On May 29, 2020 AVEO Oncology (NASDAQ: AVEO) reported the presentation of results from the final analysis of overall survival (OS) in its pivotal Phase 3 TIVO-3 trial comparing tivozanib, the Company’s next-generation vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor (TKI), to sorafenib in 3rd and 4th line renal cell carcinoma (RCC) (Press release, AVEO, MAY 29, 2020, View Source [SID1234558717]). The results, which have been submitted to the U.S. Food and Drug Administration (FDA) as part of the Company’s New Drug Application (NDA) submitted in March, are being featured today at the ASCO (Free ASCO Whitepaper) 2020 Virtual Scientific Program in a poster titled, "TIVO-3: Final OS analysis of a phase III, randomized, controlled, multicenter, open-label study to compare tivozanib to sorafenib in subjects with metastatic renal cell carcinoma (RCC)" (abstract 5062). A copy of the poster will be available at the ASCO (Free ASCO Whitepaper) virtual meeting beginning today, May 29, 2020, at 8:00 AM ET. The poster and accompanying oral presentation by Sumanta (Monty) Pal, MD, Associate Clinical Professor, Department of Medical Oncology and Therapeutics Research, and Co-director, Kidney Cancer Program, at City of Hope Comprehensive Cancer Center, can be viewed at www.aveooncology.com.

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As previously announced, the TIVO-3 trial met the primary endpoint of progression free survival (PFS) (HR=0.73; p=0.02) and the secondary endpoint of overall response rate (ORR) (18% vs. 8%; p=0.02). The final OS hazard ratio (HR), which assesses the overall relative risk of death, was 0.97 (95% CI: 0.75-1.25; p=0.82), favoring tivozanib and improving from the previously reported interim HR of 0.99. Updated median OS, representing a single point in time in the OS curve, was 16.4 months for tivozanib (95% CI: 13.4-22.2) and 19.2 months for sorafenib (95% CI: 15.0-24.2). These OS HR results are similar to those of prior VEGFR TKI vs. VEGFR TKI studies in RCC.1-4

Tivozanib was found to be generally well-tolerated, with grade 3 or higher adverse events (AEs) consistent with those observed in previous tivozanib trials. The most common AE in patients receiving tivozanib was hypertension (38% vs. 25% for sorafenib, of treated patients), an AE known to reflect effective VEGF pathway inhibition. Infrequent but severe AEs reported in greater number in the tivozanib arm were thrombotic events (5% vs. 4% for sorafenib, of treated patients) similar to those observed in previous tivozanib studies. Dose reductions and interruptions due to AEs were significantly lower for tivozanib vs. sorafenib, despite nearly double the average number of cycles initiated for the tivozanib arm (11.9 months vs. 6.7 months for sorafenib), treatment related AEs leading to permanent discontinuation were 8% for tivozanib vs. 15% for sorafenib.

"We believe the TIVO-3 data demonstrate a favorable risk/benefit profile for tivozanib in the growing population of patients who have relapsed or become refractory to multiple lines of therapy, including checkpoint inhibitors," said Dr. Pal. "The lack of clinical data to guide treatment decisions in a robust, evidence-based manner in this setting is a serious and growing unmet medical need, particularly as this population continues to grow thanks to improved treatment in earlier lines. TIVO-3 provides the first positive superiority study to help guide this important treatment decision and, furthermore, offers this highly refractory patient population a favorable tolerability profile as indicated by fewer dose reductions, interruptions and discontinuations over a less selective VEGFR TKI in sorafenib."

"This outcome marks a significant milestone in a long journey to see tivozanib fulfill its potential, and is a critical step forward in our goal to improve both efficacy outcomes and patient experience for individuals living with cancer," said Michael Bailey, president and chief executive officer of AVEO. "Tivozanib has the potential to define highly refractory kidney cancer treatment, an area with no current evidence-based standard of care. We look forward to continuing our dialogue with the FDA as we work toward a marketing authorization decision, and we will continue to build on our foundation for commercial readiness. We owe our deepest gratitude to the patients and their families for participating in the tivozanib clinical program, and to the healthcare professionals who have continued to believe in the potential of tivozanib."

Conference Call and Webcast

In connection with this announcement, AVEO will host a conference call and audio webcast today, May 29, 2020, at 8:30 am Eastern Time. Dr. Pal will join the AVEO management team to review the data announced today. The call can be accessed by dialing (844) 882-7841 (U.S. and Canada) or (574) 990-9828 (international). The passcode for the conference call is 7967605. To access the live audio webcast, or the subsequent archived recording, please visit the Investors section of the AVEO website at www.aveooncology.com. The webcast will be recorded and available for replay on AVEO’s website for two weeks.

About Tivozanib (FOTIVDA)

Tivozanib (FOTIVDA) is an oral, once-daily, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) discovered by Kyowa Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union, the United Kingdom, Norway, New Zealand and Iceland. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications.5,6 Tivozanib is being studied in the TIVO-3 trial, which is supporting a regulatory submission of tivozanib in the U.S. seeking marketing approval as a treatment for relapsed or refractory RCC. Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models7 and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC8. Tivozanib has been investigated in several tumor types, including renal cell, hepatocellular, colorectal, ovarian and breast cancers.

On May 29, 2020 Personalis, Inc., (Nasdaq: PSNL) a leader in advanced genomics for cancer, reported that the company will present new data in abstracts to be presented at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Scientific Meeting, which will be held May 29-31, 2020 (Press release, Personalis, MAY 29, 2020, View Source [SID1234558734]).

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One abstract showcases data from the ImmunoID NeXT Platform, the first platform to enable comprehensive analysis of both a tumor and its immune microenvironment from a single sample. ImmunoID NeXT can be used to investigate the key tumor- and immune-related areas of cancer biology, consolidating multiple oncology biomarker assays into one and maximizing the biological information that can be generated from a precious tumor specimen.

Another abstract highlights data from the Personalis NeXT Dx Test, one of the first cancer diagnostic platforms to profile approximately 20,000 genes in both the tumor exome and transcriptome, providing a comprehensive genomic testing solution that goes beyond many existing cancer diagnostic panels that focus on a few hundred genes. The Personalis NeXT Dx Test includes advanced analytics to provide a diagnostic report on genetic alterations in clinically-important cancer genes, as well as emerging immunotherapy composite biomarkers of medical importance.

Following are details and links to the abstracts that will be presented at the online meeting.

Abstract Number &
Session Title

Title & Presenter

Date

Location

6557
Head and Neck Cancers

Exome scale liquid biopsy characterization of putative neoantigens and genomic biomarkers pre- and post anti-PD-1 therapy in squamous cell carcinoma of the head and neck.
Presenter: Charles Abbott

May 29, 2020

Online

e15583
Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Validation of an exome and transcriptome based diagnostic platform enabling clinical cancer therapy selection and emerging composite biomarkers for immunotherapy.
Presenter: Sebastian Saldivar

On May 29, 2020 Agendia, Inc., a world leader in precision oncology for breast cancer, reported that new data from ongoing clinical research on MammaPrint and BluePrint was debuted at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Virtual Scientific Program (ASCO) (Free ASCO Whitepaper) (Press release, Agendia, MAY 29, 2020, View Source [SID1234558767]). A total of five posters were presented on Agendia’s genomic profiling assays.

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The highlighted data below further illustrate the efficacy of Agendia’s MammaPrint and BluePrint genomic testing to consistently stratify breast cancers, allowing for a highly personalized regimen throughout a patient’s treatment journey. The latest findings from Agendia deliver immediate, actionable information for doctors and patients early in the diagnosis and treatment planning process and build on research that will impact breast cancer treatment and outcomes in the future.

One scientific presentation, entitled "Adding precision to 2018 ASCO (Free ASCO Whitepaper)/CAP HER2 testing guidelines in breast cancer with genomic profiling," evaluated the concordance between human epidermal growth factor receptor 2 (HER2) status as put forth by the 2018 ASCO (Free ASCO Whitepaper)/CAP guidelines and Agendia’s BluePrint genomic testing. In this real-world diagnostic data set, the 2018 guideline recommendations led to fewer HER2 equivocal tumors overall, confirming the positive impact of the revisions. Of note, BluePrint reclassified 69 percent of HER2-positive tumors and all HER2 equivocal tumors to non-HER2 molecular subtypes, indicating that these tumors may have suboptimal responses to HER2-directed therapy. This study found that molecular classification by BluePrint adds further precision in stratifying HER2-positive patients, offering the potential to predict responsiveness to HER2-targeted therapies.

"In this study, nearly 70 percent of HER2-positive diagnoses were reclassified to non-HER2, based on molecular subtyping. This is interesting and may have the potential at some point to affect treatment decisions and patient outcomes," said Adam Brufsky, MD, PhD, and Professor of Medicine at the University of Pittsburgh School of Medicine. "Data continue to show the value of MammaPrint and BluePrint as diagnostic tools that allow physicians to make more informed decisions to address their patients’ disease."

Also at ASCO (Free ASCO Whitepaper), Agendia shared updates on the ongoing FLEX trial, the massive real-world clinical data set designed to drive the medical community forward in its approach to precision medicine. In addition to a designated FLEX study poster – "The FLEX Real World Data Platform Explores New Gene Expression Profiles and Investigator-Initiated Protocols in Early Stage Breast Cancer" – that gave general updates on the registry, Agendia also highlighted FLEX and forward-looking studies, one of which has immediate implications for how a patient’s treatment may change based on comprehensive information uncovered by BluePrint.

The FLEX scientific presentation, entitled, "TNBC subtype and clinical estrogen receptor status of genomically basal breast tumors in Caucasian, African American, and Latin American patients," evaluated the distribution of triple-negative breast cancer (TNBC) subtypes in genomically Basal-Type cancers from self-reported patient ethnicities (Caucasian, African American, and Latin American). The data show that Basal-Type tumors are heterogeneous and include all defined TNBC subtypes, independent of ethnicity.

In addition, the study evaluated the association of IHC-determined estrogen receptor status and Basal-Type tumors of each ethnicity. Analyses demonstrated that BluePrint reclassified a subset of estrogen receptor positive (ER+) tumors to molecular Basal-Type and that ER status was not significantly associated with a specific TNBC subtype or ethnicity. This highlights the clinical need to trace basal biology in ER+ patients to refine treatment for basal-like tumors.

"The reclassification of a subset of ER+ tumors identifies an urgent and actionable situation," said Cathy Graham, MD, Assistant Professor of Surgery in the Division of Surgical Oncology at Emory University School of Medicine and Director, Breast Surgery at Emory St. Joseph’s Hospital. "From a clinical perspective, when these patients are first diagnosed, they appear to have luminal breast cancer. But, when you are able to look at the underlying mechanism with comprehensive genomic testing, a large subset of these breast cancers is reclassified to Basal-Type, which is high risk. This knowledge allows us to execute a more personalized and precise treatment approach immediately."

Two other forward-looking studies reinforce the future utility of better stratifying patients, and Agendia’s ability to provide a more sophisticated platform for discovery in gene signature research.

In the first, entitled, "High Risk breast cancer genes at 8q22-24 and their role in over 5,000 patients evaluated with the MammaPrint risk of recurrence assay," FLEX researchers looked at the 8q22-24 chromosomal region, known to be associated with breast cancer. The study results provided further evidence that aberrations in this region are associated with higher-risk disease. Within the MammaPrint signature, the genes CCNE2, MTDH, and TSPYL5 have similar expression patterns and when overexpressed, represent a unique subgroup of high-risk tumors. These findings and further research on the 8q22-24 region may help to better stratify high-risk patients through ongoing clinical trials evaluating response and resistance to targeted therapies.
The second, entitled, "12-chemokine gene expression score in breast cancer patients treated with neoadjuvant chemotherapy," builds on existing research related to gene expression as a predictive biomarker for immune responses in breast cancer patients. The study found that chemokine gene expression, which indicates the presence of immune cells, was associated with pathologic complete response (pCR), MammaPrint High Risk index, and BluePrint subtypes. This research suggests that chemokine score may be further stratified by using MammaPrint and BluePrint in order to identify patients who may be more likely to benefit from neoadjuvant chemotherapy. This work also suggests that future studies may evaluate the potential utility for chemokine score and MammaPrint in predicting responses to immunotherapy in breast cancer patients.
"The research we are showcasing at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting underscores our commitment to patients and physicians," said William Audeh, MD, Chief Medical Officer at Agendia. "With our growing arsenal of data collected through prospective clinical trials such as FLEX, I-SPY2 and MINDACT, we are able to help patients now while information-gathering for future breast cancer treatment strategy."

Agendia is proud to present these findings at the ASCO (Free ASCO Whitepaper) 2020 Annual Meeting, which underscore the company’s commitment to innovation and discovery through extraordinary, patient-focused research.

On May 29, 2020 Isofol Medical AB’s (publ) (Nasdaq First North Premier Growth Market: ISOFOL) ("Isofol" or the "Company"), reported that it has been informed by Professor Bengt Gustavsson – founder and largest owner of Isofol – that Professor Gustavsson has initiated that all the subscription rights held by Biofol AB (an affiliated company to Professor Gustavsson), obtained in connection with the fully guaranteed preferential rights issue of approximately SEK 150 million, has been purchased by a consortium of investors (Press release, Isofol Medical, MAY 29, 2020, View Source [SID1234561578]).

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The consortium of investors has committed to Professor Gustavsson that they will subscribe for new shares in the rights issue by utilizing the purchased subscription rights.

Furthermore, Isofol has been informed by Professor Gustavsson that he intends to subscribe for new shares in the rights issue by utilizing the subscription rights Professor Gustavsson holds privately.

On May 29, 2020 Trillium Therapeutics Inc. ("Trillium" or the "Company") (NASDAQ/TSX:TRIL), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported data from an ongoing phase 1 dose escalation study of TTI-622 in patients with advanced relapsed or refractory lymphoma (Press release, Trillium Therapeutics, MAY 29, 2020, View Source [SID1234558668]). The data are being presented today at a poster session at the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program. TTI-622 is an innate immune checkpoint inhibitor targeting CD47, a "do not eat me" signal that cancer cells use to evade destruction by the immune system.

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"The data emerging from this dose escalation study suggest that TTI-622 is a promising and highly differentiated CD47 blocker," said Jan Skvarka, President and Chief Executive Officer of Trillium. "We are seeing strong tolerability, consistent with the red blood cell-sparing property associated with this molecule. Both drug exposure and target engagement have shown dose response relationships. Notably, in addition to the previously reported monotherapy complete response, we have observed a partial response in a second DLBCL patient."

The poster (#94, abstract #3030), entitled "Ongoing, First-in-human, Phase 1 Dose Escalation Study of the Investigational CD47-blocker TTI-622 in Patients with Advanced Relapsed or Refractory Lymphoma", will be presented by lead author Krish Patel, MD, Director of the Lymphoma Program at the Swedish Cancer Institute in Seattle. It will be available on the meeting website beginning at 8 a.m. ET on Friday, May 29 in the Developmental Therapeutics – Immunotherapy session. A copy of the poster will also be available on the Events and Presentations page of Trillium’s website.

Highlights from the Phase I Study Update

The presentation reports on data from 19 relapsed/refractory lymphoma patients who were enrolled in the first 5 cohorts, and were treated with TTI-622 monotherapy at a dose of up to 4 mg/kg.
Weekly intravenous infusions of TTI-622 were shown to be well tolerated, with no dose-limiting toxicities or drug-related grade ≥3 anemia or thrombocytopenia.
Preliminary data indicate dose-dependent increases in both drug exposure and target engagement, with receptor occupancy levels above 60% at doses of 2 mg/kg measured immediately after and 24 hours after infusion administration.
Objective responses were observed in two heavily pretreated diffuse large B-cell lymphoma (DLBCL) patients. One patient achieved a partial response (PR) at week 8 and a complete response (CR) at week 36; a second patient achieved a PR at week 8. Both patients have been continuing on study for 340 and 90 days, respectively, as of April 24, 2020.
Further dose escalation is in progress. The study is currently dosing at 8 mg/kg.
About the TTI-622 Phase I Study

This trial (NCT03530683) is a two-part, multicenter, open-label, phase 1a/1b study of TTI-622 in patients with advanced relapsed or refractory lymphoma or multiple myeloma. The objective of the study is to characterize safety, tolerability and pharmacokinetics, and to determine the maximum tolerated dose. In the phase 1b study, patients will be treated with TTI-622 in combination with other agents.

About TTI-622

TTI-622 is Trillium’s second SIRPαFc decoy receptor in clinical trials. It consists of the CD47-binding domain of human SIRPα linked to an IgG4 Fc region. It is designed to enhance phagocytosis and anti-tumor activity by preventing CD47 from delivering its inhibitory signal. Importantly, preclinical data indicate that TTI-622 does not bind appreciably to human red blood cells, providing a key differentiation feature.