On April 22, 2024 Krystal Biotech, Inc. (the "Company") (NASDAQ: KRYS), a commercial-stage biotechnology company, reported that the first patient was dosed in its Phase 1 clinical trial (KYANITE-1) evaluating inhaled KB707, a modified HSV-1 vector designed to deliver genes encoding both human interleukin-12 (IL-12) and interleukin-2 (IL-2) to the lung, for the treatment of patients with locally advanced or metastatic solid tumors of the lung (Press release, Krystal Biotech, APR 22, 2024, View Source [SID1234642213]).

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"Cytokine therapy holds significant potential for the treatment of solid tumors but its utility has been limited by a lack of safe and effective delivery options," said David Chien, M.D., Senior Vice President of Clinical Development at Krystal Biotech. "Cytokine delivery via inhalation is a first-of-its-kind therapeutic approach made possible by the unique attributes of Krystal’s HSV-1-based vector platform. Together with intratumoral KB707, inhaled KB707 has the potential to significantly expand the clinical utility of cytokine therapy to treat a wide range of otherwise difficult-to-treat and standard of care refractory solid tumors. Dosing the first patient in KYANITE-1 is an exciting step toward our goal of delivering a new class of cancer immunotherapies."

The KYANITE-1 clinical trial is an open-label, multicenter, dose escalation and expansion study to evaluate inhaled KB707 monotherapy in patients with advanced solid tumor malignancies affecting the lungs. Details of the KYANITE-1 study can be found at www.clinicaltrials.gov under NCT identifier: NCT06228326.

"Dosing the first patient in our inhaled KB707 trial is another important milestone for our oncology program and for Krystal," said Suma Krishnan, President, Research & Development, Krystal Biotech. "KYANITE-1 is our second active clinical trial evaluating KB707 and along with KB407 and KB408, our inhaled genetic medicine candidates for the treatment of cystic fibrosis and alpha-1 antitrypsin deficiency, respectively, KB707 is our third clinical stage drug candidate delivered via inhalation. With a deep pipeline of active clinical trials, we are looking forward to data readouts starting later in 2024, which we expect will showcase the breadth and potential of our proprietary, HSV-1 based gene delivery platform."

In February 2024, the U.S. Food and Drug Administration (FDA) granted Fast Track Designation for inhaled KB707 for the treatment of patients with solid tumors with pulmonary metastases that are relapsed or refractory to standard of care therapy. This is the second Fast Track Designation for the KB707 program. In July 2023, the FDA granted intratumoral KB707 Fast Track Designation for the treatment of anti-PD-1 relapsed/refractory locally advanced or metastatic melanoma.

About Fast Track Designation
Fast Track Designation is designed to facilitate the development and expedite the review of drugs to treat serious conditions and treat a serious or unmet medical need, enabling drugs to reach patients sooner. Clinical programs with Fast Track Designation may benefit from early and frequent communication with the FDA throughout the regulatory review process, and such clinical programs may be eligible to apply for Accelerated Approval and Priority Review if relevant criteria are met.

About IL-2, IL-12, and KB707
IL-2 and IL-12 are secreted cytokines with complementary functions promoting cell-mediated immunity in humans. Both IL-2 and IL-12 have been shown to elicit anti-tumor immune responses in preclinical models and in clinical settings and have been extensively studied for their potential in cancer immunotherapy. Despite promising signs of efficacy, it has proven difficult to effectively harness IL-2 and IL-12 for therapeutic benefit, as systemic administration is often poorly tolerated, and their inherently short half-lives necessitate high dose levels and extremely frequent dose intervals. KB707 is a modified HSV-1 vector designed to deliver genes encoding both human IL-12 and IL-2 directly to a patient’s tumor(s) and promote systemic immune-mediated tumor clearance. KB707 targets solid tumors that are accessible via intratumoral injection or inhalation.

On April 22, 2024 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a clinical stage biotechnology company whose proprietary INTASYL siRNA gene silencing technology is designed to make immune cells more effective in killing tumor cells, reported it is presenting new data about its lead clinical product candidate, PH-762, an INTASYL compound (Press release, Phio Pharmaceuticals, APR 22, 2024, View Source [SID1234642212]).

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Preclinical studies demonstrate:

PH-762 is rapidly taken up by cells and robustly silences PD-1 mRNA and protein in lymphocytes within the tumor microenvironment (TME)
Intratumoral injection of murine PH-762 (mPH-762) significantly inhibits tumor growth in murine tumor models and is well tolerated
mPH-762-mediated silencing of PH-762 within the TME may generate memory-specific T cells, promoting IFN-γ release in the TME
Studies in non-human primates demonstrate that PH-762 is well-tolerated and does not induce release of cytokines associated with cytokine release syndrome (CRS)
These finding support the ongoing clinical trial of PH-762’s safety and efficacy as a neoadjuvant therapy for treatment of cSCC, melanoma, or Merkel cell carcinoma
The data, authored by Melissa Maxwell, Linda Mahoney, and Dr. Mary Spellman, will be presented at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) on May 8th in Baltimore, Maryland.

Presentation Details are as follows:
Title: INTASYL PH-762: PD-1 Intratumoral Immunotherapy
Abstract Number: 774
Session Title: Cancer-Immunotherapy and Cancer Vaccines
Authors: Melissa Maxwell, Linda Mahoney, Mary Spellman, M.D.
Date and Time: May 8, 2024 12:00 PM
Location: Exhibit Hall

On April 22, 2024 Veracyte, Inc. (Nasdaq: VCYT), a leading cancer diagnostics company, reported that a new study published in JCO Precision Oncology shows that, among patients undergoing Active Surveillance (AS) for prostate cancer, the Decipher Prostate Genomic Classifier is prognostic for identifying those whose disease is likely to progress (Press release, Veracyte, APR 22, 2024, View Source [SID1234642210]). The findings make the Decipher test the only gene expression test to have treatment-outcome data from a prospective, multi-center, phase 2, randomized trial in the AS population.

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Patients whose prostate cancer is found at an early stage and who are clinically low or intermediate risk are commonly offered AS, meaning they are closely monitored rather than undergo intervention such as surgery or radiation. Identifying the optimal candidates for active surveillance, however, is not always easy, as clinical indicators are limited in their ability to identify those who may be at a higher risk of future grade reclassification or cancer progression.

"The findings from the ENACT trial analysis demonstrate that the Decipher Prostate test is a predictor of disease progression on AS," said Elai Davicioni, Ph.D., Veracyte’s medical director for Urology. "These data also further reinforce Veracyte’s commitment to evidence generation that supports the Decipher Prostate test’s ‘Level 1B’ evidence status – the highest among commercially available gene expression tests – in the most recent NCCN Guidelines* for prostate cancer."

The new findings are from the biomarker analysis study of the ENACT clinical trial (NCT02799745) that aimed to compare the efficacy and safety of enzalutamide monotherapy plus AS vs AS alone in patients with low-risk or intermediate-risk prostate cancer. The study included 121 AS patients from the randomized trial who were monitored and followed for 3 years. In the AS alone or control arm, among patients with available tumor samples (n=65), the Decipher Prostate test predicted increased rates of disease progression after adjusting for baseline clinical risk factors (MVA HR [95% CI] per 10% increase in score: 1.17 [1.01 to 1.35]; P = 0.04).

The findings also demonstrated the use of Decipher GRID (Genomic Resource for Intelligent Discovery) as a research tool to help advance scientific understanding of prostate cancer. Specifically, the researchers evaluated whole-transcriptome data derived from Decipher Prostate testing of each sample in the study to assess the Decipher Prostate test and other, research-based biomarkers that could potentially indicate which tumors would be more likely to respond to treatment with enzalutamide, an androgen receptor (AR) signaling inhibitor. They observed that the subset of patients with higher Decipher scores, as well as luminal and high AR activity subtypes, had greater responses to enzalutamide.

"Our Decipher GRID tool enables researchers to analyze whole-transcriptome data for prostate cancer samples to gain further insights about the disease, which can ultimately further improve patient care," said Dr. Davicioni. "This study is a strong example of the Veracyte Diagnostics Platform in action, whereby we use a comprehensive, whole-transcriptome approach to develop a test, which fuels our ability to demonstrate the test’s performance and utility, and also enables new discovery efforts."

About the Decipher Prostate Genomic Classifier

The Decipher Prostate Genomic Classifier is a 22-gene test, developed using RNA whole-transcriptome analysis and machine learning, that helps inform treatment decisions for patients with prostate cancer. The test is performed on biopsy or surgically resected samples and provides an accurate risk of developing metastasis with standard treatment. Armed with this information, the physician can better personalize their patients’ care and may recommend less-intensive options for those at lower risk or earlier, more-intensive treatment for those at higher risk of metastasis. The Decipher Prostate test has been validated in more than 75 studies involving more than 100,000 patients.

About the Decipher GRID

The Decipher GRID database includes more than 200,000 whole-transcriptome profiles from patients with urologic cancers and is used by Veracyte and its partners to contribute to continued research and help advance understanding of prostate and other urologic cancers. GRID-derived information is available on a Research Use Only basis.

On April 22, 2024 Vect-Horus, a privately held biotechnology company that designs and develops molecular vectors that facilitate the targeted delivery of therapeutic molecules and imaging agents, reported the publication of a paper in the open-access scientific journal Pharmaceutics Vol 26 (MDPI) (Press release, Vect-Horus, APR 22, 2024, View Source [SID1234642207]).

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The paper, entitled "LDLR-Mediated Targeting and Productive Uptake of siRNA-Peptide Ligand Conjugates In Vitro and In Vivo", outlines a study which showed how peptides developed by the company, that target the low-density lipoprotein receptor (LDLR) can support delivery of a model short interfering RNA (siRNA), both in vitro and in vivo. Because the LDLR is differentially expressed in organs and is overexpressed in many cancers including glioblastoma multiforme (GBM) and pancreatic ductal adenocarcinoma (PDAC), the results open new opportunities for delivery to different organs or tumors.

A vector belonging to this family of LDLR-targeting peptides is applied as a theragnostic agent for the diagnostic of GBM and PDAC. The agent, currently in early Phase 1 clinical trials, is co-developed with RadioMedix.

"These results reinforce the potential of vectors to significantly improve the transport and delivery of therapeutic and imaging agents to improve the diagnostic and treatment of cancer and CNS disorders," said Alexandre Tokay co-founder and CEO of Vect-Horus. "This provides further impetus to our current partnerships and builds on other recent licensing agreements, with Novo Nordisk and Ionis Pharmaceuticals."

siRNAs are promising therapeutic agents because of their specificity and their potential to modulate gene expression, but their delivery into cells and tissues of interest remains highly challenging due to the lack of efficient and selective delivery systems.

The study identified and optimized a family of peptide-based vectors that target the LDLR. The results validated the LDLR-binding peptides as viable ligands which can trigger efficient delivery of therapeutic oligonucleotides, both in a cellular model and in vivo after systemic administration.

On April 22, 2024 SynOx Therapeutics Limited ("SynOx" or the "Company"), the late-stage clinical biopharmaceutical company, reported the close of a $75m Series B financing (Press release, SynOx Therapeutics, APR 22, 2024, View Source [SID1234642206]). The financing was co-led by Forbion, HealthCap and new investor Bioqube Ventures.

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The proceeds will be used to generate registrational Phase 3 clinical and CMC data for emactuzumab, SynOx’s potentially best-in-class CSF-1(R) inhibiting monoclonal antibody (mAb) for the treatment of Tenosynovial Giant Cell Tumour (TGCT).

TGCT is a type of tumour that affects the soft tissue lining of joints and tendons and is a highly debilitating disease often impacting large, important joints such as the knee, hip and ankle.

TGCT is a chronic disease which often impacts patients throughout their lives. It seriously impacts quality of life by causing significant loss of function of the affected joints, pain, stiffness, and limiting range of motion. While most patients receive surgical intervention, more than 50% of patients with diffuse disease experience tumour recurrence within three years of surgery1..

Emactuzumab is a novel, next-generation CSF-1R mAb with a potentially best-in-class profile. In earlier clinical work in TGCT2. emactuzumab demonstrated substantial clinical activity with an objective response rate (ORR) of 71%, rapid and robust tumour reduction, a long duration of effect, and significant improvements in functional ability. Importantly, these studies also indicated that emactuzumab has good tolerability and a manageable safety profile. SynOx is initiating a Phase 3 trial (TANGENT) to assess the efficacy and safety of emactuzumab in patients with localized and diffuse TGCT.

As part of the Series B financing both Dr Carlo Incerti, M.D., and Jon Edwards, PhD, have joined the Board of Directors. Dr Incerti has more than three decades of experience in the biopharmaceutical industry and brings an extensive track record in global drug development, including from his time at Sanofi Genzyme where he played a leading role in pioneering therapies for rare and genetic diseases. Jon Edwards brings a decade of therapeutic investment expertise and company creation experience, which includes several public listings and multi-billion-dollar acquisitions.

Ray Barlow, Chief Executive Officer of SynOx Therapeutics, said: "This is a transformational time for SynOx. This substantial funding will allow us to generate registrational data for emactuzumab in TGCT. As a highly effective, next-generation therapy with a short treatment cycle, rapid onset and long duration of response, we believe that emactuzumab is differentiated from other agents in development and will provide a much needed and valuable option for patients suffering from this grievous disease."

Dirk Kersten, General Partner at Forbion, commented: "We are pleased to continue to support the SynOx team as it moves emactuzumab through to BLA and MAA submissions in TGCT. As a late-stage company with a clinically de-risked asset, focused on an attractive and underserved market, SynOx is a good example of the type of company Forbion Growth would typically invest in."

Jon Edwards, Bioqube Ventures commented: "We are excited to join the SynOx syndicate and work with this fantastic team and board. We believe this asset has the potential to generate best-in-class data and are excited to help the team develop the product through approval and launch."

Ton Logtenberg, Non-Executive Chair of SynOx Therapeutics, added: "The support of our existing and new investors is validation of SynOx’s strategy and its great potential as a company. I would like to welcome Carlo Incerti and Jon Edwards to the Board of Directors. Their broad experience and knowledge, particularly in driving forward cutting-edge therapies for rare diseases, and executing deals at the highest level, complement the expertise of our existing directors and will be instrumental as we accelerate the late-stage clinical development of emactuzumab."