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."

On April 9, 2024 Diakonos Oncology Corp., a clinical-stage immuno-oncology company, reported an interim analysis of the Phase 1 open label trial of DOC1021 showing substantially increased survival of glioblastoma multiforme (GBM) patients well beyond the expected median overall survival (mOS) of 12.7 months for patients receiving the standard of care (SOC) (Press release, Diakonos Oncology, APR 9, 2024, View Source [SID1234641970]). The median overall survival for the trial of newly diagnosed GBM has not yet been reached with 12-month survival among evaluable patients currently is 88%.

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The analysis was presented in a poster at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting. Twelve of 16 patients with newly diagnosed GBM remain alive with no serious adverse events attributable to DOC1021. As a result, DOC1021 has received Fast Track and Orphan Drug designations from the FDA.

"These very encouraging results support our confidence in the potential for our dendritic cell vaccines to significantly improve the lives of patients with the most deadly cancers," said Mike Wicks, Diakonos CEO. "DOC1021 is a first-of-its kind dendritic cell vaccine that represents an entirely new strategy for engaging a complete immune response against a patient’s cancer."

Findings from the ongoing analysis, presented April 8, 2024 at AACR (Free AACR Whitepaper), also reveal that with an average 12.9 months of follow up among the 16 newly diagnosed GBM patients enrolled in the study, median overall survival has yet to be reached. The company expects to begin Phase 2 trials of DOC1021 for GBM patients within the next year and is conducting two other clinical development programs in pancreatic cancer (NCT04157127) and angiosarcoma (NCT05799612).

Both newly diagnosed and recurrent GBM patients were enrolled in the Phase 1 study (NCT04552886) and received DOC1021 across four dose levels following SOC treatment. The first GBM patient enrolled in October 2021 survived more than two years. Each of the next four patients enrolled survived more than 15 months, and two remain alive at 20.3 months and 17.5 months, despite receiving less than 25% of the projected therapeutic dose.

In addition, Diakonos’ trial has been commended on its inclusive trial design. Fifty-six percent of patients enrolled likely would have been excluded from other GBM clinical trials due to issues such as progression prior to treatment, subtotal resection status, or advanced age. Despite their challenging prognosis, these patients saw a statistically significant improvement in expected overall survival of 7.7 months for similar patients. The trial did exclude patients with IDH mutation status as such patients are no longer classified as GBM.

Diakonos’ dendritic cell vaccines are made with a patient’s own immune cells combined with RNA and proteins prepared from a sample of their tumor. This unique approach allows targeting of the complete cancer antigen profile without any genetic modification. Based on a discovery that unlocks the antiviral immune response, the vaccines harness a powerful natural immune signaling pathway that targets and eliminates cancer cells as if they were virally infected.

On April 9, 2024 Calidi Biotherapeutics Inc. (NYSE American: CLDI) ("Calidi"), a clinical-stage biotechnology company developing a new generation of targeted immunotherapies, reported the presentation of new data detailing the molecular mechanisms of action underlying the immunomodulatory role of Calidi’s therapies at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual (AACR) (Free AACR Whitepaper) Meeting 2024, in San Diego, California (Press release, Calidi Biotherapeutics, APR 9, 2024, View Source [SID1234641969]). The poster, titled "Deciphering anticancer mechanisms of oncolytic virus-loaded stem cells," will be presented on April 9, 2024, during the Chemotherapy, Radiation, and Vaccine Mediated Immunity session.

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"Calidi’s novel approach to treating cancer has always centered around the stem cell as a means of protecting, delivering, and potentiating our tumor-killing virotherapeutic payloads. We believe this novel approach using allogeneic stem cells differentiates our technology and offers the potential of our platforms, CLD-101 and CLD-201, to serve as universal, off-the-shelf, options for patients needing improved therapeutic outcomes in their treatments for cancer," said Allan Camaisa, CEO and Chairman of the Board at Calidi Biotherapeutics.

"The data presented at AACR (Free AACR Whitepaper), in close collaboration with our long-standing partners at City of Hope, describes how stem cells may improve anticancer actions of oncolytic viruses, by not only protecting and potentiating virotherapy, but by secreting immunomodulatory molecules into the tumor microenvironment. We are excited to continue research in the field of oncology by better understanding the mechanism of action for Calidi’s lead assets, and their potential treatment for solid tumors," said Antonio F. Santidrian, Chief Scientific Officer of Calidi Biotherapeutics.

Antitumor virotherapies are capable of selectively eradicating tumor cells without endangering healthy cells in the body. Viruses that enter the body are immediately inactivated by the immune system. Calidi is developing two platforms, CLD-101 and CLD-201, that consist of oncolytic viruses loaded into stem cells, designed to cloak the tumor-killing viruses from the immune system. In the studies presented at AACR (Free AACR Whitepaper), scientists at Calidi Biotherapeutics and City of Hope researched the stem cells secretome transcriptomic of CLD-101 and CLD-201. The transcriptomic analysis showed that immunomodulatory cytokines, and chemokines, are induced following oncolytic virus infection demonstrating a potential immunotherapeutic role of the cells, in addition to the delivery and protection of the oncolytic viruses. Together these findings suggest that the enhanced antitumor actions of Calidi’s therapies are partially due to the alterations in the stem cells’ secretome, reinforcing the potential of the company’s novel approach to treat solid tumors.

Calidi previously announced that its partner, City of Hope, dosed the first patient in a Phase 1 clinical trial evaluating CLD-101 in recurrent high-grade glioma patients. The company expects to report a clinical update in the second quarter of 2024. A previously completed Phase 1 dose escalation clinical trial showed CLD-101 was well-tolerated and demonstrated stimulation of an antitumor immune response. The company expects to start clinical trials with CLD-201 by the end of 2024, subject to the company’s continued ability to raise the capital necessary to fund its clinical development programs.

This poster will be posted to the "Scientific Publications" section of the Calidi Biotherapeutics website following the conclusion of the conference.