On March 19, 2021 Isofol Medical AB (publ) ("Isofol"), (Nasdaq First North Premier Growth Market: ISOFOL) reported that the independent Data Safety and Monitoring Board (iDSMB) has recommended continuation of the global Phase III AGENT study with 440 patients, in accordance with the study design for the drug candidate, arfolitixorin (Press release, Isofol Medical, MAR 19, 2021, View Source [SID1234576913]). Isofol expects the top line results for the AGENT study to be available during H1 2022.

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The iDSMB recommendation follows a pre-scheduled interim analysis as part of the study design and was initiated when the 330th patient had been treated for 16 weeks and had two tumor evaluations. iDSMB evaluated safety and efficacy (ORR and PFS). The Company remains blinded to the interim analysis results.

"The recommendation from iDSMB is encouraging in many ways; first, it does not require us to recruit additional patients which enables us to keep our current timeline with the goal to submit a New Drug Application to FDA & EMA in H2 2022. Second, it is an additional confirmation that arfolitixorin shows no signs of increased toxicity which in combination with previous efficacy data strengthens our belief in arfolitixorin’s potential. Thirdly, we may be on the market in the US already in 2023", said Ulf Jungnelius, M.D, CEO of Isofol.

Arfolitixorin is evaluated in the AGENT study for the treatment of patients with first-line metastatic colorectal cancer (mCRC). The study is currently being conducted in Australia, Europe, Japan, Canada and the US in more than 90 clinics and includes a total of 440 patients.

This information is information that Isofol Medical AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 18:10 CET on March 19, 2021.

About arfolitixorin

Arfolitixorin is Isofol’s proprietary drug candidate being developed to increase the efficacy of standard of care chemotherapy for advanced colorectal cancer. The drug candidate is currently being studied in a global Phase III study, AGENT. As the key active metabolite of the widely used folate-based drugs, arfolitixorin can potentially benefit more patients with advanced colorectal cancer, as it does not require complicated metabolic activation to become effective.

On March 19, 2021 GlaxoSmithKline (GSK) plc reported that it will present new data across its growing women’s oncology portfolio at the upcoming Society of Gynecologic Oncology (SGO) 2021 Annual Meeting on Women’s Cancer to be held 19-25 March 2021 (Press release, GlaxoSmithKline, MAR 19, 2021, View Source [SID1234576911]).

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GSK, a leader in synthetic lethality and immuno-oncology research, will present seven abstracts at SGO that reflect the increasing depth and breadth of the company’s oncology portfolio in these research areas. There will be a plenary presentation of the results from the phase III NOVA trial that highlight the long-term follow up of secondary endpoints, including safety and survival results of ZEJULA (niraparib) in women with recurrent ovarian cancer. This research builds on the body of evidence supporting poly (ADP-ribose) polymerase (PARP) inhibitor use for maintenance treatment. GSK will also share data from the phase II OVARIO trial underscoring the potential of niraparib maintenance in combination with bevacizumab in first-line ovarian cancer.

In endometrial cancer, updated results from cohorts A1 and A2 of the phase I GARNET trial will be presented that showcase the potential of dostarlimab in women with recurrent or advanced mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) endometrial cancer.

Dr Axel Hoos, Senior Vice President and Head of Oncology R&D, GSK said: "For women with gynaecologic cancers, our priority is to continue to evaluate niraparib and dostarlimab in conditions where new treatment options are needed most. Over the last few years, data supporting the use of PARP inhibitors for ovarian cancer has grown, and data presented at SGO demonstrate the potential benefits of niraparib combination therapies and sequencing. We also believe there is significant treatment potential for dostarlimab, which may enhance the anti-cancer immune response in women with endometrial cancer and patients with other types of cancer."

Leadership in advanced ovarian cancer

Niraparib is the only oral, once-daily PARPi approved as a monotherapy maintenance treatment for women with first-line platinum-responsive advanced ovarian cancer regardless of biomarker status in both the US and EU. GSK is committed to fully exploring and maximising the potential of niraparib through a robust clinical development programme evaluating it both as a monotherapy and in combination with other therapies to further improve outcomes for women with ovarian cancer.

GSK will present updated data from three trials at SGO that demonstrates niraparib’s potential regardless of biomarker status as a monotherapy, doublet-therapy and triplet-therapy. In addition to the OVARIO and NOVA trial results, data from cohort A of the phase II OPAL trial, evaluating the triple combination therapy of niraparib (PARPi) and dostarlimab (anti-PD-1) in combination with bevacizumab (anti-VEGF) for women with platinum-resistant ovarian cancer, including several patients with primary platinum resistant disease, will be presented.

GSK also will share a post-hoc analysis from the phase III PRIMA trial on the efficacy of timing of surgery and residual disease, along with results of another study on the factors affecting PARPi use as maintenance treatment in platinum-sensitive recurrent ovarian cancer.

Transforming treatment for patients with endometrial cancer

GSK will present new data from the GARNET trial at SGO, demonstrating clinically meaningful results that reinforce the potential of dostarlimab in endometrial cancer. GARNET represents the largest dataset of an anti-PD-1 monotherapy treatment in this disease.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion last month recommending dostarlimab for use as monotherapy for women with dMMR/MSI-H recurrent or advanced endometrial cancer who have progressed on or after platinum-based chemotherapy. The application is based on data from the GARNET study, which was originally presented at SGO in 2019.

Dostarlimab is also being evaluated in combination with other therapeutic agents for people with advanced solid tumours or metastatic cancer, including combinations with niraparib, and other immuno-oncology agents. It is currently under review with the US Food and Drug Administration (FDA) for the treatment of women with recurrent or advanced endometrial cancer who have progressed on or following platinum-based chemotherapy and whose tumours are dMMR. The FDA is also currently reviewing dostarlimab for the treatment of adult patients with dMMR recurrent or advanced solid tumours. Dostarlimab is not currently approved for use anywhere in the world.

Key GSK presentations during the SGO Annual Meeting on Women’s Cancer include:

Niraparib

Abstract Name

Presenter

Presentation Details

Long-term safety and secondary efficacy endpoints in the ENGOT-OV16/NOVA phase III trial of niraparib in recurrent ovarian cancer

Matulonis, U.

Oral Presentation #11139

Phase 2 OVARIO Study of Niraparib + Bevacizumab Therapy in Advanced Ovarian Cancer Following Front-Line Platinum-Based Chemotherapy With Bevacizumab

Hardesty, M.

Oral Featured Poster #10408

Efficacy of Niraparib by Timing of Surgery and Residual Disease: A Post-Hoc Analysis of Patients in the PRIMA/ENGOT-OV26/GOG-3012 Study

O’Cearbhaill, R.

Featured Poster #10381

Factors Affecting PARP Inhibitor Use as Maintenance Treatment in Platinum-Sensitive Recurrent Ovarian Cancer

Valentine, M.

Poster #10410

An Open-Label Phase 2 Study of Dostarlimab (TSR-042), Bevacizumab (bev), and Niraparib Combination in Patients (pts) with Platinum-Resistant Ovarian Cancer (PROC): Cohort A of the OPAL Trial

Liu, J.

Oral Featured Poster #10415

Dostarlimab

Abstract Name

Presenter

Presentation Details

Interim Analysis of the Immune-Related Endpoints of the Mismatch Repair Deficient (dMMR) and Proficient (MMRp) Endometrial Cancer Cohorts From the GARNET Study

Oaknin, A.

Oral Featured Poster #10417

ENGOT-EN6/GOG-3031/NSGO-RUBY: A phase 3, randomized, double-blind, multicenter study of dostarlimab + carboplatin-paclitaxel versus placebo + carboplatin-paclitaxel in recurrent or primary advanced endometrial cancer (EC)

Mirza, M.

Trial in Progress Poster #10418

About ZEJULA (niraparib)

Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in multiple pivotal trials. GSK is building a robust niraparib clinical development programme by assessing activity across multiple tumour types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development programme for niraparib includes several combination studies.

Indication and Important Safety Information for ZEJULA

ZEJULA is indicated:

for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy
for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy
for the treatment of adult patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:
a deleterious or suspected deleterious BRCA mutation, or
genomic instability and who have progressed more than six months after response to the last platinum-based chemotherapy
Select patients for therapy based on an FDA-approved companion diagnostic for ZEJULA.
Important Safety Information

Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), including some fatal cases, was reported in 15 patients (0.8%) out of 1785 patients treated with ZEJULA monotherapy in clinical trials. The duration of therapy in patients who developed secondary MDS/cancer therapy-related AML varied from 0.5 months to 4.9 years. These patients had received prior chemotherapy with platinum agents and/or other DNA-damaging agents including radiotherapy. Discontinue ZEJULA if MDS/AML is confirmed.

Hematologic adverse reactions (thrombocytopenia, anemia, neutropenia, and/or pancytopenia) have been reported in patients receiving ZEJULA. The overall incidence of Grade ≥3 thrombocytopenia, anemia, and neutropenia were reported, respectively, in 39%, 31%, and 21% of patients receiving ZEJULA in PRIMA; 29%, 25%, and 20% of patients receiving ZEJULA in NOVA; and 28%, 27%, and 13% of patients receiving ZEJULA in QUADRA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, respectively, in 4%, 2%, and 2% of patients in PRIMA; 3%, 1%, and 2% of patients in NOVA; and 4%, 2%, and 1% of patients in QUADRA. In patients who were administered a starting dose of ZEJULA based on baseline weight or platelet count in PRIMA, Grade ≥3 thrombocytopenia, anemia, and neutropenia were reported, respectively, in 22%, 23%, and 15% of patients receiving ZEJULA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, respectively, in 3%, 3%, and 2% of patients. Do not start ZEJULA until patients have recovered from hematological toxicity caused by prior chemotherapy (≤Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months, and periodically thereafter. If hematological toxicities do not resolve within 28 days following interruption, discontinue ZEJULA, and refer the patient to a hematologist for further investigations.

Hypertension and hypertensive crisis have been reported in patients receiving ZEJULA. Grade 3-4 hypertension occurred in 6% of patients receiving ZEJULA vs 1% of patients receiving placebo in PRIMA, with no reported discontinuations. Grade 3-4 hypertension occurred in 9% of patients receiving ZEJULA vs 2% of patients receiving placebo in NOVA, with discontinuation occurring in <1% of patients. Grade 3-4 hypertension occurred in 5% of ZEJULA-treated patients in QUADRA, with discontinuation occurring in <0.2% of patients. Monitor blood pressure and heart rate at least weekly for the first two months, then monthly for the first year, and periodically thereafter during treatment with ZEJULA. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Manage hypertension with antihypertensive medications and adjustment of the ZEJULA dose if necessary.

Posterior reversible encephalopathy syndrome (PRES) occurred in 0.1% of 2,165 patients treated with ZEJULA in clinical trials and has also been described in postmarketing reports. Monitor all patients for signs and symptoms of PRES, which include seizure, headache, altered mental status, visual disturbance, or cortical blindness, with or without associated hypertension. Diagnosis requires confirmation by brain imaging. If suspected, promptly discontinue ZEJULA and administer appropriate treatment. The safety of reinitiating ZEJULA is unknown.

Embryo-fetal toxicity and lactation: Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months after receiving their final dose of ZEJULA. Because of the potential for serious adverse reactions from ZEJULA in breastfed infants, advise lactating women to not breastfeed during treatment with ZEJULA and for 1 month after receiving the final dose.

Allergic reactions to FD&C Yellow No. 5 (tartrazine): ZEJULA capsules contain FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.

First-line Maintenance Advanced Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of all patients who received ZEJULA in PRIMA were thrombocytopenia (66%), anemia (64%), nausea (57%), fatigue (51%), neutropenia (42%), constipation (40%), musculoskeletal pain (39%), leukopenia (28%), headache (26%), insomnia (25%), vomiting (22%), dyspnea (22%), decreased appetite (19%), dizziness (19%), cough (18%), hypertension (18%), AST/ALT elevation (14%), and acute kidney injury (12%).

Common lab abnormalities (Grades 1-4) in ≥25% of all patients who received ZEJULA in PRIMA included: decreased hemoglobin (87%), decreased platelets (74%), decreased leukocytes (71%), increased glucose (66%), decreased neutrophils (66%), decreased lymphocytes (51%), increased alkaline phosphatase (46%), increased creatinine (40%), decreased magnesium (36%), increased AST (35%) and increased ALT (29%).

Maintenance Recurrent Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received ZEJULA in NOVA were nausea (74%), thrombocytopenia (61%), fatigue/asthenia (57%), anemia (50%), constipation (40%), vomiting (34%), neutropenia (30%), insomnia (27%), headache (26%), decreased appetite (25%), nasopharyngitis (23%), rash (21%), hypertension (20%), dyspnea (20%), mucositis/stomatitis (20%), dizziness (18%), back pain (18%), dyspepsia (18%), leukopenia (17%), cough (16%), urinary tract infection (13%), anxiety (11%), dry mouth (10%), AST/ALT elevation (10%), dysgeusia (10%), palpitations (10%).

Common lab abnormalities (Grades 1-4) in ≥25% of patients who received ZEJULA in NOVA included: decrease in hemoglobin (85%), decrease in platelet count (72%), decrease in white blood cell count (66%), decrease in absolute neutrophil count (53%), increase in AST (36%), and increase in ALT (28%).

Treatment of Advanced HRD+ Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received ZEJULA in QUADRA were nausea (67%), fatigue (56%), thrombocytopenia (52%), anemia (51%), vomiting (44%), constipation (36%), abdominal pain (34%), musculoskeletal pain (29%), decreased appetite (27%), dyspnea (22%), insomnia (21%), neutropenia (20%), headache (19%), diarrhea (17%), acute kidney injury (17%), urinary tract infection (15%), hypertension (14%), cough (13%), dizziness (11%), AST/ALT elevation (11%), blood alkaline phosphatase increased (11%).

Common lab abnormalities (Grades 1-4) in ≥25% of patients who received ZEJULA in QUADRA included: decreased hemoglobin (83%), increased glucose (66%), decreased platelets (60%), decreased lymphocytes (57%), decreased leukocytes (53%), decreased magnesium (46%), increased alkaline phosphatase (40%), increased gamma glutamyl transferase (40%), increased creatinine (36%), decreased sodium (34%), decreased neutrophils (34%), increased aspartate aminotransferase (29%), and decreased albumin (27%).

Please see Prescribing Information for ZEJULA.

About Dostarlimab

Dostarlimab is a humanised PD-1 monoclonal antibody that binds with high affinity to the PD-1 receptor and blocks its interaction with the ligands PD-L1 and PD-L2.[1] In addition to GARNET, dostarlimab is being investigated in other registrational enabling studies, including the phase 3 RUBY study for patients with recurrent or primary advanced endometrial cancer in combination with standard of care (SOC) chemotherapy [2] and the phase 3 FIRST study of platinum-based therapy with dostarlimab and ZEJULA versus SOC platinum-based therapy as first-line treatment of stage III or IV non-mucinous epithelial ovarian cancer. It is also being evaluated in combination with other therapeutic agents for patients with advanced solid tumours or metastatic cancer.

Dostarlimab was discovered by AnaptysBio and licensed to TESARO, Inc., under a Collaboration and Exclusive License Agreement signed in March 2014. The collaboration has resulted in three monospecific antibody therapies that have progressed into the clinic. These are: dostarlimab (GSK4057190), a PD-1 antagonist; cobolimab, (GSK4069889), a TIM-3 antagonist; and GSK4074386, a LAG-3 antagonist. GSK is responsible for the ongoing research, development, commercialization, and manufacture of each of these products under the Agreement.

GSK in Oncology

GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody-drug conjugates and cell therapy, either alone or in combination.

On March 19, 2021 Purple Biotech Ltd. ("Purple Biotech") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class, effective and durable therapies by overcoming tumor immune evasion and drug resistance, reported the initiation of a Phase 1b/2 clinical trial evaluating CM24, a monoclonal antibody blocking CEACAM1, in advanced cancer patients, with expansion cohorts in subjects with non-small cell lung cancer (NSCLC) and pancreatic cancer (Press release, Purple Biotech, MAR 19, 2021, View Source [SID1234576909]). The trial will be conducted in clinical collaboration with Bristol Myers Squibb.

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"The initiation of this Phase 1b/2 clinical trial represents an important milestone for our CM24 development program," said Michael Schickler, Ph.D., Head of Clinical Operations and Regulatory Affairs of Purple Biotech. "In a Phase 1a monotherapy study, CM24 demonstrated good safety and a signal of efficacy, with a 33% disease control rate with up to 10mg/kg dosing. Moreover, pharmacokinetic (PK) and pharmacodynamic modelling demonstrated target saturation expected at higher doses of CM24 on a two-week schedule. The Phase 1b/2 study will be conducted in multiple countries, with sites anticipated in the U.S., E.U. and Israel, and we expect preliminary data from the first part of the study in the second half of this year."

"CEACAM1 levels are prognostic in a number of cancers, and relate to multiple mechanisms of action in neoplastic disease, from oncogenesis to influencing the tumor microenvironment," said Bertrand Liang, M.D., Ph.D., Chief Medical Officer of Purple Biotech. "Based on its profile and the compelling Phase 1a data, we believe this study, which will evaluate CM24 at higher doses in combination with nivolumab in NSCLC patients and in combination with nab-paclitaxel and nivolumab in pancreatic cancer patients, will provide important data on blocking CEACAM1 in these critical unmet medical needs."

CM24 will be dose escalated from 10mg/kg, targeting the 20mg/kg dose, in combination with nivolumab in Phase 1b, in patients with NSCLC, pancreatic cancer, ovarian carcinoma, colorectal adenocarcinoma, melanoma or thyroid carcinoma, with the primary objective of evaluating safety, PK and determining the recommended Phase 2 dose. In the Phase 2 component, patients with NSCLC will be treated with CM24 and nivolumab after first-line immuno-oncology failure, and patients with metastatic pancreatic adenocarcinoma will be treated with CM24, nivolumab and nab-paclitaxel after first-line therapy failure, with study endpoints being safety and preliminary efficacy. CEACAM1 level of expression, as well as a number of other immune and adhesion-related molecules, will be evaluated as potential biomarkers in the study.

On March 19, 2021 Celsion Corporation (NASDAQ: CLSN), a clinical-stage drug development company focused on DNA-based immunotherapy and next-generation vaccines, reported financial results for the year ended December 31, 2020 and provided an update on clinical development programs with GEN-1, a DNA-based immunotherapy in Phase I/II development for the localized treatment of ovarian cancer, and ThermoDox, a proprietary heat-activated liposomal encapsulation of doxorubicin under investigator-sponsored development for several cancer indications (Press release, Celsion, MAR 19, 2021, View Source [SID1234576908]). In addition, Celsion has two feasibility-stage platform technologies for the development of novel nucleic acid-based immunotherapies and next-generation infectious vaccines.

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"Celsion entered 2021 with a renewed focus and prioritization on DNA-based immunotherapies for ovarian cancer and an initiative for next-generation vaccines for preventing or treating infections from a broad range of infectious agents, including coronaviruses, using our PLACCINE DNA vaccine technology platform. All of our work is supported by a strong balance sheet and a three-year cash operating runway," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer.

"Our Phase I/II OVATION 2 Study is over one-third enrolled. With 25 clinical sites to be activated by the end of the first quarter of 2021, encouraging trial data to date and the strong commitment of our clinical investigators, we expect to complete enrollment well before the end of 2021. Initial data at the 100 mg/m² dose cohort appear to be consistent with the directionally impressive results reported from our Phase Ib dose-escalating trial (the OVATION I Study) in ovarian cancer. Of 28 patients who completed interval debulking surgery, 81% of those treated with GEN-1 had an R0 resection, compared with 58% of control patients, a 41% improvement."

Mr. Tardugno added, "During the first quarter of 2021, we announced an initiative to focus our considerable DNA plasmid experience and competencies on DNA vaccine development, an approach we believe may represent an advance in nucleic acid immunotherapy. Leveraging our clinical-stage TheraPlas platform, we envision a vaccine characterized by a single-plasmid DNA with multiple coding regions. Celsion’s plasmid vectors that are currently in development are designed to promote multiple antigens that are expressed by a single pathogen in combination with a potent immune modifier such as IL-12. IL-12 is the active ingredient currently used in our product candidate GEN-1. We are well positioned with a capital structure sufficient to support our planned R&D and clinical programs through transformative milestones. In doing so, we look to create significant value for our shareholders, patients and the medical community."

Recent Developments

GEN-1 Immunotherapy

Announced Encouraging Interim Clinical Update on Phase I/II OVATION 2 Study with GEN-1 in Patients with Advanced Ovarian Cancer. On February 25, 2021, the Company provided an update on its Phase I/II OVATION 2 Study with GEN-1 in patients with advanced ovarian cancer. The OVATION 2 Study combines GEN-1 with standard-of-care neoadjuvant chemotherapy (NACT) in patients newly diagnosed with Stage III/IV ovarian cancer. NACT is designed to shrink the cancer as much as possible for optimal surgical removal after three cycles of chemotherapy. Following NACT, patients undergo interval debulking surgery, followed by three adjuvant cycles of chemotherapy and up to nine additional weekly GEN-1 treatments, the goal of which is to delay progression and improve overall survival. To date, the Company has enrolled approximately one-third of the anticipated 110 patients to be enrolled into the OVATION 2 Study. Currently, 28 patients have had their interval debulking surgery with the following results:

13 of 16, or 81%, of patients treated with GEN-1 had a R0 resection, which indicates a microscopically margin-negative complete resection in which no gross or microscopic tumor remains in the tumor bed;
Seven of 12 patients, or 58%, of patients in the control arm had an R0 resection; and,
These interim data represent a 41% improvement in R0 resection rates for GEN-1- patients compared with control arm patients and is consistent with the reported improvement in resection scores noted in the encouraging Phase I OVATION I Study, the manuscript of which has been submitted for peer-review publication.
Received FDA Fast Track Designation for GEN-1 in Advanced Ovarian Cancer. On March 22, 2021, the Company announced receipt of Fast Track designation from the U.S. Food and Drug Administration (FDA) for GEN-1, its DNA-mediated interleukin-12 (IL-12) immunotherapy currently in Phase II development for the treatment of advanced ovarian cancer. Fast Track designation is intended to facilitate the development and expedite the regulatory review of drugs to treat serious conditions and fill an unmet medical need. According to the FDA, a Fast-Track Drug must show some advantage over available therapy, including:

Showing superior effectiveness, effect on serious outcomes or improved effect on serious outcomes
Avoiding serious side effects of an available therapy
Decreasing a clinically significant toxicity of an available therapy that is common and causes discontinuation of treatment
Vaccine Initiative

Filed Provisional U.S. Patent Application for a Broad Range of Next-Generation DNA Vaccines. On January 28, 2021, the Company announced the filing of a provisional U.S. patent application for a novel DNA-based, investigational vaccine for preventing or treating infections from a broad range of infectious agents, including coronaviruses, using its PLACCINE DNA vaccine technology platform. The provisional patent covers a family of novel composition of multi-cistronic vectors and polymeric nanoparticles that comprise the PLACCINE DNA vaccine platform technology for preventing or treating infectious agents that have the potential for global pandemics, including the SARS-CoV-2 virus and its variants, using the Company’s platform technology. Celsion’s vaccine approach is designed to optimize the quality of the immune response dictating the efficiency of pathogen clearance and patient recovery. Celsion has taken a multivalent approach in an effort to generate an even more robust immune response that not only results in a strong neutralizing antibody response, but also a more robust and durable T-cell response. Delivered with Celsion’s synthetic polymeric system, the proprietary DNA plasmid is protected from degradation and its cellular uptake is facilitated.

PLACCINE is a natural extension of the Company’s synthetic, non-viral TheraPlas delivery technology currently in a Phase II trial for the treatment of late-stage ovarian cancer with GEN-1. Celsion’s proprietary multifunctional DNA vaccine technology concept is built on the flexible PLACCINE technology platform that is amenable to rapidly responding to the SARS-CoV-2 virus, as well as possible future mutations of SARS-CoV-2, other future pandemics, emerging bioterrorism threats and novel infectious diseases. Celsion’s extensive experience with TheraPlas suggests that the PLACCINE-based nanoparticles are stable at storage temperatures of 4oC to 25oC, making vaccines developed on this platform easily suitable for broad worldwide distribution.

Formed a Vaccine Advisory Board. On February 12, 2021, the Company announced the formation of a Vaccine Advisory Board and the appointment of its first two members:

Britt A. Glaunsinger, Ph.D., Professor, Virology & Molecular Biology, Howard Hughes Medical Institute, University of California, Berkeley; and
Dr. Xinzhen Yang, M.D., Ph.D., Independent Professional Consultant for the Gerson Lehman Group and former Director of Viral Vaccines / Program Lead of the HCMV Vaccine Program at Pfizer Inc.
Corporate Developments

Strengthened Balance Sheet Through a $35 Million Registered Direct Offering of Common Shares Priced At-The-Market Under NASDAQ Rules. On January 26, 2021, the Company announced the closing of a registered direct offering of 25,925,925 shares of common stock at a purchase price of $1.35 per share, priced at-the-market under Nasdaq rules, resulting in net proceeds of $32.6 million after deducting placement agents’ fees but before expenses payable by the Company. Celsion intends to use the net proceeds for general corporate purposes, including research and development activities, capital expenditures and working capital. This financing, coupled with the pending sale of its New Jersey net operating losses in the first half of 2021, will extend the Company’s operating roadway through 2023, well beyond several important clinical and R&D milestones.

Received $2 Million Allocation Through the New Jersey Technology Business Tax Certificate Transfer (NOL) Program, with an Additional $5 Million Expected in 2021-2023. In December 2020, the Company received approval from the New Jersey Economic Development Authority’s (NJEDA) Technology Business Tax Certificate Transfer program to sell its unused New Jersey net operating losses (NOLs) and R&D tax credits. In 2019, the Company received approval from the NJEDA to sell $1.9 million of its unused New Jersey NOLs and was able to transfer this credit and receive approximately $1.8 million of net cash proceeds in the first half of 2020. The Company anticipates it will be able to transfer this current year credit and receive net proceeds of approximately $1.85 million in the first half of 2021. An additional $5.0 million allocation of NOL sales will be available to the Company during 2021-2023.

Issued Letter to Stockholders with an Update on the Phase III OPTIMA Study with ThermoDox. On February 11, 2021, the Company issued a letter to stockholders providing an update on the status of the Phase III OPTIMA Study and the decision to stop following patients in the Study. Since the surprising and incredibly disappointing second interim analysis results of the Phase III OPTIMA Study in primary liver cancer announced on July 9, 2020, in which the independent Data Monitoring Committee (DMC) found that the interim findings suggested futility, the Company continued to follow patients for overall survival (OS). Independent analyses conducted by a global biometrics contract research organization and by the National Institutes of Health (NIH) did not find any evidence of significance or factors that would justify continuing to follow patients for OS. Therefore, the Company has notified all clinical sites to discontinue following patients. The OPTIMA Study database of 556 patients was frozen at 185 patient deaths. While the analyses did identify certain patient subgroups that appear to have had a clinical benefit, the Company concluded that it would not be in its best interest to pursue these retrospective findings as the regulatory hurdles supporting further development will be significant.

Celsion will continue to work closely with and support investigations involving ThermoDox by others throughout the world in breast cancer, pancreatic cancer and in solid tumors in children. Following inquiries from the NIH, the Company intends to renew its Cooperative Research and Development Agreement (CRADA) with the Institute at a nominal cost, one goal of which is to pursue the NIH’s interest in a study of ThermoDox to treat patients with bladder cancer. Importantly, Celsion is developing a business model to support these investigator-sponsored studies in a manner that will not interfere with the Company’s focus on its GEN-1 programs and vaccine development initiative.

Financial Results for the Year Ended December 31, 2020

Celsion reported a net loss of $21.5 million ($0.67 per share) in 2020, compared with a net loss of $16.8 million ($0.77 per share) in 2019. Operating expenses were $19.0 million in 2020, which represented a $2.1 million or 10% decrease from $21.1 million in 2019.

Research and development expenses were $11.3 million in 2020, a decrease of $1.8 million or 15% from $13.1 million in 2019. Clinical development costs for the Phase III OPTIMA Study decreased by $1.9 million to $2.2 million in 2020, compared with $4.1 million in 2019. Costs associated with the OVATION 2 Study increased to $1.3 million in 2020, compared with $0.6 million in 2019. Other costs related to ThermoDox and GEN-1 clinical development programs decreased by $0.6 million in 2020, compared with 2019 due to lower regulatory costs for the ThermoDox development program.

General and administrative expenses were $7.6 million in 2020, compared with $8.0 million in 2019. This $0.4 million or 5% decrease was primarily due to lower compensation expenses including non-cash stock option compensation expense compared with 2019.

Other expenses for 2020 included:

a non-cash charge of $1.3 million, compared with a non-cash gain of $2.8 million, net of a $0.4 million charge for the issuance of 200,000 warrants related to an amendment for the potential milestone payments for the GEN-1 ovarian cancer product candidate in 2019;
a non-cash charge of $2.4 million related to the impairment of certain in-process research and development assets related to the development of the Company’s GBM cancer product candidate;
interest expense of $1.3 million and $1.4 million in 2020 and 2019, respectively; and
interest income of $0.1 million in 2020 and $0.5 million in 2019.
The Company recognized a $1.8 million income tax benefit resulting from the sale of its New Jersey net operating losses during each of the fourth quarter of 2020 and 2019. The Company has approximately $5.0 million in future tax benefits remaining under the NJEDA Technology Business Tax Certificate Transfer program for future years.

Net cash used for operating activities was $15.6 million in 2020, compared with $20.3 million in 2019. Cash, cash equivalents and investments as of December 31, 2020 were $17.2 million. Total cash provided by financing activities was approximately $18.0 million during 2020 from $22.8 million of net proceeds from sales of common stock, less $5.2 million payments on notes payable. Subsequent to year-end, the Company raised more than $40 million in net proceeds from sales of common stock during the first quarter of 2020. In addition, the Company expects to receive net proceeds of $1.85 million from the sale of its New Jersey state NOLs by the end of the first quarter of 2021.

Conference Call

The Company is hosting a conference call at 11:00 a.m. EDT today to provide a business update and discuss 2020 financial results. To participate in the call, please dial 1-800-353-6461 (Toll-Free/North America) or 1-334-323-0501 (International/Toll) and ask for the Celsion Corporation fourth quarter 2020 Earnings Call (Conference Code: 1175518). The call will also be broadcast live on the internet at www.celsion.com. The call will be archived for replay on Friday, March 19, 2021 and will remain available until April 2, 2021. The replay can be accessed at 1-719-457-0820 or 1-888-203-1112 using Conference ID: 1175518. An audio replay of the call will also be available on the Company’s website, www.celsion.com, for 90 days after 2:00 p.m. EDT Friday, March 19, 2021.

On March 19, 2021 X4 Pharmaceuticals, Inc. (Nasdaq: XFOR), a leader in the discovery and development of novel therapies targeting diseases resulting from dysfunction of the CXCR4 pathway, reported that it has agreed to sell an aggregate of 6,321,837 shares of its common stock, including pre-funded warrants to purchase common stock, to certain institutional accredited investors in a private investment in public equity (PIPE) financing (Press release, X4 Pharmaceuticals, MAR 19, 2021, View Source [SID1234576907]). X4 anticipates that gross proceeds from the PIPE will be approximately $55.0 million, before deducting fees to the placement agents and other estimated offering expenses payable by the Company, based on the offering price of $8.70 per share (or $8.69 per prefunded warrant), the last reported sale price of X4’s common stock on The Nasdaq Global Market on March 18, 2021.

The financing included participation from new investors including Abingworth, Altium Capital, Driehaus Capital Management, Lincoln Park Capital, Monashee Investment Management and Sio Capital as well as existing investors including lead investor Bain Capital Life Sciences, Ikarian Capital and OrbiMed.

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The proceeds from this transaction are expected to be used by X4 for clinical development of its pipeline, business development activities, working capital and general corporate purposes.

"We are pleased to have the support of several leading biotechnology-focused institutional investors, both new and existing investors, in this $55 million financing," said Paula Ragan, Ph.D., President and Chief Executive Officer of X4 Pharmaceuticals. "We believe these funds will enable us to continue to advance our lead candidate, mavorixafor, to potentially improve the lives of thousands of patients across a number of rare disease indications."

Citigroup, Cowen and Stifel served as joint lead placement agents for the financing.
The securities sold in this private placement are being made in a transaction not involving a public offering and have not been registered under the Securities Act of 1933, as amended, and may not be offered or sold in the U.S. except pursuant to an effective registration statement or an applicable exemption from the registration requirements. X4 has agreed to file a registration statement with the Securities and Exchange Commission registering the resale of the shares of common stock issued in this private placement.

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