On December 2, 2019 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Audentes Therapeutics, Inc. (NASDAQ: BOLD, Chairman and CEO: Matthew R. Patterson, "Audentes"), reported that they have entered into a definitive agreement for Astellas to acquire Audentes at a price of US$60.00 per share in cash, representing a total equity value of approximately US$3 billion (Press release, Astellas, DEC 2, 2019, View Source [SID1234551820]).

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"Recent scientific and technological advances in genetic medicine have advanced the potential to deliver unprecedented and sustained value to patients, and even to curing diseases with a single intervention," said Kenji Yasukawa, President and CEO, Astellas. "Audentes has developed a robust pipeline of promising product candidates which are complementary to our existing pipeline, including its lead program AT132 for the treatment of X-Linked Myotubular Myopathy (XLMTM). By joining together with Audentes’ talented team, we are establishing a leading position in the field of gene therapy with the goal of addressing the unmet needs of patients living with serious, rare diseases."

"We are very pleased to enter into this merger agreement with Astellas," stated Matthew R. Patterson, Chairman and Chief Executive Officer of Audentes. "With its focus on innovative science and a global network of research, development and commercialization resources, we believe that operating as part of the Astellas organization optimally positions us to advance our pipeline programs and serve our patients."

The acquisition of Audentes represents a key step in the expansion of the Astellas Focus Area approach, under which Astellas strives to create innovative medicines for diseases with high unmet medical needs by identifying unique combinations of biology and therapeutic modality/technology based on emerging science. In addition to the four Primary Focus in which Astellas currently prioritizes its investment, with the acquisition of Audentes, the company is adding a fifth Primary Focus in Genetic Regulation, under which gene therapy will be a key driver of the company’s future growth.

Strategic Significance of the Acquisition

Accesses the near-term growth opportunity of AT132, in development for the treatment of XLMTM, a serious, life-threatening, rare neuromuscular disease that is characterized by extreme muscle weakness, respiratory failure and early death.
Accelerates the development of a robust pipeline of potentially best-in-class genetic medicines for rare neuromuscular diseases, by combining Astellas’ scientific capabilities and global resources with Audentes’ AAV gene therapy technology platform, in-house large-scale cGMP manufacturing and neuromuscular development expertise.
Creates the opportunity for additional gene therapy partnerships and pipeline expansion through leveraging Audentes’ manufacturing capabilities and its valued relationships with patient groups, academic collaborators and scientific advisors.
Transaction Details

Under the agreement, which has been unanimously approved by the boards of directors of both Astellas and Audentes, Astellas will acquire Audentes through Asilomar Acquisition Corp., a wholly-owned subsidiary of Astellas US Holding, Inc. ("Asilomar"). Asilomar will commence a tender offer for all outstanding shares of common stock of Audentes, for a price of US$60.00 per share in cash (the "Tender Offer"). Promptly upon successful completion of the Tender Offer, Asilomar will be merged into Audentes, and any remaining shares of common stock of Audentes will be canceled and converted into the right to receive the same US$60.00 per share price. The board of directors of Audentes has resolved to recommend that Audentes stockholders tender their shares to Astellas.

Financial Details and Closing Conditions

Consummation of the transaction is subject to customary closing conditions, including US antitrust clearance and the tender of a majority of Audentes’ outstanding shares of common stock. The offer price represents a premium of 110% to Audentes’ closing share price of US$28.61 on December 2, 2019. The all-cash transaction is valued at approximately US$3 billion including the purchase of all common shares, options, restricted stock units and other securities. The Tender Offer period is expected to commence in the next few weeks and to expire 20 business days after its commencement, unless otherwise extended. If the Tender Offer conditions are not satisfied, Astellas may be required to extend the Tender Offer under certain circumstances.

Astellas is still reviewing the impact of a consummation of the transaction on its financial results for the fiscal year ending March 31, 2020.

Morgan Stanley & Co. LLC, acting through its affiliate Mitsubishi UFJ Morgan Stanley Securities Co., Ltd., is acting as exclusive financial advisor to Astellas and Covington & Burling LLP is acting as its legal counsel.

Centerview Partners LLC is acting as exclusive financial advisor to Audentes and Fenwick & West LLP is acting as its legal counsel.

On December 2, 2019 Akari Therapeutics, Plc (Nasdaq: AKTX), a biopharmaceutical company focused on innovative therapeutics to treat orphan autoimmune and inflammatory diseases where the complement and/or leukotriene systems are implicated, reported the design of a pivotal Phase III pediatric trial in HSCT-TMA following a FDA End-of-Phase II meeting (Press release, Akari Therapeutics, DEC 2, 2019, View Source [SID1234551819]). Akari also announces that, in another hematological condition, all six patients from the long-term Phase II PNH study who were transfusion dependent at entry are now transfusion independent on long-term treatment with nomacopan.

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HSCT-TMA is an orphan hematological condition with no approved treatments and an estimated mortality rate of more than 80% in children with the severe form of the disease1. It is this severe form that is being targeted with nomacopan. Following a recent End-of-Phase II meeting with the FDA, Akari plans to initiate a single arm responder-based study design, based on treatment with nomacopan for up to 24 weeks. The primary endpoints are focused on disease response defined primarily by renal improvement and reduced transfusion dependence. The study will be in two parts, with data from seven patients in Part A used to confirm dosing and endpoints for Part B, with the pharmacokinetic (PK) modelling agreed with the FDA through Akari’s participation in the Model Informed Drug Discovery Program (MIDD). Following an interim efficacy and safety readout from Part A and meeting with the FDA, patients would then be recruited into Part B of the responder study.

While the role of complement inhibition is understood to play an important role in HSCT-TMA, LTB4 may also be an important target in reducing epithelial activation in both TMA and graft versus-host disease2 (GVHD) which often occur simultaneously. Daily dosing with nomacopan is also likely to be of a particular advantage in facilitating more complete complement suppression, especially in HSCT-TMA patients with high transfusion requirements.

HSCT-TMA is Akari’s second haematological clinical program and follows a successful Phase II study in PNH completed in early 2018, after which patients continued treatment with nomacopan in a long-term safety study. New data from Akari’s ongoing long-term study, shows that all six patients from the Phase II study who were transfusion dependent at entry are now transfusion independent on nomacopan, having had in all cases no transfusions for a minimum of six months. In addition, during more than 20 cumulative patient-years of PNH patient treatment with nomacopan, there have been no reported drug-related serious adverse events.

"Following our meeting with the FDA, we look forward to starting the pivotal Phase III study of nomacopan in HSCT-TMA, a potential treatment for a high risk pediatric population which currently has no approved therapies. If successful, we expect this will be a gateway indication into a range of other poorly treated orphan TMAs," commented Clive Richardson, CEO Akari Therapeutics. "We are pleased with the progress being made across our clinical studies where recent positive clinical data in bullous pemphigoid (BP) and PNH provides further support for the underlying efficacy of nomacopan."

1 Sonata Jodele, et al. New approaches in the diagnosis, pathophysiology, and treatment of pediatric hematopoietic stem cell transplantation associated thrombotic microangiopathy. Transfus Apher Sci . 2016 April; 54(2): 181–190

2 Takatsuka, et al. Predicting the severity of intestinal graft-versus-host disease from leukotriene B4 levels after bone marrow transplantation. Transplantation 2000, 26: 1313-1316

On December 2, 2019 Eli Lilly and Company (NYSE: LLY) reported that it will participate in the Evercore ISI 2nd Annual HealthCONx Conference on Wednesday, December 4, 2019 (Press release, Eli Lilly, DEC 2, 2019, https://investor.lilly.com/news-releases/news-release-details/lilly-participate-evercore-isi-2nd-annual-healthconx-conference [SID1234551818]). Daniel Skovronsky, M.D., Ph.D., Lilly’s Chief Scientific Officer and President of Lilly Research Laboratories, will participate in a fireside chat at 9:30 a.m., Eastern Time.

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A live audio webcast will be available on the "Webcasts & Presentations" section of Lilly’s Investor website at View Source A replay of the presentation will be available on this same website for approximately 90 days.

On December 2, 2019 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that its licensing partner Specialised Therapeutics Asia (STA) has received marketing approval of NERLYNX (neratinib) in Singapore from the Health Sciences Authority (HSA), a statutory board under the Ministry of Health of the Singapore Government (Press release, Puma Biotechnology, DEC 2, 2019, View Source [SID1234551817]). NERLYNX is indicated for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

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STA Chief Executive Officer Carlo Montagner said, "The approval in Singapore is a key milestone for the company as NERLYNX is the first drug in our portfolio to be approved by the HSA for commercialization in Singapore. We look forward to extending the reach of this medicine, with regulatory dossiers also submitted in Malaysia, Brunei and the Philippines."

Alan H. Auerbach, Chief Executive Officer and President of Puma, added, "We have been extremely pleased with the strong commercial strategy implemented by Specialised Therapeutics in Australia and we look forward to their continued success throughout South East Asia. We are committed to expanding access to NERLYNX to breast cancer patients around the world."

About HER2-Positive Breast Cancer

Approximately 20 to 25 percent of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.

On December 2, 2019 Cellectis (Euronext Growth: ALCLS – Nasdaq: CLLS), a clinical-stage biopharmaceutical company focused on developing immunotherapies based on gene-edited allogeneic CAR T-cells (UCART), reported that the first patient enrolled in the dose escalation Phase 1 clinical study for its UCART22 product candidate has been dosed at The University of Texas MD Anderson Cancer Center (Press release, Cellectis, DEC 2, 2019, View Source [SID1234551816]). This clinical study, BALLI-01, will evaluate the safety, expansion, persistence and clinical activity of UCART22, a product candidate composed of engineered T-cells expressing anti-CD22 chimeric antigen receptors, in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).

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UCART22 targets CD22, which is a B-cell restricted surface antigen expressed in normal B-lineage cells, as well as in blast cells from B-ALL and other B-cell malignancies.

"By targeting the CD22 antigen, we aim at offering a therapeutic solution to patients living with B-ALL, including those patients that have relapsed or did not respond to CD19-directed therapy, such as CAR-T or bispecific antibody treatments. UCART22 is an allogeneic product candidate that can be dosed in all eligible patients even if they underwent prior autologous or allogeneic CAR-T therapies," said Dr. André Choulika, Chairman and CEO, Cellectis. "With the recent announcement of our UCARTCS1 first dosing, this milestone shows our momentum at Cellectis as we continue moving forward our portfolio of proprietary product candidates into clinical development. We have high hopes that UCART22 will address an unmet medical need for patients with B-ALL, with the potential to expand into other indications for B-cell malignancies."

The clinical trial is led by Dr. Nitin Jain, MD, Associate Professor, Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center (Houston, TX) in collaboration with Dr. Richard Larson, MD, Director of the Hematologic Malignancies Clinical Research Program at the University of Chicago Medicine (Chicago, IL) and with Dr. Gail Roboz, MD, Director, Clinical and Translational Leukemia Programs, Professor of Medicine, Weill Cornell Medical College The New York Presbyterian Hospital (New York, NY).

About UCART22

UCART22 is one of Cellectis’ wholly owned, allogeneic, off-the-shelf gene-edited T-cell product candidates, designed for the treatment of relapsed and refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). Like CD19, CD22 is a cell surface antigen expressed from the pre-B-cell stage of development through mature B-cells. CD22 expression occurs in more than 90% of patients with B-ALL.

About B-cell Acute Lymphoblastic Leukemia (B-ALL)

B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic disease characterized by the proliferation of immature lymphoid cells in the bone marrow, peripheral blood and other organs. The increase and accumulation of blast cells in the bone marrow results in suppression of the normal production of blood cell and blood plasma components, and can therefore cause anemia, thrombocytopenia, neutropenia and risk of infection. Acute lymphoblastic leukemia (ALL) can start either with early B-cells or T-cells at different stages of maturity, however, approximately 85% of ALL cases involve precursor B-cells (B-ALL).