On June 25, 2019 Taiwan Liposome Company, Ltd. ("TLC") (Nasdaq: TLC, TWO: 4152), a clinical-stage specialty pharmaceutical company dedicated to the development and commercialization of novel nanomedicines designed to target areas of unmet medical need in osteoarthritis, pain management, ophthalmology and oncology, reported the signing of a development and license agreement with Birdie Biopharmaceuticals Inc. ("Birdie"), a wholly owned subsidiary of Seven and Eight Biopharmaceuticals Corp (Press release, Taiwan Liposome Company, JUN 25, 2019, View Source [SID1234537247]). Birdie and Seven and Eight Biopharmaceuticals are clinical stage biotech companies focused on the development of immunotherapy to treat cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Under the agreement, Birdie will engage TLC in the development and manufacturing of a liposomal formulated dual agonist product against toll-like receptors 7 and 8 (TLR7/8) utilizing TLC’s NanoX technology. Birdie will be responsible for the product’s preclinical and clinical development, regulatory filing and commercialization. TLC will be responsible for the formulation development and manufacturing. TLC will receive an upfront payment and is eligible to receive up to US$49 million in potential milestone payments. In addition, TLC is also eligible to royalties based on the net sales.

"This agreement leverages our expertise and gives further validation to our technology platform’s capability to expand into other areas such as immunotherapy for the treatment of cancer," commented TLC President George Yeh. "Our NanoX liposome technology has distinct advantages of achieving desirable pharmacokinetic profiles and preferential distribution to tumor tissues. We are delighted to partner with Birdie and working together on this collaboration to bring a potential new innovative therapy to cancer patients."

"TLR7/8 are amongst the most promising targets for immuno-oncology and our dual agonists have demonstrated the ability to stimulate specific types of innate immune response, generating enhanced anti-tumor immunity," said, Walter Lau, Ph.D., Chief Executive Officer of Birdie and Seven and Eight Biopharmaceuticals. "Following our recent announced collaboration with a major pharma partner on combination trials with established checkpoint inhibitors, we are excited to be working with TLC to develop a potential best-in-class next generation product. We believe that the robust, scalable and replicable manufacturing process of TLC’s NanoX technology formulates a sustainable competitive advantage and the potential to commercialize worldwide."

On June 25, 2019 Arvinas, Inc. (Nasdaq: ARVN), a biotechnology company creating a new class of drugs based on targeted protein degradation, reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug application (IND) for ARV-471, an oral estrogen receptor (ER) PROTAC protein degrader, designed to selectively target ER for the treatment of patients with locally advanced or metastatic ER positive / HER2 negative breast cancer (Press release, Arvinas, JUN 25, 2019, View Source [SID1234537248]). Arvinas expects to initiate a Phase 1 clinical trial for ARV-471 in the third quarter of 2019.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"ARV-471 is our second program in six months to receive IND clearance, and we are pleased to be advancing it into the clinic and progressing Arvinas’ portfolio of PROTAC protein degraders for the treatment of patients with cancer and other life-threatening diseases," said John Houston, Ph.D., President and CEO of Arvinas. "We hope the activity ARV-471 demonstrated preclinically will translate into a new, beneficial treatment for patients with locally advanced or metastatic ER positive/HER2 negative breast cancer."

In the United States, breast cancer is the second most common cancer and the second leading cause of cancer death in women. The American Cancer Society estimates that in 2019, there will be approximately 268,000 women diagnosed with invasive breast cancer in the United States. Metastatic breast cancer accounts for approximately 6% of newly diagnosed cases. Approximately 80% of newly diagnosed breast cancers are ER positive, with many patients developing resistance to current treatment options over time.

ARV-471 is a PROTAC protein degrader specifically designed to target and degrade ER. The Phase 1 trial will assess the safety, tolerability, and pharmacokinetics of ARV-471, and will also include measures of anti-tumor activity and pharmacodynamic readouts as secondary endpoints.

In preclinical studies, ARV-471 demonstrated near-complete ER degradation in tumor cells, induced robust tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed superior anti-tumor activity as a single agent and in combination with a CDK4/6 inhibitor when compared to a standard of care agent, fulvestrant, dosed as single agent or in combination with a CDK4/6 inhibitor. Arvinas believes the differentiated pharmacology of ARV-471, including its iterative degradation activity, has the potential to translate into meaningful clinical benefit for patients.

On June 25, 2019 Medtronic plc (NYSE:MDT) reported that its wholly-owned subsidiary, Medtronic Global Holdings S.C.A. ("Medtronic Luxco"), has priced an offering (the "Offering") of €250,000,000 principal amount of floating rate senior notes due 2021, €750,000,000 principal amount of 0.00% senior notes due 2022, €1,000,000,000 principal amount of 0.25% senior notes due 2025, €1,000,000,000 principal amount of 1.00% senior notes due 2031, €1,000,000,000 principal amount of 1.50% senior notes due 2039, and €1,000,000,000 principal amount of 1.75% senior notes due 2049(collectively, the "Notes") (Press release, Medtronic, JUN 25, 2019, View Source;p=RssLanding&cat=news&id=2402331 [SID1234537264]).The floating rate senior notes due 2021 are further issuances of, fully fungible with, rank equally in right of payment with and form a single series with the €500,000,000 principal amount of floating rate senior notes due 2021 initially issued by Medtronic Luxco on March 7, 2019. All of Medtronic Luxco’s obligations under the Notes will be fully and unconditionally guaranteed by Medtronic plc (the "Company") and Medtronic, Inc., a wholly-owned indirect subsidiary of Medtronic Luxco, on a senior unsecured basis.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The net proceeds of the Offering will be used to fund the previously announced cash tender offers (the "Tender Offers") for several series of outstanding notes issued by Medtronic, Inc., Medtronic Luxco and Covidien International Finance S.A., a wholly-owned indirect subsidiary of the Company, and to pay accrued and unpaid interest, premiums, fees and expenses in connection with the Tenders Offers. Any remaining net proceeds of the Offering will be used for repayment of other indebtedness and general corporate purposes. The Offering is expected to close on July 2, 2019, subject to customary closing conditions. The joint book-running managers for the Offering are Barclays Bank PLC, Goldman Sachs & Co. LLC and Merrill Lynch International.

The Offering is being made only by means of a prospectus dated February 3, 2017 and prospectus supplement (together, the "Prospectus"). You may get these documents for free by visiting EDGAR on the Securities and Exchange Commission website at www.sec.gov. Alternatively, copies of the Prospectus for the Offering may be obtained by contacting Barclays Bank PLC, toll free at +1-888-603-5847, Goldman Sachs & Co. LLC, toll-free at +1-866-471-2526 and Merrill Lynch International, toll-free at +1-800-294-1322.

On June 25, 2019 Frontier Medicines reported the closing of a Series A Preferred Stock financing round of $67 million led by Deerfield Management, Droia Oncology Ventures and MPM Capital, with participation from DCVC Bio (an affiliated fund of DCVC), RA Capital Management and other investors (Press release, Frontier Medicines, JUN 25, 2019, View Source [SID1234540983]). Frontier Medicines is a new pre-clinical stage biopharmaceutical company developing breakthrough medicines to redefine the course of debilitating diseases, starting with cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

According to the American Cancer Society, approximately 1,762,000 new cancer cases and approximately 607,000 deaths from cancer are expected to occur in the US in 2019. However, even after decades of research, the majority of known cancer-causing proteins are still considered "undruggable," or inaccessible for therapeutic intervention. This reality has become one of the most critical challenges in advancing oncology therapy and is central to the research at Frontier Medicines.

"Our therapeutic programs are focused on several of the most important and difficult targets in cancer," said Chris Varma, Ph.D., co-founder and CEO of Frontier Medicines. "With our platform, we have the ability to address previously inaccessible disease-causing proteins. While we are taking on a considerable challenge, we believe this approach will have a tremendous impact on transforming patients’ lives for the better, which is our ultimate goal."

Frontier Medicines is using chemoproteomics – an innovative approach to chemically interrogate proteins in living systems – to discover and pharmacologically target new binding pockets (or "hotspots") on proteins, making them accessible to small-molecule drug discovery and development. The company’s proprietary chemoproteomics platform also integrates advanced computational approaches and machine learning to further accelerate the path to drug discovery.

"Our platform currently includes a database of hotspots that cover a majority of human proteins, including those that were previously considered ‘undruggable;’ an expanding library of diverse, covalent compounds being driven by machine learning; and a novel approach to protein degradation," said Daniel K. Nomura, Ph.D., co-founder of Frontier Medicines. "This platform enables us to go after almost any protein target of interest for therapeutic intervention."

Founders
Frontier Medicines is founded by a team of experts in chemoproteomics, cancer biology and company building:

Chris Varma, Ph.D., Co-founder, CEO and President. Dr. Varma is a serial entrepreneur, including co-founder & former CEO of Blueprint Medicines (Nasdaq: BPMC); and VC veteran, having worked with MPM Capital, Third Rock Ventures and Flagship Ventures to build and invest in several successful companies.
Daniel K. Nomura, Ph.D., Co-founder; Associate Professor of Molecular and Cell Biology, Chemistry, Nutritional Science and Toxicology, UC Berkeley. For more than eight years, the Nomura Research Group has focused on reimagining druggability using chemoproteomic platforms to develop new disease therapies.
Roberto Zoncu, Ph.D., Co-founder; Assistant Professor of Molecular and Cell Biology, UC Berkeley. Zoncu’s research focuses on fundamental mechanisms of growth regulation in both normal and cancer states. His work has been recognized by numerous awards, including the NIH Director New Innovator Award, the Pew Stewart Scholarship for Cancer Research, the Edward Mallinckrodt, Jr. Foundation Scholarship and the Damon Runyon-Rachleff Innovation Award.
Frontier Medicines’ investors include leading crossover, venture, life sciences and technology funds, positioning Frontier Medicines well for the future. The Series A financing, building on a founding investment by MPM Capital, will enable Frontier Medicines to invest in research and development, talent acquisition and advancement of its platform and therapeutic programs.

On June 25, 2019 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium") reported at SNMMI or the 2019 Society of Nuclear Medicine and Molecular Imaging Annual Meeting that effective lymphodepletion with the radioisotope Lu-177 or lutetium-177 was achieved with its ACT or Adoptive Cell Therapy program for achieving safe, effective and transient lymphodepletion prior to the administration of CAR-T and other adoptive cell therapies (Press release, Actinium Pharmaceuticals, JUN 25, 2019, View Source [SID1234537249]). The ARC’s or Antibody Radiation-Conjugates used in the ACT program combines a CD45 targeting antibody with the cell killing power of radioisotopes.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Lymphodepletion is an important step prior to CAR-T and adoptive cell therapies that facilitates infused cells to engraft, expand and persist. Currently, chemotherapy such as Flu/Cy or Fludarabine and Cyclophosphamide are used in standard practice for lymphodepletion. Patients receiving CAR-T and other adoptive cell therapies are often heavily pre-treated and their cancer is refractory or resistant to chemotherapy. Actinium is developing its ACT program to be a potential replacement of non-specific, chemotherapy-based lymphodepletion.

In vivo animal studies demonstrated that a Lu-177 labeled CD45 ARC transiently depleted CD45 positive immune cells while sparing platelets, red blood cells and bone marrow cells. A dose response was observed with 40µCi Lu-177 having a greater lymphodepletion effect on immune cells — including B-cells, CD8 and CD4 T-cells, NK cells, myeloid derived suppressor cells and regulatory T-cells — than 20µCi Lu-177. In tumor bearing mice, the Lu-177 labeled CD45 ARC was given prior to adoptive cell therapy, which demonstrated enhanced tumor control when compared to mice that were untreated and those that only received adoptive cell therapy with no lymphodepletion (Click here for the SNMMI poster).

Dr. Dale Ludwig, Actinium’s Chief Scientific Officer, said, "I am truly excited by these additional results from our ACT program that we have presented at SNMMI evaluating lutetium-177 for targeted lymphodepletion. The data generated exceeded my expectations and support the continued development of a Lu-177 CD45 ARC as part of our ACT program. As we work to establish collaborations and partnerships while advancing the ACT program into clinical trials, the expansion to multiple warheads will give us flexibility and utility that I trust will be well received. I look forward to highlighting our continued efforts in this area at future medical conferences and industry meetings."

The antigen CD45 is uniquely expressed on leukemia, lymphoma and immune cells making it an ideal target for targeted condition prior to BMT or Bone Marrow Transplant, CAR-T and adoptive cell therapies. Actinium’s Iomab-B and ACT programs utilize the anti-CD45 antibody apamistamab. Apamistamab has been studied in over 300 patients in 13 clinical trials, including the ongoing pivotal Phase 3 SIERRA trial, across multiple hematologic indications including acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia, lymphomas and multiple myeloma. The ACT program utilizes a lower dose of the radioisotope I-131 or Iodine-131 than Iomab-B and can now also utilize Lu-177.

Actinium presented initial feasibility data for its ACT program at the Transplantation and Cellular Therapies Meeting in February 2019. The data demonstrated that a CD45 targeting antibody labeled with I-131 effectively depleted greater than 90% of lymphocytes in preclinical animal models (Click here for poster).

Sandesh Seth, Actinium’s Chairman and CEO, said, "I am excited to add the lutetium-177 warhead to our targeted conditioning armamentarium and expand our ACT program beyond iodine-131. Our targeted conditioning ARC’s are demonstrating promising results across our portfolio, including in our pivotal Phase 3 Iomab-B program for BMT and the ACT program for lymphodepletion for CAR-T and adoptive cell therapies. These therapies have the potential to significantly benefit patients and, in some instances, lead to long lasting remissions or even cures. We are confident that our targeted conditioning ARC’s can increase the number of patients that can receive these important therapies and improve patient outcomes. Recognizing the growth potential of this field we are committed to continuing to drive innovation across our ARC portfolio and further strengthening our leadership position in targeted conditioning."