On March 8, 2022 AIM ImmunoTech Inc. (NYSE: American AIM) ("AIM" or the "Company"), an immuno-pharma company focused on the research and development of therapeutics to treat multiple types of cancers, immune disorders, and viral diseases, including COVID-19, the disease caused by the SARS-CoV-2 virus, reported the publication of positive data from a single-center named patient program treating advanced and metastatic pancreatic cancer patients (Press release, AIM ImmunoTech, MAR 8, 2022, View Source [SID1234609637]). The manuscript titled, "Rintatolimod (Ampligen) enhances numbers of peripheral B cells and is associated with longer survival in patients with locally advanced and metastasized pancreatic cancer pre-treated with FOLFIRINOX: a single-center named patient program1," was published in the peer-reviewed journal, Cancers Special Issue: Combination and Innovative Therapies for Pancreatic Cancer.

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In the single-center named patient program, patients with locally advanced pancreatic cancer (LAPC) or metastatic disease were treated with Ampligen for 6 weeks, at 2 doses per week with 400 mg per infusion. The study found that Ampligen improved the median survival of these patients.

"We are very encouraged by these data, which we believe reaffirm the potential of Ampligen to offer an important treatment option to patients living with pancreatic cancer. These data now in hand play a key role in the overall advancement of our pancreatic cancer program and provide valuable insight as we continue to execute the path forward. We continue to be encouraged by the favorable results demonstrated with Ampligen and are committed to securing the next phase of development of this important program," commented Thomas Equels, Chief Executive Officer of AIM.

The study’s primary endpoints were the Systemic Immune-Inflammation Index (SIII), the Neutrophils to Lymphocyte Ratio (NLR), and absolute counts of 18 different populations of circulating immune cells as measured by flow cytometry. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). The median overall survival in the Ampligen group was 19 months, compared to a historical control group and subgroup (7.5 and 12.5, respectively) that did not receive Ampligen.

"This is the first study investigating the immunomodulatory effect of the TLR-3 agonist Ampligen in patients with locally advanced or metastatic pancreatic cancer following FOLFIRINOX therapy and these results are compelling. We remain encouraged by the data demonstrating patients who were treated with Ampligen had a longer median PFS and overall survival compared to matched controls of patients who did not receive Ampligen. We look forward to further evaluation of Ampligen as a treatment for pancreatic cancer in our upcoming Phase 2 study," stated David Strayer, MD, Chief Medical Officer, Chief Scientific Officer of the Company and Board Certified in Medical Oncology.

Prof. Casper H.J. van Eijck, MD, PhD, Pancreato-biliary Surgeon at Erasmus MC and co-author of the published manuscript added, "There remains a critical need for more effective therapies to treat this devastating disease. Based on these positive data, I believe Ampligen has the potential to be a meaningful extension to the standard of care for advanced pancreatic cancer and may offer much needed hope for patients and families. Of particular note, we were pleased to see the improved overall survival rates of our patients treated with Ampligen. These initial data suggest Ampligen has the potential to be an important treatment for pancreatic cancer patients, and I look forward to being a part of the planned Phase 2 study."

From January 2017 to February 2019, a total of 42 patients with LAPC or metastasized disease were treated with Ampligen. Twenty-seven of the patients had been treated with FOLFIRINOX prior to Ampligen. Of the 27 patients, 25 patients completed the first cycle of Ampligen. Based on OS after Ampligen treatment, the 27 patients were divided into 11 long-term survivors and 16 short-term survivors.

Ampligen was administered in cycles of six weeks. Patients received treatment for a maximum of three cycles of six weeks or until progression. A treatment cycle consisted of twice per week intravenous administration of 200 milligrams in the first two weeks and 400 milligrams in the last 4 weeks. Laboratory assessments and peripheral blood sample collections for immunology flow cytometry analysis were obtained at baseline and 5 days after the last infusion of the first treatment cycle. Progression of disease was assessed by CT imaging scans according to RECIST criteria 1.1 and serum carbohydrate antigen 19-9 examinations every 3 months during follow-up, if clinically indicated or when recurrence was suspected.

Key Results Highlights

While at 6 weeks, the Systemic Immune-Inflammation Index (SIII) and the Neutrophils to Lymphocyte Ratio (NLR) values from the long-term and short-term patients combined showed no significant difference compared to baseline, the values were found to be significantly lower in 11 long-term survivors versus 16 short-term survivors.
The numbers of B-cells were significantly increased in long-term survivors. T-cells and myeloid cells were not significantly increased after treatment with Ampligen.
The median PFS was significantly longer (13 months) with rintatolimod compared to both matched controls and the subset of matched controls (5 and 8.6 months, respectively); hazard ratio was 0.51; 95% CI 0.28-0.90, p=0.007.
The median overall survival was significantly longer (19 months) with Ampligen compared to both matched controls and the subset of matched controls (7.5 and 12.5, respectively); hazard ratio was 0.52; 95% CI 0.28 – 0.90, p=0.016.
At the time of analysis in November 2021, a total of three patients with the metastasized disease were still alive.
Based on these data, the Company believes that Ampligen could be a potential effective maintenance therapy after systemic chemotherapy in patients with advanced pancreatic cancer.

The Company plans to conduct a Phase 2 study of Ampligen as a therapy for locally advanced pancreatic cancer. The planned AMP-270 clinical trial of approximately 90 subjects will be a randomized, open-label, controlled, parallel-arm study with the primary objective of comparing the efficacy of Ampligen versus a no treatment control group following FOLFIRINOX for subjects with locally advanced pancreatic carcinoma. Secondary objectives include comparing safety and tolerability.

Amarex Clinical Research will manage the AIM-sponsored Phase 2 study. The Buffett Cancer Center at the University of Nebraska Medical Center (UNMC) and Erasmus MC in The Netherlands are expected to be the primary study sites, although additional sites are anticipated.

On March 8, 2022 Aeglea BioTherapeutics, Inc. (Nasdaq:AGLE), a clinical-stage biotechnology company developing a new generation of human enzyme therapeutics as innovative solutions for rare metabolic diseases, reported financial results for the fourth quarter and full year 2021, and provided program updates (Press release, Aeglea BioTherapeutics, MAR 8, 2022, View Source [SID1234609636]).

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"2021 moved us closer to our goal of delivering life-changing medicines to people with rare metabolic diseases with positive topline data from our pivotal Phase 3 trial of pegzilarginase for Arginase 1 Deficiency and the dosing of the first patients in our Phase 1/2 trial of AGLE-177 for Homocystinuria. We enter 2022 well positioned to capitalize on the momentum we’ve built," said Anthony Quinn, M.B., Ch.B., Ph. D., president and chief executive officer of Aeglea. "We are excited about the opportunities in 2022 for a transformative year. With a strong portfolio of human enzyme therapies for rare metabolic diseases, we are looking forward to advancing all our programs, including sharing clinical data from our AGLE-177 program, progressing AGLE-325 for Cystinuria through IND-enabling studies and working with the FDA throughout the regulatory process for pegzilarginase."

Program Updates

Pegzilarginase in Arginase 1 Deficiency

Announced the PEACE Phase 3 clinical trial met its primary endpoint with an 80% plasma arginine reduction, and an accompanying positive trend in a secondary endpoint assessing mobility. Additionally, 90.5% of patients achieved normal plasma arginine levels. Pegzilarginase was well-tolerated, and no patients discontinued the trial due to adverse events.
Highlighted 104-week data from the GMFM-E and 6-Minute Walk Test assessments from the Phase 1/2 open-label extension, which underscores the sustained, long-term impact of pegzilarginase treatment on mobility.
Plan to present additional data from PEACE Phase 3 clinical trial at the Society for Inherited Metabolic Disorders (SIMD) Annual Meeting in April 2022.
Hosted a Key Opinion Leader and Patient Caregiver event to provide insights and perspectives on treating and living with Arginase 1 Deficiency.
Met with U.S. Food and Drug Administration (FDA) in late February to discuss data from the pegzilarginase program and the path towards Biologic License Application (BLA) submission.
BLA preparation on track to enable a second quarter 2022 submission.
AGLE-177 in Homocystinuria

Completed dosing in the 0.15 mg/kg intravenous cohort in the Phase 1/2 clinical trial. AGLE-177 was well tolerated with no safety concerns and data from this first cohort showed reductions in total homocysteine in all patients.
The encouraging results from the first cohort allowed the Company to advance directly to the 0.45 mg/kg subcutaneous dose, accelerating the generation of dose response data. This second cohort is currently being dosed.
Filed an Investigational New Drug (IND) application with the FDA. Acceptance of the IND would allow the Company to open clinical trial sites in the U.S. for the Phase 1/2 clinical trial and a potential pivotal Phase 3 trial.
Expect to announce Phase 1/2 clinical data in the second half of 2022.
AGLE-325 in Cystinuria

Shared preclinical data from optimized clinical candidate, which the Company believes will support an attractive clinical dosing schedule.
Plan to move through IND-enabling studies in 2022.
Upcoming Events

American College of Medical Genetics and Genomics Annual Clinical Genetics Meeting, March 22-26
American Academy of Neurology Annual Conference, April 2-7
Society for Inherited Metabolic Disorders 43rd Annual Meeting, April 10-13
Needham Virtual Healthcare Conference, April 11-14
Fourth Quarter and Full Year 2021 Financial Results

As of December 31, 2021, Aeglea had available cash, cash equivalents, marketable securities and restricted cash of $95.0 million. The Company expects its cash, cash equivalents and investments will enable it to fund its operating expenses and capital expenditure requirements into the first quarter of 2023.

Aeglea recognized development fee revenues of $3.6 million in the fourth quarter of 2021, as a result of its license and supply agreement with Immedica for the commercial rights to pegzilarginase in certain territories outside the United States (License and Supply Agreement). The revenues recorded in the fourth quarter of 2021 are related to the delivery of clinical trial and regulatory services. Aeglea recognized no revenue for the fourth quarter of 2020.

Aeglea recognized license and development fee revenues of $18.7 million in the year ended December 31, 2021, as a result of its License and Supply Agreement. The revenues recorded in the year ended December 31, 2021 are related to the transfer of the license and delivery of clinical trial and regulatory services. Aeglea recognized no revenue for the year ended December 31, 2020.

Research and development expenses totaled $16.8 million for the fourth quarter of 2021 and $15.8 million for the fourth quarter of 2020. The increase was primarily associated with a ramp-up in BLA development activities and increased enrollment in our PEACE Phase 3 trial of pegzilarginase for the treatment of patients with Arginase 1 Deficiency.

Research and development expenses totaled $57.1 million for the year ended December 31, 2021 and $59.6 million for the year ended December 31, 2020. The decrease was primarily associated with completing certain pre-commercial manufacturing activities for pegzilarginase and completing formulation, characterization, and stability studies for AGLE-177.

General and administrative expenses totaled $7.3 million for the fourth quarter of 2021 and $7.0 million for the fourth quarter of 2020. This increase was primarily due to changes in employee headcount and additional compensation to support the development of the Company’s commercial capabilities and infrastructure.

General and administrative expenses totaled $27.3 million for the year ended December 31, 2021 and $21.8 million for the year ended December 31, 2020. This increase was primarily due to changes in employee headcount and additional compensation and an increase in operational expenses to build the Company’s commercial capabilities and infrastructure.

Net loss totaled $20.4 million and $22.7 million for the fourth quarter of 2021 and 2020, respectively, with non-cash stock compensation expense of $2.1 million and $1.6 million for the fourth quarter of 2021 and 2020, respectively. Net loss totaled $65.8 million and $80.9 million for the years ended December 31, 2021 and 2020, respectively, with non-cash stock compensation expense of $8.0 million and $6.3 million for the years ended December 31, 2021 and 2020, respectively.

About Pegzilarginase in Arginase 1 Deficiency

Pegzilarginase is a novel recombinant human enzyme engineered to degrade the amino acid arginine and has been shown to rapidly and sustainably lower levels of the amino acid arginine in plasma. Aeglea is developing pegzilarginase for the treatment of people with Arginase 1 Deficiency (ARG1-D), a rare debilitating and progressive disease characterized by the accumulation of arginine. ARG1-D presents in early childhood and patients experience spasticity, seizures, developmental delay, intellectual disability and early mortality.

In December 2021, Aeglea announced the PEACE Phase 3 clinical trial met its primary endpoint with an 80% plasma arginine reduction. Additionally, 90.5% of pegzilarginase treated patients achieved normal plasma arginine levels. The arginine lowering was accompanied by a positive trend in a secondary endpoint, GMFM-E, which is a key clinical assessment of mobility. Aeglea’s Phase 1/2 and Phase 2 Open-Label Extension (OLE) data for pegzilarginase in patients with ARG1-D demonstrated clinical improvements and sustained lowering of plasma arginine. Pegzilarginase has received multiple regulatory designations, including Rare Pediatric Disease, Breakthrough Therapy, Fast Track and Orphan Drug Designations from the U.S. Food and Drug Administration as well as Orphan Drug Designation from the European Medicines Agency.

About AGLE-177 in Homocystinuria

AGLE-177 is a novel recombinant human enzyme, which is engineered to degrade the amino acid homocysteine and its dimer, homocystine. AGLE-177 is currently being studied in a Phase 1/2 clinical trial for the treatment of patients with Classical Homocystinuria, a rare inherited disorder of methionine metabolism that results in elevated levels of total homocysteine. Homocysteine accumulation plays a key role in multiple progressive and serious disease-related complications, including thromboembolic vascular events, skeletal abnormalities (including severe osteoporosis), developmental delay, intellectual disability, lens dislocation and severe near sightedness. Preclinical data demonstrated that AGLE-177 improved important disease-related abnormalities and survival in a mouse model of Homocystinuria. AGLE-177 has received both U.S. and EU Orphan Drug Designation as well as U.S. Rare Pediatric Disease Designation.

On March 8, 2022 AbbVie (NYSE: ABBV) reported that it has resolved all U.S. HUMIRA (adalimumab) litigation with Alvotech (Press release, AbbVie, MAR 8, 2022, View Source [SID1234609635]).

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Under the terms of the resolution, AbbVie will grant Alvotech a non-exclusive license to its HUMIRA-related patents in the United States, which will begin on July 1, 2023. AbbVie will make no payments of any form to Alvotech, and Alvotech will pay royalties to AbbVie for licensing its HUMIRA patents and acknowledges the validity and enforceability of the licensed patents. The resolution includes dismissal of the patent and trade secret litigation between AbbVie and Alvotech.

On March 8, 2022 VBL Therapeutics (Nasdaq: VBLT), a late-clinical stage biotechnology company focused on developing first-in-class therapeutics for difficult-to-treat malignant solid tumors and immune or inflammatory indications, reported that enrollment in the Phase 3 OVAL trial in recurrent platinum-resistant ovarian cancer has been completed, with a total of 409 patients enrolled globally (Press release, VBL Therapeutics, MAR 8, 2022, View Source [SID1234609629]). The company also announced that following a pre-planned safety review of the 370 patients randomized in the OVAL trial by December 31, 2021, the independent DSMC has unanimously recommended that the trial continue as planned.

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"We would like to take this opportunity to thank the participating physicians and patients in the Phase 3 OVAL trial," said Prof. Dror Harats, M.D., chief executive officer of VBL Therapeutics. "We are very pleased to have completed enrollment in OVAL and see this as a significant milestone in the ofra-vec clinical program. I would also like to thank the DSMC members for their work and guidance. Their analysis was particularly important, as the committee provided its recommendation following the review of unblinded data from patients representing over 90% of the targeted enrollment. We look forward to the readout of the PFS primary endpoint in the second half of this year. With positive results, we intend to submit a BLA to the FDA."

Professor Bradley Monk, in the Division of Gynecologic Oncology at University of Arizona College of Medicine – Phoenix, AZ and Creighton University School of Medicine – Phoenix, AZ commented: "Ovarian cancer is the second most common gynecological cancer, and causes more deaths than any other gynecological malignancy. Platinum-resistant recurrent disease is particularly problematic, with low response rates and limited duration of response to standard chemotherapy. Ofra-vec has a compelling dual mechanism of action that, if successful, will establish a new standard of care in ovarian cancer. I am pleased to be the clinical trial Steering Committee Chair for this important study and to have the opportunity to help improve treatment outcomes for patients."

About the OVAL Trial

OVAL (VB-111-701/GOG-3018) is an international Phase 3 randomized, pivotal registration-enabling clinical trial comparing a combination of ofra-vec (ofranergene obadevovec or VB-111) and paclitaxel to placebo plus paclitaxel, in adult patients with recurrent platinum-resistant ovarian cancer. The OVAL trial has two primary endpoints: progression free survival (PFS) and overall survival (OS). Successfully meeting either primary endpoint has the potential to support a Biologics License Application (BLA). Meeting the PFS endpoint, with a top-line readout anticipated in the second half of 2022, could accelerate BLA submission by approximately one year, subject to discussions with the U.S. Food and Drug Administration. A top-line readout of the OS primary endpoint is anticipated in 2023. OVAL is being conducted in collaboration with the GOG Foundation, Inc., an independent international non-profit organization with the purpose of promoting excellence in the field of gynecologic malignancies. For more information, refer to Clinicaltrials.gov NCT03398655.

About Ofra-Vec (ofranergene obadenovec; `VB-111`)

Ofra-vec is an investigational anti-cancer, gene-therapy agent in development to treat a wide range of solid tumors. Ofra-vec is a unique biologic agent designed to use a dual mechanism to target solid tumors. Its mechanism combines the blockade of tumor vasculature with an anti-tumor immune response. Ofra-vec is administered as an IV infusion once every 6-8 weeks. It has been observed in past clinical research to be generally well-tolerated in >300 cancer patients and demonstrated activity signals in an "all comers" Phase 1 trial as well as in three tumor-specific Phase 2 trials. Ofra-vec has received orphan designations for the treatment of ovarian cancer and for the treatment of glioma by the European Commission. The FDA granted ofra-vecorphan designation for the treatment of malignant glioma and fast track designation for the treatment of rGBM. Ofra-vec demonstrated proof-of-concept and survival benefit in Phase 2 clinical trials in radioiodine-refractory thyroid cancer (NCT01229865) and platinum-resistant ovarian cancer (NCT01711970).

On March 8, 2022 United Therapeutics Corporation (Nasdaq: UTHR) reported that James Edgemond, Chief Financial Officer and Treasurer, will provide an overview and update on the company’s business during a fireside chat session at the Oppenheimer 32nd Annual Healthcare Conference (Press release, United Therapeutics, MAR 8, 2022, View Source [SID1234609628]).

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The session will take place virtually on Tuesday, March 15, 2022, from 9:20 a.m. to 9:50 a.m., Eastern Daylight Time, and can be accessed via a live webcast on the United Therapeutics website at View Source An archived, recorded version of the session will be available approximately 24 hours after the session ends and can be accessed at the same location for 90 days.