On April 12, 2021 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that its collaborators presented positive preclinical data for the combination of TUSC2 immunogene therapy (REQORSA) in combination with chemotherapy and immunotherapies for the treatment of non-small cell lung cancer (NSCLC) (Press release, Genprex, APR 12, 2021, View Source [SID1234577930]). Collaborators also presented positive preclinical data for the use of REQORSA in combination with targeted therapies for the treatment of NSCLC. These data were presented in two presentations at the 2021 American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting. The TUSC2 gene is a tumor suppressor gene and is the active agent in REQORSA.

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"We are pleased to have these positive data that provide further support for the therapeutic potential of REQORSA in combination with immunotherapies and targeted therapies in NSCLC presented before an audience of the world’s leading cancer researchers. These data are particularly encouraging as we look to initiate our upcoming combination Acclaim-1 and Acclaim-2 clinical trials of REQORSA in NSCLC," said Rodney Varner, President and Chief Executive Officer of Genprex. "We know that many patients inevitably develop resistance to immune checkpoint blockade therapy or EGFR-TKI therapy. These data show that REQORSA in combination with immunotherapies and targeted therapies may provide enhanced efficacy in NSCLC that has become resistant to these regimens, offering hope to a large patient population who currently has limited treatment options."

Featured Genprex-supported posters presented at AACR (Free AACR Whitepaper) 21 include:

Oral Presentation
Session:

MS.IM02.02 – Overcoming Resistance in the Tumor Microenvironment: Novel Immunomodulatory Agents

Title:

"TUSC2 immunogene therapy enhances efficacy of chemo-immune combination therapy and induces robust antitumor immunity in KRAS-LKB1 mutant NSCLC in humanized mice"

Poster Number/Channel:

#76/Channel 03

Presentation Date/Time:

April 10, 2021 from 2:50-3:00 p.m. ET

Presenters:

Ismail M. Meraz, Mourad Majidi, RuPing Shao, Feng Meng, Min Jin Ha, Elizabeth Shpall, Jack A. Roth. University of Texas MD Anderson Cancer Center, Houston, TX

Poster Presentation
Session:

PO.ET03.01 – Drug Resistance in Molecular Targeted Therapies

Title:

"Overcoming resistance to osimertinib by TUSC2 gene therapy in EGFR mutant NSCLC"

Poster Number:

#1105

Presentation Date/Time:

April 10, 2021 from 8:30 a.m. – 11:59 p.m. ET

Presenters:

Ismail M. Meraz, Mourad Majidi, RuPing Shao, Lihui Gao, Meng Feng, Huiqin Chen, Min Jin Ha, Jack A

The first presentation, entitled "TUSC2 immunogene therapy enhances efficacy of chemo-immune combination therapy and induces robust antitumor immunity in KRAS-LKB1 mutant NSCLC in humanized mice," showed that the triple combination of chemotherapy, immunotherapy (immune checkpoint blockade) and REQORSA demonstrated strong antitumor efficacy and induced robust antitumor immunity in KRAS-LKB1 (KL)-mutant NSCLC in clinically relevant humanized mice models.

In this study, researchers evaluated the antitumor immune response of a chemo-immunotherapy combination with REQORSA on highly metastatic KL-mutant human lung cancer in humanized mice. Humanized mice were first treated with REQORSA, immunotherapy nivolumab (Opdivo), or the combination. The results showed synergistic antitumor activity with the combination. Next, humanized mice were treated with REQORSA, immunotherapy pembrolizumab (Keytruda), or the combination. When REQORSA was added to the chemotherapy and immune checkpoint blockade combination, metastases regression was significantly greater than either REQORSA, REQORSA and pembrolizumab, or chemotherapy and pembrolizumab treatments.

"KRAS is a frequent genomic driver in lung adenocarcinoma," said Michael Redman, Executive Vice President and Chief Operating Officer of Genprex. "LKB1 (also known as STK11) is a distinct subgroup of KRAS-mutants and is the most prevalent genomic driver of resistance to PD-1 blockade in KRAS-mutant lung cancer."

The second poster, entitled "Overcoming resistance to osimertinib by TUSC2 gene therapy in EGFR-mutant NSCLC," showed that REQORSA in combination with targeted therapy osimertinib (Tagrisso) demonstrated synergistic antitumor efficacy in EGFR mutant osimertinib resistant NSCLC tumors in H1975-OsiR isogenic tumors. Researchers also found that the upregulation of PDK1 was associated with osimertinib resistance.

In this study, researchers developed an osimertinib resistant H1975-OsiR isogenic cell line through continuous exposure to osimertinib. Xenograft tumors from both H1975-parental and H1975-OsiR cells were developed in NSG mice and were treated with osimertinib. Synergistic antitumor activity of REQORSA and osimertinib was found in H1975-OsiR tumors. The combinations showed a robust antitumor effect compared with single agent treatment groups. Reverse phase protein array (RPPA) data showed that PDK1 was significantly upregulated in the REQORSA and osimertinib group when compared with either control, osimertinib alone or REQORSA alone treated H1975-OsiR tumors, indicating that PDK1 may be associated with osimertinib resistance. No PDK1 inhibitor effect was found in the REQORSA treated group, implicating the specific role of PDK1 in osimertinib resistance.

These AACR (Free AACR Whitepaper) presentations and posters have been made available on Genprex’s website at www.genprex.com.

On April 12, 2021 InterVenn Biosciences, the leader in glycoproteomics, reported that it has developed a glycoproteomics-based signature that accurately predicts which malignant melanoma patients will respond to checkpoint inhibitor therapy (Press release, InterVenn Biosciences, APR 12, 2021, View Source [SID1234577929]). InterVenn’s assay, performed via blood-based liquid biopsy as opposed to a tumor tissue sample, demonstrated that patients who test positive for the InterVenn signature have a 9-fold higher likelihood of responding to checkpoint inhibitors compared to those who test negative. In a longitudinal study of 36 patients, all of whom received checkpoint-inhibitor therapy, 70 percent of patients who tested positive for the signature remained progression-free at 18 months after treatment initiation, as compared to patients who tested negative, 50 percent of whom showed progression as early as at 1 month. The results were presented in a poster presentation (#387) at the virtual AACR (Free AACR Whitepaper) Annual Meeting 2021: Discovery Science Driving Clinical Breakthroughs.

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Checkpoint inhibitors have proven to be powerful anti-tumor drugs, oftentimes providing long-lasting durable responses and cancer remissions in many indications. However, only approximately 1 in 3 patients will respond, exposing those not deriving any benefit needlessly to potentially serious adverse events. Efforts at finding biomarkers to predict treatment response and guide therapy using DNA-or RNA-based tests have so far had only marginal success. In contrast, InterVenn’s glycoproteomic signature was shown highly effective in identifying patients who will benefit from this therapy, thus potentially avoiding the risk of serious side effects in patients who are unlikely to benefit from these drugs. Further studies are ongoing.

The response-prediction signature was identified using InterVenn’s proprietary, patented foundational technology that leverages artificial intelligence and machine learning for ultra-high-throughput processing of mass spectrometry data to identify and apply glycopeptides as biomarkers for diagnosis and treatment selection. These findings are the latest in a series of developments from InterVenn in advancing the world’s first glycoproteomics-based LDT (Laboratory-Developed Test.) The company’s first diagnostic product, a non-invasive liquid biopsy test for ovarian cancer, will have final data from its initial clinical trial, V.O.C.A.L., in the first half of 2021. InterVenn’s on-site laboratory received CLIA certification in late 2020 to make its tests available to the medical community.

"We are getting closer to realizing the true potential of personalized medicine and to selecting the optimal therapy for each individual patient based on a deep understanding of the biology of their disease," said Klaus Lindpaintner, MD, Chief Scientific and Medical Officer of InterVenn. "By leveraging the power of AI, we have been able to make huge strides in generating and delivering valuable information to physicians to help them guide the care of their patients in ways which, without our powerful platform, have never before been possible."

To find out more about InterVenn Biosciences and how the company is leveraging artificial intelligence and mass spectrometry to the transformation of medical technology, visit View Source For all media inquiries about InterVenn Biosciences, please contact Andrea Vuturo at [email protected]

On April 12, 2021 Schrödinger (Nasdaq: SDGR), whose physics-based software platform is transforming the way therapeutics and materials are discovered, reported that new preclinical data from its CDC7 inhibitor program in a poster session on April 10, 2021, during the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Virtual Meeting (Press release, Schrodinger, APR 12, 2021, View Source [SID1234577928]). The data showed that Schrödinger’s picomolar CDC7 inhibitors were highly selective and inhibited tumor cell growth alone and in combination with several approved and investigational cancer treatments.

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CDC7 is a protein kinase that is required for DNA replication initiation and is involved in DNA replication stress response. CDC7 is thought to be linked to cancer cells’ proliferative capacity and ability to bypass normal DNA damage responses. Targeting proteins that play important roles in DNA replication and replication stress is gaining momentum as a new therapeutic approach based on the proliferative capacity of cancer cells to bypass DNA damage responses.

"Based on our preclinical data, we believe we have identified the most potent CDC7 inhibitors reported to date, capable of inhibiting cell growth and causing programmed cell death in both blood and solid tumors, while sparing healthy cells," said Karen Akinsanya, Ph.D, executive vice president, chief biomedical scientist and head of discovery R&D at Schrödinger. "We’re excited by the rapid progress in our internal pipeline. We look forward to selecting development candidates and moving multiple oncology programs into IND-enabling studies this year."

Additional Details About the Data Presented at AACR (Free AACR Whitepaper)

The presentation, "Discovery of novel CDC7 inhibitors that disrupt cell cycle dynamics and show anti-proliferative effects in cancer cells," highlighted preclinical data with multiple lead molecules discovered by Schrödinger scientists. The company’s CDC7 inhibitor compounds demonstrated dose-dependent picomolar potency as measured by in vitro inhibition of CDC7 enzymatic activity. The compounds were highly selective, inducing apoptosis in cancer cells but not in normal fibroblasts. They also showed synergy with several approved and investigational cancer therapies that modulate apoptosis, DNA repair mechanisms and DNA checkpoints, including venetoclax, olaparib, ceralasertib and adavosertib. Additionally, Schrödinger’s compounds significantly inhibited tumor growth in mouse models of both acute myeloid leukemia and colorectal cancer. Taken together, these data provide further rationale for developing CDC7 inhibitors as a potential therapeutic approach, particularly in combination with existing therapies.

Schrödinger’s MALT1 and Wee1 Programs

Schrödinger is continuing to advance its MALT1 and Wee1 inhibitor programs. Targeting MALT1 is emerging as a potential therapeutic strategy to treat certain relapsed or resistant B-cell lymphomas and chronic lymphocytic leukemia. In December 2020, Schrödinger scientists presented preclinical data at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting highlighting that its MALT1 inhibitors demonstrated anti-tumor activity alone and in combination with approved anti-cancer therapies in models of B-cell lymphoma.

Similar to CDC7, Wee1 targets cancer through replication stress and DNA repair mechanisms. The company has identified highly selective, potent Wee1 inhibitors with optimized drug-like properties, including no observable inactivation of CYP3A4, a key liver enzyme. Lead compounds exhibited favorable pharmacokinetic properties and strong anti-tumor activity in preclinical models.

Based on the strong data generated to date, Schrödinger is on track to move forward with IND-enabling studies for its MALT1, CDC7 and Wee1 programs. Subject to completion of the preclinical data packages, the company expects to submit up to three IND applications in 2022, with the first submission expected in the first half of next year.

Webcast Information

Today at 10:00 a.m. ET, Schrödinger will host a webcast to review the preclinical data presented from its CDC7 program at the virtual AACR (Free AACR Whitepaper) Annual Meeting. The company will also provide an overview of two other internal programs, MALT1 and Wee1, as well as highlight the role of its computational platform in accelerating the discovery of its novel molecules. The webcast will be available under "News & Events" in the investors section of Schrödinger’s website, View Source and will be archived for approximately 7 days.

On April 12, 2021 FairJourney Biologics S.A (FJB) and IONTAS Limited (IONTAS), leaders in the discovery and optimisation of VHH fully human antibodies, reported a collaboration with global immunology company, argenx to harness IONTAS’ proprietary mammalian display technology (Press release, FairJourney Biologics, APR 12, 2021, View Source [SID1234577927]). The goal of the collaboration is to explore diverse panels of novel antibody candidates, with the potential to advance select candidates into the argenx discovery pipeline.

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Under the terms of the agreement, FJB and IONTAS will provide argenx with access to IONTAS’ novel mammalian display technology, which can generate abundant therapeutic antibody leads, selecting for key attributes that may address the novel targets or pathways that argenx is exploring. The agreement will also provide a dedicated full-time FJB/IONTAS team assigned to the project.

FJB/IONTAS and argenx have highly complementary capabilities for identification of potential next-generation antibody candidates, including argenx’s pipeline of investigational immunology therapies aimed at improving the lives of people living with severe autoimmune diseases and cancer. Through its Immunology Innovation Program, argenx collaborates with leading researchers to translate immunology breakthroughs in disease biology into differentiated therapeutic antibodies.

Dr António Parada, CEO at FairJourney Biologics and IONTAS commented: "We have gained considerable experience in antibody discovery through mammalian display for use in generating therapeutics with specific properties.

Additionally, we continue to make improvements to the technology that will allow more diverse applications. We look forward to growing our relationship with argenx and applying our deep knowledge and experience to generate a diverse set of antibodies for potential immunological application."

For further information on mammalian display technology, please visit: fjb.pt/_mammalian-display/

On April 12, 2021 PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to discovering, developing and commercializing highly differentiated medicines for devastating diseases, reported the presentation of a scientific poster detailing additional promising preclinical results for its LYT-210 antibody at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Virtual Meeting (Press release, PureTech Health, APR 12, 2021, View Source [SID1234577926]).

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LYT-210 is a novel, fully human monoclonal antibody (mAb) directed against T cells bearing γδ1 receptors, which are known to suppress the anti-tumor immune response. The new research shared at AACR (Free AACR Whitepaper) demonstrates that LYT-210 is both highly specific and highly potent, rapidly inducing cell death of immune-suppressive γδ1 T cells, while sparing other T cells that play important roles in a healthy immune response. The research was conducted in vitro using both patient blood and cancer tissue. LYT-210 has potential as either a single agent or in combination with checkpoint inhibitors and other anti-cancer treatments.

"The role of γδ1 T cells in cancer immune suppression has come into sharp focus in recent years. We now know that these cells deploy multiple immunosuppressive signals to dampen the anti-tumor response and enable the cancer to grow and spread," said Aleksandra Filipovic, M.D. Ph.D., Head of Oncology at PureTech. "We are excited by these new data demonstrating that our LYT-210 therapeutic candidate can precisely target and swiftly deplete pathogenic γδ1 T cells. We believe that removing these culprits from the tumor microenvironment systemically may have the potential to reawaken the immune system and contribute to a strong anti-tumor response. Moreover, both we and others in the field have established that a heightened presence of pathogenic γδ1 T cells in tumor tissue and blood is correlated with more aggressive disease, poorer response to some therapies and a lower chance of survival. Given those links, we believe that the biomarker-centric approach we are developing as part of our γδ1 T cell program may have the potential to identify and select the patients who are most likely to benefit from LYT-210 in the clinic and beyond."

γδ1 T cells are upregulated in multiple solid tumors including breast cancer, glioblastoma, melanoma and pancreatic cancer. They suppress the immune response through multiple mechanisms, including blocking effector T cells, hindering antigen-presenting dendritic cells, restricting the anti-tumoral activity of γδ2 T cells and attracting tumor-associated macrophages and myeloid-derived suppressor cells to the tumor microenvironment. Pathogenic γδ1 T cells are distinct from cytotoxic γδ T cells, which are being used for adoptive T cell transfer or therapeutic engagement with bispecific antibodies. Depleting pathogenic γδ1 T cells has the capacity to modulate both innate and adaptive immunity, and their distinct phenotypic and functional properties make them excellent potential therapeutic targets.