On June 23, 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 the U.S. Food and Drug Administration (FDA) has reviewed and confirmed all comments have been addressed regarding the Company’s clinical trial protocol for the Acclaim-1 clinical trial, an open-label, multi-center Phase 1/2 clinical trial evaluating the Company’s lead drug candidate, REQORSA Immunogene Therapy, in combination with AstraZeneca’s Tagrisso in patients with late-stage non-small cell lung cancer (NSCLC) whose disease progressed after treatment with Tagrisso (Press release, Genprex, JUN 23, 2021, View Source [SID1234584270]). In January 2020, Genprex received FDA Fast Track Designation for the Acclaim-1 patient population.

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In addition, the Company has engaged its first clinical site for Acclaim-1, and Genprex is continuing to work with a number of other important cancer research centers and academic institutions to select optimal study sites.

"This feedback from the FDA on our Acclaim-1 clinical trial and the engagement of our first clinical site are key milestones for Genprex," said Rodney Varner, President and Chief Executive Officer of Genprex. "We are now looking forward to opening patient enrollment in this important study of this cutting-edge investigational gene therapy to evaluate the role it can play in the fight against lung cancer, the leading cause of cancer deaths worldwide."

The Company expects the Phase 1 portion of the Acclaim-1 trial to enroll up to 18 patients at three clinical sites and for the Phase 2 portion to enroll approximately 74 patients (a 1:1 ratio of REQORSA and Tagrisso combination therapy versus Tagrisso monotherapy) at up to 15 clinical sites. The first part of the Phase 1/2 clinical trial will be a dose escalation study. The primary endpoint of the Phase 2 portion of the trial is progression-free survival, which is defined as time from randomization after first progression on Tagrisso, to first event (second progression) or death. An interim analysis will be performed at 51 events.

Genprex recently announced the Centralized Institutional Review Board (IRB) approval for the Acclaim-1 clinical trial in NSCLC. Additional information about the Acclaim-1 clinical trial can be found by visiting ClinicalTrials.gov.

On June 23, 2021 Genomic Testing Cooperative, LCA (GTC) reported that the New York State Clinical Evaluation Program (CLEP) has completed their evaluation and approved all GTC’s Next Generation Sequencing (NGS) profiling tests for hematologic neoplasms and solid tumors (Press release, Genomic Testing Cooperative, JUN 23, 2021, View Source [SID1234584269]). This includes:

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-GTC Hematology Profile (177 genes)
-GTC Hematology Fusion/Expression (1408 genes)
-GTC Hematology PLUS (177 DNA + 1408 RNA)
-GTC Liquid Biopsy, Hematology Profile (177 genes)
-GTC Solid Tumor Profile (434 genes)
-GTC Solid Tumor Profile Fusion/Expression (1408 genes)
-GTC Solid Tumor PLUS (434 DNS + 1408 RNA)

These tests are also covered by Medicare Administrative Contractor Palmetto GBA (MolDx). The tests are carefully designed to provide cost-effective comprehensive evaluation of clinically relevant molecular abnormalities and biomarkers.

"At GTC, we believe that all patients with cancer have the right to have their cancer fully molecularly profiled and for their physicians to be able to discuss their treatment options prior to initiating therapy. Medicare coverage combined with NY state approval make this testing easily accessible for cancer patients living in NY. Our cooperative (Co-Op) business model enables other laboratories and large oncology practice groups to obtain similar coverage and approval when they internalize our tests" said Dr. Maher Albitar, GTC Chief Executive Officer and Chief Medical Officer. "Our goal is to improve lives of cancer patients by democratizing NGS-based cancer profiling. We continue to collaborate with other Co-Op members to develop and validate new tests to address minimal residual disease, early diagnosis and other specific clinical indications" added Dr. Albitar.

GTC is first-in-class diagnostic company based on a cooperative business model. Using the most recent advances in NGS technology, GTC tests can be performed on minute samples including needle aspiration samples. Analysis of sequencing runs, curating data and interpretation of results is performed using proprietary algorithms/artificial intelligence (AI) software’s specially designed and developed for GTC’s technology. Cancer profiling combining DNA and RNA data is the most thorough approach not only for selecting therapeutic approaches and targeted therapy but also to help in establishing the diagnosis and classification of tumors, prognosis, and determining early relapse risk. GTC Hematology liquid biopsy is especially designed to be comprehensive and to replace the need for performing a bone marrow biopsy, which is a painful procedure and can be associated with complications.

On June 23, 2021 Strand Therapeutics, a privately held developer of next-generation, programmable mRNA therapeutics for cancer immunotherapy and other diseases, reported that the company raised $52 million in an oversubscribed Series A financing round syndicated by Redmile Group, BeiGene, Ltd., and Camford Capital, as well as existing investors Playground Global and ANRI. Strand has raised a total of $66 million to date (Press release, Strand Therapeutics, JUN 23, 2021, View Source [SID1234584268]).

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Founded by leaders in mRNA-based synthetic biology, Strand is creating the first platform for programmable, long-acting mRNA therapeutics that are bioengineered to enable precise control of the location, timing, intensity, and duration of their therapeutic activities. With the company’s self-replicating mRNAs, Strand’s goal is to develop improved treatment options for cancer and other life-threatening diseases.

"As shown with the COVID-19 vaccines, mRNA technology has revolutionized the way we can address diseases. At Strand, we have developed the next generation mRNA drug platform that can transform cancer treatment, cell therapy, and beyond," said Jake Becraft, PhD, co-founder and CEO of Strand. "We’re excited to work with this world-class syndicate of investors to continue our development of novel mRNA therapies and bringing patients more efficacious, accessible, and cost-effective treatments."

The company’s mRNA therapies combine genes for self-replication with genetically programmed logic circuits. By sensing and classifying unique expression signatures of cell types, the breakthrough technology enables precise and controlled delivery of multiple disease treatments in a single mRNA drug.

"While mRNA technologies allow drug development pipelines to move faster, existing platforms are limited due to lack of lasting therapeutic expression and control," said Jory Bell, General Partner at Playground Global and a member of Strand’s Board of Directors. "With the groundbreaking technology of programmable mRNA therapeutics, Strand is set to bring potentially better treatment options to patients that are more effective and less toxic than current standards. We look forward to continuing our work with the incredible team at Strand."

Strand’s initial focus is to develop its self-replicating programmable mRNA therapeutics to treat cancer, with plans to begin clinical trials of its first candidate in 2022. The company is also collaborating with the global biotechnology company BeiGene under a licensing agreement aimed at developing and commercializing Strand’s multi-functional mRNA technology to develop solid tumor immuno-oncology therapeutics.

"With this newest financing, we are well equipped to enable systemic delivery of mRNA to tumor cells and immune cells to tackle solid tumors as well as hematological malignancies," said Tasuku Kitada, PhD, co-founder, President, and Head of R&D at Strand. "The next generation of mRNA therapeutics will require new technology to move beyond vaccines and into cancer and other diseases. Our rapid growth will now accelerate both deeper into cancer immunotherapies, as well as beyond into further areas of high unmet medical need."

On June 23, 2021 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that it has obtained manufacturing and marketing approval for the EZH2 inhibitor "Tazverik Tablets 200 mg" (tazemetostat hydrobromide) in Japan with the indication of relapsed or refractory EZH2 gene mutation-positive follicular lymphoma (only when standard treatment is not applicable) (Press release, Eisai, JUN 23, 2021, View Source [SID1234584266]).

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This approval is based on the results of a multicenter, open-label, single-arm clinical phase II trial (Study 206)1 in Japan conducted by Eisai and other studies2 conducted by Epizyme, Inc. (Headquarters: Massachusetts, United States) outside Japan. Study 206 enrolled patients with EZH2 gene mutation-positive, primarily follicular lymphoma, who had relapsed or were refractory. The primary endpoint of this study was objective response rate (ORR), and secondary endpoints included safety. This study achieved the primary endpoint target and exceeded a prespecified tumor response threshold with statistical significance: ORR in patients with EZH2 mutation-positive relapsed or refractory follicular lymphoma (n=17) was 76.5% (90% confidence interval (CI): 53.9-91.5) as measured by independent review. Treatment-emergent adverse events (incidence of 25% or more) observed in this study were dysgeusia (52.9%), nasopharyngitis (35.3%), lymphopenia (29.4%) and blood creatine phosphokinase increased (29.4%). Eisai will conduct a post-marketing special use results survey (all-case surveillance) in all patients who are administered "Tazverik" until a pre-determined number of patients has been reached in accordance with an approval condition imposed by the MHLW.

Created by utilizing Epizyme’s proprietary product platform, "Tazverik" is a first-in-class small molecule inhibitor of the epigenetic enzyme EZH2. It is one of the histone methyltransferases in the epigenetics-related protein group, and is thought to regulate the expression of cancer-related genes and suppress the growth of cancer cells by specifically targeting EZH2, which contributes to the cancer growth process.3 Eisai is responsible for the development and commercialization of this agent in Japan, while Epizyme, Inc. is responsible for all regions outside of Japan. In the United States, "Tazverik" received accelerated approval for the indication of epithelioid sarcoma in January 2020, and follicular lymphoma in June 2020 (Notes to editors 1).

Follicular lymphoma is a low-grade B-cell lymphoma that accounts for 10-20% of non-Hodgkin’s lymphomas. Follicular lymphoma is generally indolent and sensitive to chemotherapy. However, development of a new treatment strategy is required for follicular lymphoma which still remains difficult to cure, as recurrence often occurs repeatedly. 7-27% of follicular lymphomas are reported to have gain-of-function mutations in the EZH2 gene,4,5 and it is estimated that there are approximately 600 to 2,400 patients with follicular lymphoma with EZH2 gene mutations in Japan. A companion diagnostic test for EZH2 gene mutations, "cobas EZH2 Mutation Test" by Roche Diagnostics K.K. (Headquarters: Tokyo) was approved in May 2021.
　

Eisai aims to make continuous efforts to meet the diversified needs of and increase the benefits provided to patients with cancer, their families, and healthcare professionals, by delivering "Tazverik" as a new treatment option for EZH2 gene mutation-positive follicular lymphoma.

On June 23, 2021 AstraZeneca and HUTCHMED reported that its Orpathys (savolitinib) has been granted conditional approval in China to treat patients with non-small cell lung cancer (NSCLC) with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy (Press release, AstraZeneca, JUN 23, 2021, View Source [SID1234584265]).

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This approval follows a priority review designation by the Center for Drug Evaluation of China’s National Medical Products Administration (NMPA) and marks the first global regulatory approval for the oral, potent, and highly selective MET tyrosine kinase inhibitor (TKI).

More than a third of the world’s lung cancer patients are in China and, among those with NSCLC, approximately 2-3% have tumours with MET exon 14 skipping alterations, a targetable mutation in the MET gene.1-3 This mutation is more common (13-22%) among patients with pulmonary sarcomatoid carcinoma (PSC), a rare and aggressive subtype of NSCLC usually resistant to chemotherapy.1,4

The approval by the NMPA was based on positive results from a single-arm Phase II trial conducted in China in patients with NSCLC with this mutation, including patients with the PSC subtype. Orpathys demonstrated robust anti-tumour activity based on an independent review of objective response rate (ORR) in the trial’s primary endpoint and its disease control rate (DCR). Continued approval is contingent upon the successful completion of a confirmatory trial in this patient population.

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "This approval makes Orpathys the only targeted medicine approved for these biomarker-selected patients in China, and it adds another novel medicine to our already diverse lung cancer portfolio. We are proud that this first-ever regulatory approval of Orpathys is in China, where we have a long-standing commitment to improving patient outcomes and working with the right partners to achieve that goal. Alongside HUTCHMED, we look forward to the continued development of this medicine across a range of cancers where MET alterations and amplification are drivers of tumour growth and treatment resistance."

Christian Hogg, Chief Executive Officer, HUTCHMED, said: "It is with great pleasure that today we announce the first regulatory approval of Orpathys globally, HUTCHMED’s third self-discovered oncology drug to be commercialized. Our collaboration with AstraZeneca in 2011 has been an important driver in the development of this novel targeted oncology drug, involving both a China-based biotech and a global pharmaceutical company. This approval is a testament to the perseverance and scientific ingenuity of this long-standing alliance, and we are hopeful that this is only the beginning of the progress we can achieve for patients with MET-altered tumours."

In the Phase II trial, at a median follow up of 17.6 months, Orpathys demonstrated an ORR of 42.9% (95% confidence interval [CI] 31.1-55.3) and median progression-free survival (PFS) of 6.8 months (95% CI 4.2-9.6) in the overall trial population. PFS was clinically meaningful across subgroups, and ORR results were consistent regardless of prior treatment or tumour histology, including in patients with the PSC subtype (40.0%, 95% CI 21.1-61.3) and patients with other NSCLC subtypes (44.4%, 95% CI 29.6-60.0). DCR in the overall trial population was 82.9% (95% CI 72.0-90.8).

The safety and tolerability profile of Orpathys was consistent with previous trials, and no new safety signals were identified. Most adverse events (AEs) were Grade 1–2 and resolved with dose modification or discontinuation. Grade 3 or higher AEs occurred in 45.7% of patients, and treatment-related serious AEs occurred in 24% of patients. One treatment-related death was reported from tumour lysis syndrome in a patient with PSC.

Results from the Phase II trial were presented during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program in May 2020, and updated results were published in The Lancet Respiratory Medicine in June 2021.

As part of the joint global development programme with HUTCHMED, Orpathys is being evaluated in combination with Tagrisso and other medicines to address tumour mechanisms of resistance in NSCLC in the ORCHARD and SAVANNAH Phase II trials for the combinations to provide longer duration of benefit, and as a treatment for other MET-driven tumours, including papillary renal cell carcinoma, and gastric and gastroesophageal junction cancers.

NSCLC, PSC and MET aberrations
Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.2 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.5 The majority of NSCLC patients are diagnosed with advanced disease.6

PSC is a rare subtype of NSCLC, comprising 0.3-3% of all lung malignancies.7 Compared with other NSCLC subtypes, PSC patients have a poorer prognosis and limited treatment options.4,8-9

MET is a tyrosine kinase receptor.10 While MET genetic alterations are common in many solid tumours, MET exon 14 skipping alterations are more frequently associated with lung cancer, occurring in approximately 2-3% of patients with NSCLC and 13-22% of patients with PSC.1,4,11 MET amplification or overexpression is one of the mechanisms of acquired resistance to epidermal growth factor receptor (EGFR) TKIs for metastatic EGFR-mutated NSCLC.10

NCT02897479
The single-arm, open-label Phase II trial NCT02897479 assessed the efficacy and safety of Orpathys in the treatment of Chinese patients with locally advanced or metastatic PSC or other NSCLC subtypes with MET exon 14 skipping alterations who progressed on prior treatment or were unable to receive chemotherapy.

Patients were treated with weight-based dosing of Orpathys once-daily oral tablets (600mg/day or 400mg/day for patients weighing less than 50kg). Treatment continued until disease progression, death, intolerable toxicity, or discontinuation. The trial enrolled 70 patients across multiple centres in China. The primary endpoint was ORR, and key secondary endpoints were PFS, DCR and safety assessment.

Orpathys
Orpathys (savolitinib) is an oral, potent, and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumours. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations) or gene amplification.

Orpathys is currently under clinical development for multiple tumour types, including lung, kidney, and gastric cancers, as a single treatment and in combination with other medicines.

AstraZeneca and HUTCHMED collaboration
In 2011, AstraZeneca and HUTCHMED entered a global licensing agreement to jointly develop and commercialise Orpathys. HUTCHMED is responsible for the manufacturing and supply of Orpathys, and AstraZeneca is responsible for its commercialisation in China and worldwide. Sales of Orpathys will be recognised by AstraZeneca.

AstraZeneca in lung cancer
AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and assessing innovative approaches, the Company aims to match medicines to the patients who can benefit most.

The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi (durvalumab) and tremelimumab; Enhertu (trastuzumab deruxtecan) and datopotamab deruxtecan in collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.

AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.