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investigational cancer drugs

  • sam patrick posted an article
    MUSC teams up for new clinical trial see more

    A combination of up to five drugs normally used to treat conditions ranging from HIV to Type 2 diabetes could destroy cancer cells yet be less toxic than a chemotherapy drug used for recurring ovarian cancer.

    After promising preclinical results, researchers at MUSC Hollings Cancer Center are now launching a phase 1 clinical trial to establish safe levels of various combinations of the drugs in patients with advanced solid tumors.

    Hollings researchers Joe Delaney, Ph.D., and Michael Lilly, M.D., are collaborating on the Combination of Autophagy Selective Therapeutics (COAST) trial, which already has enrolled its first patient.

    Autophagy is a cellular recycling process that occurs in all human cells, Delaney explained. Although the drugs in question – hydroxychloroquine, nelfinavir, metformin, dasatinib and sirolimus – were developed to treat, respectively, malaria, HIV, Type 2 diabetes and chronic myeloid leukemia and to prevent organ rejection in kidney transplant patients, what they all have in common is that they affect this cellular recycling process.

    “All the drugs on this trial affect autophagy in one way or another. Even though they were originally designed for these other diseases, we’ve learned from the decades of studying them that they actually impact this process of autophagy, which all human cells have,” Delaney said. “That’s true of our normal cells. And that’s also true of cancer cells. It’s just that the cancer cells cannot perform that recycling nearly as well as our normal cells can. And so, to us, that was our therapeutic window.”

     

      This slide illustrates Delaney's concept for utilizing the effect on autophagy by drugs already approved to treat other conditions.

    The National Cancer Institute encourages researchers to look into repurposing approved drugs, Lilly said. Already approved drugs have established safety records, whereas many potential new cancer drugs fail in early trials because they’re too toxic, Delaney said.

    Repurposed drugs, on the other hand, have already been used by potentially millions of patients. “It really puts you many years ahead in the developmental pathway,” Lilly said.

    In a paper published in June in Frontiers in Toxicology, Delaney showed that 14 doses of these five drugs were less toxic than Doxil, a chemotherapy drug used to treat ovarian cancer, multiple myeloma and AIDS-related Kaposi’s sarcoma. Now, the phase 1 trial will show safety levels in humans.

    “We’re really enthusiastic that this might be that opportunity to try multiple drugs,” Delaney said. “Since we started from that side effect profile to begin with, hopefully we have something that has much less toxicity. And of course, we’ll be finding out in the coming months if that’s actually true or not.”

    The drugs will be tested in a series of various combinations. Previous studies of drugs that target autophagy have mostly focused on adding one autophagy drug to a chemotherapy regimen or immunotherapy regimen, Lilly said. By combining multiple autophagy-targeting drugs, this trial hopes to identify a combination that prevents the cancer cells from evolving resistance to the drugs.

    “We have very good evidence that it’s a synthetic lethal combination for cancer cells, which is what everybody in cancer wants, but it’s just never been tried in people before. And so, we’re really excited to see this combination in a cancer setting,” Delaney said.

    Synthetic lethality refers to when mutations in two genes together result in cell death, but a mutation in only one of the partner genes does not.

    This human trial is a result of work in the lab that was funded by both the National Cancer Institute and donor Matt Prisby, who established a fund at Hollings for research into women’s cancers after his wife died of cervical cancer in 2014.

    “This trial couldn’t have happened without Matt Prisby and everyone who donated to his fundraisers,” Delaney said. “Dedicated funding programs like the one he established at Hollings are critical for investigators to get the early results that will convince large funding entities to invest in continued research along these lines.”

    Delaney also hopes that a combination of these drugs will prove effective for a broad swath of patients. Operating within the concept of precision oncology, researchers have been looking for ways to target mutations in patients whose tumors have been sequenced. Yet fewer than 10% of patients are eligible for precision therapy, Delaney said, referring to an area of medicine that uses information about a patient’s own genes to develop specific treatments that, in terms of cancer, target that individual’s tumor.

    This trial targets aneuploid gene changes – an extra or missing chromosome – which is common in cancer cells, ranging from 20% to 95% in advanced solid tumor patients.

    “If it works, many, many more patients could be eligible than for other targeted therapies,” Delaney said.

    The phase 1 trial is accepting patients with an advanced solid tumor of any type. Once the trial moves to phase 2, the researchers will focus on specific cancer types. Lilly said early indications are that these drugs might be particularly effective against ovarian and prostate cancers.

    Lilly, who treats patients with prostate cancer and runs his own lab focused on advanced prostate cancer, said that this collaboration with Delaney would only be possible at an academic cancer center like Hollings, where researchers work alongside the doctors who provide care to patients. Delaney and Lilly, each with their own areas of expertise, can share ideas, and patients have access to early trials like this.

    “Sherlock Holmes once referred to bits of data as having cumulative force when you have three or four different things, each of which points in the same direction,” Lilly said. “And that’s the power of collaborative research at Hollings.”

    The first video shows high-grade serous ovarian cancer cells grown in the lab and labelled with fluorescent proteins to measure how the molecular recycling process of autophagy is working in live cells.

    When the movie starts, the cells had just begun a treatment of a version of COAST therapy. As the movie progresses, the cells try to turn on autophagy in response to these COAST drugs - they fluoresce brighter.

    However, properly recycling autophagy would fluoresce red, whereas these cells fluoresce yellow, indicating their recycling system is jammed and cannot complete its function. As a result, these cancer cells accumulate too much cellular debris and pop, as seen by a sudden darkening of a single cell.

    The second video shows high-grade serous ovarian cancer cells grown in the lab and labelled with fluorescent proteins that label the nucleus of each cell in both green and blue.

    In the center top of the start of the movie, a cancer cell physically latches onto another cancer cell. Astonishingly, the cell is able to absorb the blue nucleus of this attached cell, thereby adding a whole extra genome to its own genome in the process. This is a live observation of one reason why cancer cells can evolve to resist chemotherapy: once they acquire that second genome, it is easier to shuffle genes around in a way that optimizes cancer cell growth.

  • sam patrick posted an article
    Will identify and advance therapies for genetic diseases and cancers see more

    BridgeBio Pharma, Inc. (Nasdaq: BBIO), a commercial-stage biopharmaceutical company founded to discover, create, test and deliver meaningful medicines for patients with genetic diseases and cancers with clear genetic drivers, today announced three new academic collaborations with MUSC Foundation for Research Development, Stanford University and the University of Pittsburgh (Pitt) to translate cutting-edge discoveries into potential therapies for patients with genetic diseases and genetically driven cancers.

    "The chance to partner with exceptional researchers at the Medical University of South Carolina, Stanford University and University of Pittsburgh is a privilege, and we believe will help us advance our mission to discover, create, test and deliver life-changing medicines for patients in need as rapidly as possible," said BridgeBio founder and CEO Neil Kumar, Ph.D.

    To date, BridgeBio has worked with 23 leading institutions throughout the country that are focused on providing treatment options to patients as quickly and safely as possible. For a list of some of the institutions BridgeBio is partnered with, please visit Our Partners page.

    MUSC Foundation for Research Development
    MUSC Foundation for Research Development provides technology transfer services to Medical University of South Carolina (MUSC), which is a patient-centric research institution with several hospitals in South Carolina and is considered the state's top healthcare provider. MUSC's innovative and high-quality research will allow for early identification of research programs with a strong potential to be beneficial for patients. Through this partnership, BridgeBio may sponsor research programs and support the development of identified programs toward potential clinical investigation through its licensing and affiliate development model.

    "Like BridgeBio, we have a patients first mentality, so partnering together on early research will be an excellent opportunity to advance our innovation in the hope of generating new therapies for patients," said Scott Davis, Ph.D., senior director of innovation support and commercialization of MUSC Foundation for Research Development.

    About BridgeBio Pharma, Inc.
    BridgeBio Pharma (BridgeBio) is a biopharmaceutical company founded to discover, create, test and deliver transformative medicines to treat patients who suffer from genetic diseases and cancers with clear genetic drivers. BridgeBio's pipeline of over 30 development programs ranges from early science to advanced clinical trials and its commercial organization is focused on delivering the company's first two approved therapies. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com.

  • sam patrick posted an article
    Company making up to 71,000 RNA extractions available to testing laboratories see more

    GREENVILLE, S.C. – April 1, 2020 – KIYATEC, Inc., a clinical-stage leader in ex vivo 3D cell culture testing that supports cancer drug development and drug therapy decision-making, announced today that it is making high-throughput RNA extraction services available to clinical laboratories nationwide that are conducting COVID-19 testing. By creating additional capacity for RNA extraction, a critical component of the COVID-19 testing process, KIYATEC believes it will help testing laboratories normalize the processing and delivery of test results at a time of unprecedented testing demand and turnaround times.

    Most coronavirus tests rely on RNA extraction as the first technical step; without it, the test cannot be performed. Nationwide shortages and backlogs in the reagents and kits most often used to perform these extractions have created bottlenecks and delays that have impacted COVID-19 testing volume and throughput, thereby prompting the U.S. Food and Drug Administration (FDA) to approve alternate testing processes under Emergency Use Authorization (EAU) status. With an already CLIA-certified and operational high complexity lab, KIYATEC is joining the fight against this pandemic by offering its RNA extraction services to COVID-19 testing laboratories.

    While KIYATEC’s core business in oncology continues to occupy much of its laboratory testing capacity, the company has elected to make up to 71,000 RNA extractions available over the next two months, effective immediately, on a fee-for-service basis to COVID-19 testing laboratories nationwide. At a time when COVID-19 testing volume and turnaround times are surging, KIYATEC’s 24-hour turnaround time per RNA extraction could provide a cost-effective efficiency boost to laboratories performing these tests. Making RNA extraction services available to COVID-19 testing laboratories is consistent with KIYATEC’s core goals of improving patient care and outcomes.

    “Although KIYATEC traditionally serves the oncology community exclusively, we quickly determined that our existing technical infrastructure and capabilities in RNA extraction were ideally aligned to address this critical pressure point in the COVID-19 test process,” said Matthew Gevaert, PhD, CEO of KIYATEC. “Following discussions with public health thought leaders and COVID-19 testing laboratories, we realized that offering RNA extraction services could provide immediate help to these laboratories in overcoming possible supply chain challenges and optimizing their volume and turnaround time potential.”

    About KIYATEC, Inc.
    KIYATEC leverages its proprietary ex vivo 3D cell culture technology platforms to accurately model and predict response to approved and investigational cancer drugs targeting a spectrum of solid tumors. The company’s Clinical Services business is currently engaged in the validation of clinical assays as well as investigator-initiated studies in ovarian cancer, breast cancer, glioblastoma and rare tumors, in its CLIA-certified laboratory. The company’s Drug Development Services business works in partnership with leading biopharmaceutical companies to unlock response dynamics for their investigational drug candidates across the majority of solid tumor types.

    Contacts

    KIYATEC Inc.
    Lillia Holmes, Chief Operating Officer, 864-502-2013
    customer.service@Kiyatec.com
    www.kiyatec.com

  • sam patrick posted an article
    KIYATEC advances published in Scientific Reports see more

    KIYATEC, Inc. today announces that results from its prospective, multi-center pilot study, to investigate their assay’s predictive accuracy and correlation to outcome among newly diagnosed ovarian cancer patients, have been published in Scientific Reports. Study findings represent both a preliminary clinical validation for the company’s ovarian cancer assay and a significant developmental milestone for the assay’s technology platform, known as Ex Vivo 3D Cell Culture (EV3D).

    “For ovarian cancer patients and their physicians, this study represents an important step in demonstrating our ability to deliver a robust predictive assay with the potential to positively support therapeutic decision-making and improve patient outcomes,” said Matthew Gevaert, CEO of KIYATEC. “Our mission is to optimize and leverage our EV3D cell culture technology to develop response-predictive clinical assays across a range of solid tumor types and make a difference in the future of cancer care.”

    In the study, primary tissue from 92 newly diagnosed ovarian cancer patients were prospectively collected and tested for response to National Comprehensive Cancer Network (NCCN)-recommended frontline chemotherapy drugs at KIYATEC’s central laboratory. Assay results were successfully generated for 83 (90%) patient samples. All 92 patients received standard of care chemotherapy (80% adjuvant, 20% neoadjuvant) independent of the KIYATEC drug response prediction test result.

    A total of 44 patients (of the 83 patients tested) met minimum follow-up time of 6 months post-chemotherapy for inclusion in this publication. The KIYATEC assay successfully predicted responders (i.e. platinum sensitive) and non-responders (i.e. platinum resistant) with an accuracy of 89% (39/44, p<0.0001).

    Investigators also assessed assay accuracy and correlation to outcome among the 35 of 44 (80%) patients who received adjuvant chemotherapy. In this cohort, the KIYATEC assay correctly predicted responders and non-responders with 89% accuracy (31/35, p=0.0004). From date of surgical debulk, progression free survival (PFS) among test subjects predicted to respond to the first line chemotherapy they received was over 20 months v. 9 months for patients predicted not to respond (p=0.01).

    “At present, clinicians have no way of knowing, prior to treatment, which of our newly diagnosed or relapsed ovarian cancer patients will respond or not to approved drug therapies,” said Larry Maxwell, MD, Chairman of Obstetrics and Gynecology and co-director of Inova’s Women’s Health Integrated Research Center (WHIRC), and an author of the study. “To predict a complex future result with very high accuracy is a meaningful achievement, especially given that sometimes these outcomes take months to define. Similar test performance in larger, follow-on studies would establish this as a go-to tool in cancer drug selection that should help improve patient outcomes in ovarian cancer.”

    Based on these promising findings, KIYATEC has opened a prospective, pivotal clinical study, 3D-PREDICT (NCT03561207), in 500 patients to further validate EV3D-enabled clinical assays for newly diagnosed and recurrent ovarian cancer (8-drug panel) and glioblastoma (12-drug panel). The study is currently open to enrollment.

    About KIYATEC, Inc.

    KIYATEC leverages its proprietary ex vivo 3D cell culture technology platforms to accurately model and predict response to approved and investigational cancer drugs targeting a spectrum of solid tumors.  The company’s Clinical Services business is currently engaged in the validation of clinical assays as well as investigator-initiated studies in ovarian cancer, breast cancer, glioblastoma and rare tumors, in its CLIA-certified laboratory.  The company’s Drug Development Services business works in partnership with leading biopharmaceutical companies to unlock response dynamics for their investigational drug candidates across the majority of solid tumor types.