On December 13, 2023 Calidi Biotherapeutics, Inc. (NYSE American: CLDI or "Calidi"), a clinical-stage biotechnology company developing a new generation of targeted immunotherapies, reported three presentations on Calidi’s NeuroNova (NNV) and SuperNova (SNV) allogeneic stem cell-based virotherapy platforms at the upcoming 8th Oncolytic Virotherapy Summit to be held December 12-14, 2023 in Boston, Mass (Press release, Calidi Biotherapeutics, DEC 13, 2023, View Source [SID1234638548]). During presentations at the summit, Jana Portnow, M.D., principal investigator, professor in the Department of Medical Oncology & Therapeutics Research and co-director of the Brain Tumor Program at City of Hope Comprehensive Cancer Center, will present the clinical trial design and safety of a Phase 1 study opened in June 2023, using multiple doses of Calidi’s NeuroNova administered intracerebrally, to recurrent high grade glioma patients. Antonio F. Santidrian PharmD, Ph.D., Chief Scientific Officer and Boris R. Minev, M.D., President, Medical & Scientific Affairs, will present updates on the company’s targeted immunotherapies, leveraging allogeneic stem cells to target tumors and deliver anti-cancer payloads in the form of cancer-killing viruses.

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"Our cell-based virotherapeutics are designed to target tumors directly and to help the immune system recognize and attack distant tumor sites," said Boris R. Minev. M.D, President, Medical & Scientific Affairs of Calidi Biotherapeutics. "We are testing this approach in high-grade glioma and anticipate initiating a new clinical trial in several difficult-to-treat advanced solid tumors in the second half of 2024."

The company has four clinical and preclinical programs utilizing different viruses and different types of allogeneic stem cells to overcome the inactivation of Calidi’s virotherapies by the patients’ immune system. This unique approach utilizes specially selected viruses to kill tumor cells and modify the tumor microenvironment, thus enabling the release of tumor antigens. Subsequently, the antigen-presenting cells are able to induce potent antitumor immune responses to detect, attack, and destroy metastatic tumor sites.

Updates to be presented at the upcoming 8th Oncolytic Virotherapy Summit include:

Progress in Recurrent High Grade Glioma (HGG) Trial. Calidi’s collaborator: City of Hope Comprehensive Cancer Center dosed the first patient in June 2023 in a Phase 1 clinical trial of NeuroNova (NNV2) and has dosed 6 patients to-date. Dr. Portnow will present an initial update on this trial. Of note, Calidi holds an exclusive worldwide licensing agreement with City of Hope and the University of Chicago for patents covering the NSC-CRAd-S-pk7 technology (NeuroNova).
Plans to Commence a Dose Escalation Trial in Newly Diagnosed HGG in 1H 2024. Calidi plans to commence a Phase 1b/2 clinical trial for NeuroNova (NNV1) in collaboration with Northwestern University during the first half of 2024. The Phase 1b dose escalation lead portion of this anticipated trial will explore the final dosing regimen for NNV1, including the feasibility of repeated dosing.
Plans to File IND Application for Clinical Trial Initiation in Advanced Solid Tumors in 2H 2024. SuperNova (SNV1) is the company’s first internally developed preclinical product candidate utilizing the SuperNova Delivery Platform. The company plans to file its IND application for the clinical development of CLD-201 to enable the initiation of a Phase 1 clinical trial for SNV1 during the second half of 2024.
Systemic Programs for Metastatic Solid Tumors. Calidi is currently engaged in early discovery research involving its next generation cell-based virotherapies. The company’s research is focused on engineered oncolytic vaccinia virus to increase the tumor specificity and oncolytic potency with improved systemic anti-tumor immunity.
Full details for the conference presentations are below:

City of Hope Comprehensive Cancer Center Presentation:

Title: Neural Stem Cell Based-Oncolytic Virotherapy for Treatment of Glioblastoma (Calidi NNV2 Clinical Update)
Speaker: Dr. Jana Portnow
Date: December 14, 2023
Time: 4:45 p.m. EST

Calidi Presentations:

Title: The Oncolytic Virotherapy Innovation Showcase
Speaker: Dr. Antonio F. Santidrian
Date: December 13, 2023
Time: 4:15 p.m. EST

Title: Optimized Cell-Based Delivery & Potentiation of Oncolytic Virotherapies
Speaker: Dr. Boris R. Minev
Date: December 14, 2023
Time: 9:30 a.m. EST

On December 13, 2023 Vergent Bioscience, a clinical-stage biotechnology company developing tumor-targeted imaging agents, reported that the company has enrolled the first patients in a Phase 2, multi-center study evaluating the efficacy and safety of VGT-309 in patients with cancer in the lung (Press release, Vergent Bioscience, DEC 13, 2023, View Source [SID1234638547]). The international VISUALIZE study will assess the potential of Vergent’s tumor-targeted fluorescent imaging agent to improve the visibility of difficult-to-find and previously undetected tumors during minimally invasive and robotic-assisted surgical procedures, and reduce the possibility that cancer is left behind. Investigators at six clinical trial sites in the United States and Australia plan to enroll 100 patients.

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The widespread adoption of minimally invasive lung cancer surgery, coupled with increasing detection of small tumors, have made it more challenging for surgeons to see all tumor tissue during surgery. Data from three Phase 1 and 2 clinical studies, including findings presented in September 2023 at the World Conference on Lung Cancer (WCLC), have yielded favorable data that suggest VGT-309 is active and can safely be used to detect tumor tissue in the lung.

"We are thrilled to advance VGT-309 to this next stage of clinical development, working with leading thoracic surgeons, academic institutions and large community cancer centers to gather additional evidence regarding its potential utility in lung cancer surgery," said John Santini, Ph.D., president and chief executive officer at Vergent Bioscience. "We look forward to sharing the VISUALIZE results as soon as they are available."

The Phase 2, multi-center, open-label VISUALIZE study is designed to evaluate the efficacy and safety of VGT-309 with near-infrared (NIR) imaging to identify cancer in patients undergoing surgery for proven or suspected cancer in the lung. Each patient in the study will receive VGT-309 as an infusion the day prior to surgery. Following an attempt to identify each tumor using standard surgical techniques, investigators will use a commercially available NIR endoscope with VGT-309 to assess the presence of tumor tissue, which will then be confirmed by pathology. Primary efficacy endpoints include visualization of tumors intraoperatively, surgical margin assessment, and identification of additional cancers or positive lymph nodes that may not have been seen preoperatively.

"Clinical data to date suggest that VGT-309 highlights tumors that would otherwise not be visible during minimally invasive surgeries," said Sunil Singhal, M.D., William Maul Measey Professor in Surgical Research at University of Pennsylvania Perelman School of Medicine, and principal investigator for the study. "We look forward to expanding on our previous studies to further evaluate this agent and its ability to facilitate the complete removal of tumor during surgery."

About VGT-309

VGT-309 is a tumor-targeted imaging agent designed to enable a complete product solution for optimal tumor visualization during open, minimally invasive, and robotic-assisted surgical procedures. VGT-309 is delivered to patients by a short infusion several hours before surgery. Invented in Professor Matt Bogyo’s Lab at Stanford University School of Medicine, the molecule binds tightly (i.e., covalently) to cathepsins, a family of proteases that are overexpressed across a broad range of solid tumors. This approach may provide distinct clinical advantages and positions VGT-309 as an ideal tumor-imaging agent. VGT-309’s imaging component is the near infrared (NIR) dye indocyanine green (ICG), which is compatible with all commercially available NIR intraoperative imaging systems that support MIS technologies and is the preferred dye to minimize confounding background autofluorescence.

On December 13, 2023 RenovoRx, Inc. (Nasdaq: RNXT), a clinical-stage biopharmaceutical company developing novel precision oncology therapies based on a local drug-delivery platform, reported that the Company has filed an international patent application under the Patent Cooperation Treaty (PCT) for its novel Trans-Arterial Micro-Perfusion (TAMP) therapy platform (Press release, Renovorx, DEC 13, 2023, View Source [SID1234638546]). The Company already holds a strong intellectual property portfolio with 9 issued patents and 9 pending patents for its proprietary TAMP platform and delivery system in the US, EU, and Asia. The patent portfolio covers two main areas, mechanical and biological.

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The new international patent application is filed under the Patent Cooperation Treaty on methods and apparatuses that may be used to deliver one or more therapeutic agents through the vaso vasorum (small blood vessels that supply the walls of larger arteries or veins) to a target tissue. RenovoRx believes that these methods and apparatuses via the TAMP therapy platform may provide a novel and important pathway for the targeted delivery of therapeutic classes across DNA/RNA-altering modalities, cell therapy, oncolytic viruses, bi-specific antibodies, and monoclonal antibodies for the treatment of a variety of clinical indications. The Company anticipates that the patent application will be published in May of 2024.

"This patent application further expands the value of TAMP into the delivery of larger therapeutic assets, as a unique platform in oncology, beyond our current Phase III clinical asset," said Shaun Bagai, CEO, RenovoRx. "Once approved, it will further extend our IP coverage, opening up new market potential, expanding the upside value proposition of TAMP commercially. We look forward to providing further highlights and updates related to this patent, as well as our progress in our Phase III TIGeR-PaC clinical program."

TAMP is being investigated in the Company’s Phase III TIGeR-PaC clinical trial, an ongoing randomized multi-center study. The study is evaluating trans-arterial delivery of an FDA-approved chemotherapy, gemcitabine, to treat Locally Advanced Pancreatic Cancer (LAPC) following stereotactic body radiation therapy (SBRT). The study is comparing treatment of gemcitabine with TAMP versus systemic IV administration of gemcitabine and nab-paclitaxel.

The first of two interim analyses was completed in March 2023, and the Data Monitoring Committee (DMC) recommended a continuation of the study. The study is prespecified to provide a primary endpoint of a 6-month Overall Survival benefit and secondary endpoints including reduced side effects versus standard of care.

On December 13, 2023 Engimmune Therapeutics AG ("Engimmune"), a world-class developer of soluble T-cell receptor drugs (‘TCRs’) to treat solid tumours, reported that it has entered into a collaboration with the Swiss Technology Innovation Center CSEM to accelerate the identification of safe and effective drugs using Engimmune’s unique platform (Press release, Engimmune Therapeutics, DEC 13, 2023, View Source [SID1234638545]).

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The collaboration will leverage CSEM’s high-throughput microfluidics technology to speed up the nomination of soluble TCR drug candidates with enhanced affinity, potency, and safety profiles.

Engimmune’s platform technologies – which comprise genome editing, deep sequencing, functional screening, and AI – provide a head start in the hunt for suitable soluble TCR candidates.

CSEM’s expertise in microtechnologies and droplet microfluidics will enable Engimmune to accelerate clinical candidate selection by performing safety screening at increased throughput and depth.

"Ruling out potentially harmful soluble TCRs at an early stage is vital to ensure resources are not wasted pursuing unsuitable candidates," said Felix Kurth, Group Leader Biosystems Engineering with CSEM. The collaboration is supported by a grant from Innosuisse, the Swiss Innovation Agency.

Lars Nieba, CEO of Engimmune Therapeutics, said: "We are identifying targeted, highly potent ‘off-the-shelf’ soluble TCRs, with breakthrough potential for treating solid tumour cancers. Our cutting-edge proprietary platform technologies, which combine protein engineering with AI, enable us to rapidly identify and engineer stable, soluble, multi-specific TCRs that have extremely high affinity for target cancer antigens. But finding a soluble TCR that very strongly binds to a cancer-specific tumour antigen, activates a cytotoxic response, and is also very safe can be like trying to find a needle in a haystack. Our collaboration with CSEM will help greatly to speed up that process and de-risk the development of candidates by quickly ruling out those with potential toxicities."

Dr Nieba and Engimmune’s CSO Dr Rodrigo Vazquez-Lombardi recently gave an update on the company’s approach to the in-house web publication of leading research university ETH Zürich, from which the company was spun out in 2021. The article can be found here: Redirecting immune cells against cancer | ETH Zurich.

News of the collaboration with CSEM comes ahead of Dr Nieba and Dr Vazquez-Lombardi presenting Engimmune’s technologies and immuno-oncology assets at the Biotech Showcase in San Francisco on January 8.

On December 13, 2023 Halia Therapeutics, a clinical-stage biopharmaceutical company pioneering a novel class of small molecule medications designed to combat inflammation, reported the dosing of the first patient in Phase 2a clinical trial evaluating its lead candidate, HT-6184, for the treatment of lower-risk myelodysplastic syndromes (LR-MDS) (Press release, Halia Therapeutics, DEC 13, 2023, View Source [SID1234638544]). HT-6184 is a selective and orally bioavailable first-in-class inhibitor of NLRP3/NEK7 inflammasome, a main driver of inflammatory diseases, as well as hematologic and other malignancies.

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Myelodysplastic syndromes are a group of cancers in which the bone marrow produces underdeveloped (immature) cells that are abnormal in size, shape, or appearance, which are called "dysplastic. This leads to a reduced number of healthy blood cells, which can result in multiple complications, including but not limited to anemia, recurrent infections, and progression to cancer. The trial will evaluate the safety and activity of HT-6184 in up to 40 patients with LR-MDS and will be conducted at multiple sites across India. The study will measure the rate of hematological improvement, including transfusion dependency and changes in hemoglobin levels as primary endpoints for the study. Secondary endpoints will further assess the effect of HT-6184 on biomarkers of inflammasome activation in MDS and the changes in clone size of somatic gene mutations. The trial is expected to be completed by Q4 2025.

"The dosing of the first patient in our Phase 2 trial of HT-6184 marks a significant milestone for Halia in further evaluating the potential of targeting the NLRP3 inflammasome to treat a wide spectrum of immunological and inflammatory diseases," said Margit M. Janát-Amsbury, MD, Ph.D., Chief Medical Officer of Halia Therapeutics. "The recent positive results of our Phase I trial investigating HT-6184 are extremely encouraging and highlight the functional activity of HT-6184 in being able to reduce inflammatory cytokines. As we move into this next stage of clinical testing, we look forward to assessing the potential benefit of our inflammasome inhibitor for MDS patients, as well as for other patients who suffer from inflammation-related diseases."

Halia recently announced Phase I trial results evaluating HT-6184, which was shown to be safe, well tolerated and to significantly reduce NLRP3-inflammatory cytokines in healthy volunteers.

About NLRP3
NLRP3, an innate immune sensor, is activated in response to various pathogenic and sterile stimuli. Activation of NLRP3 triggers the release of the pro-inflammatory cytokines IL-1β and IL-18 and induces a lytic cell death process called pyroptosis. These processes lead to systemic chronic inflammation. Halia’s therapeutic inhibition of NLRP3 prevents the formation of the NLRP3 inflammasome and promotes its disassembly once formed, thereby inhibiting the production and release of IL-1β and IL-18. Persistent activation of the NLRP3 inflammasome is thought to drive the onset and progression of many conditions, including fibrotic, dermatological, and auto-inflammatory diseases. Significant neurodegenerative and neuroinflammatory disorders such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis are also driven by NLRP3 activation. Notably, in recent years, NLRP3 has been discovered and is gaining significance as one of the key biological drivers of ineffective hematopoiesis and inflammation in MDS.

About HT-6184
HT-6184 represents an innovative approach as it is the first drug candidate to target the protein NEK7 through an allosteric mechanism. NEK7 is an essential component of the NLRP3 inflammasome and is critical for its assembly and the maintenance of NLRP3 activity. In preclinical models, Halia has shown that inhibiting the ability of NEK7 to bind to NLRP3 leads to a disruption in the formation of the NLRP3 inflammasome complex, thereby inhibiting the signaling from the inflammasome and reducing the inflammatory response. Preclinical models also showed that in addition to disrupting the formation of the NLRP3 inflammasome, HT-6184 promotes the disassembly of the inflammasome once activated.