Genprex to Present at the 11th Annual LD Micro Main Event

On December 3, 2018 Genprex, Inc. (NASDAQ: GNPX), a clinical-stage gene therapy company developing a new approach to treating cancer based upon a novel proprietary technology platform, reported that its Chairman and Chief Executive Officer, Rodney Varner, will present at the 11th annual LD Micro Main Event at the Luxe Sunset Boulevard Hotel in Los Angeles, CA (Press release, Genprex, DEC 3, 2018, View Source [SID1234531841]).

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Genprex is scheduled to present on Wed., Dec. 5, 2018, at 10:30 a.m. PST. Genprex management will also attend one-on-one meetings with institutional investors throughout the day.

The LD Micro Main Event is the largest independent conference for small/micro-cap companies and will feature 250 companies presenting to an audience of over 1,200 attendees.

Gamida Cell Reports Immune Reconstitution Data from Completed Phase 1/2 Clinical Study of NiCord® Presented at ASH 2018 Annual Meeting

On December 3, 2018 Gamida Cell Ltd. (Nasdaq: GMDA), a leading cellular and immune therapeutics company, reported translational data showing that recipients who received NiCord, an investigational cell therapy in Phase 3 clinical development for allogeneic hematopoietic stem cell (bone marrow) transplant had rapid and robust reconstitution of key immune cells (Press release, Gamida Cell, DEC 3, 2018, View Source [SID1234531840]). Successful immune reconstitution is an important factor in the recovery of patients undergoing bone marrow transplant. These translational data from the completed Phase 1/2 study of NiCord were presented in a poster session during the American Society of Hematology (ASH) (Free ASH Whitepaper) 2018 Annual Meeting being held December 1-4 in San Diego, CA.1

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"Immune reconstitution following transplantation is critical for disease and viral control, but historically cord blood transplantation has had limitations in timely immune reconstitution in patients," said Jaap-Jan Boelens, M.D., Ph.D., Chief, Pediatric Stem Cell Transplantation and Cellular Therapies Service, Memorial Sloan Kettering Cancer Center. "We were pleased to see that NiCord treatment resulted in rapid and robust immune reconstitution when compared to younger patients who typically achieve more rapid recovery than adults."

Despite the curative potential of bone marrow transplants, it is estimated that more than 40 percent of eligible patients in the U.S. do not receive one for various reasons, including finding a matched donor.2 While umbilical cord blood provides a source of stem cells for patients who do not have a matched related donor, it provides a smaller number of stem cells, which can delay engraftment and put patients at a greater risk for prolonged hospitalizations and life-threatening infections. NiCord is designed to address these limitations by offering a therapeutic dose of expanded cells while preserving the functional characteristics of stem cells.

Data Presented at ASH (Free ASH Whitepaper) 2018
The poster presentation, "Rapid and robust CD4+ and CD8+ T-, NK-, B- and monocyte cell reconstitution after nicotinamide-expanded cord blood transplantation" (Abstract 2123), described early, in-depth immune reconstitution data from the completed Phase 1/2, multicenter clinical study of NiCord as a stand-alone graft after myeloablative therapy in patients with high-risk hematologic malignancies.3 A random subgroup of 27 patients from this study had extensive immune monitoring evaluated throughout the first year after transplant. The primary endpoint was the probability of achieving CD4+ immune reconstitution (>50×106/L) within the first 100 days, and the secondary endpoints included the recovery of B cells, CD4+ T cells and natural killer (NK) cells during the first year after transplantation. These data were compared to cohorts of adolescent and young adults with hematologic malignancies receiving unmanipulated cord blood transplantation (n=27) or unrelated bone marrow transplantation (n=20). Analyses were performed at the University Medical Centre Utrecht, Laboratory of Translational Immunology.

Key findings from the analysis include the following:

91 percent of patients achieved successful immune reconstitution of CD4+ T cells at 100 days after transplantation with NiCord.
Immune reconstitution of T cells was similar in the NiCord group (median age: 41.5 years) compared to the younger cohorts receiving unmanipulated cord blood and unrelated bone marrow (median ages 15.4 and 14.3 years, respectively).
Immune reconstitution of B cells (p = 0.02) and NK cells (p < 0.001) was significantly faster after transplantation with NiCord compared to the other groups.
Immune reconstitution after NiCord transplantation was associated with recovery of a broad spectrum of T cell, B cell and NK cell subsets representing a range of effector functions similar to that observed with other graft sources.
"These data, combined with the clinical data from our Phase 1/2 study of NiCord in patients with high-risk blood cancers, suggest that NiCord has the potential to be an important treatment option for patients undergoing bone marrow transplant," stated Ronit Simantov, M.D., chief medical officer at Gamida Cell. "We are working to advance our NiCord clinical development program and expect to complete patient enrollment in our ongoing Phase 3 study in the second half of 2019."

About NiCord
NiCord, the company’s lead clinical program, is under development as a universal bone marrow transplant solution for patients with high-risk hematologic malignancies. NiCord has been granted breakthrough status by the U.S. Food and Drug Administration, making it the first bone marrow transplant alternative to receive this designation. It has also received U.S. and EU orphan drug designation. A Phase 3 study evaluating NiCord in patients with leukemia and lymphoma is ongoing in the United States, Europe and Asia.4 For more information on NiCord clinical trials, please visit www.clinicaltrials.gov.

NeoImmuneTech Presents Hyleukin-7 and Universal CAR-T Combination Therapy Preclinical Data at ASH Annual Meeting

On December 3, 2018 NeoImmuneTech, Inc., an immunotherapy drug development company focused on advanced cancer treatments, reported the presentation of two preclinical studies supporting the potential of combining Hyleukin-7 with Universal CAR-T (UCART) treatment to enhance and prolong the activity of allogeneic "off-the-shelf" adoptive immunotherapy for the treatment of B cell and T cell lymphomas (Press release, NeoImmuneTech, DEC 3, 2018, View Source [SID1234531839]). The data were presented in an oral presentation and a poster session at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego, CA.

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The two studies, conducted in collaboration with researchers from Washington University in St. Louis, evaluated the effects that Hyleukin-7, a long-acting T cell amplifier, had in combination with different types of UCART treatments. The researchers evaluated Hyleukin-7’s effects on proliferation, differentiation and tumor killing capacity of UCARTs in tumor models of B cell lymphoma and T cell lymphoma. The T cell lymphoma model was a physiologically-relevant patient-derived xenograft (PDX) mouse model of Sézary syndrome (SS), an aggressive and highly-morbid cutaneous T cell lymphoma with no widely-effective treatments.

Hyleukin-7 was shown to dramatically enhance UCART proliferation, persistence and tumor killing in vivo, resulting in enhanced survival in both models. Furthermore, the results suggest that the addition of Hyleukin-7 dramatically increased the activity of UCART treatment and could provide a tunable, clinic-ready "enabling therapy" for suboptimal CART activity in vivo.

"NeoImmuneTech’s Hyleukin-7 has broad potential to strengthen our immune system in its battle against both foreign invaders as well as enemies within, adding a therapeutic effect wherever the body’s T cells are weak or in low numbers," said Se Hwan Yang, Ph.D., Chief Executive Officer of NeoImmuneTech. "These latest experiments in lymphoma models show that Hyleukin-7 may also strengthen and prolong the effects of T cell therapies, such as CAR-T. The beneficial effects of Hyleukin-7 when combined with UCART are highly encouraging, as developing an effective, off-the-shelf and universal CAR-T therapeutic is a major goal for immuno-oncology drug developers. NeoImmuneTech’s main focus is advancing our clinical trials with Hyleukin-7 as efficiently as possible so that we can ultimately deliver it in a timely manner to patients in need."

Dr. John F. DiPersio, M.D., Ph.D., Chief, Division of Oncology and Deputy Director of the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine added: "CAR-T therapies hold a great promise for cancer patients, as well as for other diseases. We have made incredible steps toward creating a universal CAR-T that would highly increase the percent of people that can benefit from this technology, while significantly decreasing the time to treatment and the cost of production. However, a major hurdle that still remains for both current and future CAR-T treatments is the short effective period for these cells in the body. Hyleukin-7 has the potential to boost both the time and the effectivity of CAR-T treatments, and we are looking forward to the continued clinical development of this drug candidate."

Presentation Details:
Abstract number: 340
Title: Modeling Sézary Syndrome for Immunophenotyping and Anti-Tumor Effect of Ucart and Long-Acting Interleukin-7 Combination Therapy
Type: Oral presentation
Time: Sunday, December 2, 2018: 10:15 AM
Location: Room 28D (San Diego Convention Center)

Abstract number: 2199
Title: A Long-Acting Pharmacological Grade Interleukin-7 Molecule Logarithmically Accelerates Ucart Proliferation, Differentiation, and Tumor Killing
Type: Poster presentation
Time: Saturday, December 1, 2018, 6:15 PM-8:15 PM
Location: Hall GH (San Diego Convention Center)

About Hyleukin-7
Hyleukin-7 (rhIL-7-hyFc, NT-I7), an immuno-oncology agent, is a T cell amplifier comprising a covalently linked homodimer of engineered Interleukin-7 (IL-7) molecule, biologically fused with the proprietary long-acting platform – hyFc. IL-7 is known to be a critical factor for T cells, acting to increase both the number and functionality of T cells. Hyleukin-7 could play a pivotal role in reconstituting and reinvigorating T cell immunity in the treatment of patients with cancer and lymphopenia, as well as providing unique opportunities for immuno-oncology (IO) combination strategies. Hyleukin-7 is being developed as an "IO enabling" therapy to harness T cell immunity in combination with current cancer treatments such as anti-PD-(L)1 agents or chemo/radiotherapy. NeoImmuneTech and Genexine, Inc. (Genexine) are collaborating in three Phase 1b/2a clinical trials in advanced solid tumors and glioblastoma in the US and Korea.

Spectrum Pharmaceuticals Announces Positive Results from Phase 2 Trial Evaluating Use of Oral Leucovorin to Potentially Mitigate Mucositis in Patients Treated with FOLOTYN® (pralatrexate)

On December 3, 2018 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in hematology and oncology, reported results from a prospective Phase 2 single-arm, open-label, multicenter clinical trial studying the management of oral mucositis with the use of oral leucovorin (d,l-folinic acid) as adjunct to FOLOTYN (pralatrexate) in patients with hematological malignancies, including PTCL and CTCL (Press release, Spectrum Pharmaceuticals, DEC 3, 2018, View Source [SID1234531838]). These new data were highlighted in a poster presentation at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper).

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Study results with a total of 35 patients demonstrated that use of leucovorin 25 mg tablets by oral administration for two days (a total of six doses [150 mg cumulative weekly dose]), initiated 24 hours after each FOLOTYN dose (30 mg/m2 IV administration, once weekly for six weeks in each cycle) reduced the rate of Grade 2 or greater mucositis significantly, to 5.7 percent (95% CI = 1 – 19%) from historic rate (52%) associated with FOLOTYN use. There were no reports of ≥ Grade 3 oral mucositis. Grade 1 oral mucositis was reported only in 4 (11%) patients. No patient omitted, delayed or reduced FOLOTYN dose due to oral mucositis with adjunct leucovorin therapy. The occurrence of mucositis, an impediment of FOLOTYN, has previously been reported at a rate of 52 percent at Grade 2 or higher in patients undergoing treatment with FOLOTYN in a registration study (PROPEL).1

"Mucositis is a frequent complication of FOLOTYN therapy, which can cause painful inflammation of the digestive tract. It is often managed by omitting, delaying, or reducing the dose of this medication in some patients," said Andrei R Shustov, MD, lead investigator, professor of medicine, hematology, University of Washington School of Medicine, and hematologist, Seattle Cancer Care Alliance. "We are excited about how significantly leucovorin was able to reduce the rate of mucositis in patients and believe this study established the foundation for the potential use of leucovorin as a preventive regimen for FOLOTYN patients."

"While previous studies have established the use of FOLOTYN as an option in relapsed or refractory PTCL patients, mucositis has been an issue that could impact treatment and quality of life," said Francois Lebel, MD, Chief Medical Officer, Spectrum Pharmaceuticals. "This is the first prospective study to suggest that leucovorin may prevent or reduce oral mucositis. These are welcome findings that merit further studies of leucovorin as an adjunct to FOLOTYN so we can one day provide definitive guidance to physicians to help reduce concerns of FOLOTYN treatment delay or discomfort due to oral mucositis."

About FOLOTYN

FOLOTYN, (pralatrexate injection), a folate analogue metabolic inhibitor, was discovered by Memorial Sloan-Kettering Cancer Center, SRI International and Southern Research Institute and developed by Allos Therapeutics. In September 2009, the U.S. Food and Drug Administration (FDA) granted accelerated approval for FOLOTYN for use as a single agent for the treatment of patients with relapsed or refractory PTCL. This indication is based on overall response rate. Clinical benefit such as improvement in progression-free survival or overall survival has not been demonstrated. FOLOTYN has been available to patients in the U.S. since October 2009. An updated analysis of data from PROPEL, the pivotal study of FOLOTYN in patients with relapsed or refractory PTCL, was published in the March 20, 2011 issue of the Journal of Clinical Oncology.

Important FOLOTYN Safety Information

Warnings and Precautions

FOLOTYN may suppress bone marrow function, manifested by thrombocytopenia, neutropenia, and anemia. Monitor blood counts and omit or modify dose for hematologic toxicities.

Mucositis may occur. If greater-than or equal to Grade 2 mucositis is observed, omit or modify dose. Patients should be instructed to take folic acid and receive vitamin B12 to potentially reduce treatment-related hematological toxicity and mucositis.

Fatal dermatologic reactions may occur. Dermatologic reactions may be progressive and increase in severity with further treatment. Patients with dermatologic reactions should be monitored closely, and if severe, FOLOTYN should be withheld or discontinued. Tumor lysis syndrome may occur. Monitor patients and treat if needed.

FOLOTYN can cause fetal harm. Women should avoid becoming pregnant while being treated with FOLOTYN and pregnant women should be informed of the potential harm to the fetus.

Use caution and monitor patients when administering FOLOTYN to patients with moderate to severe renal function impairment.

Elevated liver function test abnormalities may occur and require monitoring. If liver function test abnormalities are greater-than or equal to Grade 3, omit or modify dose.

Adverse Reactions

The most common adverse reactions were mucositis (70%), thrombocytopenia (41%), nausea (40%), and fatigue (36%). The most common serious adverse events are pyrexia, mucositis, sepsis, febrile neutropenia, dehydration, dyspnea, and thrombocytopenia.

Use in Specific Patient Population

Nursing mothers should be advised to discontinue nursing or the drug, taking into consideration the importance of the drug to the mother.

Drug Interactions

Co-administration of drugs subject to renal clearance (e.g., probenecid, NSAIDs, and trimethoprim/sulfamethoxazole) may result in delayed renal clearance.

Alpine Immune Sciences Showcases Key Preclinical Data at 60th American Society of Hematology Annual Meeting and Exposition

On December 3, 2018 Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading immunotherapy company focused on developing innovative treatments for cancer, autoimmune/inflammatory, and other diseases, reported positive results from multiple preclinical studies which were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper)’s (ASH) (Free ASH Whitepaper) 60th Annual Meeting & Exposition in San Diego, CA (Press release, Alpine Immune Sciences, DEC 3, 2018, View Source [SID1234531837]). Oral and poster presentations described promising efficacy of ALPN-101 in preclinical models of acute graft versus host disease (GvHD) and hemophagocytic lymphohistiocytosis (HLH), while a poster presentation described the company’s transmembrane and secreted immunomodulatory protein (TIP/SIP) platform to enhance the activity of engineered T cell therapies for cancer. Additionally, Alpine strengthened its Scientific Advisory Board with the addition of Anne Davidson, MBBS, Professor, Center for Autoimmune, Musculoskeletal, and Hematopoietic Diseases, Feinstein Institute for Medical Research.

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ALPN-101 Preclinical Study Results

Djamilatou Adom, PhD, from the Indiana University School of Medicine laboratory of Sophie Paczesny, MD PhD, and one of Alpine’s collaborators, presented an oral abstract titled, "ICOSL+ Plasmacytoid Dendritic Cells as Biomarker and Inducer of Graft-Versus-Host Disease" (publication #355), highlighting the novel role ICOS ligand (ICOSL) plays in acute GvHD and describing a strong correlation between ICOSL-positive plasmacytoid dendritic cells and the gastrointestinal manifestations of GvHD. In the investigators’ model of GvHD, ALPN-101 significantly improved survival.

"I’m excited about the potential of ALPN-101 in GvHD given its dual CD28/ICOS mechanism of action," said Dr. Paczesny, Professor of Immunology and Pediatrics at Indiana University School of Medicine and lead of the Biomarkers Stem Cell Transplantation Program. "Early biomarker development could identify patients at risk, specifically early quantification of ICOSL+ Plasmacytoid Dendritic Cells frequency may allow for identification of patients at risk of gastrointestinal and support ALPN-101 as an early intervention in this patient population."

In a poster titled, "Therapeutic Candidate ALPN-101, a Dual ICOS/CD28 Antagonist, Potently Suppresses Human/NSG Mouse Xenograft Graft vs. Host Disease (GvHD) in a Dose Ranging Study and Reduces Disease Activity in a Mouse Model of Hemophagocytic Lymphohistiocytosis (HLH)" (publication #2037), ALPN-101 was evaluated in a humanized model of GvHD and an experimental model of HLH. GvHD is a life-threatening disease reflecting immune-mediated attack of recipient tissue by donor T cells and is one of the leading causes of death following allogeneic stem cell transplantation. HLH is a rare, life-threatening inflammatory disease characterized by excessive T cell and macrophage activation. Results showed ALPN-101:

Humanized GvHD Model

Enhanced survival and suppressed disease activity in GvHD, even after administration of only a single dose.
Demonstrated superior efficacy to belatacept, an approved CD28 pathway inhibitor, in survival and disease activity, correlating with better suppression of activated T cells and circulating cytokines.
HLH Model

Reduced CD4+ T cell activation and liver inflammation
Did not appear to affect the activity of viral-specific T cells directed against lymphocytic choriomeningitis virus (LCMV), the virus used to induce the model.
The HLH data were generated in collaboration with the laboratory of Kim Nichols, MD, Director of the Cancer Predisposition Division at St. Jude Children’s Research Hospital. Dr. Nichols noted, "ALPN-101 clearly reduces inflammation in these models, but importantly the activity of viral-specific T cells was preserved, suggesting ALPN-101 may reduce pathogenic, but spare desired, immune responses."

"These results reinforce our confidence in ALPN-101 as a promising therapeutic candidate, not only in GvHD but multiple other autoimmune and/or inflammatory diseases," said Stanford Peng, M.D., Ph.D., Executive Vice President of Research and Development and Chief Medical Officer of Alpine. "We remain on track to initiate a Phase 1 study in the first quarter of 2019."

Transmembrane and Secreted Immunomodulatory Protein (TIP/SIP) Data Presented

A second poster, titled "’Switch’ Transmembrane Immunomodulatory Proteins (TIPs) Consisting of High-Affinity PD-1 Extracellular Domains (PD-1 vIgDs) and Costimulatory Intracellular Domains Potently Enhance the Activity of TCR-Engineered T Cells" (publication #2052), described for the first time an application of Alpine’s variant immunoglobulin domain (vIgD) platform to enhance the activity of engineered T cells (ECTs). Multiple formats were demonstrated, in which vIgDs expressed by TCR and/or CAR-T cells in either transmembrane or secreted forms enhanced their activity as determined by T cell proliferation, cytokine production, and/or target cell killing. Examples included CD86 costimulatory TIPs, PD-L2 checkpoint inhibitory SIPs, and PD-1 "switch" TIPs incorporating costimulatory intracellular signaling domains, using HPV-specific TCRs, as well as HER2- and CD19-specific CARs. Importantly, the success of this work relied upon Alpine’s development of a proprietary transduction vector to achieve high T cell transduction efficiencies.

Dr. Peng added, "Engineered T cell therapies continue to hold great promise but have seemed so far to demonstrate only modest efficacy in solid tumors, possibly due to an immunosuppressive and/or insufficiently immuno-stimulatory tumor environment. These data suggest Alpine’s TIPs and SIPs may represent a next-generation strategy to overcome such obstacles. We look forward to continuing to develop this potential."

Scientific Advisory Board Appointment

Dr. Anne Davidson, MBBS, Professor, Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases and Investigator at the Feinstein Institute for Medical Research, has been appointed to the Alpine Immune Sciences Scientific Advisory Board.

"We are pleased to have Anne join our ranks and lend her considerable expertise to the Alpine Scientific Advisory Board," said Andy Scharenberg, M.D., Chair of the Scientific Advisory Board. "She is a distinguished researcher and investigator, and her deep expertise in autoimmune disease processes will be valuable as Alpine works to advance its novel molecules in its autoimmune and inflammatory programs."

Dr. Davidson is a practicing rheumatologist at North Shore University Hospital and serves as program director of the Rheumatology Fellowship at Northwell Health. She has served on the medical advisory board for the S.L.E. Lupus Foundation and co-chairs a grant review committee for the Lupus Research Alliance. Her accolades include multiple grants from the National Institutes of Health, the Kirkland Scholar Award, the Dubois Award from the American College of Rheumatology, and the American College of Rheumatology Distinguished Investigator Award.

"I am pleased to join the Scientific Advisory Board at this pivotal time as Alpine advances its programs toward the clinic," said Dr. Davidson. "In particular, I am excited by what the ALPN-101 preclinical data has demonstrated to date, and I look forward to working with the team as Alpine explores this novel molecule’s potential application to a wide array of autoimmune disorders."