On April 18, 2016 Genzyme, the specialty care global business unit of Sanofi, reported that positive new brain volume data from an ongoing clinical study of Lemtrada (alemtuzumab) will be presented at the 68th American Academy of Neurology (AAN) Annual Meeting (Press release, Genzyme, APR 18, 2016, View Source [SID:1234511027]). In addition, new data from an exploratory study will be presented which demonstrate the impact of Lemtrada on retinal nerve fibers.

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Lemtrada Investigational Brain Volume Data: Relapsing-remitting multiple sclerosis (RRMS) patients treated with interferon beta-1a in CARE-MS I and II for two years who switched to Lemtrada in the extension study experienced a reduced rate of brain volume loss over the next three years.

Median yearly brain volume loss in interferon beta-1a treated patients in year two in CARE-MS I (-0.50%) and CARE-MS II (-0.33%) was reduced in years one, two and three after switching to Lemtrada (CARE-MS I: -0.07%, -0.13%, -0.09%; CARE-MS II: 0.02%, -0.05%, -0.14%).

Lemtrada Investigational Retinal Data: A measurable improvement in retinal nerve fiber layer (RNFL) thickness was seen in 26 Lemtrada-treated RRMS patients. Over two years, the change in average RNFL thickness for all eyes was +1.5 micrometers (95% CI 0.2, 2.9; p=0.032). The observed thickening of retinal fibers may reflect protection of retinal axons in these patients.

"The Lemtrada data being presented at AAN from the ongoing extension study demonstrating slowed brain volume loss over three years are consistent with sustained effects seen in prior clinical, imaging and atrophy analyses," said Dr. Anthony Traboulsee, Associate Professor of Neurology and Medical Director of the UBC Hospital MS Clinic of Vancouver Coastal Health. "In addition, given the critical importance of neuroprotection in the treatment of MS, the retinal nerve fiber data are also exciting and support further investigation."

In clinical trials, serious side effects associated with Lemtrada included infusion-associated reactions, autoimmune disorders (such as thyroid disease, autoimmune cytopenias, and nephropathies), infections and pneumonitis. Risk management programs incorporating education and monitoring help support early detection and management of key identified and potential risks. The most common side effects of Lemtrada are rash, headache, pyrexia, nasopharyngitis, nausea, urinary tract infection, fatigue, insomnia, upper respiratory tract infection, herpes viral infection, urticaria, pruritus, thyroid gland disorders, fungal infection, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pain, flushing, and vomiting. (See Important Safety Information below.)

About Lemtrada (alemtuzumab)
Lemtrada is approved in more than 50 countries, with additional marketing applications under review by regulatory authorities globally. Lemtrada is supported by a comprehensive and extensive clinical development program that involved nearly 1,500 patients worldwide and 5,400 patient-years of follow-up.

In CARE-MS I, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates; the difference observed in slowing disability progression did not reach statistical significance. In CARE-MS II, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates, and accumulation of disability was significantly slowed in patients given Lemtrada vs. interferon beta-1a.

The precise mechanism by which alemtuzumab exerts its therapeutic effects in MS is unknown. Alemtuzumab is a monoclonal antibody that targets CD52, a protein abundant on T and B cells. Circulating T and B cells are thought to be responsible for the damaging inflammatory process in MS. Lemtrada depletes circulating T and B lymphocytes after each treatment course. Lymphocyte counts then increase over time with a reconstitution of the lymphocyte population that varies for the different lymphocyte subtypes.

Genzyme holds the worldwide rights to alemtuzumab and has responsibility for its development and commercialization in multiple sclerosis. Bayer Healthcare receives contingent payments based on global sales revenue.

Lemtrada (alemtuzumab) U.S. Indication
LEMTRADA is a prescription medicine used to treat adults with relapsing forms of multiple sclerosis (MS). Because of its risks, LEMTRADA is generally used in people who have tried 2 or more MS medicines that have not worked well enough. It is not known if LEMTRADA is safe and effective for use in children under 17 years of age.

Do not receive LEMTRADA if you are infected with human immunodeficiency virus (HIV).

IMPORTANT SAFETY INFORMATION

LEMTRADA can cause serious side effects including:

Serious autoimmune problems: Some people receiving LEMTRADA develop a condition where the immune cells in your body attack other cells or organs in the body (autoimmunity), which can be serious and may cause death. Serious autoimmune problems may include:

• Immune thrombocytopenia, which is when reduced platelet counts in your blood cause severe bleeding that, if not treated, may cause life-threatening problems. Call your healthcare provider right away if you have any of the following symptoms: easy bruising; bleeding from a cut that is hard to stop; heavier menstrual periods than normal; bleeding from your gums or nose that is new or takes longer than usual to stop; small, scattered spots on your skin that are red, pink, or purple

• Kidney problems called anti-glomerular basement membrane disease, which can, if untreated, lead to severe kidney damage, kidney failure that needs dialysis, a kidney transplant, or death. Call your healthcare provider right away if you have any of the following symptoms: blood in the urine (red or tea-colored urine); swelling of legs or feet; coughing up blood

It is important for you to have blood and urine tests before you receive, while you are receiving and every month, for 4 years or longer, after you receive your last LEMTRADA infusion.

Serious infusion reactions: LEMTRADA can cause serious infusion reactions that may cause death. Serious infusion reactions may happen while you receive, or up to 24 hours or longer after you receive LEMTRADA.

• You will receive your infusion at a healthcare facility with equipment and staff trained to manage infusion reactions, including serious allergic reactions, and urgent heart or breathing problems. You will be watched while you receive, and for 2 hours or longer after you receive, LEMTRADA. If a serious infusion reaction happens while you are receiving LEMTRADA, your infusion may be stopped.

Tell your healthcare provider right away if you have any of the following symptoms of a serious infusion reaction during the infusion, and after you have left the healthcare facility:

• swelling in your mouth or throat

• trouble breathing

• weakness

• fast, slow, or irregular heartbeat

• chest pain

• rash

To lower your chances of getting a serious infusion reaction, your healthcare provider will give you a medicine called corticosteroids before your first 3 infusions of a treatment course. You may also be given other medicines before or after the infusion to try to reduce your chances of having these reactions or to treat them after they happen.

Certain cancers: Receiving LEMTRADA may increase your chance of getting some kinds of cancers, including thyroid cancer, skin cancer (melanoma), and blood cancers called lymphoproliferative disorders and lymphoma. Call your healthcare provider if you have the following symptoms that may be a sign of thyroid cancer:

• new lump

• swelling in your neck

• pain in front of neck

• hoarseness or other voice changes that do not go away

• trouble swallowing or breathing

• cough that is not caused by a cold

Have your skin checked before you start receiving LEMTRADA and each year while you are receiving treatment to monitor for symptoms of skin cancer.

Because of risks of autoimmunity, infusion reactions, and some kinds of cancers, LEMTRADA is only available through a restricted program called the LEMTRADA Risk Evaluation and Mitigation Strategy (REMS) Program.

Thyroid problems: Some patients taking LEMTRADA may get an overactive thyroid (hyperthyroidism) or an underactive thyroid (hypothyroidism). Call your healthcare provider if you have any of these symptoms:

• excessive sweating

• unexplained weight loss

• eye swelling

• nervousness

• fast heartbeat

• unexplained weight gain

• feeling cold

• worsening tiredness

• constipation

Low blood counts (cytopenias): LEMTRADA may cause a decrease in some types of blood cells. Some people with these low blood counts have increased infections. Call your doctor right away if you have symptoms of cytopenias such as:

• weakness

• chest pain

• yellowing of the skin or whites of the eyes (jaundice)

• dark urine

• fast heartbeat

Serious infections: LEMTRADA may cause you to have a serious infection while you receive and after receiving a course of treatment. Serious infections may include:

• Herpes viral infections. Some people taking LEMTRADA have an increased chance of getting herpes viral infections. Take any medicines as prescribed by your healthcare provider to reduce your chances of getting these infections.

• Tuberculosis. Your healthcare provider should check you for tuberculosis before you receive LEMTRADA.

• Hepatitis. People who are at high risk of, or are carriers of, hepatitis B (HBV) or hepatitis C (HCV) may be at risk of irreversible liver damage.

These are not all the possible infections that could happen while on LEMTRADA. Call your healthcare provider right away if you have symptoms of a serious infection such as fever or swollen glands. Talk to your healthcare provider before you get vaccinations after receiving LEMTRADA. Certain vaccinations may increase your chances of getting infections.

Swelling of lung tissue (pneumonitis): Some people have had swelling of the lung tissue while receiving LEMTRADA. Call your healthcare provider right away if you have the following symptoms:

• shortness of breath

• cough

• wheezing

• chest pain or tightness

• coughing up blood

Before receiving LEMTRADA, tell your healthcare provider if you:

• are taking a medicine called Campath (alemtuzumab)

• have bleeding, thyroid, or kidney problems

• have HIV

• have a recent history of infection

• have received a live vaccine in the past 6 weeks before receiving LEMTRADA or plan to receive any live vaccines. Ask your healthcare provider if you are not sure if your vaccine is a live vaccine

• are pregnant or plan to become pregnant. LEMTRADA may harm your unborn baby. You should use birth control while receiving LEMTRADA and for 4 months after your course of treatment

• are breastfeeding or plan to breastfeed. You and your healthcare provider should decide if you should receive LEMTRADA or breastfeed. You should not do both.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. LEMTRADA and other medicines may affect each other, causing side effects. Especially tell your healthcare provider if you take medicines that increase your chance of getting infections, including medicines used to treat cancer or to control your immune system.

The most common side effects of LEMTRADA include:

• rash

• headache

• thyroid problems

• fever

• swelling of your nose and throat

• nausea

• urinary tract infection

• feeling tired

• trouble sleeping

• upper respiratory infection

• herpes viral infection

• hives

• itching

• fungal infection

• joint pain

• pain in your arms or legs

• back pain

• diarrhea

• sinus infection

• mouth pain or sore throat

• tingling sensation

• dizziness

• stomach pain

• sudden redness in face, neck, or chest

• vomiting

Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of LEMTRADA.

You are encouraged to report side effects of prescription drugs to the FDA. Visit View Source or call 1-800-FDA-1088

Please click here for full U.S. Prescribing Information, including boxed WARNING and Medication Guide, for additional Important Safety Information

On April 18, 2016 Oncolytics Biotech Inc. ("Oncolytics" or the "Company") (TSX: ONC) (OTCQX: ONCYF) (FRA: ONY) reported that two poster presentations covering preclinical work in multiple myeloma and colorectal cancer are being made by the Company’s research collaborators at the 2016 American Association of Cancer Research annual meeting being held from April 16th to 20th, 2016 in New Orleans, LA (Filing, 6-K, Oncolytics Biotech, APR 18, 2016, View Source [SID:1234510978]).

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"Both multiple myeloma and colorectal cancer are target indications for later-stage clinical testing of REOLYSIN," said Dr. Brad Thompson, President and CEO of Oncolytics. "These important preclinical findings continue to advance our understanding of how REOLYSIN interacts with the immune system and how immunomodulatory interventions could improve its cancer cell killing capabilities."

The first abstract/poster is titled "Successful oncolytic virotherapy in a bortezomib resistant syngeneic mouse model of multiple myeloma: implications for translation significance," and was authored by Thirukkuamaran, et al. Using the VK*MYC bortezomib resistant transplantable multiple myeloma mouse model, the authors demonstrated that mice harboring bortezomib insensitive multiple myeloma tumors significantly responded to reovirus treatment. These data are supportive of previous and ongoing preclinical and clinical work in this indication and the Company is currently enrolling patients in a Phase 1b study of REOLYSIN in combination with bortezomib in patients with relapsed or refractory multiple myeloma.

The second abstract/poster is titled "Toll like receptor 3 as an immunotherapeutic target for Kras mutated colorectal cancer," and was authored by Goel, et al. The authors hypothesized that effective expression of toll like receptors 3 ("TLR3") would dampen the infection potential of reovirus through the mounting of an innate immune response. Using a xenograft model with HCT116 colorectal cancer cells, those with TLR3 downregulated cells showed improved control of tumor growth with reovirus treatment compared to those expressing TLR3 (p=0.04). Down regulation of the host immune response improved virus mediated cell cytotoxicity and the findings could result in improved and beneficial killing of cancer cells by reovirus.

On April 18, 2016 Varian Medical Systems (NYSE: VAR) reported it is supporting a phase III trial comparing outcomes of radiosurgery versus surgical resection for the treatment of early-stage, high-risk, operable non-small cell lung cancer (NSCLC) (Press release, Varian Medical Systems, APR 18, 2016, View Source [SID:1234511001]).

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Known as the "Stablemates Trial," the randomized study will test the hypothesis that the 3-year overall survival in high risk operable patients with stage I NSCLC is equivalent or greater in patients who undergo stereotactic ablative radiotherapy (SAbR) as compared with conventional sublobar resection (SR) surgery. Led by co-chairs Hiran Fernando, MD, Boston Medical Center, and Robert Timmerman, MD, University of Texas Southwestern Medical Center, the study currently involves 34 institutions and 258 patients.

"In addition to a potentially longer survival rate, SAbR may benefit some lung cancer patients by offering them a noninvasive, outpatient treatment option that is easier to tolerate and that doesn’t interfere greatly with their normal, everyday living activities," said Dr. Timmerman.

Sponsored by the Joint Lung Cancer Trialist’s Coalition, the study is being administered by the Department of Radiation Oncology at the University of Texas Southwestern Medical Center. Over the next five years, the study will examine patients’ overall, disease-free, and regional recurrence-free survival rates three years after treatment, as well as adverse events and post-treatment quality of life measures.

"Varian believes in supporting high quality clinical research," said Kolleen Kennedy, president of Varian’s Oncology Systems business. "This clinical trial presents the opportunity to advance radiation oncology and enhance the standard of patient care by giving clinicians a noninvasive treatment option in determining the appropriate therapy for patients."

On April 18, 2016 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported that preclinical data from its collaboration with Heat Biologics, Inc (Press release, OncoSec Medical, APR 18, 2016, View Source [SID:1234510979]). ("Heat") focused on evaluating the combination of immunotherapy platforms were presented yesterday at the American Conference for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (www.aacr.org).

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In the poster entitled "In vivo intra-tumoral electroporation of gp96-Ig/Fc-OX40L stimulates CD8+ T cell cross-priming to tumor specific neoantigens" (Abstract #567), researchers concluded that combining Heat’s ComPACT vaccine with OncoSec’s intratumoral DNA electroporation delivery platform stimulated an expansion of neoantigen-specific CD8+ T cells, leading to a regression in both treated and untreated cancer lesions in two mouse studies (melanoma and colorectal cancer). OncoSec and Heat announced their collaboration last year to evaluate the preclinical efficacy of delivering Heat’s immunotherapy vaccines via OncoSec’s ImmunoPulse platform.

"We are excited by our collaboration with Heat and by these initial findings. The ability of the tumor’s microenvironment to evade immune recognition and remain non-immunogenic is a significant challenge, which we believe needs to be addressed when designing new immuno-therapies," said Robert H. Pierce, MD, OncoSec’s Chief Scientific Officer. "The initial feasibility data between our two platforms are encouraging and we are currently exploring the potential synergy between our platforms with both ComPACT and interleukin-12 expressing plasmids."

"In this first preclinical study demonstrating the feasibility of electroporating ComPACT DNA plasmids, we saw robust neoantigen T cell response and tumor regression in both treated and untreated tumors, indicating a systemic anti-tumor response that could be reflective of what we might see in metastatic lesions," said Taylor Schreiber, MD, PhD, Heat’s Chief Scientific Officer. "We believe that this approach is promising and that further studies are merited, especially as this combination approach has the potential to stimulate shared and private tumor antigens without introducing the complexities associated with personalized therapies."

Copies of the abstract are available and can be viewed online through the AACR (Free AACR Whitepaper) website at www.aacr.org. The poster is available in the Publications section of OncoSec’s website.

On April 18, 2016 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new cancer immunotherapies, reported results from two programs will be presented in oral sessions at the upcoming 19th Annual American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Meeting (Press release, Ziopharm, APR 18, 2016, View Source [SID:1234511002]). The first presentation highlights preclinical data from the Company’s novel viral gene therapy candidate for the controlled expression of IL-12 in combination with inhibition of programmed cell death protein 1 (PD-1) in a mouse model of glioma. The second presentation highlights preclinical data from the Company’s evolution of the Sleeping Beauty (SB) non-viral transposon-transposase system in a mouse model of leukemia. The ASGCT (Free ASGCT Whitepaper) meeting will take place May 4-7 at the Marriott Wardman Park Hotel in Washington, D.C.

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Title: Regulated Expression of IL-12 as Gene Therapy Concomitant with Blockade of PD-1 for Treatment of Glioma
Session Title: Cancer-Immunotherapy, Cancer Vaccines II
Date and Time: Friday, May 6, 2016 4:00 PM – 6:00 PM ET
Abstract Number: 509
Room: Washington 1-2
Summary: The utility of clinically-feasible immunotherapy in the investigational treatment of glioma may be improved through combination therapies that enhance cytotoxic immune-activation while concomitantly reducing immunosuppression. ZIOPHARM and Intrexon evaluated the combination of controlled local interleukin 12 (IL-12) administration using a virus (Ad-RTS-IL-12) activated by an oral ligand (veledimex) (Ad +V) and blockade of PD-1 using a checkpoint inhibitor:

Results demonstrated that survival of mice treated with Ad +V and anti-PD-1 therapy was superior to either treatment alone;
Combination showed 100% survival;
Because Ad-RTS-IL-12 and anti-PD-1 are clinically available, these data provide impetus for evaluating this combination immunotherapy in humans;
ZIOPHARM plans to initiate a combination study in 2016 and is currently in discussion with partners to provide anti PD-1 therapy.
"The use of PD-1 checkpoint inhibitors in solid tumors has yielded impressive clinical outcomes, yet these results have not yet translated to gliomas, due in part to the immunologic privilege of the central nervous system," said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM. "By combining PD-1 inhibitors, which release a brake on the immune system, with the controlled tumor-directed release of IL-12, which steps on the immune system’s accelerator, we see significant anti-tumor activity. These data provide a strong rationale for studying Ad-RTS-IL-12 + veledimex in combination with anti-PD-1 in the clinic, a trial we look forward to initiating later this year."

Title: Next-Generation Non-Viral Gene Transfer to Redirect T-Cell Specificity
Session Title: Cancer-Immunotherapy, Cancer Vaccines I
Date and Time: Thursday, May 5, 2016 4:00 PM – 5:45 PM ET
Abstract Number: 278
Room: Washington 5-6
Summary: Non-viral gene transfer using the SB transposon/transposase system has been successfully tested in humans to express a chimeric antigen receptor (CAR) to redirect T-cell specificity to CD19. A next-generation SB system has been modified by MD Anderson Cancer Center researchers to improve the design of a CD19-specific CAR as well as reduce the time to manufacture:

Changing the "stalk" of the CAR improved the anti-tumor activity of SB-modified T cells;
These data support the use of new CAR in an ongoing clinical trial (IND#16474).
Decreasing the time the SB-modified T cells were in culture improved the anti-tumor effect;
These data provide support for ZIOPHARM’s efforts to address the challenges of cost and time of bioprocessing cell therapies;
"Targeting CD19 with CAR-modified T cells is an effective approach to treating CD19-expressing leukemias and lymphomas, as demonstrated by current clinical studies," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. "Fundamental to advancing this approach, and any modified cell-based therapy, into a broadly deployed treatment option is a streamlined and simplified manufacturing process, with a reduction in the associated cost. These data demonstrate our ability to address these challenges by leveraging the less costly, non-viral Sleeping Beauty system and reducing cell culture time, all while improving the effectiveness of the CD19-specific CAR. We look forward to understanding how these next-generation ideas translate into outcomes in an ongoing Phase 1 study and future clinical studies."