On December 9, 2020 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) and SOLTI-Innovative Breast Cancer Research reported an electronic poster at the 2020 San Antonio Breast Cancer Symposium (SABCS) with data from the AWARE-1 window-of-opportunity study in patients with early-stage breast cancer showing pelareorep delivers a significant boost known to increase the effectiveness of checkpoint inhibitors (Press release, Oncolytics Biotech, DEC 9, 2020, View Source [SID1234572519]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In the AWARE-1 study, a collaboration between Oncolytics Biotech and SOLTI, early-stage breast cancer patients are treated with pelareorep, with or without atezolizumab (Tecentriq), plus an appropriate therapy for each patient’s breast cancer subtype, followed by surgery. The SABCS poster includes 17 out of the 20 HR+/HER2- breast cancer patients comprising the study’s first two cohorts, the targeted patient population for our intended phase 3 study. Treatment with pelareorep increased the CelTIL score in tumor biopsies, which has been associated with improved clinical outcomes. In addition, pelareorep treatment dramatically upregulated PD-L1 expression in the tumor microenvironment (TME). These findings highlight the potential of pelareorep to act synergistically with checkpoint inhibitors and also provides a basis for the near doubling of overall survival observed in a prior phase 2 trial when pelareorep was added to chemotherapy in HR+/HER2- breast cancer patients (link to PR, link to poster).

"AWARE-1 data demonstrate pelareorep’s consistent remodeling of the tumor immune environment," said Dr. Aleix Prat, M.D., Ph.D., Translational Investigator of AWARE-1, SOLTI President and Head of the Medical Oncology Department at Hospital Clinic in Barcelona. "Pelareorep seems to train the immune system to target cancer cells while simultaneously promoting tumor inflammation and priming a response to immune checkpoint blockade. This demonstrates pelareorep’s potential to overcome the immunosuppressive nature of the tumor microenvironment which could limit checkpoint inhibitor efficacy."

Key data and conclusions from the SABCS poster include:

72% of evaluated patients (n=18) saw an increase in CelTIL, the study’s primary endpoint that is associated with favorable clinical outcomes.
The maximum percentage increase in CelTIL (~300%) was achieved in a cohort 2 patient receiving pelareorep in combination with checkpoint blockade therapy.
On average, there was a 105-fold increase in TME PD-L1 expression (n=13) from baseline (pre-pelareorep administration) to surgery (21-days post-administration).
Tumor microenvironment PD-L1 expression increased in all evaluated patients (n=13).
Preliminary imaging mass cytometry analysis showed pelareorep treatment promoted broad anti-tumor changes in the TME, including enhanced CD8+ T cell activation and the recruitment of memory T cells.
Thomas Heineman, M.D., Ph.D., Global Head of Clinical Development and Operations at Oncolytics, commented, "In the AWARE-1 study, pelareorep delivered consistent increases in tumor PD-L1 expression and recruitment of anti-cancer immune cells into tumors, as well as increases in CelTIL score for over 70% of the patients. This is highly encouraging given the association between CelTIL and clinical outcomes, and we hope to observe the same success from our phase 2 BRACELET-1 trial, which is exclusively enrolling HR+/HER2- breast cancer patients."

Andrew de Guttadauro, President of Oncolytics Biotech U.S. and Global Head of Business Development, added, "Immune deserts or immunosuppressive tumor microenvironments limit tumor PD-L1 expression levels and thereby limit regulatory approval and commercial success of checkpoint inhibitors in certain breast and other malignancies. AWARE-1 data show that pelareorep can alter the tumor microenvironment and induce robust PD-L1 expression, highlighting the potential of pelareorep to boost the efficacy of checkpoint inhibitors and increase the proportion of patients eligible for these therapies. We expect this synergistic potential to enable the continued execution of our strategy to develop pelareorep-based therapies in collaboration with industry leaders."

The electronic poster, titled "A window-of-opportunity study with atezolizumab and the oncolytic virus pelareorep in early breast cancer (REO-027, AWARE-1)" is available in the SABCS virtual poster hall and on the Posters & Publications page of Oncolytics’ website (LINK).

Ongoing ‘trial-in-progress’ posters giving an overview of Oncolytics’ IRENE and BRACELET-1 study designs were also presented at SABCS and are available at the same locations.

About AWARE-1

AWARE-1 is an open-label window-of-opportunity study in early-stage breast cancer enrolling 38 patients into five cohorts:

Cohort 1 (n=10), HR+ / HER2- (pelareorep + letrozole)
Cohort 2 (n=10), HR+ / HER2- (pelareorep + letrozole + atezolizumab)
Cohort 3 (n=6), TNBC (pelareorep + atezolizumab)
Cohort 4 (n=6), HR+ / HER2+ (pelareorep + trastuzumab + atezolizumab)
Cohort 5 (n=6), HR- / HER2+ (pelareorep + trastuzumab + atezolizumab)
The study combines pelareorep, with or without atezolizumab, and the standard of care therapy according to breast cancer subtype. Patients are biopsied as part of their initial breast cancer evaluation, then again on day three following initial treatment, and a final tissue sample after three weeks, on the day of their mastectomy. Data generated from this study are intended to confirm that the virus is acting as a novel immunotherapy and to provide comprehensive biomarker data by breast cancer subtype. The primary endpoint of the study is overall CelTIL (a measurement of cellularity and tumor-infiltrating lymphocytes). Secondary endpoints for the study include CelTIL by breast cancer subtype, safety, and tumor and blood-based biomarkers.

For more information about the AWARE-1 study, refer to View Source

Tecentriq (atezolizumab) is a registered trademark of Genentech, a member of the Roche Group.

About Breast Cancer

Breast cancer is the most common cancer in women worldwide, with over two million new cases diagnosed in 2018, representing about 25 percent of all cancers in women. Incidence rates vary widely across the world, from 27 per 100,000 in Middle Africa and Eastern Asia to 85 per 100,000 in Northern America. It is the fifth most common cause of death from cancer in women globally, with an estimated 522,000 deaths.

Breast cancer starts when cells in the breast begin to grow out of control. These cells usually form a tumor that can often be seen on an x-ray or felt as a lump. The malignant tumor (cancer) is getting worse when the cells grow into (invade) surrounding tissues or spread (metastasize) to distant areas of the body.

About Pelareorep

Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.

On December 9, 2020 Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the "Company"), a clinical-stage biopharmaceutical company focused on the development of GP2, an immunotherapy to prevent breast cancer recurrences in patients who have previously undergone surgery, reported the publication of a poster for the GP2 Phase IIb clinical trial final efficacy analysis at the San Antonio Breast Cancer Symposium in a virtual format (Press release, Greenwich LifeSciences, DEC 9, 2020, View Source [SID1234572537]). The CEO of Greenwich LifeSciences, Snehal Patel, also recorded an audio track providing an overview. The full poster with figures, tables, and audio can be accessed or downloaded here on the Company website, as well as on the conference website by attendees.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The poster presents the final 5 year follow-up disease-free survival curves evaluating the reduction of breast cancer recurrences for both HER2/neu 3+ (Figure 1) and HER2/neu 1-2+ (Figure 2) patient populations, including the demographics (Table 1) for stage of cancer, hormone receptor status, node status, and prior treatment with chemotherapy, radiation, endocrine therapy, or trastuzumab (Herceptin).

Mr. Patel commented, "The poster presented at the SABCS is important because the Kaplan Meier survival curves and demographic data further validate our promising HER2 3+ Phase IIb data and support our plan to commence a Phase III trial in 2021. Recurring breast cancer affects 1 in 8 women. Approximately 50% of women with recurring breast cancer do not respond to Herceptin or Kadcyla, resulting in metastatic breast cancer and a poor prognosis. Approximately 80-85% of metastatic breast cancer patients do not survive. By addressing this unmet need, GP2 may reach a potential market exceeding $5 billion."

The conclusions of the poster are as follows:

‒ The trial met all of its clinical endpoints for HER2/neu 3+ patients, concluding that the first 6 intradermal injections of GP2+GM-CSF safely elicited a potent immune response and reduced recurrence rates to 0% in HER2/neu 3+ patients, who received a standard course of Herceptin after surgery. This reduction of recurrence rate was maintained over the gold standard of 5 years of follow-up. A pivotal Phase III trial is being initiated to treat HER2/neu 3+ patients in the neoadjuvant setting.

‒ GP2 may also be effective when administered in combination with Herceptin based therapeutics in HER2/neu 1-2+ patient populations or other HER2/neu expressing cancers.

Excerpts of the poster are below:

Poster PS10-23: San Antonio Breast Cancer Symposium Poster Presentation of Median 5 Year Top-Line Data

The median 5 year top-line data described below was presented at the San Antonio Breast Cancer Symposium in a poster on December 9, 2020, entitled "Five year median follow-up data from a prospective, randomized, placebo-controlled, single-blinded, multicenter, Phase IIb study evaluating the reduction of recurrences using HER2/neu peptide GP2+GM-CSF vs. GM-CSF alone after adjuvant trastuzumab in HER2 positive women with operable breast cancer."

The final analysis of the GP2 prospective, randomized, placebo-controlled, single-blinded, multicenter Phase IIb trial investigating GP2+GM-CSF administered in the adjuvant setting to node-positive and high-risk node-negative breast cancer patients with tumors expressing any degree of HER2 (immuno-histochemistry [IHC] 1-3+) (NCT00524277) is now complete with 5 year follow-up. The trial enrolled HLA-A02 patients randomized to receive GP2+GM-CSF versus GM-CSF alone. The trial’s primary objective was to determine if treatment with GP2, a HER2-derived peptide, reduces recurrence rates.

Each enrolled and consented subject was randomized and scheduled to receive a total of 6 GP2+GM-CSF (500 mcg GP2:125 mcg GM-CSF) or placebo (125 mcg GM-CSF alone) intradermal injections every 3-4 weeks as part of the Primary Immunization Series ("PIS") for the first 6 months and 4 GP2+GM-CSF booster or placebo intradermal injections every 6 months thereafter. Boosters were introduced during the trial, thus some patients did not receive all 4 boosters.

This 168 patient (Intent to Treat, "ITT": n=180) basket trial across 16 clinical sites explored 96 HER2 3+ patients, who received a standard course of trastuzumab after surgery and subsequently completed the full PIS or placebo, starting the PIS at median 17.1 months after surgery, and 72 HER2 1-2+ patients, who did not receive trastuzumab after surgery and subsequently completed the full PIS or placebo, starting the PIS at median 10.8 months after surgery. Subject disease characteristics are described in Table 1 of the poster.

Since GP2 is synergistic with trastuzumab, and the HER2 1-2+ patients did not receive trastuzumab, it was prespecified to compare recurrence rates ITT versus per protocol in these 2 distinct, independently reported populations, excluding those patients who did not complete the PIS.

Figure 1 of the poster depicts evidence that disease free survival ("DFS") is more likely in HER2 3+ GP2-treated subjects. After 5 years of follow-up, the Kaplan-Meier estimated 5-year DFS rate in the 46 HER2 3+ patients treated with GP2+GM-CSF, if the patient completed the PIS, was 100% versus 89.4% (95% CI:76.2, 95.5%) in the 50 placebo patients treated with GM-CSF (p = 0.0338). As shown in Table 1, the treated versus placebo HER2 3+ patients were well-matched, where approximately 53% were stage T1, 41% were stages T2-T4, 55% were node positive, 58% were hormone receptor positive and received endocrine therapy, 77% received adjuvant radiation, 77% received adjuvant chemotherapy, and 89% received trastuzumab.

GP2 was shown to be well tolerated with no SAEs and elicited a potent immune response measured by local skin tests and immunological assays, which suggest peak immunity is reached at 6 months upon completion of the PIS.

About SABCS

The 43rd annual SABCS has grown to be the industry’s premier breast cancer conference for basic, translational, and clinical cancer research professionals. It is well-known for presenting the latest breast cancer data from all over the world. More than 7,500 health care professionals from more than 90 countries attend annually. Baylor College of Medicine became a joint sponsor of SABCS in 2005. The Cancer Therapy & Research Center at UT Health Science Center San Antonio and American Association for Cancer Research (AACR) (Free AACR Whitepaper) began collaborations with SABCS in 2007. For more information, please visit the conference website at: View Source

About Breast Cancer and HER2/neu Positivity

One in eight U.S. women will develop invasive breast cancer over her lifetime, with approximately 266,000 new breast cancer patients and 3.1 million breast cancer survivors in 2018. HER2/neu (human epidermal growth factor receptor 2) protein is a cell surface receptor protein that is expressed in a variety of common cancers, including in 75% of breast cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels.

On December 9, 2020 Natera, Inc. (NASDAQ: NTRA), a pioneer and global leader in cell-free DNA testing, reported that new data will be presented on its personalized and tumor-informed molecular residual disease (MRD) test, Signatera, in an oral presentation on December 10, 2020 at the 2020 European Society for Medical Oncology Immuno-Oncology (ESMO IO) Virtual Congress (Press release, Natera, DEC 9, 2020, View Source [SID1234572554]). The abstract is available to view here.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The oral presentation will report results from a prospective circulating tumor DNA (ctDNA) analysis of 581 muscle invasive urothelial carcinoma (MIUC) patients who participated in IMvigor010, an open-label, global, randomized and controlled Phase III study that evaluated adjuvant treatment with the PD-L1 inhibitor atezolizumab compared with observation. Results at an interim analysis show that patients who were ctDNA-positive after surgery (37%) had an increase in overall survival (OS) in the treatment arm, with a median of 25.8 months with Tecentriq, compared with 15.8 months for observation (HR=0.59; 95% CI: 0.41–0.86), while those patients who were ctDNA-negative after surgery derived no benefit. The study also shows that ctDNA clearance was higher in the treatment arm vs. the observation arm (p=0.0048).

"In this study, we show that personalized ctDNA analysis is highly accurate not only for identifying molecular residual disease, but also for predicting better outcomes with immune therapy," said Thomas Powles, M.D., Professor, Barts Cancer Institute, and Principal Investigator of the study. "This opens new avenues for patient selection in the future and is an important step in the drive towards personalized cancer therapy."

"We are honored to partner with Genentech on this groundbreaking study," said Alexey Aleshin, M.D., Natera’s Senior Medical Director of Oncology. "This randomized Phase III study demonstrates for the first time, unequivocally, that Signatera can identify which patients are likely to benefit from adjuvant therapy and which are unlikely to benefit. It also highlights the significance of ctDNA clearance as an early endpoint for the evaluation of drug efficacy."

Details about the presentation are as follows:

Presentation #10 | Presenter: Thomas Powles, M.D. | Date and time: Dec 10, 13:50 – 14:02 CET

Clinical outcomes in post-operative ctDNA-positive muscle-invasive urothelial carcinoma (MIUC) patients after atezolizumab adjuvant therapy

About Signatera

Signatera is a custom-built circulating tumor DNA (ctDNA) test for treatment monitoring and molecular residual disease (MRD) assessment in patients previously diagnosed with cancer. The test is available for clinical and research use, and in 2019, it was granted Breakthrough Device Designation by the FDA. The Signatera test is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual’s tumor. This maximizes accuracy for detecting the presence or absence of residual disease in a blood sample, even at levels down to a single tumor molecule in a tube of blood. Unlike a standard liquid biopsy, Signatera is not intended to match patients with any particular therapy; rather, it is intended to detect and quantify how much cancer is left in the body, to detect recurrence earlier and to help optimize treatment decisions. Signatera test performance has been clinically validated in multiple cancer types including colorectal, non-small cell lung, breast, and bladder cancers. Signatera has been developed and its performance characteristics determined by Natera, the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the US Food and Drug Administration (FDA). CAP accredited, ISO 13485 certified, and CLIA certified.

On December 9, 2020 West Pharmaceutical Services, Inc. (NYSE: WST), a global leader in innovative solutions for injectable drug administration, reported that the Company’s Board of Directors has approved a first-quarter 2021 dividend of $0.17 per share (Press release, West Pharmaceutical Services, DEC 9, 2020, View Source [SID1234572495]). The dividend will be paid on February 3, 2021, to shareholders of record as of January 20, 2021.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On December 8, 2020, the Company’s Board of Directors authorized a share repurchase program for calendar-year 2021 of up to 631,000 shares of the Company’s common stock from time to time on the open market or in privately-negotiated transactions, as permitted under Exchange Act Rule 10b-18. The number of shares to be repurchased and the timing of such transactions will depend on a variety of factors, including market conditions. The share repurchase program is expected to be completed by December 31, 2021. The Company’s previously-authorized share repurchase program will expire on December 31, 2020.

The Company also announced that management will be presenting an overview of the business at the J.P. Morgan Healthcare Conference at 5:20 p.m. EST on Wednesday, January 13, 2021. A live audio webcast of the presentations and a copy of the presentation materials will be accessible from the Company’s website at www.westpharma.com/en/investors.

On December 9, 2020 Biochain reported that There have been tremendous advances in cancer treatment since President Richard Nixon declared war on malignancies in 1971 (Press release, Biochain, DEC 9, 2020, View Source [SID1234572520]). Despite having treatments such as targeted radiation, estrogen blockers, and CAR-T cell immunotherapies, early detection of cancer remains one of the most important factors. For instance, the five-year relative survival rate for non-small cell lung cancer is 61% when cancer has not yet spread outside the lung. The survival rate drops to 35% once the cancer invades nearby structures, and to 6% once it metastasizes to other organ systems.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

However, early detection of cancer has proven easier said than done, and not without risks. When screening for cancer certain number of patients experience anxiety and undergo unnecessary invasive procedures based on false positives. While some cancers make for relatively easy screening such as cervical cancer via the Pap test, many cancers are inaccessible, and tissue biopsy too invasive for population-level screenings.

The oncologist’s objective is to come up with a less invasive way of screening the healthy population for specific and accurate indications of early-stage cancer. This motivated scientists to develop "liquid biopsy," where doctors hope to detect tumor-specific protein biomarkers or cancer-associated genetic mutations in circulating free DNA (cfDNA) blood samples.

In an article published in the journal Science, Johns Hopkins researchers Bert Vogelstein and Nickolas Papadopoulos and their colleagues appear to have done exactly that.

A leap in early cancer detection

A breakthrough was achieved using a liquid biopsy test called "DETECT-A" ̶̶ Detecting cancers Earlier Through Elective mutation-based blood Collection and Testing ̶ which involved more than 9,911 women who had no history of cancer. The study used a multi-cancer blood test, to identify 26 undiagnosed cancers in 10 different organ systems: appendix, breast, colorectal, kidney, lung, lymphomas, ovary, thyroid, uterine and unknown primary site. The tumors were then localized using techniques such as PET-CT, a combination that was 99.6% specific.

Importantly, 17 of the cancers detected by the blood test were diagnosed at an early stage. Twelve of the 26 patients were in remission and eight were still in treatment or had stable disease nine months post-diagnosis.

This was a landmark result for the liquid biopsy field and the industry took note. A more advanced version of the multi-cancer blood test known as CancerSEEK had been licensed by Johns Hopkins to Thrive Earlier Detection Corp for development. On Oct. 27, Exact Sciences announced it would acquire Thrive for $2.15 billion.

Foundational technology

Although much of the liquid biopsy breakthrough has come from next-generation sequencing (NGS) and machine learning, the fundamentals of the field are still focused on an accurate and successful sampling process. If there is no adequate sample in the first place, no algorithm can support it. The DETECT-A study made use of the cfPure extraction kit from BioChain, a magnetic bead-based technology that demonstrated high yields in extracting cfDNA from blood plasma. "In order to get that cfDNA, you need to have the right tools," says BioChain’s Production and R&D Manager Dr. Franklin Chin, "and we have them. Our extraction kit is the first step in any research that involves cfDNA biomarker discovery"

The cfPure kits are available from BioChain in three different sizes for the extraction of a maximum of 250 ml of cfDNA from human plasma samples. The kit has two different versions: the original cfPure kit which maximizes yield, and the "V2," which minimizes carryover of genomic DNA into the final elution.

Dr. Bert Vogelstein and his colleagues used the original version of cfPure kits, and the fact that such pioneering researchers used BioChain’s technology in a groundbreaking study to process tens of thousands of samples is a source of pride for BioChain. "Dr. Vogelstein is one of the pioneers of liquid biopsy research," Chin says, "that he is using our kit is pretty big for us."

Detection of early-stage cancer using the DETECT-A test is just the first of many breakthroughs BioChain hopes their technology will enable. Beyond early diagnosis, for instance, there are efforts at precision tumor treatment and companion diagnostics, according to Chin. Many cancers are drug-resistant, and that resistance is based on their mutational profile. Pairing the cfPure kit with NGS using specific biomarker panels can help identify the mutational landscape for a patient, indicating the therapies best suited to treating their specific cancer.

Chin also hopes to see BioChain’s technology used in the creation of biomarker panels to help identify mutations with a strong correlation to oncogenesis. "You need to have a solid foundation," he says. "You need to collect as many samples as possible, analyze them, and come up with a panel of biomarkers." That will expand the reach and accuracy of liquid biopsy, and, ultimately, the success of cancer treatments. That’s something Chin and BioChain are excited to be a part of.

A menu of research solutions

Whatever your research needs, BioChain offers a cfPure cell-free DNA extraction kit providing market-leading yields for the best possible input for NGS or other processing.

BioChain also offers blood plasma and tissue samples for researchers who need inputs to develop and test their technologies and offers the cfPure cell-free DNA extraction process as a service for those who cannot perform the extractions themselves.