On April 14, 2023 Novocure (NASDAQ: NVCR) reported 27 presentations on Tumor Treating Fields (TTFields) will be delivered at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, to be held April 14 to 19 in Orlando, Florida (Press release, NovoCure, APR 14, 2023, View Source [SID1234630104]).

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The research described in the presentations includes real-world evidence supporting the safety and efficacy of TTFields therapy in glioblastoma (GBM) and preclinical research spanning 15 tumor types suggesting the broad applicability and effectiveness of TTFields alone and together with other therapies.

Presentation highlights include research on:

the largest global post-marketing safety dataset of more than 25,000 TTFields-treated patients with high-grade glioma from the last decade demonstrating the safety and broad applicability of TTFields therapy regardless of diagnosis, age, or sex
a systematic review and meta-analysis examining the overall survival (OS) benefit of TTFields therapy in newly diagnosed GBM, finding improved overall survival for TTFields-treated patients relative to those not treated with TTFields, and demonstrating that ≥ 75% average TTFields use was consistently associated with longer survival relative to < 75% average TTFields use
preclinical investigations that demonstrated TTFields with cisplatin or paclitaxel increased the effectiveness of both chemotherapies in cervical cancer cells
in vitro and in vivo investigations of TTFields for treatment of spinal metastasis provides first evidence that TTFields could become an effective therapy for spinal metastasis
TTFields selectively enhanced cancer cell membrane permeability, while not affecting normal cells, improving doxorubicin accumulation in vitro and in vivo breast cancer models
adding TTFields to the PULSAR paradigm for radiotherapy and demonstrating it is most effective when added prior to each radiation dose, an effect that is enhanced when also used with an immune checkpoint inhibitor
the application of the ability of TTFields to induce a state of BRCAness (DNA repair deficiency) in ovarian cancer cell lines, and combining TTFields with either carboplatin or PARP inhibitors: demonstrating that TTFields display a synergistic interaction with either of these drugs in a wild type ovarian cell line, and an additive effect in a BRCA mutant cell line
"Through ongoing research, we continue to discover that TTFields therapy has great potential for applicability across many solid tumor types and concomitant use with other therapies," said Moshe Giladi, Novocure’s Chief Science Officer. "We are honored to share new insights about TTFields therapy and participate in the exchange of scientific information with researchers from around the world at the AACR (Free AACR Whitepaper) Annual Meeting."

Presentations from Novocure-sponsored and partner programs include:

(Abstract #: CT061) TRIDENT phase 3 study (EF-32): First-line Tumor Treating Fields (TTFields; 200 kHz) therapy concomitant with chemo-radiation, followed by maintenance TTFields/temozolomide in newly diagnosed glioblastoma. W. Shi. (Phase II and Phase III Clinical Trials in Progress)

(Abstract #: 20) In vitro and in vivo investigation of Tumor Treating Fields for treatment of spinal metastasis. C. E. Tatsui. (Mouse Models of Human Cancer)

(Abstract #: 729) The economic and healthcare resource utilization of metastatic non-small cell lung cancer. C. Koh. (Science and Health Policy/Regulatory Science and Policy)

(Abstract #: 1102) Establishing the cytotoxic benefit of Tumor Treating Fields on radiation sensitive and acquired radiation resistant glioblastoma patient derived xenograft pairs. T. L. Schanel. (Radiation Oncology / Radiation Science)

(Abstract #: 1103) Theoretical basis and formula for Tumor Treating Fields dose-response curves. K. Carlson. (Radiation Oncology / Radiation Science)

(Abstract #: 1371) Tumor Treating Fields exposure causes an imbalance of reactive oxygen homeostasis likely through the cytosolic function of the Fanconi anemia genes. N. Karanam. (Autophagy, Mitochondrial Function, and Ferroptosis)

(Abstract #: 1425) TTFields reduce sensitivity in glioblastoma is associated with the functional expression of the chloride intracellular channel 1 and with voltage dependent sodium channel. S. Castiglione. (Cell Cycle Progression, Checkpoint, and Telomeres)

(Abstract #: 1738) Sensitizing cancer cell to doxorubicin by Tumor Treating Fields (TTFields)-induced, elevated membrane permeability. B. Koltun. (Reversal of Drug Resistance)

(Abstract #: 2279) Tumor Treating Fields induce immune modulation in non-small cell lung cancer. S. Wang. (Immune Response to Therapies)

(Abstract #: 2666) Preclinical investigations of concomitant tumor treating fields (TTFields) with cisplatin or paclitaxel for treatment of cervical cancer. R. Frechtel-Gerzi. (Chemotherapeutic Combinations)

(Abstract #: 2723) Treatment of gastric cancer cells with tumor treating fields (TTFields) and concomitant FOLFOX. N. Flint-Brodsly. (Drug Delivery Systems)

(Abstract #: 2825) Investigation of sponge property for enhanced concurrent Tumor Treating Fields and radiotherapy for glioblastoma. J. Zheng. (Radiosensitizers and Radio-immunomodulators)

(Abstract #: 3213) Association of Tumor Treating Fields (TTFields) with survival in newly diagnosed glioblastoma: A systematic review and meta-analysis. P. Conlon. (Cancer Outcomes 1)

(Abstract #: 3221) Patients with glioblastoma (GBM) treated with Tumor Treating Fields (TTFields) therapy: post-marketing safety data over the last decade. M. M. Mrugala. (Cancer Outcomes 1)

(Abstract #: 3224) TTFields-prolonged the PFS of epithelioid glioblastoma patient: a case report. Y. Ding. (Cancer Outcomes 1)

(Abstract #: 3252) TTFields combined with temozolomide and immunotherapy show long-term PFS on a GBM patients with multiple negative prognostic factors. Z. Li. (Combination Immunotherapies 1)

(Abstract #: 3272) Tumor Treating Fields combined with the PULSAR paradigm for radiotherapy and an immune checkpoint inhibitor enhances antitumor efficacy in vivo. N. Karanam. (Combination Immunotherapies 2)

(Abstract #: CT113) Safety and efficacy of Tumor Treating Fields (TTFields) combined with bevacizumab and systemic chemotherapy in recurrent GBM. X. Kang. (Phase I Clinical Trials in Progress)

(Abstract #: 4573) Evaluation of tumor treating fields (TTFields) effects at 200 kHz on a glioblastoma, an anaplastic ependymoma and an oligodendroglioma sample in a patient-derived ex vivo organoid model. V. Nickl. (3D and Tissue Recombinant Models)

(Abstract #: 4860) PI3K inhibition sensitize cancer cells to tumor treating fields (TTFields). A. Klein-Goldberg. (Anticancer Approaches Targeting Signal Transduction Pathways)

(Abstract #: 4883) Pan cancer transcriptomic response to Tumor Treating Fields (TTFields). K. Wainer-Katsir. (Anticancer Approaches Targeting Signal Transduction Pathways)

(Abstract #: 5050) Case report: A 17-year-old patient developed glioblastoma secondary to intracranial germ cell tumor and was stabilized with chemoradiotherapy combined with Tumor Treating Fields. S. Li. (Theranostics and Radionuclides / Pharmacologic Approaches)

(Abstract #: 5802) The impact of Tumor Treating Fields on cancer stem-like cells isolated from the sub-ventricular zone of glioblastoma patients. Y. Licon Munoz. (Cancer Stem Cells and Therapeutic Resistance)

(Abstract #: 5961) Inhibition of AURKA destabilizes glioblastoma primary cilia and sensitizes cells to Tumor Treating Fields (TTFields) in vitro and ex vivo. J. Tian. (Tumor-Stromal Cell (Including Immune Cell) Interactions and Therapy Responses)

(Abstract #: 6176) Enhancing treatment efficacy of glioblastoma cell lines by adding Tumor Treating Fields (TTFields) to temozolomide and lomustine. H. Fishman. (DNA Damage Response)

(Abstract #: 6182) Tumor Treating Fields (TTFields) concomitant with PARP inhibitors or carboplatin for treatment of ovarian cancer cell lines. A. Martinez-Conde. (DNA Damage Response)

(Abstract #: 6715) CLIC1 and CLIC4 ion channels as bioelectric targets for Tumor Treating Fields in pediatric high-grade glioma. M. Griffin. (Preclinical Therapies and Clinical Observations in Pediatric Oncology)

About Tumor Treating Fields Therapy

Tumor Treating Fields (TTFields) are electric fields that exert physical forces to kill cancer cells via a variety of mechanisms. TTFields do not significantly affect healthy cells because they have different properties (including division rate, morphology, and electrical properties) than cancer cells. The multiple, distinct mechanisms of TTFields therapy work together to selectively target and kill cancer cells. Due to its multimechanistic actions, TTFields therapy can be added to cancer treatment modalities in approved indications and demonstrates enhanced effects across solid tumor types when used with chemotherapy, radiotherapy, immune checkpoint inhibition, or PARP inhibition in preclinical models. TTFields therapy provides clinical versatility that has the potential to help address treatment challenges across a range of solid tumors. To learn more about Tumor Treating Fields therapy and its multifaceted effect on cancer cells, visit tumortreatingfields.com.

On April 14, 2023 RenovoRx, Inc. ("RenovoRx" or the "Company") (Nasdaq: RNXT), a biopharmaceutical company focused on the localized treatment of solid tumors, reported that Poster #CT084 is presenting detailed, open label, Phase III TIGeR-PaC study interim data analysis of its innovative RenovoGem therapy for pancreatic cancer patients at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, on Monday, April 17, 2023, at 9:00 AM ET in Orlando, Florida (Press release, Renovorx, APR 14, 2023, View Source [SID1234630103]). AACR (Free AACR Whitepaper) is underway through Wednesday, April 19, 2023.

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The interim analysis shows a 6-month median overall survival benefit for patients with locally advanced pancreatic cancer ("LAPC") which is a 60% improvement over systemic chemotherapy, the current standard of care and study control arm (intravenous (IV) administration of gemcitabine and nab-paclitaxel). RenovoGem patients also demonstrated greater than 65% reduction in adverse events. These can include nausea, fatigue, and a decline in white blood cells.

On Monday, April 17, "Targeted Intra-arterial Gemcitabine vs. Continuation of IV Gemcitabine plus Nab-Paclitaxel following Induction with sequential IV Gemcitabine plus Nab-Paclitaxel and Radiotherapy for Unresectable Locally Advanced Pancreatic Cancer (TIGeR-PaC) – Phase III Trial Interim Analysis," is being presented on Poster #CT084 by Michael Pishvaian, MD, Johns Hopkins Medicine Director of Gastrointestinal, Developmental Therapeutics and Clinical Research Programs, Amer H. Zureikat, MD, Professor of Surgery at the University of Pittsburgh School of Medicine, and other researchers.

This is the first interim analysis of the randomized multi-center Phase III open label TIGeR-PaC clinical trial, designed to investigate the Company’s first product candidate, RenovoGem. In this interim analysis, the control and treatment arms demonstrated divergence in median overall survival for patients. The study is designed to randomize 114 patients (57 in each arm) with all patients receiving upfront induction chemotherapy and stereotactic body radiation therapy (SBRT). The TIGeR-PaC Data Monitoring Committee ("DMC") met and determined the interim data is promising and warrants continuation of this pivotal trial. As of the analysis date, 45 patients from U.S. sites had been randomized in this trial. The survival status of all subjects was used for the analysis.

Twenty-three patients were randomized to intra-arterial gemcitabine (RenovoGem investigational treatment) arm and 22 to continuation of IV gemcitabine and nab-paclitaxel (standard of care control) arm.
The median overall survival in the IV gemcitabine and nab-paclitaxel control arm was 10 months, versus 16 months in the intra-arterial RenovoGem arm from time of randomization. (NOTE: Both arms’ median overall survival calculations do not include 4 to 5-months of life from diagnosis to randomization during the induction chemotherapy and radiation phase of the trial.)
Observed a positive trend in median overall survival by 24-weeks (6 months); in this interim analysis, the statistical significance was not reached to stop the study early (p=0.051).
Observed a 65% reduction in adverse events from control arm to treatment arm.
RenovoRx CEO, Shaun Bagai, commented, "Our RenovoGem therapy has demonstrated the potential to positively change the current standard of care for Locally Advanced Pancreatic Cancer (LAPC). Not only does analysis demonstrate that our therapy may give these patients more time, but it also shows RenovoGem can decrease adverse side effects common with systemic chemotherapy. Our mission is to help patients impacted by difficult-to-treat cancer enjoy better quality of and longer life."

Mr. Bagai added, "We look forward to the TIGeR-PaC researchers presenting this poster at AACR (Free AACR Whitepaper), and continuing strong enrollment with the second interim analysis expected mid to late next year."

About Locally Advanced Pancreatic Cancer (LAPC)

According to American Cancer Society’s Cancer Facts & Figures 2023, Pancreatic cancer has a 5-year combined overall survival rate of 12% (Stages I-IV) and is on track to be the second leading cause of cancer-related deaths before 2030. LAPC is diagnosed when the disease has not spread far beyond pancreas, however, has advanced to the point where it cannot be surgically removed. LAPC is typically associated with patients in stage 3 of the disease as determined by the TNM (tumor, nodes and metastasis) grading system.

About RenovoGem

RenovoGem is the first drug-device combination product candidate that utilizes the RenovoTAMP therapy platform via pressure-mediated delivery technology to deliver gemcitabine, an FDA-approved systemic chemotherapy, locally across the arterial wall to bathe tumor tissue in the chemotherapy. RenovoGem is currently being evaluated in the Phase III TIGeR-PaC clinical trial study in Locally Advanced Pancreatic Cancer (LAPC) patients. The Company plans to investigate RenovoGem in extrahepatic Cholangiocarcinoma (eCCA) in a clinical trial, which is anticipated to begin in the first half of 2023. RenovoGem is currently under investigation for the intra-arterial delivery of gemcitabine and has not been approved for commercial sale.

On April 14, 2023 MiNA Therapeutics Limited, the pioneer in small activating RNA (RNAa) therapeutics, reported that it will present positive updated biomarker data from its Phase 1a/b TIMEPOINT study of MTL-CEBPA in combination with the anti-PD1 checkpoint inhibitor, pembrolizumab, in adults with advanced solid tumors at the annual meeting of the American Association of Cancer Research (AACR) (Free AACR Whitepaper) in Orlando, Florida (Press release, MiNA Therapeutics, APR 14, 2023, View Source [SID1234630102]). Findings from the Phase 1b portion of the study validate the clinical proof of mechanism of MTL-CEBPA as a combination treatment and identify a novel predictive biomarker of clinical response. The data will be presented on Tuesday, April 18, during a late-breaking research session beginning at 9:00 am EDT.

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MTL‑CEBPA is the first therapy that specifically up-regulates CCAAT/enhancer binding protein alpha (C/EBP-α), a transcription factor that acts as a master regulator of myeloid cells. Dysregulated myeloid cells are implicated in several diseases including solid tumor cancers. MTL-CEBPA is designed to improve the effectiveness of checkpoint inhibitors and other immunotherapies by enhancing the body’s immune response and ability to attack the cancerous cells. Interim data from an open-label, multi-center study demonstrated the safety, tolerability, immunological and clinical activity of MTL-CEBPA in combination with pembrolizumab.

"Anti-PD1 checkpoint inhibition has significantly advanced the treatment of cancer, but many patients are resistant to treatment and present with tumors that resemble an ‘immune-desert’," said Robert Habib, CEO of MiNA Therapeutics. "The updated analysis of TIMEPOINT shows that MTL-CEBPA used in combination with anti-PD1 checkpoint inhibitors profoundly reprograms the tumor microenvironment, reducing resistance and enabling infiltration of disease-fighting T-cells."

The TIMEPOINT study also identified a novel predictive biomarker of clinical response to the combination treatment, presenting an opportunity for further evaluation as a potential companion diagnostic. The novel biomarker predicted clinical response across multiple tumor types.

MiNA plans to explore out-licensing opportunities for its immuno-oncology portfolio, which uniquely combines the capability to specifically restore or boost any dysregulated gene target with clinically validated in vivo delivery to myeloid immune cells.

MiNA’s immuno-oncology portfolio includes the following programs:

MTL‑CEBPA, which has been cleared for evaluation in a global Phase 2 clinical trial in combination with the tyrosine kinase inhibitor, sorafenib, in advanced hepatocellular carcinoma (HCC or liver cancer) and in a Phase 1 clinical trial in pediatric patients with MPS1 Hurler Syndrome
MTL-STING currently in pre-clinical development
Additional programs currently in discovery
About TIMEPOINT
TIMEPOINT is a global Phase 1a/b clinical study in patients with solid tumor malignancies to assess the safety and tolerability of MTL‑CEBPA in combination with pembrolizumab in patients who are ineligible or resistant to standard therapies. The study has received clearance from the U.S. Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). To learn more about the TIMEPOINT clinical study, visit ClinicalTrials.gov (NCT04105335).

The poster presentation at AACR (Free AACR Whitepaper) entitled, "MTL-CEBPA in combination with pembrolizumab converts an immune desert to an inflamed TME in solid tumors resistant to checkpoint blockade," will be available on MiNA’s website in the Publications section under "RNA Activation".

About MTL-CEBPA
MTL-CEBPA is the first therapy that specifically up-regulates CCAAT/enhancer binding protein alpha (C/EBP-α), a transcription factor that acts as a master regulator of myeloid cell lineage determination and differentiation. Dysregulated myeloid cells have been implicated in several diseases, and in solid tumor cancers these cells have been identified as a critical barrier to induction of clinical response for many therapies. In pre-clinical studies, MTL-CEBPA has been shown to improve the anti-tumor activity of cancer therapies by targeting dysregulated myeloid cells and reducing or eliminating their suppressive effect on immune response and therapies in the tumor microenvironment.

On April 14, 2023 Immune-Onc Therapeutics, Inc. ("Immune-Onc"), a private, clinical-stage cancer immunotherapy company developing novel biotherapeutics targeting myeloid checkpoints, reported encouraging Phase 1 dose escalation data for IO-108, a novel myeloid checkpoint inhibitor targeting Leukocyte Immunoglobulin-Like Receptor B2 (LILRB2, also known as ILT4) (Press release, Immune-Onc Therapeutics, APR 14, 2023, View Source [SID1234630101]). The data will be presented in an oral session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Orlando, Florida, April 18. Preclinical data for IO-312, a novel bispecific antibody targeting LILRB4 (ILT3) and CD3 (LILRB4 x CD3) will also be presented on April 18 as a late-breaking poster at AACR (Free AACR Whitepaper) 2023.

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We have great news to share this year at #AACR23! Data from our Ph 1 study show encouraging clinical benefit for IO-108 as a monotherapy & when combined with pembrolizumab. Don’t miss the oral presentation on Tue., April 18 at 4:05-4:15 PM ET (CT040)

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"We are very encouraged to see promising signs of clinical activity across multiple solid tumor types and a favorable safety profile with our first-in-class myeloid checkpoint inhibitor, IO-108," said Charlene Liao, Ph.D., chief executive officer and board chair of Immune-Onc. "Our data demonstrates the utility of IO-108 as a new therapeutic modality to address key unmet needs for patients with solid tumors that do not respond to, develop resistance to, or relapse following, treatment with T cell checkpoint inhibitors."

The Phase 1 dose escalation study of IO-108 is intended to evaluate primary objectives of safety and tolerability, and secondary and exploratory objectives of pharmacokinetics, immunogenicity, pharmacodynamic (PD) biomarker effects, and antitumor activity of IO-108 as a monotherapy and in combination with pembrolizumab in patients with advanced solid tumors. The trial enrolled 25 advanced cancer patients with relapsed/refractory solid tumors. Patients received escalating doses of IO-108 (60 mg -1800 mg) intravenously once every three weeks (Q3W). Treatment with IO-108 was well-tolerated to the maximum administered dose (1800 mg Q3W); the maximum tolerated dose was not reached. Among 23 evaluable patients (11 monotherapy, 12 combination therapy plus 1 crossover), results showed 1 complete response and 4 stable disease patients in the monotherapy cohorts and 3 partial responses and 4 stable disease patients in the combination cohorts.

The 4 responding patients remain on study with an ongoing treatment duration of 8 to 12+ months as of abstract submission. Clinical benefit correlated with baseline characteristics and post-treatment changes in PD biomarkers including reprogramming of myeloid cells and activation of T cells.

"Treating patients who are refractory to treatment with T-cell immune checkpoint inhibitors remains an ongoing challenge across many tumor types," said IO-108 Phase 1 investigator, Matthew H. Taylor, M.D., Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon. "I am very encouraged by these results, particularly the complete response to IO-108 monotherapy treatment in the Merkel cell carcinoma patient who had progressed on prior anti-PD-1 treatments. These findings suggest that LILRB2 is a critically important immunotherapy target."

The initial data from dose escalation supports further development of IO-108. The preliminary recommended Phase 2 dose (RP2D) is 1200 mg Q3W which is projected to achieve full receptor occupancy in at least 90% of patients. The ongoing IO-108 Phase 1 study is actively enrolling several biomarker-driven dose expansion cohorts, using IO-108 at RP2D as a monotherapy and in combination with anti-PD-1 antibodies (pembrolizumab, cemiplimab or tislelizumab), both in the U.S. and China.

Immune-Onc oral and poster presentation details are as follows:

Abstract Number: 9498
Title: A first-in-human phase 1 trial of IO-108, an antagonist antibody targeting LILRB2 (ILT4), as monotherapy and in combination with pembrolizumab in adult patients with advanced relapsed or refractory solid tumors: Dose escalation study
Presenter: Matthew H. Taylor, M.D., Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon
Session Title: Novel Immunotherapy Combination Clinical Trials
Session Date and Time: Tuesday, April 18, 2:30 p.m. – 4:30 p.m. ET
Presentation Number: CT040

Abstract Number: LB217
Title: A novel bispecific LILRB4/CD3 antibody with potent killing of monocytic acute myeloid leukemia cells
Presenter: Charlene Liao, Ph.D., chief executive officer of Immune-Onc Therapeutics, Inc.
Session Title: Late-Breaking Research: Immunology 2
Session Date and Time: Tuesday, April 18, 9:00 a.m. – 12:30 p.m. ET
Location: Poster Section 36, Poster Board #10

Abstracts and full session details can be accessed through the AACR (Free AACR Whitepaper) Online Program Planner

ABOUT IO-108

IO-108 is a fully human IgG4 monoclonal antibody with high affinity and specificity towards LILRB2 (also known as ILT4). It blocks the interaction of LILRB2 with multiple ligands that are involved in cancer-associated immune suppression, including HLA-G, ANGPTLs, SEMA4A and CD1d. Preclinical data presented at the 2020 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting and the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting demonstrate that IO-108 functions as a myeloid checkpoint inhibitor and promotes innate and adaptive anti-cancer immunity.

The ongoing Phase 1 study of IO-108 in adult cancer patients has completed dose escalation in the U.S. (NCT05054348) and is actively enrolling several expansion cohorts, as a monotherapy and in combination with anti-PD-1 antibodies (pembrolizumab, cemiplimab or tislelizumab), both in the U.S. and China. To date, IO-108 has been well tolerated with demonstrated clinical activity in multiple tumor types, both as a monotherapy and in combination with pembrolizumab.

On April 14, 2023 AstraZeneca reported that it will present new data across its diverse, industry-leading Oncology pipeline and portfolio at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, 14 to 19 April 2023 (Press release, AstraZeneca, APR 14, 2023, View Source [SID1234630100]).

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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

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Data from 70 presentations will be featured, including eight oral presentations, a plenary presentation of the AEGEAN Phase III trial of Imfinzi (durvalumab) based regimen in resectable non-small cell lung cancer (NSCLC), and the first disclosures of preclinical data for five novel molecules across the Company’s Antibody Drug Conjugate (ADC), Cell Therapy and Epigenetics scientific platforms.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "It’s exciting to see our strategy to attack cancer from multiple angles come to life at AACR (Free AACR Whitepaper) this year through data from our proprietary antibody drug conjugates, next generation cell therapies and epigenetics molecules. Furthermore, results from the AEGEAN trial show the potential of treating lung cancer patients early with Imfinzi before and after surgery which reinforces the importance of diagnosing lung cancer early."

Improving outcomes for patients with resectable lung cancer with Imfinzi
A late-breaking presentation of the AEGEAN Phase III trial results will highlight the potential of a novel Imfinzi-based treatment before and after surgery for patients with resectable early-stage (IIA-IIIB) NSCLC. AEGEAN has met its two primary endpoints, demonstrating improvements in event-free survival and pathologic complete response with Imfinzi in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy versus neoadjuvant chemotherapy alone followed by surgery.

Delivering the next wave of ADCs with proprietary platform
Two oral presentations will feature the first preclinical and translational results for AZD9592, a bispecific ADC designed to deliver targeted chemotherapy to cancer cells with a topoisomerase inhibitor 1 (TOP1i) warhead using the Company’s proprietary linker technology.

AZD9592 binds to two known oncogenic drivers: epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (cMET). These two drivers are often co-expressed in solid tumours including in NSCLC and head and neck squamous cell carcinoma (HNSCC). This is the Company’s first bispecific ADC to enter the clinic and shows a promising efficacy and safety profile in preclinical models, with evidence for DNA damage dependent tumour cell death as the mechanism of action.

In addition, the first preclinical results will be presented for another ADC, AZD5335, a promising therapeutic candidate for the treatment of certain ovarian cancers. This ADC has a folate receptor alpha (FRα) targeting antibody linked to a proprietary TOP1i warhead. A robust anti-tumour response is reported in FRα-expressing preclinical models that are resistant to another FRα ADC with a microtubule inhibitor warhead. In addition, AZD5335 is active in models with either high or low levels of target expression as detected by computational pathology.

Preclinical data for AZD8205, an ADC targeting B7-H4, will also be presented both as monotherapy and in combination with the PARP-1 selective inhibitor, AZD5305. Robust anti-tumour activity is evident in preclinical models across multiple B7-H4 positive tumour types, including ovarian and cholangiocarcinoma tumours, with combination therapy resulting in higher anti-tumour activity than monotherapy.

Building the next generation of cell therapies in solid tumours
In cell therapy, the first clinical data will be presented for C-CAR031, a novel transforming growth factor-beta (TGFβ) armoured Glypican 3 (GPC3) targeting chimeric antigen receptor T cell (CAR-T) therapy that is being investigated for liver cancer. Early results show it is well tolerated with promising anti-tumour activity seen with objective responses in several patients to date.

The CAR-T is based on AZD5851, a novel cell therapy that was designed by AstraZeneca, and is being developed and manufactured by Cellular Biomedicine Group (CBMG). AstraZeneca’s TGFβ armouring is designed to resist the immuno-suppressive tumour microenvironment and enhance the potential effectiveness of CAR-Ts in solid tumours.

In addition, the first preclinical data will be shared on AZD0754, a novel TGFβ armoured CAR-T targeting STEAP2, a protein commonly overexpressed in prostate cancer. This is the first cell therapy to be designed, manufactured and developed by AstraZeneca. The presentation will show encouraging preclinical safety data and supports future clinical development of this potential first-in-class CAR-T therapy.

First disclosure and preclinical data for an epigenetics molecule targeting PRMT5
Epigenetic therapy is one of AstraZeneca’s six core scientific areas of focus. The modality is the latest addition to the Company’s diverse portfolio, which is designed to attack cancer from multiple angles and redefine outcomes for patients with high unmet needs.

At AACR (Free AACR Whitepaper), the first preclinical data will be presented for the novel lead epigenetics molecule, AZ-PRMT5i-1, a potent methylthioadenosine phosphorylase (MTAP)-selective PRMT5 inhibitor with anti-tumour activity in MTAP-deleted tumours. Loss of the MTAP gene occurs across approximately 15% of all cancers, which provides an opportunity to use a biomarker selection strategy and also spare healthy tissue. The preclinical results demonstrate MTAP selectivity and promising anti-tumour activity.

Harnessing transformational technologies
Transformational technologies, including circulating tumour DNA (ctDNA), computational pathology, and data science and artificial intelligence (AI), underpin the success of progressing AstraZeneca’s pipeline. Several presentations at AACR (Free AACR Whitepaper) showcase the Company’s efforts to harness the power of these technologies to better understand complex cancer biology, identify and select patients for treatment and increase the probability of success in the clinic.

Key AstraZeneca presentations during AACR (Free AACR Whitepaper) 2023

Lead author

Abstract title

Presentation details

IO

Heymach, JV

CT005 – AEGEAN: A phase 3 trial of neoadjuvant durvalumab + chemotherapy followed by adjuvant durvalumab in patients with resectable NSCLC

Abstract #CT005

Plenary

Harnessing the Immune System in the Clinic

16 April 2023

14:45 – 15:00 ET

Iyer S

Immunomodulatory effects of ceralasertib in combination with durvalumab in NSCLC patients with progression on anti-PD-(L)1 treatment (HUDSON, NCT03334617)

Abstract #CT039

Clinical Trials Minisymposium

Novel Immunotherapy Combination Clinical Trials

18 April 2023

15:50 – 16:00 ET

ADCs

Gymnopoulos, M

First disclosure of AZD5335, a TOP1i-ADC targeting low and high FRα-expressing ovarian cancer with superior preclinical activity vs FRα-MTI ADC

Abstract #LB025 / 17

Poster

Late-Breaking Research: Experimental and Molecular Therapeutics 1

16 April 2023

13:30 – 17:00 ET

Comer, F

AZD9592: an EGFR-cMET bispecific antibody-drug conjugate (ADC) targeting key oncogenic drivers in non-small-cell lung cancer (NSCLC) and beyond

Abstract #5736

Minisymposium

New Tricks for Known Targets: Novel Approaches to Inhibit Oncogenic Signaling

18 April 2023

15:22 – 15:37 ET

McGrath, L

Evaluation of the relationship between target expression and in vivo anti-tumour efficacy of AZD9592, an EGFR/c-MET targeted bispecific antibody drug conjugate

Abstract #5737

Minisymposium

New Tricks for Known Targets: Novel Approaches to Inhibit Oncogenic Signaling

18 April 2023

15:37 – 15:52 ET

Cazes, A

Preclinical evaluation of a novel B7-H4-targeted antibody-drug conjugate AZD8205 as a single agent and in combination with novel PARP inhibitor and checkpoint blockade

Abstract #2947 / 25

Poster

Therapeutic Antibodies 2

17 April 2023

13:30 – 17:00 ET

Meric-Bernstam, F

TROPION-PanTumor03: Phase 2, multicenter study of datopotamab deruxtecan (Dato-DXd) as monotherapy and in combination with anticancer agents in patients (pts) with advanced/metastatic solid tumours

Abstract #CT058 / 16

Poster

Phase II and Phase III Clinical Trials in Progress

17 April 2023

9:00 – 12:30 ET

Bhavsar, D

Combination of T-DXd with the irreversible pan-HER TKI afatinib drives combination benefit in HER2-low gastric and lung tumours

Abstract #3999 / 22

Poster

Oncogenes and Tumour Suppressor Genes as Targets for Therapy 3

18 April 2023

9:00 – 12:30 ET

Wray, R.

Improving Treatment Outcomes: A Digital Solution for Remote Patient Monitoring of Stomatitis for Patients receiving Dato-DXd

Abstract #LB143 / 7

Poster

Late-Breaking Research: Population Sciences

17 April 2023

13:30 – 17:00 ET

Cell Therapy

van Dyk, D

Antitumour activity of AZD0754, a dnTGFbR2 armored STEAP2 targeted CAR-T therapy, in preclinical models of prostate cancer

Abstract #LB085 / 1

Poster

Late-Breaking Research: Immunology 1

17 April 2023

9:00 – 12:30 ET

Zhang, Q

First report of preliminary safety, efficacy, and pharmacokinetics of C-CAR031 (GPC3-specific TGFBRIIDN CAR-T) in patients with advanced HCC

Abstract #CT097 / 5

Poster

First-in-Human Phase I Clinical Trials 1

17 April 2023

13:30 – 17:00 ET

Epigenetics

Smith, JM

Identification of a novel series of MTAP-selective PRMT5 inhibitors, and first disclosure of AZ-PRMT5i-1

Abstract #3088 / 1

Poster

Targeted Drug Design and Development for Cancer Therapy

17 April 2023

13:30 – 17:00 ET

Lynch, J

AZ-PRMT5i-1: A potent MTAP-selective PRMT5 inhibitor with pharmacodynamic and monotherapy anti-tumour activity in MTAP-deleted tumours

Abstract #6272 / 10

Poster

Epigenetics

19 April 2023

9:00 – 12:30 ET

TDR1

Zhi Peng

A Multicenter Phase II Study of Savolitinib in Patients with MET-Amplified Gastroesophageal Junction Adenocarcinomas or Gastric Cancer

Abstract # CT152

Phase II Clinical Trials 1

17 April 2023

13:30 – 17:00 ET

ctDNA

Labrousse, P

The evolution of MRD assays; moving beyond the tumour-informed bespoke NGS panel

Abstract #LB293 / 6

Poster

Late-Breaking Research: Clinical Research 3

19 April 2023

9:00 – 12:30 ET

Russell, H

Evaluation of a tumour informed MRD assay with contrived breast cancer samples

Abstract #3384 / 27

Poster

Liquid Biopsies: Circulating Nucleic Acids and Circulating Tumour Cells 3

17 April 2023

13:30 – 17:00 ET

Munugalavadla V

Utility of ctDNA-based targeted methylation MRD assay for hematological malignancies

Abstract #3369 / 12

Poster

Liquid Biopsies: Circulating Nucleic Acids and Circulating Tumour Cells 3

17 April 2023

13:30 – 17:00 ET

Hartmaier, R

Baseline and on-treatment plasma-based genomics as a predictor of outcomes in SAVANNAH: savolitinib + osimertinib in EGFRm MET overexpressed/amplified NSCLC post-osimertinib

Abstract #LB294 / 7

Poster

Late-Breaking Research: Clinical Research 3

19 April 2023

9:00 – 12:30 ET

Data Science & AI

Arango G

Translating state-of-the-art deep learning predictions of IO treatment efficacy to clinical practice

Abstract #5359 / 8

Poster

Artificial Intelligence and Machine/Deep Learning 1

18 April 2023

13:30 – 17:00 ET

Arango G

Enhancing the utilization of deep learning to predict patient response in small immunotherapy cohorts using real world data

Abstract #1174

Minisymposium

Advancing Cancer Research Through an International Cancer Registry: AACR (Free AACR Whitepaper) Project GENIE Use Cases

16 April 2023

15:36 – 15:51 ET

Nikolau N

Improving survival prediction using flexible late fusion machine learning framework for multi-omics data integration

Abstract #5395 / 11

Poster

Artificial Intelligence and Machine/Deep Learning 2

18 April 2023

13:30 – 17:00 ET

Arango G

Improved identification of CHIP mutations from cell free DNA without matched normal samples using machine learning

Abstract #5360 / 9

Poster

Artificial Intelligence and Machine/Deep Learning 1

18 April 2023

13:30 – 17:00 ET

Ellen JG

Autoencoder-based multimodal prediction of survival for non-small cell lung cancer

Abstract #5373 / 22

Poster

Artificial Intelligence and Machine/Deep Learning 1

18 April 2023

13:30 – 17:00 ET

Computational Pathology

Potdevin, G

A first assessment of CD8-PET/CT with 89-Zr-Crefmirlimab as predictive biomarker for response to standard of care immunotherapy in patients with solid tumours

Abstract #3577 / 2

Poster

PET, MRI, and CT Imaging

18 April 2023

9:00 – 12:30 ET

Brieu, N

A unified computational pathology method to quantify HER2 expression from raw IHC and IF images in breast cancer

Abstract #5388 / 4

Poster

Artificial Intelligence and Machine/Deep Learning 2

18 April 2023

13:30 – 17:00 ET