On November 3, 2023 Fulgent Genetics, Inc. (NASDAQ: FLGT) ("Fulgent" or the "Company"), a technology-based company with a well-established clinical diagnostic business and a therapeutic development business, reported data from two poster presentations being presented tomorrow, November 4, 2023, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting in San Diego, CA (Press release, Fulgent Genetics, NOV 3, 2023, View Source [SID1234636929]).

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"These data support our mission to build a holistic platform to provide comprehensive solutions and services across the cancer care continuum, including early detection, diagnostics, and monitoring, as well as drug discovery and development," said Ming Hsieh, Chairman and CEO of Fulgent Genetics and co-founder of Fulgent Therapeutics. "We see strong momentum in our precision diagnostics business as a driver of core revenue, and we are encouraged by the steady progress of our therapeutic development for FID-007 in oncology indications."

The poster titled, "Critical clinical evaluation of plasma to tumor tissue concordance by cancer type using Illumina’s cell-free ctTSO500 commercial liquid biopsy assay," explores the critical role of comparing ctDNA variants detected in plasma with those found in tissue, shedding light on the practical implementation of liquid biopsy technology. The research presents a meticulous analysis of plasma-to-tissue concordance across various cancer types, offering valuable insights into the considerations for validation, using Illumina’s cutting-edge ctTSO500 commercial liquid biopsy assay. The clinical research findings, based on a comprehensive examination of 124 cases across different cancers, reveal significant concordance variations, often linked to the cancer stage and the timing of biopsy and blood sample collection. In uterine cancers, the researchers detected 65.9% of the SNV/indel variants in plasma that were also in FFPE, 47% in colon cancer, 67% in gastric cancer, 56% in bladder cancer, 51% in larynx cancer, and 41% in prostate. The study calls for the involvement of certified labs, highlighting the need for stringent quality management and regulatory alignment. The research ultimately underscores the reproducibility, sensitivity, and practical importance of Illumina’s ctTSO500 liquid biopsy, particularly for patients who either cannot or prefer not to undergo traditional solid biopsies for cancer screening.

The poster titled, "FID-007: Nanoencapsulated Paclitaxel Derived from a Novel Nano-Drug Delivery Platform," highlights progress for Fulgent Pharma’s lead therapeutic oncology candidate, FID-007, in various cancers. Similar to data presented at the ASCO (Free ASCO Whitepaper) Annual Meeting in June, of 40 evaluable patients with weekly dose levels from 15 mg/m2 to 160 mg/m2, 7 (18%) had a partial response (PR) by RECIST 1.1 (pancreatic, biliary tract, and HNSCC) and 14 (35%) had stable disease. Three out of 4 HNSCC patients with PR had previously been treated with taxane. The duration of follow-up (months), median (range) is 12.0 (0.4 – 38.9). No high-grade neuropathy has been noted to date. Preliminary clinical data suggests FID-007 may have anti-tumor activity in heavily pre-treated patients across various tumor types. Based on the lack of adverse events, pharmacokinetics, and early indications of treatment effect, 125 mg/m2 has been chosen as the recommended Phase 2 dose. In addition, subgroup analysis based on 7 patients for Head and Neck cancer and 4 patients for Ampullary/Pancreatic cancer showed 57% and 50% objective response rate, respectively.

The posters will be available on the Investor Relations section of the company’s website at View Source

About FID-007

FID-007 consists of paclitaxel encapsulated in a polyethyloxazoline (PEOX) polymer excipient designed to enhance PK, biodistribution, and tolerability. In addition to allowing the drug to remain in solution until it can enter a cancer cell, the PEOX nanoparticle is designed to preferentially deliver paclitaxel to the tumor through the leaky hyperpermeable vasculature.

On November 3, 2023 SQZ Biotechnologies Company (OTC: SQZB), focused on unlocking the full potential of cell therapies, reported clinical data for three programs focused on the treatment of Human Papillomavirus 16 positive (HB16+) driven cancers at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting 2023 (Press release, SQZ Biotech, NOV 3, 2023, View Source [SID1234636928]).

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"Our programs have shown a favorable safety profile and the ability to effect clinical benefit for patients," said Howard Bernstein, M.D., Ph.D., Interim Chief Executive Officer and Member of the Board of Directors. "While these results are early, the management team and the board of directors are encouraged by the potential of Cell Squeeze based therapeutics and are committed to exploring strategic alternatives for the company and its proprietary technology."

Key findings:

SQZ Activating Antigen Carriers ("AAC") Platform in Oncology
Poster# 693: SQZ-AAC-HPV-101: Initial data from a phase I dose escalation/expansion study of SQZ-AAC-HPV, a red blood cell-based therapeutic cancer vaccine for HPV16+ solid tumors

Of the five patients treated, one patient experienced a confirmed complete response and two patients experienced stable disease
SQZ-AAC-HPV monotherapy is considered generally safe and well-tolerated at all dose levels
SQZ Enhanced Antigen Presenting Cell ("eAPC") Platform in Oncology
Poster# 692: COMMANDER-001: Safety data from a phase I/II dose escalation/expansion study of SQZ-eAPC-HPV, a cell-based mRNA therapeutic cancer vaccine for HPV16+ solid tumors

Completed enrollment for highest-dose cohort of monotherapy dose escalation trial
Observed BOR of Stable Disease in 40 Percent (8 of 20) of Treated Patients
SQZ-eAPC-HPV monotherapy is considered generally safe and well-tolerated at all dose levels
SQZ Antigen Presenting Cell ("APC") Platform in Oncology:
Poster# 594: SQZ-PBMC-HPV-101: Increased overall survival in a subset of patients with recurrent, locally advanced, or metastatic HPV16+ tumors treated with cell-based vaccine, SQZ-PBMC-HPV

A subset of patients with paired biopsies (6 of 18) showed increased CD8 T cell infiltration when compared to baseline
These patients with increased CD8 T cell infiltration demonstrated an improved overall survival ("OS") when compared to patients with decreased CD8 T cell infiltration
Median OS [95% CI) for Increase in CD8: 606.5 days [314.0, 713.0] compared to median OS [95% CI) for Decrease in CD8: 170.0 days [54.0, 220.0]
SQZ-PBMC-HPV monotherapy is considered generally safe and well-tolerated at all dose levels
About Human Papillomavirus Positive Cancers

Human papillomavirus (HPV) is one of the most common viruses worldwide and certain strains persist for many years, often leading to cancer. According to the Centers for Disease Control (CDC), in the United States HPV+ tumors represent 3% of all cancers in women and 2% of all cancers in men, resulting in over 39,000 new cases of HPV+ tumors every year. HPV infection is larger outside of the U.S., and according to the International Journal of Cancer, HPV+ tumors account for 4.5% of all cancers worldwide resulting in approximately 630,000 new cases every year. According to the CDC, HPV infection plays a significant role in the formation of more than 90% of anal and cervical cancers, and most cases of vaginal (75%), oropharyngeal (70%), vulval (70%) and penile (60%) cancers.

On November 3, 2023 Flare Therapeutics Inc., a clinical-stage biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, reported molecular real-world data (RWD) demonstrating that high PPARG expression in patients with MIUC is associated with an immunosuppressive tumor microenvironment (TME) and shorter real-world progression-free survival to anti-PD1 treatment (Press release, Flare Therapeutics, NOV 3, 2023, View Source [SID1234636927]). The translational data were shared at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 38th Annual Meeting (SITC) (Free SITC Whitepaper) 2023 taking place November 1-5, 2023 in San Diego, California.

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"While immunotherapy approvals have changed the treatment landscape for MIUC, approximately 70% of patients will still succumb to refractory or acquired resistance," said Michaela Bowden, Ph.D., Chief Development Officer at Flare Therapeutics. "These results offer a unique opportunity to further investigate an immune-mediated mechanism of action for FX-909 with potential to combine with an anti-PD1 agent."

In the poster presentation titled, "PPARG amplification is associated with lack of response to anti-PD1 in Muscle-Invasive Urothelial Cancer," molecular RWD, comprising 1,393 genomic and/or transcriptomic profiles from MIUC patients were utilized to evaluate baseline PPARG expression and amplification associated with anti-PD1 response in MIUC patients. Additional key takeaways are as follows:

Higher PPARG expression and PPARG amplification are negatively correlated with PD-L1 expression in MIUC.
Tumors with elevated PPARG levels and PPARG amplification exhibited a suppressive immune phenotype, typified by an inverse association with CD8+ T cell infiltration.
PPARG amplification is significantly associated with shorter real-world Progression Free Survival to anti-PD1.
FX-909, a first-in-class covalent PPARG inhibitor, entered the clinic this year and is currently being evaluated in a Phase 1 study. The data presented today suggest that FX-909 in combination with ICI agents could potentially provide a new therapeutic strategy that helps MIUC patients with high PPARG expression overcome resistance to immunotherapy.

About FX-909
Flare Therapeutics’ lead investigational compound, FX-909, is a first-in-class novel, highly potent and selective small molecule that inhibits the transcription factor peroxisome proliferator-activated receptor gamma (PPARG) to treat patients with the luminal subtype of advanced urothelial carcinoma (UC) and potentially other solid tumors. Preclinical data for FX-909 has demonstrated robust anti-tumor activity, excellent PK/PD correlation, durable efficacy, and a favorable safety profile in mouse models of UC (PPARG-amp and RXRA-mut) at very low oral doses.

About the FX-909 Phase 1 Study
The ongoing phase 1 study is a first-in-human, dose-escalation and -expansion study of FX-909 in patients with advanced solid malignancies, including advanced urothelial carcinoma. The study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical activity of FX-909. FX-909 will be given initially in a dose-escalation phase (Part A) to determine the recommended phase 2 dose. FX-909 will be given initially orally once daily in 28-day cycles. Part B will be a monotherapy expansion phase to further evaluate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of FX-909 in patients with locally advanced (unresectable) or metastatic urothelial carcinoma. Additional information on this clinical trial can be found on www.clinicaltrials.gov (NCT05929235).

About Advanced Urothelial Carcinoma (UC)
In 2020, there were an estimated 725,549 people living with bladder cancer in the United States alone, making it the sixth most common cancer overall, and fourth most common among men (SEER – 2020). Each year, there are more than 83,000 new cases diagnosed among men and women, and about 25% of those cases are classified as muscle-invasive UC (DRG 2020). Advanced UC has high rates of recurrence, where treatment outcomes have remained poor with typical five-year survival rates of 8% in advanced metastatic disease (SEER – 2020). The transcription factor peroxisome proliferator-activated receptor gamma (PPARG) is associated with the luminal lineage subtype reflecting approximately 65% of all advanced UC cases (Robertson, Cell 2017). Recurrent genetic alterations in PPARG are characteristic of this molecular subtype.

On November 3, 2023 Verismo Therapeutics, a clinical-stage CAR-T company developing novel KIR-CAR platform technology reported that it will be presenting at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting (SITC 2023), to be held in San Diego and virtually November 1-5, 2023 (Press release, Verismo Therapeutics, NOV 3, 2023, View Source [SID1234636926]).

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Presentation Details

Title: Preclinical potency assessment of SynKIR-110, a mesothelin-specific KIR-CAR T cell therapy for mesothelioma
Abstract Number: 321
Date and Time: Friday, November 3rd: 12:00-1:30 p.m. and 5:10-6:40 p.m.
Presenting Authors: Dr. Jun Xu, PhD & Dr. Laura Johnson, PhD
Description: We conducted in vivo potency studies to assess the impact of the engineered T cell dose of the first mesothelin (MSLN)-specific KIR-CAR T cell therapy (SynKIRTM-110) in an NSG mouse xenograft model of human mesothelioma. Our data demonstrate for the first time that anti-tumor efficacy of SynKIRTM-110 is dose-dependent with greater potency compared with MSLN-41BBz CAR T cells previously evaluated in the clinic. This enhanced potency of SynKIRTM-110 was observed both at the primary tumor site and metastatic sites as demonstrated by histopathologic analysis. This increased potency did not impact any serum markers of toxicity, which remained the same regardless of CAR/KIR-CAR treatments. This data supports further clinical development of SynKIRTM-110 in patients with advanced solid tumors. SynKIRTM-110 is currently being investigated in a Phase I clinical trial STAR-101 (NCT05568680).

About the KIR-CAR Platform
The KIR-CAR platform is a dual-chain CAR T cell therapy and has been shown in preclinical animal models to be capable of maintaining antitumor T cell activity even in challenging solid tumor environments. DAP12 acts as a novel costimulatory molecule for T cells using additional T cell stimulating pathways, further sustaining chimeric receptor expression and improving KIR-CAR T cell functional persistence. This continued T cell function and persistence can lead to ongoing regression of solid tumors in preclinical models, including those resistant to traditional CAR T cell therapies. The KIR-CAR platform is being investigated in combination with additional emerging technologies.

On November 3, 2023 Actym Therapeutics, pioneering a new drug modality to treat solid tumors, reported that it will present preclinical data of its lead asset, ACTM-838, in a poster presentation at the 2023 38th Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in San Diego, California (Press release, Actym Therapeutics, NOV 3, 2023, View Source [SID1234636925]). The presentation will feature data examining the tumor-specific enrichment and payload delivery of ACTM-838 in multiple tumor models.

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"Utilizing genetically modified bacteria to elicit a potent and comprehensive immune response has the potential to bring a new level of therapeutic impact to cancer patients across multiple solid tumor types," said Dr. Christopher D. Thanos, President, CEO, and Co-founder of Actym. "The data presented at this year’s SITC (Free SITC Whitepaper) Meeting highlights ACTM-838’s ability to specifically accumulate in the tumor microenvironment and deliver two potent engineered payloads. We believe that these results further validate our scientific approach and provide a strong rationale to advance our candidate into the clinic."

ACTM-838 is a novel immunotherapy designed to locally deliver engineered IL-15 (IL-15plex) and engineered STING (eSTING) payloads to phagocytic tumor-resident myeloid cells to induce a durable anti-tumor immune response, following intravenous administration. The data that will be presented demonstrates specific uptake by tumor-resident myeloid cells in a mouse model of breast cancer, leading to the expression of IL-15plex and eSTING in the tumor microenvironment (TME), with no evidence of payload expression in other tissues. TME-specific payload delivery and efficacy was also observed in a mouse breast cancer model of metastatic disease. Actym will also show that treatment with ACTM-838 induces tumor-antigen-specific cytolytic T cells and effector T cells. Furthermore, Actym will show that in healthy human donor cells, ACTM-838 treatment results in significantly lowered inflammatory cytokines than a control strain lacking ACTM-838’s genetic modifications. Patient tumor database analysis revealed numerous tumor types that have both an adenosine pathway signature for tumor-specific enrichment, and a tumor-associated myeloid cell signature for payload delivery, by ACTM-838. In addition to demonstrating compelling efficacy characteristics, intravenously administered ACTM-838 exhibits a strong safety profile in mice and non-human primates with a first-in-human clinical trial planned in Australian cancer patients in early 2024.

SITC Poster Presentation details:

Abstract Title: PK/PD biomarker analysis to assess tumor-specific enrichment and payload delivery of ACTM-838, a microbial-based immunotherapy
Abstract number: 408
Presenter: Dr. Akshata Udyavar
Location: Ground Level – Exhibit Halls A and B1 – San Diego Convention Center
Date/Time: Saturday, November 4, 11:55 AM – 1:25 PM and 7:00 PM – 8:30 PM (PST)