On October 16, 2018 Tiziana Life Sciences plc (AIM: TILS), a clinical stage biotechnology company developing targeted drugs for cancer and inflammatory diseases, reported that it will present results from preclinical studies demonstrating synergistic activity of milciclib with sorafenib (NexavarR) to suppress tumor growth in an orthotopic mouse model of HCC (Press release, Tiziana Life Sciences, OCT 16, 2018, View Source [SID1234530004]). Additional preclinical studies will be presented which also demonstrated synergism between Milciclib and other tyrosine kinase inhibitors (TKIs) such as Regorafenib (StivargaR) and Lenvatinib (LenvimaR). The presentation will take place at the American Association for the Study of Liver Diseases (AASLD) Meetingin San Francisco on 9-11 November 2018.

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The details of the presentation are:

Poster #1543 entitled "Oral Treatment with Milciclib Either Alone or in Combination with Sorafenib Inhibited Tumor Growth in an Orthotopic Model ofHepatocellular Carcinoma"will be presented at the Poster Session III on November 11, 2018.

The data results from pre-clinic studies in mouse models which will inform future research but the information to be presented is an extension of previously announced research and does not, in the view of the Company and its directors, constitute material data requiring dissemination via a regulatory news service. According this information is being released via RNS Reach to inform interested parties of the direction and results of our continuing research activity.

MAJOR HIGHLIGHTS OF THE DATA

· Oral treatment with milciclib (30mg/kg/day) in combination with sorafenib (20mg/kg/day) produced synergistic effect on reduction of HCC-tumor growth in an orthotopic animal model. Since, the doses of milciclib and sorafenib used were sub-optimal, it is possible that the combination treatment at sub-optimal doses may reduce the toxicities of sorafenib or other TKIs.

· While treatment with milciclib as a single agent significantly suppressed growth in cell cultures as well as in animal models, it also exhibited strong synergistic anti-HCC effects with TKIs such as sorafenib, regorafenib and lenvatinib in other pre-clinical studies

· Mechanism of action studies suggest that milciclib exhibits broad-spectrum anti-HCC activity through a different mechanism from TKIs to produce the pronounced synergism.

"We reported earlier that oral treatment with Milciclib was found to be well-tolerated and it achieved both primary and secondary clinical endpoints in two separate phase 2 trials in thymic carcinoma and thymoma. The new pre-clinical research data demonstrating synergism with TKIs is exciting and suggests the potential of Milciclib in combination with one of these approved TKIs to develop a safe and an improved treatment option for HCC patients" said Gabriele Cerrone, Chairman of Tiziana Life Sciences

The complex multi-factorial etiology of HCC warrants an immediate need for drugs with different mechanisms that may produce improved efficacy and safety. The data we have announced from the interim analysis of the ongoing phase 2a clinical study of orally administered milciclib in sorafenib-resistant patients suggests that the treatment is well-tolerated and seems to provide clinical benefits to these patients. We are pleased to see that milciclib produces strong synergistic anti-HCC activity in preclinical studies as these data are important milestones to move forward in our evaluation the potential of Milciclib in combination with one of the approved TKIs to improve safety, efficacy and clinical response rate in HCC patients" said Kunwar Shailubhai, CEO & CSO of Tiziana Life Sciences.

About Hepatocellular Carcinoma

Hepatocellular cancer is the 5th most common cancer and the 3rd cause of cancer mortality worldwide. In 2007 the approval by the European Medical Agency (EMA) and Food and Drug Administration (FDA) of sorafenib in HCC represented the first systemic therapy for improving outcome in patients unsuitable for loco-regional and surgical therapies and created a new standard of treatment for the disease. However, although significant in respect to placebo, the benefits of sorafenib are modest; the response rate is less than 3%, the improvement in median survival is 2-3 months and the drug-related symptoms are not ordinary. Therefore, more effective systemic therapy is required for both naive patients presenting with unresectable, advanced stage and those who suffer recurrence after curative treatments (resection, ablation and transplantation).

About Milciclib

Milciclib (PHA-848125AC) is a small molecule inhibitor of several cyclin dependent kinases such as CDK1, CDK4, CDK5 and CDK7. CDKs are serine threonine kinases that play crucial roles in progression of the cell cycle from G1 to S phase. Overexpression of CDKs and other downstream signaling pathways that regulate cell cycles have been frequently found to be associated with development of resistance towards chemotherapies. In a phase I study, oral treatment with Milciclib was found to be well-tolerated and the drug showed promising clinical responses in patients with advanced solid malignancies such as in NSCLC, Pancreatic and colon cancer, thymic carcinoma and thymoma.

A phase 2a multi-centre and multi-country clinical trial (CDKO-125A-010) in sorafenib-refractory or -intolerable patients with unresectable or metastatic HCC is currently being conducted in Greece, Italy and Israel.

On October 16, 2018 Johnson & Johnson (NYSE: JNJ) reported sales of $20.3 billion for the third quarter of 2018, an increase of 3.6% as compared to the third quarter of 2017 (Press release, Johnson & Johnson, OCT 16, 2018, View Source [SID1234529991]).

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Operational sales results increased 5.5%, partially offset by the negative impact of currency of 1.9%. Domestic sales increased 3.6%. International sales increased 3.5%, reflecting operational growth of 7.5% and a negative currency impact of 4.0%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 6.1%, domestic sales increased 3.9% and international sales increased 8.5%.*

Net earnings and diluted earnings per share for the third quarter of 2018 were $3.9 billion and $1.44, respectively. Third-quarter 2018 net earnings included after-tax intangible amortization expense of approximately $1.0 billion and a net charge for after-tax special items of approximately $0.7 billion, primarily consisting of a non-cash charge attributed to a partial write-down of an in-process research and development asset associated with the acquisition of Alios BioPharma Inc. Third-quarter 2017 net earnings included after-tax intangible amortization expense of approximately $0.9 billion and a charge for after-tax special items of approximately $0.5 billion. Excluding after-tax intangible amortization expense and special items, adjusted net earnings for the current quarter were $5.6 billion and adjusted diluted earnings per share were $2.05, representing increases of 7.3% and 7.9%, respectively, as compared to the same period in 2017.* On an operational basis, adjusted diluted earnings per share also increased 9.5%.* A reconciliation of non-GAAP financial measures is included as an accompanying schedule.

"We are pleased with our strong third-quarter performance, which reflects continued above-market growth in our Pharmaceutical business, accelerating sales momentum in our Consumer business and consistent progress in our Medical Devices business," said Alex Gorsky, Chairman and Chief Executive Officer. "I’m confident that with our collaborative and inspired J&J colleagues around the world, unique broad-based business model and strategic investments in innovation, we are well positioned for success today and into the future."

The Company issued sales guidance for the full-year 2018 in a range of $81.0 to $81.4 billion. This reflects an increase in expected operational growth to a range of 5.5% to 6.0%, partially offset by the estimated lower favorable impact of currency. Additionally, the Company increased its adjusted earnings guidance for full-year 2018 to a range of $8.13 to $8.18 per share. This reflects an increase in expected operational EPS growth to a range of 9.3% to 10.0%.

Segment Sales Performance
Worldwide Consumer sales of $3.4 billion for the third quarter 2018 represented an increase of 1.8% versus the prior year, consisting of an operational increase of 4.9% and a negative impact from currency of 3.1%. Domestic sales increased 6.6%, while international sales decreased 1.3%, which reflected an operational increase of 3.7% and a negative currency impact of 5.0%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 6.1%, with domestic sales increasing 6.4% and international sales increasing 5.9%.*

Worldwide operational results, excluding the net impact of acquisitions and divestitures, were driven by over-the-counter products including MOTRIN and TYLENOL analgesics, ZYRTEC upper respiratory and IMODIUM digestive health products; beauty products including NEUTROGENA, OGX and DR. CI LABO; as well as domestic sales of JOHNSON’s baby care products.

During the quarter, the acquisition of Zarbee’s, Inc., a leader in naturally-based healthcare products, was completed.

Worldwide Pharmaceutical sales of $10.3 billion for the third quarter 2018 represented an increase of 6.7% versus the prior year with an operational increase of 8.2% and a negative impact from currency of 1.5%. Domestic sales increased 4.8%, international sales increased 9.5%, which reflected an operational increase of 13.2% and a negative currency impact of 3.7%. Acquisitions and divestitures had a negligible impact to sales growth in the quarter.

Worldwide operational results, excluding the net impact of acquisitions and divestitures, were driven by ZYTIGA (abiraterone acetate), an oral, once-daily medication for use in combination with prednisone for the treatment of metastatic, castration-resistant prostate cancer, IMBRUVICA (ibrutinib), an oral, once-daily therapy approved for use in treating certain B-cell malignancies, a type of blood or lymph node cancer, STELARA (ustekinumab), a biologic for the treatment of a number of immune-mediated inflammatory diseases, DARZALEX (daratumumab), for the treatment of multiple myeloma, TREMFYA (guselkumab), for the treatment of adults living with moderate to severe plaque psoriasis, INVEGA SUSTENNA/XEPLION/INVEGA TRINZA/TREVICTA (paliperidone palmitate), long-acting, injectable atypical antipsychotics for the treatment of schizophrenia in adults, SIMPONI/SIMPONI ARIA (golimumab), a biologic for the treatment of a number of immune-mediated inflammatory diseases, OPSUMIT (macitentan), an oral endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension to delay disease progression, and UPTRAVI (selexipag), an oral prostacyclin receptor agonist used to treat pulmonary arterial hypertension and reduce hospitalization.

During the quarter, the U.S. Food and Drug Administration (FDA) approved an additional indication for IMBRUVICA (ibrutinib) in combination with rituximab as a non-chemotherapy combination regimen for patients with Waldenström’s Macroglobulinemia, a rare blood cancer. The European Commission (EC) granted marketing authorization for DARZALEX (daratumumab) in combination with VELCADE (bortezomib), a proteasome inhibitor, melphalan, an alkylating agent, and prednisone for the treatment of newly diagnosed multiple myeloma patients who are ineligible for autologous stem cell transplant. In addition, the FDA approved and the EC granted marketing authorization for SYMTUZA (D/C/F/TAF), a complete darunavir-based single-tablet regimen for the treatment of HIV-1 infection.

A New Drug Application was submitted to the FDA for esketamine nasal spray, a rapidly acting antidepressant for treatment-resistant depression in adults and erdafitinib, a once-daily, oral pan-fibroblast growth factor receptor (FGFR) inhibitor for the treatment of locally advanced or metastatic urothelial cancer. A supplemental New Drug Application was submitted to the FDA seeking to broaden the use of IMBRUVICA (ibrutinib) in chronic lymphocytic leukemia or small lymphocytic lymphoma to include combination use with a non-chemotherapy agent, obinutuzumab, in the frontline setting. A Type II Variation was submitted to the European Medicines Agency (EMA) seeking to expand the indication of OPSUMIT (macitentan) to include the treatment of adults with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), WHO Group 4, to improve exercise capacity and pulmonary vascular resistance. In addition, the Company also submitted a supplemental Biologics License Application to the FDA and a Type II Variation to the EMA seeking approval of a split dosing regimen for DARZALEX (daratumumab).

Subsequent to the quarter, the FDA approved an additional indication for XARELTO (rivaroxaban) to reduce the risk of major cardiovascular (CV) events, such as CV death, myocardial infarction and stroke, in people with chronic coronary or peripheral artery disease. Additionally, a Marketing Authorization Application was submitted to the EMA for esketamine nasal spray, a rapidly acting antidepressant for treatment-resistant depression in adults. The Company also entered into an exclusive worldwide license agreement with Arrowhead Pharmaceuticals, Inc. to develop and commercialize a new treatment for chronic Hepatitis B viral infection.

Worldwide Medical Devices sales of $6.6 billion for the third quarter 2018 represented a decrease of 0.2% versus the prior year consisting of an operational increase of 1.7% and a negative currency impact of 1.9%. Domestic sales increased 0.3%, while international sales decreased 0.6%, which reflected an operational increase of 3.0% and a negative currency impact of 3.6%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 2.9%, domestic sales increased 1.2% and international sales increased 4.4%.*

Worldwide operational results, excluding the net impact of acquisitions and divestitures, were driven by the growth of electrophysiology products in the Interventional Solutions business; ACUVUE contact lenses in the Vision business; endocutters and biosurgicals in the Advanced Surgery business; and wound closure products in the General Surgery business, partially offset by declines in the Diabetes Care business.

During the quarter, the Company received European CE mark approval for its BRAVO Flow Diverter for use in the treatment of patients suffering from intracranial aneurysms. In addition, the acquisition of Emerging Implant Technologies GmbH, a privately held manufacturer of 3D-printed titanium interbody implants for spinal fusion surgery, was completed. Lastly, the Company accepted the binding offer from Fortive Corporation to acquire its Advanced Sterilization Products business for an aggregate value of approximately $2.8 billion, subject to customary adjustments.

Subsequent to the quarter, the Company announced the completion of the divestiture of its LifeScan business to Platinum Equity for approximately $2.1 billion, subject to customary adjustments.

On October 16, 2018 Epigene Therapeutics Inc. reported that data on NEO2734, its investigational, first-in-class, dual inhibitor of both the Bromodomain (BRD) and Extra-Terminal domain (BET) family of proteins and the Cyclic AMP response element binding protein (CREB)-binding protein (CBP) and E1A interacting protein of 300 kDa (EP300 or P300) will be presented at the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress taking place in Munich, Germany from October 19th to the 23rd, 2018 (Press release, Epigene Therapeutics, OCT 16, 2018, View Source [SID1234529949]). The data being presented at ESMO (Free ESMO Whitepaper) 2018 will include a poster presentation on NEO2734 activity in the VCaP prostate cancer model and the MC38 colon cancer model.

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"Epigenetic changes are a major force in the genetic dysregulation that underlies the development and progression of human cancer", stated Professor Razelle Kurzrock, Chief, Division of Hematology and Oncology, University of California, San Diego, Senior Deputy Center Director, Clinical Science, Director, Center for Personalized Cancer Therapy University of California, San Diego – Moores Cancer Center, San Diego, CA and member of the Epigene Therapeutics Scientific Advisory Board (SAB). "We have made limited progress in deriving meaningful clinical benefit from the use of epigentic modifying agents. While the traditional BET inhibitors have shown consistent clinical promise in a spectrum of both hematologic maligancies and solid tumors, none have been granted regulatory approval. Developmental therapeutics efforts are now focused primarily on finding the right partner agents for BET inhibitors in order to increase their activity in patients. NEO2734 mediates multiple epigenetic modifer effects in a single agent and thus represents a unique, very exciting novel therapeutic approach"

"NEO2734 simultaneously inhibits two very well established classes of major epigenetic targets in patients with cancer", said Dr. Elena Garralda, Principal Investigator and Executive Director of the Early Drug Development Unit Vall d’ Hebron Institute of Oncology, Barcelona, who is also a member of the Epigene Therapeutics SAB. "Intensive efforts are ongoing to define the role of BET inhibitors as anti-cancer therapies while the CBP-EP300/P300 family of transcriptional coactivators are emerging as independent important therapeutic targets in oncology. NEO2734 offers us the unique opportunity to inhibit chromatin readers and writers with a single agent. The pre-clinical data being presented at ESMO (Free ESMO Whitepaper) on its activity in both colon and prostate cancers are particularly important in this context as our knowledge on the connections between specific epigenetic changes, deficiencies in DNA repair mechanisms, and therapeutic targets rapidly evolve."

"Synergistic activity against two independent important targets in cancer delivered by a single agent is a very rare phenomenon," said Francis Giles, Epigene Therapeutics’ Chief Medical Officer & Chief Operating Officer. "NEO2734 is unique in delivering that activity against both the BET and CBP-P300 targets and thus provides novel opportunities to both optimize the activity of the BET inhibitors and utilize CBP-P300 as a target. On-going IND-enabling work combined with multiple collaborations between Epigene Therapeutics and global academic leaders are rapidly defining the path to clinic for NEO2734"

Poster details:

"NEO2734: A novel potent oral dual BET and P300/CBP inhibitor"
(Abstract #429P, poster display session Hall A3 – Developmental Therapeutics)
– Monday, 22 October 2018 from 12:45 p.m. CEST to 1:45 p.m. CEST

Full session details and data presentation listings for ESMO (Free ESMO Whitepaper) 2018 can be found at: View Source

On October 16, 2018 Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported that it will report its third quarter 2018 financial results on Wednesday, October 24, 2018 after the financial markets close (Press release, Vertex Pharmaceuticals, OCT 16, 2018, View Source [SID1234529948]). The company will host a conference call and webcast at 4:30 p.m. ET. To access the call, please dial (866) 501-1537 (U.S.) or +1 (720) 545-0001 (International).

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The conference call will be webcast live and a link to the webcast can be accessed through Vertex’s website at www.vrtx.com in the "Investors" section. To ensure a timely connection, it is recommended that participants register at least 15 minutes prior to the scheduled webcast. An archived webcast will be available on the company’s website

On October 16, 2018 Alkermes plc (Nasdaq: ALKS) reported that it will host a conference call and webcast presentation at 8:30 a.m. ET (1:30 p.m. BST) on Tuesday, Oct. 23, 2018, to discuss the company’s third quarter 2018 financial results (Press release, Alkermes, OCT 16, 2018, View Source;p=irol-newsArticle&ID=2371934 [SID1234529947]). Management will also provide an update on the company.

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The webcast player and accompanying slides may be accessed on the Investors section of Alkermes’ website at www.alkermes.com. The conference call may be accessed by dialing +1 888 424 8151 for U.S. callers and +1 847 585 4422 for international callers. The conference call ID number is 6037988.

A replay of the conference call will be available from 11:00 a.m. ET (4:00 p.m. BST) on Tuesday, Oct. 23, 2018, through 5:00 p.m. ET (9:00 p.m. GMT) on Tuesday, Oct. 30, 2018, and may be accessed by visiting Alkermes’ website or by dialing +1 888 843 7419 for U.S. callers and +1 630 652 3042 for international callers. The replay access code is 6037988.