On March 31, 2019 Personalis, Inc., a leader in advanced genomics for cancer, reported that the company will present one oral presentation and five posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held this year in Atlanta, GA from March 31 – April 3, 2019 (Press release, Personalis, MAR 31, 2019, View Source [SID1234534789]).

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Personalis presentations will highlight how fundamental oncology research informs the ongoing evolution of our leading immunogenomics analysis platform. The presentations will also detail the alignment between our genomics solutions and AACR (Free AACR Whitepaper)’s 2019 theme: Integrative Cancer Science • Global Impact • Individualized Patient Care.

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

Presentation # Title & Presenter Day & Time Location
MS.BSB01.01
905 (Oral Presentation)
Comprehensive immunogenomic profiling of anti-PD-1 treated melanoma patients reveals subject-specific tumor escape mechanisms

March 31
3:05 pm-3:20 pm Room B206
PO.MCB09.04
2512 / 8
A comprehensive genomics platform for precision immunotherapy: Simultaneously characterizing the tumor and tumor microenvironment from a single FFPE sample

April 1
1-5pm Poster section 33
PO.BSB01.01
3377/8
T-cell receptor repertoire profiling using an augmented transcriptome

April 2
8 am-12 pm Poster section 31
PO.TB11.02
3788 / 5
Sensitive detection of oncoviruses integrated into a comprehensive tumor immuno-genomics platform

April 2
1 pm-5 pm Poster section 8
PO.CH03.01
4536 / 9
Applying Immuno-Peptidomics and Machine Learning to Improve Neoantigen Prediction for Therapeutic and Diagnostic Use

April 3
8 am-12 pm Poster section 2
PO.TB10.03
4695 / 8
Development and Validation of an Accurate Exome-Scale cfDNA Detection Platform

April 3
8 am-12 pm

On March 31, 2019 Cyteir Therapeutics, a leader in the discovery and development of novel therapeutics based on the biology of DNA repair and synthetic lethality for the treatment of cancer and autoimmune diseases, reported the presentation of promising new preclinical data for the company’s lead compound, CYT-0851. The data are being shared this week at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting and suggest that the novel RAD51 inhibitor could be active as a monotherapy against B-cell lymphomas and multiple solid tumors, including pancreatic cancer (Press release, Cyteir Therapeutics, MAR 31, 2019, View Source [SID1234534791]). Data also show that CYT-0851 is potentially synergistic in combination with PARP inhibitors and may overcome PARP inhibitor resistance. Cyteir expects to initiate clinical trials with CYT-0851 in mid-2019.

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Cyteir’s platform is based on the groundbreaking discovery of a relationship between activation-induced cytidine deaminase (AID), a DNA-damaging enzyme, and RAD51, a protein that is essential to the repair of DNA breaks. AID overexpression causes elevated DNA damage in high numbers of patients with B-cell malignancies and many patients with solid tumors. Cyteir is developing selective small-molecule compounds that the company believes inhibit RAD51. In preclinical models, reducing the ability of diseased cells to self-repair in this way causes them to become overwhelmed by their own DNA damage and undergo cell death – resulting in the therapeutic effect known as "synthetic lethality." Kevin Mills, Ph.D., Cyteir’s co-founder and chief scientific officer, led the research that first identified the synthetic lethality relationship between RAD51 and AID.

"The data being presented at this year’s AACR (Free AACR Whitepaper) meeting validate the mechanism-of-action underlying our novel synthetic-lethality approach and confirm that we have identified a potent, selective oral inhibitor that has the potential to broadly target multiple cancers with high levels of DNA damage induced by AID," said Markus Renschler, M.D., Cyteir president and CEO. "We are on track to file an IND mid-year and look forward to seeing how this exciting new mechanism performs in clinical trials as we look to improve outcomes for patients with advanced cancers."

Three presentations at AACR (Free AACR Whitepaper) 2019 support the potential of CYT-0851 to provide an effective, targeted new treatment option for a variety of hematologic cancers and solid tumors. Data presented by the company today demonstrate in vitro that CYT-0851 is synergistic and may be active as a combination therapy with PARP inhibitors (Poster Section 14, Board 363/24). Researchers tested five PARP inhibitors, each in combination with CYT-0851 in multiple tumor-derived cell lines with varying levels of AID expression and PARP inhibitor sensitivity. Findings suggest that CYT-0851 enhances the synthetic lethal activity of PARP inhibitors and may re-sensitize tumors that are resistant to this class of therapy.

Data scheduled for presentation tomorrow validate – in preclinical models – the mechanism-of-action of CYT-0851 in AID overexpressing cancers, demonstrating that the compound reduces activity of RAD51, reduces levels of DNA repair, and increases levels of DNA damage leading to the death of cancer cells (Poster Section 35, Board 2566/10).

On Wednesday, Cyteir will present data from a preclinical study evaluating the in vivo activity of CYT-0851 in AID-overexpressing B-cell lymphomas and solid tumors, particularly pancreatic cancer (Poster Section 10, Board 4730/20). In this study, oral administration of the compound in three patient-derived pancreatic cancer xenograft models led to significant anti-tumor activity.

On March 31, 2019 Apexigen, Inc., a clinical-stage biopharmaceutical company, reported the presentation of new clinical data on APX005M in combination therapy in patients with metastatic pancreatic cancer (Press release, Apexigen, MAR 31, 2019, View Source [SID1234534792]). The data are being presented in a plenary session today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place March 29 – April 3, 2019 in Atlanta, GA, by Parker Institute for Cancer Immunotherapy (PICI) researchers at the University of Pennsylvania. Apexigen’s lead immuno-oncology (I-O) therapeutic, APX005M, a monoclonal antibody targeting CD40, is being evaluated in multiple clinical trials in different types of solid tumors.

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In an interim analysis of an ongoing Phase 1b clinical trial, 20 of 24 evaluable patients with metastatic pancreatic cancer demonstrated tumor shrinkage following treatment with APX005M in combination with standard-of-care chemotherapy, with or without Bristol-Myers Squibb’s PD-1 inhibitor nivolumab. Several patients remained on therapy after one year of treatment.

"Our CD40 agonist APX005M is critical for activating the body’s innate and adaptive immunity, potentially enabling the immune system to fight even the most difficult-to-treat forms of cancer," said co-author Ovid Trifan, M.D., Ph.D., Chief Medical Officer and Senior Vice President of Clinical Development of Apexigen. "We are encouraged by these interim results and are excited to see this trial advance to the next phase in evaluating a novel combination therapy for patients with metastatic pancreatic cancer. In addition to these results, we look forward to a second presentation of clinical data at AACR (Free AACR Whitepaper) tomorrow on APX005M in combination therapy for patients with metastatic or unresectable melanoma who have progressed on anti-PD-1/PD-L1 therapy. We are committed to advancing a broad clinical development program for APX005M in multiple types of cancer as we work toward transforming the standard of care for patients across a wide range of cancer indications."

First author Mark H. O’Hara, M.D., Assistant Professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania, commented, "In this interim analysis of this trial, we are encouraged by the safety and activity signals from anti-CD40 immunotherapy APX005M in combination with chemotherapy with or without checkpoint inhibition as a new approach to treating metastatic pancreatic cancer. Given that most patients with metastatic pancreatic cancer have evidence of progression of their cancer within about 5 months of starting first line chemotherapy, seeing several patients stay on treatment on this trial for more than one year is exciting. We look forward to exploring the benefits of CD40 activation to treat this aggressive form of cancer."

About the Phase 1b/2 Clinical Trial
In the Phase 1b portion of the clinical trial, previously untreated patients with metastatic pancreatic ductal adenocarcinoma received APX005M in combination with gemcitabine and nab-paclitaxel, a standard-of-care chemotherapy regimen for this patient population, and half of the patients also received Bristol-Myers Squibb’s PD-1 inhibitor nivolumab. The combination therapy treatment was well-tolerated. Several patients remained on treatment for about a year, and had a durable response. 20 of 24 evaluable patients demonstrated tumor shrinkage. The trial has progressed to the Phase 2 portion.

For additional information on this trial (NCT03214250), please visit www.clinicaltrials.gov.

APX005M Data Presentations at AACR (Free AACR Whitepaper) 2019 Annual Meeting
Plenary Session Presentation Title: A Phase 1b Study of CD40 Agonistic Monoclonal Antibody APX005M Together with Gemcitabine (Gem) and nab-Paclitaxel (NP) with or without Nivolumab (Nivo) in Untreated Metastatic Ductal Pancreatic Adenocarcinoma (PDAC) Patients (Abstract #CT004)
Presenter: Mark O’Hara, M.D., Assistant Professor of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Plenary Session Date and Time: Sunday, March 31, 2019 2:25 PM – 2:45 PM ET
Plenary Session: Clinical Trials Plenary Session 1
Location: Georgia World Congress Center, Building A, Marcus Auditorium

Late-breaking Abstract Title: Phase Ib/II clinical trial of CD40 agonistic antibody APX005M in combination with nivolumab (nivo) in subjects with metastatic melanoma (M) or non-small cell lung cancer (NSCLC) (Abstract #CT089)
Poster Session Date and Time: Monday, April 1, 2019 1:00 PM – 5:00 PM ET
Poster Session: Phase 1 Clinical Trials
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 16

About APX005M
APX005M is a humanized monoclonal antibody designed to stimulate the anti-tumor immune response. APX005M targets CD40, a co-stimulatory receptor that is essential for activating both innate and adaptive immune systems. Binding of APX005M to CD40 on antigen presenting cells (i.e., dendritic cells, monocytes and B-cells) is believed to initiate a multi-faceted immune response that enables multiple components of the immune system (e.g., T cells, macrophages) to work in concert against cancer. APX005M is currently in Phase 2 clinical development for the treatment of cancers such as pancreatic cancer, melanoma, esophageal and gastroesophageal junction cancers, non-small cell lung cancer, renal cell carcinoma, sarcomas, and pediatric brain cancer in various combinations with immunotherapy, a cancer vaccine, chemotherapy or radiation therapy. Additional information on clinical trials for APX005M can be found at www.clinicaltrials.gov.

On March 30, 2019 Maverick Therapeutics Inc., a private biopharmaceutical company pioneering next-generation redirected T-cell targeted immunotherapies, reported that it will unveil pre-clinical data characterizing its novel COBRATM therapeutic platform at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 being held from March 29 to April 3 in Atlanta, Georgia (Press release, Maverick Therapeutics, MAR 30, 2019, View Source [SID1234534787]). COBRA is the most advanced bispecific T-cell engaging platform in its class, designed to safely target solid tumors with highly specific and potent activity. These pre-clinical data characterize the conditional and potent activity of the COBRATM platform in vitro as well as demonstrate the regression of established solid tumors in in vivo models.

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COBRATM is a proprietary approach to cancer immunotherapy. The COBRATM molecules are designed to bind to a specific target but are engineered to activate only after they enter the tumor microenvironment, allowing for specific T-cell engagement and activation at the site of the cancer. Focusing T-cell activation and killing at the tumor site is ideal for the treatment of solid tumors, which account for 90% of all cancers1. COBRATM molecules include a component that extends their half-life in the circulation prior to activation within the tumor site; once activated, this component is lost, allowing the active molecules to then be cleared from the body more rapidly after targeting and killing the cancer cells. This further increases their safety window by reducing the potential for active COBRATM molecules to travel outside the tumor to healthy tissues and cause damage.

"We are encouraged by the inaugural data on our proprietary COBRATM platform, as they provide proof-of-concept for our approach to overcome the challenges current T-cell engagers face when addressing solid tumors," said Maverick Therapeutics Chief Executive Officer Jim Scibetta. "With its scientifically elegant design, COBRATM has the potential to deliver increased specificity, higher potency and reduced toxicity, all of which may help extend both the duration and quality of life of people living with solid tumor cancers."

Full abstracts are available online at View Source Details of the poster presentation are listed below.

Title: COBRATM: A Novel Conditionally Active Bispecific Antibody that Regresses Established Solid Tumors in Mice
Session Title: Immunology – Therapeutic Antibodies 1
Abstract Number: 557
Poster Board Number: 21
Presentation Time: Sunday, March 31, 1pm – 5pm ET
Location: Georgia World Congress Center – Exhibit Hall B, Poster Section 23

About COBRA Therapeutic Platform

The company’s proprietary COBRA, or COnditional Bispecific Redirected Activation, therapeutic platform is the most advanced bispecific T-cell engagement platform, designed to target solid tumors with highly potent and specific activity, while avoiding damage to normal healthy tissues. COBRATM molecules are designed to bind to a specific target, but are engineered to activate only after they enter the tumor microenvironment, allowing for specific T-cell engagement and activation at the site of the cancer. COBRATM molecules include a component that extends their presence in the circulation prior to activation within the tumor site; once activated this component is lost, allowing the active molecule to then be cleared from the body more rapidly after targeting and killing the cancer cells. This increases their safety window by reducing the potential for active COBRA molecules to escape the tumor and travel to healthy tissues.

On March 29, 2019 Seattle Genetics, Inc. (Nasdaq:SGEN) reported completion of enrollment in the potentially pivotal innovaTV 204 phase 2 clinical trial evaluating the efficacy, safety and tolerability of tisotumab vedotin as monotherapy for patients with recurrent and/or metastatic cervical cancer who have relapsed or progressed after standard of care treatment (Press release, Seattle Genetics, MAR 29, 2019, View Source [SID1234534761]). Tisotumab vedotin is being developed in collaboration with Genmab A/S. The innovaTV 204 trial is intended to support potential registration under the U.S. Food and Drug Administration’s (FDA) accelerated approval regulations. Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) designed to target Tissue Factor antigen on cancer cells and deliver the cell-killing agent monomethyl auristatin E (MMAE) directly inside cancer cells. Tissue Factor is overexpressed in cervical cancer and many other solid tumors.

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"Cervical cancer is a devastating disease with a significant need to develop improved therapies for patients with metastatic disease who have progressed after treatment," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "Completing enrollment in this potentially pivotal phase 2 trial marks an important step forward in evaluating tisotumab vedotin for women with previously treated recurrent and/or metastatic cervical cancer."

For more information about the phase 2 innovaTV 204 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.

About innovaTV 204 Trial

The innovaTV 204 trial (also known as GCT1015-04) is an ongoing single-arm, global, multicenter study of tisotumab vedotin for patients with recurrent and/or metastatic cervical cancer who progressed on or relapsed after treatment with doublet chemotherapy used alone or in combination with bevacizumab (Avastin). The study enrolled over 100 patients at multiple centers. The primary endpoint of the trial is objective response rate as assessed by blinded independent central review. Key secondary endpoints include duration of response, progression-free survival, overall survival, safety and tolerability.