On June 25, 2020 Cernostics, a leader in the development of AI-driven image analysis technologies for precision medicine testing, reported publication of new clinical results demonstrating further validation of how its TissueCypher diagnostic test predicts future disease progression in patients with Barrett’s Esophagus (BE) (Press release, Cernostics, JUN 25, 2020, View Source [SID1234561465]). (Abstract available here. Full article available via journal subscription.) By identifying "at-risk" patients much earlier than traditional methods, TissueCypher provides actionable results that allow physicians to target early therapeutic interventions to prevent cancer.

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TissueCypher is the first and only precision medicine test designed, developed, and commercialized to predict which patients with Barrett’s Esophagus will progress to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC).

In this study, funded by the NIH/NCI, patients with BE who progressed to HGD or EAC after at least one year following endoscopy (n=58) were matched to patients with BE without disease progression after a median of seven years surveillance (n=210). Results demonstrated that patients classified as high-risk by TissueCypher were at 4.7-fold increased risk for HGD/EAC compared to those classified as low-risk (p<0.0001). Furthermore, this study demonstrated that patients with non-dysplastic BE who TissueCypher scored high-risk progressed to HGD or EAC at a rate of more than 5%/year, which is at least a 10-fold increase in reported progression rates for NDBE, based on large population studies.

In an editorial accompanying the published results, Prasad G. Iyer, MD, MSc, at Mayo Clinic in Rochester, Minnesota, describes TissueCypher as the potential "Holy Grail" for Barrett’s Esophagus. "Identification of those at higher risk may allow either intensive endoscopic surveillance (to detect incident dysplasia/EAC) or proactive EET, whereas surveillance intervals could be lengthened in those at low risk. This risk prediction has been referred to as the ‘Holy Grail’ in BE."

"This is the third independent study showing that TissueCypher gives physicians crucial predictive power beyond expert diagnosis, especially in that difficult subset of patients whose true risk may go unnoticed if we rely solely on traditional methods," said lead author Jon M. Davison, MD, Associate Professor of Pathology at University of Pittsburgh in Pittsburgh, Pennsylvania.

TissueCypher’s unique advantages stem from its patented, AI-based digital platform with multi-channel fluorescence imaging that provides physicians with a more in-depth, accurate, and comprehensive view of each patient’s unique pathology.

"The TissueCypher image analysis platform simultaneously and objectively extracts protein expression information from multiple biomarkers, as well as provides a digital expression of tissue architecture and nuclear morphology," says Vani J.A. Konda, MD, Clinical Director, Center for Esophageal Diseases, at Baylor University Medical Center in Dallas, Texas, and a key opinion leader in the use of imaging and novel screening techniques to improve early detection and treatment. "The information physicians receive is meaningful, accurate, and immediately actionable." Dr. Konda has published extensively on the role of biomarkers for improving risk stratification in patients with Barrett’s Esophagus, including an upcoming review paper in the July 2020 issue of Gastroenterology & Endoscopy News.

Cernostics’ innovative technology is unique in today’s market, because tissue structure is preserved while immune, stromal, stem cell and tumor biomarkers are analyzed – all of which is done by evaluation of standard esophageal pinch biopsies readily available from the endoscopy procedure. Biomarker intensity and spatial relationships within the tissue structure are also analyzed and reported, creating an in-depth picture of the patient’s risk from which the physician can create successful patient management protocols.

TissueCypher has been tested and validated in five independent clinical studies at leading centers around the world, including Cleveland Clinic, University of Pennsylvania Medical Center, Geisinger Health, and Academic Medical Center in Amsterdam. Most recent peer-reviewed results are published currently in the June 2020 issue of the American Journal of Gastroenterology.

Using a pinch biopsy specimen routinely collected by the gastroenterologist during an endoscopy procedure, TissueCypher is easily incorporated into a physician’s current practice. The test requires no additional tools or collection devices, as are needed with other currently available diagnostic options.

About Barrett’s Esophagus

Barrett’s Esophagus (BE) affects more than three million Americans, occurring when chronic exposure to stomach acid causes the esophageal cell lining to deteriorate and undergo changes that can create an environment for cancer. Without treatment, Barrett’s can lead to EC, with a poor 5-year survival of less than 20%. Today, Barrett’s is commonly managed by surveillance, involving regular endoscopic procedures with biopsy, monitoring disease progression, and GERD-related drug therapy to control symptoms and prevent esophageal injury.

On June 25, 2020 IntelGenx Technologies Corp. (TSX-V:IGX) (OTCQB:IGXT) ("IntelGenx" or the "Corporation") reported that the holders ("Debentureholders") of its 8.0% convertible unsecured subordinated debentures due June 30, 2020, originally issued on July 12, 2017 and August 8, 2017 (the "Debentures"), have approved the proposed amendments to the Debentures at the convened meeting of debentureholders held today (Press release, IntelGenx, JUN 25, 2020, View Source [SID1234561466]). As a result, the maturity date of the CDN$7,577,000 principal amount Debentures will be extended from June 30, 2020 to June 30, 2022 and the conversion price will be reduced from CDN$1.35 to CDN$0.50. The changes are expected to be effective as of June 30, 2020.

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As a result of the extension of the maturity date of the Debentures, the previously announced intention to repay the principal on the Debentures in common Shares on June 30, 2020 is no longer required and will not occur.

Listing and Trading Information

The Debentures are listed on the TSX Venture Exchange (the "Exchange") under the symbol "IGX.DB". They will continue to be listed under the symbol "IGX.DB" following the amendments. The Debentures will not trade or be quoted on an accrued interest basis (i.e. they will trade and be quoted on an interest flat basis). All bids, offers and trades in the Debentures must reflect both the capital portion of the Debentures and all accrued interest. The Exchange will not report accrued interest in regard to any trade in the Debentures made through the facilities of the Exchange. The Debentures, which were issued in the minimum principal amount of $1,000 each, will be quoted based on $1,000 principal amounts with all trades being made in multiples of $1,000 principal amounts (excluding any amount for interest). For example, an order to buy $5,000 principal amount will be given as an order to buy 5,000. An order to sell $20,000 principal amount will be shown as an order to sell 20,000. An order for 1,500, for example, is not acceptable since all trades must be made in multiples of $1,000. The minimum trading unit of Debentures is $1,000 principal amount and a board lot of Debentures is $1,000 principal amount.

On June 25, 2020 Aldevron, a leading provider of products and services for the biotechnology industry, reported an agreement with Ziopharm Oncology to produce plasmid DNA for T cell therapy of solid tumors(Press release, Aldevron, JUN 25, 2020, View Source [SID1234561484]). Aldevron has developed the neoGMP service level designed to address this new and rapidly growing market.

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"We are pleased to collaborate with Ziopharm Oncology on their innovative approach to expressing T cell receptors (TCRs) using the Sleeping Beauty non-viral gene transfer system," said Michael Chambers, Aldevron CEO. "Plasmid DNA is a key component in this process and Aldevron’s 22 years of experience enabled us to develop the neoGMP service to support this exciting area of personalized cancer treatment."

"Our strategic collaboration with Aldevron is an important part of our TCR-T therapy, as we advance our clinical programs for solid tumors targeting neoantigens," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of Ziopharm Oncology. "The rapid production of clinical-grade DNA plasmids expressing TCRs within the Sleeping Beauty system will help us achieve our goals of infusing genetically modified T cells to patients with solid tumors."

Under the agreement Ziopharm, based on their analyses of patient tumors, will identify TCRs on a patient-by-patient basis as well as assemble TCRs in a library for use in clinical trials. The company will use Aldevron’s neoGMP service to manufacture multiple DNA plasmids in an expedient, cost-effective manner.

For more information on Aldevron’s neoGMP service please visit aldevron.com/neoGMP.

On June 25, 2020 MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (Code Number: 4875), reported positive preclinical findings published in Frontiers in Immunology regarding the prospect of MN-166 (ibudilast) as an adjunct treatment for glioblastoma (Press release, MediciNova, JUN 25, 2020, View Source [SID1234561500]).

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The publication, entitled "Glioblastoma myeloid-derived suppressor cell subsets express differential macrophage migration inhibitory factor receptor profiles that can be targeted to reduce immune suppression", was a collaborative effort between MediciNova and the Cleveland Clinic, led by Tyler Alban (doctoral candidate) and Dr. Justin Lathia, Co-Director of the Brain Tumor Research and Therapeutic Development Center of Excellence at the Lerner Research Institute, Cleveland Clinic, and Associate Professor, Department of Molecular Medicine at Case Western Reserve University. Dr. Lathia, Dr. Michael Vogelbaum (previously at the Cleveland Clinic, now at Moffitt Cancer Center in Tampa, FL) and colleagues previously reported on findings that GBM patients had higher levels of immune suppressive myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment and they tended to be resistant to and dependent on macrophage migration inhibitory factor (MIF). In this research publication, in collaboration with Dr. Richard Bucala (Yale University), they report the monocytic subset of MDSCs (M-MDSCs) expressed high levels of the MIF cognate receptor CD74 in the tumor microenvironment. This finding is meaningful in that targeting M-MDSCs with ibudilast, a brain penetrant MIF-CD74 interaction inhibitor, resulted in decreased MDSC function and enhanced CD8 T cell activity in the tumor microenvironment. They note that clinical trial results to date suggest that treatment with an immune stimulatory therapy alone is not effective in treating GBM and hypothesized that better clinical outcomes will be seen when an immune stimulatory therapy is combined with ibudilast, which has been shown to reverse tumor-induced immune suppression.

Dr. Justin Lathia commented, "We found that the receptor CD74 may play a greater role in GBM MDSC biology because the subset of MDSCs primarily found in the tumor microenvironment were M-MDSCs, which predominantly express CD74 as a MIF receptor. These findings are significant for treating patients diagnosed with GBM. Among multiple anti-MIF agents we tested, ibudilast was most potent with reducing M-MDSCs. Ibudilast readily crosses the blood-brain barrier, an advantage over other agents, and has a strong safety profile. Our hope is that combining ibudilast and immune stimulatory therapy will translate to decreased disease progression in clinical trials."

Yuichi Iwaki, MD, PhD, President and Chief Executive Officer of MediciNova, Inc., commented, "We have an ongoing clinical trial evaluating MN-166 in combination with temozolomide for the treatment of GBM at the Dana-Farber Cancer Institute, Harvard Medical School. Recently, we expanded our target population to include patients with either recurrent or newly diagnosed GBM. A recently published GBM animal model study showed that median survival was longer in the group treated with MN-166 plus temozolomide than in the group treated with temozolomide alone. The new findings reported by Dr. Lathia and his colleagues may lead to the use of MN-166 as combination therapy with immune stimulatory treatment and may offer a new treatment option to patients with GBM, one of the most serious refractory cancers."

About Glioblastoma

According to the American Association of Neurological Surgeons, glioblastoma is an aggressive brain cancer that often results in death within 15 months of diagnosis. Glioblastoma develops from glial cells (astrocytes and oligodendrocytes), grows rapidly, and commonly spreads into nearby brain tissue. Glioblastoma is classified as Grade IV, the highest grade, in the World Health Organization (WHO) brain tumor grading system. The American Brain Tumor Association reports that glioblastoma represents about 15% of all primary brain tumors and approximately 10,000 cases of glioblastoma are diagnosed each year in the U.S. Despite decades of advancements in neuroimaging, neurosurgery, chemotherapy and radiation therapy, only modest improvements have been achieved and the prognosis has not improved for individuals diagnosed with glioblastoma. Median survival is approximately 11-15 months for adults with more aggressive glioblastoma (IDH-wildtype) who receive standard treatment of surgery, temozolomide, and radiation therapy.

About MN-166 (ibudilast)

MN-166 (ibudilast) is a first-in-class, orally bioavailable, small molecule macrophage migration inhibitory factor (MIF) inhibitor and phosphodiesterase (PDE) -4 and -10 inhibitor that suppresses pro-inflammatory cytokines and promotes neurotrophic factors. Our earlier human studies demonstrated significant reductions of serum MIF level after treatment with MN-166 (ibudilast). It also attenuates activated glial cells, which play a major role in certain neurological conditions. MN-166 (ibudilast)’s anti-neuroinflammatory and neuroprotective actions have been demonstrated in preclinical and clinical studies, which provide the rationale for treatment of amyotrophic lateral sclerosis (ALS), progressive multiple sclerosis (MS) and other neurological diseases such as glioblastoma (GBM), and substance abuse/addiction. MediciNova is developing MN-166 for ALS, progressive MS and other neurological conditions such as degenerative cervical myelopathy (DCM), glioblastoma, substance abuse/addiction, and chemotherapy-induced peripheral neuropathy. MediciNova has a portfolio of patents which covers the use of MN-166 (ibudilast) to treat various diseases including ALS, progressive MS, and drug addiction.

On June 25, 2020 Intensity Therapeutics, Inc., a clinical-stage biotechnology company pioneering a novel, immune-based drug approach to treat solid tumor cancers through direct tumor injection, reported the publication of results from the Company’s nonclinical research in the International Journal of Molecular Sciences (IJMS) (Press release, Intensity Therapeutics, JUN 25, 2020, View Source [SID1234561467]). The paper titled, "Intratumoral Administration of a Novel Cytotoxic Formulation with Strong Tissue Dispersive Properties Regresses Tumor Growth and Elicits Systemic Adaptive Immunity in In Vivo Models," was published in IJMS as part of a Special Issue titled The Immune Landscape in Solid Tumors. The Special Issue addresses various aspects of the molecular and cellular biology of immune cells in the context of tumors and invites experts in the field to contribute an original research article or a comprehensive review. The paper is available online (doi.org/10.3390/ijms21124493).
The paper describes the Company’s lead product candidate, INT230-6, a novel combination of cisplatin and vinblastine formulated with a unique amphiphilic diffusion enhancer molecule (SHAO) that non-covalently interacts with payloads to increase intratumoral (IT) drug dispersion when injected into solid tumors. The data reported demonstrated that INT230-6 achieved greater inhibition of tumor growth and improved survival compared to the same drugs without enhancer given intravenously or IT. INT230-6 treatment increased the number of immune infiltrating cells within injected tumors. Animals demonstrating complete responses developed systemic immunity to the cancer. INT230-6 when combined with anti-programmed cell death protein 1 (PD-1), antibodies resulted in improved survival and increased rate of complete responses. INT230-6 induced significant tumor necrosis, which induced a systemic immune-based anti-cancer attack. This research demonstrates a novel, local treatment approach for cancer that minimizes systemic toxicity while stimulating adaptive immunity.

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"The results reported in the paper provided the pre-clinical rationale to advance INT230-6 into clinical development," said Lewis H. Bender Founder, President and CEO of Intensity Therapeutics and lead author on the paper. "Our clinical research conducted to-date is consistent with the results of this paper; data suggests that the dispersion, tumor-killing and immune activation properties of INT230-6 observed in mice are translating to humans. We are looking forward to initiating phase 2 clinical cohorts later this year combining INT230-6 with our partners’ products, Merck’s pembrolizumab and Bristol Myers Squibb’s ipilimumab, in cancers with high unmet medical need."

About INT230-6

INT230-6, Intensity’s lead proprietary product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRxSM technology platform. The drug is comprised of two proven, potent anti-cancer agents, cisplatin and vinblastine, and a penetration enhancer molecule that helps disperse the drugs throughout tumors for diffusion into cancer cells. In preclinical studies, INT230-6 eradicated tumors by a combination of direct tumor killing, release of tumor antigens and recruitment of immune cells to the tumor. Results generated by both the Company and the National Cancer Institute (NCI) showed treatment with INT230-6 in in vivo models of severe cancer resulted in substantial improvement in overall survival compared to standard therapies. Further, INT230-6 provided complete responses in animals with long-term protection from multiple re-challenges of the initial cancer and resistance to other cancers. The Company’s research published in the International Journal of Molecular Sciences and jointly with the NCI as part of Intensity’s collaborative research, published in July 2019 in the Journal OncoImmunology, also showed strong synergy when INT230-6 was combined with anti-PD-1 and anti-CTLA-4 antibodies. INT230-6 is being evaluated in a Phase 1/2 clinical study (NCT03058289) in patients with various advanced solid tumors. There have been no dose limiting adverse events observed in patients to date, even when dosing into deep tumors in the lung and liver. Several patients demonstrated tumor shrinkage, symptomatic improvement, and evidence of cancer cell death and immune cell activation on tumor biopsy. In combination cohort with pembrolizumab the Company reported the safety of combination was comparable to INT230-6 monotherapy.