On September 24, 2020 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical-stage biotechnology company focused on discovering and developing novel small-molecule drugs for the treatment of cancer and other life-threatening diseases, reported treatment of the first patient in a randomized Phase 2 non-small cell lung cancer (NSCLC) clinical trial of the glutaminase inhibitor telaglenastat (CB-839) in combination with pembrolizumab, carboplatin and pemetrexed (Press release, Calithera Biosciences, SEP 24, 2020, View Source [SID1234565565]). The KEAPSAKE study will evaluate the safety and anti-tumor activity of telaglenastat plus standard-of-care immunotherapy as front-line therapy among patients with stage IV non-squamous NSCLC whose tumors have a KEAP1 or NRF2 mutation determined by next-generation sequencing.

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Mutations in the KEAP1/NRF2 pathway, which occur in an estimated 20 percent of NSCLC patients, are associated with aggressive tumor growth. Recently presented clinical data demonstrate that activation of this pathway, either through the loss of KEAP1 function or activation of NRF2, are associated with poor clinical outcomes among patients with NSCLC receiving front-line standard-of-care chemoimmunotherapy. Pre-clinical models have shown that activation of the KEAP1/NRF2 pathway results in dependence on glutaminase activity for growth and survival, making these tumors exquisitely sensitive to inhibition of glutaminase activity by telaglenastat.

"Therapies that inhibit glutaminase in tumors with KEAP1/NRF2 pathway activation could have a meaningful clinical impact for a substantial percentage of people with NSCLC," said Susan Molineaux, PhD, president and chief executive officer of Calithera. "We’re proud that KEAPSAKE is among the first clinical trials investigating a potential new therapy for these patients who have a poor prognosis. Based on both the clear mechanistic rationale for telaglenastat in this indication and strong preclinical data, we’re hopeful that the study will provide valuable insights."

The double-blind KEAPSAKE trial will enroll approximately 120 patients with stage IV non-squamous NSCLC with tumors that have the KEAP1 or NRF2 mutation. Patients will be randomized to receive telaglenastat or placebo, in combination with pembrolizumab, carboplatin and pemetrexed. The study will evaluate the safety and investigator-assessed progression-free survival (PFS) of telaglenastat plus this standard-of-care chemoimmunotherapy regimen. Guardant360 liquid biopsy test will be provided by the study sponsor as an investigational use only (IUO) testing option for patient selection. Calithera anticipates sharing interim data from the KEAPSAKE trial in 2021.

About Telaglenastat

Telaglenastat (CB-839) is an investigational, first-in-class, novel glutaminase inhibitor specifically designed to block cancer cells from using glutamine for growth and survival. Tumors commonly exhibit metabolic alterations that increase their dependence on glutamine. In preclinical studies, telaglenastat produced synergistic antitumor effects when used in combination with standard-of-care therapies. Calithera is evaluating telaglenastat in combination therapy approaches for multiple solid tumor types, including metastatic renal cell carcinoma and non-small cell lung cancer.

About Lung Cancer

Lung cancer is one of the most common cancers, with approximately 228,820 new cases and 135,720 deaths in the U.S. projected in 2020, according to the American Cancer Society. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 84 percent of all lung cancer diagnoses. A recently published observational study demonstrated that the survival of patients with KEAP1 genomic alterations treated with standard-of care first-line chemo-immunotherapy was statistically significantly shorter when compared with patients without the mutations (7.8 months vs. 20.4 months p=0.002).1

On September 24, 2020 IDEAYA Biosciences, Inc. (NASDAQ: IDYA), an oncology-focused precision medicine company committed to the discovery and development of targeted therapeutics to treat cancer, reported that it has expanded its clinical trial collaboration and supply agreement with Pfizer Inc. (NYSE: PFE) for an IDEAYA sponsored clinical combination study of IDE196, a Protein Kinase C (PKC) inhibitor, and crizotinib, a cMET inhibitor to which Pfizer has exclusive worldwide rights (Press release, Ideaya Biosciences, SEP 24, 2020, View Source [SID1234565558]). The study will evaluate IDE196 and crizotinib combination therapy in patients with solid tumors having GNAQ or GNA11 mutations (GNAQ/11), including metastatic uveal melanoma (MUM), skin melanoma, lung cancer and colorectal cancer.

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Evaluating MUM patient clinical samples, IDEAYA identified cMET expression or activation as a potentially valuable biomarker that may guide IDE196 clinical treatment in this indication. IDEAYA also demonstrated preclinical synergy in MUM with the combination of IDE196 and crizotinib, which further supports the potential biomarker on cMET expression.

"We are excited to expand our agreement with Pfizer to evaluate the clinical combination of IDE196 and crizotinib in MUM and other solid tumors with GNAQ or GNA11 mutations," said Mick O’Quigley, Vice President, Head of Development Operations, IDEAYA Biosciences. "Through our translational research we have identified cMET expression as a potential biomarker, and we are excited to explore this rational combination between IDE196 and crizotinib clinically," said Mark Lackner, Ph.D., Senior Vice President, Head of Biology and Translational Sciences.

IDEAYA’s clinical development plan in MUM for IDE196 is based on combination therapies, including with binimetinib, a MEK inhibitor, and crizotinib, a cMET inhibitor, enabled through our clinical trial collaboration and drug supply agreement with Pfizer. The company announced First-Patient-In (FPI) for the IDE196 and binimetinib clinical combination in June 2020 and is targeting FPI for the crizotinib clinical trial combination in late 2020 to early 2021. IDEAYA is also evaluating IDE196 as monotherapy in an ongoing GNAQ/11 non-MUM basket trial in additional solid tumor types, including in skin melanoma, where the company announced Phase 2 expansion.

IDEAYA and Pfizer have established a Joint Development Committee (JDC), and there will be joint decision making and data sharing of the clinical trial results between the parties. IDEAYA will sponsor the study and Pfizer will provide the crizotinib drug supply. If there is clinical data from the collaboration studies that could be used to obtain regulatory approvals or label changes, IDEAYA and Pfizer will enter into good faith negotiations to determine a regulatory submission strategy.

On September 24, 2020 Taiho Pharmaceutical Co., Ltd. and The University of Texas MD Anderson Cancer Center reported a three-year strategic collaboration to accelerate the development of treatments for significant unmet medical needs in oncology, including patients with brain metastases and those with cancers refractory to available therapies (Press release, Taiho, SEP 24, 2020, View Source [SID1234565553]).

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This collaboration will bring Taiho’s unique portfolio of preclinical and clinical brain-penetrant therapies together with both the industry-scale translational research capabilities of MD Anderson’s Translational Research to Advance Therapeutics and Innovation in Oncology (TRACTION) platform as well as insights and clinical development infrastructure from MD Anderson’s Brain Metastasis Clinic.

"Our collaboration with MD Anderson exemplifies a direct line of sight from target development to therapies for patients with limited treatment options," said Teruhiro Utsugi, Ph.D., managing director at Taiho. "Investigating our novel portfolio of drug candidates in this innovative research structure will enable us to more rapidly identify and develop effective treatment strategies."

According to the American Brain Tumor Association, metastases to the brain and spine are diagnosed in more than 200,000 patients annually in the US. However, the development of effective treatment approaches for these patients has been hampered because they often are excluded from clinical trials. However, recent studies in melanoma, lung and breast cancers have demonstrated that patients with brain metastases can gain significant clinical benefit from immunotherapy and targeted therapies, leading to improvements in quality of life and survival.

MD Anderson’s Brain Metastasis Clinic is a patient-focused, multidisciplinary center designed to reduce the time from a diagnosis to treatment for patients with brain metastases while improving access to clinical trials. The TRACTION platform, an industry-scale translational research unit within MD Anderson’s Therapeutics Discovery division, has established a robust integrated research framework with the Brain Metastasis Clinic to identify innovative treatment approaches and execute novel clinical trials.

"MD Anderson’s commitment to delivering novel therapeutic strategies to patients with unmet clinical needs is exemplified in the development of the Brain Metastasis Clinic and its close collaboration with the TRACTION platform," said Timothy Heffernan, Ph.D., executive director of TRACTION at MD Anderson. "Our alliance with Taiho combines outstanding drug discovery with expertise in translational research and clinical development to advance new treatment options for patients diagnosed with brain metastases."

On September 23, 2020 Athenex, Inc. (NASDAQ: ATNX), a global biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies for the treatment of cancer and related conditions, reported that the U.S. Food and Drug Administration (FDA) has allowed its Investigational New Drug (IND) application for TCRT-ESO-A2, an autologous T cell receptor (TCR)-T cell therapy targeting solid tumors that are NY-ESO-1 positive in HLA-A*02:01 positive patients (Press release, Athenex, SEP 23, 2020, View Source [SID1234573871]).

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TCRT-ESO-A2 is being developed by Axis Therapeutics Limited, a joint venture between Athenex and Xiangxue Life Sciences Limited ("XLifeSc"), a subsidiary of Xiangxue Pharmaceutical Co., Ltd. (Shenzhen Exchange: 300147). TCRT-ESO-A2 is similar to TAEST16001, an autologous cell-based therapy being developed simultaneously by XLifeSc for clinical application in China in that both therapies express the same affinity-enhanced TCR.

"The FDA’s allowance of this IND application for TCRT-ESO-A2 represents another important milestone for Athenex, as we further expand our oncology-focused pipeline in the field of T cell based cancer immunotherapy," stated Dr. Johnson Lau, Chairman and Chief Executive Officer of Athenex, and Chief Executive Officer of Axis Therapeutics. "We are extremely pleased by the allowance of this IND application, which represents the 10th IND allowed by the FDA for Athenex. We were also excited by the observed preliminary, positive clinical signals in pilot studies in China using TAEST16001 conducted by our partner, XLifeSc."

Mr. YongHui Wang, Chairman and Chief Executive Officer of Xiangxue Pharmaceutical, and Chief Executive Officer of XLifeSc, said, "This achievement with TCRT-ESO-A2 follows the IND allowance of TAEST16001 in China by the National Medical Products Association and represents the successful collaboration of our joint development team at Axis Therapeutics. XLifeSc has initiated a Phase I trial of TAEST16001 in China and we are excited to continue working with the team at Athenex to potentially bring a differentiated and valuable immunotherapy technology to cancer patients around the world."

Dr. Daniel Lang, President of Axis Therapeutics, added, "Our TCR-T cell therapy is based on the proprietary TAEST (T cell receptor Affinity Enhancing Specific T cell therapy) technology platform that provides high binding affinity of TCRs while reducing their off-target toxicity. We are encouraged by the preclinical and early clinical findings that indicate this TCR-T cell therapy technology could potentially be an effective treatment for multiple tumor types. We look forward to rapidly advancing the therapy into clinical development in the U.S."

On September 23, 2020 LifeArc, an independent medical research charity, reported a £3.0m co-investment in British biotech Avvinity Therapeutics alongside the UK government’s Future Fund (Press release, LifeArc, SEP 23, 2020, View Source [SID1234571031]). Lead investor LifeArc leveraged £1.5m of seed funding provided to Avvinity to secure matched funding of £1.5m from the Future Fund. The investment will help progress studies to validate first-in-class novel therapeutics as potential drug candidates for the treatment of solid tumours including gastric cancer, which is a historically intractable disease with limited treatment options.

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Dr David Holbrook, LifeArc’s Head of Seed Funds, said: "We are delighted to be backing Avvinity Therapeutics and its great science with the added endorsement of Future Fund. Alphamers are an entirely novel way to target disease that represent an exciting new approach to amplifying host immunity, and we look forward to translating this exciting and novel innovation towards benefits for patients with difficult to treat cancers."

Avvinity Therapeutics will focus on the development of novel immunotherapeutic molecules known as Alphamers, which harness a strong immune response to target and kill tumour cells. The proprietary Alphamer technology is a "plug-and-play" approach to enhance the performance of antibodies, or any other targeting moiety, so that multiple arms of the immune system are engaged specifically against cancer cells overexpressing the cell-surface targets of the antibodies. Avvinity’s most advanced project targets Epidermal Growth Factor Receptor (EGFR), which is overexpressed in a significant number of solid tumours including gastric tumours, head and neck, colon and lung cancers. Avvinity anticipates that by engaging the immune system Alphamers will have a far greater impact on treating these diseases than existing EGFR targeting agents. Alphamers also show potential in treating haematological cancers.

Avvinity’s patent portfolio exemplifies the use of antibodies, antibody fragments, RNA/DNA Aptamers and small molecules as targeting domains. When conjugated to these targeting agents, Avvinity’s Linker technology drives immune destruction of tumours or diseased tissue with minimal impact on healthy tissue.

Dr Jon Moore, co-founder and Interim CEO of Avvinity Therapeutics said: "LifeArc has an excellent reputation in backing first-in-class therapeutics, and we look forward to working with its team of scientists to help progress Alphamers as important new immuno-oncology medicines."