225. Stability and target engagement was similar between the unlabeled and actinium-225 labeled antibody, demonstrating that the Company’s AWE Technology can successfully label a CD38 targeting agent without disrupting binding. In-vitro experiments with both the labeled and unlabeled antibody were performed in the same cell lines that initially established daratumumab’s proof of concept. In each CD-38 expressing cell line, improved cell killing was observed with the actinium-225 enabled daratumumab. The previous maximum reported cell killing was 62% with the naked daratumumab. However, at 1/10 of that antibody concentration the cell killing was 97% with the actinium-225 enabled daratumumab. Additionally, the cell-killing effect demonstrated both a time and concentration dependency. Importantly, specificity is demonstrated as no cell killing was observed when a cell line that does not express the target CD38 was treated with the actinium-225 labeled daratumumab. Data from this study were accepted as an abstract for poster presentation at the upcoming 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting Annual which can be viewed in the following link: View Source

Sandesh Seth, Actinium’s Chairman and CEO said, "The element actinium-225 is tremendously potent yet highly specific given its short path length, making it the ideal warhead for oncology indications when labeled to monoclonal antibodies. Through the development of our drug candidates, we have gained significant expertise and know-how in the application of actinium-225 and we look forward to providing our proprietary technology and highly specialized know how and supply chain capabilities to potential partners via our AWE Program. This expertise is evidenced by the recent results showing that actinium-225 increased the cell killing power of the blockbuster multiple myeloma antibody therapy daratumumab at 10-fold lower antibody concentration in Daudi cells. We are currently utilizing our technology toward generating potential "Biobetters" of selected commercial targeting agents and believe that our technology can be applied to a significant number of antibodies, peptides, Fab fragments or other targeting moieties. We look forward to working in collaboration via the AWE Program with biopharmaceutical companies that would like to increase the efficacy of their commercial or development stage antibodies to improve patient outcomes and also to better manage the lifecycle of their commercial antibodies."

About Our Actinium Warhead Enabling Technology Platform

The Actinium Warhead Enabling (AWE) Technology Platform enables a highly potent and selective form of targeted therapy that combines the powerful alpha-emitting radioisotope actinium-225 with targeting agents, which are designed to seek out cancer cells in the body that express particular markers. Actinium-225 emits significant alpha radiation making it a potent treatment modality against targeted cancer cells while limiting damage to healthy tissues as its radiation travels extremely short distances in the body. When labeled to targeting agents, actinium-225 can be delivered directly to cancer cells where the high linear energy transfer resulting from the emission of alpha particles results in irreparable DNA double stranded breaks and ultimately cancer cell death. Despite this superior cell killing power, actinium-225 when delivered in a targeted manner is sparing of the surrounding environment in the body due to the short path length of its alpha-particle radiation and can result in a superior safety profile. Actinium Pharmaceuticals owns or has licensed the rights to several issued and pending patents that pertain to its AWE Technology Platform including technology to manufacture actinium-225 in a cyclotron. In addition, the Company obtains actinium-225 from various sources such as the U.S. Department of Energy at Oak Ridge National Laboratories and has developed considerable know-how, expertise and validated processes related to production of radioimmunoconjugates, management of the supply chain and dealing with various regulatory bodies. The AWE Technology Platform can be utilized to potentially improve the cell-killing power of targeting agents such as antibodies, peptides, Fab fragments, nanobodies etc. via labeling with actinium-225. In addition to increased efficacy, these actinium-225 enhanced targeting agents can offer optimized dosing or administration and in the case of approved targeting agents provide an opportunity to extend intellectual property protection by the creation of "Biobetters" or improved versions of the approved agent. The Company’s Actinium Warhead Enabling (AWE) Program can be accessed by biopharmaceutical companies that are interested in creating Biobetters through the utilization of the AWE Platform Technology. To learn more about the AWE Technology Platform or the AWE Program please contact Keisha Thomas, Ph.D., Corporate Development at [email protected].

On November 14, 2017 Bayer reported that the company has entered into an exclusive global collaboration with Loxo Oncology, Inc., a biopharmaceutical company based in Stamford, Connecticut, US, (NASDAQ: LOXO) for the development and commercialization of larotrectinib (LOXO-101) and LOXO-195 (Press release, Bayer, NOV 14, 2017, View Source [SID1234522040]). Both compounds are being investigated in global studies for the treatment of patients with cancers harboring tropomyosin receptor kinase (TRK) gene fusions, which are genetic alterations across a wide range of tumors resulting in uncontrolled TRK signaling and tumor growth.

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"The collaboration with Loxo Oncology represents another milestone in our endeavor to strengthen our oncology presence and underlines our commitment to this therapeutic area", said Dieter Weinand, Member of the Board of Management of Bayer AG and President of the Pharmaceuticals Division. "Loxo Oncology’s very innovative approach complements Bayer’s oncology pipeline with highly differentiated compounds across different treatment modalities, which are being developed to make a meaningful difference for patients suffering from various types of cancer."

Larotrectinib is an oral, potent and highly selective TRK inhibitor. LOXO-195 is a next-generation, selective TRK inhibitor capable of addressing potential mechanisms of acquired resistance that may emerge in patients receiving larotrectinib or multikinase inhibitors with anti-TRK activity. Larotrectinib is currently the only selective TRK inhibitor in clinical development with the comprised clinical data set showing clinically meaningful and durable responses with an overall response rate of 75 percent, confirmed by an independent review committee, regardless of tumor type and age. The first filing for larotrectinib is planned in the U.S. in late 2017 or early 2018, with the EU filing expected in 2018.

"We see great potential in larotrectinib and moreover the follow-on compound LOXO-195 which has the potential to provide additional benefit for patients who might progress on an initial TRK inhibition therapy. These agents have the potential to fullfil the promise of precision medicine, where tumor genetics rather than tumor site of origin define the treatment approach for patients", said Robert LaCaze, Executive Vice President and Head of the Oncology Strategic Business Unit at Bayer.

"This is a transformational collaboration for the company as we prepare for commercialization," said Jacob Van Naarden, chief business officer of Loxo Oncology. "Bayer has a history of successful co-promotion efforts with emerging biopharmaceutical companies and we are confident that their oncology team has the global reach and expertise, including an existing field force dedicated to cancer, to complement our existing commercial plans. We look forward to working with Bayer and believe that together we can bring our TRK inhibitors to more patients more quickly."

Under the terms of the agreement, Loxo Oncology will receive an upfront payment of USD 400 million and is eligible for USD 450 million in milestone payments upon larotrectinib regulatory approvals and first commercial sale events in certain major markets and an additional USD 200 million in milestone payments upon LOXO-195 regulatory approvals and first commercial sale events in certain major markets. Bayer and Loxo Oncology will jointly develop the two products, larotrectinib and LOXO-195, and share development costs on a 50/50 basis. Bayer will lead ex-U.S. regulatory activities, and worldwide commercial activities. In the U.S., where Bayer and Loxo Oncology will co-promote the products, the parties will share commercial costs and profits on a 50/50 basis. Loxo Oncology will remain responsible for the filing in the U.S. Bayer will pay Loxo Oncology tiered double-digit percentage royalties on future net sales outside of the U.S. and U.S. and ex-U.S. sales milestones totaling USD 500 million.

About Larotrectinib (LOXO-101) and LOXO-195
Larotrectinib (LOXO-101) is a potent, oral and selective investigational new drug in clinical development for the treatment of patients across a wide range of cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body.

In an analysis of 55 RECIST-evaluable TRK fusion adult and pediatric patients, larotrectinib demonstrated a 75 percent independently-reviewed confirmed overall response rate (ORR) and an 80 percent investigator-assessed confirmed ORR, across many different types of solid tumors. Larotrectinib received orphan drug designation in the US for the treatment of solid tumors harboring NTRK-fusion proteins and in Europe for soft tissue sarcoma. Additionally, the FDA granted breakthrough therapy designation to larotrectinib for the treatment of unresectable or metastatic solid tumors with NTRK-fusion proteins in adult and pediatric patients who require systemic therapy and who have either progressed following prior treatment or who have no acceptable alternative treatments.

LOXO-195 is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that have acquired resistance to initial TRK therapy such as larotrectinib. Though drugs such as larotrectinib can induce durable responses in these patients, the cancer may eventually begin to grow again. This phenomenon is called "acquired resistance," in that the cancer has acquired features conferring resistance to the initial therapy that was once effective. Emerging data in the field of TRK inhibition suggest that acquired resistance may emerge due to TRK kinase point mutations. LOXO-195 was designed to address these new point mutations and induce a new response in the patient’s cancer. In July 2017, a multi-center Phase I/II trial in patients with TRK fusion cancers who have progressed while receiving another TRK inhibitor or are intolerant to another TRK inhibitor was initiated.

For additional information about the larotrectinib or LOXO-195 clinical trials, please refer to www.clinicaltrials.gov or visit www.loxooncologytrials.com. Neither larotrectinib nor LOXO-195 are approved by the U.S. Food and Drug Administration, the European Medicines Agency or any other health authority.

About TRK Fusion Cancer
TRK fusions are chromosomal abnormalities that occur when one of the NTRK genes (NTRK1, NTRK2, NTRK3) becomes abnormally connected to another, unrelated gene (e.g. ETV6, LMNA, TPM3). This abnormality results in uncontrolled TRK signaling that can lead to cancer. TRK fusions occur rarely but broadly in various adult and pediatric solid tumors, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, GIST, infantile fibrosarcoma, lung cancer, mammary analogue secretory carcinoma of the salivary gland, melanoma, pancreatic cancer, thyroid cancer, and various sarcomas. TRK fusions can be identified through various diagnostic tests, including targeted next-generation sequencing (NGS), immunohistochemistry (IHC), polymerase chain reaction (PCR), and fluorescent in situ hybridization (FISH). For more information, please visit www.TRKtesting.com.

Cancers Harboring Genetic Alterations
Scientists have long been working to better understand how a normal cell becomes a cancer cell to deliver better therapies with fewer side effects. Some people develop cancers that are caused by a single inappropriate DNA change, known as "oncogenic drivers." When a genetic test identifies a patient with an oncogenic driver, there is the potential for use of highly selective drugs that inhibit oncogenic drivers in cancer. While there has been made notable progress in improving outcomes for people living with cancer over the last several decades, there has been a growing interest in developing highly targeted medicines to treat cancer, to further maximize the patients’ clinical benefit. This development is supported by the increasing use of genetic testing in cancer clinical medicine and improving chemistry approaches to building highly selective inhibitors against single targets in the cancer cell.

About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes four marketed products and several other compounds in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.