On April 12, 2022 Celsion Corporation (NASDAQ:CLSN), a clinical-stage company focused on DNA-based immunotherapy and next-generation vaccines, reported it would highlight its PLACCINE platform technology in an oral presentation at the World Vaccine Congress taking place in Washington D.C. on April 18-21, 2022 (Press release, Celsion, APR 12, 2022, View Source [SID1234612050]).

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Dr. Khursheed Anwar, Chief Scientific Officer at Celsion will present the Company’s technology platform during the Cancer and Immunotherapy session, in his presentation entitled: "Novel DNA Approaches for Cancer Immunotherapies and Multivalent Infectious Disease Vaccines." Details of the presentation are as follows:

Session: Cancer and Immunotherapy – M4
Location: Liberty Salon I-K
Title: Novel DNA Approaches for Cancer Immunotherapies and Multivalent Infectious Disease Vaccines
Presenter: Dr. Khursheed Anwar, Chief Scientific Officer, Celsion
Date: Thursday, April 21, 2022
Time: 12:00 pm Eastern Time

A replay of Dr. Anwar’s presentation along with his slides will be available after his presentation on the investor portion of the Celsion website under Scientific Presentations.

On April 12, 2022 Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer and autoimmune and inflammatory diseases, reported the oral presentation of results from the dose-escalation portion of NEON-1 (NCT04186637), a first-in-human, dose-escalation and expansion study of davoceticept monotherapy in participants with advanced malignancies, at the 2022 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Alpine Immune Sciences, APR 12, 2022, View Source [SID1234612049]).

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Highlights from the presentation include:

Despite a highly heterogeneous, heavily pretreated, advanced solid tumor population – the majority classically considered to be unresponsive to immunotherapy – 11 (23%) of 48 evaluable participants demonstrated tumor volume reduction; 26 (54%) achieved clinical benefit as defined as a best response of stable disease or better; Three (6%) remained on treatment beyond 6 months. Two partial responses were observed in colorectal and renal cell carcinoma.
Davoceticept was well-tolerated with no reported events of cytokine release syndrome. Adverse events of interest included immune-related adverse events and infusion-related reactions, the majority of which were grades 1-2. A single dose-limiting toxicity of gastritis was observed at 3 mg/kg, but a maximum tolerated dose was not reached.
Immunophenotyping demonstrated favorable increases in activated and central memory T cells, as well as reductions in regulatory T cells. Overall, pharmacodynamic analyses suggest 1 or 3 mg/kg every 3 weeks as the optimal biological dose.
Monotherapy expansion cohorts in metastatic cutaneous melanoma, renal cell carcinoma, and PD-L1-positive tumors are planned.
"These results indicate that it is indeed feasible to engage CD28 for cancer immunotherapy, and further suggest that this approach may be clinically advantageous, even for heavily pretreated cancers," remarked Stanford Peng, MD PhD, Alpine’s President and Head of Research and Development. "We eagerly look forward to advancing to expansion cohorts as soon as possible."

A copy of the oral presentation slides is available on the Scientific Publications page of Alpine’s website.

About NEON-1

NEON-1 is a first-in-human dose escalation and expansion study of davoceticept monotherapy in advanced malignancies. Dose escalation enrolled adults with advanced solid tumors refractory or resistant to standard therapy, exploring 0.001-10 mg/kg every 1 and/or 3 weeks. Expansion cohorts are planned to include cutaneous melanoma, renal cell carcinoma, or PD-L1-positive tumors at 1 or 3 mg/kg every 3 weeks. Preliminary results were previously reported at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. More information is available at www.clinicaltrials.gov (NCT04186637).

About Davoceticept (ALPN-202)

Davoceticept (ALPN-202) is a first-in-class, conditional CD28 costimulator and dual checkpoint inhibitor intended for the treatment of cancer. Preclinical studies of davoceticept have successfully demonstrated superior efficacy in tumor models compared to checkpoint inhibition alone. NEON-1 (NCT04186637), a Phase 1 monotherapy dose escalation and expansion trial in advanced malignancies, was initiated in June 2020 and is progressing to expansion cohorts. NEON-2 (NCT04920383), a combination study of davoceticept (ALPN-202) and pembrolizumab was initiated in June 2021 and is currently on partial clinical hold.

On April 12, 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 an update on its development program evaluating Ampligen for the treatment of pancreatic cancer (Press release, AIM ImmunoTech, APR 12, 2022, View Source [SID1234612048]).

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Ampligen is AIM’s dsRNA product candidate being developed for globally important cancers, viral diseases and disorders of the immune system. Ampligen has demonstrated in the clinic the potential for standalone efficacy in a number of solid tumors. Additionally, Ampligen has shown success in increasing survival rates and efficacy in the treatment of animal tumors when used in combination with checkpoint blockade therapies. Ampligen is currently being evaluated as a combinational therapy for the treatment of a variety of solid tumor types in multiple clinical trials – both underway and planned – at major cancer research centers around the country. Ampligen is also being used as a monotherapy to treat pancreatic cancer patients in a named patient program approved by the Inspectorate of Healthcare in the Netherlands at Erasmus Medical Center.

"We continue to be encouraged by the progress and data demonstrated by Ampligen for the treatment of pancreatic cancer. Over the past couple of months, we have made noteworthy advancements on multiple fronts, including FDA notice that we are authorized to proceed with our Phase 2 study. Additionally, we continue to amass an encouraging growing body of data that supports our belief in Ampligen to offer an important treatment option to patients living with pancreatic cancer. We are committed to driving this program forward and working hand-in-hand with our CRO, Amarex, to advance our Phase 2 study, which is on track to commence in the third quarter of this year," commented Thomas Equels, Chief Executive Officer of AIM.

The Company recently received notification from the U.S. Food and Drug Administration ("FDA") that the FDA’s Clinical Hold on AIM’s investigational new drug ("IND") application for a Phase 2 study of Ampligen as a therapy for locally advanced pancreatic cancer (AMP-270) has been lifted and the Company may proceed with the study.

The AMP-270 clinical trial is planned to 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 adenocarcinoma. Secondary objectives include comparing safety and tolerability. The AMP-270 is expected to enroll approximately 90 subjects in up to 30 centers across the U.S. and Europe. 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.

To manage the AIM-sponsored Phase 2 study, on April 7, 2022, the Company engaged Amarex Clinical Research LLC, a CRO with strong track record on advising sponsors through the product development process and providing customized solutions for clinical studies. The AMP-270 clinical trial is on track to commence in Q3 2022.

Additionally, recently published data from a single-center named patient program indicated that patients receiving Ampligen had a longer median survival time than matched historical controls. For the study, patients with locally advanced pancreatic cancer (LAPC) or metastatic disease were treated with Ampligen at 2 doses per week with 400 mg per infusion. The manuscript detailing the positive data from the program, 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 March 2022 in the peer-reviewed journal, Cancers Special Issue: Combination and Innovative Therapies for Pancreatic Cancer. Based on these data, the Company believes that Ampligen could prove to be a potential effective maintenance therapy after systemic chemotherapy in patients with advanced pancreatic cancer.

On April 12, 2022 AbbVie (NYSE: ABBV) reported new data from a Phase 2 trial of navitoclax in combination with ruxolitinib in patients with myelofibrosis (Press release, AbbVie, APR 12, 2022, View Source [SID1234612040]). The results were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting (AACR 2022, abstract #LB108). Navitoclax is an investigational, first-in-class, oral BCL-XL/BCL-2 inhibitor that is designed to activate programmed cell death (apoptosis) in cancer cells. Navitoclax and its safety and efficacy are under evaluation as part of ongoing Phase 2 and registrational Phase 3 studies.

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"Myelofibrosis is a cancer that originates in the bone marrow, leading to fibrosis. Currently, available therapies do not address the underlying disease biology and have not shown a consistent effect on both biomarkers of disease modification and overall survival. Disease control with reversal of bone marrow fibrosis is a key objective for improving patient outcomes," said Mohamed Zaki, M.D., Ph.D., vice president and global head of oncology clinical development at AbbVie. "That’s why we are especially pleased about these early results of navitoclax in combination with ruxolitinib that indicate its novel mechanism of action of inducing cell death may cause reversal of bone marrow fibrosis and extend survival for patients who respond to treatment."

Myelofibrosis is a rare, difficult-to-treat blood cancer that results in excessive scar tissue formation (fibrosis) in the bone marrow. Anti-fibrosis activity, measured by reversal of bone marrow fibrosis (BMF) and reduction in driver gene variant allele frequency (VAF) have been suggested as potential biomarkers to measure disease modification in myelofibrosis, but their association with a survival benefit have not been widely described.1 These data build on AbbVie’s history of transforming standards of care in blood cancers with significant unmet needs.

The results presented at AACR (Free AACR Whitepaper) 2022 were from REFINE (NCT03222609) – a Phase 2 trial evaluating navitoclax in combination with ruxolitinib (a JAK1/2 inhibitor), which included patients with myelofibrosis who had progressed on or had a suboptimal response to at least 12 weeks of ruxolitinib monotherapy. Median exposure to prior ruxolitinib was 91 weeks (range: 19 weeks – 391 weeks) in the first 34 patients enrolled earlier in the trial.

In the exploratory analysis of 32 patients who were evaluable for improvements in BMF, 12 (38%) had a ≥1 grade improvement during any time point in the study. For driver gene VAF reduction, 26 patients were evaluable and 6 (23%) achieved a ≥20% reduction at week 24. Five patients achieved both BMF and VAF responses.

Median overall survival (OS) for all patients was not reached as presented previously by Harrison2 et al. For patients who had a ≥1 grade improvement BMF median OS was not reached compared with 28.5 months for patients who did not experience an improvement. Similarly, median OS was also not reached for patients who achieved a ≥20% driver gene VAF reduction versus 28.5 months for patients who did not.

All 34 patients (100%) experienced at least one adverse event (AE), and 15 (44%) experienced a serious adverse event (SAE).2 The most common AEs of any grade were thrombocytopenia (n= 30, 88%), diarrhea (n= 24, 71%), fatigue (n= 21, 62%), and nausea (n= 13, 38%). The most common SAEs were pneumonia (n= 4, 12%) and splenic infarction (n= 2, 6%).2 There were no SAEs of bleeding and thrombocytopenia was manageable and reversible with dose reduction/interruption of navitoclax and/or ruxolitinib.2 REFINE was a dose-finding study and the target dose of navitoclax was reduced subsequent to these findings.

"Data obtained from this exploratory analysis holds promise for potential future clinical research," said Jacqueline S. Garcia, M.D., Dana-Farber Cancer Institute, assistant professor of medicine at Harvard Medical School. "What is most notable in this analysis is the overall survival among patients who demonstrate VAF and BMF responses and all patients were alive at time of analysis. Patients in this Phase 2 trial had suboptimal response to ruxolitinib at time of study entry and then had navitoclax added to ruxolitinib on the trial. VAF and BMF responses occurred despite the presence of high molecular risk mutations, which suggests the potential efficacy of combination navitoclax and ruxolitinib could be independent of underlying risk factors."

About Navitoclax
Navitoclax is an investigational, oral BCL-XL/BCL-2 inhibitor. The BCL-2 family of proteins are known regulators of the apoptosis pathway.3 Navitoclax is not approved by the U.S. Food and Drug Administration (FDA). Its safety and efficacy are under evaluation as part of ongoing Phase 2 and registrational Phase 3 studies.

AbbVie is currently recruiting for two Phase 3 trials of navitoclax (TRANSFORM-1 and TRANSFORM-2) in combination with ruxolitinib for the treatment of myelofibrosis that will enroll more than 500 patients. The company anticipates pivotal trial readouts and regulatory submission for navitoclax in 2023.

About the REFINE Study
REFINE is a Phase 2, open-label, multicenter study evaluating the tolerability and efficacy of navitoclax alone or when added to ruxolitinib in patients with myelofibrosis.1 The primary outcome measure is the percentage of patients who achieve Spleen Volume Reduction of greater than or equal to 35% (SVR35) from baseline to Week 24. Secondary outcomes measures include percentage of participants achieving 50% reduction in Total Symptom Score from baseline to Week 24 and change in grade of bone marrow fibrosis assessed according to the European Consensus Grading System. More information can be found on www.clinicaltrials.gov (NCT03222609).

About Myelofibrosis
Myelofibrosis is a rare, difficult-to-treat blood cancer that results in excessive scar tissue formation (fibrosis) in the bone marrow. Patients living with myelofibrosis experience symptoms such as an enlarged spleen, fatigue, weakness, and severe anemia, that are often debilitating and greatly impact quality of life. Myelofibrosis also carries a risk of transformation to more aggressive disease such as acute myeloid leukemia.3

On April 12, 2022 Pacira BioSciences, Inc. (Nasdaq: PCRX), the industry leader in its commitment to non-opioid pain management and regenerative health solutions, reported preliminary revenues of $157.4 to $158.4 million for the first quarter of 2022, compared with $119.0 million for the first quarter of 2021 (Press release, Pacira Pharmaceuticals, APR 12, 2022, View Source [SID1234612039]). The company’s revenues include net product sales of EXPAREL (bupivacaine liposome injectable suspension), ZILRETTA (triamcinolone acetonide extended-release injectable suspension), and the iovera° system. Pacira currently reports a range for preliminary quarterly ZILRETTA net product sales as the required adjustments for certain product rebate programs are calculated after the end of the quarter. The company began recognizing sales of ZILRETTA in November 2021 after completing its acquisition of Flexion Therapeutics, Inc.

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"We are excited to report that March marked record EXPAREL monthly sales, underscoring both our near- and long-term expectations for growth of this product. The increase was driven by the continued expansion and institutionalization of EXPAREL-based blocks as the foundation of enhanced recovery protocols across a variety of surgical procedures," said Dave Stack, chairman and chief executive officer of Pacira BioSciences. "We are also making strong progress incorporating ZILRETTA into our operations and recently introduced a simplified pricing and discounting program for our customers. Preliminary findings from our collaborative observational studies have continued to highlight the potential benefits of iovera° cold therapy as a novel approach to treating spasticity. We look forward to meeting with the U.S. Food and Drug Administration later this year to discuss our regulatory strategy for broadening the iovera° label to include this indication."

First Quarter and March 2022 Preliminary Revenue Highlights

•EXPAREL net product sales were $129.2 million and $114.7 million for the first quarters of 2022 and 2021 and $51.2 million and $44.3 million for the months March 2022 and 2021, respectively. EXPAREL daily sales were 113 percent of the prior year for the first quarter and 116 percent for the month of March, respectively. The company reports average daily growth rates for EXPAREL to account for differences in the number of selling days per reporting period. For the first quarter, EXPAREL selling days were 63 in both 2022 and 2021. For the month of March, EXPAREL selling days were 23 in 2022 and 2021. Sales of bupivacaine liposome injectable suspension to a third-party licensee for use in veterinary practice were $1.6 million and $0.8 million in the first quarters of 2022 and 2021, respectively.

•ZILRETTA net product sales are expected to be between $23.0 million and $24.0 million for the first quarter of 2022, compared with $24.6 million for the first quarter of 2021. First quarter 2021 ZILRETTA sales occurred prior to the company’s acquisition of Flexion in November 2021. Pacira is currently not reporting preliminary monthly ZILRETTA net product sales as the required adjustments for certain product rebate programs are calculated after the end of the quarter.
•iovera° net product sales were $3.0 million and $3.3 million for the first quarters of 2022 and 2021 and $1.1 million and $1.5 million for the months of March 2022 and 2021.
•First quarter 2022 royalty revenue was $0.6 million, compared with $0.3 million in 2021.

Since early 2020, the company’s revenues have been impacted by COVID-19 and pandemic-related challenges that included the significant postponement or suspension in the scheduling of elective surgical procedures due to public health guidance and government directives. While the degree of impact has diminished during the course of the pandemic due to the introduction of vaccines and the lessening of elective surgery restrictions, certain pandemic-related operational challenges persist. It remains unclear how long it will take the elective surgery market to normalize or if restrictions on elective procedures will recur due to future COVID-19 variants or otherwise.

The company is not providing 2022 revenue or gross margin guidance at this time given the continued uncertainty around COVID-19 and the pace of recovery for the elective surgery market. To provide greater transparency, the company is reporting monthly intra-quarter unaudited net product sales for EXPAREL and iovera° until it has gained enough visibility around the impacts of COVID-19. The company is also providing weekly EXPAREL utilization and elective surgery data within its investor presentation, which is accessible at investor.pacira.com. Pacira completed its acquisition of Flexion Therapeutics on November 19, 2021, which added ZILRETTA to its commercial offering.

The financial information included in this press release is preliminary, unaudited, and subject to adjustment. It does not present all information necessary for an understanding of the company’s financial results for the first quarter or full year 2022.