On April 9, 2021 AstraZeneca reported that it will share updates from the Company’s innovative early oncology pipeline across multiple strategic platforms during the virtual American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, 10 to 15 April 2021 (Press release, AstraZeneca, APR 9, 2021, View Source [SID1234577781]).

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Five presentations will unveil the next-generation PARP1 selective inhibitor AZD5305, underscoring AstraZeneca’s commitment to advancing therapies that selectively kill cancer cells by targeting the system that cells rely on to repair damage to DNA. Additionally, research across multiple presentations will highlight novel technologies that enable early detection of disease recurrence to inform earlier interventions for patients who are more likely to benefit from treatment.

In total, data from more than 40 presentations will showcase progress with the next wave of anticancer medicines, novel insights in targeting resistance to therapy, and approaches that are advancing the personalised treatment of cancer.

Susan Galbraith, Senior Vice President and Head of Research and Early Development, Oncology R&D, said: "Our data at AACR (Free AACR Whitepaper) reflect a robust early-stage pipeline, poised to deliver life-changing medicines to patients living with cancer. Data for AZD5305 will demonstrate how the next wave of DNA damage response medicines can build on the success of PARP inhibitors, potentially allowing patients to stay on treatment longer. This innovative molecule is designed to optimise the therapeutic window of PARP inhibition, providing new opportunities for combination treatment with chemotherapy and targeted medicines."

The Company will share a Spotlight Theater Presentation: The Orchestrated Immune Response: Dynamic Forces Guiding Cancer Immunity, introducing a novel framework for understanding the role of the immune system in cancer, with the potential to reshape the way scientists develop medicines to counteract tumour growth.

AstraZeneca leaders will also participate in two educational symposia:

DNA Damage Response (DDR) Treatment: Evolving Diagnostic Approaches, Understanding of Replication Stress, and Resistance Mechanisms to DDR Targeting Therapies (Session #ADT04), with a discussion on targeting the replication stress response, which occurs when the genome is exposed to stresses that impede DNA replication.
Advances in Drug Delivery (Session #ADT08), with a discussion on the advances and innovations fueling the development of the next generation of antibody drug conjugates.
Key presentations will include:

Structural disclosure and key preclinical data for AZD5305, a next-generation PARP1 selective inhibitor
The introduction of AZD8853, a novel antibody targeting GDF15 for tumours refractory to immunotherapy treatment
Research from the HUDSON Phase II trial using deep learning algorithms on pathological images to identify features associated with progression on immunotherapy for patients with non-small cell lung cancer
A pooled analysis of interstitial lung disease data in patients treated with Enhertu across eight cancer trials
Two presentations from genome-wide CRISPR screenings that identify signalling in the Hippo pathway as an important driver of resistance in EGFR-mutated lung cancer and BRAF-mutated colon cancer
Data identifying a novel immunosuppressive myeloid gene signature for clinical biomarker development
Results from the ATRiUM Phase I trial, externally sponsored scientific research evaluating ceralasertib, an ATR inhibitor, and gemcitabine as combination therapy in biliary tract cancer
Key AstraZeneca presentations during AACR (Free AACR Whitepaper) 2021

Key AstraZeneca presentations during AACR (Free AACR Whitepaper) 2021
1Unless otherwise specified, all posters/presentations will be available starting 08:30 EDT on 10 April 2021.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On April 9, 2021 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported new preclinical data supporting the ongoing development of three of its drug candidates, repotrectinib, TPX-0022 and TPX-0131 (Press release, Turning Point Therapeutics, APR 9, 2021, View Source [SID1234577798]). The findings will be presented this weekend at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, which is convening virtually through April 14.

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For lead drug candidate, repotrectinib, poster presentations will highlight new preclinical combination data with MEK and MEK/Raf inhibitors, as well as repotrectinib’s potency against wildtype and mutant TRKA/B/C as compared to approved TRK inhibitors. The preclinical studies found that repotrectinib combinations with approved MEK inhibitor, trametinib, or investigational MEK/Raf inhibitor, VS-6766, were more effective than single-agent treatment in patient-derived KRAS mutant G12D/V lung and G12D/V/R pancreatic cancer models. Based on the findings and additional preclinical support presented previously, Turning Point anticipates the first cohort of its planned Phase 1/2 TRIDENT-2 study will examine the safety, tolerability, pharmacokinetics, and any early signals of efficacy of repotrectinib in combination with trametinib in patients with KRAS mutant G12D advanced solid tumors.

"We are encouraged by the new preclinical data our research team has generated in support of our ongoing development of repotrectinib, TPX-0022 and TPX-0131," said Athena Countouriotis, M.D., president and CEO. "In particular, our preclinical models continue to suggest that the combination of repotrectinib with MEK inhibitors can suppress mutant KRAS signaling to achieve more potent and durable anti-tumor activity. We look forward to studying this further in the first cohort of our planned TRIDENT-2 combination study.

"In addition, preclinical studies show repotrectinib is highly potent against wild type TRK fusions and is less affected by NTRK resistance mutations than approved therapies, with strong potency in both in vitro and in vivo studies. We look forward to sharing additional clinical data from our TRIDENT-1 study of repotrectinib in the second half of the year."

TPX-0022, MET, SRC, CSF1R Inhibitor
For MET/SRC/CSF1R inhibitor TPX-0022, the company will present preclinical data demonstrating potential utility in combination with immune checkpoint inhibitors. In a syngeneic xenograft tumor model, TPX-0022 treatment downregulated immunosuppressive cytokines, increased anti-tumor M1 macrophages, and enriched levels of CD8+ cytotoxic T cells. TPX-0022 had single agent in vivo efficacy and enhanced the efficacy of an anti-PD-1 inhibitor. With the new data, Turning Point is evaluating a potential additional combination study of TPX-0022 and an anti-PD-1 checkpoint inhibitor. In the second half of 2021, the company plans to provide a clinical data update from the Phase 1 dose finding portion of its ongoing SHIELD-1 study and initiate its planned Phase 1b/2 SHIELD-2 clinical study of TPX-0022 in combination with an EGFR targeted therapy.

TPX-0131, ALK Inhibitor
For its ALK-inhibitor, TPX-0131, Turning Point will present preclinical data showing its potential to cross the blood-brain barrier and its potency against wild type ALK and a broad spectrum of acquired ALK resistance mutations, including the G1202R solvent front mutation, L1196M gatekeeper mutation, and the G1202R/L1196M and /L1198F compound mutations. Turning Point plans to initiate a Phase 1/2 study in patients with ALK-positive TKI-pretreated advanced non-small cell lung cancer in the second quarter of 2021.

AACR plans to make poster presentations available via its website on Saturday, April 10. The four posters to be presented are:

Title: Repotrectinib increases effectiveness of MEK inhibitors in KRAS mutant cancer models
Abstract Number: 1104

Title: Molecular characteristics of repotrectinib that enable potent inhibition of TRK fusion proteins and broad mutant selectivity
Abstract Number: 1119

Title: TPX-0022, a potent MET/SRC/CSF1R inhibitor that modulates the tumor immune microenvironment in preclinical models
Abstract Number: 1444

Title: TPX-0131, a potent inhibitor of wild type ALK and a broad spectrum of both single and compound ALK resistance mutations
Abstract Number: 1469

On April 9, 2021 Oasmia Pharmaceutical AB, an innovation-focused specialty pharmaceutical company, reported that it will host a conference call on April 12 at 14:00 CEST to present final Cantrixil Phase 1 data set to be released at the 2021 AACR (Free AACR Whitepaper) annual meeting (Press release, Oasmia, APR 9, 2021, View Source [SID1234577782]).

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The call will be hosted by CEO Francois Martelet and CSO Reinhard Koenig. The presentation will be in English.

On April 9, 2021 Aptevo Therapeutics Inc. (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIRTM and ADAPTIR-FLEXTM platform technologies, reported that it will present two new posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting, to be held in two virtual sessions – Saturday, April 10th to Thursday, April 15th, 2021 and Monday, May 17th to Friday, May 21st, 2021 (Press release, Aptevo Therapeutics, APR 9, 2021, View Source [SID1234577799]).

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The posters will provide preclinical updates on APVO603 and Aptevo’s newest pipeline candidate, APVO442.

Title: APVO603: A Dual 4-1BB and OX40 bispecific approach utilizing ADAPTIR technology designed to deliver a conditional T cell/NK response against solid tumors (LB173)

Summary: The data to be presented will highlight the potential benefits of dual targeting of 4-1BB and OX40 by APVO603. In vitro data includes demonstration of APVO603’s ability to reduce or reverse the negative effects of T-cell exhaustion and suppressive immune responses by augmenting cytokine production and reducing markers of T-cell exhaustion following repeat stimulation. In preclinical in vivo studies, APVO603 therapy induced a dose-dependent anti-tumor response and significantly increased the survival of mice in a murine bladder cancer model. A non-GLP NHP PK/Tox study was completed and it was found that APVO603 had a favorable safety profile without liver toxicity and a PK profile that supports clinical dosing. CMC activities are in progress and IND-enabling studies are underway to progress the program towards clinical development.

Title: APVO442: A bispecific T cell-engaging candidate utilizing the ADAPTIR-FLEX platform technology with unique properties designed to optimize drug tumor distribution and cytotoxic response against PSMA-expressing solid tumors

Summary: The data to be presented will highlight the unique properties of APVO442, Aptevo’s first molecule utilizing our ADAPTIR-FLEX technology, designed with low affinity, monovalent targeting of CD3 and high affinity, bivalent targeting of PSMA to potentially reduce safety signals and improve efficacy for treatment of a solid tumor. In vitro, APVO442 retains strong binding to tumor cell lines with a range of (high to low) surface PSMA expression, and demonstrates reduced binding to CD3+ T cell lines when compared to higher affinity CD3 binding molecules. In vitro efficacy studies show that, despite lower CD3 binding affinity, APVO442 elicits equivalent T-cell activation, proliferation, and cytotoxicity against PSMA+ tumor cells, while limiting cytokine release, when compared to higher affinity CD3 engaging molecules. In vivo, APVO442 demonstrated a dose-dependent ability to limit tumor burden at responses comparable to a high affinity T-cell engager response in a murine xenograft PSMA+ prostate cancer model. APV0442 retains key manufacturability characteristics of the ADAPTIR platform and preclinical data to support the potential for a beneficial safety and efficacy profile. Continued pre-clinical evaluation and CMC efforts are ongoing to progress APVO442 toward clinical development.

Details of the e-Poster Presentations: The abstracts and the accompanying e-posters will be available in the Virtual Poster Hall to registered attendees from 8:30 am EST on Saturday, April 10th, 2021, until the Virtual Poster Hall closes on Monday June 21st, 2021. Chat and live meeting requests will be available for questions and discussion with the presenters. Details can be found on the AACR (Free AACR Whitepaper) abstract website and will also be posted on the Aptevo Therapeutics website.

On April 9, 2021 Seagen Inc. (Nasdaq: SGEN) and Genmab A/S (Nasdaq: GMAB) reported that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) seeking accelerated approval for tisotumab vedotin (Press release, Seagen, APR 9, 2021, View Source [SID1234577783]). This BLA requests FDA approval of tisotumab vedotin for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of October 10, 2021. Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) directed to tissue factor (TF), a cell-surface protein expressed on multiple solid tumors including cervical cancer, and is associated with tumor growth, angiogenesis, metastasis and poor prognosis.1

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"The FDA’s filing of the tisotumab vedotin BLA with Priority Review marks an important step forward for this ADC as a potential treatment for patients with recurrent or metastatic cervical cancer," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "We are collaborating closely with the FDA throughout the review process to make this important therapy available to patients."

"We are pleased that the tisotumab vedotin BLA has been accepted with Priority Review by the FDA as there is an unmet need for effective therapies for women with recurrent or metastatic cervical cancer, who have disease progression on or after chemotherapy," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "This is an important milestone for Genmab as it brings us closer to our goal of bringing differentiated therapies to patients and transforming cancer treatment."

The BLA for tisotumab vedotin was submitted in February 2021. The submission is based on the results of the innovaTV 204 pivotal phase 2 single-arm clinical trial evaluating tisotumab vedotin as monotherapy in patients with previously treated recurrent or metastatic cervical cancer. These data were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020.

About Cervical Cancer

Cervical cancer originates in the cells lining the cervix. Over 13,500 women are expected to be diagnosed with invasive cervical cancer in the U.S. in 2020, with approximately 4,200 deaths.2 Cervical cancer remains one of the leading causes of cancer death in women globally, with over 311,000 women dying annually; the vast majority of these women being in the developing world.3 Routine medical examinations and human papillomavirus (HPV) vaccines have lowered the incidence of cervical cancer in the developed world. Despite these advances, women are still diagnosed with cervical cancer, which often recurs or becomes metastatic. Current therapies for previously treated recurrent or metastatic cervical cancer generally result in limited objective response rates of typically less than 15 percent with median overall survival ranging from 6.0 to 9.4 months.4-10

About the innovaTV 204 Trial

The innovaTV 204 trial (also known as GCT1015-04 or innovaTV 204/GOG-3023/ENGOT-cx6) is an ongoing single-arm, global, multicenter study of tisotumab vedotin for patients with recurrent or metastatic cervical cancer who were previously treated with doublet chemotherapy with or without bevacizumab. Additionally, patients were eligible if they had received up to two prior lines of therapy in the recurrent or metastatic setting. In the study, 101 patients were treated with tisotumab vedotin at multiple centers in the U.S. and Europe. The primary endpoint of the trial was confirmed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by independent central review. Key secondary endpoints included duration of response, progression-free survival, overall survival, safety and tolerability.

The study was conducted by Genmab in collaboration with Seagen, European Network of Gynaecological Oncological Trial Groups (ENGOT) and the Gynecologic Oncology Group (GOG) Foundation. For more information about the phase 2 innovaTV 204 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.

About Tisotumab Vedotin

Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) composed of Genmab’s fully human monoclonal antibody specific for tissue factor and Seagen’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody and releases it upon internalization, inducing target cell death. In cancer biology, tissue factor is a cell-surface protein and associated with tumor growth, angiogenesis, metastasis and poor prognosis.1 Based on its elevated expression in multiple solid tumors and its rapid internalization, tissue factor was selected as a target for an ADC approach. Tisotumab vedotin is being co-developed by Genmab and Seagen, under an agreement in which the companies share all costs and profits for the product on a 50:50 basis.

Tisotumab vedotin is being evaluated in a global phase 3, randomized clinical trial called innovaTV 301 versus investigator’s choice of chemotherapy in recurrent or metastatic cervical cancer. The primary endpoint is overall survival and secondary endpoints include progression-free survival, duration of response, objective response rate, safety and tolerability. Enrollment is ongoing and the study is intended to support global registrations. In addition, tisotumab vedotin is being evaluated in ongoing clinical trials as monotherapy in recurrent or metastatic cervical cancer, ovarian cancer, and other solid tumors and in combination with commonly used therapies in recurrent or metastatic cervical cancer. These trials are evaluating tisotumab vedotin on a weekly or every three-week dosing schedule. More information about the innovaTV 301 clinical trial, including enrolling sites, as well as other ongoing clinical trials is available at www.clinicaltrials.gov.