Study Shows Guardant360® Liquid Biopsy Test Helps Guide Treatment for Patients with HER2-Driven Metastatic Colorectal Cancer

On November 11, 2021 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported that a study published in Nature Medicine reinforces the benefits of using the Guardant360 liquid biopsy test to help guide treatment decisions for patients with HER2-driven metastatic colorectal cancer (mCRC) (Press release, Guardant Health, NOV 11, 2021, View Source [SID1234595292]). Led by the National Cancer Center Hospital East (NCCHE) in Japan, the study demonstrates that the Guardant360 test can select patients for HER2-directed therapy, identify which patients are responding to treatment, as well as identify genetic alterations that predict resistance.

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The Phase 2 TRastuzumab combIned with pertuzUMab for Patients with Her2-positive mCRC (TRIUMPH) study evaluated the efficacy of targeted therapy pertuzumab plus trastuzumab in patients with mCRC harboring HER2 amplification as detected by analysis of circulating tumor DNA (ctDNA) or tissue genotyping. All patients were previously treated with monoclonal antibodies targeting EGFR. Additional exploratory analyses were conducted to evaluate the utility of ctDNA genotyping to predict treatment efficacy, monitor response, and identify the resistance mechanisms.

The study, which follows on last year’s SCRUM-Japan GOZILA study, found that while efficacy of HER2-directed treatment was similar in patients with HER2 amplification detected in tissue or in ctDNA, the ctDNA analysis provided an added benefit of identifying additional alterations that predicted which patients would benefit from HER2-directed therapy. In addition, decreases in ctDNA shortly after treatment initiation corresponded with radiographic response and resistance-related alterations were identified by ctDNA genotyping after disease progression.

"This study demonstrates the clinical utility of the Guardant360 test in helping guide treatment decisions for patients with metastatic colorectal cancer," said Dr. Yoshiaki Nakamura, NCCHE, principal investigator of the TRIUMPH study. "Based on our results, we believe that ctDNA genotyping is beneficial in clinical practice to identify patients who are most likely to benefit from treatment with pertuzumab plus trastuzumab."

"Our Guardant360 blood test consistently demonstrates that it is a critical test in not only determining actionable biomarkers, but helping to guide treatment decisions," said Helmy Eltoukhy, Guardant Health Co-CEO. "This study reinforces the breadth and applicability of our Guardant360 test to help inform clinical decisions for patients with advanced cancer across their treatment journey."

The Guardant360 liquid biopsy test is part of the market leading Guardant360 portfolio that offers oncologists end-to-end testing solutions from treatment selection to treatment response monitoring. The portfolio includes the Guardant360 CDx test, the first FDA-approved liquid biopsy for comprehensive tumor mutation profiling across all solid tumor cancers, and Guardant360 TissueNext to provide oncologists with another option for comprehensive genomic profiling. Also included is Guardant360 Response, the first blood-only liquid biopsy that enables oncologists to view molecular response, or changes in ctDNA levels, from a simple blood draw to get an early indication of whether a patient is responding to treatment. This tool assists oncologists when considering whether to continue, stop, or explore other treatment options for their patients with late-stage or metastatic cancer.

Since it was first introduced, the Guardant360 blood test has become widely accepted for blood-based comprehensive genomic profiling (CGP) with more than 250 peer-reviewed publications including over 60 clinical outcomes studies. It has been trusted by more than 9,000 oncologists with more than 150,000 tests performed to date.

Silverback Therapeutics to Participate in the Stifel 2021 Virtual Healthcare Conference

On November 11, 2021 Silverback Therapeutics, Inc. (Nasdaq: SBTX) ("Silverback"), a clinical-stage biopharmaceutical company leveraging its proprietary ImmunoTAC technology platform to develop systemically delivered, tissue targeted therapeutics for the treatment of cancer, chronic viral infections, and other serious diseases, reported that the Company will participate in the Stifel 2021 Virtual Healthcare Conference from November 15-17, 2021 (Press release, Silverback Therapeutics, NOV 11, 2021, View Source [SID1234595291]).

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Laura Shawver, Ph.D., Silverback’s Chief Executive Officer, and Valerie Odegard, Ph.D., Silverback’s President and Chief Scientific Officer, will participate in a fireside chat on Wednesday, November 17, 2021 at 2:40 PM ET (11:40 AM PT). The live webcast of the event will be available on Silverback’s investor relations website and a replay will be available for 30 days following the event. Members of the Silverback management team will also host investor meetings during the conference.

Personalis to Present New Data at the Society for Immunotherapy of Cancer (SITC) 36th Annual Meeting

On November 11, 2021 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for cancer, reported that the company will participate in the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, November 12-14, including online poster presentations and online industry sponsored symposium (Press release, Personalis, NOV 11, 2021, View Source [SID1234595290]).

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The company will showcase the Personalis NeXT Platform which enables comprehensive analysis of both a tumor and its immune microenvironment from a single sample. The NeXT Platform 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.

Following is a list of abstracts that will be presented online at the meeting.

Scientific Poster Presentations

Poster Number & Category

Title & Presenter

Day & Time

19

Biomarkers, Immune Monitoring, and Novel Technologies

Exome-scale liquid biopsy characterization of emerging immune resistance mechanisms in treatment-resistant GIST

Presenter: Charles W. Abbott, PhD

NOV 12 -14 | Online

20

Biomarkers, Immune Monitoring, and Novel Technologies

Tumor-informed liquid biopsy monitoring of evolving therapeutic resistance mechanisms in head and neck squamous cell carcinoma patients receiving anti-PD-1 therapy

Presenter: Charles W. Abbott, Ph.D.

NOV 12 -14 | Online

75

Biomarkers, Immune Monitoring, and Novel Technologies

Comprehensive profiling of the tumor-immune microenvironment using an augmented transcriptome

Presenter: Eric Levy, PhD

NOV 12 -14 | Online

79

Biomarkers, Immune Monitoring, and Novel Technologies

Extensively validated HLA LOH algorithm demonstrates an association between HLA LOH and genomic instability

Presenter: Rachel M. Pyke, PhD

NOV 12 -14 | Online

Following are details of an industry-sponsored symposium which will be presented online at the meeting.

Industry Sponsor Symposium

Presentation Category


Title & Presenter

Day & Time

Sponsored Symposia


Leveraging comprehensive genomic data for diagnostic capabilities and composite biomarker discovery in immunotherapy

Presenter: Erin N. Newburn, PhD

NOV 12 | 1:30 – 2:00 PM EST

Personalis will also be exhibiting during the online portion of conference. Representatives will be available online to answer questions about the company’s cancer immunogenomics services.

Moleculin Reports Third Quarter 2021 Financial Results and Provides Programs Update

On November 11, 2021 Moleculin Biotech, Inc., (Nasdaq: MBRX) (Moleculin, we or the Company), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors and viruses, reported its financial results for the quarter ended September 30, 2021 (Press release, Moleculin, NOV 11, 2021, View Source [SID1234595289]). The Company also provided an update on its portfolio of oncology drug candidates for the treatment of highly resistant tumors and viruses.

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Moleculin Biotech, Inc. is a clinical stage pharmaceutical company focused on the development of a broad portfolio of oncology drug candidates for the treatment of highly resistant tumors. (PRNewsfoto/Moleculin Biotech, Inc.)

"With up to six clinical trials that are either currently underway or expected to have regulatory clearance by the end of 2021, we have made tremendous fundamental progress, and this is truly an exciting time at Moleculin. Furthermore, we believe at least one additional trial will be approved in early 2022. We continue to be encouraged by both the demonstrated potential and data seen across our portfolio of drug candidates," commented Walter Klemp, Chairman and CEO of Moleculin.

He continued, "We are extremely pleased that the STS lung metastases trial recently expanded to a total of three sites and that we are now in the third cohort with the first patient already treated and the final two patients in screening. This trial continues to recruit rapidly, and, on this pace, we could see the Phase 2 begin in the first half of 2022."

Concluding, he added, "The unmet medical needs that people with highly resistant tumors and viruses are faced with continue to be a driving force as we work to develop safe and effective treatments in a number of oncology and viral indications. We are dedicated to advancing our three core technologies and, I believe, are well-positioned to achieve the key value drivers we expect to see over the next 18 months."

Recent Highlights

Received authorization from the Medicines and Healthcare Products Regulatory Agency (MHRA) to commence a Phase 1a clinical trial of WP1122 in the United Kingdom for inhibition of viral replication and disease manifestations in humans infected with SARS-CoV-2, the virus responsible for COVID-19. The Company also announced it has received a favorable opinion from the London – Riverside Research Ethics Committee in the UK to begin the study, which is expected to be conducted at the Medicines Evaluation Unit in Manchester, United Kingdom.
Reported interim results from its U.S. Phase 1b/2 clinical trial evaluating Annamycin for the treatment of soft tissue sarcoma (STS) lung metastases, which documented preliminary clinical activity for Annamycin.
Programs Update

Next Generation Anthracycline – Annamycin

Annamycin, the Company’s next-generation anthracycline was designed to be noncardiotoxic (unlike all currently approved anthracyclines) and has demonstrated its lack of cardiotoxicity in recently conducted human clinical trials for the treatment of AML. The Company believes that, because of this unique improvement in safety, the use of Annamycin may not face the same usage limitations imposed on doxorubicin and other currently approved anthracyclines. Additionally, Annamycin has been shown in animal models to accumulate in the lungs at up to 30-fold the level of doxorubicin. Annamycin is currently in development for the treatment of AML and STS lung metastases. For more information about the Phase 1b/2 study evaluating Annamycin for the treatment of STS lung metastases, please visit clinicaltrials.gov and reference identifier NCT04887298.

Upcoming Milestones Expectations

H2 2021: Report cohort topline results from the ongoing Phase 1/2 study for treatment of AML and report the study’s topline results.
H2 2021: Report cohort topline results from the ongoing Phase 1/2 study for treatment of STS lung metastases and report the study’s topline results.
H2 2021: Initiate Phase 1/2 study in Europe for the treatment of AML evaluating combination therapy of Annamycin + Ara-C.
H1 2022: Commencement of an investigator-funded, second Phase 1b/2 clinical trial of Annamycin in sarcoma lung metastases in Europe.
H1 2022: Complete Phase 1b portion of ongoing Phase 1b/2 study of Annamycin for the treatment of sarcoma lung metastases in the US.
First-in-class p-STAT3 inhibitors – WP1066 and WP1220

WP1066 is one of several Immune/Transcription Modulators, designed to stimulate the immune response to tumors by inhibiting the errant activity of Regulatory T-Cells (TRegs) while also inhibiting key oncogenic transcription factors, including p-STAT3 (phosphorylated signal transducer and activator of transcription 3), c-Myc (a cellular signal transducer named after a homologous avian virus called Myelocytomatosis) and HIF-1α (hypoxia inducible factor 1α). These transcription factors are widely sought targets that are believed to contribute to an increase in cell survival and proliferation, and the angiogenesis (coopting vasculature for blood supply), invasion, metastasis and inflammation associated with tumors. They may also play a role in the inability of immune checkpoint inhibitors to affect more resistant tumors. WP1220 is a close analog to WP1066 that the Company has developed as a potential topical therapy for skin-related diseases.

WP1220 was evaluated for the treatment of Cutaneous T-Cell Lymphoma (CTCL) and, based on those results, we are seeking collaborators for future development. WP1066 is currently being evaluated for the treatment of pediatric brain tumors, including Diffuse Interstitial Pontine Glioma (DIPG). Additionally, WP1066 + radiation is being evaluated, pre-clinically, in the treatment of Glioblastoma Multiforme (GBM).

Upcoming Milestones Expectations

H2 2021: File a US Investigational New Drug application (IND) for the treatment of certain adult cancer(s) with WP1066 and begin to identify an institution to commence an associated investigator-funded Phase 1a/1b study.
H1 2022: Report topline results from Phase 1 physician-sponsored pediatric brain tumor clinical trial.
H2 2022: Facilitate launch of physician-sponsored Phase 2 study of WP1066 for the treatment of pediatric brain tumors including DIPG.
Actively seek collaboration with a strategic partner in the near term for external funding for the continued development of WP1220 in a Phase 2 clinical trial as a topical therapy for CTCL.
Infectious Disease and Metabolism/Glycosylation Inhibitors- WP1122, WP1096 and WP1097 Portfolio

Moleculin has new compounds designed to target the roles of glycolysis and glycosylation in both cancer and viral diseases. The Company’s lead Metabolism/Glycosylation Inhibitor, WP1122, is a prodrug of 2-DG that appears to improve the drug-like properties of 2-DG by increasing its circulation time and improving tissue/organ distribution. Based on recently published research that has identified that 2-DG has antiviral potential against SARS-CoV-2 in vitro, Moleculin believes WP1122 has significant potential as a COVID-19 therapy. Its unique mechanism of action may also be well-suited for combinations that potentiate existing therapies, including checkpoint inhibitors.

The Company recently received authorization from the Medicines and Healthcare Products Regulatory Agency (MHRA) to commence a Phase 1a clinical trial of WP1122 in the United Kingdom. The Company also received a favorable opinion from the London – Riverside Research Ethics Committee in the UK to begin the study, which is expected to be conducted at the Medicines Evaluation Unit in Manchester, United Kingdom. The Phase 1a study in healthy human volunteers will investigate the effects of a single ascending dose (SAD) and multiple days of ascending dosing (MAD) of WP1122 administered as an oral solution. Dose escalation will take place in sequential SAD cohorts, and MAD will start as soon as SAD has completed at least 3 dosing cohorts in which WP1122 is found to be safe and well-tolerated. This study in healthy volunteers will explore safety and pharmacokinetics (PK), and subsequent clinical development will be in patients infected with SARS-CoV-2 to further evaluate safety and establish a favorable risk/benefit profile. The Company expects to enroll approximately 80 healthy volunteers in the United Kingdom.

Additionally, the Company is in the process of identifying countries where potential future Phase 2 clinical studies could occur. The Company is also engaged in preclinical development of additional antimetabolites (WP1096 and WP1097) targeting glucose and mannose metabolism.

Upcoming Milestones Expectations

H2 2021: Commence Phase 1a study of WP1122 for the treatment of COVID-19 in the UK.
H2 2021: File an IND in the US for the treatment of certain cancers such as GBM and pancreatic cancer with WP1122.
H1 2022: Potential to launch Phase 2 pivotal study of WP1122 for the treatment of COVID-19 outside of the US.
Ongoing preclinical development work in anti-viral indications such as HIV, Zika, and Dengue. Collaborations targeted for 2022.
Summary of Financial Results for Third Quarter 2021

Research and development (R&D) expense was $4.1 million and $4.4 million for the three months ended September 30, 2021 and 2020, respectively. The decrease of $0.3 million is mainly related to the timing of costs incurred in 2020 of producing additional drug product for Annamycin clinical trials.

General and administrative expense was $2.0 million and $1.7 million for the three months ended September 30, 2021 and 2020, respectively. The increase of $0.3 million is mainly related to an increase in consulting and advisory fees and an increase in our corporate insurance.

For the nine months ended September 30, 2021 and 2020, the Company incurred net losses of $13.1 million and $14.7 million, respectively, and had net cash flows used in operating activities of $14.7 million and $14.6 million, respectively.

The Company ended the quarter with $75.2 million of cash. The Company believes that this cash is sufficient to meet its projected operating requirements, which include a forecasted increase over its current R&D rate of expenditures, into 2024.

Aptevo Therapeutics Announces Preclinical Data for Bispecific Antibody APVO603 at the Society for Immunology in Cancer Annual Meeting

On November 11, 2021 Aptevo Therapeutics Inc. ("Aptevo" or the "Company") (Nasdaq:APVO), a clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIR and ADAPTIR-FLEX platform technologies, reported the presentation of preclinical data for APVO603, the Company’s bispecific antibody targeting 4-1BB (CD137) and OX40 (CD134), at the Society for Immunology in Cancers (SITC) (Free SITC Whitepaper) 2021 Annual Meeting (Press release, Aptevo Therapeutics, NOV 11, 2021, View Source [SID1234595288]).

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Poster #795 entitled, "APVO603: A dual 4-1BB and OX40 bispecific approach utilizing ADAPTIR technology designed to deliver a conditional T cell/NK response against solid tumors," will be presented and displayed on-site on Saturday, November 13th in Washington, D.C. Data in the poster showed that APVO603 enhanced dose-dependent control of in vitro tumor cell lysis when paired with a bispecific T-cell engager when compared either alone. Of note, investigators show that APVO603 has minimal impact on regulatory T cell suppression of CD8+ T cells’ proliferation in vitro.

"APVO603 is a differentiated bispecific antibody with the potential to leverage the benefits of 4-1BB and OX40 in a single agent. Further, the tethering of molecules has the potential to reduce safety risks and improve potency profiles by targeting responses specifically to sites of active inflammation and limiting on-target toxicity," said Hilario Ramos, Senior Director of Immunobiology at Aptevo. "In addition, the data presented here demonstrate that this combination has the potential to promote anti-tumor responses two-fold. First, by improving the fitness of exhausted effector CD8+ T cells. Second, by reducing the potential for activation of suppressive responses by T regulatory subsets. This dual biological mechanism of action offers the potential for development of a compound that acts against both solid and hematologic tumors and in the presence of addition immunomodulatory treatments or modalities such as CAR T or adoptive immune cell therapies."

Aptevo CEO Marvin White commented, "We are very encouraged by the results reported in this poster, and we are excited to continue to develop APVO603 and provide this update on our progress as we work to advance the compound."

Title: APVO603: A dual 4-1BB and OX40 bispecific approach utilizing ADAPTIRTM technology designed to deliver a conditional T cell/NK response against solid tumors
Presenter: Hilario Ramos, Senior Director of Immunobiology at Aptevo
Date/Time: Saturday, November 13, 2021

About APVO603

APVO603 is a dual agonist bispecific antibody employing a novel mechanism of action to simultaneously target 4-1BB (CD137) and OX40 (CD134), both members of the TNF Receptor Superfamily. Dual targeting of 4-1BB and OX40 provides synergistic co-stimulation of T cells with the potential to amplify the cytotoxic function of activated T cells and NK cells, potentially leading to more robust anti-tumor responses.