On March 30, 2017 Third Rock Ventures, LLC reported the launch of Tango Therapeutics, a new cancer therapeutics company discovering and developing novel medicines designed to target cancer vulnerabilities beyond mutated oncogenes to deliver transformational new therapies for patients (Press release, Tango Therapeutics, MAR 30, 2017, View Source [SID1234520724]).

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Tango was launched with a $55 million Series A investment from Third Rock Ventures. The company has established a robust product engine that leverages advances in DNA sequencing and CRISPR-based target discovery to generate breakthrough medicines that will provide deeper, more sustained benefit than today’s targeted therapies, and extend the benefit of available immuno-oncology agents.

"Cancers are complex genetic diseases marked by multiple lesions in each tumor. These include genes that are turned on to drive cancer growth and those that are inactivated and thus, unable to function as tumor suppressors," said Barbara Weber, M.D., Tango’s interim Chief Executive Officer and a Venture Partner at Third Rock Ventures. "Loss of tumor suppressor genes is a hallmark of cancer, but the genes, themselves, are not tractable targets for drug discovery. The availability of comprehensive DNA sequencing, coupled with CRISPR-enabled target discovery, provides us with new paths to identify novel drug targets and combinations that take advantage of vulnerabilities created by loss of tumor suppressor gene function — something we have been unable to do effectively in the past. With the sophisticated genomics tools now available, the time is right for Tango to take on this challenge and focus on patients without effective treatment options."

Tango is focused on three areas of drug development, each in well-defined patient populations currently lacking effective treatment options, and each with hallmarks of cancer that have not been targeted yet. These include:

Loss of tumor suppressor gene function: A universal feature of cancer is the inactivation of genes which normally protect against tumor development. Tango is working to turn tumor suppressor gene loss from cancer’s strength into a weakness by identifying associated targetable vulnerabilities, an effect known as synthetic lethality. Drugs against synthetic lethal targets have the potential added benefit of effectiveness against cancer cells without damaging normal cells.

Multiple oncogenic drivers: To address the multiple genetic changes that give rise to cancer, Tango is working to identify novel targets for rational combinations that will offer more robust treatment effects than is possible with single-agent approaches. Decades of cancer research have shown that with the right drug combinations in the right patients, cancers can be curable.

Immune evasion: Complementing current, immune-cell-directed cancer therapies, Tango is working to identify and target the genetic alterations in cancer cells responsible for helping them avoid immune destruction. Drugs against these targets could substantially increase the benefit of current immuno-oncology drugs without increasing immune damage to normal tissues.

Tango product engine: Putting patient selection first to accelerate discovery

What fuels each of Tango’s programs is an increasingly sophisticated ability to utilize synthetic lethality, the interaction between two genes that causes cell death when both are inactivated. In cancer cells, one of these genes is inactivated by mutation; the other will be inactivated by a drug. This approach leaves normal cells largely unaffected, with the potential to greatly enhance anti-tumor efficacy and reduce associated toxicity.

The first FDA-approved example of synthetic lethality in cancer treatment is the use of PARP inhibitors for BRCA-mutant ovarian cancer. Alan Ashworth, Ph.D., a scientific Founder of Tango, discovered that combining a BRCA1/2 mutation and PARP inhibition creates synthetic lethality. Recent data show that continuing treatment with a PARP inhibitor after chemotherapy in patients with BRCA-mutant ovarian cancer extends progression-free survival for more than two years, compared to placebo. The Tango product engine is designed to systematically discover other such context-specific vulnerabilities, uncovering weaknesses created by genetic alterations in cancer and targeting them for therapeutic benefit.

In executing this strategy, Tango will upend the traditional paradigm by doing target discovery in cancer subgroups with a pre-defined patient selection approach. The company will use data from DNA sequencing of patient-derived tumor samples to define genetic contexts, and deploy CRISPR-based target discovery techniques in those cancer subtypes to identify novel drug targets.

Tango’s success will be driven by its depth of understanding of the genetic subtypes of cancer, and corresponding insights into novel drug targets and combinations uniquely relevant to each subtype. By shaping discovery efforts in this way, Tango has the potential to reach the clinic quickly, and with a clear plan for identifying the patients most likely to benefit from each new treatment, an approach that will increase both speed and probability of success in translating novel target discoveries into transformational new medicines for patients.

World-leading team spanning diverse disciplines

The Tango management team includes recognized leaders in target discovery, cancer biology, functional genomics, translational medicine and company building. Company leaders include Barbara Weber, M.D., interim Chief Executive Officer; Cary Pfeffer, M.D., interim Chief Business Officer; Daniella Beckman, C.P.A., Chief Financial Officer; Alan Huang, Ph.D., Senior Vice President, Head of Biology; John Maxwell, Ph.D., Vice President, Head of Chemistry; and Janid Ali, Ph.D., Vice President, Head of Biochemistry.

The Tango founders are a group of internationally recognized scientists and clinicians who have shaped the current state of knowledge and practice in cancer biology and genetics, translational medicine and CRISPR technology:

Alan Ashworth, Ph.D., FRS, President of the University of California San Francisco Helen Diller Family Comprehensive Cancer Center

José Baselga, M.D., Ph.D., Physician-in-Chief at Memorial Sloan Kettering Cancer Center

Levi Garraway, M.D., Ph.D., Senior Vice President of Global Oncology at Eli Lilly and Company

William Kaelin, M.D., Professor in the Department of Medicine at the Dana-Farber Cancer Institute, Harvard Medical School and a Howard Hughes Medical Institute Investigator

Timothy K. Lu, M.D., Ph.D., Associate Professor of Biological Engineering, Electrical Engineering and Computer Science at the Massachusetts Institute of Technology

Antoni Ribas, M.D., Ph.D., Professor of Medicine, Surgery, and Molecular and Medical Pharmacology at the University of California Los Angeles

About Tango Therapeutics

Tango Therapeutics is a biotechnology company developing novel medicines for patients by discovering and drugging context-dependent vulnerabilities in cancers. Tango was launched in 2017 by Third Rock Ventures and is headquartered in Cambridge, Mass.

On March 30, 2017 Samus Therapeutics, Inc. ("Samus" or the "Company"), a privately held Boston-based biopharmaceutical company developing novel therapeutics and diagnostics targeting the epichaperome reported the launch of an expanded development program for the Company’s lead anti-epichaperome candidates, including PU-H71 in various cancers and PU-AD in neurodegenerative diseases (Press release, Samus Therapeutics, MAR 30, 2017, View Source [SID1234519320]).

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Samus was established in concert with the Memorial Sloan Kettering Cancer Center (MSKCC) in 2011 by Larry Norton, MD, and Gabriela Chiosis, PhD, based on research from the Chiosis Laboratory at the Sloan Kettering Institute ("SKI"), together with collaborators at Rockefeller University and Weill Cornell Medicine. Jonathan Lewis, MD, PhD, was recruited to Samus in 2016 to serve as Executive Chairman and Chief Executive Officer to lead and accelerate the development of the Company’s epichaperome platform.

Epichaperomes are foundational protein complexes that emerge from multiple diseases, including cancer and neurological disorders, the Company’s initial areas of focus. Following various forms of cellular stress, chaperome units are rewired into the epichaperome network. Targeting the epichaperome in cancer results in cell death, and, in neurodegenerative diseases, neuronal survival, with no effect in normal cells. Recent, seminal research on the molecular characteristics and composition of the epichaperome and PU-H71 in cancer were published by the Chiosis lab in the journal Nature (Rodina, A. et al., 538, 397–401, 20 October 2016). This research revealed a direct correlation between the abundance of epichaperomes in cancer cells, and their responsiveness to the cell killing effects of PU-H71, in a manner that is independent of the mutational diversity of the tumor cells, suggesting that PU-H71 may have activity in a wide range of human tumors.

"Samus Therapeutics was founded on novel insights into the structure and function of the epichaperome complex, the modulation of which has been shown to have profound and highly specific effects in preclinical models of cancer, neurodegenerative and other diseases," said Dr. Lewis. "These insights have translated into meaningful and durable results in early clinical Page 2 of 4 study, including responses lasting greater than 24 months in patients with myelofibrosis who stopped responding to ruxolitinib.

" Dr. Lewis added: "We are extremely excited to further elucidate these seminal insights and early results in studies conducted under the support and leadership of Drs. Larry Norton, James Armitage, and Daniel Von Hoff, who will focus on breast, hematologic, and pancreatic cancers, respectively. We also look forward to leveraging the deep experience and expertise of Dr. Geoffrey Ling in neurological disease by exploring the tremendous potential of antiepichaperome small molecules in this challenging and vastly underserved area of medical need."

The Company’s advisors are each a preeminent thought leader in their area of study,
• Larry Norton, MD, is Deputy Physician-in-Chief for Breast Cancer Programs, Medical Director of the Evelyn H. Lauder Breast Center and Norma S. Sarofim Chair in Clinical Oncology.
• Gabriela Chiosis, PhD, is a Member in the Chemical Biology Program of SKI and a TriInstitutional Professor at Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine and Rockefeller University.
• James Armitage, MD, is the Joe Shapiro Professor of Medicine, Division of Oncology & Hematology, at the University of Nebraska Medical Center; and former Dean, University of Nebraska Medical School.
• Daniel D. Von Hoff, MD, is the Physician in Chief, Distinguished Professor, Translational Research at the Translational Genomics Research Institute ("TGen") Senior Consultant, Clinical Investigations for the City of Hope, and Professor of Medicine at the Mayo Clinic.
• Geoffrey Ling, MD, PhD, is Professor of Neurology at the Johns Hopkins School of Medicine, and the former Director of the DARPA Biological Technologies Office, and professor and Acting Chair of the Department of Neurology at the Uniformed Services University of the Health Sciences.

Clinical Development Programs in Cancer and Neurodegenerative Disease

PU-H71, the Company’s lead program targeting the epichaperome network, has demonstrated potent anticancer activity in preclinical in vitro and in vivo studies, including both therapeutic synergy, and reversal of resistance, in combination with multiple standard of care therapies. A Phase 1 study, conducted under an MSKCC-initiated investigational new drug application (IND), has been completed, identifying a maximum tolerated dose, establishing a well-tolerated toxicity profile, and demonstrating activity supporting further combination clinical study.
The Company announces today the launch of several studies in cancer including:
• A Phase 1b/2 combination study in myelofibrosis under a second Company IND, expected to be filed in early Q2. In Phase 1, treatment with PU-H71 demonstrated durable results (>24 months) in this indication in patients who had previously failed ruxolitinib;
• A Phase 1b combination study in advanced breast cancer at MSKCC, with the first patient expected to be treated in early Q2; •
A Phase 1b combination study in chemo-naïve front-line metastatic pancreatic cancer under the Company’s first IND, recently accepted by the U.S. Food and Drug Administration (FDA), with the first patient expected to be treated early Q2.

A companion diagnostic for determining patient selection, response to treatment and dose and schedule, PU-H71-PET, is also being explored in an ongoing Phase 1 study, and the Company Page 3 of 4 is developing a companion diagnostic for in vitro measurement of circulating epichaperome positive cells in blood by flow cytometry ("PU-CYT"). Further, the Company is evaluating trials in other hematologic cancers, and the Chiosis lab was recently awarded a SKI "Big Bet" grant for the study of epichaperome inhibitors in combination with immunotherapy in oncology.

Samus’ second anti-epichaperome small molecule, PU-AD, along with the diagnostic PU-ADPET, are expected to move into neurodegenerative disease-directed clinical studies, including Alzheimer’s disease and chronic traumatic encephalopathy ("CTE"). A Phase 1 positron emission tomography ("PET") diagnostic study is currently active and recruiting Alzheimer’s patients at MSKCC, which the Company expects to expand to include patients with CTE. The Company expects to file an IND for the PU-AD therapeutic and diagnostic in neurodegenerative disease, and an exploratory Phase 1 clinical study for CTE with outside collaborators is currently in the planning stage.

The development of Samus’ candidates will be led by a deeply experienced management and advisory team, including Dr. Lewis, who brings more than 20 years of experience in leadership roles in biotechnology and medicine, Dick Bagley, President and Chief Financial Officer, who has over 40 years of senior leadership in both pharma and biotechnology, and senior level professionals with experience in translational research, clinical trial design and execution, manufacturing, quality control, intellectual property, and global regulatory approvals.

On March 31 2017 Johnson & Johnson (NYSE: JNJ) reported that its Swiss subsidiary, Janssen Holding GmbH ("Janssen"), published the provisional notice of the interim result of its all-cash public tender offer in Switzerland to acquire all publicly held shares of Actelion Ltd (("Actelion") SIX:ATLN) for $280 per share, payable in U.S. dollars, per the offer prospectus of February 16, 2017 (Press release, Actelion, MAR 30, 2017, View Source [SID1234518407]).

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At the expiration of the main offer period on March 30, 2017, 10:00 a.m. EDT, 4:00 p.m. CEST, a total of 78,629,955 Actelion shares were tendered, corresponding to 73.25% of the 107,339,642 Actelion shares covered by the tender offer. Including the Actelion shares tendered, Janssen and Actelion, a person acting in concert with Janssen, held as of the end of the main offer period 83,195,346 Actelion shares, corresponding to 77.20% of the voting rights and the share capital of Actelion.

Subject to the satisfaction of certain conditions, Janssen has declared the tender offer successful. The additional acceptance period of ten trading days (at the SIX Swiss Exchange) for the subsequent acceptance of the tender offer will commence on April 6, 2017 and expire on April 21, 2017, 10:00 a.m. EDT, 4:00 p.m. CEST.

Johnson & Johnson also announced that the applicable waiting periods under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended, with respect to Janssen’s proposed acquisition of Actelion have either expired or been terminated early. The Japan Fair Trade Commission and the Israeli Antitrust Authority have cleared the proposed acquisition of Actelion.

Based on the current understanding of the regulatory approval proceedings in different jurisdictions, the settlement of the tender offer is expected to occur, subject to the satisfaction of all relevant conditions to the tender offer, including regulatory approvals, in the second quarter of 2017.

As previously announced, as part of the transaction, Actelion will spin out its drug discovery operations and early-stage clinical development assets into a newly created Swiss biopharmaceutical company ("Idorsia Ltd"). The shares of Idorsia Ltd are expected to be distributed to Actelion’s shareholders as a dividend in kind and listed on the SIX Swiss Exchange on the day of the settlement of the tender offer. Johnson & Johnson will initially hold 16 percent of the shares of Idorsia Ltd and have rights to potentially increase to 32 percent through a convertible note.

On March 2017 Oxford BioMedica plc ("Oxford BioMedica" or "the Group") (LSE:OXB), a leading gene and cell therapy group, reported the announcement by Novartis that the US Food and Drug Administration (FDA) has accepted its Biologics License Application (BLA) filing and granted priority review for CTL019 (tisagenlecleucel-T), an investigational chimeric antigen receptor T cell (CAR-T) therapy, in relapsed and refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL) (Press release, Oxford BioMedica, MAR 30, 2017, View Source [SID1234518317]). The priority review designation is expected to shorten the anticipated review time by the FDA.

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Oxford BioMedica is the sole manufacturer of the lentiviral vector expressing CTL019 for Novartis. As announced in October 2014, Oxford BioMedica will also receive undisclosed royalties on potential future sales of Novartis CAR-T products.

John Dawson, Chief Executive Officer of Oxford BioMedica, commented: "The news that the FDA has accepted the BLA for CTL019 and granted it priority review is an important development for Oxford BioMedica. We continue to work closely with Novartis in delivering the lentiviral vector expressing CTL019, a product described earlier this year by Novartis as having "blockbuster" potential."

(Filing, Annual, Rosetta Genomics, 2016, MAR 29, 2017, View Source [SID1234518386])

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