On March 29, 2018 Amgen (NASDAQ:AMGN) reported that the U.S. Food and Drug Administration (FDA) has approved the supplemental Biologics License Application (sBLA) for BLINCYTO (blinatumomab) for the treatment of adults and children with B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1 percent (Press release, Amgen, MAR 29, 2018, View Source;p=RssLanding&cat=news&id=2340390 [SID1234525475]). This indication is approved under accelerated approval based on MRD response rate and hematological relapse-free survival (RFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. BLINCYTO, the first-and-only approved bispecific CD19-directed CD3 T cell engager (BiTE) immunotherapy, is now also the first-and-only therapy to be FDA-approved for MRD.

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!

MRD refers to the presence of cancer cells that remain detectable, despite a patient’s having achieved complete remission by conventional assessment.1 MRD is only measurable through the use of highly sensitive testing methods that detect cancer cells in the bone marrow with a sensitivity of at least one cancer cell in 10,000 cells — versus about one in 20 with a conventional microscope-based evaluation.1,2,3

"Until today, no therapy has been satisfactory in eradicating MRD or approved specifically to treat this high-risk patient population," said David M. Reese, M.D., senior vice president of Translational Sciences and Oncology at Amgen. "This approval not only supports the use of BLINCYTO earlier in the ALL treatment continuum, but represents a paradigm shift in the management of ALL."

"The detection of remaining cancer cells after a complete remission is the strongest prognostic factor for relapse in patients with ALL. It’s critical to test for and know your patients’ MRD status, because we know that treating to MRD-negativity will help to obtain better possible clinical outcomes for patients," said Elias Jabbour, M.D., associate professor, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston. "In the BLAST study, blinatumomab led to no detectable cancer cells in approximately 80 percent of patients with MRD-positive ALL. This approval provides a much-needed treatment option to destroy the remaining detectable traces of leukemia."

The accelerated approval is based on results from the Phase 2 single-arm BLAST study (n=86), which found that BLINCYTO converted most patients to an MRD-negative state after a single cycle of therapy. BLINCYTO met the primary endpoint, inducing a complete MRD response, which is no detectable MRD, in 81 percent of patients (95 percent CI: 71.6, 89.0). Median hematological RFS was 22.3 months.

Safety results among MRD-positive patients were consistent with the known safety profile of BLINCYTO in relapsed or refractory B-cell precursor ALL. The most common adverse reactions (greater than 20 percent) were pyrexia, infusion related reactions, headache, infections (pathogen unspecified), tremor and chills.

The FDA-approved prescribing information for BLINCYTO includes a boxed warning for cytokine release syndrome and neurologic toxicities. BLINCYTO is also under a risk evaluation and mitigation strategy (REMS) program in the U.S.

About BLINCYTO (blinatumomab)
BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE) immunotherapy that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells. BLINCYTO was granted breakthrough therapy and priority review designations by the FDA in 2014, and is now fully approved in the U.S. for the treatment of relapsed or refractory B-cell precursor ALL in adults and children. BLINCYTO is now also approved under accelerated approval for the treatment of adults and children with B-cell precursor ALL in first or second complete remission with MRD greater than or equal to 0.1 percent. This indication is approved under accelerated approval based on MRD response rate and hematological relapse-free survival (RFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

In November 2015, BLINCYTO was granted conditional marketing authorization in the European Union for the treatment of adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor ALL. Additional regulatory applications for BLINCYTO are underway and have been submitted to health authorities worldwide.

About the BLAST Study
The BLAST study is the largest ever prospective trial in patients with MRD-positive ALL. It is an open-label, multicenter, single-arm, Phase 2 study evaluating the efficacy, safety and tolerability of BLINCYTO in adult patients with MRD-positive B-cell precursor ALL in complete hematologic remission after three or more cycles of intensive chemotherapy. Patients received continuous IV infusion of BLINCYTO 15 μg/m2/d for four weeks, followed by two weeks off. Patients received up to four cycles of treatment and could undergo hematopoietic stem cell transplantation (HSCT) at any time after the first cycle, if eligible. The primary endpoint was the rate of complete MRD response within the first treatment cycle. The key secondary endpoint was RFS at 18 months. Additional secondary endpoints included incidence and severity of adverse events, overall survival (OS), time to hematological remission and duration of complete MRD response.

To evaluate the association between complete MRD response and subsequent RFS and OS, landmark analyses were performed at 45 days (day by which all first cycle MRD responses had been assessed) for patients with and without a complete MRD response in the first cycle. Patients who relapsed, died, or were censored before day 45 were excluded to correct for immortal time bias. Improvement in median RFS was seen for BLINCYTO patients achieving a complete MRD response compared to MRD nonresponses, 23.6 months versus 5.7 months, respectively (p=0.002).

Results from the BLAST study were presented at the 57th Annual Meeting and Exposition of the American Society of Hematology (ASH) (Free ASH Whitepaper) in 2015 and published in Blood in 2018.

About ALL and MRD
ALL is a rare and rapidly progressing cancer of the blood and bone marrow that occurs in both adults and children.4,5 Nearly 50 percent of adult patients and 25 percent of pediatric patients with B-cell ALL eventually relapse or are refractory to treatment.6,7 Poor outcomes have been observed in patients who relapse after achieving a complete response but have persistent MRD, or disease that remains at the molecular level after treatment.1,8 Five-year OS rates are as high as 75 percent for patients that achieve MRD-negative status, compared with 33 percent among patients that remain MRD-positive.8 In pediatric patients, MRD-positive status after treatment is associated with a 15-times higher risk of relapse compared with those with undetectable residual disease.9 For more information about MRD, please visit AmgenOncology.com.

About BiTE Technology
Bispecific T cell engager (BiTE) antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body’s immune system to detect and target malignant cells. The modified antibodies are designed to bridge T cells to tumor cells, using the patient’s own immune system to eradicate cancer. BiTE antibody constructs help place the T cells within reach of the targeted cell, with the intent of causing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE antibody constructs are currently being investigated for their potential to treat a wide variety of cancers.

BLINCYTO U.S. Product Safety Information

Indication and Important Safety Information, including Boxed WARNINGS, for BLINCYTO (blinatumomab) for injection, for intravenous use

INDICATION

BLINCYTO is indicated for the treatment of adults and children with:

B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%. This indication is approved under accelerated approval based on MRD response rate and hematological relapse-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Relapsed or refractory B‑cell precursor acute lymphoblastic leukemia (ALL)
IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES

Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Contraindications

BLINCYTO is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions

Cytokine Release Syndrome (CRS): CRS, which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. The median time to onset of CRS is 2 days after the start of infusion. Closely monitor patients for signs and symptoms of serious adverse events such as fever, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), and disseminated intravascular coagulation (DIC). The manifestations of CRS after treatment with BLINCYTO overlap with those of infusion reactions, capillary leak syndrome (CLS), and hemophagocytic histiocytosis/macrophage activation syndrome (MAS). In clinical trials of BLINCYTO, CRS was reported in 15% of patients with relapsed or refractory ALL and in 7% of patients with MRD-positive ALL. Interrupt or discontinue BLINCYTO as outlined in the PI.
Neurological Toxicities: Approximately 65% of patients receiving BLINCYTO in clinical trials experienced neurological toxicities. The median time to the first event was within the first 2 weeks of BLINCYTO treatment and the majority of events resolved. The most common (≥ 10%) manifestations of neurological toxicity were headache and tremor. Severe, life‐threatening, or fatal neurological toxicities occurred in approximately 13% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. Manifestations of neurological toxicity included cranial nerve disorders. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO as outlined in the PI.
Infections: Approximately 25% of patients receiving BLINCYTO in clinical trials experienced serious infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-site infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO as needed.
Tumor Lysis Syndrome (TLS), which may be life-threatening or fatal, has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on-treatment hydration, should be used during BLINCYTO treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO as needed to manage these events.
Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters (including, but not limited to, white blood cell count and absolute neutrophil count) during BLINCYTO infusion and interrupt BLINCYTO if prolonged neutropenia occurs.
Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO is being administered.
Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO treatment with a median time to onset of 3 days. In patients receiving BLINCYTO, although the majority of these events were observed in the setting of CRS, some cases of elevated liver enzymes were observed outside the setting of CRS, with a median time to onset of 19 days. Grade 3 or greater elevations in liver enzymes occurred in approximately 7% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase (GGT), and TBILI prior to the start of and during BLINCYTO treatment. BLINCYTO treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.
Pancreatitis: Fatal pancreatitis has been reported in patients receiving BLINCYTO in combination with dexamethasone in clinical trials and the post-marketing setting. Evaluate patients who develop signs and symptoms of pancreatitis and interrupt or discontinue BLINCYTO and dexamethasone as needed.
Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO, especially in patients previously treated with cranial irradiation and antileukemic chemotherapy.
Preparation and administration errors have occurred with BLINCYTO treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).
Immunization: Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to the start of BLINCYTO treatment, during treatment, and until immune recovery following last cycle of BLINCYTO.
Risk of Serious Adverse Reactions in Pediatric Patients due to Benzyl Alcohol Preservative: Serious and fatal adverse reactions including "gasping syndrome," which is characterized by central nervous system depression, metabolic acidosis, and gasping respirations, can occur in neonates and infants treated with benzyl alcohol-preserved drugs including BLINCYTO (with preservative). When prescribing BLINCYTO (with preservative) for pediatric patients, consider the combined daily metabolic load of benzyl alcohol from all sources including BLINCYTO (with preservative) and other drugs containing benzyl alcohol. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known. Due to the addition of bacteriostatic saline, 7-day bags of BLINCYTO solution for infusion with preservative contain benzyl alcohol and are not recommended for use in any patients weighing < 22 kg.
Adverse Reactions

The most common adverse reactions (≥ 20%) in clinical trial experience of patients with MRD-positive B-cell precursor ALL (BLAST Study) treated with BLINCYTO were pyrexia, infusion related reactions, headache, infections (pathogen unspecified), tremor, and chills. Serious adverse reactions were reported in 61% of patients. The most common serious adverse reactions (≥ 2%) included pyrexia, tremor, encephalopathy, aphasia, lymphopenia, neutropenia, overdose, device related infection, seizure, and staphylococcal infection.
The most common adverse reactions (≥ 20%) in clinical trial experience of patients with Philadelphia chromosome-negative relapsed or refractory B-cell precursor ALL (TOWER Study) treated with BLINCYTO were infections (bacterial and pathogen unspecified), pyrexia, headache, infusion-related reactions, anemia, febrile neutropenia, thrombocytopenia, and neutropenia. Serious adverse reactions were reported in 62% of patients. The most common serious adverse reactions (≥ 2%) included febrile neutropenia, pyrexia, sepsis, pneumonia, overdose, septic shock, CRS, bacterial sepsis, device related infection, and bacteremia.
Adverse reactions that were observed more frequently (≥ 10%) in the pediatric population compared to the adult population were pyrexia (80% vs. 61%), hypertension (26% vs. 8%), anemia (41% vs. 24%), infusion-related reaction (49% vs. 34%), thrombocytopenia (34% vs. 21%), leukopenia (24% vs. 11%), and weight increased (17% vs. 6%).
In pediatric patients less than 2 years old (infants), the incidence of neurologic toxicities was not significantly different than for the other age groups, but its manifestations were different; the only event terms reported were agitation, headache, insomnia, somnolence, and irritability. Infants also had an increased incidence of hypokalemia (50%) compared to other pediatric age cohorts (15-20%) or adults (17%).
Dosage and Administration Guidelines

BLINCYTO is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm.
It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide, for BLINCYTO

On March 29, 2018 Delcath Systems, Inc. (OTCQB:DCTH), an interventional oncology company focused on the treatment of primary and metastatic liver cancers, reported that a comparative summary of recently published research on the Company’s PHP Therapy was presented at the 2018 Society of Surgical Oncology Annual Cancer Symposium (SSO), held in Chicago, IL March 21-24, 2018 (Press release, Delcath Systems, MAR 29, 2018, View Source;p=RssLanding&cat=news&id=2340305 [SID1234525454]).

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!

In a presentation entitled Percutaneous Hepatic Perfusion (PHP) in Hepatic Liver Metastases, Jonathan Zager, MD, FACS, Chair of Graduate Medical Education at Moffitt Cancer Center and Professor of Surgery at the University of South Florida School of Medicine, compared the results from the Company’s prior Phase 3 study, published by Hughes, et al (Annals of Surgical Oncology, 2015) with more recent results published by Karydis, et al (Journal of Surgical Oncology, 2017) and Abbott, et al (American Journal of Clinical Oncology, 2017). The Hughes study was conducted from 2005 to 2010, and used an earlier generation of the Melphalan/HDS system, whereas the Karydis and Abbott studies evaluated patients primarily treated with the Generation Two version of the Melphalan/HDS system along with other refinements to the peri- and post-procedure management of patients.

Dr. Zager highlighted that in all three studies results with PHP provided evidence of improved efficacy, with Hughes showing a 5x increase in hPFS over the study control arm (PHP 245 days vs BAC 49 days), and Abbott showing significantly longer hPFS for PHP than treatment with chemoembolization (CE) and Yttrium-90 beads (Y90) (PHP 310 days, CE 80 days, Y-90 54 days). Karydis showed an overall response rate with PHP of 47%, a >84% disease control rate and hPFS of 9.1 months.

Regarding safety, Dr. Zager compared select safety data in the Hughes study conducted with the generation one system with data from the Karydis study conducted primarily in patients treated with the generation two system. The Hughes study was characterized by high percentages of hematologic side effects ranging from 60%-86% (anemia, thrombocytopenia, neutropenia). In the Karydis study, Grade 3 and 4 hematologic side effects (anemia, neutropenia, thrombocytopenia) were seen in approximately 30% of patients treated with PHP. Dr. Zager attributed this improvement in the safety profile to improvements in filtration with the generation two system, improved peri- and post-procedure management of patients, and greater experience in the treating centers. Dr. Zager concluded that PHP Therapy can be administered safely in high-volume cancer centers.

"Dr. Zager’s presentation at SSO provided a very useful overview of the efficacy consistently seen with PHP Therapy in appropriately selected patients, both in our original Phase 3 trial and in the more recent research," said Jennifer K. Simpson Ph.D., MSN, CRNP President and CEO of Delcath. "Importantly, the improvement in the safety profile noted by Dr. Zager provides confidence that our current Phase 3 FOCUS Trial in ocular melanoma liver metastases can address safety concerns expressed by the FDA after our original Phase 3 trial data was submitted, and can meet its objective of supporting an application for FDA approval for this important therapy."

On March 29, 2018 Fate Therapeutics, Inc. (NASDAQ:FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported initial clinical data from the ongoing APOLLO Phase 1 study of FATE-NK100 as a monotherapy following outpatient chemotherapy for the treatment of women with ovarian cancer resistant to, or recurrent on, platinum-based treatment (Press release, Fate Therapeutics, MAR 29, 2018, View Source [SID1234525382]). No dose-limiting toxicities were reported in either of the two subjects receiving NK100, the Company’s first-in-class, donor-derived adaptive memory natural killer (NK) cell cancer immunotherapy. Additionally, the Day 28 response evaluation for Subject 2 following a single intraperitoneal infusion of NK100 showed stable disease with evidence of tumor reduction.

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!

"We are very encouraged by our initial clinical observations of FATE-NK100 in heavily pre-treated patients with recurrent ovarian cancer," said Melissa Geller M.D., Associate Professor of Gynecologic Oncology, Department of Obstetrics, Gynecology and Women’s Health at the University of Minnesota and Principal Investigator of the APOLLO clinical trial at the Masonic Cancer Center. "Currently approved single-agent therapies for platinum-resistant ovarian cancer typically have low response rates and short median progression-free survival. The administration of NK100 directly within the peritoneal cavity is a novel therapeutic strategy to potentially improve these dismal outcomes."
Subject 2 enrolled with platinum-resistant stage III fallopian tube carcinoma having been treated with five prior lines of therapy and most recently progressing following three cycles of Avastin (bevacizumab) plus Cytoxan (cyclophosphamide) and 12 cycles of Zejula (niraparib). Stable disease with evidence of tumor reduction was observed at Day 28 following a single intraperitoneal infusion of NK100 (2×107 cells/kg). The subject elected to receive a second infusion of NK100. Both doses were well-tolerated and persistence of each dose was observed in the intraperitoneal cavity at two weeks following infusion.

The data were featured in an oral presentation by Jeffrey S. Miller, M.D., Professor of Medicine, Deputy Director of the Masonic Cancer Center, University of Minnesota at the Innate Killer Summit 2018 being held in San Diego, CA, March 28-29, 2018.

"We continue to be impressed with the safety profile and enhanced persistence of FATE-NK100. These data in ovarian cancer reinforce our experience with NK100 in the VOYAGE study for relapsed refractory AML and strengthen our conviction that NK100 is capable of addressing a broad range of tumors, including those that are known to be unresponsive to current immunotherapies," said Dr. Miller.
Longer-term follow-up assessments of response are pending for Subject 2. Subject 1 enrolled at the first dose level (1×107 cells/kg) with platinum-resistant ovarian cancer having failed five prior lines of therapy, and showed progressive disease at Day 28 follow-up. APOLLO is currently enrolling at the third dose level (≥3×107 cells/kg to 1×108 cells/kg). Ten subjects are expected to be enrolled at the maximum dose level.

About Ovarian Cancer
Ovarian cancer is the fifth leading cause of cancer-related death among women and is the deadliest of gynecologic cancers. The American Cancer Society estimates that in 2017, about 22,440 new cases of ovarian cancer will be diagnosed and 14,080 women will die of ovarian cancer in the United States. While a high proportion of women respond to initial platinum-based chemotherapy, around 70% of patients diagnosed with ovarian cancer will have a recurrence. While recurrent ovarian cancer is treatable, it is rarely curable and there is a significant need for more effective, better-tolerated therapies.

About FATE-NK100
FATE-NK100 is a first-in-class, allogeneic donor-derived natural killer (NK) cell cancer immunotherapy comprised of adaptive memory NK cells, a highly specialized and functionally distinct subset of activated NK cells expressing the maturation marker CD57. Higher frequencies of CD57+ NK cells in the peripheral blood or tumor microenvironment in cancer patients have been linked to better clinical outcomes. In preclinical studies, FATE-NK100 has demonstrated enhanced anti-tumor activity across a broad range of hematologic and solid tumors, with augmented cytokine production, improved persistence, enhanced antibody-dependent cellular cytotoxicity and increased resistance to immune checkpoint pathways compared to other NK cell therapies that are being clinically administered today. FATE-NK100 is produced through a seven-day, feeder-free manufacturing process during which NK cells sourced from a healthy donor are activated ex vivo with pharmacologic modulators. In August 2017, non-clinical data describing the unique properties and anti-tumor activity of FATE-NK100 were published by Cancer Research (doi:10.1158/0008-5472.CAN-17-0799), a peer-reviewed journal of the American Association of Cancer Research.
About APOLLO

APOLLO is an ongoing open-label, accelerated dose-escalation, Phase 1 clinical trial of FATE-NK100 in women with ovarian, fallopian tube or primary peritoneal cancer resistant to, or recurrent on, platinum-based treatment. The primary objective of the clinical trial is to assess the safety and determine the maximum dose of a single infusion via intraperitoneal catheter of FATE-NK100 as a monotherapy when administered after outpatient chemotherapy followed by a short course of intraperitoneal IL-2 infusion. Up to three dose levels of FATE-NK100 are intended to be assessed, proceeding in cohorts of one subject per dose level until a dose-limiting toxicity is observed. A total of ten subjects are expected to be enrolled at the maximum dose level. Other endpoints include objective response rates at 28 days and progression-free and overall survival at six months. The clinical trial is being conducted at the Masonic Cancer Center, University of Minnesota as an investigator-initiated study.

On March 29, 2018 Altimmune, Inc. (Nasdaq: ALT), a clinical-stage immunotherapeutics company, reported financial results for the year ended December 31, 2017 (Press release, Altimmune, MAR 29, 2018, View Source [SID1234525052]).

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!

Corporate Highlights

Enrolled first two cohorts of government funded Phase 1 trial of NasoShield, an intranasal vaccine against anthrax infection

Positive data in two Phase 2 clinical programs:

Announced positive proof-of-concept Phase 2 flu vaccine trial results with our NasoVAX vaccine

Announced positive pre-clinical data from the Company’s SparVax-L trial comparing SparVax-L and BioThrax against anthrax infection

Extended its IP protection of NasoShield in the U.S. with a Notice of Allowance from the U.S. Patent Office

Elected Mitchel Sayare, Ph.D., as Chairman of its Board of Directors

Raised approximately $30 million in financing, including through a Series B preferred offering, cash acquired in connection with the reverse merger with PharmAthene and a pre-merger private placement with existing investors, providing cash into the first quarter of 2019
"We have had a very data-rich few weeks with results being reported from our NasoVAX, HepTcell, and SparVax-L programs and moving forward on enrollment in our Phase 1 trial of NasoShield," said William J. Enright, Chief Executive Officer of Altimmune. "We are very excited by the positive results from our NasoVAX trial and look forward to continuing to advance that program. NasoVAX is a very different type of flu vaccine that has tremendous potential as an effective, easy-to-use vaccine that potentially provides better protection than current vaccines. We are also excited by the results on our SparVax-L trial and look forward to moving that program forward once we secure additional government funding. We continue to evaluate our HepTcell results will update investors on our next steps as we better understand those results."

Mr. Enright continued, "operationally, we are pleased with our progress. In 2017 we closed the reverse merger with PharmAthene, allowing us to leverage our resources and create a focused immunotherapeutics company. We strengthened our scientific team with the promotion of Dr. Sybil Tasker to Chief Medical Officer in early 2017. Additionally, in January 2018, Mitchel Sayare, Ph.D. was elected as Chairman of our Board of Directors bringing in-depth biotechnology experience as the former CEO of Immunogen. We anticipate continuing to build on our momentum in 2018 as we move forward with our NasoVAX, SparVax-L and NasoShield programs."

LOGO

Financial Results for the Year Ended December 31, 2017

Revenue for the year ended December 31, 2017 was $10.7 million compared to $3.2 million for 2016. The increase was due to $5.7 million increase in revenue from our contract with BARDA and $1.8 million revenue from the NIAID contract we assumed from our merger with PharmAthene in May 2017.

Research and development expenses were $18.4 million for the year ended December 31, 2017 compared to $7.2 million for 2016. The increase in research and development expenses was primarily the result of increases relating to NasoShield, NasoVAX, HepTcell, and SparVax-L clinical and preclinical trial costs, partially offset by $0.5 million reduced spending on the Oncosyn program. Research and development expenses for the year ended December 31, 2016 did not include PharmAthene or costs incurred under the NIAID contract.

General and administrative expenses were $8.5 million for the year ended December 31, 2017, compared to $7.1 million for 2016. The increase was the combined result of increased professional fees related to the merger with PharmAthene and costs incurred by us as a public company, including insurance costs and stock compensation expense, offset by $2.4 million of costs related to our initial public offering incurred in 2016 that did not recur in 2017.

We determined that our goodwill was impaired and a non-cash goodwill impairment charge of $35.9 million was recorded during the year ended December 31, 2017 which was classified as a component of operating expenses. The non-cash charge resulted from our goodwill assessment based on our market capitalization plus an implied control premium relative to the carrying value of our net assets. The non-cash charge has no effect on our current cash balance or operating cash flows.

We recorded an income tax benefit of $5.6 million during the year ended December 31, 2017, which reflected estimated tax refunds we expect to receive from carrying back our 2017 net operating losses to offset the 2016 federal and state income taxes paid by PharmAthene.

Net loss attributable to common stockholders for the year ended December 31, 2017 was $51.4 million compared with $11.5 million for 2016. Excluding the non-cash goodwill impairment charges, net loss attributable to common stockholders for the year ended December 31, 2017 was $15.4 million compared to $11.5 million for 2016.

Net loss per share attributable to common stockholders for the year ended December 31, 2017 was ($4.01) compared with ($1.66) for 2016. Excluding the non-cash goodwill impairment charges, net loss per share attributable to common stockholders for the year ended December 31, 2017 was ($1.21), compared to ($1.66) for 2016.

At December 31, 2017, the Company had cash, cash equivalents, and restricted cash of approximately $12.3 million, of which $3.5 million was restricted under the terms of the Series B preferred offering.

LOGO

Non-GAAP Measures

To supplement the Company’s unaudited financial statements presented in accordance with generally accepted accounting principles ("GAAP"), this press release includes a discussion of adjusted net loss attributable to common stockholders and adjusted net loss per share attributable to common stockholders, in each case adjusted for the loss due to a goodwill impairment charge. The Company believes that these non-GAAP measures, when taken into consideration with the corresponding GAAP financial measures, provide investors with meaningful comparisons of current results to prior period results by excluding items that the Company does not believe reflect its fundamental business performance. See the attached schedule for a reconciliation of net loss to adjusted net loss and loss per share to adjusted loss per share for the twelve months ended December 31, 2017 and 2016.

On March 29, 2018 Institut Curie and Freenome reported a strategic collaboration to evaluate Freenome’s artificial intelligence (AI) genomics platform as a novel tool to predict patient response to immuno-oncology therapies by observing changes in circulating cell-free biomarkers (Press release, Institut Curie, 29 29, 2018, View Source [SID1234525067]).

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!

In recent years so-called liquid biopsies have established the possibility of detecting circulating fragments of tumor DNA (ctDNA) and circulating tumor cells (CTCs) in the blood of patients with cancer. Institut Curie has been a pioneer in the field since the late 90’s with the first program on disseminated tumor cell (DTC) detection in the bone marrow of patients with early breast cancer. Since then, Institut Curie’s Circulating Tumor Biomarkers Laboratory has developed numerous innovative ctDNA techniques (ddPCR and NGS-based techniques).

Meanwhile, Freenome’s breakthrough use of machine learning looks beyond tumor DNA and processes the full range of cell-free (cf) biomarkers in the blood. By assembling an ever-expanding library of cell-free disease signatures, Freenome is developing a range of non-invasive blood tests for the early detection of cancer and early prediction of response to various oncology therapies. As a first step in this collaboration with Institut Curie, Freenome will analyze samples from the Analysis of Circulating Tumor Markers in the Blood (ALCINA) Trial, an umbrella trial allowing assessment of different circulating biomarkers and their correlation with clinical and pathological characteristics pertaining to response to PD-1 inhibitors alone and in combination with other therapies.

"Our machine learning scientists and molecular biologists are evaluating the cell-free genome – given 60-80%1,2,3 of cfDNA comes from immune cells – and other analytes. These provide a more complete picture of the dynamic interaction between the tumor and its environment," said Blandine Merino, VP of Business Development at Freenome. "Our approach incorporates a variety of biological signals, such as genomic, proteomic and epigenetic changes, providing new insights into possible mechanisms of resistance and guiding treatment selection for patients."

There is currently a high unmet need for biomarkers with high sensitivity and specificity for response prediction in immuno-oncology. The analysis of these data could open the way to new targets in precision oncology and improve therapeutic decision-making, particularly with the limitations associated with current approaches such as PD-L1 expression testing and assessing tumor mutational burden. Freenome’s tests would help to identify patients who are more likely to respond to PD-1 inhibitors; currently, approximately 80% of patients with advanced non-small-cell lung cancer, for example, do not respond to PD-1 inhibitors.4,5

According to Pr. François-Clement Bidard, Principal Investigator at Institut Curie, "Freenome is developing a novel approach which could revolutionize the way we analyze cell-free biomarkers for patients with cancer treated with immunotherapy; this approach complements a pipeline of innovative research projects that is ongoing at Institut Curie Circulating Tumor Biomarkers Laboratory."

Amaury Martin, Head of Institut Curie Technology Transfer and Industrial Partnerships Office and Director of the Institut Carnot Curie Cancer, added, "This agreement is one of the first at the Institut Curie with a company specializing in both cell free biomarkers and applying machine learning to large data sets. The Institut Curie MC21 strategic plan has identified innovation around liquid biopsy and big data as a major axis of medical-scientific research. With the arrival of a Data Director, Institut Curie, through its Carnot Institute, is determined to take a leading position in this key area for personalized medicine in oncology. The technologies developed by Freenome will fully benefit our patients and its access within the Institute will speed up future collaborations for developing and validating predictive tests."

About Freenome

Freenome is an AI genomics company on a mission to empower everyone with the tools they need to prevent, detect, and treat their diseases. By applying advanced machine learning techniques to recent breakthroughs in genomic science, Freenome is developing noninvasive blood tests to detect early-stage cancer and make treatments more effective. The company has raised $78 million from investors such as Andreessen Horowitz, Google Ventures, Polaris Partners, and Founders Fund.

For more information: View Source