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Prabhu V.V.,Penn State College of Medicine | Prabhu V.V.,Molecular Therapeutics | Allen J.E.,Oncoceutics | Dicker D.T.,Penn State College of Medicine | And 3 more authors.
Cancer Research | Year: 2015

Self-renewing colorectal cancer stem/progenitor cells (CSC) contribute to tumor maintenance and resistance to therapy. Therapeutic targeting of CSCs could improve treatment response and prolong patient survival. ONC201/TIC10 is a first-in-class antitumor agent that induces TRAIL pathway-mediated cell death in cancer cells without observed toxicity. We have previously described that ONC201/TIC10 exposure leads to transcriptional induction of the TRAIL gene via transcription factor Foxo3a, which is activated by dual inactivation of Akt and ERK. The Akt and ERK pathways serve as important targets in CSCs. Foxo3a is a key mediator of Akt and ERK-mediated CSC regulation. We hypothesized that the potent antitumor effect of ONC201/TIC10 in colorectal cancer involves targeting CSCs and bulk tumor cells. ONC201/TIC10 depletes CD133+CD44+Aldefluor+ cells in vitro and in vivo. TIC10 significantly inhibits colonosphere formation of unsorted and sorted 5-fluorouracil-resistant CSCs. ONC201/TIC10 significantly reduces CSC-initiated xenograft tumor growth in mice and prevents the passage of these tumors. ONC201/TIC10 treatment also decreased xenograft tumor initiation and was superior to 5-fluorouracil treatment. Thus, ONC201/TIC10 inhibits CSC self-renewal in vitro and in vivo. ONC201/TIC10 inhibits Akt and ERK, consequently activating Foxo3a and significantly induces cell surface TRAIL and DR5 expression in both CSCs and non-CSCs. ONC201/TIC10-mediated anti-CSC effect is significantly blocked by the TRAIL sequestering antibody RIK-2. Overexpression of Akt, DR5 knockdown, and Foxo3a knockdown rescues ONC201/TIC10-mediated depletion of CD44+ cells and colonosphere inhibition. In conclusion, ONC201/TIC10 is a promising agent for colorectal cancer therapy that targets both non-CSCs and CSCs in an Akt-Foxo3a-TRAIL-dependent manner. © 2015 American Association for Cancer Research. Source


This disclosure relates, at least in part, to a method of treatment. In one embodiment, the method of treatment comprises administering to a subject in need of such treatment a first therapeutic agent including compound (1): or a pharmaceutically acceptable salt thereof in combination with a second therapeutic agent, wherein the first therapeutic agent and the second therapeutic agent are administered either simultaneously or sequentially.


News Article | October 6, 2015
Site: www.businesswire.com

HUMMELSTOWN, Pa.--(BUSINESS WIRE)--Oncoceutics announced the closing of a Series A financing round, led by Spring Mountain Capital, LP, with participation by additional private investors. The company will use the proceeds of the financing in conjunction with non-dilutive grant awards, public-private partnerships and academic alliances to continue the development of its lead drug compound, ONC201, a first-in-class, orally-active small molecule that penetrates the blood-brain barrier and exhibits strong anticancer activity in aggressive preclinical models of a number of different types of cancer, including lymphoma and glioblastoma multiforme (GBM). The company recently completed the first-in-man study of ONC201 at the Rutgers Cancer Institute of New Jersey and defined the recommended phase II dose (RP2D) that will be used in subsequent clinical studies. "Oncoceutics’ progress in the past year since our initial investment is impressive,” said Raymond Wong, Managing Director and Head of Private Equity at SMC, and member of the Oncoceutics Board of Directors. “The company successfully completed a phase I study and is transitioning into several phase II trials, extended its IP position through the issuance of additional patents, and determined that ONC201 engages a clinically-validated signaling pathway by a novel trigger that is clearly distinct from available therapies. We are excited about deepening our partnership with Oncoceutics by leading this Series A financing round and look forward to bringing this potentially breakthrough first-in-class cancer drug to patients.” "We are very grateful for support from Spring Mountain Capital and our other private investors,” said Lee Schalop, MD, Chief Business Officer and co-founder of Oncoceutics. “They have elected to significantly increase their investment in Oncoceutics based on our substantial progress since the closing of our Series Seed financing round a year ago. We’ll be able to complete our Phase II program in both solid tumors and hematologic malignancies using the funds from this financing round along with additional resources available to our company from alliances and grant awards, including a recent award from National Cancer Institute." Wolfgang Oster, MD PhD, CEO, Chairman and co-founder of Oncoceutics, added, “This funding round marks important progress for Oncoceutics that sets the stage to definitively prove the clinical value of its lead drug ONC201 and its analogs in cancer therapy. It demonstrates the mutual confidence our leadership team, supporters and collaborators have in the merit of our products.” "The promise that ONC201 holds and that may be extended through the portfolio of analogs under development could provide a significant benefit to several major cancer populations,” commented Keith Flaherty, MD, Director of Developmental Therapeutics, Cancer Center, Massachusetts General Hospital, and a member of Oncoceutics’ Scientific Advisory Board. “It is remarkable that this compound demonstrates potent anti-cancer effects in preclinical models, yet exhibits a benign safety profile as identified in the first human phase I study with ONC201.” Oncoceutics, Inc. is a clinical-stage drug discovery and development company targeting the most potent suppressor pathways in human cancer. The first lead compound to result from this program is ONC201, a small molecule drug with a unique mechanism of action that causes significant anti-tumor activity in a variety of types of human cancer. The company is currently enrolling patients in clinical trials of ONC201 that began in January 2015, following acceptance by the U.S. Food and Drug Administration of Oncoceutics’ Investigational New Drug (IND) application for ONC201 in 2014. Oncoceutics and collaborative organizations have received grants over the last two years from the National Institutes of Health, the Pennsylvania Department of Health and The Musella Foundation. The company has also leveraged additional funding for multiple Phase I/II clinical trials from academic medical research partners. Founded in 2001 and located in New York City, Spring Mountain Capital, LP (“SMC”) is a private investment management firm that focuses on alternative asset investing. SMC’s Private Equity Group provides expansion stage capital to lower middle market companies that are capitalizing on breakthrough innovations, paradigm shifts or fundamental market or behavioral changes. The Private Equity Group at SMC focuses on the two sectors of the U.S. economy with the most change and highest growth potential: technology-enabled and healthcare businesses. Within these high-growth areas, it seeks to make value investments by capitalizing on market dislocations, information asymmetry, illiquidity and complexity. For further information, please visit http://www.springmountaincapital.com/. To the extent that statements in this press release are not strictly historical, including statements as to revenue projections, business strategy, outlook, objectives, future milestones, plans, intentions, goals, future financial conditions, future collaboration agreements, the success of the Company's development, events conditioned on stockholder or other approval, or otherwise as to future events, such statements are forward-looking, and are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The forward-looking statements contained in this release are subject to certain risks and uncertainties that could cause actual results to differ materially from the statements made.


News Article | March 31, 2015
Site: oncoceutics.com

Hummelstown, PA (March 31, 2015) – Oncoceutics, Inc. announced that the company was awarded a Small Business Innovation Research (SBIR) grant by the National Cancer Institute (NCI). The combined Phase I/II Fast Track grant will support a clinical trial in ONC201 in advanced brain cancer, furthering the clinical development of the company’s lead compound. ONC201 is a first-in-class small molecule with consistent antitumor activity in difficult-to-treat cancers. Preclinical research has demonstrated that ONC201 penetrates the blood-brain barrier and is robustly effective in models of glioblastoma multiforme (GBM), the most common and aggressive form of human brain cancer with very limited treatment options. The Fast-Track SBIR grant is awarded in two parts to support multiple aspects of ONC201 clinical development over a two and a half year period. The first phase of the grant will support the development of formulation and GMP-manufacturing of ONC201. The second phase of the grant will support the evaluation of ONC201 in patients with advanced GBM in a Phase II clinical trial that will be conducted by Dr. Andrew Chi at Massachusetts General Hospital and the Dana-Farber / Harvard Cancer Center. “ONC201 exhibits a compelling monoagent efficacy profile against several cancers with a particularly strong efficacy profile against GBM,” said Joshua Allen, PhD, VP Development, of Oncoceutics. “Multiple facets of the chemical and biological profile of ONC201 point to GBM as an ideal lead indication for this exciting first-in-class drug.” “We greatly appreciate the NCI’s support and endorsement as we work with preeminent leaders in GBM research to evaluate the therapeutic potential of ONC201 for this indication, which is in dire need of meaningful treatment options,” commented Martin Stogniew, PhD, Chief Development Officer of Oncoceutics. “The chemical attributes of ONC201 are ideally suited to traverse the blood brain barrier. That dovetails with the powerful effect of the compound that we observed in preclinical testing of ONC201 in GBM.” About Oncoceutics Oncoceutics, Inc. is a drug discovery and development company targeting the most potent suppressor pathways in human cancer. The first lead compound to result from this program is ONC201, a small molecule drug with a unique mechanism of action that causes significant anti-tumor activity in a variety of types of human cancer. The Company is currently enrolling patients in clinical trials of ONC201, which began in January 2015, following acceptance by the U.S. Food and Drug Administration of the Company’s Investigational New Drug (IND) application for ONC201 in 2014. Oncoceutics and collaborative groups have received approximately $5 million in grants over the last two years from the National Institutes of Health, the Pennsylvania Department of Health, and The Musella Foundation, and the company has leveraged additional funding from academic medical research partners that support multiple Phase I/II clinical trials. Visit Oncoceutics or contact Rohinton Tarapore for more information. Safe Harbor Forward-Looking Statements To the extent that statements in this press release are not strictly historical, including statements as to revenue projections, business strategy, outlook, objectives, future milestones, plans, intentions, goals, future financial conditions, future collaboration agreements, the success of the Company’s development, events conditioned on stockholder or other approval, or otherwise as to future events, such statements are forward-looking, and are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The forward-looking statements contained in this release are subject to certain risks and uncertainties that could cause actual results to differ materially from the statements made.


Hummelstown, PA (February 25, 2015) – Oncoceutics, Inc. announced the publication of a second article in the journal Cancer Research. This new research article, which follows an article published last week on biomarkers and combination therapies, describes the ability of ONC201 to target colorectal cancer stem cells. These findings suggest that ONC201 could improve treatment response and ultimately prolong patient survival because colorectal cancer stem cells play a significant role in tumor maintenance and disease relapse. Furthermore, cancer stem cells are not responsive to most chemotherapies and so new therapies that can deplete these special cells are needed to result in complete cures. “The ability to target cancer stem cells, which is demonstrated for ONC201 in these studies, is an important property of any oncology therapeutic,” said Joshua Allen, PhD, VP-Development of Oncoceutics and co-author of the article. “Depletion of cancer stem cells is expected to lead to more durable responses and fewer disease relapses in the clinic.” “ONC201-induced depletion of multiple CSC markers in colorectal cancer cell lines and mouse xenograft tumors increases the potential of ONC201 to prolong disease-free survival in the clinic,” commented Wafik El-Deiry, MD, PhD, FACP, Professor, Co-Program Leader of Molecular Therapeutics, Deputy Cancer Center Director for Translational Research at Fox Chase Cancer Center, Scientific Founder of Oncoceutics and senior author of the article. “This is yet another endorsement of the robust anti-tumor activity of ONC201 that addresses critical shortcomings of our current chemotherapies and targeted therapies.” These articles are part of Oncoceutics’ effort to publish in leading scientific journals results that demonstrate the excellent safety profile and promising efficacy profile of ONC201. The link to the journal article is available here About Fox Chase Cancer Center Fox Chase Cancer Center, part of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet status for excellence four consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. For more information, visit Fox Chase’s web site at www.foxchase.org or call 1-888-FOX CHASE or (1-888-369-2427). About Oncoceutics Oncoceutics, Inc. is a drug discovery and development company targeting the most potent suppressor pathways in human cancer. The first lead compound to result from this program is ONC201, a small molecule drug with a unique mechanism of action that causes significant anti-tumor activity in a variety of types of human cancer. The Company is currently enrolling patients in clinical trials of ONC201, which began in January 2015, following acceptance by the U.S. Food and Drug Administration of the Company’s Investigational New Drug (IND) application for ONC201 in 2014. Oncoceutics and collaborative groups have received approximately $5 million in grants over the last two years from the National Institutes of Health, the Pennsylvania Department of Health, and The Musella Foundation, and the company has leveraged additional funding from academic medical research partners that support multiple Phase I/II clinical trials. Visit Oncoceutics or contact Rohinton Tarapore for more information. Safe Harbor Forward-Looking Statements To the extent that statements in this press release are not strictly historical, including statements as to revenue projections, business strategy, outlook, objectives, future milestones, plans, intentions, goals, future financial conditions, future collaboration agreements, the success of the Company’s development, events conditioned on stockholder or other approval, or otherwise as to future events, such statements are forward-looking, and are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The forward-looking statements contained in this release are subject to certain risks and uncertainties that could cause actual results to differ materially from the statements made.

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