On September 9, 2021 GlaxoSmithKline (GSK) plc reported that it will present new data across the Company’s oncology pipeline and portfolio at the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021 (16-21 September), including new data on JEMPERLI (dostarlimab) and ZEJULA (niraparib), as well as early-stage research in immuno-oncology and oncology cell therapy (Press release, GlaxoSmithKline, SEP 9, 2021, https://www.gsk.com/en-gb/media/press-releases/gsk-to-highlight-continued-progress-in-oncology-pipeline-and-portfolio-with-data-presented-at-esmo/ [SID1234587454]). With 13 presentations at the meeting (12 GSK-sponsored and one GSK-supported), GSK will demonstrate its momentum in advancing dostarlimab and niraparib, and provide new insights into investigational therapies through early-stage research.

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The data being presented at ESMO (Free ESMO Whitepaper) reflect GSK’s commitment to strengthening its oncology pipeline across its focus areas of immuno-oncology, synthetic lethality and oncology cell therapy. GSK has a diverse portfolio and pipeline, including three marketed oncology medicines and 16 assets in clinical development that leverage the science of the immune system, human genetics and advanced technologies to address a variety of tumour types.

Continuing to advance immuno-oncology therapies

Presentations from the phase I GARNET study will address anti-tumour activity by tumour mutational burden in patients with recurrent or advanced endometrial cancer (Abstract #76P) in addition to treatment-related adverse events occurring during the study (Abstract #991P). GSK will also present a real-world analysis of the demographics and survival outcomes in patients from England with advanced or recurrent endometrial cancer following platinum-based doublet therapies (Abstract #812P).

Dostarlimab is the first anti-PD-1 monotherapy approved for endometrial cancer in the European Union (EU) and received a conditional approval in April for the treatment of women with mismatch repair-deficient (dMMR) /microsatellite instability-high (MSI-H) recurrent or advanced endometrial cancer who have progressed on or following prior treatment with a platinum containing regimen. The treatment also received accelerated approval in the United States (US) for adult patients with dMMR recurrent or advanced endometrial cancer, as determined by an FDA-approved test, who have progressed on or following prior treatment with a platinum-containing regimen.

Last month, the FDA granted accelerated approval of an additional indication for dostarlimab for the treatment of adult patients with dMMR recurrent or advanced solid tumours, as determined by an FDA-approved test, who have progressed on or following prior treatment and who have no satisfactory alternative treatment options. The new indication for dostarlimab is the fourth approval for GSK oncology in less than 1.5 years, demonstrating GSK’s unyielding commitment to address the unmet needs of cancer patients.

Continued research and development in synthetic lethality

Results from the phase III PRIMA trial will examine quality-adjusted time without symptom or toxicity of niraparib in patients with advanced ovarian cancer (Abstract #738P). Additionally, GSK will present real-world analyses from three studies in patients with advanced ovarian cancer across the UK, France and US.

Niraparib is a once-daily oral monotherapy maintenance treatment approved for women with first-line platinum-responsive advanced ovarian cancer regardless of biomarker status in the US and the EU. The research that will be presented at ESMO (Free ESMO Whitepaper) bolsters the understanding of the use of this poly (ADP-ribose) polymerase (PARP) inhibitor for maintenance treatment in ovarian cancer.

GSK will also present a trial in progress poster on the recently initiated phase III ZEAL-1L study in advanced or metastatic non-small cell lung cancer, expanding the Company’s clinical development programme into other solid tumours to potentially bring niraparib to more patients.

The complete list of GSK sponsored and supported abstracts accepted by ESMO (Free ESMO Whitepaper) for presentation and/or publication from the company’s areas of oncology research is below.

Immuno-oncology

Abstract Name

Presenter

Abstract Number

Analysis of antitumor activity of dostarlimab by tumor mutational burden (TMB) in patients (pts) with endometrial cancer (EC) in the GARNET trial

Oaknin, A

#76P

Demographics and survival outcomes in patients with advanced or recurrent endometrial cancer (EC) following platinum-based doublet (PBD) in the English real-world (RW) setting

Heffernan, K

#812P

Treatment-related adverse events (TRAEs) occurring during dostarlimab therapy in the GARNET study​

Andre, T

#991P

ENGOT-EN6/GOG-3031/NSGO-RUBY Part 2: A phase 3, randomized, double-blind, study of dostarlimab + carboplatin-paclitaxel followed by

dostarlimab + niraparib versus placebo (PBO) + carboplatin-paclitaxel followed by PBO in recurrent or advanced endometrial cancer (EC)

Mirza, MR

#820TiP

Adverse event management during treatment with bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1: treatment guidelines based on experience in clinical trials

Gulley, J

#1689P

Long-term follow-up of patients (pts) with human papillomavirus (HPV)–associated malignancies treated with bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1

Strauss, J

#957O

Synthetic Lethality

Abstract Name

Presenter

Presentation Details

Impact of residual disease on outcomes in patients with ovarian cancer: A meta-analysis

Chase, D

#761P

Ovarian Cancer Retrospective European (O’CaRE) observational study to assess burden of disease and time to next treatment in real-world clinical practice: results from the United Kingdom (UK)​

McGrane, J

#745P

Quality-Adjusted Time without Symptom or Toxicity​ (Q-TWiST) and Quality-Adjusted Progression-Free Survival (QA-PFS) of First-Line (1L) maintenance niraparib in patients with advanced Ovarian Cancer (OC) – Results from the PRIMA trial

Barretina-Ginesta, P​

#738P

Real-world clinical outcomes of patients with de novo advanced high-grade epithelial ovarian cancer eligible to niraparib maintenance in France

Rodrigues, M

#746P

Survival in patients (pts) with advanced ovarian cancer (AOC) changes with cumulative number of risk factors (RFs), a US real-world (RW) analysis

Chase, D

#742P

First-line (1L) maintenance therapy with niraparib (nira) + pembrolizumab (pembro) vs placebo + pembro in advanced/metastatic non-small cell lung cancer (NSCLC): Phase III ZEAL-1L study​

Ramalingam, S

#1360TiP

Oncology Cell Therapy

Abstract Name

Presenter

Presentation Details

A novel, comprehensive glimpse at NY-ESO-1 expression, mRNA to protein translation, & potential impact on clinical studies

​Blouch, K

#109P

About Dostarlimab

Dostarlimab is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2.[1] In addition to GARNET, dostarlimab is being investigated in other registrational enabling studies, as monotherapy and as part of combination regimens, including in women with recurrent or primary advanced endometrial cancer, women with stage III or IV non-mucinous epithelial ovarian cancer, and in patients with other advanced solid tumours or metastatic cancers.

Dostarlimab was discovered by AnaptysBio and licensed to TESARO, Inc., under a Collaboration and Exclusive License Agreement signed in March 2014. The collaboration has resulted in three monospecific antibody therapies that have progressed into the clinic. These are: dostarlimab, a PD-1 antagonist; cobolimab, (GSK4069889), a TIM-3 antagonist; and GSK4074386, a LAG-3 antagonist. GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of each of these Products under the Agreement.

Important Information for JEMPERLI in the EU

Indication

JEMPERLI is indicated as monotherapy for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability‑high (MSI‑H) recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum‑containing regimen.

Refer to the JEMPERLI Prescribing Information for a full list of adverse events and the complete important safety information in the EU.

About Niraparib

Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in multiple pivotal trials. GSK is building a robust niraparib clinical development programme by assessing activity across multiple tumour types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development programme for niraparib includes several combination studies.

Important Information for ZEJULA

Indication

ZEJULA is indicated as monotherapy for the maintenance treatment of adult patients with advanced epithelial (FIGO Stages III and IV) high-grade ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy.

Refer to the ZEJULA Prescribing Information for a full list of adverse events and the complete important safety information.

GSK in Oncology

GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, tumour cell targeting therapies and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody-drug conjugates and cell therapy, either alone or in combination.

GSK is a science-led global healthcare company. For further information please visit www.gsk.com/about-us.

On September 9, 2021 Anticancer Bioscience (ACB), pioneers in synthetic lethal approaches to precision oncology, reported its first granted US patent (11104633), entitled "cancer treatment using compounds that selectively target polyploid cancer cells for disruption", which was issued by the US Patent and Trademark Office (USPTO) on August 31 (Press release, Anticancer Bioscience, SEP 9, 2021, View Source [SID1234587452]).

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The method covered in this patent has been used to identify compounds that selectively kill polyploid cells, key to the discovery of inhibitors of MYC, overexpression of which occurs in over half of tumors, and is correlated with poorly differentiated and aggressive cancer.

Dun Yang PhD, Founder, President, and CEO of ACB, said: "The grant of our first patent in the USA is a key milestone and underlines our innovative approach to identifying first-in-class and best-in-class approaches for the treatment of cancer, using synthetic lethal approaches. It forms part of our growing patent estate with nine additional patents pending, covering both methods and composition of matter."

ACB is applying synthetic lethal approaches to develop targeted cancer therapies. These have the potential to be much safer and more effective than current therapies. ACB has access to world-leading cancer biology expertise and drug discovery platforms that enable the company to identify novel compounds that can target both genetic and epigenetic vulnerabilities of cancer cells. ACB has bespoke chemical compound libraries and has invested in developing one of the world’s largest natural product libraries, providing a rich screening resource for potential cancer therapeutics.

With five drug discovery programs, ACB is progressing rapidly through optimization to candidate selection toward IND enabling studies, with the aim of initiating two clinical trials in the USA in 2022.

On September 9, 2021 Anavex Life Sciences Corp. ("Anavex" or the "Company") (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome and other central nervous system (CNS) disorders, reported that Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex, will present at the H.C. Wainwright 23rd Annual Global Investment Conference being held from September 13-15, 2021 (Press release, Anavex Life Sciences, SEP 9, 2021, https://www.anavex.com/anavex-life-sciences-to-present-at-the-h-c-wainwright-23rd-annual-global-investment-conference/ [SID1234587451]).

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A webcast of the on-demand presentation will be available beginning Monday, September 13, 2021, at View Source or on the Company’s website at www.anavex.com. The on-demand presentation will open on September 13 at 7:00 A.M. (ET). A webcast replay will be accessible for 30 days following the event.

On September 8, 2021 Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, reported a clinical trial collaboration and supply agreement with Pfizer Inc. (NYSE: PFE) for the BRAF inhibitor encorafenib (BRAFTOVI) (Press release, Erasca, SEP 8, 2021, View Source [SID1234639384]).

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This agreement will support a clinical proof-of-concept study evaluating ERAS-007, an oral ERK1/2 inhibitor, in combination with encorafenib and the EGFR inhibitor cetuximab for the treatment of patients with BRAF V600E-mutant mCRC. This combination will be investigated as part of the Phase 1b/2 HERKULES-3 trial expected to initiate in the second half of 2021. Erasca will sponsor the study, and Pfizer will supply encorafenib. The two companies will form a Joint Development Committee to review the clinical trial results.

"We are excited to work with Pfizer to explore this promising combination in colorectal cancer," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "MAPK signaling is constitutively activated in patients with BRAF V600E mutations, who often have a poor prognosis. Combining upstream EGFR inhibition, midstream BRAF inhibition, and downstream ERK inhibition fits squarely within Erasca’s strategies to erase cancer and has potential to limit pathway reactivation, offering the therapeutic potential to comprehensively shut down the RAS/MAPK pathway in this tumor type."

Worldwide, approximately 1.8 million cases of CRC are diagnosed annually, with BRAF V600E mutations occurring in approximately 10% of these patients. The combination of encorafenib and cetuximab was approved in April 2020 for previously treated patients with BRAF V600E-mutant mCRC. The combination demonstrated improved overall survival compared to the chemotherapy control arm; however, only 20% of patients experienced an objective response, and the progression-free survival was approximately four months. Therefore, emergence of resistance is a major therapeutic barrier to long-term clinical benefit. Erasca is exploring whether ERK inhibition with ERAS-007 in combination with encorafenib plus cetuximab can reduce the emergence of resistance and further improve treatment benefit for patients with BRAF V600E-mutant mCRC.

About ERAS-007
ERAS-007 is a potential best-in-class ERK1/2 inhibitor being investigated alone or in combination with different inhibitors targeting upstream nodes of the MAPK pathway as part of Erasca’s MAPKlamp strategy. The extracellular signal-regulated kinases (ERK), ERK1 and ERK2, belong to a family of serine-threonine kinases that regulate cellular signaling and comprise the terminal node of the RAS/MAPK pathway. ERAS-007 is being investigated across a series of four HERKULES clinical trials that span multiple tumor types and includes both monotherapy and combinations with approved and investigational agents, such as RTK, SHP2, RAS, RAF, and/or cell cycle inhibitors. HERKULES-1 is a Phase 1b/2 clinical trial for ERAS-007 as a single agent and in combination with the SHP2 inhibitor ERAS-601 (together, Erasca’s first MAPKlamp) in advanced solid tumors. HERKULES-2 is a Phase 1b/2 clinical trial for ERAS-007 in combination with various agents in patients with non-small cell lung cancer. HERKULES-3 is a Phase 1b/2 clinical trial for ERAS-007 in combination with various agents in patients with gastrointestinal cancers. HERKULES-4 is a Phase 1b/2 clinical trial for ERAS-007 in combination with various agents in patients with hematologic malignancies.

On September 8, 2021 A-Alpha Bio, a biotechnology company that works with pharmaceutical industry partners to accelerate drug discovery with massively multiplexed measurements of protein interactions, reported that it has closed a $20M Series A Financing Round to dramatically expand capabilities and throughput (Press release, A-Alpha Bio, SEP 8, 2021, View Source [SID1234636941]). The round was led by Madrona Venture Group with participation from Perceptive Advisors’ Perceptive Xontogeny Venture Fund (PXV Fund) and Lux Capital. Madrona Venture Group’s Matt McIlwain and Xontogeny’s Ben Askew, Ph.D. have joined A-Alpha Bio’s Board of Directors as part of the financing.

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A-Alpha Bio is building a high-resolution model of biology by measuring millions of protein-protein interactions, leveraging the intersection of synthetic biology, protein engineering, and machine learning. Compared to traditional technologies for screening protein interactions, including biophysical and display platforms, A-Alpha Bio’s proprietary AlphaSeq platform is able to measure protein interactions at a scale and to a degree of precision that is otherwise inaccessible. The quantity and quality of AlphaSeq data is ideal for drug discovery and also critical for training highly predictive ML-models for protein-protein binding.

"Understanding and characterizing protein-protein interactions is fundamental to the future of drug discovery and development and we are excited to back this impressive team that is at the intersection of innovation – bringing together life and computer sciences to uncover previously inaccessible discoveries," said Matt McIlwain, Managing Director, Madrona Ventures Group. "We have been impressed by the traction David and the team have made since we invested in the seed round and believe they are well on their way to helping to develop treatments for diseases and create a data advantage that could change the future of antibody and small molecule discovery."

A-Alpha Bio will deploy the new capital announced today to build a new production laboratory, generate the largest ever database of protein interaction measurements, and fill key roles in their rapidly growing team. These investments will enhance the company’s partnerships with leading pharmaceutical companies to discover new drugs – with a focus on antibodies and molecular glues. With a massive and ever-growing protein interaction data asset, A-Alpha Bio also plans to expand their machine-learning capabilities to uncover the complex rules of protein binding and enable in silico modeling of complex protein interaction networks.

"Our mission is to improve human health by accelerating drug discovery with synthetic biology and machine learning. I’m incredibly proud of the phenomenal team we’ve built and the impactful work we’ve already accomplished with leading pharma and biotech partners," said Dr. David Younger, Co-Founder and CEO of A-Alpha Bio. "Our Series A investors share our vision and optimism for the future of medicine. I’m especially delighted to welcome Matt McIlwain and Ben Askew as Board Members who bring decades of experience building high-impact companies across the technology and pharmaceutical industries."

Protein interactions are central to antibody and small-molecule drugs, and AlphaSeq represents the first high-throughput and quantitative approach for measuring protein-protein binding. By leveraging AlphaSeq, partners have been able to accelerate antibody discovery by measuring millions of interactions between antibodies and antigens for high-throughput determination of properties like affinity, specificity, cross-reactivity, and epitope. Instead of narrowly funnelling an antibody library and characterizing the few strongest binders, AlphaSeq allows partners to maintain a wide funnel with thousands of antibodies to avoid missing therapeutic candidates with unique and desirable properties. AlphaSeq is also leveraged for molecular glue target discovery by measuring weak and likely druggable interactions between a library of E3 ubiquitin ligases and a library of neo-substrates.

"When it comes to measuring protein-protein interactions and assisting pharma in the discovery of antibodies and molecular-glue targets, AlphaSeq is unmatched," said Ben Askew Ph.D., Partner, PXV Fund. "AlphaSeq is enabling pharma companies to find the high-value needles in the haystack, a process so prohibitively expensive, rare, or slow that these opportunities might have never been found. We’re thrilled to support A-Alpha Bio’s next phase of growth as they continue to set new standards for protein and molecular glue research."

To date, A-Alpha Bio has worked with a number of partners across the pharmaceutical and biotech industry to advance drug discovery, ranging from mid-sized biotechs to top-ten pharma. Additionally, A-Alpha Bio has ongoing awards from the Bill & Melinda Gates Foundation to support the discovery of therapeutics for infectious diseases and the National Science Foundation to support molecular-glue target discovery and ML-guided antibody discovery.