On June 4, 2021 Candel Therapeutics, Inc., a late clinical stage biopharmaceutical company developing novel oncolytic viral immunotherapies, reported initial results from an ongoing Phase 1 clinical trial of its oncolytic virus, CAN-3110, in patients with high-grade glioma (HGG) that has recurred after initial treatment (Press release, Candel Therapeutics, JUN 4, 2021, View Source [SID1234583579]). The data are presented today in an Oral Abstract Session of the Clinical Science Symposium at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"This is the first clinical trial of a novel oncolytic HSV engineered to selectively express ICP34.5 in tumor cells, leading to tumor-specific cell death. This novel oncolytic viral immunotherapy has been shown to be well tolerated with primarily low grade, and manageable side effects"

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Highlights from the Oral Abstract Session of the Clinical Science Symposium at ASCO (Free ASCO Whitepaper) 2021

An ongoing Phase 1 study is evaluating the safety and activity of CAN-3110, an engineered replication-competent herpes simplex virus (HSV) oncolytic viral immunotherapy, in patients with HGG who have experienced disease progression following prior treatment with standard of care therapies. As of the data cutoff date of April 21, 2021:

30 patients were evaluable for safety.
Nine dose levels ranging from 1×106 to 1×1010 plaque forming units (PFU) were administered.
No dose-limiting toxicity was observed. The maximum administered dose was 1×1010 PFU.
CAN-3110 was well-tolerated and all but one adverse events (AEs) were Grade 1 or 2.
A preliminary Kaplan-Meier estimate of median overall survival was 11.7 months.
All patients have been treated for more than 12 months.
One patient who responded for over a year, a 56-year-old male with multifocal glioblastoma, demonstrated a significant reduction in both an injected and an uninjected lesion, suggesting an abscopal effect of CAN-3110.
An additional 12 patients have been enrolled into a dose expansion arm of the trial.
"CAN-3110 has demonstrated a significant number of durable responses in patients with high-grade glioma who experienced disease progression following prior standard of care therapy," said Antonio Chiocca, MD, PhD, FAANS, Neurosurgeon-in-Chief and Chairman, Department of Neurosurgery at Brigham and Women’s Hospital. "The results of this first-in-human study are encouraging as they demonstrate a median overall survival that was substantially longer than the six to nine months typically observed for these patients as well as a favorable safety profile."

"This is the first clinical trial of a novel oncolytic HSV engineered to selectively express ICP34.5 in tumor cells, leading to tumor-specific cell death. This novel oncolytic viral immunotherapy has been shown to be well tolerated with primarily low grade, and manageable side effects," said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel Therapeutics. "There are few treatment options for patients with high-grade glioma whose tumors progress following initial surgery and chemoradiation. We are encouraged by the duration of the responses observed to date in this patient population given the extremely limited treatment options. Based on these data, we are excited to advance this innovative agent into further clinical trials."

Details of the presentation are as follows:

Abstract Title: First-in-human CAN-3110 (ICP34.5 expressing HSV-1 oncolytic virus) in patients with recurrent high-grade glioma

Presenter: Dr. E. Antonio Chiocca

Session Date and Time: The presentation is available to ASCO (Free ASCO Whitepaper) attendees beginning June 4, 2021 at 9 AM EDT/ 6 AM PDT and has been reposted to the Candel Therapeutics website at www.candeltx.com/news

Abstract Link: View Source

Session Title: CNS Targeting: From Delivery to Biomarker Assessment

Abstract Number: 2009

About CAN-3110

CAN-3110 is an HSV replication-competent oncolytic virus engineered to enhance selective killing of malignant cells while sparing healthy normal neighboring cells. CAN-3110 selectively expresses ICP34.5, a key gene in HSV replication, in tumor cells that overexpress nestin, a cytoskeletal protein. Nestin is highly expressed in glioma cells and other tumor tissue but is absent in the healthy adult brain.

Candel is evaluating the effects of treatment with CAN-3110 for recurrent glioblastoma. For more information on this clinical study, please visit View Source

On June 4, 2021 Foundation Medicine, Inc. and its collaborators reported the presentation of new data analyzing the genomic landscape, comprehensive genomic profiling (CGP) utilization and treatment patterns among more than 11,000 men with advanced prostate cancer, including 12% with a predicted African genomic ancestry (Press release, Foundation Medicine, JUN 4, 2021, View Source [SID1234583578]). In what is believed to be the largest known cohort of its kind, researchers found that despite similar rates of actionable gene alterations between men of European and African ancestry, men of African ancestry were less likely to receive CGP early in their treatment course and less likely to be enrolled in clinical trials. These findings highlight the importance of additional factors, beyond inherent differences in disease biology, in potentially driving disparities in outcomes. They also underscore the need to expand access to precision medicine and clinical trial enrollment. Data will be presented during an oral presentation on June 8 at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Scientific Program (ASCO21).

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Prostate cancer incidence and clinical outcomes vary widely across race and ethnicity, and the underlying drivers of these outcomes are multifactorial, including systemic barriers that lead to differences in access to genomic and precision medicine. Men of African ancestry are particularly underrepresented in prostate cancer research. With this study, Foundation Medicine and collaborators at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, the University of Michigan and Harvard Medical School explored the interplay between ancestry and patient care.

"Men of African ancestry experience the greatest burden of disease in prostate cancer, and this research indicates that differences in cancer care are not solely based on biological factors, but rather points to socioeconomic factors such as access to comprehensive genomic profiling and clinical trial enrollment," said study investigator Brandon Mahal, M.D., Assistant Professor, Radiation Oncology and Assistant Director of Community Outreach and Engagement, Sylvester Comprehensive Cancer Center. "To ensure equitable opportunities for precision medicine, we need to expand access to and awareness of advances that impact patient care and outcomes, including timely use of genomic testing to help make informed treatment decisions."

The study analyzed 11,741 men with advanced prostate cancer who received CGP as part of routine clinical care, along with a subset of 897 patients with real-world clinical data from Foundation Medicine and Flatiron Health’s joint clinico-genomic database (CGDB). Results showed that the rates of genomic alterations were largely similar across ancestry, including alterations in BRCA1/2, androgen receptor, DNA damage response pathway genes and actionable genes with therapy implications. Within the CGDB cohort, the proportion of patients receiving immunotherapy and PARP inhibitors was also similar across ancestry. However, men of African ancestry were less likely to receive a clinical study drug than men of European ancestry (11% vs. 30%). Further, men of African ancestry received a median of two lines of therapy prior to CGP, compared to one line of therapy for men of European ancestry, highlighting the extended time from diagnosis to implementation of precision medicine. These factors may potentially impact the genomic landscape, outcomes, and ultimately disparities.

"At Foundation Medicine, we strive to better understand barriers at different stages of a patient’s journey and identify opportunities to mitigate disparities in cancer care. Our study highlights the need for the cancer community to understand and systematically define barriers to care across different populations, especially those traditionally underrepresented in clinical research," said study co-lead Smruthy Sivakumar, PhD, scientist at Foundation Medicine. "The results contribute to our knowledge of comprehensive genomic profiling and real-world data to better understand the barriers patients face in accessing quality cancer care – a critical step toward addressing persistent disparities," added Jessica Lee, study co-lead and scientist at Foundation Medicine.

A full list of research being presented by Foundation Medicine and its collaborators at ASCO (Free ASCO Whitepaper)21 can be found at www.foundationmedicine.com/event/asco2021.

On June 4, 2021 GRAIL, Inc., a healthcare company whose mission is to detect cancer early,reported the first results from the interventional PATHFINDER study evaluating Galleri, a multi-cancer early detection (MCED) blood test (Press release, Grail Bio, JUN 4, 2021, View Source [SID1234583577]). The results, presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting, support Galleri’s performance in clinical settings. The company also announced today that Galleri is now available in the U.S. by prescription only.

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"The interim results of PATHFINDER demonstrate that a routine blood test is capable of detecting many different cancers even before symptoms arise, an approach that has significant potential advantages," said Dr. Tomasz M. Beer, deputy director at the OHSU Knight Cancer Institute and presenting author. "Most importantly, it can detect cancers that have no recommended screening tests today, and more than two-thirds of cancers go unscreened for this reason. These results are a pivotal step toward extending early detection to many more types of cancer."

Clinical Data from PATHFINDER

PATHFINDER was designed to assess the implementation and performance of Galleri in a clinical care setting, evaluate the clinical care pathways following a "signal detected" Galleri test result, and measure the time required to achieve diagnostic resolution.

The study analyzed 6,629 individuals aged 50 years or older, an age group at elevated risk for cancer, but with no suspicion of active cancer. Compared to the general population, participants had equal or higher compliance with recommended breast and colon cancer screening tests.

In the interim analysis, an earlier version of Galleri accurately detected 29 cancers across 13 types: breast, colon or rectum, head and neck, liver and bile duct, lung, lymphoid leukemia, lymphoma, ovary, pancreas, plasma cell neoplasm, prostate, small intestine, and Waldenstrom macroglobulinemia. Of the new cancers detected, nearly 40% (9/23) were localized (stage I-II), and more than half (13/23) were detected before distant metastases (stage I-III). PATHFINDER participants will continue to be followed for 12 months, with final results expected in the first half of 2022.

"Finding cancer early, when treatment is more likely to be successful, is one of the most significant opportunities we have to reduce the burden of cancer," said Dr. Joshua Ofman, chief medical officer and head of external affairs at GRAIL. "These data suggest that, if used at scale alongside existing screening tests, the Galleri test could have a profound impact on how cancer is detected and, ultimately, on public health."

The interim PATHFINDER positive predictive value (PPV), or the likelihood that a person has cancer when a positive test result is returned, was 44.6% (95% CI: 33.2-56.7%), which is consistent with findings from GRAIL’s case-controlled Circulating Cell-free Genome Atlas (CCGA) Study.

When cancer was confirmed, Galleri’s first or second cancer signal origin prediction was 96.3% accurate (95% CI: 81.7-99.8%), with a median observed time to cancer diagnosis of 50 days. The interim analysis identified only four study-related adverse events (two related to mild anxiety before the test, one related to mild anxiety about the blood draw, and one related to mild bruising).

"Early cancer detection is critical to reducing the burden of cancer-related morbidity and mortality. These results reflect the potential real-world ability of Galleri to find deadly cancers earlier, and represent a leap forward in the effort to treat cancer more effectively," Dr. Beer said.

Data is presented by Dr. Beer, and the presentation will be available at View Source

Introducing Galleri

Galleri is now available in the U.S. by prescription only. The Galleri test is intended for use in those with an elevated risk of cancer, such as adults aged 50 or older, and as a complement to existing single cancer screening tests.

In an observational study, Galleri has demonstrated the ability to detect more than 50 types of cancer1, over 45 of which lack recommended screening tests today in the U.S., with a low false positive rate of less than 1%. When cancer is detected, Galleri can determine the cancer signal origin with high accuracy. New CCGA data published today in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), also demonstrate the ability of GRAIL’s technology to preferentially detect cancers that are more aggressive than expected based on age, and the cancer stage and type.

The blood test is supported by what is believed to be the largest clinical study program in genomic medicine, with over 140 clinical study sites, including the Mayo Clinic, Dana-Farber Cancer Institute, Cleveland Clinic, Sutter Health, OHSU, Intermountain Healthcare, and U.S. Oncology Research.

Cancer is expected to become the leading cause of death in the United States this year, in large part because the majority of cancers are found too late when outcomes are poor. Recommended screening tests save lives, but only cover five cancer types in the U.S. In fact, 71% of cancer deaths in the U.S. have no recommended early detection screening.

For more information about Galleri, visit www.galleri.com.

REFLECTION Registry

GRAIL also announced it will establish a real-world evidence study, REFLECTION, to understand the experience and clinical outcomes of 35,000 individuals in the U.S. who are prescribed the Galleri test from a healthcare provider. This follows an announcement last fall that Galleri will be offered to eligible patients in the United Kingdom (UK) later this year as part of a partnership with the UK National Health Service to support its Long Term Plan for earlier cancer diagnoses.

On June 4, 2021 Pacylex Pharmaceuticals, an oncology company unlocking a new approach to cancer therapy, and Greenfire Bio, a new Life Science development and investment company, reported the closing of Series A financing for Pacylex (Press release, Greenfire, JUN 4, 2021, View Source [SID1234583545]). These funds will be used to support the initial Phase 1 clinical investigation of PCLX-001, a first-in-class N-myristoyltransferase (NMT) inhibitor, in Diffuse Large B-Cell Lymphoma and solid tumor patients. Pacylex is leading the development of novel therapies targeting the biological process of myristoylation in cancer.

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"We are excited to be a catalyst for this new innovation in oncology" said Ajit Gill, CEO of Greenfire Bio. "Our goal is to build a portfolio of potential breakthroughs in medicine, and we look forward to seeing PCLX-001 move into the clinic."

"The support from Greenfire Bio is essential for our transformation into a clinical stage company", said Michael Weickert, CEO of Pacylex. "Pioneering a new target and first-in-class therapy is extraordinarily important to expand cancer treatment options and improve patient outcomes. We are delighted to find the right investor with an appreciation for this groundbreaking work."
Clinical site preparations are underway for the open label, dose escalation, Phase 1 clinical trial, principally to evaluate the safety of PCLX-001. The study will enroll 20-30 patients and the Company anticipates that enrollment will begin within the next month. A No Objection Letter from Health Canada was received by Pacylex on March 8, 2021, authorizing the planned Phase 1 Trial of PCLX-001 in relapsed/refractory B-cell Non-Hodgkin Lymphoma and advanced solid malignancies. PCLX-001 is believed to be the first NMT inhibitor that will be clinically tested. Three principal investigators will oversee the clinical study at three clinical sites in Canada: Dr. John Kuruvilla at Princess Margaret Cancer Centre in Toronto, Dr. Randeep Sangha at the Cross Cancer Institute in Edmonton and Dr. Laurie Sehn at the British Columbia Cancer Center in Vancouver.

PCLX-001

PCLX-001 is a small molecule, first-in-class NMT inhibitor, originally developed by the University of Dundee Drug Discovery Unit as part of a program to treat African sleeping sickness funded by Wellcome Trust. Pacylex is developing PCLX-001, which has excellent oral bioavailability, to treat leukemia and lymphoma. PCLX-001 selectively kills cancer cells and completely regresses (eliminates) tumors in animal models of acute myeloid leukemia (AML), diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). PCLX-001 has also been shown to inhibit the growth of lung and breast cancer tumors in animal models. In leukemia, lymphoma and breast cancer patients, the level of NMT2 is correlated with survival, suggesting an important biological role in these cancers. In tests using cultured cancer cells in vitro, PCLX-001 is at least ten times as potent as ibrutinib (Imbruvica) and dasatinib (Sprycel), two clinically approved drugs currently used to treat hematologic malignancies.

On June 4, 2021 Merus N.V. (Nasdaq: MRUS) ("Merus", "the Company", "we", or "our"), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported interim efficacy data, as of an April 13, 2021 cutoff date, from the phase 1/2 eNRGy trial and Early Access Program (EAP) of bispecific antibody zenocutuzumab (Zeno) in patients with NRG1+ cancers, presented virtually by Lead Author, Dr. Alison Schram of Memorial Sloan Kettering Cancer Center (MSKCC) at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting (Press release, Merus, JUN 4, 2021, View Source [SID1234583576]).

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Dr. Andrew Joe, Chief Medical Officer at Merus said, "With confirmed partial responses observed in 42% of pancreatic cancer patients, and partial responses across several NRG1+ tumor types, we remain encouraged that Zeno has the potential to become a new treatment for patients with NRG1 fusion positive cancers. The data, including durability, continue to mature with 40% of evaluable patients remaining on therapy as of the data cutoff date."

Dr. Alison Schram said, "It is very exciting to witness the emergence of a potential new treatment for patients with NRG1 fusion-positive cancers, a population with unmet need. The data presented today are the first to clinically validate NRG1 fusions as drivers of cancer and show that Zeno is capable of blocking tumor growth in patients harboring these fusions."

The reported data are from the ongoing phase 1/2 eNRGy trial and EAP which are investigating the safety and anti-tumor activity of Zeno monotherapy in NRG1+ cancers. The eNRGy trial consists of three cohorts: NRG1+ pancreatic cancer; NRG1+ non-small cell lung cancer (NSCLC); and NRG1+ other solid tumors.

Key findings in the presentation include:

Enrollment of 61 patients with NRG1+ pancreatic, NSCLC, and other cancers.
47 patients were evaluable for primary analysis , with a median age of 56 (range 22-84), previously treated with a median of 2 lines of prior therapy.
45 patients were evaluable for response by local review with measurable disease and the opportunity for ≥ 1 post-baseline tumor assessment (two patients with non-measurable disease are included in the primary analysis of 47 patients, but not included in the 45 evaluable for response).
Partial responses (PRs) achieved across four different NRG1+ tumor types and multiple different fusion partners
Across NRG1+ tumor types, 29% overall response rate (ORR) with 13 of 45 achieving PRs, one additional unconfirmed PR was confirmed after the April 13, 2021 data cutoff date (14 of 45, 31%); median duration of exposure is 5.5 months, with 40% of evaluable patients continuing on treatment; the duration of response ranges from 1+ to approximately 12 months.
34 of 45 (76%) patients had tumor reduction
42% ORR with 5 of 12 PRs in pretreated NRG1+ pancreatic cancer
Median duration of exposure as of the April 13, 2021 data cut-off is 5.7 months, with 7 of 12 patients continuing on treatment.
In NSCLC, 25% ORR, with 6 of 24 PRs; one additional unconfirmed PR was confirmed after the data cutoff date (7 of 24, 29%).
Among all other solid tumors, 22% ORR with 2 of 9 PRs.
Zeno was observed to have a favorable and tolerable safety profile (across 157 patients treated with Zeno monotherapy as of the Jan 12, 2021 safety data cutoff date).
The majority of adverse events were mild or moderate (Grade 1 or 2) in severity.
Absence of severe gastrointestinal and skin toxicities and clinical cardiotoxicity.
Low incidence (7%) of infusion reactions
First prospective clinical validation of NRG1 fusions as actionable oncogenic drivers that may be amenable to targeted therapy with Zeno.
Merus plans the next program and clinical update for Zeno at a major medical conference by the first half of 2022.

Company Conference Call and Webcast Information

Merus will hold a conference call and webcast for investors on Sunday, June 6, 2021 at 6:00 PM ET to discuss the Zeno clinical data. A replay will be available after the completion of the call in the Investors and Media section of our website.

Date: Sunday, June 6 at 6:00 pm ET
Webcast link: available on our website
Dial-in: Toll-Free: 1-877-260-1463 / International: 1-706-643-5907
Conference ID: 9678617

About the eNRGy Clinical Trial
Merus is currently enrolling patients in the phase 1/2 eNRGy trial to assess the safety and anti-tumor activity of Zeno monotherapy in NRG1+ cancers. The eNRGy trial consists of three cohorts: NRG1+ pancreatic cancer; NRG1+ non-small cell lung cancer; and NRG1+ other solid tumors. Further details, including current trial sites, can be found at www.ClinicalTrials.gov and Merus’ trial website at www.nrg1.com or by calling 1-833-NRG-1234.

About Zeno
Zeno is an antibody-dependent cell-mediated cytotoxicity (ADCC)-enhanced Biclonics that utilizes the Merus Dock & Block mechanism to inhibit the neuregulin/HER3 tumor-signaling pathway in solid tumors with NRG1 gene fusions (NRG1+). Through its unique mechanism of binding to HER2 and potently blocking the interaction of HER3 with its ligand NRG1 or NRG1-fusion proteins, Zeno has the potential to be particularly effective against NRG1+ cancers. In preclinical studies, Zeno also potently inhibits HER2/HER3 heterodimer formation and tumor growth in models harboring NRG1 fusions.