Product Development Research Portfolio
CPRIT's Product Development Research Program funds projects at Texas-based companies developing novel products or services intended to benefit cancer patients. Groundbreaking science is most valuable when it is translated into cancer drugs, diagnostics, and therapies available to Texans. Product development activities translate a novel laboratory finding into a safe and reliable product available to treat cancer patients.
The mission of AERase, Inc. a recently established biopharmaceutical company located in Austin, TX, is to develop novel cancer treatments by exploiting the unique metabolism of cancer cells. Cancer cells, unlike normal cells, lack the ability to make certain amino acids (AA), the building blocks of proteins. Efforts have been made to exploit this vulnerability, seen in many different cancers, by depriving tumors of key AA using naturally occurring compounds. The use of these compounds has been complicated by poor activity, (human-derived drugs) and by the development of immune reactions, (microbe-derived drugs); nonetheless, tumor shrinkage has been seen in several different cancer types, such as melanoma, and liver cancer.
AERase, Inc. has developed a variation on a human molecule that promises to be effective in the depletion of a key AA an to be unlikely to cause an immune reaction. Before this compound can be used as a cancer treatment, it must be manufactured and tested in animals and humans. During drug development, AERase, Inc. will do cell and animal studies at contract laboratories in TX. The human trials proposed will include clinical sites in TX, and use contract research and other providers in TX. To guide product development, the company has recruited key personnel to TX from companies in other states, and the company expects to grow from its current staff of 4 to a permanent staff of 10, based in TX, to support development of this novel cancer treatment.
This proposal will develop a “biobetter” Rituxan - a monoclonal antibody therapy that has dramatically changed the outlook for patients with Non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. Our biobetter, produced in hydroponic plants, will have enhanced ability to kill cancer cells, but impose no additional risks or side effects to patients. Because of our unique plant-based biomanufacturing platform, the biobetter will be substantially less expensive, reducing costs by at least one third.
In the first two years of the project, we will develop the biobetter and perform all testing and preclinical evaluation required by the FDA. In the third year, we will perform the initial clinical trial in humans with cancer. Caliber Biotherapeutics is uniquely positioned to develop this new generation of cancer cures. Caliber will utilize its expert scientists, physicians, and pharmaceutical production facility that have been brought together by the US government as a core asset for the national response to pandemic influenza.
Caliber’s facility is the largest known plant-made pharmaceutical facility in the world; it will have the ability to produce approximately 20,000 doses of biobetter Rituxan each month, at substantially reduced cost. At the end of this project Caliber will be positioned to develop biobetter forms of other cancer therapies, such as Herceptin and Avastin, and will be one of the largest economic engines fueling the economy and job growth within Texas.
Cell Medica is a leader in the development of cellular immunotherapy for cancer applications. Cell Medica is applying for a Relocation Award to achieve FDA approval for two cell therapies: Cytorex EBV for the treatment of cancers associated with the Epstein Barr virus (EBV) and Cytovir CMV for cytomegalovirus (CMV) infections in patients following bone marrow transplant.
Support for Cytorex EBV fits with CPRIT’s mission to foster new therapies for cancer treatment. 1) Cellular immunotherapies provide powerful tools for the treatment of cancer and Cytorex EBV is a breakthrough for patients with EBV-associated cancers. 2) The safety of Cytorex EBV will improve long-term outcomes allowing treatment of older patients not suitable for standard regimes. 3) Cell Medica will relocate its headquarters to Texas, creating 20 jobs and also establish a manufacturing and distribution facility. 4) Cell Medica is developing Cytorex EBV with Baylor College of Medicine; a successful collaboration will enhance the research capability of this institution. 5) Clinical trials will include large centers in Texas and maintain these institutions at the leading edge of cancer research.
Similarly, the development of Cytovir CMV provides the opportunity for CPRIT to support a new approach to treating viral infections in cancer patients following bone marrow transplant. Cytovir CMV is commercially available in Europe and will likely require an additional clinical trial in the US for FDA approval.
Curtana Pharmaceuticals is developing the first truly targeted small molecule drug for the treatment of glioblastoma (GBM), diffuse intrinsic pontine glioma (DIPG), and other brain cancers. GBM is the most common and deadliest of the malignant primary brain tumors in adults. DIPG, which occurs in the brainstem, is one of the most deadly pediatric brain tumors.
Curtana is applying for a New Company Product Development Award to bring a novel, first-in-class therapy from the laboratory to clinical trials in patients within 3 years. Support for Curtana’s drug development program fits with CPRIT’s mission to expedite innovation in the area of new product development and to attract companies to Texas that will create new jobs. Specifically, Curtana will relocate to Texas, where the company will operate its research facility, create 12 high-quality life science jobs, and support numerous Texas-based businesses.
In line with CPRIT’s strategic focus, the Award will allow Curtana to 1) bridge the translational research gap, 2) address the unmet medical needs of patients with devastating orphan diseases, and 3) bring a breakthrough new drug to a highly under-served pediatric patient population. If successful, Curtana would deliver to patients the first drug that both kills the cancer cells responsible for tumor progression and makes other therapies, such as chemotherapy and radiation, much more effective, thereby significantly reducing patients’ suffering and prolonging patients’ lives.
DNAtrix, Inc. is a Texas-based company developing modified viruses for the treatment of the most aggressive type of brain cancer called glioblastoma. Scientists have modified the common cold virus called adenovirus in 2 specific ways so that it can recognize and kill cancer cells very effectively without harming normal brain. The first product of its kind, called Delta-24-RGD, has just completed its first big test in more than 35 patients with GB at the MD Anderson Cancer Center in Houston.
Many patients with GB who participated had a remarkable response to the therapy, with evidence of tumor killing and improved survival. Perhaps equally important, there were no safety concerns or side-effects such as those that can arise from chemotherapy. If Delta-24-RGD continues to produce benefits for patients in additional clinical trials, the FDA will support its use for treating this devastating disease. This therapy could have a major impact for patient care in Texas and around the world as there are currently very few therapeutic options for patients if the tumor recurs.
ESSA Pharma Inc. (ESSA) intends to treat castrate-resistant prostate cancer (CRPC). Growth of prostate cancer cells is driven by male hormones. ESSA’s drugs block the hormone-fueled growth of prostate cancer tumors by an entirely novel mechanism. Specifically, our drugs covalently block the N-terminus of the androgen receptor, preventing activation of the receptor by any means. Thus our drugs may overcome all of the known mechanisms for hormone-therapy resistance.
Our goal is that all men with recurrent prostate cancer will enjoy more months or even years of progression-free lifespan than current therapy offers. ESSA is currently in the clinical candidate selection stage, and expects to commence clinical trials in 2013. Our efforts will contribute meaningfully to the CPRIT mission by:
• Improving the health of all Texans: - if therapy is successful, many Texans will be directly benefited through increased progression-free lifespan - our efforts can increase prostate cancer awareness.
• Bringing more resources to Texas: - the IP related to our program will be located in Texas.
• Supplementing CPRIT resources: - relocated ESSA personnel will bring significant experience to Texas; - expect to hire additional personnel who will be Texas-based.
• Ensuring high awareness of CPRIT: - prostate cancer is a very high-profile medical arena, and will attract significant media coverage.
The development of cancer drugs in the future mandates innovation. Central to that innovation in Texas is the ability to advance drug discovery to clinical trial scale up. Texas’ preeminent cancer research institutes and biotech companies are often stymied in development of their discoveries due to the inability to scale up the drug for clinical trials and commercial launch. While renowned for its discoveries, Texas offers little manufacturing capability.
In 2009, the State, through the Emerging Technology Fund, sought to fill this need by funding The Texas A&M University System to construct The National Center for Therapeutics Manufacturing (NCTM), a multi-product, flexible-by-design drug manufacturing facility for Phase I and II clinical trials. In May 2010, MD Anderson Cancer Center and the System signed a collaboration agreement which will, in part, lead to the Phase I and II manufacturing of cancer drugs at the NCTM.
Even with promising cancer drugs from the likes of MD Anderson, an often over-looked step in the drug advancement timeline is process development; the recipe for making the drug in larger quantities. This application proposes the formation of “The Texas Cancer Therapeutics Process Development Lab” at the NCTM which would be a resource available for all emerging cancer drug discoveries. Using innovative and unique manufacturing technologies, the operation of the PD Lab would be leveraged by collaboration with the College of Engineering at Texas A&M.
Immatics GmbH (Germany) has been successfully developing off-the-shelf cancer immunotherapies for the past decade. Immatics US Inc. (Houston, Texas), a newly created subsidiary of Immatics GmbH, is a first-in-class biopharmaceutical company dedicated to the development of novel personalized cancer immunotherapies including (1) adoptive cellular therapy (ACT) and (2) actively personalized vaccines (APVACs). Both types of immunotherapies activate the patient’s immune cells (so-called T cells) either outside or inside the body, respectively. Both types are tailored to characteristics of the individual tumor tissue, thus maximizing chances of successful therapy for the individual patient.
T-cell based immunotherapy is emerging as a standard of care for patients suffering from certain skin and blood cancers based in part on work at MD Anderson Cancer Center (MDACC). However, the field lacks suitable and safe targets to translate these initial successes to other cancer types. Immatics will bring to Texas its globally leading antigen discovery platform, XPRESIDENT®, enabling rapid discovery of new, suitable and safe cancer targets for immunotherapy. A critical mass of leading immunotherapy experts and the unique clinical infrastructure available in Houston will strongly accelerate Immatics US Inc.’s mission to build a sustainable, world-class cancer immunotherapy company in Texas and translate the value of novel cancer targets into better and longer lives for cancer patients.
Beta Cat Pharmaceuticals specializes in developing novel cancer drugs that attack molecular targets never before addressed clinically. Our first drug, BC2059, inhibits the beta catenin pathway and represents a major breakthrough. Many cancers have abnormal activation of this pathway but despite much industry effort, no drugs have been developed previously that address it. Beta Cat has succeeded by attacking a novel target in the pathway. BC2059 has very low toxicity but is highly effective at killing tumor cells.
We first will test the drug in colorectal carcinoma and in myelodysplastic syndrome, an orphan drug indication. We also have a promising second generation program that we hope to move from intravenous to oral administration and further enhance the pharmacokinetics of attacking the target, broadening the potential applications for our therapies. In addition, we will continue to work to develop sustained release formulations for our lead molecule for patient convenience.
We plan to locate in Texas to develop our innovative drug, our second generation compounds, as well as add and discover drugs targeting additional pathways. In addition to our internal research programs, we also plan to collaborate with Texas academic centers to identify compounds that broaden and extend our pipeline, in order to develop into a pharmaceutical company that could have a large economic impact in Texas. Beta Cat seeks to transition from a virtual to a “bricks and mortar” company.
Medicenna Therapeutics Inc. is an immuno-oncology company led by experienced entrepreneurs with proven track records win cancer drug development. Medicenna is developing treatments for brain cancers that affect both adults and children, including glioblastoma multiforme (GBM). GBM tumors are the most common form of adult brain cancer, with 11,000 new cases annually in US. They are the second most common cause of brain cancer deaths. These cancers make a protein on the cancer cells' surface called the IL-4 receptor (IL-4R). Most normal cells have no IL-4R.
Medicenna has developed an anti-cancer agent, MDNA55, which is administered directly into tumors. MDNA55 targets and kills brain cancer cells, while not harming healthy cells. MDNA55 has the potential to save lives and extend survival for brain cancer patients, especially among the 60% of patients whose tumors recur. MDNA55 has shown promising clinical results among 72 adult GBM patients. The FDA has already granted MDNA55 Orphan Drug and Fast Track Designations.
Medicenna's goal is to conduct two clinical trials for GBM patients to test MNDA55's safety, effectiveness and dosage. Texas-based drug manufacturing, clinical research organizations and clinics will support the trials in Texas and across the U.S. Medicenna' drug development platform will expand Texas' cancer research capacity benefiting patients and their families, while expanding Texas' research infrastructure and creating new high-quality jobs.
Mirna Therapeutics, Inc., is a Texas-based company developing a new class of cancer treatments that are based on naturally occurring tumor suppressor microRNAs. In April 2013, Mirna’s lead product, a liposomal mimic of miR-34 (MRX34), entered a Phase I clinical trial for liver cancer. A key benefit of these therapies is the ability to simultaneously block multiple cancer processes which is important for the successful treatment of cancer that frequently originates from multiple mutations and thrives on multiple pathways. The ability to interfere with multiple cancer pathways is a new paradigm in cancer therapy that has the potential to create more effective cancer drugs.
Because most cancer drugs are more effective in drug combinations, we propose here the preclinical and clinical development of one or more MRX34 combination therapies to maximize efficacy. Our primary focus will be the MRX34+erlotinib (Tarceva®) combination in non-small cell lung cancer (NSCLC), the number one cause of cancer deaths in Texas. Our preclinical data show strong synergy between the miR-34 therapy and erlotinib in erlotinib-resistant cancer cells. Because erlotinib alone, an FDA-approved drug to treat NSCLC, only benefits a limited fraction of patients, combining it with MRX34 is likely to maximize efficacy and broaden the base of patients that can be treated with this drug. Mirna will use Texas based resources and leverage relationships established with the ongoing clinical development of MRX34.
Radiation therapy remains an essential component of treatment for most cancers, including primary brain tumors. Theoretically, any tumor can be controlled if a sufficient dose of radiation is delivered. The main limiting factor is the potential for damage to the surrounding normal body. This is especially true with brain tumors, as damage to the surrounding normal brain can result in profound side effects.
We have developed a method of loading radiation molecules into fatty particles about one thousandth the size of a cell, termed nanoliposomes or RNL. This can be injected into a tumor where it is essentially ‘ingested’ by the tumor cells, and the tumor is irradiated from the inside out. Due to the limited distance the particles can travel, the surrounding normal brain receives less radiation exposure and allows treatment with significantly higher doses.
Experiments in rodents showed that these nanoliposomes could safely deliver over 30x the amount of radiation that is delivered by standard techniques. Tumors were largely eliminated without evidence of significant injury. Studies in dogs showed that no toxicity was observed at the highest levels tested.
The FDA has provided permission to begin the clinical trial and patients will be treated soon. Financial support is needed to fund the upcoming clinical trial, develop the supporting technology, and establish infrastructure that is critical to the development of 186RNL. We believe RNL will have a significant impact on cancer.
Surgical resection and radiotherapy are used frequently in the treatment of prostate, cervical, and rectal cancers. While they can be life-saving therapies, these procedures often burden cancer survivors with secondary conditions such as overactive bladder (OAB). For some cancer patients and survivors, OAB symptoms are an understood outcome of life-saving cancer therapy, while others may view the risk of urinary dysfunction as a reason to forego or substitute potentially inferior forms of treatment. There is a pressing need for treating OAB in cancer patients and survivors; however, existing treatment protocols may not be suitable for patients developing symptoms secondary to cancer or treatments directed at these malignancies.
Rosellini Scientific, a medical technology company headquartered in Dallas, is developing a small, implantable neurostimulation device to restore bladder function and improve quality of life for patients suffering from OAB as a result of their cancer therapy. The nUro Wireless Neurostimulation system combines the latest in wireless implantable technology with clinically proven efficacy of neurostimulation to offer flexible, convenient, and cost-effective treatment.
Rosellini Scientific will foster this technology in collaboration with Dr. Gary Lemack from UT Southwestern Medical Center and through the UT-Dallas incubator program. The current proposal will culminate in clinical data used to support regulatory approval of the nUro therapy.
OncoNano Medicine, a Dallas-based University of Texas Southwestern Medical Center (UTSWMC) spinout, is developing nanotechnology-enabled fluorescent probes to help a cancer surgeon excise tumors. Surgery is a major mode of cancer treatment with over 550,000 cancer resection procedures per year in the US.
A major challenge in these cancer surgeries is in differentiating tumors from healthy tissue. Incomplete tumor removal is a major concern in cancer surgery as the remaining tumor could regrow and metastasize to other organs. Conversely, excess and critical healthy tissue removal can have adverse effects such as the ability to swallow in head and neck surgery, or have severe cosmetic scarring effects such as in breast cancer surgery.
The initial markets targeted by OncoNano include breast lumpectomies, Mohs surgery, melanoma surgeries and head and neck cancer surgeries. OncoNano’s origin and heritage have strong ties to Texas. OncoNano is headquartered in Dallas and will operate in UTSWMC’s incubator. OncoNano will contribute to the cancer ecosystem in Texas by creating high quality cancer research jobs, recruiting talent into the state, and funding collaborations and clinical trials with leading Texas oncology hospitals including UTSWMC and MD Anderson Cancer Centers.