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 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 28, 2018 Molecular Templates, Inc. (Nasdaq:MTEM) ("Molecular"), a clinical-stage oncology company focused on the discovery and development of the company’s proprietary engineered toxin bodies (ETBs), which are differentiated, targeted, biologic therapeutics for cancer, reported financial results for the fourth quarter of 2017. As of December 31, 2017, cash and cash equivalents totaled $58.9 million (Press release, Molecular Templates, MAR 28, 2018, View Source [SID1234525039]). Molecular’s current cash balance is expected to fund operations into late 2019.

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 excited by the continued progress of our pipeline as well as our partnership with Takeda," said Eric Poma, Ph.D., CEO and CSO of Molecular Templates. "We expect the remainder of 2018 to bring more data on our lead program MT-3724 in DLBCL, additional IND filings for other pipeline programs, and the potential for more business development transactions that would support additional programs with non-dilutive capital."

Company Highlights and Upcoming Milestones

Corporate

In 4Q17, Molecular expanded its senior management team with the additions of Adam Cutler as Chief Financial Officer; Barbara Ruskin J.D. Ph.D. as SVP, General Counsel and Chief Patent Officer; Nenad Sarapa M.D. M.S. as SVP of Clinical Development, and Conrad Jordaan as SVP of Finance and Corporate Controller.
On March 2, 2018, Molecular closed a $10 million debt facility with Perceptive Advisors. The proceeds were used to repay an existing debt facility with Silicon Valley Bank and will support Molecular’s build out of its GMP manufacturing facility, which should shorten the time from lead development to IND and better support Molecular’s own pipeline as well as partnerships.
MT-3724

MT-3724 (an ETB targeting CD20) is in an ongoing Phase Ib expansion study intended to better define the overall response rate to this candidate as a single-agent in heavily pre-treated diffuse large B-cell lymphoma (DLBCL) patients.
A brief update on the first three patients dosed in the MT-3724 Phase Ib expansion study was delivered at the World ADC Summit Europe today. Observations included the following:
One of the three patients achieved a partial response (PR) after a single dose of MT-3724. The PR was confirmed at the end of cycle 2 per protocol and the patient remains on study with continued dosing of MT-3724. The other two patients were assessed as having stable disease (SD) and progressive disease (PD).
A dose interruption and reduction was required in two of the first three patients in Phase Ib expansion. These patients had high body weights which resulted in high absolute doses of MT-3724 based on 75 mcg/kg dosing. The adverse events observed (grade 2 and 3) were reversible and dosing resumed at 50 mcg/kg, which has been generally well tolerated.
Based on these data, the deep and sustained clinical responses to MT-3724 observed at doses as low as 5 mcg/kg, as well as the near-complete peripheral B-cell depletion at doses up to 50 mcg/kg, the maximum tolerated dose (MTD) of MT-3724, has been defined as 50 mcg/kg with a maximum total drug per dose of 6,000 mcg, or 6 mg.
Enrollment in the Phase Ib expansion study continues, with further updates on results expected in 2Q18.
Nine DLBCL patients with low serum levels of rituximab have been treated at doses ranging from 5 mcg/kg to 75 mcg/kg in the Phase I dose-finding and Phase Ib expansion studies. In these nine patients, one complete response, two partial responses, three patients with stable disease (including one patient with a 48% reduction in tumor size), and three patients with progressive disease, were observed.
Based on the peripheral B-cell depletion observed at 50 mcg/kg and responses seen at doses as low as 5 mcg/kg, 50 mcg/kg appears to be an efficacious and well-tolerated dose.
Molecular also expects to initiate combination studies with MT-3724 in earlier lines of DLBCL therapy in 2Q18.
Takeda Collaboration

In December 2017, Takeda selected two targets for further research using Molecular’s ETBs. This has triggered $4 million in milestone payments to be paid by Takeda in 2018.
Takeda and Molecular are evaluating CD38 ETBs and could select a drug candidate for development by the end of 2Q18.
MT-4019

MT-4019, an ETB candidate that is designed to target CD38-expressing myeloma cancer cells, is progressing through IND enabling studies. If Takeda and Molecular do not select a joint candidate for development, Molecular anticipates filing an IND application for MT-4019 in mid-2018 to initiate a Phase I clinical trial in the United States in 2H18.
Research

Preclinical data for Molecular’s ETBs targeting PD-L1 (which incorporates Molecular’s Antigen Seeding Technology – a differentiated immune-oncology approach) and HER2 will be presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in April 2018
Molecular expects to file an IND application for an ETB targeting HER2 in 4Q18
Molecular expects to file an IND application for an ETB targeting PD-L1 (with antigen seeding) in 1Q19
Several other ETB candidates are in preclinical development targeting both solid and hematological cancers
Financial Results

The net loss attributable to common shareholders for the fourth quarter was $6.9 million, or $0.26 per basic and diluted share. This is compared to a net loss attributable to common shareholders for the same period in 2016, of $2.9 million, or $13.82 per basic and diluted share.

Revenues for the fourth quarter of 2017 were $0.8 million, compared to $0.4 million for the same period in 2016. Revenues in the fourth quarters of 2017 and 2016 were comprised of grant revenue from the Cancer Prevention & Research Institute of Texas ("CPRIT"). Total research and development (R&D) expenses for the fourth quarter of 2017 were $4.7 million, compared with $1.7 million for the same period in 2016. Total general and administrative (G&A) expenses for the fourth quarter of 2017 were $3.5 million, compared with $1.1 million for the same period in 2016.

Revenues for the year ended December 31, 2017 were $3.4 million, compared to $1.9 million for 2016. These revenues were primarily comprised of research and development revenues from our collaboration with Takeda of $1.9 million, and grant revenue from CPRIT of $1.0 million. Revenues for the same period in 2016 comprised of grant revenue from CPRIT. Total R&D expenses for the year ended December 31, 2017 were $9.5 million, compared to $8.0 million for 2016. Total G&A expenses for the year ended December 31, 2017 were $11.8 million, compared to $4.5 million for 2016.

The net loss attributable to common shareholders for the year ended December 31, 2017 was $24.1 million, or $2.11 per basic and diluted share, compared to a net loss attributable to common shareholders of $12.6 million or $59.04 per basic and diluted share, for 2016. As of December 31, 2017, cash and cash equivalents totaled $58.9 million. Molecular’s current cash balance is expected to fund operations into late 2019.

On March 28, 2018 MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (Code Number:4875), reported that it plans to initiate a pilot study to evaluate MN-166 (ibudilast) in chemotherapy-induced peripheral neuropathy (Press release, MediciNova, MAR 28, 2018, View Source;p=RssLanding&cat=news&id=2340230 [SID1234525383]).

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!

The clinical trial is a collaborative effort between MediciNova, Inc. and Dr. Janette Vardy, Professor of Cancer Medicine, University of Sydney Concord Cancer Centre in Australia. The proposed clinical trial will evaluate MN-166 (ibudilast) as a potential treatment for individuals with chemotherapy-induced peripheral neuropathy. A Concord Cancer Centre Research grant will provide funding for this study and MediciNova will provide study drug.
Yuichi Iwaki, MD, PhD, President and Chief Executive Officer of MediciNova, Inc. commented, "We are excited to collaborate with Dr. Vardy on this grant-funded study to explore the potential of MN-166 as a pharmacotherapy for chemotherapy-induced peripheral neuropathy. There is a large unmet medical need for patients with this disorder."
Dr. Janette Vardy, the Principal Investigator for this study, commented, "This is an exciting new project and we are enthusiastic to partner with MediciNova to evaluate MN-166 in chemotherapy-induced peripheral neuropathy patients. As chemotherapy-induced peripheral neuropathy is believed to be caused by glial activation, we believe ibudilast’s ability to reduce glial activation could be beneficial in treating this common disorder following chemotherapy."

About the Trial
This is a prospective, open-label, sequential cross-over pilot study assessing acute neurotoxicity, chemotherapy-induced peripheral neuropathy, and drug interactions of ibudilast in 20 patients with metastatic gastrointestinal cancer (colorectal cancer and upper gastrointestinal cancers) who are receiving oxaliplatin.
The study aims to determine: 1) whether ibudilast can prevent the development of acute neurotoxicity in patients receiving oxaliplatin for the treatment of metastatic gastrointestinal cancer; 2) the effect of ibudilast co-administration, if any, on the pharmacokinetics of oxaliplatin and fluorouracil; and 3) whether ibudilast might decrease the severity of chemotherapy-induced peripheral neuropathy
.
Participants will undertake pharmacokinetics assay and neurotoxicity assessment for a cycle of their usual chemotherapy, followed by identical assessments the following cycle with concurrent administration of oral ibudilast 30 mg twice daily. Assessments for chemotherapy-induced peripheral neuropathy will occur at baseline, day 3 of chemotherapy, end of each cycle, and 3 months after baseline, and will be compared to determine a clinical benefit, as well as safety and medication adherence.

About Concord Cancer Centre
Concord Cancer Centre, part of the University of Sydney, is based at Concord Repatriation General Hospital, a major tertiary hospital in Sydney Local Health District in Australia. Concord Repatriation General Hospital is one of the best cancer treatment and research facilities in New South Wales.

About Chemotherapy-Induced Peripheral Neuropathy
Peripheral neuropathy is a set of symptoms caused by damage to the nerves that are away from the brain and spinal cord. These distant nerves are called peripheral nerves. Some of the chemotherapy and other drugs used to treat cancer can damage peripheral nerves that carry sensations to the hands and feet. This damage results in chemotherapy-induced peripheral neuropathy (CIPN) and is a common side effect of cancer chemotherapy. Most commonly, people complain of "pins and needles" in their toes and fingers. CIPN may affect cancer outcomes due to reductions in chemotherapy dosing and/or premature treatment discontinuation and have a profound impact on quality of life and survivorship. According to a meta-analysis which included more than 4,000 patients, CIPN prevalence was 68% when measured in the first month after chemotherapy, 60% at 3 months, and 30% at 6 months or more ("Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis," Seretny M et al 2014). Long-term neurotoxicity is an important issue for the growing number of cancer survivors, with the highest number of affected patients having been treated for breast and/or colon cancer.

About Oxaliplatin-induced Peripheral Neuropathy
Oxaliplatin is shown to improve survival of patients with colorectal cancer and other gastrointestinal cancers. The neurotoxicity seen with oxaliplatin treatment, in the form of the acute and chronic syndrome, ranks among the most frequent non-hematological toxicity due to this treatment. The acute, transient neurotoxicity occurs in nearly all patients, is rapid in onset, and occurs during or within hours of the oxaliplatin infusion. The dose-limiting, cumulative sensory neurotoxicity may be severe enough to limit patients from performing their activities of daily living. A proposed mechanism for this process is central and dorsal root ganglion neuroinflammation caused by oxaliplatin.

About MN-166 (ibudilast)
MN-166 (ibudilast) has been marketed in Japan and Korea since 1989 to treat post-stroke complications and bronchial asthma. MN-166 (ibudilast) is a first-in-class, orally bioavailable, small molecule phosphodiesterase (PDE) -4 and -10 inhibitor and a macrophage migration inhibitory factor (MIF) inhibitor that suppresses pro-inflammatory cytokines and promotes neurotrophic factors. It attenuates activated glia cells, which play a major role in certain neurological conditions. Ibudilast’s anti-neuroinflammatory and neuroprotective actions have been demonstrated in preclinical and clinical study results and provide the rationale for its therapeutic utility in substance use disorders, neurodegenerative diseases (e.g., ALS and progressive MS), and chronic neuropathic pain. MediciNova is developing MN-166 for various neurological conditions such as progressive MS, ALS and substance abuse/addiction

On March 28, 2018 Moleculin Biotech, Inc. (NASDAQ: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company focused on the development of oncology drug candidates, all of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, reported its financial results for the year ended December 31, 2017 (Press release, Moleculin, MAR 28, 2018, View Source [SID1234525040]). Additionally, the Company announced potential upcoming milestones and recent corporate developments.

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!

Management Discussion
Walter Klemp, Chairman and CEO of Moleculin, said, "We continued to make significant progress in developing Moleculin’s distinctive cancer treatment technologies during 2017. We firmly believe that all three of our highly differentiated technologies have breakthrough potential in effectively treating various cancers. From those three core technologies, we now have six potential drug candidates, two of which we expect will commence clinical trials in 2018, with the possibility of a third before the end of the year.

"Our potentially disruptive technologies include Annamycin, a chemotherapy agent that is active against multidrug resistant tumor cells and has been designed to be non-cardio toxic (unlike currently approved drugs in this class); immuno-stimulating STAT3 inhibitors WP1066 and WP1732 that target glioblastoma and pancreatic cancer; and WP1122, an inhibitor of glycolysis that has been shown in preclinical testing to effectively block the energy supply required by cancer cells and effectively starves the cancer cells to death. Our diverse development portfolio gives Moleculin what I like to call multiple shots on goal."

The Company submitted an application in October 2017 for a Clinical Trial Authorization ("CTA") for Annamycin in Poland. Having met all the requirements, the Ethics Committee in Poland approved the Phase I/II trial of Annamycin for the treatment of relapsed or refractory acute myeloid leukemia ("AML") in December 2017. In March the Company received requests for and provided additional information to the Polish National Office. It expects a response from the Polish National Office in the first half of 2018 and at the earliest mid-April 2018. The start of clinical trials in Poland remains subject to confirmation and approval of the CTA by the Polish National Office. The Company can provide no assurance that it will receive such confirmation on a timely basis, if at all.

In addition, the Company continues to recruit and contract clinics both in the United States and Poland. In the U.S., the Company has one site — University Hospitals Cleveland Medical Center ("UHCMC") — recruiting patients and enrollment has begun. The Company can provide no assurance that it will continue enrollments or begin treatment on a timely basis, if at all.

Mr. Klemp continued, "Additionally, this past December we announced that a physician-sponsored Investigational New Drug ("IND") application for a Phase I trial of Moleculin’s WP1066 in patients with recurrent malignant glioma and brain metastasis from melanoma was allowed by the U.S. Food and Drug Administration ("FDA"). This will be our second drug in clinical trials. The trial will be conducted at the MD Anderson Cancer center to evaluate safety and efficacy. We believe WP1066 represents a new class of oncology drugs able to fight tumors on two fronts by directly inhibiting cell signaling supporting tumor activity, and independently stimulating a natural immune response. This constitutes a new approach to treating brain tumors and tumor metastasis to the brain.

"We also intend to request a clinical trial authorization in Poland for WP1220 for the topical treatment of Cutaneous T-Cell Lymphoma (CTCL), which we expect will become our third compound in clinical trials in 2018. WP1220 is one of our patented STAT3 inhibitors designed to be compatible with topical formulations and was selected based on its preclinical activity in CTCL cell lines and based on the need for better topical treatments for skin cancer.

"As we look ahead to 2019 and beyond, we are excited about a new molecule that we recently licensed from MD Anderson — WP1732 — that shares many of the same characteristics of WP1066, especially its ability to inhibit activated STAT3, which is widely considered a key transcription factor involved in the development and progression of tumors. WP1732 has demonstrated significantly different organ distribution in animal models, suggesting it could be especially well-suited to target systemic solid tumors including pancreatic cancer, one of the most deadly and difficult to treat.

"An important attribute of WP1732 is that it is more water-soluble than WP1066. So, while we have been focused on oral delivery of WP1066, WP1732 is ideally suited to intravenous ("IV") administration, which makes the delivery of the drug potentially more convenient and efficacious. We’ve already started the process of preparing the preclinical data necessary for an IND for WP1732 and we hope to have that preparation completed in 2018.

"I also want to acknowledge the outstanding Scientific Advisory Board that is part of the Moleculin brain trust. Waldemar Priebe, PhD., a Founder of Moleculin and the Company’s Founding Scientist, leads a team of world renown experts in various cancer fields that includes John Paul Waymack, MD; Elihu Estey, MD; and Jorge Cortes, MD. Together with our two Chief Medical Officers, Robert Shepard, MD (Annamycin), and Sandra Silberman, MD (New Products), their expertise and guidance have enabled us at Moleculin to successfully proceed in the development of our highly differentiated compounds. Our expectation is that 2018 will see significant progress in advancing our portfolio of unique cancer treatments," concluded Mr. Klemp.

Fourth Quarter Highlights and Recent Corporate Developments
Moleculin Announces Grant-Funded Collaboration to Expand Understanding of New Discovery – March 20, 2018, the Company announced it has entered into a collaboration with a team of scientists in Poland who have received a $300,000 research grant to expand the understanding of how Moleculin’s leading STAT3 inhibitor WP1066 and the Company’s newly discovered drug candidate, WP1732, create a blockade of transcription factor STAT3 leading to tumor cell death and immune-stimulating effects.

Moleculin Announces Pricing of $9 Million Registered Direct Offering – February 16, 2018, the Company announced that it has entered into a definitive agreement with institutional investors for a registered direct offering of securities with gross proceeds of approximately $9 million.

Moleculin Announces Breakthrough Discovery of a New Molecule for Cancer Treatment – February 15, 2018, the Company announced that, pursuant to its continued collaboration with MD Anderson it has developed and licensed what it believes, based on preclinical testing, is a major breakthrough in its effort to develop a new cancer treatment that selectively kills highly resistant tumors. Specifically, the Company has preclinical evidence to suggest it is capable of influencing a process known as ‘ubiquitination’ to block the activated form of STAT3, an important oncogenic transcription factor. The lead molecule resulting from this new discovery is called WP1732 and it not only appears to share the same key mechanistic properties with WP1066, it has markedly different organ distribution and its dramatically increased solubility makes it ideal for administration via standard IV injection. Importantly, preclinical testing has also shown that WP1732’s properties make it a promising candidate for treating pancreatic cancer.

Moleculin Announces Collaboration with Emory University to Develop Novel Treatment of Pediatric Brain Cancer – February 13, 2018, the Company announced it has entered into an agreement with Emory University to enable expanded cancer research on Moleculin’s WP1066 molecule for the possible treatment of medulloblastoma, a pediatric malignant primary brain tumor. Physician-scientists at Emory University and Children’s Healthcare of Atlanta have requested support to continue research aimed at the development of a novel treatment of medulloblastoma using WP1066 and Moleculin has agreed to supply them with a pure form of WP1066 for preclinical testing for the potential future treatment of patients with the disease. Emory studies so far have indicated that medulloblastoma may be particularly vulnerable to the ability of WP1066 to block the activated form of STAT3, a key signaling protein believed to contribute to the growth and survival of many tumors, including medulloblastoma.

Moleculin Announces Activity with Pancreatic Cancer Drug – February 7, 2018, the Company announced it has been able to show promising tumor suppression activity with its inhibitor of glycolysis, WP1122. The Company’s glycolysis inhibitors have shown a remarkable affinity for concentrating in the pancreas and has solid data showing the ability of WP1122 to inhibit pancreatic tumor growth in mice.

Leading Leukemia Experts Join Moleculin’s Science Advisory Board – January 17, 2018, the Company announced the expansion of its Science Advisory Board to include Drs. Jorge Cortes and Elihu Estey.

Jorge Cortes, M.D., is deputy chair and professor of medicine in the Department of Leukemia at MD Anderson Cancer Center where he directs the CML and AML Programs. Dr. Cortes received his medical degree in 1986 from the Universidad Nacional Autonoma de Mexico, and has been at MD Anderson since 1991. Dr. Cortes, whose clinical interest focuses on new drug development and the management of patients with myelodysplatic syndromes, acute and chronic leukemias, and myeloproliferative disorders, has authored over 900 peer-reviewed medical publications in top-tier journals including New England Journal of Medicine, Lancet Oncology, Lancet Hematology, Journal of Clinical Oncology, Leukemia, Blood and many others.

Elihu Estey, M.D., is a Professor of Medicine in the Division of Hematology at the University of Washington School of Medicine and a Full Member and Director of AML Clinical Research (non-transplant) Clinical Research Division, Fred Hutchinson Cancer Research Center. Dr. Estey has built a distinguished career in cancer research approaching 40 years of active clinical practice with AML patients, providing mentorships for many physicians that have risen to prominence in AML, lectured globally to professional audiences on cancer research and published more than 700 articles on hematologic malignancies, specifically on AML. Additionally, Dr. Estey serves on the European Leukemia Net (ELN) guidelines committee for AML and has served as an advisor for AML studies to the Oncology Drugs Advisory Committee ("ODAC") of the FDA.

Moleculin Expands Leukemia Development Portfolio with Immuno-Stimulating STAT3 Inhibitor – January 10, 2018, the Company announced it has expanded the Company’s development pipeline for the treatment of AML with an immuno-stimulating STAT3 inhibitor. Leading experts in the treatment of AML, Dr. Jorge Cortes and Dr. Sanjay Awasthi requested the Company to expand its clinical research to include WP1066, an immuno-stimulating agent and STAT3 inhibitor, to increase therapeutic options for AML patients. This would potentially be complementary and synergistic with Annamycin and existing first line treatments.

Moleculin Announces Polish Approval for Leukemia Clinical Trial – December 21, 2017, the Company announced that the Ethics Committee in Poland has approved the Company’s Phase I/II clinical trial of Annamycin for the treatment of relapsed or refractory AML.

Moleculin’s WP1066 Drug gets FDA Brain Tumor IND Clearance – December 5, 2017, the Company announced the physician-sponsored IND application for a Phase I trial of Moleculin’s drug WP1066 in patients with recurrent malignant glioma and brain metastasis from melanoma has been allowed by the FDA. WP1066 is the second of Moleculin’s drugs to enter clinical stage and represents a new class of oncology drugs able to fight tumors on two fronts by directly inhibiting cell signaling and independently stimulating a natural immune response. This IND was sponsored by Dr. Amy Heimberger, who will serve as the principal investigator for the Phase I trial at MD Anderson Cancer Center to evaluate safety and efficacy.

Moleculin Appoints Dr. Sandra Silberman as Chief Medical Officer – New Products – November 8, 2017, the Company announced the appointment of Dr. Sandra Silberman as Chief Medical Officer ("CMO") in charge of New Products.

Moleculin Announces MD Anderson has Filed an IND with the FDA on its Drug WP1066 for the Treatment of Brain Tumors – November 1, 2017, the Company announced that responses have been submitted to FDA requests for additional information relating to the physician-sponsored IND application to study WP1066 as a potential treatment for brain tumors.

Moleculin Requests Authorization from the Polish Government to Advance Annamycin – October 24, 2017, the Company announced that it has submitted its request for CTA in Poland which, if allowed, will enable a clinical trial to study Annamycin for the treatment of relapsed or refractory AML in Poland. This will be in addition to the previously announced allowance of Moleculin’s IND filing with the FDA.

Moleculin Announces 14 Qualified Clinical Sites Requesting Participation in Annamycin Trial – October 18, 2017, the Company announced that 14 qualified cancer clinics have requested to participate in its clinical trial to study Annamycin for the treatment of relapsed or refractory AML.

Moleculin Announces Strategic Collaboration to Develop Immuno-stimulating Drug – October 11, 2017, the Company announced that it has entered into an agreement to collaborate with the University of Bergen to expand research on WP1066 and early indications of a possible dual ability to increase immune system response to tumors while also suppressing tumor cell proliferation tumor cell and survival.

Moleculin Signs Agreement with First Hospital for Annamycin Trials – October 3, 2017, the Company announced it has entered into an agreement with the first of several hospitals desiring to become treatment sites for its clinical trial to study Annamycin for the treatment of relapsed or refractory AML.

Moleculin Announces FDA Approval of Annamycin IND – September 26, 2017, the Company announced that the FDA has allowed Moleculin’s IND for the study of Annamycin in relapsed or refractory AML to proceed. This allows Moleculin to begin clinical trials of Annamycin in the U.S.

Anticipated Milestone Potential Timeframe
Announcement that our IND for Annamycin has become effective and that we may begin clinical trials Accomplished
Initial IRB (Institutional Review Board) approvals and site initiations of various clinical sites participating in our Phase I/II clinical trial of Annamycin Accomplished and ongoing through Second Half of 2018
Establishment of a new RP2D for Annamycin Second Half of 2018
A clinician sponsored IND for WP1066 for treatment of adult brain tumors moving forward IND Accomplished; Trial expected to begin First Half of 2018
Announcement of initial Clinical Data for Annamycin trial 2018
Announcement of further benefits of our sponsored research agreement with MD Anderson Accomplished and Ongoing into 2019
Announce CTA for WP1220 for the treatment of cutaneous T-cell lymphoma (CTCL) 2018
Announce WP1122 and WP1732 move into preclinical work 2018
Announce the fourth drug approved for clinical trial 2019
Financial Results for the Year Ended December 31, 2017
Research and Development Expense. Research and development (R&D) expense was $4.5 million and $1.5 million for the years ended December 31, 2017 and 2016, respectively. The increase in R&D of approximately $3.0 million mainly represents an increase of approximately: $2.0 million associated with developing and testing drug product as we prepared for clinical trials; $0.4 million related to an increase in R&D headcount and associated payroll costs; $0.3 million for sponsored research and related expenses; and $0.3 million associated with license fees. The increase in R&D headcount mainly represents the associated costs of increasing the commitments of the Company’s part-time employees and the addition of a second Chief Medical Officer – New Products. These all are a reflection of the increased clinical and pre-clinical activity for its drug portfolio as compared to 2016.

General and Administrative Expense. General and administrative (G&A) expense was $4.1 million and $2.4 million for the years ended December 31, 2017 and 2016, respectively. The increase in G&A of approximately $1.7 million was mainly attributable to: (a) the increase in headcount and associated payroll costs, including additional stock-based compensation expense of $1.0 million; (b) approximately $0.4 million in legal, accounting, consulting, and other professional expenses; (c) $0.2 million in insurance expense; and (d) approximately $0.1 million in occupancy, office and other costs. These increases reflect the increase in support of the Company’s clinical activity described above as compared to 2016.

Net Loss. The net loss for the twelve months ended December 31, 2017 was $9.8 million, which included non-cash expenses of approximately $0.7 million, which was comprised almost completely of stock-based compensation.

Liquidity and Capital Resources
As of December 31, 2017, we had $7.7 million in cash. During 2017, via an equity offering in February of 2017 (the February 2017 Offering), the Company’s at-the-market issuance agreement (ATM), and the exercise of warrants associated with the February 2017 Offering, the Company issued 7.2 million shares of common stock and received $10.1 million in net proceeds. Subsequent to year-end the Company entered into a Purchase Agreement with certain Investors for the sale of 4,290,000 shares of its common stock at a purchase price of $2.10 per share. Concurrently with the sale of the common shares, pursuant to the Purchase Agreement, the Company also sold warrants to purchase 2,145,000 shares of common stock, which have an exercise price of $2.80 per share. This sale of common shares and warrants generated aggregate gross proceeds of approximately $9.0 million with net proceeds approximating $8.3 million (February 2018 Offering). The Company believes that its existing cash and cash equivalents as of December 31, 2017 along with the cash generated by the February 2018 Offering, will be sufficient to fund its planned operations into the first quarter of 2019. Such plans are subject to change depending on clinical enrollment and regulatory progress and the use and supply of drug product.