On July 18, 2022 Sumitomo Pharma Oncology, Inc., a clinical-stage company focused on novel cancer therapeutics, reported the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for DSP-0390, an investigational emopamil-binding protein (EBP) inhibitor for the treatment of brain cancer (Press release, Sumitomo Pharmaceuticals, JUL 18, 2022, View Source [SID1234616741]).

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"This designation for DSP-0390 underscores the profound need for novel brain cancer treatment options," said Patricia S. Andrews, CEO and Global Head of Oncology, Sumitomo Pharma Oncology, Inc. "We are excited to contribute to advancing critical research in brain cancer."

The FDA’s Orphan Drug Designation is granted to investigational therapies addressing rare medical diseases or conditions that affect fewer than 200,000 people in the United States. Brain cancer refers to brain tumors, made up of abnormal growth of cells in the brain, that are malignant. The exact cause of most brain cancer is unknown.1

"DSP-0390 is an emopamil-binding protein (EBP) inhibitor that mediates de novo cholesterol synthesis for cell membrane structure and signaling, enabling aberrant growth of tumors,"2-5 detailed Jatin J. Shah, M.D., Chief Medical Officer of Sumitomo Pharma Oncology, Inc. "Notably, in patients with glioblastoma multiforme (GBM), a form of high-grade glioma, increased de novo cholesterol synthesis is correlated with poor survival and preclinical evidence has shown that DSP-0390 has cytotoxic activity against GBM cell lines."6

DSP-0390 is currently being evaluated in a Phase 1 clinical trial to evaluate the safety and efficacy of DSP-0390 in patients with recurrent, high-grade glioma, which is being conducted in the United States and Japan. To learn more about the study and eligibility for enrollment, visit clinicaltrials.gov (NCT05023551).

This is the second recently announced Orphan Drug Designations from SMP Oncology. TP-3654, the company’s proprietary investigational oral inhibitor of PIM kinases, was also granted Orphan Drug Designation for the treatment of myelofibrosis (NCT04176198).

About DSP-0390

DSP-0390 is an investigational emopamil-binding protein (EBP) inhibitor. EBP is an endoplasmic reticulum membrane protein involved in cholesterol biosynthesis.2 DSP-0390 has shown cytotoxic activity against GBM, colorectal cancer, and triple-negative breast cancer in vitro. DSP-0390 is currently being evaluated in a Phase 1, interventional clinical trial to evaluate the safety and efficacy of DSP-0390 in patients with recurrent high-grade glioma (NCT05023551).

On July 18, 2022 Delfi Diagnostics, Inc., a pioneering developer of a new class of high-performance, accessible liquid biopsy tests for early cancer detection and monitoring, reported a Series B funding of $225 million (Press release, Delfi Diagnostics, JUL 18, 2022, View Source [SID1234616740]).

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This round of financing was led by DFJ Growth with participation from Eli Lilly and Company, Point72, Brown Advisory, Point Field Partners, Initiate Ventures, Open Field Capital, PTX Capital, and all existing investors including Cowen Healthcare Investments, Foresite Capital, Menlo Ventures, OrbiMed, funds and accounts advised by T. Rowe Price Associates, Inc., Northpond Ventures, Samsara BioCapital, Rock Springs Capital, AV8 Ventures, Illumina Ventures, Osage University Partners, and Windham Venture Partners.

"Cancer is a global public health problem and addressing it requires a solution that is accessible around the world," said Victor Velculescu, MD, PhD, Delfi’s CEO and Founder. "We believe our approach is uniquely capable of delivering high performing, cost effective, and clinically relevant tests for multiple applications to meet the needs of patients and providers everywhere."

This funding will support the continued development and commercialization of high-quality and accessible blood tests for single cancer early detection, multi-cancer early detection, and treatment monitoring.

"With this financing, Delfi is even better positioned to make high-quality liquid biopsy applications broadly available regardless of geographic and socioeconomic constraints," said Doug Schenkel, Delfi’s CFO. "We recognize that a fundraising of this magnitude is a notable achievement and with that comes great responsibility. Our focus on the Delfi mission to save lives through early cancer detection has never been higher."

Delfi’s platform is designed to efficiently develop high-quality liquid biopsy applications via a proprietary and uniquely scalable whole genome fragmentation approach. Rather than looking for relatively scarce signs of cancer found in DNA mutations or methylation changes within narrow regions of the genome, Delfi analyzes cell-free DNA fragments across the entire genome. This allows for a single, low-cost, and straightforward lab process for any test developed on the platform. When combined with breakthroughs in machine learning, the Delfi platform can deliver high-performing results for multiple applications.

Delfi is currently validating the technology for early detection of lung and other cancers in a 15,000-person prospective trial called CASCADE-LUNG, and is working with multiple research institutions to develop additional applications including screening for other cancer types, multi-cancer early detection, and treatment monitoring.

"Delfi has made incredible progress in a short amount of time," said DFJ Growth Partner Justin Kao, who joins Delfi’s board of directors. "We believe that Delfi’s low cost approach is critical to bringing early cancer detection to millions of patients globally. But the most exciting thing about Delfi is its potential to create a next-generation diagnostics company that innovates on data and analytics rather than focusing on ever-more complicated wet lab techniques. Delfi’s cutting-edge machine learning enables new products to be built on the same flexible assay, which has the potential to revolutionize the way we detect and manage cancer. I am thrilled to be joining this board to help Delfi fulfill this potential."

On July 18, 2022 GRAIL, LLC, a healthcare company whose mission is to detect cancer early when it can be cured, reported that the NHS-Galleri trial successfully completed enrollment in just over 10 months (Press release, Grail, JUL 18, 2022, View Source [SID1234616739]). The trial, which is the largest-ever study of a multi-cancer early detection (MCED) test, has enrolled 140,000 healthy volunteers aged 50-77 from select regions throughout England who have not had a cancer diagnosis or undergone treatment for cancer in the last three years.

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The NHS-Galleri trial is a randomized, controlled clinical trial being conducted in England alongside standard cancer screening with diagnostic follow-up in the NHS’ clinical practice setting. Regions were selected to include areas of high cancer mortality, socioeconomic disparities, and ethnic diversity, using innovative methods to enroll a study population with participants traditionally less likely to take part in medical research. Participants visited one of 150 mobile clinics operating at locations around England and were recruited through activities including community group briefings, leaflet distribution in community settings, engagement through community champions, and targeted social media campaigns.

"Meeting the goal of enrolling 140,000 people is a significant achievement, allowing us to evaluate an unprecedented number of volunteers without symptoms of cancer and representing diverse socio-economic and ethnic populations," said Charles Swanton, MD, PhD, a cancer researcher and oncologist at University College London and the Francis Crick Institute, chief clinician at Cancer Research UK, and co-chief investigator of the study. "Whilst the first year of the trial may pick up cancers that have existed for some time, the second and third years provide the best opportunity to explore the expected benefits of picking up new cancers at an early stage when treatment is generally more successful. By screening participants annually over three years, we will be able to explore how MCED tests can be used alongside existing NHS screening programs."

The study’s aim is to determine if the Galleri test, alongside standard cancer screening, can find asymptomatic cancers at earlier stages than they are found in clinical care today. The study will assess absolute numbers of stage 3 and 4 cancers diagnosed following three annual Galleri tests. The first screen will aim to identify the prevalent cancers in the population, while the second and third screens will aim to identify cancers that have newly emerged.

"NHS-Galleri has set a new standard in the speed of set-up and recruitment to clinical trials," said Professor Peter Sasieni, Director of The Cancer Research UK & King’s College London Cancer Prevention Trials Unit and one of the trial’s lead investigators. "Previous trials of this magnitude would typically have taken five times as long. Accelerating research means that we will find out sooner whether new technology has a role in the control of cancer and, if it does, introducing it within the NHS quickly so that more people can benefit."

This trial supports the NHS Long Term Plan ambition to catch three quarters of cancers at an early stage, when they are less advanced, and treatment has a higher chance of being successful and potentially curative. Based on initial results, the NHS may roll out the test to an additional 1 million people.

"Today marks an important milestone in our long-term efforts to catch and treat cancer earlier," said Amanda Pritchard, chief executive at NHS. "We know that certain cancers are harder to detect and a late diagnosis can be devastating for patients and their families, and this trial means thousands could benefit from a diagnosis even before symptoms appear."

In a previous clinical study, the Galleri test demonstrated the ability to detect a shared signal from more than 50 types of cancer, many of which lack recommended screening tests today in the UK. Early clinical trials report that GRAIL’s Galleri test has a false positive rate under 1% and can predict where a cancer signal originated with 89% accuracy.

"We are so grateful for the public’s enthusiasm for this trial and to all those who have volunteered," said Sir Harpal Kumar, president at GRAIL Europe. "We are hopeful Galleri will work well alongside existing cancer screening in the UK, can provide clinicians with an accurate prediction of where the cancer is located in the body, and help the NHS reduce the number of cancers detected at a late stage."

The study is sponsored by GRAIL and is being run by The Cancer Research UK and King’s College London Cancer Prevention Trials Unit (UK), in collaboration with eight cancer alliances in England. The study design of the trial was presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract #TPS6606) in June 2022.

About NHS-Galleri Trial

For the prospective, blinded, randomized controlled trial, study participants will provide a blood sample during three annual visits to a mobile health clinic—at baseline, year 1 and year 2. After the first visit, participants are randomized 1:1 into either the intervention or control arm. Participants in the intervention arm will have their blood tested by the Galleri test. Blood samples from subjects in the control arm will not be tested immediately, but will be stored for potential future testing. If a cancer signal is detected for those in the intervention arm, research staff will explain the result and schedule an appointment for follow-up tests at an NHS hospital local to the participant. All participants in the study will be followed for cancer and other related outcomes via NHS databases and will be reminded to continue to have guideline-recommended cancer screenings.

On July 18, 2022 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, and Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151), a global specialty pharmaceutical company creating innovative medical solutions utilizing the latest biotechnology, reported that publication of data from the Phase 1b clinical study of zandelisib, an orally administered investigational phosphatidylinositol 3-kinase delta ("PI3Kδ") inhibitor, in patients with relapsed or refractory (R/R) B-cell malignancy in The Lancet Oncology (Press release, MEI Pharma, JUL 18, 2022, View Source [SID1234616737]). The published data demonstrate that an intermittent dosing regimen of zandelisib resulted in lower cumulative risk of Grade 3 or worse adverse events of special interest compared to a continuous daily dosing regimen without loss of efficacy. The publication, entitled "Zandelisib with continuous or intermittent dosing as monotherapy or in combination with rituximab in patients with relapsed or refractory B-cell malignancy: a multicentre, first-in-patient, dose-escalation and dose-expansion, phase 1b trial," is available on the journal website.

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"The results observed in our Phase 1b study reinforce the potential of zandelisib, an investigational clinical candidate, to provide a well-tolerated clinical profile either as a single-agent or in combination with other therapies without a loss of efficacy via a unique intermittent schedule compared to continuous daily dosing," said Richard Ghalie, M.D., chief medical officer of MEI Pharma. "We remain encouraged by zandelisib’s potential as we continue its development using the intermittent schedule as an oral, chemotherapy-free, time-limited, therapeutic option to meet the needs of patients."

"Based on the results of the Phase 1b study, zandelisib could establish a potential alternative to chemotherapy with a unique dosing schedule for this class, both as a single agent and in combination with other drugs," said Yoshifumi Torii, Ph.D., Executive Officer, Vice President, Head of R&D Division of Kyowa Kirin. "We will continue to work with MEI to develop new treatment options for patients with B-cell malignancies."

The Phase 1b study (NCT02914938) is an open-label, dose escalation and expansion study evaluating zandelisib in patients with B-cell malignancies. The manuscript reported on a total of 97 patients, including 31 patients in the dose escalation stage that established 60 mg once daily as the recommended Phase 2 dose. The study evaluated zandelisib in 56 patients as a monotherapy and 41 patients in combination with rituximab. Zandelisib was administered either on a continuous schedule of 60 mg once daily (n=38) or an intermittent dosing schedule of 60 mg once daily for the initial two 28-day cycles followed by the intermittent dosing (ID) schedule of 60 mg once daily on days 1-7 in cycles ≥3 (n=59).

In the initial monotherapy dose-finding part of the study, no dose-limiting toxicities were observed across the evaluated doses of 60 mg, 120 mg and 180 mg given daily continuously, and anti-tumor activity was similar across doses. With a median duration of treatment of 10.4 months and 15.2 months, in the continuous and intermittent dosing group respectively, Grade 3 or worse adverse events of special interest occurred less frequently in the intermittent dosing group than in the continuous dosing group. For example, Grade 3 diarrhea or colitis in 8% vs 24%, and Grade 3 lung infection or pneumonia in 2% vs 16%, of patients in the intermittent dosing group vs the continuous dosing group, respectively. Grade 3 or worse AST or ALT elevation (5%) and rash (5%) were uncommon with each dosing schedules. There was a continued increased risk of Grade 3 diarrhea or colitis in the continuous dosing group, compared with a decreased risk over time in the intermittent dosing group after switching to the intermittent dosing. At a median follow-up of 24.9 months in the continuous dosing group and 15.7 months (95% CI 6·5-33·9) in the intermittent dosing group the cumulative incidence of Grade 3 or worse adverse events of special interest was 45% in the continuous dosing group and 20% in the intermittent dosing group.

Intermittent dosing showed comparable efficacy to continuous dosing. Patients with indolent B-cell malignancies (follicular lymphoma, chronic lymphocytic leukemia or small lymphocytic lymphoma, and marginal zone lymphoma) demonstrated an objective overall response rate of 87%.

The published Phase 1b safety and efficacy results for zandelisib 60 mg once daily on an intermittent dosing schedule warranted initiating the ongoing global Phase 2 TIDAL and Phase 3 COASTAL studies evaluating zandelisib alone or in combination with rituximab, respectively.

About Zandelisib

Zandelisib, a selective PI3Kδ inhibitor, is an investigational cancer treatment being developed as an oral, once-daily, potential therapeutic option for patients with B-cell malignancies. Clinical trials are investigating the efficacy and safety of zandelisib as a single agent and in combination with other modalities while administered on an Intermittent Dosing Regimen (ID) and in a time-limited manner when dosed in combination. The ID leverages molecular and biologic properties specific to zandelisib.

Ongoing zandelisib studies include the cohort in TIDAL evaluating patients with r/r marginal zone lymphoma (MZL) and continuing evaluation of the cohort of patients in the study with r/r FL. Also ongoing is the Phase 3 COASTAL study (NCT04745832), comparing zandelisib plus rituximab to standard of care chemotherapy plus rituximab in patients with r/r FL or MZL who received more than one prior line of therapy, which must have included an anti-CD20 antibody in combination with chemotherapy or lenalidomide. COASTAL, which is also evaluating time-limited intermittent administration of zandelisib, is intended to support marketing applications in the U.S. and globally.

Other ongoing studies include a Phase 2 pivotal study in Japan (NCT04533581) in patients with indolent B-cell non-Hodgkin’s lymphoma (iB-NHL) without small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), and Waldenström’s macroglobulinemia (WM) conducted by Kyowa Kirin.

In March 2020, the FDA granted zandelisib Fast Track designation for the treatment of adult patients with r/r follicular lymphoma who have received at least two prior systemic therapies. In November 2021, the FDA granted zandelisib Orphan Drug designation for the treatment of patients with follicular lymphoma.

In April 2020, MEI and Kyowa Kirin entered a global license, development, and commercialization agreement to further develop and commercialize zandelisib. MEI and Kyowa Kirin will co-develop and co-promote zandelisib in the U.S., with MEI booking all revenue from the U.S. sales. Kyowa Kirin has exclusive commercialization rights outside of the U.S.

On July 18, 2022 MAIA Biotechnology, Inc., a targeted therapy, immuno-oncology company focused on developing potential first-in-class oncology drugs ("MAIA"), reported that the first patient has been dosed in MAIA’s Phase 2 clinical trial, THIO-101, evaluating the administration of THIO, in sequence with cemiplimab, in patients with advanced Non-Small Cell Lung Cancer (NSCLC) (Press release, MAIA Biotechnology, JUL 18, 2022, View Source [SID1234616736]).

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The THIO-101 Phase 2 trial is designed to evaluate THIO’s potential immune system activation effects in NSCLC patients by administering THIO in advance of administration of the checkpoint inhibitor cemiplimab (developed by Regeneron), allowing for immune activation and PD-1 sensitivity to take effect. The primary objectives of the trial are to evaluate the safety and tolerability of THIO administered as a direct anticancer and priming immune system agent prior to cemiplimab administration, as well as the clinical efficacy of THIO in patients with advanced NSCLC who either progressed or relapsed through treatment with an immune-check point inhibitor alone or in combination with chemotherapy. The first patient in THIO-101 was dosed in Australia in July 2022 after the Company’s application received regulatory approval in March 2022. The Company also plans to submit a similar application in the second quarter of 2022, to conduct the same Phase 2 study in Europe.

"Dosing our first patient in this Phase 2 trial with THIO is an important milestone for MAIA, marking the continued development of our telomere-targeting approach," said Vlad Vitoc, M.D., MAIA’s Chairman and Chief Executive Officer. "Despite the advancements made in the field with checkpoint inhibitors, monoclonal antibodies and newer immunotherapies, very limited treatment options exist for patients that have progressed beyond the standard-of-care regimens. We believe THIO has the potential to hold a significant place in the NSCLC treatment paradigm."

Sergei Gryaznov, Ph.D., Chief Scientific Officer of MAIA, added, "Lung cancer is the second most diagnosed cancer worldwide and NSCLC is the most common form of lung cancer, accounting for more than eighty percent of all lung cancer diagnoses. This represents a significant unmet medical need across the globe, and we remain enthusiastic about THIO’s observed mechanism of action."

About THIO-101, a Phase 2 Clinical Trial

THIO-101 is a multicenter, open-label, dosing finding Phase 2 clinical trial. It is the first trial designed to evaluate THIO’s potential immune system activation effects in NSCLC patients by administering THIO in advance of administration of the checkpoint inhibitor cemiplimab (developed by Regeneron), potentially allowing for immune activation and PD-1 sensitivity to take effect. The trial will test the hypothesis that low doses of THIO administered prior to checkpoint inhibitor treatment will enhance and prolong immune response in patients with advanced NSCLC who previously did not respond or progressed after first-line treatment regimen containing a checkpoint inhibitor. The trial design has two primary objectives: (1) to evaluate the safety of THIO administered as an anticancer agent and a priming immune system agent prior to cemiplimab administration and (2) to assess the clinical efficacy of THIO followed by cemiplimab using Overall Response Rate (ORR) as the primary clinical endpoint. For more information on this Phase II trial, please visit ClinicalTrials.gov using the identifier NCT05208944.

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is an investigational telomere-targeting agent currently in clinical development to evaluate its activity in NSCLC. Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. THIO is being developed for patients with NSCLC that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.