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NEW DATA SHOW BLUEPRINT® IDENTIFIES ESTROGEN RECEPTOR POSITIVE BREAST CANCER PATIENTS WITH POOR RESPONSE TO ANTI-ESTROGEN THERAPY WHO MAY BENEFIT FROM NEOADJUVANT CHEMOTHERAPY

By: Cancer-News | April 25, 2019 | 2 view(s)

NEW DATA SHOW BLUEPRINT® IDENTIFIES ESTROGEN RECEPTOR POSITIVE BREAST CANCER PATIENTS WITH POOR RESPONSE TO ANTI-ESTROGEN THERAPY WHO MAY BENEFIT FROM NEOADJUVANT CHEMOTHERAPY   ER+ breast cancer patients reclassified as ER+ basal-type demonstrated significant response to chemotherapy underscoring critical role of advanced diagnostic tools   Results published in Nature Publishing Group’s npj Breast Cancer   IRVINE, CALIF., U.S., and AMSTERDAM, NETHERLANDS –24 April, 2019 – Agendia, Inc., a world leader in precision oncology, today announced the publication of study results for BluePrint®, its 80-gene proprietary molecular subtyping test, in Nature Breast Cancer. It is well known that a significant subset of patients diagnosed with early stage, estrogen receptor (ER) positive (ER+) breast cancer appear to be poorly responsive to standard anti-estrogen therapy and may benefit significantly to the addition of chemotherapy. This latest study suggests that use of BluePrint® can more precisely predict tumor response to treatment and clinical outcome.   Published this week, the study, “Estrogen Receptor variants in ER-positive basal-type breast cancers responding to therapy like ER-negative breast cancers” sought to conduct a molecular analysis and clinical follow up of patients that were reclassified as ER+ Basal-type (n=91) in the Neoadjuvant Breast Registry Symphony Trial (NBRST) (n=1072). The results of the analysis showed: ER+ Basal-type patients revealed missing sections from the messenger RNA (mRNA) for the ER gene, ESR1, rendering the translated ER protein non-functional ER+ Basal-type patients experienced a far higher rate of pCR with neoadjuvant chemotherapy than did ER+ Luminal patients (34 vs. 5%) 3-year outcomes were comparable to triple-negative patients   Pat Whitworth, MD, Director, Nashville Breast Center and study author said, “Traditionally, the medical community has been challenged by a certain subtype of ER+ tumors that respond poorly to standard treatment. These “bad actors” read out as ER+ on standard assays even though their ER does not function well in the cell. This study shows that through diagnostic tools like BluePrint®, we now have the ability to predict and identify how a tumor might respond to treatment that goes beyond traditional molecular classifiers, to seeing the fundamental biology of an individual tumor. This diagnostic step is critical to ensuring patients get the right treatment from the start, and helps drive better long-term outcomes.”   In partnership with the Breast Cancer Research Foundation (BCRF), NBRST took breast cancers categorized by traditional pathology measures (immunohistochemistry or IHC) as ER-positive (ER+), and molecularly reclassified them with BluePrint® into one of three subtypes – Luminal, HER2 or Basal – based on gene expression patterns. Thirteen percent of these ER+ patients were reclassified as having Basal-type breast cancer and were observed to have similar clinical outcomes and response to therapy as “triple-negative” breast cancer which typically indicates chemotherapy as standard treatment. Similar to patients with triple-negative breast cancer, these ER+ Basal-type patients experienced a six-fold increase in pathologic complete response (pCR) to neoadjuvant chemotherapy compared to other ER+ patients, which resulted in significant improvement in long-term outcomes.   “What we now understand is that a diagnosis of breast cancer may encompass up to a dozen distinct diseases, all with differing prognoses and treatments. This data offers additional clarity to the oncology community’s understanding of the complexity of breast cancer, and provides further data regarding this clinically important subset of ER+ cancers. Because routine pathology cannot reliably distinguish these cancers, identifying these ER+ Basal-type cancers through subtyping with BluePrint® provides valuable new information for the optimal management of early breast cancer,” added William Audeh, MD, Medical Oncologist and Agendia Chief Medical Officer.   The study is available open access and can be found on-line at https://rdcu.be/bxGN9.   About MammaPrint®   MammaPrint is an in vitro diagnostic medical device, performed as a testing service in a central laboratory, using the 70-gene expression profile of breast cancer tissue samples to assess a patient’s risk for distant metastasis. The device is FDA-cleared and CE-marked, enabling use in the European Union. MammaPrint is indicated for use by physicians as a prognostic marker only, along with other clinical-pathological factors. It is not intended to determine the outcome of disease, nor to suggest or infer an individual patient’s response to therapy. MammaPrint is the only test of its kind recommended for lymph node-negative and lymph node-positive patients by both the American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN®). The test is also recommended by many other national and international clinical practice guidelines.   About BluePrint®   BluePrint® is an 80-gene complementary gene expression test provided with MammaPrint which allows functional molecular subtyping of a breast cancer sample into three distinct subtypes: Luminal-type, HER2-type and Basal-type, each with marked differences in long-term outcome and response to neoadjuvant chemotherapy.   About Agendia   Agendia is a privately held, leading precision oncology company focused in breast cancer that develops and markets genomic diagnostic products, which help support physicians with their complex treatment decisions. Agendia’s breast cancer tests were developed using an unbiased gene selection by analyzing the complete human genome. The company’s offerings include the MammaPrint Breast Cancer Risk-of-Recurrence Test, and the BluePrint® Molecular Subtyping Test, both on microarray technology, whereas the new MammaPrint BluePrint® Breast Cancer Recurrence and Molecular Subtyping Kit, is on NGS technology. The MammaPrint BluePrint® next-generation sequencing-based kit is a CE-marked device currently available for use in cancer centers in select regions of the world. In addition, Agendia has a pipeline of other genomic products in development. The company collaborates with pharmaceutical companies, leading cancer centers and academic groups to develop companion diagnostic tests in the area of oncology. For more information on Agendia or the MammaPrint and BluePrint® tests, visit www.agendia.com.

Case Report in the Journal of Neurosurgery Highlights Potential of ONC201 in H3 K27M-mutant DIPG

By: Cancer-News | April 09, 2019 | 15 view(s)

Philadelphia, PA (April 9, 2019) –  Oncoceutics announced today the publication of an article entitled "First clinical experience with DRD2/3 antagonist ONC201 in H3 K27M–mutant pediatric diffuse intrinsic pontine glioma: a case report” in the Journal of Neurosurgery (authored by Matthew D. Hall, M.D., MBA). The article summarizes the medical history of a 10-year-old girl with a diffuse intrinsic pontine glioma (DIPG) brain tumor. Following radiation therapy and treatment with ONC201 on a compassionate use basis, she developed near complete resolution of her presenting neurological symptoms for almost one year, enabling her return to school and participation in many normal activities.DIPG is a serious and rare disease with a dismal prognosis and no viable treatment options. It predominantly affects children and young adults, and it is the most common form of brainstem glioma in this age group. DIPG.org, a resource network for the disease, summarizes the disease characteristics as follows: "Currently, outcomes for most patients are poor, with a median survival of less than 1 year from diagnosis. Radiation therapy can shrink tumors, temporarily improving some symptoms and delaying the progression of the disease, but in almost all cases, the tumor continues to grow. So far, clinical trials have not shown that currently available chemotherapy drugs, radiosensitizing drugs (drugs that make tumor cells more likely to be killed by radiation therapy), or biologics (medical products created by biological processes, such as vaccines or gene therapy) benefit patients. Because of their location in the brainstem, DIPGs cannot be removed surgically. New approaches to treating DIPG are urgently needed." ONC201 is an investigational drug developed by Oncoceutics that is being studied in several clinical trials for use against DIPG and other brain tumors. The underlying mechanism of the drug involves the interception of a specific receptor for dopamine, called DRD2. DRD2 is a neurotransmitter that is misused by malignant glioma cells to boost their growth. Tumors that harbor a certain mutation of a highly conserved histone protein, i.e. H3 K27M, are particularly sensitive to ONC201 in spite of the otherwise aggressive growth that this mutation confers. DIPG is one of the tumor types that exhibit a high prevalence of this mutation. The patient described in the article has shown prolonged clinical benefits and is approaching almost two years from diagnosis, although ONC201 was administered only when symptoms progressed after radiation was completed.  This supports further investigation of ONC201 in H3 K27M-mutant gliomas, including DIPG. As a result, Oncoceutics has significantly expanded its pediatric clinical program for ONC201. The company's ongoing pediatric trial for ONC201 in H3 K27M-mutant high-grade gliomas including DIPG (NCT03416530) was extended with additional treatment arms, a pediatric oral solution formulation was introduced, and ONC201 treatment was extended to newly diagnosed DIPG patients with concomitant radiation.The company further implemented an intermediate size Expanded Access Protocol (EAP) to provide access to ONC201 for patients that might benefit from the drug but are not eligible for participation in the ongoing clinical trials. The EAP was made possible by the support of the Food and Drug Administration and their high priority effort to facilitate access to promising medicines for patients with serious or immediately life-threatening diseases or conditions when no comparable or satisfactory alternative therapy options are available (see recent FDA statement). The program is also supported by The Musella Foundation, The Cure Starts Now Foundation, The Michael Mosier Defeat DIPG Foundation, Cancer Commons and xCures. “We are delighted to see a novel concept to treat this horrible disease emerge and show traction in clinical settings,” said Keith Desserich, Chairman of the Board and Co-Founder of The Cure Starts Now. “We have followed the development of ONC201 for some time and are excited about the emerging data in both, children as well as young adults that are expected to become public later in this year. About OncoceuticsOncoceutics, Inc. is a clinical-stage drug discovery and development company with a novel class of compounds, called “imipridones,” that selectively target G protein-coupled receptors for oncology. The first lead compound to emerge from this program is ONC201, an orally active small molecule DRD2 antagonist. The company is supported by grants from NCI, FDA, Musella Foundation, XCures, Cancer Commons, and a series of private and public partnerships. Visit Oncoceutics.com for more information.About The Musella FoundationThe Musella Foundation For Brain Tumor Research & Information, Inc is a 501(C)3 nonprofit public charity dedicated to helping brain tumor patients through emotional and financial support, education, advocacy and raising money for brain tumor research. Visit virtualtrials.com for more information.About The Cure Starts Now FoundationThe Cure Starts Now Foundation is a 501(c)3 nonprofit organization with international chapters in nearly 40 locations around the world.  It is has funded universal cancer cure strategies starting with cancers such as DIPG and organizes the biennial International DIPG Symposium showcasing innovative research methods. You can learn more at www.thecurestartsnow.org.About Michael Mosier Defeat DIPG FoundationMichael Mosier Defeat DIPG Foundation is committed to finding a cure for brainstem tumors known as diffuse intrinsic pontine gliomas (DIPG).  Nearly every day one child in the United States is diagnosed with DIPG and another child dies from it. The Foundation seeks to make a difference and defeat DIPG both by raising awareness of DIPG and by providing funding for research into effective treatments for DIPG. Visit defeatdipg.org for more information.About Cancer CommonsCancer Commons is a nonprofit collaborative of patients, physicians, and scientists, dedicated to improving patient outcomes by tightly coupling clinical research and care. We arm patients and their physicians with the knowledge they need to achieve the best possible outcomes, help them access the relevant treatments and trials, and track their results to continuously learn. Vistitcancercommons.org for more information.About xCuresxCures is developing an AI-based methodology and platform to run ‘Virtual Trials’, which continuously learn from the clinical experiences of all patients, on all treatments, all the time. Each patient’s treatment regimen is adaptively planned by a ‘Virtual Tumor Board’ to optimize their individual outcome, and these plans are coordinated across the whole patient population to maximize collective learning. Visit xcures.com for more information.

Fusion Pharmaceuticals Raises $105 Million in Oversubscribed Series B Financing

By: Cancer-News | April 02, 2019 | 15 view(s)

Fusion Pharmaceuticals, a clinical-stage biopharmaceutical company developing targeted alpha-particle radiotherapeutics for treating cancer, today announced the completion of a $105 million Series B financing led by Varian and new investor OrbiMed. Additional investors participating in the round are Perceptive Advisors, Pivotal bioVenture Partners, and Rock Springs Capital, along with the existing group of leading international investors, that include HealthCap, Adams Street Partners, Johnson & Johnson Innovation – JJDC, Inc. (JJDC), TPG Biotech, Seroba Life Sciences, Genesys Capital, and FACIT. In conjunction with the new financing, Deepak Khuntia, Senior Vice President (SVP) and Chief Medical Officer (CMO) at Varian, Chau Q. Khuong, Partner at OrbiMed, and Heather Preston, Managing Director at Pivotal bioVenture Partners, will join Fusion’s Board of Directors. The financing will be used to advance and broaden the scope of Fusion’s ongoing clinical program in targeted alpha therapeutics, and accelerate a pipeline of new radiopharmaceuticals and combination therapy strategies. The company’s lead product candidate [225Ac]-FPI-1434, combines the precision targeting of an antibody with the potency of alpha-particle emitting medical isotopes to specifically attack and eradicate cancer cells across multiple tumor types. “Fusion is delighted to welcome this group of preeminent healthcare investors to our existing and highly distinguished series A investors. We have made tremendous progress in the last two years, and this financing reflects strong support for our platform, people and pipeline,” said John Valliant, Ph.D., Fusion’s Chief Executive Officer. “The investment positions us to implement our clinical and partnering strategies around [225Ac]-FPI-1434, expand our team and fully exploit the unique advantages of our linker technology.” Fusion’s proprietary Fast-Clear™ Linker Technology Platform promotes the rapid excretion of medical isotopes that are not specifically bound to cancer cells. The Fast-Clear™ Linker (the “connector” between a molecule and a medical isotope) is engineered to clear medical isotopes at a faster rate, compared to traditional technologies, with the aim of expanding the therapeutic window. Given the power and versatility of the Fast-Clear™ Platform, Fusion is applying this technology to different classes of molecules. “We were attracted to Fusion by the excellent science, broad patient applicability, and great promise for its targeted alpha therapeutics, which have the potential to eradicate even the most resistant types of cancer,” said Deepak Khuntia, SVP, CMO, at Varian. “The investment will enable Fusion to advance a pipeline of novel therapeutics that can deliver effective and personalized radiation therapies to cancer patients.” “OrbiMed is excited to co-lead the financing of Fusion, which is the industry leader in targeted alpha therapeutics. Fusion has a unique platform and an exciting lead program in early stage clinical trials that holds promise for improving the lives of cancer patients,” said Chau Q. Khuong, Partner at OrbiMed. “There is significant re-emerging commercial interest in radiopharmaceuticals given recent advances in the field and Fusion is at the forefront. We are excited to work with the Fusion team to meet the aggressive goals of the company.” If you’d like to interview John Valliant, CEO at Fusion Pharma, contact me at kimberly.ha@kkhadvisors.com or 917-291-5744. About Fusion Pharmaceuticals, Inc. Fusion Pharmaceuticals is a biopharmaceutical company located in Hamilton, Ontario, Canada and Boston, MA, focused on targeted alpha therapy. Fusion exploits its unique expertise in linking medical isotopes to targeting molecules to create novel therapeutics. In addition to its lead program, [225Ac]-FPI-1434, Fusion is expanding its pipeline of products through a proprietary protein discovery platform, in-licensing targeting molecules, and forming new strategic partnerships. For more information, please visit www.fusionpharma.com or contact info@fusionpharma.com. Contacts InvestorsFusion PharmaceuticalsLynn Wickinfo@fusionpharma.com MediaKKH AdvisorsKimberly HaKimberly.ha@kkhadvisors.com917-291-5744

ORIC Pharmaceuticals Presents Evidence of Glucocorticoid Receptor-Mediated Cancer Treatment Resistance at the AACR Annual Meeting

By: Cancer-News | April 02, 2019 | 24 view(s)

SOUTH SAN FRANCISCO, Calif., April 2, 2019 /PRNewswire/ -- ORIC Pharmaceuticals, a privately held, clinical-stage oncology company focused on the discovery and development of novel therapies against treatment-resistant cancers, today presented new preclinical data on its lead program ORIC-101, a selective and potent glucocorticoid receptor (GR) antagonist, at the American Association of Cancer Research (AACR) Annual Meeting in Atlanta, GA. The data were presented in a poster "ORIC-101 Reverses a GR-Driven EMT-like Phenotype and Sensitizes TNBC Cells to Chemotherapy (Abstract #3822)" during the Experimental and Molecular Therapeutics poster session. The Company's research findings provide insight into the molecular basis of GR-mediated resistance to chemotherapy in triple-negative breast cancer (TNBC). GR was found to activate multiple biological pathways involved in therapy resistance, including epithelial-mesenchymal transition (EMT), stemness and anti-apoptosis. Using a murine TNBC xenograft model, oral administration of ORIC-101 reversed these effects and restored sensitivity to chemotherapy. The Company plans to initiate multiple Phase 1b studies of ORIC-101 in combination with other anti-cancer agents in patients with advanced solid tumors, the first of which is expected to initiate in the second quarter of 2019. About ORIC Pharmaceuticals ORIC Pharmaceuticals is a privately held, clinical-stage oncology company focused on making cancer treatments more effective by addressing mechanisms of resistance. ORIC's lead asset, ORIC-101, is a potent and selective small molecule antagonist of the glucocorticoid receptor. ORIC's pipeline also includes an orally-available small molecule inhibitor of CD73, as well as other undisclosed programs targeting mechanisms of oncology therapy resistance. ORIC's scientific founders are Charles Sawyers, MD, and Scott Lowe, PhD, who have strong records of discovering novel targets in cancer that have led to innovative treatments. The company has assembled strong leadership and scientific teams and a board with extensive experience in drug development and financing. ORIC is funded by leading biotechnology investors, including The Column Group, Topspin Partners, OrbiMed, EcoR1, Fidelity, Foresite and others. ORIC is headquartered in South San Francisco, California. For more information, please contact: Krys Corbett 650-388-5622 212084@email4pr.com http://oricpharma.com/  SOURCE Oric Pharmaceuticals

Cybrexa Therapeutics Unveils Rucaparib as FDA- and EMA-Approved PARP Inhibitor in Lead Candidate CBX-11, Which Demonstrates Synergistic Efficacy with Chemotherapy Without Compounded Toxicity

By: Cancer-News | April 02, 2019 | 6 view(s)

April 02, 2019 08:00 ET | Source: Cybrexa Therapeutics     Tumor-selective CBX-11 allows full dose co-administration with chemotherapy, enabling synergistic efficacy in HRD negative tumors   Poster presentation today during AACR Annual Meeting 2019 NEW HAVEN, Conn., April 02, 2019 (GLOBE NEWSWIRE) -- Cybrexa Therapeutics, a biotechnology company developing a new class of cancer therapeutics through its alphalex™ tumor targeting platform, today announced that the FDA- and EMA-approved poly ADP-ribose polymerase (PARP) inhibitor rucaparib (marketed as Rubraca®) is conjugated in lead candidate CBX-11 (alphalex™-rucaparib). The first set of preclinical data supporting CBX-11 demonstrate that Cybrexa’s proprietary alphalex™ platform can enable full dose administration with DNA damaging chemotherapy, creating synergistic efficacy in destroying solid tumors independent of homologous recombination deficiency (HRD) status. In particular, CBX-11 selectively delivers rucaparib to tumor tissue, avoiding the bone marrow toxicity that has prevented optimal dosing of DNA damaging chemotherapy in combination with PARP inhibitors.   These data were exhibited today in a poster presentation by Vishwas Paralkar, PhD, Chief Scientific Officer of Cybrexa, during the American Association for Cancer Research (AACR) Annual Meeting 2019. “These mark the first results demonstrating that combination of the potent PARP inhibitor rucaparib and chemotherapy is able to effectively kill cancer cells independent of HRD status and without the extreme bone marrow toxicity historically observed in this combination, which previously resulted in significant dose reduction and therefore efficacy reduction,” said Vishwas Paralkar, PhD, Chief Scientific Officer of Cybrexa. “The synergistic efficacy allowing full dose administration of both rucaparib and chemotherapy is a direct result of our alphalex™ technology platform that selectively targets tumor cells to overcome this barrier for combination therapies.” In the study, tumor targeting of rucaparib was achieved using the alphalex™ platform, which allows small molecule anti-cancer agents to penetrate cell membranes only at the low pH associated with the tumor microenvironment. These data demonstrate that the alphalex™ conjugate inserts only across cancer cell membranes to deliver its cargo directly into the cancer cell.  The safety and efficacy of the approach was confirmed in vivo using CBX-11, which was safely administered with cytotoxic chemotherapies to selectively kill both HRD-positive and HRD-negative tumors with significant sparing of bone marrow.  Per Hellsund, President and CEO of Cybrexa, commented, “These preclinical results highlight an entirely new approach to applying PARP inhibitors against solid tumors independent of HRD status and directly support our Phase 1 clinical trial evaluating CBX-11 in combination with chemotherapy, which is planned to start in the first quarter of 2020. Furthermore, our alphalex™ platform approach can be applied to a diverse range of DNA damage repair inhibitors to enable combinations with chemotherapy and chemo-radiation in a tissue-agnostic manner and we look forward to discussing these applications.” About the alphalex™ Technology Platform The Cybrexa alphalex™ technology platform enables the delivery of small molecules across the cell membrane under low pH conditions, which is a universal feature of cancer cells. As a result, alphalex™ technology – which consists of a novel peptide, linker and small molecule anti-cancer agent – allows for antigen-independent, intracellular delivery of small molecule anti-cancer agents directly into the tumor cell. View a video of the mechanism of action of the technology at http://www.cybrexa.com/our-technology/. About CybrexaCybrexa is a privately-held biotechnology company dedicated to developing an entirely new class of cancer therapies using its alphalex™ platform to deliver anti-cancer agents directly into tumor cells. The Company’s lead candidate, CBX-11, an alphalex™-rucaparib combination, is in preclinical development with advancing plans to initiate clinical development by 1Q 2020. Cybrexa was founded by physician-scientists, and has an experienced management team that has built numerous successful life sciences companies and raised hundreds of millions of dollars in venture capital. For more information about Cybrexa, please visit www.cybrexa.com. Contacts The Ruth Group Investor RelationsLee Rothlroth@theruthgroup.com Media RelationsKirsten Thomas kthomas@theruthgroup.com  

Kymera Therapeutics to Present New Preclinical Data for its First-In-Class Oral IRAK4 Degrader in MYD88-Mutant Lymphoma

By: Cancer-News | April 02, 2019 | 16 view(s)

Kymera Therapeutics to Present New Preclinical Data for its First-In-Class Oral IRAK4 Degrader in MYD88-Mutant Lymphoma at Late-Breaking Session of the American Association for Cancer Research Annual Meeting Cambridge, Mass. (March 29, 2019) - Kymera Therapeutics Inc., a biotechnology company pioneeringtargeted protein degradation to create breakthrough medicines for patients, will present new preclinical data for its first-in-class oral IRAK4 protein degrader, KYM-001, in MYD88-mutant lymphoma. Data will be presented in a late-breaking research session at the American Association for Cancer ResearchAnnual Meeting on April 3 from 8 a.m. – 12 p.m. (Poster #18, Session: Experimental and Molecular Therapeutics 2). The study showed that KYM-001 led to highly selective degradation of IRAK4 and tumor regression upon oral dosing, both alone and in combination with BTK inhibition. “IRAK4 degraders offer an entirely new therapeutic approach to treat MYD88-driven B cell lymphomas, which are often aggressive and have a poor prognosis,” said Nello Mainolfi, PhD, co-founder and Chief Scientific Officer, Kymera Therapeutics and study co-author. “IRAK4 kinase and scaffolding functions are critical to MYD88-driven Myddosome signaling. Unlike conventional kinase inhibitors, our novel degrader KYM-001 removes both the kinase and scaffolding function of IRAK4 to effectively block Myddosome signaling, resulting in tumor growth arrest and subsequent regression. The team has been able to very quickly identify orally active degraders that offer ease and flexibility of dosing. ” MYD88-activating mutations occur in 30-40% of patients with activated B cell-like (ABC) diffuse large B cell lymphoma (DLBCL). This study assessed the antitumor activity of Kymera’s orally active small molecule degraders in human ABC DLCBL cell lines in vitro and in tumor xenograft models in vivo, aloneand in combination with the BTK inhibitor ibrutinib. Study Highlights “KYM-001, a first-in-class oral IRAK4 protein degrader, induces tumor regression in xenograft models of MYD88-mutant ABC DLBCL alone and in combination with BTK inhibition”: • KYM-001 induced potent and selective E3 ligase-dependent degradation of IRAK4 in multiple cellular models, resulting in 90% degradation at concentrations less than 100 nM.• KYM-001 induced comparable levels of IRAK4 degradation in both MYD88 mutant and MYD88 WT human ABC DLBCL cell lines.• KYM-001 impacted viability in MYD88 mutant, but not WT, ABC DLBCL cell lines, inducing apoptotic effects within 72 hours.• Oral dosing of KYM-001 showed dose-dependent antitumor activity against the MYD88 L265P mutant ABC DLBCL cell line OCI-LY10, with >80% degradation of IRAK4 correlating with tumor regression in xenograft-bearing mice.• KYM-001 was synergistic with the BTK inhibitor ibrutinib in vitro in ABC DLBCL cell lines bearing both MYD88 L265P and CD79 mutations. In vivo, this combined activity resulted in tumor regression at concentrations that were sub-optimal in single-agent studies, supporting further exploration of combinations that target oncogenic NFκB signaling. About Kymera TherapeuticsKymera Therapeutics is a biotechnology company pioneering a transformative new approach to treating previously untreatable diseases. The company is advancing the field of targeted protein degradation, accessing the body’s innate protein recycling machinery to degrade dysregulated, disease-causing proteins. Powered by PegasusTM, a game-changing integrated degradation platform, Kymera is accelerating drug discovery with an unmatched ability to target and degrade the most intractable of proteins, and advance new treatment options for patients. For more information visit, www.kymeratx.com. About PegasusTMPegasusTM is Kymera Therapeutics’ proprietary protein degradation platform, created by its team of experienced drug hunters to improve the effectiveness of targeted protein degradation and generate a pipeline of novel therapeutics for previously undruggable diseases. The platform consists of informatics driven target identification, novel E3 ligases, proprietary ternary complex predictive modeling capabilities and degradation tools. Media Contact:Lissette SteeleVerge Scientific Communicationslsteele@vergescientific.com202.930.4762

Oncoceutics Expands Patent Family to Include Composition of Matter for ONC206 in Europe

By: Cancer-News | March 29, 2019 | 34 view(s)

Oncoceutics Expands Patent Family to Include Composition of Matter for ONC206 in Europe  Philadelphia, PA (March 4, 2019) – Oncoceutics, Inc. announced that the European Patent Office (EPO) has issued EP 3,068,401 entitled “7-benzyl-4-(2-methylbenzyl)-2,4,6,7,8,9-hexahydroimidazo[1,2-a]pyrido[3,4-e]pyrimidin-5(1H)-one, Salts Thereof and Methods of Use” with an expiration date of September 12, 2034.  This patent covers the composition of matter for ONC206, its di-salt formulation, and its use in the treatment of cancer.  ONC206, a member of the imipridone family of anti-cancer small molecules, has demonstrated anti-cancer activity and safety in preclinical models and is planned to enter the clinic in 2019. These patents pave the path for the next generation of imipridones to enter the clinic and eventually the market. This patent is the second issued on ONC206, following the composition of matter patent issued by the US Patent Office on June 28th, 2016, and greatly expands the company’s global IP protection. “We are pleased that the European Patent Office has recognized ONC206 as an exciting novel invention and granted the appropriate patent protections,” said Martin Stogniew, Ph.D., Chief Development Officer of Oncoceutics. “The company’s current patent portfolio provides Oncoceutics with the opportunity to continue imipridone development and eventually provide ONC206 to European patients.”About Oncoceutics Oncoceutics, Inc. is a clinical-stage drug discovery and development company with a novel class of compounds, i.e. the “imipridones,” that selectively target G protein-coupled receptors for oncology. The first lead compound to emerge from this program is ONC201, an orally active small molecule DRD2 antagonist. The company is supported by grants from NCI, FDA, Musella Foundation, XCures, Cancer Commons, and a series of private and public partnerships. Visit Oncoceutics for more information.

Bavencio and Talzenna’s trial discontinuation points to stark future in ovarian cancer, says GlobalData

By: Cancer-News | March 21, 2019 | 26 view(s)

Following the news on March 19, 2019 that Merck KGaA and Pfizer have discontinued the ongoing Phase III JAVELIN Ovarian PARP 100 study for previously untreated advanced ovarian cancer, Paul Jeng, Pharma Analyst at GlobalData, a leading data and analytics company, offers his view on Talzenna (talazoparib) in ovarian cancer: “The combination of Bavencio and Talzenna has seen a steady erosion of its prospects in ovarian cancer since the JAVELIN Ovarian PARP 100 study was initiated less than a year ago. Merck & Co. and AstraZeneca’s Lynparza has widened its lead over other PARP inhibitors in ovarian cancer with an approval as first-line maintenance therapy, while Pfizer’s Talzenna remains the only drug in its class that has yet to authorized for this indication. “Merck KGaA and Pfizer have the option to initiate another Phase III Talzenna combination study using Lynparza as a new comparator. However, it may be more advantageous for the developers to cut their losses and reorient to other indications. Bavencio has already faced clinical failures in advanced ovarian cancer, missing the mark in two late-stage trials in late 2018. “Talzenna is currently approved for treatment of patients with BRCA-mutated, HER2-negative breast cancer, and experts believe it has the potential to be a best-in-class breast cancer drug on the basis of its potent, single-pill oral regimen. Pfizer’s best chances for success will be to continue development of Talzenna in patients with breast cancer or gain a foothold in metastatic castration-resistant prostate cancer, where it is currently being assessed in combination with enzalutamide.” ENDSFor more information To gain access to our latest press releases: GlobalData Media CentreAnalysts available for comment. Please contact the GlobalData Press Office: EMEA & Americas: +44 (0)207 832 4399Asia-Pacific: +91 40 6616 6809 GlobalData.com | LinkedIn | Twitter- Information based on GlobalData’s report: PARP Inhibitors in Oncology   - Include any relevant further information here, such as definitions, clarifications or research scopes   - Comments provided by Paul Jeng, PhD, Healthcare Analyst at GlobalData About GlobalData4,000 of the world’s largest companies, including over 70% of FTSE 100 and 60% of Fortune 100 companies, make more timely and better business decisions thanks to GlobalData’s unique data, expert analysis and innovative solutions, all in one platform. GlobalData’s mission is to help our clients decode the future to be more successful and innovative across a range of industries, including the healthcare, consumer, retail, financial, technology and professional services sectors.

Brain Cancer Study of Viral and Checkpoint Immunotherapy Initiates Accrual

By: Cancer-News | March 21, 2019 | 19 view(s)

AUBURNDALE, Mass., March 21, 2019 /PRNewswire/ -- Candel Therapeutics (a.k.a. Advantagene, Inc.) announced today the treatment of the first high grade glioma patients in a study of its Gene Mediated Cytotoxic Immunotherapy (GMCI™; aglatimagene besadenovec plus prodrug) in combination with the checkpoint inhibitor nivolumab and standard of care (SOC) surgery, radiation and temozolomide.  Extensive clinical and preclinical data suggests that GMCI and this combination can significantly improve clinical outcomes. This newest study, BrTK04, is being conducted in collaboration with the Adult Brain Tumor Consortium, composed of eleven of the top clinical institutions in the country, and Bristol-Myers Squibb, manufacturer of nivolumab (Opdivo®).  The study chair is Dr. Patrick Wen, Director, Center for Neuro-Oncology at Dana Farber Cancer Center, Harvard Medical School.  The primary clinical end-point of BrTK04 is to determine the safety of GMCI, nivolumab, SOC surgery and chemoradiation.   In BrTK02, a previous phase 2 study of GMCI with SOC, the treatment was well tolerated with an indication of survival benefit as GBM patients with successful surgical outcomes had a median overall survival of 25.1 months compared to 16.3 months for the control group.  Data from another recently concluded study at Boston Children's Hospital, under the direction of Dr. Mark Kieran, showed that GMCI can also be safely combined with SOC in pediatric patients.  "The data generated with GMCI in the upfront high-grade glioma setting is some of the more compelling clinical data in the field in the last few years.  The scientific rationale for the combination of GMCI and nivolumab is sound and is supported by pre-clinical data.  When one further considers GMCI's compelling clinical data in various other indications, there is a strong rationale for moving forward with this combination study," stated Dr. Wen. Additional ongoing clinical studies with GMCI include a Phase 3 in localized prostate cancer and Phase 1/2 studies in prostate, lung and pancreatic cancers. "The application of our GMCI platform in combination with nivolumab further expands Candel's glioma franchise beyond single use application and is an important milestone for the company," stated Dr. Estuardo Aguilar-Cordova, Chairman and CEO of Candel Therapeutics. "We are excited for the opportunity to work on a potential new treatment for patients with this devasting disease and we are grateful to our collaborators, the patients participating in this study, and their families." For more information about this study, please visit www.clinicaltrials.gov (NCT03576612). About Candel Therapeutics Advantagene, Inc. d.b.a. Candel Therapeutics is developing proprietary immuno-oncology platforms, including its Gene Mediated Cytotoxic Immunotherapy (GMCI™) and the oncolytic rQNestin34.5 platforms for the treatment of solid tumors. GMCI™, an "off-the-shelf" adenovirus-based product, generates a robust personalized immune response against a patient's own cancer.  GMCI™ has been evaluated in 16 clinical trials with over 1,200 patient doses and 650 patients, including an ongoing registration study for localized prostate cancer under a Special Protocol Assessment agreement with the U.S. FDA. ContactMedia & Investor RelationsAdvantagene, Inc.440 Lexington AvenueAuburndale, MA 02466(617) 916-5445 211367@email4pr.com

Kanazawa University research: Origin of resistance to lung-cancer drug discovered

By: Cancer-News | March 21, 2019 | 23 view(s)

(Kanazawa, 21 March 2019) Researchers at Kanazawa University report in Nature Communications what causes some lung-cancer patients to have an intrinsic resistance to the drug osimertinib: AXL, a protein belonging to the class of receptor tyrosine kinases.  The combined application of osimertinib and an AXL inhibitor is shown to limit intrinsic resistance to the drug. For treating cancer, drugs based on molecules known as tyrosine kinase inhibitors are sometimes used.  One such tyrosine kinase inhibitor, called osimertinib, has been used to treat EGFR-mutated lung cancer with a certain degree of efficacy.  (EGFR refers to “epidermal growth factor receptor”, a protein that plays an important role in signaling from the extracellular environment to a cell.) However, in some patients, intrinsic resistance and inadequate response to osimertinib has been seen to occur.  Seiji Yano from Kanazawa University and colleagues have now discovered that a particular protein known as AXL causes the resistance to osimertinib and the emergence of osimertinib-tolerant cells. The researchers first showed that in vitro, osimertinib activated AXL in EGFR-mutated lung cancer cells.  Then, they demonstrated an inverse correlation between AXL and susceptibility to tyrosine kinase inhibitors; AXL expression correlated with a poor response to treatment with osimertinib and with early tumor relapse. Yano and colleagues checked whether drug-tolerant cells (cells with significantly reduced sensitivity to drugs) exhibited higher levels of AXL.  Indeed, tolerant cells were found to display a higher expression of AXL compared to parental cells.  Application of an AXL inhibitor called NPS1034 led to a decrease in survival of the drug-tolerant cells. The scientists then investigated the effect of the AXL inhibitor combined with osimertinib in a mouse model.  Treatment with only NPS1034 had no effect on the tumors.  Treament with only osimertinib initially led to tumor regression, but tumor regrowth was observed within 7 weeks. Simultaneous treatment with NSP1034 and osimertinib led to tumor regression within a week, and the size of the tumors being stable for 10 weeks.  No adverse effects, such as weight loss, were observed during treatment. The findings of Yano and colleagues provide important insights into the molecular mechanisms causing the tolerance to osimertinib in EGFR-mutated lung cancer cells and, particularly, into the role of AXL — and the effect of inhibiting its activity.  Quoting the scientists: “these results suggest that treatment during the initial phase with a combination of osimertinib and an AXL inhibitor may prevent the development of intrinsic resistance to osimertinib and the emergence of drug-tolerant cells in EGFT-mutated lung cancer overexpressing AXL.” Background Tyrosine kinase inhibitors A tyrosine kinase inhibitor is a drug inhibiting (that is, preventing or reducing the activity of) a specific tyrosine kinase. A tyrosine kinase is a protein (enzyme) involved in the activation of other proteins by signaling cascades. The activation happens by the addition of a phosphate group to the protein (phosphorylation); it is this step that a tyrosine kinase inhibitor inhibits.  Tyrosine kinase inhibitors are used as anticancer drugs.  One such drug is osimertinib, used to treat EGFR-mutated lung cancer. AXL AXL is a receptor tyrosine kinase — a tyrosine kinase consisting of an extracellular part, a transmembrane part (‘sitting’ within a cell membrane) and an intracellular part.  AXL regulates various important cellular processes, including proliferation, survival and motility.  In recent years, it has become clear that AXL is a key facilitator of drug tolerance by cancer cells.  Seiji Yano from Kanazawa University and colleagues have found that this is also the case for EGFR-mutated lung cancer: a high expression of AXL correlates with resistance to osimertinib, a tyrosine kinase inhibitor, and the emergence of osimertinib-tolerant cells. Reference Hirokazu Taniguchi, Tadaaki Yamada, Rong Wang, Keiko Tanimura, Yuta Adachi, Akihiro Nishiyama, Azusa Tanimoto, Shinji Takeuchi, Luiz H. Araujo, Mariana Boroni, Akihiro Yoshimura, Shinsuke Shiotsu, Isao Matsumoto, Satoshi Watanabe, Toshiaki Kikuchi, Satoru Miura, Hiroshi Tanaka, Takeshi Kitazaki, Hiroyuki Yamaguchi, Hiroshi Mukae, Junji Uchino, Hisanori Uehara, Koichi Takayama, and Seiji Yano. AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells, Nature Communications 10, 259 (January 16, 2019) DOI: 10.1038/s41467-018-08074-0 URL: https://doi.org/10.1038/s41467-018-08074-0 Treatment with osimertinib alone, AXL inhibitor NPS1034 alone, and osimertinib and NPS1034 combined.  Further information Hiroe Yoneda Vice Director of Public Affairs WPI Nano Life Science Institute (WPI-NanoLSI) Kanazawa University Kakuma-machi, Kanazawa 920-1192, Japan Email: nanolsi-office@adm.kanazawa-u.ac.jp Tel: +81 (76) 234-4550 About Nano Life Science Institute (WPI-NanoLSI) https://nanolsi.kanazawa-u.ac.jp/en/ Nano Life Science Institute (NanoLSI), Kanazawa University is a research center established in 2017 as part of the World Premier International Research Center Initiative of the Ministry of Education, Culture, Sports, Science and Technology. The objective of this initiative is to form world-tier research centers. NanoLSI combines the foremost knowledge of bio-scanning probe microscopy to establish ‘nano-endoscopic techniques’ to directly image, analyze, and manipulate biomolecules for insights into mechanisms governing life phenomena such as diseases.   About Kanazawa University http://www.kanazawa-u.ac.jp/e/   As the leading comprehensive university on the Sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since it was founded in 1949. The University has three colleges and 17 schools offering courses in subjects that include medicine, computer engineering, and humanities.   The University is located on the coast of the Sea of Japan in Kanazawa – a city rich in history and culture. The city of Kanazawa has a highly respected intellectual profile since the time of the fiefdom (1598-1867). Kanazawa University is divided into two main campuses: Kakuma and Takaramachi for its approximately 10,200 students including 600 from overseas.