On April 10, 2024 Bexion Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company developing a novel class of biologic therapy to treat solid tumor cancers and chemotherapy-induced peripheral neuropathy (CIPN), reported that the Company presented a poster on BXQ-350 during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 which took place April 5-10, 2024, in San Diego, CA. Poster details are included below (Press release, Bexion, APR 10, 2024, View Source [SID1234641976]).

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Poster Details:

Abstract Title: BXQ-350: A novel biologic that allosterically activates glucosylcerebrosidase and demonstrates signs of activity in cancer patients
Abstract Number: 3072
Poster Board Number: 12
Session Title: Signaling Pathways That Regulate Metabolism 1
Session Date: Monday Apr 8, 2024
Presenter: Gilles Tapolsky, PhD, Vice President of Pharmacology & Translational Sciences, Bexion Pharmaceuticals

The abstracts were posted to the AACR (Free AACR Whitepaper) Online Program Planner at 4:30 PM ET on Tuesday, March 5.

About AACR (Free AACR Whitepaper)
The American Association for Cancer Research (AACR) (Free AACR Whitepaper) is the first and largest cancer research organization dedicated to accelerating the conquest of cancer. The AACR (Free AACR Whitepaper) Annual Meeting program covers the latest discoveries across the spectrum of cancer research—from population science and prevention; to cancer biology, translational, and clinical studies; to survivorship and advocacy—and highlights the work of the best minds in research and medicine from institutions all over the world.

About BXQ-350
Bexion’s lead drug candidate is BXQ-350, a first-in-class biologic containing the multifunctional, sphingolipid activator protein, Saposin C, and a phospholipid. Clinically, two Phase 1 clinical trials, one in adults and one in pediatric DIPG patients, have demonstrated a robust safety profile for BXQ-350 with evidence of single agent activity across multiple solid tumor types. Additionally, other clinical and non-clinical data suggest BXQ-350 has activity in chemotherapy-induced peripheral neuropathy, an area of high unmet medical need in solid tumor patients treated with oxaliplatin and other chemotoxic agents.

On April 10, 2024 Aprea Therapeutics, Inc. (Nasdaq: APRE) ("Aprea", or the "Company"), a clinical-stage biopharmaceutical company focused on precision oncology through synthetic lethality, reported details about four poster presentations at the ongoing American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 5 to 10, 2024 in San Diego, CA (Press release, Aprea, APR 10, 2024, View Source [SID1234641975]). The posters feature APR-1051, Aprea’s next-generation inhibitor of WEE1 kinase, as well as a clinical update on ATRN-119, its novel macrocyclic ATR inhibitor. The Company also presented a poster highlighting a new set of preclinical data in glioblastoma with a next-generation macrocyclic ATR inhibitor, ATRN-333.

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"The four poster presentations at this prestigious conference highlight our growing pipeline and commitment to help cancer patients in need," said Dr. Oren Gilad, President and CEO of Aprea. "We are pleased to share the strong pre-clinical data and future clinical strategy for our promising next-generation WEE1 kinase inhibitor, APR-1051. We are also very excited to provide an encouraging update on the ongoing clinical study of our novel macrocyclic ATR inhibitor, ATRN-119."

Copies of the posters will be available on the Aprea corporate website here, at the conclusion of the AACR (Free AACR Whitepaper) meeting.

APR-1051

The novel WEE1i, APR-1051, is a potentially well tolerated and effective treatment for cyclin E-overexpressing cancers

Lead Author and Presenter: Molly Hansbarger
Abstract Number: 7121

This poster summarizes the pre-clinical data of APR-1051
APR-1051 exhibits high potency for WEE1 inhibition in vitro
Selectivity is key for success. APR-1051 shows low off-target inhibition of the PLK family of kinases.
To measure the potential for off-target inhibition of the PLK family of enzymes, in vitro experiments were conducted to determine the IC50s of APR-1051 vs ZN-c3 (Zentalis Pharmaceuticals)
The results showed significantly lower off-targeting of PLK1, PLK2 and PLK3 as indicated by higher IC50 values for APR-1051 compared to ZN-c3.
IC50 of APR-1051 over IC50 of ZN-c3
• PLK1: > 150-fold
• PLK2: > 50-fold
• PLK3: > 600-fold
• Off-targeting of PLK1 by other WEE1 inhibitors may compromise the efficacy of these drugs.
• Off-targeting of the PLK family may increase the risk of producing PLKi-associated adverse effects.

Cyclin E as a potential biomarker for APR-1051 treatment
APR-1051 demonstrated effectiveness in suppressing the growth of Cyclin E-overexpressing breast and ovarian cancer cell lines.
The dose and scheduling of APR-1051 that causes significant suppression of CCNE1-amplified high-grade serous ovarian cancer tumors in mice is well tolerated.
Red blood cell and platelet counts remained within non-pathogenic ranges after a 28-day treatment period, consistent with proposed minimal off target PLK1 inhibition
APR-1051 will potentially exhibit low cardiotoxicity.
Inhibition WEE1 by APR-1051 occurs at an IC50 that is 200-fold lower on average than the IC50 of hERG potassium channel inhibition.
Strong evidence for combination therapy
APR-1051 was evaluated in combination with Aprea’s second-generation ATR inhibitors (ATRN-330 and ATRN-354) in xenografted tumors. The results showed higher anti-tumor activity for the combinations, compared with vehicle or monotherapy.
APR-1051 received U.S. FDA clearance for a clinical trial, now with plans to dose the first patient in June 2024
ASECOT-1051: First-in-human phase 1 study of WEE1 inhibitor APR-1051 in patients with advanced solid tumors harboring cancer-associated gene alterations.

Presenter: Nadeem Q. Mirza, M.D., MPH
Lead author: Timothy Yap, M.D.
Abstract Number: CT196

This poster summarizes the strategy for the upcoming clinical trial of APR-1051
The aim of this first-in-human Phase 1 study (ACESOT-1051: A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051) is to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent APR-1051 in advanced solid tumors harboring cancer-associated gene alterations (NCT06260514)
This biomarker-driven study will include patients with advanced/metastatic solid tumors harboring cancer-associated gene alterations, such as CCNE1 or CCNE2, FBXW7, PPP2R1A, or KRAS G12
Oral APR-1051 will be administered once daily for 28-day cycles.
The study will consist of two parts.
Part 1 will be dose escalation and is expected to enroll up to 39 patients with advanced solid tumors harboring cancer-associated gene alterations. In the dose escalation phase the first three dose levels will use accelerated titration followed by Bayesian Optimal Interval (BOIN) design for the remaining dose levels
Part 2 (up to 40 patients) is designed for dose optimization, with the goal of selecting the Recommended Phase 2 Dose (RP2D)
The primary objectives are to measure safety, dose-limiting toxicities (DLTs), maximum tolerated dose or maximum administered dose (MTD/MAD), RP2D; Secondary objectives are to evaluate pharmacokinetics, preliminary efficacy according to RECIST or PCWG3 criteria; Pharmacodynamics is an exploratory objective.
Enrollment is anticipated to begin in Q2 2024
MD Anderson Cancer Center is the lead site, and the study will be performed at between 3 and 10 sites in the U.S
ATRN-119

Nadeem Mirza, MD, MPH, Senior Medical Advisor to Aprea commented, "Enrollment of patients continues in the dose escalation portion of our Phase 1/2a clinical trial evaluating ATRN-119 in patients with advanced solid tumors having mutations in defined DDR-related genes. We are now enrolling patients in the 550 mg cohort (Cohort 5). ATRN-119 continues to be safe and well tolerated, with no dose-limiting toxicities and no signs of significant hematological toxicity reported. We are encouraged by the preliminary signs of clinical benefit. Stable disease has been reported in two patients, one of which continues to be on treatment out to Day 188. Dose escalation will proceed throughout 2024."

First-in-human phase 1/2a trial of a macrocyclic ATR inhibitor (ATRN-119) in patients with advanced solid tumors

Presenter: Nadeem Q. Mirza, M.D., MPH
Lead author: Fiona Simpkins, M.D.
Abstract Number: CT195

This poster reports on the ongoing first-in-human Phase 1 study of ATRN-119 in patients with advanced solid tumors harboring specific DDR mutations (NCT04905914)
As of March 12, 2024, 16 patients were enrolled in the first five cohorts of the dose escalation stage (50 mg/day, 100 mg/daily, 200 mg/daily, 350 mg/daily, and 550 mg/daily)
ATRN-119 is being administered daily on a continuous schedule
ATRN-119 has been found to be safe and well tolerated.
No reported DLTs and no treatment-related Grade 4 or higher AEs have been reported.
At doses up to 550 mg once daily, there have been no signs of hematological toxicity.
Pharmacokinetic studies show ATRN-119 serum concentrations are entering the expected therapeutic range at the current highest dose level (550 mg). The Company currently has FDA clearance to evaluate doses up to 800mg, with a planned protocol amendment to add doses up to 1300 mg.
Preliminary signs of clinical benefit have been observed.
Two patients have achieved stable disease (SD) – one each in the 50 mg and 200 mg cohorts.
The latter patient at 200 mg/day had SD at Days 55, 112, and 168, and continues to be on treatment as of Day 188 without significant adverse events reported. This patient is now receiving 350 mg daily, as per the trial protocol, and is tolerating treatment well.
ATRN-333

Convection-enhanced delivery of a novel ATR inhibitor synergizes with systemic lomustine for improved treatment of glioblastoma.

Presenter: Teresa Lee, Ph.D.
Lead Authors: Alexander Josowitz Ph.D., Teresa Lee Ph.D.
Abstract Number: 7117

This poster describes a combination approach using a next-generation macrocyclic ATR inhibitor, ATRN-333, to sensitize glioblastoma (GBM) tumors to lomustine, an oral DNA alkylating agent.
The DNA damage response and DNA repair mechanisms such as the ataxia telangiectasia and Rad3-related (ATR) pathway are key mediators of therapeutic responses in glioblastoma (GBM). Recent studies have shown that targeting DNA repair proteins alongside standard-of-care options is a promising anti-tumor strategy for this disease.
To overcome difficulties associated with drug delivery to the brain, a convection-enhanced delivery (CED) system in conjunction with nanoparticle (NP) technology was used for direct intracranial administration of ATRN-333 to orthotopic GBM tumors.
Both free and NP-encapsulated ATRN-333 showed high potency in inhibiting ATR function in cell-based assays.
There was a clear synergistic effect between lomustine and ATRN-333 in GBM cell lines.
ATRN-333 effectively sensitized both flank and intracranial tumors to lomustine in vivo.
When administered via CED, ATRN-333 showed favorable intracranial retention and was well tolerated in mice when combined with lomustine.
These results suggest that ATR inhibitor/lomustine combination therapy, used in conjunction with a CED platform, is a powerful avenue for GBM treatment.
The results support further investigation and potential clinical implementation of ATRN-333 and other macrocyclic ATR inhibitors as chemosensitizers for glioblastoma.

On April 10, 2024 AIM ImmunoTech Inc. (NYSE American: AIM) ("AIM") reported top-line interim data indicating that combining Ampligen (rintatolimod) with Keytruda (pembrolizumab) in the treatment of recurrent ovarian cancer may have a powerful synergistic effect, leading the investigator to conclude that the combination therapy could be far more effective than pembrolizumab alone as a therapy for the disease (Press release, AIM ImmunoTech, APR 10, 2024, https://aimimmuno.com/aim-immunotech-announces-positive-top-line-protocol-planned-interim-report-data-from-the-study-of-ampligen-combined-with-pembrolizumab-for-the-treatment-of-recurrent-ovarian-cancer/ [SID1234641974]).

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See further details on the study "Systemic Immune Checkpoint Blockade and Intraperitoneal Chemo-Immunotherapy in Recurrent Ovarian Cancer" at ClinicalTrials.gov: NCT03734692. Additionally, the immunological signature supporting this synergistic enhancement has been seen in other clinical trials, including with pancreatic cancer (1,2) metastatic triple-negative breast cancer and colorectal cancer metastatic to the liver.

Ampligen is a dsRNA product candidate that acts via the TLR-3 receptor present on several immune cells, epithelial cells and most solid tumors. In the ongoing, investigator-initiated Phase 2, single-arm efficacy/safety trial, University of Pittsburgh Medical Center researchers saw an Objective Response Rate ("ORR") of 45% when combining Ampligen, pembrolizumab and cisplatin in platinum-sensitive subjects with recurrent ovarian cancer. ORR includes complete response ("CR") and partial response ("PR") to treatment. There was a total Clinical Benefit Rate ("CBR") of 55% when including patients who experienced stable disease ("SD"). Researchers also reported a median Progression-Free Survival ("PFS") of 7.8 months.

Robert Edwards, MD, Chair of the Department of Obstetrics, Gynecology & Reproductive Sciences and Co-Director of Gynecologic Oncology Research at Magee-Womens Hospital of UPMC, stated: "These results are incredibly favorable when compared to data from the hallmark Phase 2 study Keynote-100, which looked at the use of pembrolizumab alone in the treatment of recurrent ovarian cancer in both platinum-resistant and platinum-sensitive subjects. Keynote-100 reported an ORR of approximately 8% in these subjects – meaning that the new data analysis showed that combining pembrolizumab treatment with Ampligen created a greater than 500% increase in ORR over the Keynote-100 findings. Additionally, Keynote-100’s median PFS was 2.1 months, or significantly less than that seen in the ongoing Ampligen study. Additionally, the new ovarian cancer data analysis revealed an acute increase in anti-tumor immunity – specifically in biomarkers CXCL9, CXCL10, CXCL11 – which is consistent with the immune-stimulatory effects of Ampligen that researchers have seen in clinical studies of other solid tumors, including triple-negative breast cancer, pancreatic cancer and colorectal cancer. We look forward to publishing a more detailed analysis of these data in a peer-reviewed clinical journal this summer."

AIM Chief Executive Officer Thomas K. Equels stated: "These interim data clearly suggest that there may be a massive positive impact on efficacy when Ampligen is combined with pembrolizumab for the treatment of recurrent ovarian cancer. Other research suggests a similar effect in other solid tumor types. We therefore see an Ampligen combination therapy as having potential across multiple types of cancers. We look forward to the additional clinical studies underway and planned in many of these types of tumors to further confirm these effects."

On April 9, 2024 Amira Therapeutics, an innovative biotechnology company dedicated to improving the lives of pediatric patients with cancer and their families, proudly announces that the Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to AMI463 for the treatment of soft tissue sarcoma (Press release, Amira Therapeutics, APR 9, 2024, View Source [SID1234643099]). This crucial milestone underlines our commitment to address unmet needs in pediatric oncology.

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Soft tissue sarcoma (STS), a rare and diverse group of tumors arising from embryologically derived mesenchymal connective tissues, often leads to a poor prognosis, with limited treatment options beyond chemotherapy. Amira is at the forefront of the development of AMI463, particularly for Rhabdomyosarcoma (RMS), the most common STS in children. The RMS, with an annual incidence of about 500 new cases in the United States and about 400 in children under 18 years of age in Europe, is a muscle-related cancer characterized by an activation of the Hedgehog signaling pathway, primarily impacting muscular tissue and hollow organs.

AMI463, a first-in-class inhibitor that blocks the cell adhesion molecule (CAM)-related down-regulated by oncogenes (CDON), is very promising in the treatment of RMS and other sarcomas, as well as various solid tumors. This innovative compound, which targets Hedgehog’s CDON co-receptor, has demonstrated exceptional efficacy in preclinical studies, especially against the most aggressive subtypes of RMS. These studies have been carried out in collaboration with the Vall d’Hebron University Hospital Research Institute Foundation (VHIR), with whom Amira has been collaborating since the beginning of the project. Within the framework of this collaboration, a family of shared ownership patents has been developed that protect the use of the compound for different indications. These patents have recently been granted in Europe, the USA and Japan.

The ODD is granted to promising treatments for rare diseases, offering benefits such as protocol assistance and market exclusivity, further supporting our efforts to bring AMI463 to patients who need it.

In addition to our current designation as an orphan drug from FDA, the compound AMI463 has recently been recognized, also by the FDA, with the Rare Pediatric Disease Designation (RPDD), as well as had previously received the ODD from the European Medicines Agency (EMA), which will mean support for development and protection during marketing also in Europe. These recognitions by the regulatory agencies reinforce our commitment to expand the scope of our innovative treatments and address the global challenge of pediatric cancer.

On April 9, 2024 Essential Pharma, an international specialty pharma group focused on ensuring that patients have sustainable access to low volume, clinically differentiated, niche pharmaceutical products across key therapeutic areas, reported that it has completed the acquisition of the entire issued share capital of Renaissance Pharma Ltd (Press release, Renaissance Pharma, APR 9, 2024, View Source [SID1234642048]).

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The acquisition adds a second product candidate to Essential Pharma’s rare disease portfolio and underlines the group’s strategy of seeking out clinically differentiated medicines in small patient populations. This will be Essential’s first clinical development-stage asset and is targeted at addressing significant unmet needs in paediatric oncology patients. Simon Ball, CEO and co-founder of Renaissance Pharma, who has significant scientific and commercial expertise within the space, will continue to work with Essential Pharma on Hu14.18’s development, as will many of the Renaissance Pharma team.

Neuroblastoma represents 7-10% of all childhood cancers and is the most common extracranial cancer in children and the most common cancer in children under one year of age1,2. Each year, more than 1500 people are diagnosed in Europe and 800 in the US2,3. Approximately half of all neuroblastoma patients have high risk (HRNB) disease which has an overall survival of ~50% over five years2,3. The current standard of care includes multiple cycles of chemotherapy, surgery, radiotherapy, stem cell transplantation and anti-GD2 monoclonal antibody (mAb) treatment2. There remains a significant unmet need in the availability of effective and suitable treatments for HRNB.

A Phase II trial incorporating Hu14.18 into first-line therapy and additionally, within post-consolidation therapy for HRNB patients, demonstrated positive patient outcomes with 3-year event-free survival (EFS) of 73.7% and overall survival (OS) of 86.0%. Data from this study was published in the Journal of Clinical Oncology in December 2021 and is approaching five-year OS readouts4.

Essential Pharma will work with St Jude Children’s Hospital in accordance with the exclusive license agreement that was signed between St Jude’s and Renaissance in 2023, in order to drive forward the development and commercialisation of Hu14.18 across the territories licensed to Renaissance. Essential Pharma will be responsible for clinical development and defining the optimal route for regulatory approval and eventual commercial launch of Hu14.18

Emma Johnson, CEO of Essential Pharma, commented: "Our acquisition of Hu14.18, the group’s second product for treatment of a rare disease, and the first development-stage asset in our portfolio, is a significant milestone for Essential Pharma, demonstrating our commitment to enabling access to clinically-differentiated medicines. Hu14.18 has enormous potential to help high risk neuroblastoma patients, the majority of whom are young children. It has already produced positive data in Phase II clinical trials, demonstrating a significant improvement in survival, and we are now committed to developing this immunotherapy to be able to bring it to market and to patients as quickly as possible."

Lee Morley, Executive Chairman, Renaissance Pharma Ltd, and Non-Executive Director, Essential Pharma, said: "Essential Pharma is the right partner to take Hu14.18 forward. Having worked alongside Emma at EUSA Pharma, a company specialising in oncology and rare disease, I know that she and the Essential Pharma team have the experience and expertise to bring this important product to market and make it available for children with high-risk neuroblastoma."