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.

On April 17, 2018 Rigel Pharmaceuticals, Inc. reported that the U.S. Food and Drug Administration (FDA) approved TAVALISSE (fostamatinib disodium hexahydrate) for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment (Press release, Rigel, APR 17, 2018, View Source [SID1234605501]). TAVALISSE is an oral spleen tyrosine kinase (SYK) inhibitor that targets the underlying autoimmune cause of the disease by impeding platelet destruction, providing an important new treatment option for adult patients with chronic ITP. Rigel plans to launch TAVALISSE in the United States in late May 2018.

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"Chronic ITP is challenging to treat because the heterogeneity of the disease makes it difficult to predict how an individual patient will respond to available treatments and not all patients can find a treatment that works well for them," said James Bussel, M.D., professor emeritus of pediatrics at Weill Cornell Medicine and the principal study investigator on the FIT Phase 3 program. Dr. Bussel has served as a consultant and paid member of the advisory board for Rigel Pharmaceuticals, Inc. "The FDA approval of fostamatinib arms physicians with a new treatment option, which works via a novel mechanism."

The FDA approval of TAVALISSE was supported by data from the FIT clinical program, which included two randomized placebo-controlled Phase 3 trials (Studies 047 and 048) and an open-label extension (Study 049), as well as an initial proof of concept study. The New Drug Application (NDA) included data from 163 ITP patients and was supported by a safety database of more than 4,600 subjects across other indications in which fostamatinib has been evaluated.

"People living with chronic ITP often feel they have an invisible disease — one that can not only impact quality of life, but also be life threatening," said Caroline Kruse, executive director of the Platelet Disorder Support Association, a patient advocacy organization dedicated to ITP patients. "That’s why we encourage members of our community to learn about their disease, understand treatment strategies, and seek support so that they can advocate for their best care. The availability of a new treatment option provides the ITP community with more choices."

Different Treatment Approach
TAVALISSE is designed to inhibit SYK, a key signaling component in the body’s immune process that can lead to platelet destruction in ITP patients. TAVALISSE may address an underlying autoimmune cause of ITP by impeding platelet destruction.

"We are excited to bring this new medicine to the population of adult patients with chronic ITP in need of additional therapies. I want to thank the patients, caregivers and physicians who contributed to our fostamatinib clinical program, and also the Rigel team for all of their dedication and hard work to bring the company to this historic day," said Raul Rodriguez, president and CEO of Rigel Pharmaceuticals. "This regulatory milestone, our first product approval, validates the therapeutic effect of SYK inhibition in an autoimmune disease."

Rigel will be providing product information at the ASCO (Free ASCO Whitepaper) Annual Meeting being held June 1-5, 2018 in Chicago, Booth #24160, or you can visit www.TAVALISSE.com.

About ITP
In patients with ITP, the immune system attacks and destroys the body’s own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP include excessive bruising, bleeding and fatigue. People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPOs) and splenectomy. However, not all patients have an adequate treatment response with existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP.

About TAVALISSE
Indication
TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Important Safety Information
Warnings and Precautions

Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required.
Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to >3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation.
Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE.
Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation.
TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose.
Drug Interactions

Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose.
It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406.
Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug.
Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug.
Adverse Reactions

Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%).
Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.
Please see www.TAVALISSE.com for full Prescribing Information.

To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).

Trademarks for TAVALISSE are owned by or licensed by Rigel.

Conference Call and Webcast Today at 5:00PM Eastern Time
Rigel will hold a live conference call and webcast today at 5:00pm Eastern Time (2:00pm Pacific Time).

Participants can access the live conference call by dialing (855) 892-1489 (domestic) or (720) 634-2939 (international) and using the Conference ID number 5189918. The slide presentation accompanying the conference call can be accessed from Rigel’s website at www.rigel.com/webcasts. The webcast will be archived and available for replay after the call via the Rigel website.

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 Alligator Bioscience (Nasdaq Stockholm: ATORX), a biotechnology company developing antibody-based pharmaceuticals for tumor-directed immunotherapy, reported preclinical data on the immune activating antibody ATOR-1015 at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018 taking place in Chicago, Illinois American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018 taking place in Chicago, Illinois. ATOR-1015 is a first-in-class bispecific tumor-directed antibody, targeting CTLA-4 and OX40, designed to selectively activate the immune system in the tumor, without increasing systemic toxicity.

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The preclinical data demonstrate that ATOR-1015 physically localizes to the tumor and selectively activates the immune system in the tumor area, confirming the intended ATOR-1015 mechanism of action.

ATOR-1015 is primarily designed for combination therapy with a PD-1 blocking antibody, and the potential of this approach is supported with preclinical data reporting enhanced anti-tumor effect of ATOR-1015 in combination with an anti-PD-1 antibody, as compared to anti-PD-1 monotherapy. In addition, ATOR-1015 demonstrated superior efficacy compared to mono-targeting CTLA-4 and OX40 antibodies.

"The results presented in Chicago confirm that our CTLA-4 bispecific antibody ATOR-1015 selectively activates the immune system in the tumor area. 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", said Per Norlén CEO of Alligator Bioscience.

Alligator is planning to initiate an ATOR-1015 Phase I study during the second half of 2018.

A poster with the title "CTLA-4 x OX40 bispecific antibody ATOR-1015 induces anti-tumor effects through tumor-directed immune activation" is showcased today at 8-12 a.m. EDT and is also available on the company web page View Source

For further information, please contact:
Cecilia Hofvander, Director Investor Relations & Communications
Phone +46 46 286 44 95
E-mail: [email protected]

The information was submitted for publication, through the agency of the contact person set out above, at 3 p.m. CEST on 17 April 2018.