On April 12, 2023 Synthekine Inc., an engineered cytokine therapeutics company, reported that two poster presentations showcasing its next series of oncology programs will be delivered at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 taking place in Orlando, FL from April 14-19, 2023 (Press release, Synthekine, APR 12, 2023, View Source [SID1234630022]).

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"We are excited to present on two programs from our maturing oncology pipeline at AACR (Free AACR Whitepaper) 2023," said Debanjan Ray, chief executive officer of Synthekine. "We are introducing the clinical trial design for our orthogonal IL-2 and CD19 CAR-T combination therapy, STK-009 + SYNCAR-001. This unique combination pioneers new ground in the field of cytokine supported cell therapy, and is our second oncology program to enter clinical studies, behind STK-012, our alpha/beta-biased IL-2 partial agonist."

Ray continued, "We are also introducing STK-026, our IL-12 partial agonist program, which is currently in IND-enabling studies and shows promise as a potent immunotherapy for the treatment of cancer. Systemically administered wild-type IL-12 has been shown to cause significant toxicity. Our approach with STK-026 leverages Synthekine’s expertise in structural biology, immunology, and protein engineering to bias IL-12 activity and expand the therapeutic index."

Details are as follows and available on the AACR (Free AACR Whitepaper) online itinerary planner:

Title: Trial in Progress: A Phase 1 Study to Evaluate the Safety and Tolerability of a Combination Autologous CD19 CAR T Cell Therapy (SYNCAR-001) and Orthogonal IL-2 (STK-009) in Subjects With Relapsed or Refractory CD19+ Hematologic Malignancies (NCT05665062)
Session Title: Phase I Clinical Trials in Progress
Session Date & Time: Monday Apr 17, 2023 1:30 PM – 5:00 PM ET
Location: Poster Section 46
Poster Board Number: 13
Abstract Number: CT125
Summary: A first-in-human, open-label, dose escalation study of combination SYNCAR-001 + STK-009 in adults with relapsed or refractory (r/r) CD19+ hematologic malignancies (NCT05665062). The objectives of this study are to evaluate the safety, preliminary efficacy, pharmacokinetics, immunogenicity, and pharmacodynamics of SYNCAR-001 + STK-009. Recruitment in the Phase 1 study is underway.

Title: Novel IL-12 Partial Agonist For Cancer Immunotherapy Avoids NK-cell Mediated Toxicity
Session Title: Immunomodulatory Agents and Interventions 2
Session Date & Time: Monday Apr 17, 2023 9:00 AM – 12:30 PM ET
Location: Poster Section 24
Poster Board Number: 5
Abstract Number: 1833
Summary: A novel human IL-12 partial agonist (STK-026) has been designed to more selectively engage antigen activated T-cells and to reduce stimulation of NK cells. In preclinical models, a mouse surrogate of STK-026 retained anti-tumor efficacy without induction of severe toxicities and spike in NK cell activation associated with wild-type mouse IL-12 treatment. Similarly, STK-026 avoided NK hyperactivation on human cells. These data suggest IL-12 partial agonists may represent a novel immunotherapy approach to maintain efficacy while avoiding classical toxicity associated with IL-12 therapy.

Copies of the posters will be available on Synthekine’s website following presentation at the meeting.

On April 12, 2023 Naveris, Inc., a leader in molecular diagnostics for viral cancers, reported the launch of the DART 2.0 prospective clinical trial (NCT05541016) by Mayo Clinic (Press release, Mayo Clinic, APR 12, 2023, View Source [SID1234630021]).

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The DART 2.0 trial will evaluate the ability of NavDx, Naveris’ flagship blood test for tumor tissue modified viral (TTMV)-HPV DNA, to improve treatment selection in patients with HPV-driven head and neck cancer. NavDx provides a non-invasive and precise method for monitoring molecular residual disease (MRD) and recurrence by analyzing tumor-derived viral DNA in patients’ blood samples.

Barry M. Berger MD, Chief Medical Officer of Naveris, added, "This trial will build upon the validation of NavDx as a valuable tool for assessing the risk of post-treatment cancer recurrence in these patients, enabling earlier detection of recurrence and application of therapeutic interventions."

Head and neck cancer is a significant health concern worldwide, with HPV-driven head and neck cancer being the fastest growing type of this cancer. NavDx has the potential to improve outcomes for patients by enabling physicians to select the best treatment options for each individual patient, with the goal of improving patient outcomes while reducing the side-effects and morbidity of medical treatment.

"This clinical trial represents a significant step forward in personalized medicine for head and neck cancer patients," said Piyush B. Gupta PhD, Founder and CEO of Naveris. "NavDx has the potential to be a game-changer in treatment selection, allowing physicians to tailor treatment plans to individual patients based on their unique biomarker profiles."

DART 2.0 builds upon the results of the previously reported phase III MC1675 DART clinical trial, where NavDx-detected molecular residual disease (MRD) was a significant risk factor for cancer recurrence in patients with head and neck cancer. The presence of MRD, both post-operatively and at 3 months post-treatment, was strongly associated with shorter progression-free survival. The MC1675 trial results were presented at the ASTRO 2022 annual meeting.

For more information on NavDx and the DART 2.0 clinical trial please visit ClinicalTrials.gov, NCI and Naveris.

On April 12, 2023 ESSA Pharma Inc. ("ESSA", or the "Company") (NASDAQ: EPIX), a clinical-stage pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, reported that the Company has entered into a clinical trial support agreement (the "Agreement") with Janssen Research & Development, LLC ("Janssen") to enable evaluation of ESSA’s first-in-class N-terminal domain androgen receptor inhibitor, EPI-7386, in combination with apalutamide as well as the combination of EPI-7386 with abiraterone acetate plus prednisone in patients with prostate cancer (Press release, ESSA, APR 12, 2023, View Source [SID1234630020]).

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Under the terms of the Agreement, ESSA will sponsor and conduct a Phase 1 clinical trial evaluating the safety, pharmacokinetics, drug-drug interactions, and preliminary anti-tumor activity of EPI-7386 when administered in combination with either apalutamide or abiraterone acetate plus prednisone. Janssen will supply apalutamide and abiraterone acetate. ESSA will retain all rights to EPI-7386.

Cohort A of the Phase 1 clinical trial will assess EPI-7386 in combination with abiraterone acetate plus prednisone in patients with metastatic castration-resistant prostate cancer ("mCRPC") and high-risk metastatic castration-sensitive prostate cancer ("mCSPC"). Cohort B is a Window of Opportunity study in which patients with non-metastatic CRPC will receive up to 12 weeks of single agent EPI-7386 before adding standard-of-care apalutamide.

"We are pleased to have this agreement in place in order to further investigate EPI-7386 in combination with apalutamide and abiraterone acetate plus prednisone in a variety of prostate cancer patient populations," said David R. Parkinson, President and Chief Executive Officer of ESSA. "Preliminary clinical data from EPI-7386 combination studies with standard-of-care antiandrogens in mCRPC patients have shown a favorable safety profile and encouraging early signs of anti-tumor activity. We look forward to examining EPI-7386 with apalutamide and abiraterone acetate with prednisone in additional prostate cancer populations to assess the safety, tolerability, optimal dose(s) and preliminary anti-tumor activities of these approaches."

About EPI-7386
EPI-7386 is an investigational, highly-selective, oral, small molecule inhibitor of the N-terminal domain of the androgen receptor. EPI-7386 is currently being studied in a Phase 1 clinical trial (NCT04421222) in men with castration-resistant prostate cancer ("CRPC") whose tumors have progressed on standard-of-care therapies. The U.S. FDA has granted Fast Track designation to EPI-7386 for the treatment of adult male patients with mCRPC resistant to standard-of-care treatment. ESSA is also conducting a Phase 1/2 clinical trial (NCT05075577) of EPI-7386 in combination with enzalutamide in metastatic CRPC patients who have not yet been treated with second-generation antiandrogen therapies. ESSA retains all rights to EPI-7386 worldwide.

On April 12, 2023 ImaginAb Inc., a global biotechnology company developing 89Zr crefmirlimab berdoxam (CD8 ImmunoPET) imaging agent and radiopharmaceutical therapies (RPT), reported the execution of a new non-exclusive License and Supply Agreement with Leucid Bio (Leucid), a biotech company pursuing a differentiated approach to develop next generation Chimeric Antigen Receptor T-cell (CAR-T) therapies using the Company’s proprietary Lateral CAR Platform (Press release, ImaginAb, APR 12, 2023, View Source [SID1234630019]).

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Under the terms of the agreement, ImaginAb will license and supply clinical doses of ImaginAb’s investigational CD8 ImmunoPET tracer, 89Zr crefmirlimab berdoxam, to Leucid for use in its basket study in solid tumors, with LEU011 targeting NKG2DL, Autologous CAR T-cells.

Ian Wilson, Chief Executive Officer of ImaginAb, said: "We are delighted that Leucid Bio will use our investigational CD8 ImmunoPET for the first time in conjunction with CAR-T therapies. This agreement with Leucid Bio is an opportunity for ImaginAb to continue expanding our partnerships and showcases the increasing adoption of our CD8 ImmunoPET technology."

Artin Moussavi, Chief Business Officer of Leucid Bio, commented: "This is an exciting partnership for Leucid as this cutting edge technology will provide evidence of the biodistribution of LEU011 CAR T-cells. This will be the first time this technology will be used in a solid tumor CAR-T clinical setting allowing Leucid to generate data that demonstrates the tracking of LEU011 to tumor sites in the first phase of the trial. This data would validate, in humans, the significant improvements already demonstrated with LEU011 in preclinical studies.

On April 12, 2023 Byondis B.V., an independent, clinical-stage Dutch biopharmaceutical company creating precision medicines, reported that Molecular Cancer Therapeutics (an American Association for Cancer Research (AACR) (Free AACR Whitepaper) journal) has published encouraging preclinical data on its investigational, next generation antibody-drug conjugate (ADC) BYON3521 (Press release, Byondis, APR 12, 2023, View Source [SID1234630018]).

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The article, "Preclinical profile of BYON3521 predicts an effective and safe c-MET-antibody-drug conjugate," suggests that BYON3521 has an encouraging safety/efficacy window with potential for clinical benefit in patients. A First-in-Human dose escalation study is currently ongoing to determine the maximum tolerated dose and recommended dose for expansion (NCT05323045). The study is enrolling patients in leading oncology centers in Belgium, Italy, the Netherlands and the United Kingdom.

The data from in vitro and in vivo studies showed that BYON3521 potently and selectively kills tumor cells expressing c-MET, even at low c-MET-expressing levels. In addition, the nonclinical safety evaluation showed that BYON3521 is well tolerated, predicting a substantial clinical therapeutic window.

"The c-MET/HGF pathway is one of the most dysregulated pathways in human solid tumors and is generally associated with a poor prognosis," said Byondis Chief Scientific Officer Wim Dokter, Ph.D. "Being able to use that pathway to deliver clinical benefit to patients will therefore be extra rewarding."

c-MET (also called tyrosine-protein kinase MET [Mesenchymal Epithelial Transition] factor or HGFR [Hepatocyte Growth Factor Receptor]) is a receptor expressed on the surface of epithelial cells of many different organs. Binding of the growth factor HGF to c-MET leads to normal cell division, growth and differentiation, important in the generation of new tissue, e.g., during the development of a fetus, or during growth or wound repair.

But in many tumor cells, c-MET activation is dysregulated: too much c-MET is expressed, c-MET is mutated or c-MET is active even without the binding of HGF. c-MET is overexpressed in a variety of solid tumors, such as renal cell cancer, uveal (ocular) melanoma, non-small cell lung cancer and head and neck squamous cell cancer.

BYON3521, a Next Generation Antibody-Drug Conjugate

BYON3521 is comprised of the humanized IgG1 c-MET-targeting monoclonal antibody, SYD2884, and a cleavable linker-drug called valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA or SYD980). The antibody part of BYON3521 binds to c-MET on the surface of the cancer cell and the ADC is internalized. After proteolytic cleavage of the linker in the lysosome, the inactivated cytotoxin is activated, binds to the DNA and DNA damage is induced, eventually resulting in tumor cell death. BYON3521 is considered a form of targeted chemotherapy.

Byondis’ Distinctive, Proprietary Linker-Drug and Site-Specific Conjugation Technology

BYON3521 incorporates Byondis’ distinctive, proprietary duocarmazine linker-drug (LD) technology ByonZine and its site-specific conjugation technology ByonShieLD. The characteristic design of the selectively cleavable linker connecting the antibody to the duocarmycin drug leads to high stability in circulation and induces efficient release of the cytotoxin in the tumor. Uptake of the activated payload by neighboring tumor cells with lower or no c-MET expression may improve the efficacy potential through the so-called bystander effect.