On April 17, 2018 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) reported the presentation of preclinical data exploring the mechanism of action of APTO-253, the company’s clinical stage product candidate (Press release, Aptose Biosciences, APR 17, 2018, View Source;p=RssLanding&cat=news&id=2343016 [SID1234525432]). The data, demonstrating heightened sensitivity of BRCA1 or BRCA2 mutated cancer cells to APTO-253, were presented in a poster Tuesday, April 17 at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 14-18, in Chicago, IL.

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The poster, entitled APTO-253 is a new addition to the repertoire of drugs that can exploit DNA BRCA1/2 deficiency, explored the mechanism of action of APTO-253, a small molecule with anti-proliferative activity against cell lines derived from a wide range of human malignancies. This study investigated the mechanism of action of APTO-253 to identify synthetic lethal interactions that can guide combination drug studies.

The research team found that APTO-253 stabilizes certain quadruplex DNA structures, causes DNA damage, and exhibits synthetic lethality comparable to olaparib – an FDA-approved targeted therapy that acts against cancers in people with hereditary BRCA1 or BRCA1 mutations, including some ovarian, breast and prostate cancers – albeit through a different mechanism. Unlike other drugs for which loss of this DNA repair function results in hypersensitivity, APTO-253 does not produce myelosuppression even at the maximum tolerated dose. The observations reported also identify γH2AX as a potential biomarker of clinical effect and open the window to more detailed studies of how APTO-253 promotes DNA damage and how it might be used clinically to treat patients with tumors harboring deficiencies in DNA repair.

The presentation will be published in the AACR (Free AACR Whitepaper) Conference Proceedings. The poster can also be accessed here or at the Publications & Presentations section of the Aptose website, www.aptose.com.
"We have clarified the mechanism of APTO-253 during the past year or so, including its mechanism to inhibit expression of the MYC gene, an oncogene that promotes tumor growth and resistance to drugs in AML and other cancers," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "AML remains our primary focus for APTO-253, and we hope to re-initiate dosing of AML patients with APTO-253 in an open phase Ib trial during the 2nd quarter of 2018. In the current presentation at AACR (Free AACR Whitepaper), we report that cancer cells deficient in the BRCA1/2 DNA repair functions are hyper-sensitive to APTO-253, analogous to the FDA-approved PARP inhibitor olaparib, but acting through a different mechanism. The findings reveal potential new solid tumor indications for APTO-253. Importantly, APTO-253 does not produce myelosuppression even at the maximum tolerated dose, which significantly distinguishes it from other cancer chemotherapies."

About APTO-253
APTO-253 is a clinical-stage small molecule targeted therapeutic agent that inhibits expression of the c-Myc oncogene, leading to cell cycle arrest and programmed cell death (apoptosis) in human-derived solid tumor and hematologic cancer cells, without causing general myelosuppression of the healthy bone marrow. The c-Myc oncogene is overexpressed in hematologic cancers, including acute myeloid leukemia (AML). Aptose researchers have reported the ability of APTO-253 to induce cell death, or apoptosis, in multiple blood cancer cell lines including AML, as well as in vitro synergy with various classes of conventional approved and investigational therapies for AML or myelodysplastic syndromes (MDS). New findings reveal that APTO-253 might also serve certain solid tumor patients with BRCA1/2 mutations, but without causing toxicity to the normal bone marrow functions.

Now in its fourth day, the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018 held in Chicago, has had plenty of news, much of it preclinical or early-clinical data (Press release, BioSpace, APR 17, 2018, View Source [SID1234525433]). Here’s a roundup of some of the top stories.

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Compugen and Bayer AG presented efficacy data of BAY 1905254 in cancer immunotherapy. The compound is a first-in-class antibody candidate that targets ILDR2, a novel immune checkpoint discovered by Israeli company Compugen. Bayer expects to move it into human trials sometime this year.

"ILDR2 is a completely new immune checkpoint that we discovered through our computational discovery capabilities," said Anat Cohen-Dayag, Compugen’s president and chief executive officer, in a statement. "This immune checkpoint, together with the discovery of TIGIT and PVRIG, clearly demonstrate the power and value of Compugen’s predictive discovery capabilities in the discovery of new drug targets and pathways, enabling the development of first-in-class product opportunities."
Sierra Oncology, based in Vancouver, presented data for its Checkpoint kinase 1 (Chk1) inhibitor SRA737, as a monotherapy and in combination with a poly ADP-ribose polymerase inhibitor (PARPi) like Tesaro’s Zejula (niraparib). It is being evaluated in an ongoing Phase I/II trial in replication stress-driven cancer. It also plans to initiate a Phase Ib/II trial in metastatic castration-resistant prostate cancer in the fourth quarter.

Tarveda Therapeutics, headquartered in Watertown, Massachusetts, presented preclinical data related to PEN-866. PEN-866 is a miniature drug conjugate to treat patients with solid tumor types that are sensitive to topoisomerase 1 inhibitors like SN-38, which is PEN-866’s payload. It is being evaluated in models of ovarian cancer, lung cancer and colorectal cancer. PEN-866 utilizes the activation of Heat Shock Protein 90 (HSP90) in tumors in order to accumulate and release its payload.

Lycera Corp., located in New York and Ann Arbor, Michigan, released clinical findings from the Phase I part of its Phase I/IIa ARGON trial of the company’s novel immuno-oncology candidate, LYC-55716. LYC-55716 is a first-in-class oral, selective retinoic acid-related orphan receptor-gamma (RORgamma) agonist that reprograms the immune system in solid tumor patients. In the 32 patients enrolled in six dosing cohorts, the drug was well tolerated and no dose-limiting toxicities were seen.
"The promising safety results and early signals of efficacy with LYC-55716 as a monotherapy are very encouraging," said Judy Wang, associate director of Drug Development, Florida Cancer Specialists and Sarah Cannon Research Institute, in a statement. "We are very pleased to be participating in the development of this novel immunotherapeutic, and are actively enrolling patients with advanced solid tumor cancers in the Phase IIa portion of the study."

Lund, Sweden’s Alligator Bioscience presented preclinical data on its immune activating antibody ATOR-1015. ATOR-1015 is a first-in-class bispecific tumor-directed antibody that targets CTLA-4 and OX40. The data shows the compound localizes to the tumor and activates the immune system in the surrounding area, which confirms the drug’s mechanism of action. It is designed mostly for a combo-therapy with PD-1 blocking antibody.
"The results presented in Chicago confirm that our CTLA-4 bispecific antibody ATOR-1015 selectively activates the immune system in the tumor area," said Per Norlen, Alligator’s chief executive officer, in a statement. "This offers great potential for an improved benefit/risk profile for cancer patients. We are more and more excited about the significant prospects for this unique compound, particularly in combination with PD-1 blockers, and are looking forward to initiate clinical development later in the year."
CBT Pharmaceuticals, based in Pleasonton, California, a U.S. and China-based biopharmaceutical company, presented preclinical in-vivo data and animal safety pharmacology studies of CBT-102. This compound is a multi-targeted kinase inhibitor that targets VEGFR, PDGFR, MAPK, B-RAF, C-RAF, C-KIT and CSF1R. It showed tumor regression in 52 patient-derived xenograft models, including non-small cell lung, colorectal, gastric, and hepatocellular carcinoma.
"We are highly encouraged by the preclinical safety and efficacy data of CBT-102," said Sanjeef Redkar, president and chief executive officer of CBT Pharma, in a statement. "Based on this data set, we plan to advance CBT-102 into GLP toxicology studies in 2018 with an aim to enter the clinic in early 2019 in combination with other agents in our portfolio."

On April 17, 2018 Johnson & Johnson reported a strong first quarter with $20 billion in sales that was fueled by significant growth in its pharmaceuticals business (Press release, BioSpace, APR 17, 2018, View Source [SID1234525487]).

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About half of the healthcare giant’s quarterly sales was driven by the company’s pharma business. In its quarterly report, the healthcare giant said pharmaceutical sales generated $9.8 billion in the first quarter. That was an increase of 19.4 percent over the same period last year. The bulk of the company’s pharma sales were made overseas, according to the data. J&J said international sales increased by 33.1 percent and domestic sales increased 9.9 percent.

The company noted that strong sales were driven by drugs such as Darzalex (daratumumab), a treatment for multiple myeloma, Tremfya (guselkumab) a treatment for moderate to severe plaque psoriasis and blood-cancer treatment Imbruvica (ibrutinib). During the first quarter J&J filed a supplemental New Drug Application for Imbruvica as a treatment for Waldenström’s macroglobulinemia.

Johnson and Johnson noted other strong-performing drugs including Zytiga (abiraterone acetate), which is used for the treatment of metastatic, castration-resistant prostate cancer. During the quarter Zytiga gained approval for an additional indication as at treatment of metastatic high-risk castration-resistant prostate cancer. Two other strong performers included inflammatory disease treatment Stelara (ustekinumab) and the anti-blood clotting drug Xarelto.

Also, during the first quarter, J&J gained approval from the U.S. Food and Drug Administration for Erleada, an oral androgen receptor inhibitor for the treatment of patients with non-metastatic castration-resistant prostate cancer.

Johnson & Johnson noted that the pharmaceutical business gained a 7.6 percent boost from the company’s 2017 $30 billion acquisition of Swiss-based Actelion, which manufactures Tracleer, a drug used to treat pulmonary arterial hypertension a form of high blood pressure in the arteries of the lungs. While J&J saw an increase in earnings from the deal, the company noted that it discontinued development of one of the drug candidates picked up in that acquisition. In its earnings report, J&J said it terminated development of cadazolid, a Phase III program for the treatment of clostridium difficile-associated diarrhea. Months after the deal was announced Actelion disclosed that cadazolid saw mixed results in two identical studies. The drug hit the mark in reducing diarrhea in patients in one study but failed to do so in a joint-study.

Alex Gorsky, chief executive officer of Johnson & Johnson, said the company’s pharmaceutical business delivered robust returns for the company.

In addition to its strong pharma showing, J&J said its medical device business saw sales of $6.8 billion for the first quarter, which represented an increase of 7.5 percent over the prior year.

Not only did J&J see strong revenues from its pharma business, Gorsky added that the company is also benefitting from a revamping of U.S. tax laws. He said the new legislation that reduced corporate tax rates in the United States will allow the company to invest more than $30 billion in research and development, as well as capital investments over the next four years. Gorsky said that investment is an increase of 15 percent over the previous four years.

On April 17, 2018 Paris-based Sanofi has reported that agreed to sell its generics division, Zentiva, to Advent International (Press release, BioSpace, APR 17, 2018, View Source [SID1234525434]).

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The deal is expected to wrap by the end of this year. Advent, a private equity firm, will acquire the company for 1.9 billion euros, or about $2.4 billion (U.S.).

Reuters notes, "Sanofi has been reshaping its business in recent months, spending more than $16 billion to buy biotech company Ablynx and U.S. hemophilia specialist Bioverativ, but also selling off some assets. This week, it sold some brands to Charterhouse Capital Partners’ Cooper-Vemedia drugs manufacturing arm for 158 million euros."
"Zentiva is a robust business with a highly talented workforce and we believe it has demonstrated its potential for growth," said Olivier Brandicourt, Sanofi’s chief executive officer, in a statement. "Following a comprehensive review of strategic options for our generics unit in Europe, we have determined that transferring this business to Advent is the best option to ensure its long-term success."

This specific sale planning began in October 2017. However, it has been up for grabs for some time, including plans made in November 2015. Sanofi had spent much of the year prior to restructuring Zentiva as a stand-alone company in order to be sold. In February, Reuters reported that the short list of potential buyers included Carlyle, BC Partners and a consortium of Blackstone and Nordic Capital. Two pharma companies were also on the list, Brazilian company EMS and India’s Torrent Pharma.

Since at least 2015, Sanofi has been restructuring as part of a new strategy. This included spinning off its animal health unit, Merial, and the European generics business. In mid-December 2015, Sanofi and Germany-based Boehringer Ingelheim GmbH announced plans to exchange business units. The intention was for Sanofi to swap Merial with Boehringer Ingelheim’s consumer healthcare business. Boehringer Ingelheim’s consumer healthcare business in China was not part of that deal.

The sale of Zentiva was delayed partly to decide which parts of the division to sell. Some of the rationale behind the sale is related to distributor consolidation. Distributors buy generic versions to sell to patients, and once merged, they have more leverage to negotiate lower prices. For the last three years, there has been significant consolidation of generics distributors worldwide.

Zentiva does business in 50 markets, particularly in Eastern Europe—the Czech Republic, Slovakia and Romania. Its portfolio of generic drugs includes products for cardiovascular indications and gastrointestinal drugs, in addition to versions of ibuprofen and leflunomide.
Jerome Schupp, fund manager at Geneva-based Prime Partners, which currently does not hold Sanofi shares, told Reuters, "The sale price is decent, but nothing that extraordinary. Sanofi will probably re-invest the proceeds in looking to make pharma or biotech acquisitions. They are looking to strengthen their pipeline, which is a bit weak at the moment."

The news follows yesterday’s announcement that Shire was selling its oncology business to France’s Servier for $2.4 billion. And Japan’s Takeda Pharmaceuticals announced several weeks ago its interest in buying Shire. Under UK acquisition laws, Takeda has until April 25 to announce an official bid. Shire’s market value is about $47 billion.
Pfizer has also been trying to unload its consumer healthcare business. Most recently, GlaxoSmithKline walked away from the deal, as had Reckitt Benckiser Group. The Pfizer business unit is valued at about $15 to $20 billion.

On April 17, 2018 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it has launched atezolizumab, a recombinant humanized anti-PD-L1 monoclonal antibody, (brand name, "TECENTRIQ Intravenous Infusion 1200 mg;" hereafter, "TECENTRIQ") for the treatment of "unresectable advanced or recurrent non-small cell lung cancer (NSCLC) today (Press release, Chugai, APR 17, 2018, View Source [SID1234525488]). TECENTRIQ received a manufacturing and marketing approval on January 19, 2018 and was listed on the National Health Insurance (NHI) reimbursement price list today.

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"Cancer immunotherapy is expected to be a breakthrough therapy which may significantly change cancer treatment. As our mission is to deliver innovative therapeutic drugs to patients, it is a great pleasure for us to finally being able to launch TECENTRIQ," said Chugai’s President & CEO, Tatsuro Kosaka. "We will continue our research and development activities in multiple cancer types and combination therapies to realize sustained therapeutic effects and improvement of survival rate, as well as cure in more patients with cancer."

TECENTRIQ is an immune checkpoint inhibitor targeting PD-L1 (Programmed Death-Ligand 1) which is a protein expressed on tumor cells and tumor-infiltrating immune cells. PD-L1 blocks T-cell activity by binding with PD-1 and B7.1 receptors on T-cell surface. By inhibiting PD-L1, TECENTRIQ may enable the activation of T-cells and boost immune response against cancer cells.

In Japan, the annual prevalence of lung cancer is estimated to be approximately 128,700 in 2017 (male: 86,700, female: 42,000). The annual mortality of lung cancer, the leading cause of cancer deaths (the second leading cause in women) in Japan, is approximately 78,000 (male: 55,600, female: 22,400; predicted figure for 2017).*

As a top company in the field of oncology in Japan, Chugai firmly believes that the launch of TECENTRIQ in Japan as a new therapeutic option for the treatment of "unresectable advanced or recurrent NSCLC," will allow us to further contribute to treat patients and promote appropriate use of drugs.