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HOUSTON, May 10, 2017 (GLOBE NEWSWIRE) -- PLx Pharma Inc. (NASDAQ:PLXP) (“PLx” or the “Company”), a specialty pharmaceutical company, has been awarded a $1.9 million grant by the National Cancer Institute (NCI) of the National Institutes of Health (NIH) in support of PLx’s novel formulation of aspirin for chemoprevention of colorectal cancer. “This NCI grant will enable us to further advance research of our novel formulation of aspirin for the prevention of colorectal cancer, the fourth most commonly diagnosed cancer in the U.S. today,” stated Natasha Giordano, President and Chief Executive Officer of PLx. The role of aspirin in platelet pharmacology is well-established, and aspirin itself remains the foundational drug used for cardiovascular disease prevention. Dr. Lenard M. Lichtenberger, Professor of Integrative Biology & Pharmacology at The University of Texas Health Science Center at Houston (UTHealth), will be the Principal Investigator of studies funded by this grant. The research will be conducted at UTHealth, Baylor College of Medicine and The University of Texas MD Anderson Cancer Center and will focus on further investigating this novel formulation of aspirin’s role in colorectal cancer prevention. Further development of PLx’s novel phosphatidylcholine (PC)-associated aspirin (Aspirin-PC) for the prevention of colorectal cancer and potentially other cancers is supported by two recently published studies in peer-reviewed journals of the American Association for Cancer Research (AACR). Cancer Prevention Research (February 2017) published a study by Dr. Lichtenberger et al on the mechanism of Aspirin-PC in colon cancer, both in cell culture and in a chemically-induced murine model of colon cancer.1   This study demonstrated Aspirin-PC’s activity with regard to antiplatelet effect and chemoprevention in these preclinical models. A December 2016 paper published in Molecular Cancer Therapeutics described in vitro dose response studies comparing the growth-inhibitory effect of Aspirin-PC versus regular aspirin on three human and one murine ovarian cancer cell line over an 8-day culture period and three independent mouse models of ovarian cancer, two carrying different cell lines of human ovarian cancer and one where a mouse ovarian cancer cell line was passaged.2 These studies, conducted by Dr. Anil Sood and co-first authors Dr. Yan Huang and Dr. Lichtenberger, et al, demonstrated Aspirin-PC’s activity in inhibiting ovarian cancer growth under both in vitro and in vivo conditions.  Drs. Sood and Huang were with MD Anderson Cancer Center, while Dr. Lichtenberger led a team at UTHealth that included Drs. Elizabeth Dial and Dexing Fang. The NCI grant, Award Number R42CA171408, will be disbursed in two installments: $961,499 in 2017 and $966,160 in 2018. 2 Huang Y et al. Antitumor and Antiangiogenic Effects of Aspirin-PC in Ovarian Cancer. Mol Cancer Ther; 15(12) December 2016. PLx Pharma Inc. is a specialty pharmaceutical company focused on developing its clinically validated and patent-protected PLxGuard™ delivery system to provide safe and effective aspirin products. PLx Pharma’s lead product Aspertec™ Aspirin Capsules, 325 mg is FDA approved.  PLx is focused on completing manufacturing scale-up and label finalization for Aspertec 325 mg aspirin dose strength and preparing an sNDA for Aspertec 81 mg maintenance dose strength. PLxGuard works by targeting delivery of active pharmaceutical ingredients to various portions of the gastrointestinal (GI) tract. PLx believes this delivery system has the potential to improve the absorption of many drugs currently on the market or in development, such as aspirin, and may provide high-risk cardiovascular and stroke patients with more reliable and predictable antiplatelet efficacy as compared to enteric coated aspirin. PLx also believes PLxGuard has the potential to reduce acute GI side effects—including erosions, ulcers and bleeding—associated with aspirin and ibuprofen, and potentially other drugs. To learn more about PLx Pharma Inc. and its pipeline, please visit www.plxpharma.com. NCI leads the National Cancer Program and the NIH’s efforts to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI website at cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER. About the National Institutes of Health (NIH) NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih.gov. Any statements made in this press release relating to future financial or business performance, conditions, plans, prospects, trends, or strategies and other financial and business matters, including without limitation, the prospects for commercializing or selling any products or drug candidates, are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In addition, when or if used in this press release, the words “may,” “could,” “should,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “plan,” “predict” and similar expressions and their variants, as they relate to PLx may identify forward-looking statements. PLx cautions that these forward-looking statements are subject to numerous assumptions, risks, and uncertainties, which change over time. Important factors that may cause actual results to differ materially from the results discussed in the forward-looking statements or historical experience include risks and uncertainties, including the failure by PLx to secure and maintain relationships with collaborators; risks relating to clinical trials; risks relating to the commercialization, if any, of PLx’s proposed product candidates (such as marketing, regulatory, product liability, supply, competition, and other risks); dependence on the efforts of third parties; dependence on intellectual property and risks that PLx may lack the financial resources and access to capital to fund proposed operations. Further information on the factors and risks that could affect PLx’s business, financial conditions and results of operations are contained in PLx’s filings with the U.S. Securities and Exchange Commission (SEC), which are available at www.sec.gov. Other risks and uncertainties are more fully described in the Registration Statement on Form S-4 filed with the SEC in connection with the merger of PLx and Dipexium Pharmaceuticals, Inc., and in other filings that PLx will make going forward. The forward-looking statements represent PLx’s estimate as of the date hereof only, and PLx specifically disclaims any duty or obligation to update forward-looking statements.


BOSTON, May 12, 2017 (GLOBE NEWSWIRE) -- ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new immunotherapies, today announced that it has priced an underwritten follow-on offering of 9,708,738 shares of its common stock at an offering price of $5.15 per share to a single institutional investor, before underwriting discounts and commissions. All of the shares are being offered by ZIOPHARM. Proceeds to ZIOPHARM from this offering are expected to be $50 million, before deducting underwriting discounts and commissions and estimated offering expenses. ZIOPHARM intends to use the net proceeds from the offering for general corporate and working capital purposes, including the advancement of its clinical programs. Given ZIOPHARM’s current development plans and assuming that the offering closes as expected, ZIOPHARM anticipates that its current cash resources, after giving effect to the proceeds of the proposed offering, will be sufficient to fund its operations into the fourth quarter of 2018. The offering is expected to close on May 16, 2017, subject to customary closing conditions. Guggenheim Securities, LLC is acting as the sole book-running manager for the offering. These securities being offered are registered pursuant to an automatic shelf registration statement filed with the U.S. Securities and Exchange Commission on February 2, 2015 and the offering is being made only by means of a written prospectus. A copy of the final prospectus relating to these securities, when available, may be obtained from Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Ave., New York, NY 10017, via telephone at (212) 518-9658 or by email to GSEquityProspectusDelivery@guggenheimpartners.com. This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. ZIOPHARM Oncology is a Boston, Massachusetts-based biotechnology company employing novel gene expression, control and cell technologies to deliver safe, effective and scalable cell- and viral-based therapies for the treatment of cancer and graft-versus-host-disease. The Company’s immuno-oncology programs, in collaboration with Intrexon Corporation (NYSE:XON) and the MD Anderson Cancer Center, include chimeric antigen receptor T cell (CAR-T) and other adoptive cell-based approaches that use non-viral gene transfer methods for broad scalability. The Company is advancing programs in multiple stages of development together with Intrexon Corporation’s RheoSwitch Therapeutic System® technology, a switch to turn on and off, and precisely modulate, gene expression in order to improve therapeutic index. The Company’s pipeline includes a number of cell-based therapeutics in both clinical and preclinical testing which are focused on hematologic and solid tumor malignancies. Any statements in this press release about future expectations, plans and prospects for ZIOPHARM Oncology, Inc., including statements about the anticipated closing of the offering, the amount and use of the anticipated proceeds the Company expects to receive from the offering, clinical development of the Company’s product candidates, expectations regarding the Company’s cash resources to fund its future operations and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including the risks and uncertainties related to the satisfaction of customary closing conditions related to the offering and such other factors as are discussed in the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2016, its Quarterly Report on Form 10-Q for the quarter ended March 31, 2017 and the Company’s other filings with the Securities and Exchange Commission. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof, and the Company does not undertake any obligation to revise and disseminate forward-looking statements to reflect events or circumstances after the date hereof, or to reflect the occurrence of or non-occurrence of any events.


HOUSTON, May 10, 2017 (GLOBE NEWSWIRE) -- PLx Pharma Inc. (NASDAQ:PLXP) (“PLx” or the “Company”), a specialty pharmaceutical company, has been awarded a $1.9 million grant by the National Cancer Institute (NCI) of the National Institutes of Health (NIH) in support of PLx’s novel formulation of aspirin for chemoprevention of colorectal cancer. “This NCI grant will enable us to further advance research of our novel formulation of aspirin for the prevention of colorectal cancer, the fourth most commonly diagnosed cancer in the U.S. today,” stated Natasha Giordano, President and Chief Executive Officer of PLx. The role of aspirin in platelet pharmacology is well-established, and aspirin itself remains the foundational drug used for cardiovascular disease prevention. Dr. Lenard M. Lichtenberger, Professor of Integrative Biology & Pharmacology at The University of Texas Health Science Center at Houston (UTHealth), will be the Principal Investigator of studies funded by this grant. The research will be conducted at UTHealth, Baylor College of Medicine and The University of Texas MD Anderson Cancer Center and will focus on further investigating this novel formulation of aspirin’s role in colorectal cancer prevention. Further development of PLx’s novel phosphatidylcholine (PC)-associated aspirin (Aspirin-PC) for the prevention of colorectal cancer and potentially other cancers is supported by two recently published studies in peer-reviewed journals of the American Association for Cancer Research (AACR). Cancer Prevention Research (February 2017) published a study by Dr. Lichtenberger et al on the mechanism of Aspirin-PC in colon cancer, both in cell culture and in a chemically-induced murine model of colon cancer.1   This study demonstrated Aspirin-PC’s activity with regard to antiplatelet effect and chemoprevention in these preclinical models. A December 2016 paper published in Molecular Cancer Therapeutics described in vitro dose response studies comparing the growth-inhibitory effect of Aspirin-PC versus regular aspirin on three human and one murine ovarian cancer cell line over an 8-day culture period and three independent mouse models of ovarian cancer, two carrying different cell lines of human ovarian cancer and one where a mouse ovarian cancer cell line was passaged.2 These studies, conducted by Dr. Anil Sood and co-first authors Dr. Yan Huang and Dr. Lichtenberger, et al, demonstrated Aspirin-PC’s activity in inhibiting ovarian cancer growth under both in vitro and in vivo conditions.  Drs. Sood and Huang were with MD Anderson Cancer Center, while Dr. Lichtenberger led a team at UTHealth that included Drs. Elizabeth Dial and Dexing Fang. The NCI grant, Award Number R42CA171408, will be disbursed in two installments: $961,499 in 2017 and $966,160 in 2018. 2 Huang Y et al. Antitumor and Antiangiogenic Effects of Aspirin-PC in Ovarian Cancer. Mol Cancer Ther; 15(12) December 2016. PLx Pharma Inc. is a specialty pharmaceutical company focused on developing its clinically validated and patent-protected PLxGuard™ delivery system to provide safe and effective aspirin products. PLx Pharma’s lead product Aspertec™ Aspirin Capsules, 325 mg is FDA approved.  PLx is focused on completing manufacturing scale-up and label finalization for Aspertec 325 mg aspirin dose strength and preparing an sNDA for Aspertec 81 mg maintenance dose strength. PLxGuard works by targeting delivery of active pharmaceutical ingredients to various portions of the gastrointestinal (GI) tract. PLx believes this delivery system has the potential to improve the absorption of many drugs currently on the market or in development, such as aspirin, and may provide high-risk cardiovascular and stroke patients with more reliable and predictable antiplatelet efficacy as compared to enteric coated aspirin. PLx also believes PLxGuard has the potential to reduce acute GI side effects—including erosions, ulcers and bleeding—associated with aspirin and ibuprofen, and potentially other drugs. To learn more about PLx Pharma Inc. and its pipeline, please visit www.plxpharma.com. NCI leads the National Cancer Program and the NIH’s efforts to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI website at cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER. About the National Institutes of Health (NIH) NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih.gov. Any statements made in this press release relating to future financial or business performance, conditions, plans, prospects, trends, or strategies and other financial and business matters, including without limitation, the prospects for commercializing or selling any products or drug candidates, are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In addition, when or if used in this press release, the words “may,” “could,” “should,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “plan,” “predict” and similar expressions and their variants, as they relate to PLx may identify forward-looking statements. PLx cautions that these forward-looking statements are subject to numerous assumptions, risks, and uncertainties, which change over time. Important factors that may cause actual results to differ materially from the results discussed in the forward-looking statements or historical experience include risks and uncertainties, including the failure by PLx to secure and maintain relationships with collaborators; risks relating to clinical trials; risks relating to the commercialization, if any, of PLx’s proposed product candidates (such as marketing, regulatory, product liability, supply, competition, and other risks); dependence on the efforts of third parties; dependence on intellectual property and risks that PLx may lack the financial resources and access to capital to fund proposed operations. Further information on the factors and risks that could affect PLx’s business, financial conditions and results of operations are contained in PLx’s filings with the U.S. Securities and Exchange Commission (SEC), which are available at www.sec.gov. Other risks and uncertainties are more fully described in the Registration Statement on Form S-4 filed with the SEC in connection with the merger of PLx and Dipexium Pharmaceuticals, Inc., and in other filings that PLx will make going forward. The forward-looking statements represent PLx’s estimate as of the date hereof only, and PLx specifically disclaims any duty or obligation to update forward-looking statements.


BOSTON, May 12, 2017 (GLOBE NEWSWIRE) -- ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new immunotherapies, today announced that it has priced an underwritten follow-on offering of 9,708,738 shares of its common stock at an offering price of $5.15 per share to a single institutional investor, before underwriting discounts and commissions. All of the shares are being offered by ZIOPHARM. Proceeds to ZIOPHARM from this offering are expected to be $50 million, before deducting underwriting discounts and commissions and estimated offering expenses. ZIOPHARM intends to use the net proceeds from the offering for general corporate and working capital purposes, including the advancement of its clinical programs. Given ZIOPHARM’s current development plans and assuming that the offering closes as expected, ZIOPHARM anticipates that its current cash resources, after giving effect to the proceeds of the proposed offering, will be sufficient to fund its operations into the fourth quarter of 2018. The offering is expected to close on May 16, 2017, subject to customary closing conditions. Guggenheim Securities, LLC is acting as the sole book-running manager for the offering. These securities being offered are registered pursuant to an automatic shelf registration statement filed with the U.S. Securities and Exchange Commission on February 2, 2015 and the offering is being made only by means of a written prospectus. A copy of the final prospectus relating to these securities, when available, may be obtained from Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Ave., New York, NY 10017, via telephone at (212) 518-9658 or by email to GSEquityProspectusDelivery@guggenheimpartners.com. This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. ZIOPHARM Oncology is a Boston, Massachusetts-based biotechnology company employing novel gene expression, control and cell technologies to deliver safe, effective and scalable cell- and viral-based therapies for the treatment of cancer and graft-versus-host-disease. The Company’s immuno-oncology programs, in collaboration with Intrexon Corporation (NYSE:XON) and the MD Anderson Cancer Center, include chimeric antigen receptor T cell (CAR-T) and other adoptive cell-based approaches that use non-viral gene transfer methods for broad scalability. The Company is advancing programs in multiple stages of development together with Intrexon Corporation’s RheoSwitch Therapeutic System® technology, a switch to turn on and off, and precisely modulate, gene expression in order to improve therapeutic index. The Company’s pipeline includes a number of cell-based therapeutics in both clinical and preclinical testing which are focused on hematologic and solid tumor malignancies. Any statements in this press release about future expectations, plans and prospects for ZIOPHARM Oncology, Inc., including statements about the anticipated closing of the offering, the amount and use of the anticipated proceeds the Company expects to receive from the offering, clinical development of the Company’s product candidates, expectations regarding the Company’s cash resources to fund its future operations and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including the risks and uncertainties related to the satisfaction of customary closing conditions related to the offering and such other factors as are discussed in the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2016, its Quarterly Report on Form 10-Q for the quarter ended March 31, 2017 and the Company’s other filings with the Securities and Exchange Commission. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof, and the Company does not undertake any obligation to revise and disseminate forward-looking statements to reflect events or circumstances after the date hereof, or to reflect the occurrence of or non-occurrence of any events.


BOSTON, May 12, 2017 (GLOBE NEWSWIRE) -- ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new immunotherapies, today announced that it has priced an underwritten follow-on offering of 9,708,738 shares of its common stock at an offering price of $5.15 per share to a single institutional investor, before underwriting discounts and commissions. All of the shares are being offered by ZIOPHARM. Proceeds to ZIOPHARM from this offering are expected to be $50 million, before deducting underwriting discounts and commissions and estimated offering expenses. ZIOPHARM intends to use the net proceeds from the offering for general corporate and working capital purposes, including the advancement of its clinical programs. Given ZIOPHARM’s current development plans and assuming that the offering closes as expected, ZIOPHARM anticipates that its current cash resources, after giving effect to the proceeds of the proposed offering, will be sufficient to fund its operations into the fourth quarter of 2018. The offering is expected to close on May 16, 2017, subject to customary closing conditions. Guggenheim Securities, LLC is acting as the sole book-running manager for the offering. These securities being offered are registered pursuant to an automatic shelf registration statement filed with the U.S. Securities and Exchange Commission on February 2, 2015 and the offering is being made only by means of a written prospectus. A copy of the final prospectus relating to these securities, when available, may be obtained from Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Ave., New York, NY 10017, via telephone at (212) 518-9658 or by email to GSEquityProspectusDelivery@guggenheimpartners.com. This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. ZIOPHARM Oncology is a Boston, Massachusetts-based biotechnology company employing novel gene expression, control and cell technologies to deliver safe, effective and scalable cell- and viral-based therapies for the treatment of cancer and graft-versus-host-disease. The Company’s immuno-oncology programs, in collaboration with Intrexon Corporation (NYSE:XON) and the MD Anderson Cancer Center, include chimeric antigen receptor T cell (CAR-T) and other adoptive cell-based approaches that use non-viral gene transfer methods for broad scalability. The Company is advancing programs in multiple stages of development together with Intrexon Corporation’s RheoSwitch Therapeutic System® technology, a switch to turn on and off, and precisely modulate, gene expression in order to improve therapeutic index. The Company’s pipeline includes a number of cell-based therapeutics in both clinical and preclinical testing which are focused on hematologic and solid tumor malignancies. Any statements in this press release about future expectations, plans and prospects for ZIOPHARM Oncology, Inc., including statements about the anticipated closing of the offering, the amount and use of the anticipated proceeds the Company expects to receive from the offering, clinical development of the Company’s product candidates, expectations regarding the Company’s cash resources to fund its future operations and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including the risks and uncertainties related to the satisfaction of customary closing conditions related to the offering and such other factors as are discussed in the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2016, its Quarterly Report on Form 10-Q for the quarter ended March 31, 2017 and the Company’s other filings with the Securities and Exchange Commission. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof, and the Company does not undertake any obligation to revise and disseminate forward-looking statements to reflect events or circumstances after the date hereof, or to reflect the occurrence of or non-occurrence of any events.


BEVERLY, Mass., May 10, 2017 (GLOBE NEWSWIRE) -- Cellceutix Corporation, (OTCQB:CTIX) (“the Company”), a clinical stage biopharmaceutical company developing innovative therapies with dermatology, oncology, anti-inflammatory and antibiotic applications, today is pleased to provide a corporate update on current operations and upcoming clinical milestones across its pipeline of First-in-Class drug candidates, Prurisol, Kevetrin and Brilacidin, as summarized in our recent Quarterly Report (Form 10-Q), available for download at the link below. The ongoing randomized, double-blind, parallel-group and placebo-controlled study (see NCT02949388) increases the total daily oral dosing of Prurisol from a previous high of 200 mg, which earlier was shown to be well-tolerated and efficacious, to include oral Prurisol 300 mg per day, oral Prurisol 400 mg per day, and placebo (3:1:3 randomization). Enrolling approximately 189 patients with moderate-to-severe chronic plaque psoriasis, treatment duration is 12 weeks (84 days). Interim analysis is planned at 6 weeks. Currently, between patients already enrolled and those presently in screening, the Company has reached over 70 percent of the anticipated number of trial participants. Efficacy is being evaluated using the Psoriasis Area and Severity Index (PASI). Cellceutix believes now is an opportune time to develop an oral treatment for psoriasis. Currently approved treatments, including injectable biologics, are limited, with many options costly, not easily administered, associated with undesirable side-effects and/or diminishing effectiveness over time. A novel psoriasis drug, particularly one that is oral, safe and effective, which could expand patient and physician choices for treatment, likely would command significant market value. The ongoing open-label study (see NCT03042702) is evaluating intravenous (IV) administration of Kevetrin 3 times per week, over 3 weeks, at an initial dose of 250mg/m2, with dose escalation in the 2nd cohort, in patients with platinum-resistant ovarian cancer. Modulation of the p53 pathway to further inform Kevetrin’s mechanism of action (MOA) is being measured via various RNA and protein biomarkers. Endpoints will include safety, efficacy (based on RECIST criteria) and pharmacodynamics. Running in parallel, the Company continues to make substantial progress in developing Kevetrin as an oral formulation. Preliminary bioavailability and other laboratory studies are encouraging and support its potential as an oral formulation. Currently there are no approved p53-modulating drugs, much less in pill form. An oral formulation of Kevetrin one day could position the drug candidate as a go-to cancer treatment. The ongoing randomized, double-blind, placebo-controlled study (see NCT02324335) is evaluating Brilacidin as an oral rinse, 3 times daily for 7 weeks, to prevent and control Oral Mucositis (OM) in patients receiving chemoradiation therapy for Head and Neck Cancer. Even though over 450,000 patients in the U.S. suffer from this condition, presently there are no approved drugs for the treatment of OM in this population, with only limited palliative care options available. In March 2017, preliminary interim analysis revealed that Brilacidin markedly reduced the occurrence of Severe OM, defined as Grade > 3 on the World Health Organization OM Grading Scale—only 2 of 9 patients (22.2%) receiving Brilacidin developed Severe OM compared to 7 of 10 (70%) patients on placebo. Cellceutix’s goal with this trial is to show that Brilacidin has dual functionality in preventing the onset of the condition and shortening the duration of OM, an accomplishment no other pharmaceutical company has achieved. The ongoing open-label, proof-of-concept trial includes enrolling 18 patients treated with Brilacidin divided evenly into three cohorts (6 patients per cohort)—Cohort A (50 mg); Cohort B (100 mg); Cohort C (200 mg). In March 2017, after Cohorts A and B were completed (presently, three patients in Cohort C have completed their treatment), Cellceutix released the interim results. The Primary Efficacy Endpoint of Clinical Remission (accounting for Stool Frequency, Rectal Bleeding and Endoscopy Findings subscores) was met by 50 percent of patients in Cohort A (3 of 6) and 50 percent of patients in Cohort B (3 of 6); all 6 of the remaining patients in Cohorts A and B had a Partial Response, as they met 2 of the 3 specified criteria. Brilacidin was generally well-tolerated. Patient Quality of Life (as assessed by the Short Inflammatory Bowel Disease Questionnaire, SIBDQ) showed notable improvements in all 12 patients. Limited systemic exposure to Brilacidin was demonstrated as measured by plasma Brilacidin concentrations. These data, along with the OM findings, suggest that other inflammatory conditions may, likewise, be treated locally and efficaciously with Brilacidin. Cash Position—As of March 31, 2017, the Company had approximately $5.6 million in cash and $16 million remaining available for stock sales under the terms of the purchase agreement with Aspire Capital, compared to $6.3 million of cash as of June 30, 2016. Shelf Registration—The Company has in place an effective shelf registration statement on Form S-3, registering the sale of up to $75 million of the Company’s securities, with approximately $42.8 million remaining available. Management Discussion—The Company anticipates that future budget expenditures will be approximately $14 million over the next 12 months, including approximately $10 million for clinical trials. Management believes that financing available from Aspire Capital and under the Company’s effective Form S-3 shelf registration statement as well as any potential future Form S-1 filing to register the sale of its securities will be sufficient to fund the Company’s operations for the next 12 months. “We are extremely proud of our accomplishments to date and are thrilled at the company’s prospects going forward into the latter half of 2017,” said Leo Ehrlich, Chief Executive Officer of Cellceutix. “Within a matter of months, we anticipate completing multiple mid-phase clinical trials for indications in areas with serious unmet medical needs. Based on highly encouraging clinical data received so far, we look forward to sharing complete clinical results with shareholders, members of the pharmaceutical industry interested in our drug candidates, and the public at large, to further establish the true potential of our clinical pipeline.” “Much-needed drugs and tremendous value creation await patients and shareholders alike should we continue to deliver compelling trial results,” commented Arthur P. Bertolino, MD, PhD, MBA, President and Chief Medical Officer at Cellceutix. Cellceutix reminds shareholders and other interested parties of two upcoming events. First, on June 8, 2017, at 11AM EST, the Company will hold a live shareholder and investor conference call. We are fielding questions in advance, which may be submitted by emailing conference@cellceutix.com and must be received by June 1, 2017 at 5pm EST. Dial-in instructions for participants will be announced one week prior. Second, the Company will be presenting topline findings from the Brilacidin-UP/UPS trial as well as additional interim data from its Phase 2 trial of Brilacidin for Oral Mucositis at Drug Discovery and Therapy World Congress 2017, to be held July 10 – 13, 2017, in Boston. More details to come. Alerts Sign-up for Cellceutix email alerts is available at: www.cellceutix.com/email-alerts About Cellceutix Headquartered in Beverly, Massachusetts, Cellceutix is a publicly-traded company under the symbol “CTIX”. Cellceutix is a clinical stage biopharmaceutical company developing innovative therapies in multiple diseases. Cellceutix believes it has a world-class portfolio of first-in-class lead drug candidates and is now advancing them toward market approval, while actively seeking strategic partnerships. Cellceutix’s psoriasis drug candidate Prurisol completed a Phase 2 trial and Cellceutix recently launched a Phase 2b study. Prurisol is a small molecule that acts through immune modulation and PRINS reduction. Cellceutix’s anti-cancer drug Kevetrin successfully concluded a Phase 1 clinical trial at Harvard Cancer Centers’ Dana Farber Cancer Institute and Beth Israel Deaconess Medical Center, and Cellceutix has commenced a Phase 2 study. In the laboratory, Kevetrin has shown to induce activation of p53, often referred to as the “Guardian Angel Gene” due to its crucial role in controlling cell mutations. Brilacidin-OM, a defensin mimetic compound, has shown in an animal model to reduce the occurrence of severe ulcerative oral mucositis by more than 94% compared to placebo. Cellceutix is in a Phase 2 clinical trial with its novel compound Brilacidin-OM for the prevention of oral mucositis in patients with head and neck cancer; interim results have shown a marked reduction in the incidence of severe oral mucositis (WHO Grade ≥ 3). Cellceutix’s lead antibiotic, Brilacidin, has completed a Phase 2b trial for Acute Bacterial Skin and Skin Structure Infection, or ABSSSI. Top-line data have shown a single dose of Brilacidin to deliver comparable clinical outcomes to the FDA-approved seven-day dosing regimen of daptomycin. Brilacidin has the potential to be a single-dose therapy for certain multi-drug resistant bacteria (“superbugs”). In an ongoing Phase 2 open label Proof-of-Concept trial, favorable interim results have been observed in the first two cohorts of patients treated with Brilacidin for Ulcerative Proctitis/Ulcerative Proctosigmoiditis (UP/UPS), two types of Inflammatory Bowel Disease (IBD). Cellceutix has formed research collaborations with world-renowned research institutions in the United States and Europe, including MD Anderson Cancer Center, Beth Israel Deaconess Medical Center, and the University of Bologna. More information is available on the Cellceutix web site at www.cellceutix.com. Forward-Looking Statements: This press release contains forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 including statements concerning projected timelines for the initiation and completion of clinical trials, our future drug development plans, other statements regarding future product developments, including with respect to specific indications, and any other statements which are other than statements of historical fact. These statements involve risks, uncertainties and assumptions that could cause Cellceutix’s actual results and experience to differ materially from anticipated results and expectations expressed in these forward-looking statements. Cellceutix has in some cases identified forward-looking statements by using words such as “anticipates,” “believes,” “hopes,” “estimates,” “looks,” “expects,” “plans,” “intends,” “goal,” “potential,” “may,” “suggest,” and similar expressions. Among other factors that could cause actual results to differ materially from those expressed in forward-looking statements are Cellceutix’s need for, and the availability of, substantial capital in the future to fund its operations and research and development; including the amount and timing of the sale of shares of common stock to Aspire Capital; the fact that Cellceutix’s compounds may not successfully complete pre-clinical or clinical testing, or be granted regulatory approval to be sold and marketed in the United States or elsewhere. A more complete description of these risk factors is included in Cellceutix’s filings with the Securities and Exchange Commission. You should not place undue reliance on any forward-looking statements. Cellceutix undertakes no obligation to release publicly the results of any revisions to any such forward-looking statements that may be made to reflect events or circumstances after the date of this press release or to reflect the occurrence of unanticipated events, except as required by applicable law or regulation.


News Article | May 10, 2017
Site: globenewswire.com

DURHAM, N.C., May 10, 2017 (GLOBE NEWSWIRE) -- Argos Therapeutics Inc. (NASDAQ:ARGS), an immuno-oncology company focused on the development and commercialization of individualized immunotherapies based on the Arcelis® precision immunotherapy technology platform, today provided an update on the ADAPT trial, a randomized, active controlled, open-label, multi-center Phase 3 trial of Rocapuldencel-T in combination with sunitinib/standard-of-care for the treatment of newly diagnosed metastatic renal cell carcinoma (mRCC), following a meeting with the FDA. As previously reported, the Company has continued to conduct the ADAPT trial notwithstanding the recommendation by the Independent Data Monitoring Committee in February 2017 to terminate the trial for futility. In making this determination, Argos considered, among other factors, the degree of maturity of the data set, the mechanism of action of Rocapuldencel-T, which involves the induction of a long-term memory immune response, and the IDMC's assessment of the safety profile of Rocapuldencel-T. Of note, at the time of the IDMC's February interim analysis, the median duration of follow-up was 20.0 months and more than half the patients in both treatment groups were still alive. The Company submitted information related to its analysis of the interim data to the FDA and met with the FDA to discuss the future direction of the ADAPT trial and the Rocapuldencel-T development program. Participating in the meeting along with representatives from the Company were Robert Figlin, MD, Chairman of Hematology Oncology and Professor of Medicine, Cedars Sinai Medical Center; Nizar Tannir, MD, Professor and Deputy Chairman, Department of Genitourinary Medical Oncology, MD Anderson Cancer Center; and Gary Koch, PhD, Professor of Biostatistics, University of North Carolina. The FDA agreed with the Company’s plan to continue the trial in accordance with the current protocol to 290 events, the pre-specified number of events at which the analysis of overall survival, the primary endpoint, is to be conducted. The Company believes that 290 events will have occurred by late 2017 or early 2018. The Company also proposed to submit, and the FDA agreed to review, a protocol amendment to increase the pre-specified number of events for the primary analysis of overall survival beyond 290 events, which the Company believes could enhance its ability to detect whether Rocapuldencel-T has a delayed treatment effect. The Company can extend the study past 290 events without needing to enroll additional patients. As previously reported, the Company has analyzed interim data from a predefined subset of patients who demonstrated an immune response to Rocapuldencel-T at 48 weeks, whose immune response is consistent with the mechanism of action of the therapy and correlates with survival, suggesting that the treatment is biologically active. Analysis of the data from the ADAPT trial, including immune response data, remains ongoing. The Company expects to provide further updates on the future direction of the ADAPT trial and the Rocapuldencel-T program following further analysis of the data from the trial and further discussions with the FDA. “We are pleased to be able to continue the ADAPT trial,” noted Robert Figlin, MD, principal investigator for the trial. “We believe that Rocapuldencel-T may offer patients and their physicians an important new option for the treatment of mRCC, a disease that remains an area of high unmet medical need. By amending the protocol to extend the ADAPT trial, we believe we can potentially increase the likelihood of detecting a treatment effect, if one exists, given that immunotherapy is expected to result in a delayed treatment effect. We appreciate the collaborative efforts of the FDA as we seek to determine the potential utility of Rocapuldencel-T in the treatment of this difficult disease.“ “We remain committed to the clinical development of Rocapuldencel-T, and look forward to providing additional updates on the ADAPT trial and the Rocapuldencel-T development program moving forward,” noted Jeff Abbey, CEO of Argos. “We appreciate the continued commitment of the investigators and patients in the ADAPT trial as we continue to explore the potential benefit of this unique therapy.” Arcelis® is a precision immunotherapy technology that captures both mutated and variant antigens that are specific to each patient's individual disease. It is designed to overcome immunosuppression by producing a specifically targeted, durable memory T cell response without adjuvants that may be associated with toxicity. The technology is potentially applicable to the treatment of a wide range of different cancers and infectious diseases, and is designed to overcome many of the manufacturing and commercialization challenges that have impeded other personalized immunotherapies. The Arcelis® process uses only a small disease sample or biopsy as the source of disease-specific antigens, and the patient's own dendritic cells, which are optimized from cells collected by a single leukapheresis procedure. The proprietary process uses RNA isolated from the patient's disease sample to program dendritic cells to target disease-specific antigens. These activated, antigen-loaded dendritic cells are then formulated with the patient's plasma, and administered via intradermal injection as an individualized immunotherapy. Argos Therapeutics is an immuno-oncology company focused on the development and commercialization of individualized immunotherapies for the treatment of cancer and infectious diseases using its Arcelis® technology platform. Argos' most advanced product candidate, Rocapuldencel-T, is being evaluated in the pivotal ADAPT Phase 3 clinical trial for the treatment of metastatic renal cell carcinoma (mRCC). In addition, Rocapuldencel-T is being studied in a Phase 2 investigator-initiated clinical trial as neoadjuvant therapy for renal cell carcinoma (RCC). Argos is also developing a separate Arcelis®-based product candidate, AGS-004, for the treatment of human immunodeficiency virus (HIV), which is currently being evaluated in an investigator-initiated Phase 2 clinical trial aimed at HIV eradication in adult patients. Any statements in this press release about Argos' future expectations, plans and prospects, including statements about the ADAPT trial and the interim data from the trial, Argos' anticipated discussions with the FDA, clinical development of Argos' product candidates and future expectations and plans and prospects for Argos and other statements containing the words "believes," "anticipates," "estimates," "expects," "intends," "plans," "predicts," "projects," "targets," "may," "potential," "will," "would," "could," "should," "continue," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether Argos' cash resources will be sufficient to fund its continuing operations for the periods anticipated and through completion of the trial; the impact of the planned analysis of the data and discussions with the FDA on the development of Rocapuldencel-T; the impact of the recommendation of the IDMC on the continuation of the ADAPT trial; whether preliminary or interim clinical data such as the interim data referenced in this release will be indicative of the final data from a clinical trial; whether results obtained in clinical trials will be indicative of results obtained in future clinical trials; whether Argos' product candidates will advance through the clinical trial process on a timely basis; whether the results of such trials will warrant submission for approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether Argos' product candidates will receive approval from regulatory agencies on a timely basis or at all; whether, if product candidates obtain approval, they will be successfully distributed and marketed; whether Argos can successfully establish commercial manufacturing operations on a timely basis or at all; and other factors discussed in the "Risk Factors" section of Argos' Form 10-K for the year ended December 31, 2016, which is on file with the SEC, and in other filings Argos makes with the SEC from time to time. In addition, the forward-looking statements included in this press release represent Argos' views as of the date hereof. Argos anticipates that subsequent events and developments will cause Argos' views to change. However, while Argos may elect to update these forward-looking statements at some point in the future, Argos specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Argos' views as of any date subsequent to the date hereof.


Receive press releases from Pulmotect, Inc: By Email US China Innovation and Investment Summit Panel on Biopharmaceuticals to Feature Pulmotect CEO Molfino, a respiratory medicine specialist, will provide his perspective on balancing the costs of developing and delivering innovative technologies, drug safety and regulatory issues, important learnings to date and the future outlook of therapeutics in modern healthcare. Houston, TX, May 10, 2017 --( The 40-minute panel discussion will take place at 1 p.m. in Colonnade Salon A. Industry experts joining Molfino in the discussion on therapeutics are Mike Moradi, CEO and co-founder of Sensulin and Jon Northrup, CEO and co-founder of Beta Cat Pharmaceuticals. Molfino, a respiratory medicine specialist, will provide his perspective on balancing the costs of developing and delivering innovative technologies, drug safety and regulatory issues, important learning to date and the future outlook of therapeutics in modern healthcare. Molfino previously served as an independent consultant to biopharmaceutical companies, clinical research organizations (CROs), investors and patient organizations in the planning, designing and execution of drug development and commercial strategies. He was also the Chief Medical Officer at South San Francisco-based KaloBios Pharmaceuticals, Inc. In addition to the panel discussion, Molfino will represent Pulmotect in the InnoSTARS preliminary stage pitch competition on Monday, May 15 for a chance to earn an expense-paid trip to China to showcase the company’s technology to potential partners and investors during a three-city tour. The US China Innovation and Investment Summit will focus on five areas of industry including healthcare and biotechnology, agriculture and food safety, renewable energy, advanced manufacturing and information and communication technology. In addition to panel discussions, the summit will feature B2B Matchmaking sessions, an exhibition of technology companies and VIP meetings. To learn more about the 2017 conference, visit http://uschinainnovation.org. About Pulmotect, Inc. Founded in 2007, Pulmotect’s technology is licensed from The Texas A&M University System and The University of Texas MD Anderson Cancer Center. Pulmotect partnered in 2008 with Fannin Innovation Studio, a Houston-based early-stage life science management and investment company, to assist in the drug’s commercial development. Pulmotect is the recipient of multiple early stage investments and grants, as well as recognition and awards from the biotechnology community, and the Company was awarded $7.1 million from the Cancer Prevention Institute of Texas (CPRIT). For more information, visit www.pulmotect.com. Houston, TX, May 10, 2017 --( PR.com )-- Pulmotect, Inc., clinical stage biotechnology company developing and commercializing an inhalant designed to prevent respiratory infections, announced today that Nestor Molfino, M.D., CEO, will participate in a panel discussion entitled “Innovation in Biopharmaceuticals” at the US China Innovation and Investment Summit, being held at the Omni Houston Hotel in Houston, Texas on May 16, 2017.The 40-minute panel discussion will take place at 1 p.m. in Colonnade Salon A. Industry experts joining Molfino in the discussion on therapeutics are Mike Moradi, CEO and co-founder of Sensulin and Jon Northrup, CEO and co-founder of Beta Cat Pharmaceuticals.Molfino, a respiratory medicine specialist, will provide his perspective on balancing the costs of developing and delivering innovative technologies, drug safety and regulatory issues, important learning to date and the future outlook of therapeutics in modern healthcare.Molfino previously served as an independent consultant to biopharmaceutical companies, clinical research organizations (CROs), investors and patient organizations in the planning, designing and execution of drug development and commercial strategies. He was also the Chief Medical Officer at South San Francisco-based KaloBios Pharmaceuticals, Inc.In addition to the panel discussion, Molfino will represent Pulmotect in the InnoSTARS preliminary stage pitch competition on Monday, May 15 for a chance to earn an expense-paid trip to China to showcase the company’s technology to potential partners and investors during a three-city tour.The US China Innovation and Investment Summit will focus on five areas of industry including healthcare and biotechnology, agriculture and food safety, renewable energy, advanced manufacturing and information and communication technology. In addition to panel discussions, the summit will feature B2B Matchmaking sessions, an exhibition of technology companies and VIP meetings.To learn more about the 2017 conference, visit http://uschinainnovation.org.About Pulmotect, Inc.Founded in 2007, Pulmotect’s technology is licensed from The Texas A&M University System and The University of Texas MD Anderson Cancer Center. Pulmotect partnered in 2008 with Fannin Innovation Studio, a Houston-based early-stage life science management and investment company, to assist in the drug’s commercial development. Pulmotect is the recipient of multiple early stage investments and grants, as well as recognition and awards from the biotechnology community, and the Company was awarded $7.1 million from the Cancer Prevention Institute of Texas (CPRIT). For more information, visit www.pulmotect.com. Click here to view the list of recent Press Releases from Pulmotect, Inc


News Article | May 10, 2017
Site: phys.org

"Historically, radiation has been a blunt tool," said Matt Vaughn, Director of Life Science Computing at the Texas Advanced Computing Center. "However, it's become ever more precise because we understand the physics and biology of systems that we're shooting radiation into, and have improved our ability to target the delivery of that radiation." The science of calculating and assessing the radiation dose received by the human body is known as dosimetry - and here, as in many areas of science, advanced computing plays an important role. Current radiation treatments rely on imaging from computed tomography (CT) scans taken prior to treatment to determine a tumor's location. This works well if the tumor lies in an easily detectable and immobile location, but less so if the area is moving, as in the case of lung cancer. At the University of Texas MD Anderson Cancer Center, scientists are tackling the problem of accurately attacking tumors using a new technology known as an MR-linac that combines magnetic resonance (MR) imaging with linear accelerators (linacs). Developed by Elekta in cooperation with UMC Utrecht and Philips, the MR-linac at MD Anderson is the first of its kind in the U.S. MR-linacs can image a patient's anatomy while the radiation beam is being delivered. This allows doctors to detect and visualize any anatomical changes in a patient during treatment. Unlike CT or other x-ray based imaging modalities, which provide additional ionizing radiation, MRI is harmless to healthy tissue. The MR-linac method offers a potentially significant improvement over current image-guided cancer treatment technology. However, to ensure patients are treated safely, scientists must first correct for the influence of the MRI's magnetic field on the measurements used to calibrate the radiation dose being delivered. Researchers use software called Geant4 to simulate radiation within the detectors. Originally developed by CERN to simulate high energy particle physics experiments, the MD Anderson team has adapted Geant4 to incorporate magnetic fields into their computer dosimetry model. "Since the ultimate aim of the MR-linac is to treat patients, it is important that our simulations be very accurate and that the results be very precise," said Daniel O'Brien, a postdoctoral fellow in radiation physics at MD Anderson. "Geant4 was originally designed to study radiation at much higher energies than what is used to treat patients. We had to perform tests to make sure that we had the accuracy that we needed." Using the Lonestar supercomputer at the Texas Advanced Computing Center (TACC), the research team simulated nearly 17 billion particles of radiation per detector to get the precision that they needed for their study. In August 2016, they published magnetic field correction factors in Medical Physics for six of the most-used ionization chamber detectors (gas-filled chambers that are used to ensure the dose delivered from a therapy unit is correct). They are now working on verifying these results experimentally. "The MR-linac is a very promising technology but it also presents many unique challenges from a dosimetry point of view," O'Brien said. "Over time, our understanding of these effects has improved considerably, but there is still work to be done and resources like TACC are an invaluable asset in making these new technologies safe and reliable." "Our computer simulations are important because their results will serve as the foundation to extend current national and international protocols to perform calibration of conventional linacs to MR-linacs," said Gabriel Sawakuchi, assistant professor of Radiation Physics at MD Anderson. "However, it is important that our results be validated against measurements and independent simulations performed by other groups before used clinically." X-ray radiation is the most frequently used form of high-energy treatment, but a new treatment is emerging that uses a beam of protons to deliver energy directly to the tumor with minimal damage to surrounding tissues and without the side effects of x-ray therapy. Like x-ray radiation, proton therapy blasts tumors with beams of particles. But whereas traditional radiation uses photons, or focused light beams, proton therapy uses ions - hydrogen atoms that have lost an electron. Proton beams have a unique physical characteristic known as the 'Bragg peak' that allows the greatest part of its energy to be transferred to a specific area within the body, where it has maximum destructive effect. X-ray radiation, on the other hand, deposits energy and kills cells along the whole length of the beam. This can lead to unintended cell damage and even secondary cancer that can develop years later. In comparison with current radiation procedures, proton therapy saves healthy tissue in front of and behind the tumor. Since the patient is irradiated from all directions and the intensity of beams can be well modulated, the method provides further reduction of adverse effects. Proton therapy is particularly effective when irradiating tumors near sensitive organs—for instance near the neck, spine, brain or lungs—where stray beams can be particularly damaging. Medical physicists and radiation oncologists from Mayo Clinic in Phoenix, Arizona in collaboration with MD Anderson researchers, recently published a series of papers describing improved planning and use of proton therapy. Writing in Medical Physics in January 2017, they showed that in the three clinical cases included in this study, their chance-constrained model was better at sparing organs at risk than the current method. The model also provided a flexible tool for users to balance between plan robustness and plan quality and was found to be much faster than the commercial solution. The research used the Stampede supercomputer at TACC to conduct computationally intensive studies of the hundreds of factors that go into maximizing the effectiveness of, and minimizing the risk and uncertainties involved in, these treatments. Proton therapy was first developed in the 1950s and came into mainstream in the 1990s. There are currently 12 proton therapy centers nation-wide and the number is growing. However, the cost of the proton beam devices—$200 million dollars, or 30 to 50 times more expensive than a traditional x-ray system—means they are still rare. They are applied only in cases that require extra precision and doctors must maximize their benefit when they are used. Mayo Clinic and MD Anderson operate the most advanced versions of these devices, which perform scanning beam proton therapy and are able to modulate the intensity of the beam. Wei Liu, one of the lead proton therapy researchers at Mayo Clinic, likens the process to 3-D printing, "painting the tumor layer by layer." However, this is accomplished at a distance, through a protocol that must be planned in advance. The specificity of the proton beam, which is its greatest advantage, means that it must be precisely calibrated and that discrepancies from the ideal must be considered. For instance, hospital staff situate patients on the operating surface of the device, and even placing a patient a few millimeters off-center can impact the success of the treatment. Moreover, every patient's body has a slightly different chemical composition, which can make the proton beam stop at a different position from what is intended. Even patients' breathing can throw off the location of the beam placement. "If a patient has a tumor close to the spinal cord and this level of uncertainty exists, then the proton beam can overdose and paralyze the patient," Liu said. The solution to these challenges is robust optimization, which uses mathematical techniques to generate a plan that can manage and mitigate the uncertainties and human errors that may arise. "Each time, we try to mathematically generate a good plan," he said. "There are many unknown variables. You can choose different beam angles or energy or intensity. There are 25,000 variables or more, so generating a plan that is robust to these mistakes and can still get the proper dose distribution to the tumor is a large-scale optimization problem." To solve these problems, Liu and his team use supercomputers at the Texas Advanced Computing Center. "It's very computationally expensive to generate a plan in a reasonable timeframe," he continued. "Without a supercomputer, we can do nothing." Liu has been working on developing the proton beam planning protocols for many years. Leading commercial companies have adopted methods similar to those that Liu and his collaborators developed as the basis for their radiation planning solutions. Recently, Liu and his collaborators extended their studies to include the uncertainties presented by breathing patients, which they call "4D robust optimization," since it takes into account the time component and not just spatial orientation. In the May 2016 issue of the International Journal of Radiation Oncology, they showed that compared to its 3D counterpart, 4D robust optimization for lung cancer treatment provided more robust target dose distribution and better target coverage, while still offering normal tissue protection. "We're trying to provide the patient with the most effective, most reliable, and most efficient proton therapy," Liu said. "Because it's so expensive, we have to do the best job to take advantage of this new technology." Like many forms of cancer therapy, clinicians know that proton therapy works, but precisely how it works is a bit of a mystery. The basic principle is not in question: proton ions collide with water molecules, which make up 70 percent of cells, triggering the release of electrons and free radicals that damage the DNA of cancerous cells. The proton ions also collide with the DNA directly, breaking bonds and crippling DNA's ability to replicate. Because of their high rate of division and reduced ability to repair damaged DNA, cancerous cells are much more vulnerable to DNA attacks than normal cells and are killed at a higher rate. Furthermore, a proton beam can be focused on a tumor area, thus causing maximum damage on cancerous cells and minimum damage on surrounding healthy cells. However, beyond this general microscopic picture, the mechanics of the process have been hard to determine. "As happens in cancer therapy, they know empirically that it works but they don't know why," said Jorge A. Morales, a professor of chemistry at Texas Tech University and a leading proponent of the computational analysis of proton therapy. "To do experiments with human subjects is dangerous, so the best way is through computer simulation." Morales has been running computer simulations of proton-cell chemical reactions using quantum dynamics models on TACC's Stampede supercomputer to investigate the fundamentals of the process. Computational experiments can mimic the dynamics of the proton-cell interactions without causing damage to a patient and can reveal what happens when the proton beam and cells collide from start to finish, with atomic-level accuracy. Quantum simulations are necessary because the electrons and atoms that are the basis for proton cancer therapy's effectiveness do not behave according to the laws of classical physics. Rather they are guided by the laws quantum mechanics which involve probabilities of location, speed and reactions' occurrences rather than to the precisely defined versions of those three variables. Morales' studies on Stampede, reported in PLOS One in March 2017, as well as in Molecular Physics, and Chemical Physics Letters (both 2014), have determined the basic byproducts of protons colliding with water within the cell, and with nucleotides and clusters of DNA bases - the basic units of DNA. The studies shed light on how the protons and their water radiolysis products damage DNA. The results of Morales' computational experiments match the limited data from physical chemistry experiments, leading to greater confidence in their ability to capture the quantum behavior in action. Though fundamental in nature, the insights and data that Morales' simulations produce help researchers understand proton cancer therapy at the microscale, and help modulate factors like dosage and beam direction. "The results are all very promising and we're excited to extend our research further," Morales said. "These simulations will bring about a unique way to understand and control proton cancer therapy that, at a very low cost, will help to drastically improve the treatment of cancer patients without risking human subjects." Explore further: What is cancer radiotherapy, and why do we need proton beam therapy? More information: Austin J. Privett et al, Exploring water radiolysis in proton cancer therapy: Time-dependent, non-adiabatic simulations of H+ + (H2O)1-6, PLOS ONE (2017). DOI: 10.1371/journal.pone.0174456

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