On December 9, 2020 Exact Sciences Corp. (NASDAQ: EXAS) reported that data from the Rx for Positive Node, Endocrine Responsive Breast Cancer, or RxPONDER, trial successfully defined the benefit of chemotherapy in early-stage, node-positive breast cancer patients with Oncotype DX Breast Recurrence Score results of 0 to 25 (Press release, Exact Sciences, DEC 9, 2020, View Source [SID1234572515]). First results from the study, led by the independent SWOG Cancer Research Network, and sponsored by the National Cancer Institute (NCI), identified the majority of women with 1-3 positive nodes who received no benefit from chemotherapy.i The data will be presented on December 10 at the 2020 San Antonio Breast Cancer Symposium (SABCS).

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!

RxPONDER showed a different effect of chemotherapy based on Recurrence Score results for postmenopausal and premenopausal women. Postmenopausal women with Recurrence Score results 0-25 were not observed to show benefit from chemotherapy and may avoid the associated side effects of the treatment. Importantly, no chemotherapy benefit was observed regardless of the number of affected nodes, tumor grade, or size. Two-thirds of the women in the trial were postmenopausal.

The first results also demonstrated, after a median of five years of follow-up, that premenopausal women with Recurrence Score results 0-25 were observed to have a statistically significant chemotherapy benefit, with an average improvement in distant recurrence rates at 5 years of 3%.

Approximately 85% of women with node- positive disease have Recurrence Score results of 0 to 25. ii Postmenopausal and premenopausal women with Recurrence Score results 26-100 were not included in the study because investigators reviewed prior studies and determined that this patient group had chemotherapy benefit. The SWOG investigators intend to publish the detailed RxPONDER results in a peer-reviewed publication.

"Every day in clinics around the world, physicians wrestle with the question of how to best treat women with this common form of breast cancer," said study lead author Kevin Kalinsky, MD, a long-time SWOG investigator and director of the Glenn Family Breast Center at the Winship Cancer Institute of Emory University. "These results are practice changing and demonstrate that the great majority of postmenopausal women can be spared unnecessary chemotherapy and receive only hormone therapy. This should bring more clarity to physicians and some relief for patients."

Approximately 25% of patients diagnosed with hormone receptor (HR)-positive, HER2-negative early breast cancer have tumor that has spread to their lymph nodes and two out of three are postmenopausal.iii The vast majority of these patients currently receive chemotherapy.iv

"With the RxPONDER and TAILORx trials, there is now definitive and undeniable clarity on who does and who does not benefit from chemotherapy among early-stage breast cancer patients, with either node-negative or node positive disease," said Steven Shak, MD, chief medical officer at Exact Sciences. "These long-awaited results, which continue to build on the body of evidence supporting the role of the Oncotype DX test in shaping clinical practice, are estimated to impact tens of thousands of women worldwide."

One of the largest clinical trials in women with node-positive HR+, HER2- early breast cancer, RxPONDER is a prospective, randomized Phase III study conducted at 632 sites in nine countries – the United States, Canada, Mexico, Colombia, Ireland, France, Spain, South Korea, and Saudi Arabia. The study enrolled more than 5,000 women with up to three positive nodes. Women with a Recurrence Score result 0-25 were randomized for treatment with hormone therapy alone or chemotherapy followed by hormone therapy. Randomized patients were stratified based on their Recurrence Score result, menopausal status, and the type of lymph node surgery.

The use of the Oncotype DX test in early-stage breast cancer is supported by prospective outcomes from more than 17,000 patients with node-positive disease and more than 83,000 patients with node-negative disease, including the TAILORx study. Results from TAILORx, published in 2018, showed that the Oncotype DX test identifies the vast majority of women with node-negative disease who receive no substantial benefit from chemotherapy (approximately 80%), as well as the important minority for whom chemotherapy can be life-saving.

About Oncotype DX
The Oncotype DX portfolio of breast, colon and prostate cancer tests applies advanced genomic science to reveal the unique biology of a tumor in order to optimize cancer treatment decisions. In breast cancer, the Oncotype DX Breast Recurrence Score test is the only test that has been shown to predict the likelihood of chemotherapy benefit as well as recurrence in invasive breast cancer. Additionally, the Oncotype DX Breast DCIS Score test predicts the likelihood of recurrence in a pre-invasive form of breast cancer called DCIS. In prostate cancer, the Oncotype DX Genomic Prostate Score test predicts disease aggressiveness and further clarifies the current and future risk of the cancer prior to treatment intervention, and the Oncotype DX AR-V7 Nucleus Detect test helps determine which patients with metastatic castration-resistant prostate cancer (mCRPC) are resistant to androgen receptor (AR)-targeted therapies. The Oncotype DX AR-V7 Nucleus Detect test is performed by Epic Sciences at its centralized, CLIA-certified laboratory in San Diego and offered exclusively by Exact Sciences. With more than 1 million patients tested in more than 90 countries, the Oncotype DX tests have redefined personalized medicine by making genomics a critical part of cancer diagnosis and treatment. To learn more about Oncotype DX tests, visit www.OncotypeIQ.com, www.MyBreastCancerTreatment.org or www.MyProstateCancerTreatment.org.

On December 9, 2020 Tmunity Therapeutics, Inc., a private clinical-stage biotherapeutics company focused on saving and improving lives by delivering the full potential of next-generation T-cell immunotherapy, reported that President & CEO Usman "Oz" Azam will participate in a Fireside Chat at the 2020 RBC Capital Markets Healthcare Private Company Conference on Tuesday, December 15, 2020 at 11:20 am Eastern Time (Press release, Tmunity Therapeutics, DEC 9, 2020, View Source [SID1234572533]).

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!

To access a live webcast of the Tmunity presentation, please visit: View Source Company presentations will be available to view on-demand via this same link within 24 hours of the session.

On December 9, 2020 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported updates on the clinical development of the company’s novel Bcl-2 inhibitor APG-2575, further demonstrating the drug candidate’s therapeutic potential (Press release, Ascentage Pharma, DEC 9, 2020, View Source [SID1234572550]).

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!

APG-2575 is a novel, orally administered small-molecule Bcl-2‒selective inhibitor being developed by Ascentage Pharma. APG-2575 is designed to treat hematologic malignancies and solid tumors by selectively blocking antiapoptotic protein Bcl-2 to restore the normal apoptosis process in cancer cells. As a bona fide Bcl-2 inhibitor, APG-2575 demonstrated desired target engagement. APG-2575 selectively binds to Bcl-2, disrupts Bcl-2:BIM complexes, and releases the proapoptotic protein BIM. Freed BIM subsequently activates BAX/BAK for pore formation on the mitochondria membrane, leading to mitochondrial outer-membrane permeabilization (MOMP), cytochrome c release, caspase activation, and apoptosis of cancer cells. APG-2575 is the first China-developed Bcl-2 inhibitor having entered clinical development in China. As a single agent, APG-2575 has potent antitumor activity in Bcl-2-dependent tumor cells, and has shown a broad range of antitumor activities when combined with other oncologic drugs. Previously, APG-2575 had received clearances and approvals for multiple Phase Ib/II clinical studies in China, Australia, and the US, and is currently being developed in a range of hematologic malignancies globally.

Highlights of the update

In total, 9 clinical studies are ongoing globally, with over 100 patients who have been administered APG-2575 at doses ranging from 20 mg to 1200 mg for the treatment of chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM), acute myeloid leukemia (AML), and high leukocyte acute leukemia (HCL), etc.
Studies of APG-2575 in the treatment of relapsed/refractory CLL (r/r CLL) have enrolled over 30 patients. Preliminary results show that an objective response rate (ORR) of 70% has been reached in evaluable patients.
On safety:
Maximum tolerated dose (MTD) has not been reached, and no dose-limiting toxicity (DLT) was observed.
No clinical or laboratory tumor lysis syndrome (TLS) was observed.
Most treatment-related adverse events (TRAEs) were of Grade 1 or 2.
Limited cases of neutropenia and thrombocytopenia.
APG-2575 has been granted three Orphan Drug Designations (ODDs) by the US FDA, for the treatment of CLL, MM, and Waldenström macroglobulinemia (WM).
"APG-2575 is a key drug candidate of Ascentage Pharma’s apoptosis-targeted pipeline," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "As the first China-developed Bcl-2 inhibitor having entered clinical development in China, APG-2575 as a single agent or in combinations has demonstrated great therapeutic potential and clinical advantages. We are accelerating the global clinical development of this drug candidate, which we hope will soon translate into a new therapeutic option for patients in China and around the world."

On December 9, 2020 Evelo Biosciences, Inc. (Nasdaq:EVLO), a clinical stage biotechnology company developing a new modality of orally delivered medicines which act in the small intestine with systemic effects, reported that it is prioritizing EDP1908 as its lead clinical candidate in oncology given its superior preclinical activity over EDP1503 (Press release, Evelo Biosciences, DEC 9, 2020, View Source [SID1234572516]). The Company will halt patient recruitment in the Phase 1/2 clinical trial of EDP1503 and will wind down the study. The Company also announced that additional interim clinical data from its Phase 1/2 open-label study evaluating EDP1503 in combination with pembrolizumab in patients with triple-negative breast cancer (TNBC) were presented today in a poster session at the San Antonio Breast Cancer Symposium (SABCS) 2020 Virtual Meeting. The presentation showed that as of a cutoff date of October 30, 2020, EDP1503 was well-tolerated, with an overall response rate (ORR) of 17 percent and a disease control rate (DCR) of 25% in the 12 patients who received the higher dose of EDP1503. These results suggest that the small intestinal axis, SINTAX, has the potential to be targeted with oral, gut-restricted medicines.

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 EDP1908 preclinical data presented last month at the Society for Immunotherapy for Cancer (SITC) (Free SITC Whitepaper) meeting showed that orally administered bacterial extracellular vesicles (EV) showed encouraging preclinical activity without systemic distribution. Based on the strength of the preclinical results from EDP1908 compared to those we observed during our early development of EDP1503, combined with the EDP1503 clinical results, we have decided to focus on advancing EDP1908 as our lead oncology product candidate," said Duncan McHale, M.B.B.S., Ph.D., Chief Medical Officer of Evelo. "EVs may offer oncology patients better outcomes and serve as the foundation of a new class of potentially safe, effective, and affordable immuno-oncology medicines. We are now scaling up manufacturing in order to advance EDP1908 into the clinic in the first half of 2022."

Reminder of Data Presented at SITC (Free SITC Whitepaper) Annual Meeting
In the preclinical study presented at SITC (Free SITC Whitepaper), tumor-bearing mice were treated with ascending doses of either oral EDP1908 or the parental microbial strain of EDP1908, or with anti-PD-1. Treatment with EDP1908 resulted in superior tumor growth control versus either the parent microbial strain or anti-PD-1 therapy, with an observed dose-dependent reduction in tumor growth. The effects were at least comparable to those reported in the literature for intra-tumorally administered immune stimulators.

Treatment with EDP1908 significantly reduced tumor growth in syngeneic mice compared to vehicle, and activated IFNγ-positive cytolytic and helper lymphocytes, dendritic cells, and interferon gamma-induced protein 10 (IP-10) in the tumor microenvironment. Fluorescent biodistribution analysis showed that EDP1908 was not detected outside the gastrointestinal tract. These data suggest that EDP1908 activated innate immunity locally on host immune cells in the gut and triggered distal immune responses within the tumor microenvironment, with no apparent adverse safety or tolerability issues.

Additional Interim Data Presented at SABCS from the Phase 1/2 Clinical Trial of EDP1503 in Combination with Pembrolizumab
As of the data cutoff date of October 30, 2020, 15 patients had been treated across two EDP1503 doses, including three patients treated with low dose EDP1503 (two capsules twice daily (BID)) and 12 patients treated with high dose EDP1503 (four capsules BID). 27 percent of patients had received prior anti-PD-(L)1 therapy.

Interim Safety Results
As of the cutoff date, the combination of EDP1503 and pembrolizumab was generally well-tolerated with the majority of treatment-related adverse events (AEs) reported by investigators being Grade 1 or 2. Across all grades, treatment-related AEs reported by investigators most commonly included abdominal distension (20%), decreased appetite (20%), diarrhea (13%), flatulence (13%), nausea (13%), pruritis (13%) and rash maculo-papular (13%). Investigators reported a single treatment-related Grade 3 AE in one patient (diarrhea). No treatment-related Grade 4 or 5 AEs or serious AEs were reported, and one patient discontinued EDP1503 due to a treatment-related AE.

Interim Efficacy Results
Fifteen patients were evaluable for response assessment as of the cutoff date, as measured using the Response Evaluation Criteria in Solid Tumors (RECIST). Among all 15 patients treated, the ORR was 13 percent, and the DCR was 20 percent. In patients receiving high dose EDP1503 therapy (n=12), the ORR was 17 percent and the DCR was 25 percent, with partial responses observed in two patients and stable disease observed in one patient. One patient who had relapsed on prior therapy with an anti-PD-L1 inhibitor combination had a partial response to the EDP1503 and pembrolizumab combination treatment. The patient was on treatment for 10.5 months and had no measurable disease visible on their latest PET scan as of the data cutoff date.

About Extracellular Vesicles
Some bacteria produce EVs that share molecular content with the parent bacterium, in particles that are roughly one-one thousandth the volume and are not capable of self-replicating. EVs enable bacterial communication and survival during stress, host-immune modulation, material exchange and cell-cell interactions. EV’s significantly smaller size compared to microbes may enable improved distribution and target engagement.

On December 9, 2020 Tyme Technologies, Inc. (NASDAQ: TYME), an emerging biotechnology company developing cancer metabolism-based therapies (CMBTs), reported that an abstract highlighting clinical data for TYME’s lead candidate, oral SM-88 (racemetyrosine), in patients with metastatic pancreatic cancer, has been selected for poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual 2021 Gastrointestinal Cancers Symposium being held on January 15 – 17, 2021 (Press release, TYME, DEC 9, 2020, View Source [SID1234572534]).

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!

Additional information on the meeting can be found on the ASCO (Free ASCO Whitepaper) 2021 Gastrointestinal Cancers Symposium website View Source

Details for the poster presentation are as follows:

Title: Phase 2/3 Study of SM-88 in Patients with Metastatic Pancreatic Cancer
Session Title: Hepatobiliary Cancer, Neuroendocrine/Carcinoid, Pancreatic Cancer, and Small Bowel Cancer
Virtual Session Date and Time: Sunday, January 17, 2021 3:30 PM ET – 4:15 PM ET
Virtual Session Location: ASCO (Free ASCO Whitepaper) poster website
Abstract Number: 321873

About SM-88

SM-88 is an oral investigational modified proprietary tyrosine derivative that is believed to interrupt the metabolic processes of cancer cells by breaking down the cells’ key defenses and leading to cell death through oxidative stress and exposure to the body’s natural immune system. Clinical trial data have shown that SM-88 has demonstrated encouraging tumor responses across 15 different cancers, including pancreatic, lung, breast, prostate and sarcoma cancers with minimal serious grade 3 or higher adverse events. Learn more.

About TYME-88-Panc Pivotal Trial

The TYME-88-Panc pivotal trial applies the latest advances in the field of cancer metabolism by evaluating the efficacy and safety of an oral investigational compound that targets the metabolic mechanisms of the disease at its source. A prospective, open label pivotal trial in metastatic pancreatic cancer for patients who have failed two lines of any prior systemic therapy. The trial is designed to evaluate the safety and efficacy of SM-88 used with MPS (methoxsalen, phenytoin and sirolimus) in advanced pancreatic cancer and will measure multiple endpoints, including overall survival, progression free survival, relevant biomarkers, quality of life, safety, and overall response rate. Learn more.