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Clovis Oncology to Announce First Quarter 2019 Financial Results and Host Webcast Conference Call on May 7

On April 24, 2019 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that it will announce its first quarter 2019 financial results on Tuesday, May 7, 2019, before the open of the U.S. financial markets (Press release, Clovis Oncology, APR 24, 2019, View Source [SID1234535367]). Clovis’ senior management will host a conference call and live audio webcast at 8:30 a.m. ET to discuss the company’s results in greater detail.

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The conference call is being webcast and can be accessed from the Clovis Oncology website at www.clovisoncology.com. A replay of the webcast will be available for 30 days.

Conference Call Details

Clovis will hold a conference call to discuss first quarter 2019 results on Tuesday, May 7, at 8:30 a.m. ET. The conference call will be simultaneously webcast on the Company’s web site at www.clovisoncology.com, and archived for future review. Dial-in numbers for the conference call are as follows: US participants 877.698.7048, International participants 647.689.5448, conference ID: 8567356.

Tiziana Reports Encouraging Interim Clinical Data from an Ongoing Phase 2a Clinical Trial with Milciclib in Patients With Advanced Liver Cancer

On April 24, 2019 Tiziana Life Sciences plc (NASDAQ: TLSA / AIM: TILS), a biotechnology company focusing on the discovery and development of innovative therapeutics for inflammation and oncology indications, reported results from the interim safety review conducted by the Independent Data Monitoring Committee ("IDMC") on 21 March 2019 (Press release, Tiziana Life Sciences, APR 24, 2019, View Source [SID1234535366]). The IDMC reviewed safety data from patients as of 26 February 2019, and concluded that the administration of milciclib to patients with advanced hepatocellular carcinoma ("HCC") was not associated with unexpected signs or signals of toxicity. Additionally, a number of patients are continuing with treatment under compassionate use. Topline data from this multi-center trial is expected to be available by the end of Q3 2019.

Tiziana’s Milciclib Phase 2a clinical trial is a single-arm, repeated-dose (100 mg once daily; 4 days on/3 days off every 4 weeks defining each cycle), 6-month duration study to evaluate the safety, tolerability and anti-tumor activity of Milciclib in Sorafenib-refractory or intolerant patients with unresectable or metastatic advanced HCC, the most common form of liver cancer. Enrollment of 31 patients in Italy, Greece, and Israel was completed on 30 November 2018.

The IDMC evaluated data from 28 out of the 31 patients who were evaluable. As of 16 April 2019, a total of 10 out of 27 patients have completed the study per protocol (6 cycles, 6 months). Four patients are still under treatment, while 3 are in cycle 6 and 1 is in cycle 5. Eight out of the 10 patients who completed treatment initially expressed interest to continue with treatment. Seven of these 8 patients were approved to continue with treatment under compassionate use by their respective ethical committees. Three of the patients under compassionate use have completed 9, 13, and 16 months of treatment with Milciclib. The other 4 patients are continuing with treatment.

To date, no drug-related deaths have been recorded. Overall, the treatment with Milciclib is well-tolerated with manageable drug-related toxicities. These safety and clinical activity are consistent with the earlier reported long-term safety and clinical activity of Milciclib in thymic carcinoma, thymoma and other solid cancers.

"Demonstration of safety and clinical activity is an important milestone to move forward with strategic options for further clinical development of Milciclib either as a single agent or in combination with one of the FDA approved drugs for treatment of HCC patients," said Dr Kunwar Shailubhai, CEO & CSO of Tiziana. "We previously reported data from preclinical studies demonstrating that Milciclib produced pronounced synergistic anti-HCC activity in combination with any one of the U.S. Food and Drug Administration approved drugs such as sorafenib (Nexavar), regorafenib (Stivarga), and lenvatinib (Lenvima)."

The person who arranged for the release of this announcement on behalf of the Company was Dr Kunwar Shailubhai, CEO of Tiziana.

Cited References

Besse, B,, Garassino, M,, Rajan, A., Novello, S.,Mazieres, J., Weiss, G., Kocs, D., Barnett, J, Davite, C, Crivori, P and G. Giaccone. Efficacy of Milcicilib (PHA-848125AC), a pan-cyclin D -dependent kinase inhibitor in tow phase II studies with Thymic carcinoma and B3 thymoma patients. (2018) J. Clin. Onc 36 (15 suppl): 8519

Aspeslagh, S., Shailubhai, K., Bahleda, R. et al. (2017). Phase I dose-escalation study of milciclib in combination with gemcitabine in patients with refractory solid tumors. Cancer Chemother Pharmacol. 79:1257-1265.

Jindal, A., Palejwala, V. and Shailubhai, K. (2018). Oral treatment with milciclib either alone or in combination with sorafenib inhibited tumor growth in an orthotopic model of hepatocellular carcinoma. Hepatology 68 Number 1 (Suppl): 879A (Abstract 1543)

About HCC

HCC is the fifth most common cancer and the third highest cause of cancer mortality worldwide. In 2007, the approval by the European Medical Agency and U.S. Food and Drug Administration of Sorafenib (Nexavar), an inhibitor of several receptor tyrosine kinases, 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, with a response rate less than 3%, an improvement in median survival of 2-3 months and drug-related symptoms that are not ordinary. More recently, lenvatinib (Lenvima ), another multi-tyrosine kinase inhibitor was also approved for first line treatment of HCC. The complex multi-factorial etiology of HCC warrants a need for systemic therapies that target different signaling cascades to provide improved efficacy and safety 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 associated with development of resistance towards chemotherapies. In a Phase 1 study, oral treatment with Milciclib was 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. Additionally, milciclib met its primary endpoint in two separate Phase 2 multi-center clinical trials (CDKO-125A-006: 72 patients and CDKO-125A-007: 30 patients) in thymic carcinoma and thymoma patients.

X4 Pharmaceuticals Appoints E. Lynne Kelley, M.D. as Chief Medical Officer

On April 24, 2019 X4 Pharmaceuticals, Inc. (Nasdaq: XFOR), a clinical-stage biopharmaceutical company focused on the development of novel therapeutics for the treatment of rare diseases, reported the appointment of E. Lynne Kelley, M.D., FACS, as the company’s Chief Medical Officer (CMO) (Press release, X4 Pharmaceuticals, APR 24, 2019, View Source [SID1234535364]). Dr. Kelley brings more than a decade of experience driving clinical development and global expansion of novel pharmaceutical products at both emerging and established life sciences companies. Dr. Kelley is a Board Certified General and Vascular Surgeon.

"We are thrilled to have Lynne join our team as Chief Medical Officer," said Paula Ragan, Ph.D., President and Chief Executive Officer of X4 Pharmaceuticals. "Her broad medical and biopharmaceutical industry experience, along with her deep understanding of complex regulatory applications, will be invaluable as we execute our global Phase 3 pivotal trial in WHIM syndrome, a rare genetic, primary immunodeficiency disease, and advance our pipeline across additional rare and ultra-rare diseases."

"This is an incredibly exciting time for X4 with its many recent accomplishments and ongoing clinical development efforts. I look forward to working with this very talented and dedicated team of industry experts to deliver on a shared goal of bringing novel therapies to patients with rare disease who have limited treatment options," commented Dr. Kelley.

Before joining X4, Dr. Kelley was CMO of Massachusetts-based biopharmaceutical company Histogenics Corporation (Nasdaq: HSGX), where she led the development of restorative cell therapies to replace damaged cartilage and oversaw the completion of a Phase 3 clinical trial and regulatory submission for the company’s lead program. Dr. Kelley previously served as CMO of Senseonics Holdings, Inc. (Nasdaq: SENS) and held leadership positions in clinical development roles at global companies such as Becton, Dickinson and Company, Kimberly-Clark Corporation, and Boston Scientific Corporation.

Dr. Kelley received her medical degree from Dartmouth Medical School and her bachelor’s degree in biology from Boston University. Dr. Kelley is a fellow of the American College of Surgeons and has authored numerous articles for peer-reviewed publications. She trained at Dartmouth Hitchcock Hospital and Massachusetts General Hospital, and was a practicing surgeon at Yale University. Dr. Kelley was named Fellow of the American College of Surgeons and was awarded an NIH research grant at Harvard and the Marco Polo Fellowship studying at Hospital Henri Mondor of the University Paris Hospital System.

Kite Announces Plans for New State-of-the-Art Facility to Expand Cell Therapy Production Capabilities

On April 24, 2019 Kite, a Gilead Company (Nasdaq: GILD), reported plans for a new facility in Frederick County, Maryland, which will produce innovative cell therapies for people with cancer (Press release, Kite Pharma, APR 24, 2019, View Source [SID1234535363]). The 20-acre site will significantly expand Kite’s ability to manufacture a variety of chimeric antigen receptor T (CAR T) therapies, including Yescarta (axicabtagene ciloleucel), Kite’s first commercially available CAR T cancer therapy, and investigational T cell receptor (TCR) cell therapies being evaluated in solid tumors.

"This new facility in Frederick County builds on our substantial technical capabilities and rapid progress in making personalized CAR T and TCR cell therapies for people with cancer. As we advance our industry-leading cell therapy pipeline and seek to help a growing number of people with cancer, expanding and investing in our manufacturing capabilities is essential," said Tim Moore, Executive Vice President of Technical Operations at Kite. "With the Frederick County site, we will have the opportunity to build and design the facility tailored to our own innovative processes and with state-of-the-art features that will enable us to meet the future needs for cell therapies."

CAR T therapies require many complex and carefully controlled, multi-step processes. The Frederick County facility will become part of Kite’s growing commercial manufacturing network that includes sites in California and the Netherlands.

Important Safety Information and Indication for Yescarta
BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving Yescarta. Do not administer Yescarta to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving Yescarta, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Yescarta. Provide supportive care and/or corticosteroids as needed.
Yescarta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta REMS.
CYTOKINE RELEASE SYNDROME (CRS): CRS occurred in 94% of patients, including 13% with ≥ Grade 3. Among patients who died after receiving Yescarta, 4 had ongoing CRS at death. The median time to onset was 2 days (range: 1-12 days) and median duration was 7 days (range: 2-58 days). Key manifestations include fever (78%), hypotension (41%), tachycardia (28%), hypoxia (22%), and chills (20%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Ensure that 2 doses of tocilizumab are available prior to infusion of Yescarta. Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for 4 weeks after infusion. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.

NEUROLOGIC TOXICITIES: Neurologic toxicities occurred in 87% of patients. Ninety-eight percent of all neurologic toxicities occurred within the first 8 weeks, with a median time to onset of 4 days (range: 1-43 days) and a median duration of 17 days. Grade 3 or higher occurred in 31% of patients. The most common neurologic toxicities included encephalopathy (57%), headache (44%), tremor (31%), dizziness (21%), aphasia (18%), delirium (17%), insomnia (9%) and anxiety (9%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events including leukoencephalopathy and seizures occurred with Yescarta. Fatal and serious cases of cerebral edema have occurred in patients treated with Yescarta. Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of neurologic toxicities. Monitor patients for signs or symptoms of neurologic toxicities for 4 weeks after infusion and treat promptly.

YESCARTA REMS: Because of the risk of CRS and neurologic toxicities, Yescarta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta REMS. The required components of the Yescarta REMS are: Healthcare facilities that dispense and administer Yescarta must be enrolled and comply with the REMS requirements. Certified healthcare facilities must have on-site, immediate access to tocilizumab, and ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after Yescarta infusion, if needed for treatment of CRS. Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense or administer Yescarta are trained about the management of CRS and neurologic toxicities. Further information is available at www.YESCARTAREMS.com or 1-844-454-KITE (5483).

HYPERSENSITIVITY REACTIONS: Allergic reactions may occur. Serious hypersensitivity reactions including anaphylaxis may be due to dimethyl sulfoxide (DMSO) or residual gentamicin in Yescarta.

SERIOUS INFECTIONS: Severe or life-threatening infections occurred. Infections (all grades) occurred in 38% of patients, and in 23% with ≥ Grade 3. Grade 3 or higher infections with an unspecified pathogen occurred in 16% of patients, bacterial infections in 9%, and viral infections in 4%. Yescarta should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after Yescarta infusion and treat appropriately. Administer prophylactic anti-microbials according to local guidelines. Febrile neutropenia was observed in 36% of patients and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids and other supportive care as medically indicated. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients treated with drugs directed against B cells. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

PROLONGED CYTOPENIAS: Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and Yescarta infusion. Grade 3 or higher cytopenias not resolved by Day 30 following Yescarta infusion occurred in 28% of patients and included thrombocytopenia (18%), neutropenia (15%), and anemia (3%). Monitor blood counts after Yescarta infusion.

HYPOGAMMAGLOBULINEMIA: B-cell aplasia and hypogammaglobulinemia can occur. Hypogammaglobulinemia occurred in 15% of patients. Monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following Yescarta treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during Yescarta treatment, and until immune recovery following treatment.

SECONDARY MALIGNANCIES: Patients may develop secondary malignancies. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following Yescarta infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

ADVERSE REACTIONS: The most common adverse reactions (incidence ≥ 20%) include CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections-pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.

INDICATION

Yescarta is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.

Limitation of Use: Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma.

TC BioPharm Initiates Phase I Trial of Allogeneic Gamma Delta T Cell Therapy in Acute Myeloid Leukemia Patients

On April 24, 2019 TC BioPharm (TCB), a developer of allogeneic CAR-T immuno-oncology products, and leaders in Gamma Delta T (GDT) cell therapies, reported it has initiated a Phase I clinical study of TCB002, an allogeneic cell therapy consisting of activated and expanded gamma delta T cells (Press release, TC Biopharm, APR 24, 2019, View Source [SID1234535362]). The trial, for treatment of patients suffering from Acute Myeloid Leukemia (AML), is being conducted at the Institute of Hematology and Blood Transfusion (ÚHKT) in Prague, Czech Republic. Patient recruitment commenced January 2019 following regulatory approval late 2018. Dose escalation is in progress, with completion of treatment imminent for the first patient cohort. The clinical trial is registered with identifier NCT03790072.

Developed by TC BioPharm, TCB002 comprises GDT cells sourced from healthy donors, expanded and activated in large numbers before being purified and formulated for infusion into patients. The donors are selected based on criteria designed to ensure that the cells are potent killers of cancer cells, and can be a more effective and consistent treatment compared to the patient’s own cells. GDT cells are a subset of lymphocytes which have both innate and adaptive immune properties and represent an emerging therapeutic option for cancer and other diseases. Use of allogeneic GDT cells from healthy donor cell banks paves the way for development of superior drug products through screening and selection of the highest quality starting material, facilitating preparation of consistent batches capable of treating many patients.

The study in Prague is designed to provide safety data on allogeneic use of GDTs prior to subsequent use of CAR-modified variants later in the year. GDTs are an obvious vehicle for allogeneic cell therapies as they do not elicit ‘graft versus host’ rejection. TCB is developing its proprietary GDT CAR-T (Chimeric Antigen Receptor T Cell) platform in a stepwise manner, evolving the clinical development program from autologous to allogeneic to CAR-modified products.

The first human trial of TCB002 is an ICH GCP compliant, open-label single arm study expected to enroll 9 patients, with three escalating doses of the drug product. Cancer patients in the study are suffering from relapsed or refractory AML and are ineligible or non-consenting to a stem cell transplant. The product is manufactured at TCB’s GMP-compliant manufacturing site in the UK using cells sourced from healthy allogeneic donors. The development of this allogeneic product has been supported by a €4m grant from the European Union’s Horizon 2020 research and innovation program.

Angela Scott, Chief Operating Officer, TC BioPharm, said: "Treatment of the first patients with TCB002 represents the culmination of a concerted collective effort from our in-house product development, quality, manufacturing, regulatory and clinical teams, as well as the expert physicians at ÚHKT. We are now focused on successful completion of this trial and the progression of our CAR-T products to treat further patient groups with unmet clinical needs, as part of our strategic plan of delivering allogeneic CAR-T medicines as mainstream cancer therapies."

Prof. Petr Cetkovský, Director, ÚHKT, added: "Collaborating with TC BioPharm on clinical evaluation of Advanced Therapy Medicinal Products allows us to offer experimental options to patients with acute clinical need, and builds upon our position of expertise with pioneers of cellular immuno-oncology products."

This project has received funding from the European Union’s Horizon 2020 Research and Innovation program.