On July 12, 2018 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, reported it submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for venetoclax in combination with a hypomethylating agent (HMA) or in combination with low-dose cytarabine (LDAC) for the treatment of newly diagnosed patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy (Press release, AbbVie, JUL 12, 2018, View Source [SID1234527661]).

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The sNDA submission is based on investigational data from two studies: M14-358, a Phase 1b trial evaluating venetoclax in combination with an HMA (azacitidine or decitabine), and M14-387, a Phase 1/2 trial of venetoclax in combination with LDAC.

"AML is an especially lethal and aggressive form of blood cancer with limited advances in care in three decades and few treatment options for patients ineligible for intensive chemotherapy," said Michael Severino, M.D., executive vice president of research and development and chief scientific officer, AbbVie. "The data submitted to the FDA may potentially reshape how AML is treated. We look forward to working with the FDA and other health authorities during the review of these data."

AML, primarily a disease of older patients, is the most common form of acute leukemia in adults, in which the bone marrow makes abnormal, immature types of white blood cells, red blood cells or platelets.2,3 AML is an aggressive blood cancer that, if left untreated, can progress quickly.2 In the U.S., it is estimated there will be 19,520 new cases and 10,670 deaths due to AML in 2018.3

Approximately 27 percent of patients diagnosed with AML will survive five years or more.3 Disease recurrence occurs in most patients with AML within three years of diagnosis.1,4,5 Although few treatments are available, AML patients who are ineligible for intensive remission induction therapy may be treated with LDAC or HMAs.1,6 Only about one-third of AML patients older than age 60 are able to tolerate the intensive chemotherapy required to achieve optimal results.7 Median survival is five to 10 months in older AML patients who are ineligible for intensive chemotherapy.1

The challenges of treating AML, including in older adults, is an ongoing topic of discussion among the medical community. Daniel Pollyea, M.D., director of Leukemia Services at University of Colorado Hospital, recently reflected on his experience treating patients with AML. "We have an incredible opportunity to develop better treatment options for people with AML. Still, right now every aspect of this disease represents an unmet need," he said. For more on Dr. Pollyea’s perspective, please read "A Physicians View: Facing the Challenges of Treating AML in Older Adults."

Venetoclax, an oral B-cell lymphoma-2 (BCL-2) inhibitor, has been granted four Breakthrough Therapy Designations (BTDs) from the FDA including for the combination of venetoclax with an HMA (azacitidine or decitabine) for treatment-naïve patients with AML who are ineligible to receive standard induction therapy (high-dose chemotherapy) and for the combination of venetoclax with LDAC for treatment-naïve patients with AML who are ineligible for intensive chemotherapy. According to the FDA, BTD is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).8

If approved in AML, venetoclax would be available for use in two blood cancers, chronic lymphocytic leukemia (CLL) and AML. Venetoclax recently received expanded approval in the U.S. for use alone or in combination with rituximab for the treatment of relapsed/refractory (R/R) CLL or small lymphocytic lymphoma (SLL) patients, with or without 17p deletion, who have received at least one prior therapy.9

In addition to CLL and AML, venetoclax is being studied in a range of hematologic malignancies including multiple myeloma (MM), non-Hodgkin lymphoma (NHL) and myelodysplastic syndrome (MDS).10,11,12 Venetoclax is being developed by AbbVie and Roche and is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. Together, the companies are committed to BCL-2 research with venetoclax, which is currently being evaluated in clinical trials in several hematologic cancers.10,11,12,13,14

Additional information regarding venetoclax clinical trials is available on www.clinicaltrials.gov.

About VENCLEXTA (venetoclax tablets) (US)

VENCLEXTA is an oral BCL-2 inhibitor that targets a specific protein in the body called BCL-2.9 When you have CLL or SLL, BCL-2 may build up and prevent cancer cells from self-destructing naturally. VENCLEXTA targets BCL-2 in order to help restore the process of apoptosis.9

VENCLEXTA is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.

VENCLEXTA (VENCLYXTO in the EU) is currently approved as a monotherapy in 53 nations, including the U.S. AbbVie, in collaboration with Roche and Genentech, is currently working with regulatory agencies around the world to bring this medicine to additional eligible patients in need.

VENCLEXTA was first approved in April 2016 when the U.S. FDA granted accelerated approval of VENCLEXTA for the treatment of patients with CLL with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy.15 The FDA approved this indication under accelerated approval based on overall response rate.15 Based on the results of the MURANO study, VENCLEXTA was approved in June 2018 for the treatment of patients with CLL or SLL, with or without 17p deletion, who have received at least one prior therapy in combination with rituximab or as monotherapy.9

Use and Important Safety Information (US)

Use
What is VENCLEXTA (venetoclax tablets)?
VENCLEXTA is a prescription medicine used to treat people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with or without 17p deletion, who have received at least one prior treatment.

It is not known if VENCLEXTA is safe and effective in children.

Important VENCLEXTA (venetoclax tablets) Safety Information

What is the most important information I should know about VENCLEXTA?
VENCLEXTA can cause serious side effects, including:
Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. Your health care provider will do tests for TLS. It is important to keep your appointments for blood tests. You will receive other medicines before starting and during treatment with VENCLEXTA to help reduce your risk of TLS. You may also need to receive intravenous (IV) fluids into your vein. Tell your health care provider right away if you have any symptoms of TLS during treatment with VENCLEXTA, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain.

Drink plenty of water when taking VENCLEXTA to help reduce your risk of getting TLS. Drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before your first dose, on the day of your first dose of VENCLEXTA, and each time your dose is increased.

Who should not take VENCLEXTA?
Certain medicines must not be taken when you first start taking VENCLEXTA and while your dose is being slowly increased because of the risk of increased tumor lysis syndrome.

Tell your health care provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. VENCLEXTA and other medicines may affect each other, causing serious side effects.
Do not start new medicines during treatment with VENCLEXTA without first talking with your health care provider.
Before taking VENCLEXTA, tell your health care provider about all of your medical conditions, including if you:

Have kidney or liver problems.
Have problems with your body salts or electrolytes, such as potassium, phosphorus, or calcium
Have a history of high uric acid levels in your blood or gout
Are scheduled to receive a vaccine. You should not receive a "live vaccine" before, during or after treatment with VENCLEXTA until your health care provider tells you it is okay. If you are not sure about the type of immunization or vaccine, ask your health care provider. These vaccines may not be safe or may not work as well during treatment with VENCLEXTA.
Are pregnant or plan to become pregnant. VENCLEXTA may harm your unborn baby. If you are able to become pregnant, your health care provider should do a pregnancy test before you start treatment with VENCLEXTA, and you should use effective birth control during treatment and for 30 days after the last dose of VENCLEXTA.
Are breastfeeding or plan to breastfeed. It is not known if VENCLEXTA passes into your breast milk. Do not breastfeed during treatment with VENCLEXTA.
What should I avoid while taking VENCLEXTA?
You should not drink grapefruit juice, eat grapefruit, Seville oranges (often used in marmalades), or starfruit while you are taking VENCLEXTA. These products may increase the amount of VENCLEXTA in your blood.

What are the possible side effects of VENCLEXTA?
VENCLEXTA can cause serious side effects, including:

Low white blood cell count (neutropenia). Low white blood cell counts are common with VENCLEXTA but can also be severe. Your health care provider will do blood tests to check your blood counts during treatment with VENCLEXTA. Tell your health care provider right away if you have a fever or any signs of an infection.
The most common side effects of VENCLEXTA when used in combination with rituximab include low white blood cell count, diarrhea, upper respiratory tract infection, cough, tiredness, and nausea.

The most common side effects of VENCLEXTA when used alone include low white blood cell count, diarrhea, nausea, upper respiratory tract infection, low red blood cell count, tiredness, low platelet count, muscle pain and joint pain, swelling or your arms, legs, hands, and feet, and cough.

VENCLEXTA may cause fertility problems in males. This may affect your ability to father a child. Talk to your health care provider if you have concerns about fertility.

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

People are encouraged to report negative side effects of prescription drug to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

The full U.S. prescribing information, including Medication Guide, for VENCLEXTA can be found here. Globally, prescribing information varies; refer to the individual country product label for complete information.

Patient Assistance
For those who qualify, patient assistance options are available for people taking VENCLEXTA in the U.S. If people cannot afford their medication, they should contact www.pparx.org for assistance.

On July 11, 2018 ArQule, Inc. (Nasdaq: ARQL) reported the pricing of an underwritten public offering of 11 million shares of its common stock at a price to the public of $5.50 per share (Press release, ArQule, JUL 11, 2018, View Source [SID1234532696]). ArQule has granted the underwriters a 30-day option to purchase up to an additional 1.65 million shares of its common stock. The offering is expected to close on or about July 13, 2018, subject to satisfaction of customary closing conditions. The gross proceeds to ArQule from the offering, excluding any exercise by the underwriters of their 30-day option to purchase additional shares, are expected to be $60.5 million, before deducting underwriting discounts and commissions and other offering expenses payable by ArQule.

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The Company intends to use the net proceeds of the offering to fund its core clinical programs and for general corporate purposes.

Leerink Partners is acting as sole book-running manager for the offering. Needham & Company, LLC is acting as lead co-manager, and Roth Capital Partners, B. Riley FBR and JonesTrading Institutional Services LLC are acting as co-managers for the offering.

The securities described above are being offered by ArQule pursuant to an effective shelf registration statement on Form S-3 (File. No. 333-213456), including a base prospectus, that was previously filed by ArQule with the Securities and Exchange Commission ("SEC"). A final prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website located at www.sec.gov or on ArQule’s website, www.arqule.com. Copies of the final prospectus supplement and the accompanying prospectus relating to the offering, when available, may be obtained from Leerink Partners LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at (800) 808-7525, ext. 6132 or by email at [email protected].

This press release does not constitute an offer to sell or a solicitation of an offer to buy, nor will there be any sales of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such jurisdiction.

On July 11, 2018 Asterias Biotherapeutics, Inc. (NYSE American:AST), a biotechnology company dedicated to developing cellular immunotherapies to treat cancer and cell-based therapeutics to treat neurological conditions associated with demyelination, reported that the Safety Review Committee (SRC) for the first clinical trial of AST-VAC2, held a scheduled meeting to review the safety and tolerability data generated in the first patient enrolled in the study and recommended continuation of the study and moving to parallel enrollment of the second and third patients in the advanced cancer cohort (Arm A), as planned per the study’s protocol (Press release, Asterias Biotherapeutics, JUL 11, 2018, View Source;date=July+11%2C+2018&title=Asterias+Biotherapeutics+Announces+Positive+Outcome+from+Safety+Review+Committee+for+AST-VAC2%3B+Recommends+Continuation+of+Clinical+Trial+in+Non-Small+Cell+Lung+Cancer+%28NSCLC%29 [SID1234527937]). This initial clinical trial, which is being sponsored, managed and funded by Cancer Research UK under a collaboration between Asterias and Cancer Research UK, will examine the safety and tolerability of AST-VAC2 in non-small cell lung cancer (NSCLC) as the study’s primary endpoints. Secondary and tertiary endpoints of the study include evaluations of the immunogenicity of AST-VAC2 in NSCLC.

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"Based on its review of all available study data after five doses in the first patient, the Safety Review Committee’s recommendation to continue the trial without modification reaffirms our belief that AST-VAC2 is safe and well-tolerated," commented Dr Edward Wirth, Chief Medical Officer of Asterias Biotherapeutics. "The committee concluded that the trial can proceed as planned per protocol – an important step as we continue the clinical development of AST-VAC2."

The Safety Review Committee reviewed all of the accumulated safety data generated to date for the first patient in Arm A (advanced disease), who by the time of the review had received five, weekly doses of 10 million AST-VAC2 cells.

As specified in the AST-VAC2 clinical trial protocol, the Safety Review Committee meets on a dosing-driven basis to review safety and tolerability data from the ongoing trial. The committee is comprised of a group of medical and scientific experts and is responsible for reviewing and evaluating patient safety data in order to safeguard the wellbeing of trial participants.

About AST-VAC2

AST-VAC2 is an innovative immunotherapy product that contains mature dendritic cells derived from pluripotent stem cells. These non-patient specific (allogeneic) AST-VAC2 cells are engineered to express a modified form of telomerase, a protein widely expressed in tumor cells, but rarely found in normal cells. The modified form of telomerase invokes enhanced stimulation of immune responses to the protein. Similar to an earlier, Asterias-sponsored, hematological cancer program which provided proof-of-concept data in [AML], the AST-VAC2 dendritic cells instruct the immune system to generate responses against telomerase and, through this mechanism, target tumor cells. AST-VAC2’s mode of action is complementary to and potentially synergistic with other immune therapies such as checkpoint inhibitors or other immune pathway inhibitors.

About Non-Small Cell Lung Cancer and the AST-VAC2 Trial

Lung cancer (both small cell and non-small cell) is the leading cause of cancer-related death, accounting for about one-quarter of all cancer deaths and more than colorectal, breast, and prostate cancers combined. Non-small cell lung cancer (NSCLC) accounts for about 80% to 85% of lung cancers, according to the American Cancer Society. The three main types of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. The American Cancer Society’s estimates for lung cancer in the United States for 2017 are: about 222,500 new cases of lung cancer, and about 155,870 deaths from lung cancer. Despite the large number of people afflicted by non-small cell lung cancer, patients remain vastly underserved due to a scarcity of effective treatments. According to statistics published by Cancer Research UK, the five year survival rate for lung cancer patients in England and Wales is less than 10%.

As currently designed, the first AST-VAC2 clinical trial will enrol up to 24 subjects into one of two cohorts, depending on the stage of their non-small cell lung cancer. The first cohort will evaluate AST-VAC2 in up to 12 subjects with advanced non-small cell lung cancer. Subjects in this cohort, who carry the major histocompatibility gene, HLA-A2, will receive six weekly injections of AST-VAC2 and will be followed for safety, immune responses to telomerase and overall clinical survival. Assuming safety is demonstrated in the first cohort, enrolment will advance to a second cohort. In the second cohort, early stage subjects who have had successful resection of their tumour with no evidence of metastasis will be enrolled. Up to 12 subjects in this second cohort who carry the major histocompatibility allele HLA-A2 will receive six, weekly injections of AST-VAC2 and will be followed for safety, immune responses to telomerase, overall clinical survival and time to relapse. Both cohorts will also have a control group consisting of patients that meet all inclusion/exclusion criteria for the study but who do not have the HLA-A2 marker. Subjects will be followed for one year for immune response to telomerase and for 2 years for the survival endpoints. The supply of AST-VAC2 to be used in this trial is being manufactured by Cancer Research UK’s Biotherapeutics Development Unit.

On July 11, 2018 Mitra RxDx (dba Mitra Biotech), a privately held biotech company and global leader in advancing truly personalized oncology treatment, reported the completion of a $40 million financing round (Press release, Mitra Biotech Pvt, JUL 11, 2018, View Source [SID1234527687]). The round was led by Northpond Ventures, headquartered in Bethesda, Maryland. Existing investors Accel, Sequoia Capital, Sands Capital Ventures, and RA Capital Management also participated. Cumulative funding to date now totals $76 million.

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Mitra’s CANscript platform delivers powerful, individualized treatment response predictions — with exceptionally high correlation to clinical outcomes — to inform patient-specific cancer treatment selection and support more effective and efficient cancer drug development.

"Northpond is excited to join Mitra, as the CANscript platform has the potential to meaningfully improve how we treat cancer patients," said Michael P. Rubin, M.D., Ph.D., Founder and CEO at Northpond. "We are proud to begin working with the current investors to help Mitra accomplish their clinical and commercial goals." Michael will join existing investor representatives from Accel, Sequoia, Sands, and Tata Capital Innovation Fund on the Mitra board.

"These funds will allow us to expand our commercial efforts, while also continuing to build the clinical evidence necessary to accelerate adoption and secure reimbursement in the U.S. and other key markets," said Mallikarjun Sundaram, President, Co-Founder, and CEO of Mitra. "We enthusiastically welcome Northpond, and greatly appreciate the continued support from our current investors."

On July 11, 2018 Bavarian Nordic A/S (OMX: BAVA, OTC: BVNRY) reported that the first patient has been dosed in a Phase 2 study evaluating the combination therapy of its cancer vaccine, CV301, and Bristol Myers Squibb’s checkpoint inhibitor, nivolumab (OPDIVO), for the treatment of patients with resectable hepatic-limited metastatic colorectal cancer (mCRC) (Press release, Bavarian Nordic, JUL 11, 2018, View Source [SID1234527657]).

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Bavarian Nordic’s CV301 is designed to create a T-cell response against the tumor antigens CEA and MUC1, which are overexpressed on multiple solid tumors, including colorectal cancers. Preclinical data supports the premise that CV301 is highly synergistic with checkpoint inhibitors and holds the potential to broaden their efficacy in cancers where monotherapy has been ineffective.

The randomized, multiple-site, Phase 2 trial is being led by Darren Carpizo, M.D., Ph.D., the Director of the Liver Cancer and Bile Duct Cancer Program at Rutgers Cancer Institute, with material support from Bavarian Nordic and Bristol Myers Squibb. The study is expected to enroll 78 patients. Prior to surgical removal of their tumors, patients will be randomized to receive four cycles of either chemotherapy plus nivolumab or a combination of chemotherapy, nivolumab, and CV301. After resection, patients will continue receiving respective treatments in each study arm. Overall survival (OS) and several secondary measures will be evaluated in each arm.

"We are thrilled to see the first dose administered in this trial to evaluate the combination therapy of CV301 and nivolumab in patients with resectable, oligometastatic, microsatellite stable colorectal cancer (MSS)," said Paul Chaplin, President and CEO of Bavarian Nordic. "While checkpoint inhibitors have been impressive in some tumors, there are hundreds of thousands of cancer patients in dire need of new treatments, particularly in MSS. We are eager to explore how CV301 enhances the overall survival and lowers the risk of reoccurrence in these patients."

For more information on how to take part in this trial, individuals should call Rutgers Cancer Institute’s Office of Human Research Services at 732-235-8675 or e-mail [email protected].

About CV301
CV301 is an immunotherapy candidate which is being developed under a CRADA with the National Cancer Institute (NCI). CV301 targets two tumor-associated antigens, CEA and MUC1, which are over-expressed in multiple solid tumors, including lung, bladder, colorectal and pancreatic cancers. CV301 is a poxvirus-based prime/boost vaccine that incorporates a modified version of vaccinia (MVA-BN, a proprietary technology of Bavarian Nordic) as a priming dose, followed by multiple fowlpox boosts, and encodes the TRICOM costimulatory molecules.

Preclinical data shows that MVA-BN vaccines encoding a tumor antigen transgene (like CEA and MUC-1) upregulate PD-L1 by mounting an immune response against a tumor target. The upregulation of PD-L1 is a marker indicating the tumor is under attack from T-cells, presenting an opportunity for a greater response in patients who might otherwise not benefit from treatment with a checkpoint inhibitor alone.