On January 10, 2017 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) has accepted for review the supplemental Biologics License Application (sBLA) for KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, plus chemotherapy (pemetrexed plus carboplatin) for the first-line treatment of patients with metastatic or advanced non-squamous non-small cell lung cancer (NSCLC) regardless of PD-L1 expression and with no EGFR or ALK genomic tumor aberrations (Press release, Merck & Co, JAN 10, 2017, View Source [SID1234517337]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This is the first application for regulatory approval of KEYTRUDA in combination with another treatment. The FDA granted Priority Review with a PDUFA, or target action, date of May 10, 2017. The sBLA will be reviewed under the FDA’s Accelerated Approval program.

"Through our monotherapy and combination studies, we are working to find new approaches to help a broad range of patients with lung cancer," said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. "KEYTRUDA in combination with chemotherapy has shown promise versus chemotherapy alone in the first-line treatment of non-squamous metastatic non-small cell lung cancer, regardless of PD-L1 levels. If approved, this could be the first regimen combining chemotherapy with an immuno-oncology agent for patients with advanced non-small cell lung cancer."

The application seeks accelerated approval for KEYTRUDA at a fixed dose of 200 mg administered intravenously every three weeks in combination with pemetrexed 500 mg/m2 administered as an IV infusion over 10 minutes every three weeks, and carboplatin AUC 5 mg/mL/min every three weeks for four cycles. KEYNOTE-021, Part 2, Cohort G, the pivotal cohort that forms the basis of the submission, studied 123 previously untreated patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations and regardless of PD-L1 expression.

KEYTRUDA (pembrolizumab) is currently approved in lung cancer for the first-line treatment of patients with metastatic NSCLC whose tumors have high PD-L1 expression (tumor proportion score [TPS] of 50 percent or more) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations; and for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS of one percent or more) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Merck has an extensive development program in NSCLC and is currently advancing multiple registration-enabling studies with KEYTRUDA as monotherapy and in combination with other treatments.

About Lung Cancer

Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of cancer death worldwide. Each year, more people die of lung cancer than die of colon, breast, and prostate cancers combined. The two main types of lung cancer are non-small cell and small cell. NSCLC is the most common type of lung cancer, accounting for about 85 percent of all cases. The five-year survival rate for patients suffering from highly advanced, metastatic (Stage IV) lung cancers is estimated to be two percent.

About KEYTRUDA (pembrolizumab)

KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

KEYTRUDA is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single use vial.

KEYTRUDA (pembrolizumab) Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a dose of 2 mg/kg every three weeks until disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%) pneumonitis, and occurred more frequently in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA (pembrolizumab) for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in patients with HNSCC occurring in 28 (15%) of 192 patients with HNSCC, including Grade 3 (0.5%) hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA (pembrolizumab) and administer antihyperglycemics in patients with severe hyperglycemia.

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

KEYTRUDA can cause other clinically important immune-mediated adverse reactions. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), exfoliative dermatitis, bullous pemphigoid, rash (1.4%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma.

KEYTRUDA can cause severe or life-threatening infusion-related reactions, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for signs and symptoms of infusion-related reactions, including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). Adverse reactions leading to interruption of KEYTRUDA (pembrolizumab) occurred in 21% of patients; the most common (≥1%) was diarrhea (2.5%). The most common adverse reactions with KEYTRUDA vs ipilimumab were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs 23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are listed for ipilimumab only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.

In KEYNOTE-002, KEYTRUDA was discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (≥1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). Adverse reactions leading to interruption of KEYTRUDA occurred in 14% of patients; the most common (≥1%) were dyspnea (1%), diarrhea (1%), and maculopapular rash (1%). The most common adverse reactions with KEYTRUDA vs chemotherapy were fatigue (43% with KEYTRUDA), pruritus (28% vs 8%), rash (24% vs 8%), constipation (22% vs 20%), nausea (22% with KEYTRUDA), diarrhea (20% vs 20%), and decreased appetite (20% with KEYTRUDA). Corresponding incidence rates are listed for chemotherapy only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.

KEYTRUDA was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC. The most common adverse event resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.8%). Adverse reactions leading to interruption of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most common adverse reactions (occurring in at least 20% of patients and at a higher incidence than with docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea (20% vs 18%).

KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (reported in at least 20% of patients) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC, with the exception of increased incidences of facial edema (10% all Grades; 2.1% Grades 3 or 4) and new or worsening hypothyroidism.

It is not known whether KEYTRUDA (pembrolizumab) is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.

Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

On January 10, 2017 Alligator presented the corporate presentation (Press release, Alligator Bioscience, JAN 10, 2017, View Source [SID1234538700]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On January 9, 2017 DelMar Pharmaceuticals, Inc. (NASDAQ: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported an increase in funding of up to CDN$413,000 from the National Research Council of Canada Industrial Research Assistance Program (NRC-IRAP) to support ongoing research with VAL-083 (Press release, DelMar Pharmaceuticals, JAN 9, 2017, View Source [SID1234517323]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

DelMar Pharmaceuticals Logo
This increased funding will support additional research into VAL-083’s mechanism of action including validation of molecular targets responsible for the drug’s activity against cancer, investigation of combination therapies and pivotal in vivo models in new indications.

Research will be conducted in collaboration with the University of British Columbia, the Vancouver Prostate Centre and the B.C. Cancer Agency.

"We are very pleased with NRC-IRAP’s continued support of our non-clinical research of our lead product candidate VAL-083," said Jeffrey Bacha, chairman & CEO of DelMar Pharmaceuticals. "NRC-IRAP’s support to date has been instrumental in the progress our team has made in understanding VAL-083’s unique mechanism of action and to broadening the focus of our research into new indications."

About VAL-083
VAL-083 is a "first-in-class," small-molecule chemotherapeutic. In more than 40 Phase I and II clinical studies sponsored by the U.S. National Cancer Institute, VAL-083 demonstrated clinical activity against a range of cancers including lung, brain, cervical, ovarian tumors and leukemia both as a single-agent and in combination with other treatments.

DelMar’s research has demonstrated that VAL-083 is active against GBM cell lines that are resistant to standard-of-care chemotherapy due to features such as high expression of MGMT, in vitro.

DelMar presented data from its Phase I/II clinical trial in refractory GBM at the 2016 American Association of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual meeting demonstrating that the median survival of 22 patients receiving an assumed therapeutic dose of VAL-083 (≥20mg/m2) was 8.35 months following Avastin (bevacizumab) failure compared to published literature where survival of approximately two to five months has been reported.

VAL-083 has received an orphan drug designation in Europe for the treatment of malignant gliomas and the U.S. FDA Office of Orphan Products has granted an orphan designation to VAL-083 for the treatment of glioma, medulloblastoma and ovarian cancer.

Further details can be found at View Source

On January 9, 2017 Advaxis, Inc. (NASDAQ:ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, reported its 2017 business outlook to provide an overview of anticipated events and key milestones for the coming year, as well as a look back at clinical and business highlights from 2016 (Press release, Advaxis, JAN 9, 2017, View Source [SID1234517383]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Advaxis made significant strides in its clinical development programs and expanded its pipeline with additional preclinical assets in 2016. The company’s lead product candidate, axalimogene filolisbac, received Fast Track designation and a Special Protocol Assessment (SPA) for the global Phase 3 AIM2CERV study, a randomized study of axalimogene filolisbac following chemoradiation in patients with high-risk, locally advanced cervical cancer (HRLACC). Also in 2016, axalimogene filolisbac was classified as an advanced therapy medicinal product (ATMP) for the treatment of cervical cancer by the European Medicines Agency’s (EMA) Committee for Advanced Therapies (CAT). Late in 2016, the company initiated AIM2CERV and announced positive, final data from the GOG-0265 Phase 2 trial that supports pursuing a second global Phase 3 study in a metastatic recurrent cervical cancer. Also in 2016, Advaxis entered into a collaboration with Amgen Inc. (Amgen) for the global development and commercialization of Advaxis’ preclinical neoantigen technology, ADXS-NEO, to create a personalized approach to cancer treatment.

In 2016, Advaxis expanded its capabilities and added significant resources to support execution of two global registrational clinical trials and future commercialization of its immuno-oncology products. The company added close to $100 million in capital from proceeds from the Amgen collaboration, a direct placement and a state grant. Advaxis expanded its management team in 2016 with the appointment of Chris Duke as Chief Operating Officer, and added approximately 30 more employees in key areas, as the company grew its headcount to 80 over the course of the year. In September, the company completed the buildout of its clinical manufacturing facility to produce clinical trial supplies and expanded its research laboratory facility. Also, the company began construction of its commercial manufacturing facility, all at its Princeton headquarters.

2017 OPERATIONAL MILESTONES

Advaxis anticipates the following development milestones in 2017:

Clinical Operations

Axalimogene Filolisbac

Present a detailed data analysis of the completed Phase 2 GOG-0265 trial, which was conducted by the GOG Foundation, Inc. (GOG, now part of NRG Oncology), evaluating patients with persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC), at a medical meeting in the first half of 2017. Top-line data released in 2016 showed a 12-month overall survival rate of 38 percent observed in 50 patients in the trial. This is a 52 percent improvement over the 12-month overall survival rate that was expected in the trial’s patient population based on prognostic factors.
Attend an end-of-Phase-2 meeting with respect to PRmCC with the U.S. Food and Drug Administration (FDA) to discuss the results of GOG-0265.
Submit a marketing authorization application to the EMA for approval of axalimogene filolisbac to treat patients with metastatic cervical cancer in the second half of 2017.
Open approximately 150 clinical sites for the global, 450-patient Phase 3 AIM2CERV trial in patients with HRLACC, with a trial enrollment update to be issued at a medical meeting in the first half of 2017. There are 10 active trial sites in the United States as of this week.
Initiate a second global, registrational Phase 3 study in patients with metastatic cervical cancer in the second half of 2017.
Present updated clinical data from the Phase 1/2 combination trial with AstraZeneca’s investigational anti-PD-L1 inhibitor, durvalumab, in patients with recurrent, persistent or metastatic cervical cancer or HPV+ squamous cell cancer of the head and neck (HNSCC) at a medical meeting in the second half of 2017.
Present additional data from the Phase 2 BrUOG trial in high-risk, locally advanced anal cancer, conducted in collaboration with Brown University’s Oncology Research Group, at a medical meeting in the first half of 2017.
Present additional data from the Phase 2 window of opportunity trial in HPV-positive head and neck cancers at a medical meeting in the first half of 2017.
With full enrollment achieved in Stage 1 of the FAWCETT Phase 2 trial in patients with persistent or recurrent metastatic anal cancer, the company plans to present a preliminary trial update at a medical meeting in the second half of 2017.
ADXS-PSA

Complete initial dosing of Part B of the Phase 1/2 trial evaluating ADXS-PSA in combination with KEYTRUDA (pembrolizumab) in advanced, metastatic castration-resistant prostate cancer (mCRPC) and present preliminary data at a medical meeting in 2017.
Initiate and complete enrollment of the expansion cohort by year-end 2017.
ADXS-HER2

Initiate a study in pediatric osteosarcoma in collaboration with the Children’s Oncology Group in 2017.
Expanding Pipeline

ADXS-NEO Collaboration with Amgen

Submit an Investigational New Drug (IND) application to the FDA in early 2017.
Initiate the first-in-human ADXS-NEO clinical trial.
Accelerate the discovery of personalized cancer immunotherapies derived from neoantigens as part of the TESLA (Tumor neoantigEn SeLection Alliance) with the Parker Institute for Cancer Immunotherapy and the Cancer Research Institute.
ADXS-HOT

Prepare and file an IND with the FDA for ADXS-HOT constructs that target tumor driver genes, so-called hotspot mutations or public mutations, found in various cancer types in the second half of 2017.
Enhanced Manufacturing and Research Capabilities

Increase capacity to include in-house clinical and commercial manufacturing capabilities, initially to manufacture clinical supplies for the ADXS-NEO program in 2017.
Reduce lead times and improve overall supply chain by operationalizing several technology transfers with its partners and by installing new innovative technologies.
Corporate Development

Pursue research, clinical and commercial partnerships to optimize the cancer immunotherapy portfolio, including to enable development of lead asset, axalimogene filolisbac, in combination with other novel cancer therapies and to support its registration and potential commercialization in the EU.
Explore the application of detoxified Listeriolysin O (dtLLO) technology and optimize the research and development as an adjuvant molecule in the development of vaccines.
2016 REVIEW

Advaxis achieved several regulatory, clinical, business and operational milestones in 2016:

Clinical Milestones

Axalimogene Filolisbac

June: Presented preliminary data at American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) from stage 1 of the Phase 2 GOG-0265 clinical study showing a 6-month survival rate of 38.5 percent in 26 patients, which exceeds prior historical GOG trials in this patient population. Of particular note, a patient from this stage experienced a complete response following three doses which remains ongoing.
June: Dosed the first patient in the first stage of the Phase 2 FAWCETT trial in patients with persistent or recurrent metastatic anal cancer.
July: Reached an agreement with the FDA under the SPA process for the Phase 3 AIM2CERV trial.
July: Received classification as an ATMP for the treatment of cervical cancer by the EMA’s CAT and received Fast Track Designation from the FDA for high-risk, locally advanced cervical cancer.
October: Entered Phase 3 with initiation of AIM2CERV evaluating axalimogene filolisbac as an adjuvant therapy following chemotherapy and radiation.
October: Announced updated data from the Phase 2 GOG-0265 clinical study which showed a patient with recurrent cervical cancer achieved a durable complete response, as well as a 12-month overall survival rate of 38 percent across all study subjects (n=50), surpassing historical 12-month survival rates in GOG studies which have never exceeded 30 percent.
November: As presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting, a patient with cervical cancer participating in the combination trial with AstraZeneca’s durvalumab achieved a complete response, and two patients with HNSCC achieved stable disease.
April: The window of opportunity trial, as presented as American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, showed increased systemic HPV-reactive T-cell responses in patients with late-stage HPV-positive oropharyngeal cancer, allowing for the trial to advance to the second stage, being conducted at the Icahn School of Medicine at Mount Sinai.
ADXS-PSA

April: Finalized the part A dose-escalation cohort of the Phase 1/2 KEYNOTE-046 combination trial with Merck, which evaluated maximum tolerability of ADXS-PSA in patients with previously treated mCRPC.
October: Initiated the combination portion evaluating ADXS-PSA in combination with KEYTRUDA.
ADXS-HER2

May: As published in Clinical Cancer Research, in a dose-escalation study of ADXS-HER2 in canine osteosarcoma, antigen-specific T-cell responses were seen within 6 months of immunotherapy administration.
April: FDA granted Fast Track designation for ADXS-HER2 for patients with newly diagnosed, non-metastatic, surgically-resectable osteosarcoma.
Expanding Pipeline

ADXS-NEO

January: Established a five-year exclusive supply agreement with Synthetic Genomics, Inc. to manufacture the synthetic DNA used in ADXS-NEO.
August: Advaxis entered into a global collaboration with Amgen to develop and commercialize ADXS-NEO. Under the collaboration agreement, Advaxis will lead the clinical development of ADXS-NEO through proof-of-concept, retain manufacturing responsibilities, and receive development, regulatory and sales milestone payments of up to $475 million. Amgen received worldwide rights to develop and commercialize ADXS-NEO.
December: Advaxis joined the TESLA (Tumor neoantigEn SeLection Alliance) collaboration with the Parker Institute for Cancer Immunotherapy and the Cancer Research Institute, along with 30 leading academia and industry partners, to further cancer neoantigen research.
Business & Operations

Advaxis achieved the following operational milestones in 2016:

Over the course of 2016, Advaxis expanded its leadership team, deepening its clinical operations, manufacturing and business development functions:
Christopher Duke, Senior Vice President and Chief Operating Officer.
Ranya Dajani, Vice President, Corporate Development
January: Established a Scientific Advisory Board, including Antoni Ribas, M.D., Ph.D., Jedd Wolchok, M.D., Ph.D., Nancy Freitag, Ph.D., Marc Lecuit, M.D., Ph.D.
January: Added two more patents to its growing patent portfolio; European Patent No. 1804831 expands the composition of matter claims covering HER-2 tumor antigens, and U.S. Patent No. 9,226,958 expands the use of the Company’s Lm Technology beyond oncology, specifically to induce an immune response in parasitically infected patients.
February: Bradley Monk, co-primary investigator of the GOG-0265 Phase 2 study, joined Advaxis as the company’s Lead Cervical Cancer Advisor to head the development of Advaxis’ Lm Technology platform and lead the AIM2CERV program.
February: Agreement established with Especificos Stendhal SA de CV ("Stendhal") to co-develop and commercialize axalimogene filolisbac in Latin America.
February: Daniel O’Connor, president and chief executive officer of Advaxis, was appointed to the Board of Trustees of BioNJ.
April: Advaxis became the first biotechnology company to receive the Vision of Hope Award from the Sarcoma Foundation of America for its ADXS-HER2 osteosarcoma immunotherapy platform.
August: Advaxis secured $30 million in direct placement financing from healthcare institutional specialist investors.
September: Advaxis unveiled its state-of-the-art laboratory and manufacturing facility to develop immuno-oncology therapeutics in Princeton N.J. where Governor Chris Christie led the ribbon-cutting event.
October: Advaxis received $2.5M through the New Jersey Economic Development Authority’s (NJEDA) New Jersey Technology Business Tax Certificate Transfer (NOL) program.

On January 9, 2017 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the fields of cancer metabolism and rare genetic metabolic diseases, reported key 2017 milestones in conjunction with its presentation at the 35th Annual J.P. Morgan Healthcare Conference in San Francisco (Press release, Agios Pharmaceuticals, JAN 9, 2017, View Source;p=RssLanding&cat=news&id=2234926 [SID1234517384]). The presentation will outline important milestones as Agios evolves into a commercial stage company, including potential launches for enasidenib and AG-120 in R/R AML, pivotal development for its second wholly owned asset, AG-348 in pyruvate kinase (PK) deficiency, and an investigational new drug (IND) application submission for the company’s next development candidate, focused on MTAP deleted cancers. The company will webcast its presentation on Monday, January 9, 2017 at 10:00 a.m. PT (1:00 p.m. ET) at www.agios.com.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This is the year Agios will evolve into a commercial-stage organization with the anticipated launch of enasidenib for patients with R/R AML, followed by the NDA submission of AG-120 and AG-348 preparing to enter a pivotal trial in PK deficiency," said David Schenkein, M.D., chief executive officer of Agios. "We believe these milestones will enable us to achieve our vision of delivering important medicines with the potential to transform patients’ lives. Additionally, our robust research engine continues to be highly productive with an IND submission for the company’s sixth development candidate in eight years anticipated by the end of 2017."

The company expects to achieve the following key milestones by the end of 2017:

Potential approval of enasidenib in the United States for IDH2m positive R/R AML in collaboration with Celgene.
Submit a new drug application (NDA) to the U.S. FDA for AG-120 by the end of 2017. AG-120 is a wholly owned, first-in-class, oral, selective, potent inhibitor of IDH1m, in IDH1m positive R/R AML.
Initiate a global, registration-enabling Phase 3 study combining AG-120 and VIDAZA in frontline AML patients with an IDH1 mutation ineligible for intensive chemotherapy in the first half of 2017.
Finalize design and operational activities for a global pivotal trial of AG-348 to initiate in the first half of 2018. AG-348 is a wholly owned, first-in-class, oral activator of both wild-type (normal) and mutated pyruvate kinase-R (PKR) enzymes, in PK deficiency.
File an IND application for the MTAP pathway development candidate by the end of 2017.
The company also provided an update on the following 2016 milestones achieved in December:

Supported Celgene’s submission of an NDA for enasidenib in IDH2m positive R/R AML.
Initiated a global, registration-enabling randomized Phase 3 trial for AG-120 in IDH1m positive cholangiocarcinoma. The FDA also granted AG-120 Fast Track Designation for the treatment of patients with previously treated, unresectable or metastatic cholangiocarcinoma with an IDH1 mutation.
Selected a development candidate focused on the MTAP pathway to enter IND-enabling studies.
2016 Year-End Cash and Guidance

Agios ended 2016 with approximately $574 million of cash, cash equivalents and marketable securities. Based on its current operating plans, the company expects that its existing cash, cash equivalents and marketable securities as of December 31, 2016, together with anticipated interest income, and anticipated expense reimbursements under its collaboration agreements with Celgene, but excluding any additional program-specific milestone payments from Celgene, will enable the company to fund its anticipated operating expenses and capital expenditure requirements through at least the end of 2018.