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.
Allterum Therapeutics, a Houston, TX based company, is developing a new drug for the treatment of pediatric T-cell acute lymphoblastic leukemia – a common form of childhood cancer. Although current treatments are effective for a majority of children with this disease, approximately 20% of patients experience a recurrence of the disease. Unfortunately, no drugs exist to effectively help patients who experience this relapse.
Our drug is an antibody which is able to much more specifically target and kill cancer cells without the broader side-effects typically observed with conventional chemotherapies. Therefore, Allterum Therapeutics is addressing a major unmet medical need, as our drug is expected to be effective not only in children with recurring leukemia, but could also be used to aid conventional chemotherapies when patients are first treated. Our technology fits within CPRIT’s mission as we are developing a new agent for the treatment of cancer. Furthermore, our research will help further the scientific community’s understanding of pediatric leukemias and the ability of targeted therapies to aid conventional chemotherapies to elicit a better patient response, and to hopefully result in a better prognosis for patients and their families.
Colorectal cancer is the third most commonly diagnosed cancer and the second most common cause of cancer death in the United States, while gastric cancer is the most common malignancy in the world. Each year, over 26 million individuals undergo screening colonoscopies to identify early stage colorectal cancer. However, once a suspicious lesion is found, physicians are limited in their ability to treat, and cancer surgery anywhere in the GI tract will leave a patient with a lifetime of digestive complications.
Apollo has developed a set of flexible surgical devices, compatible with existing flexible endoscopes, which enable a revolutionary new procedure to remove early stage lesions from the colon, esophagus, and stomach. These tools were developed in a unique collaboration with the Mayo Clinic, University of Texas Medical Branch, MUSC, and Johns Hopkins University. These technologies and their patents were licensed from these prestigious Universities and brought to Texas.
Apollo’s device approach, named SuMO for Submucosal Operation, is a conceptual leap that takes advantage of the layered structure of the GI tract tissue. Unique devices create a space inside the GI tract wall, providing access to additional flexible surgical tools to safely and quickly remove the suspicious tissue. This allows multiple stages and sizes of lesions to be treated endoscopically, allowing patients to avoid debilitating surgery.
Ruga Corporation is a late preclinical stage pharmaceutical company developing Ruga-S6, an engineered decoy soluble AXL receptor, for targeted therapy against acute myeloid lymphoma (AML) and certain solid tumor indications including ovarian, pancreatic, and breast cancer.
AML is a hematologic cancer affecting both pediatric and adult patients. While the pediatric population is small (~800), over 18,000 adults are diagnosed in the US annually, with the majority of these patients over 65. Based on 1996-2002 SEER statistics, the 5-year survival rate for adults older than 65 diagnosed with AML was a mere 4.3%. In the past 20 years, there has been little improvement in overall survival for AML patients, particularly those older and with unfavorable cytogenetics like FLT3-ITD mutations (~20-25% of AML patients). Older AML patients are more likely to experience treatment-related toxicity and less likely to achieve complete remission and remain relapse-free. As such, an efficacious drug without significant risk of toxicity is a major unmet clinical need in this underserved population.
Research indicates that activation of the GAS6-AXL signaling pathway acts as a “survival switch” required for adaptation of tumors for increased in vivo tumor growth, survival, and metastasis as well as development of resistance to commonly-used chemotherapeutic agents. Ruga-S6 is a novel Fc-fusion protein that potently neutralizes GAS6 and effectively “turns off” AXL signaling in tumor cells. It shows >100 fold tighter affinity for GAS6 and provides significantly higher specificity for the AXL/GAS6 pathway that other kinase inhibitors (e.g. small molecules and antibodies) cannot match. Ruga-S6’s neutralization of GAS6 and inhibition of AXL-GAS6 pathway offers the potential for a novel, targeted therapeutic approach that may be used alone with low toxicity or in combination with other standard of care anti-cancer agents.
Ruga-S6 has the potential to impact the current standard of care for FLT3-ITD(+) AML by inhibiting activation of AXL/GAS6 signaling, which is correlated with increased clinical rates of metastasis, progression, recurrence, and overall poorer survival in AML and other cancers. It offers a more targeted therapy, with minimal systemic toxicity and less severe side effects than current AML chemotherapeutics. Ruga-S6 could also be delivered as a combination therapy for AML with approved chemotherapeutic agents such as cytarabine.
While AML is planned as the initial target indication for Ruga-S6, Ruga has built a compelling rationale to pursue certain solid tumors in the clinic such as ovarian, renal, breast, lung, and pancreatic cancers. In solid tumors, AXL/GAS6 inhibition has shown to have dual anti-cancer effects, including direct anti-tumor effects on survival, invasion, and chemo-resistance, and also indirect anti-tumor effects via stimulating innate anti-cancer immunity, given GAS6 role as an innate immunity check point.
To date, Ruga has conducted several preclinical proof-of-principle studies and established compelling data demonstrating Ruga-S6’s efficacy and tolerability in multiple in vitro studies and in vivo models of cancer. In preclinical models of AML, including patient-derived leukemic cells from FLT3-ITD(+) patients, treatment with Ruga-S6 has been associated with remarkable anti-tumor effects coupled with exceptional tolerability, making Ruga-S6 a potentially ideal drug for AML patients. In preclinical models of advanced, drug resistant ovarian cancer, the treatment with Ruga-S6 led to greater than 95% of animals becoming disease free without any tolerability issues. Preclinical studies in breast, lung, renal and pancreatic cancer models generated equally compelling data.
Furthermore, Ruga has developed a proprietary companion diagnostic assay for the measurement of free and total GAS-6 levels, which provides for the identification of patients that could preferentially benefit from therapy with Ruga-S6. In order to advance to commercial development, Ruga has developed a comprehensive plan to complete the manufacturing, preclinical, and clinical development necessary to seek approval of Ruga-S6 with the US Food and Drug Administration (FDA). Preclinical toxicology, immunogenicity, and biomarker studies will position Ruga for filing for an Investigational New Drug (IND) application by Q1 2017. Ruga will then commence Phase 1/2 clinical studies, which will include parallel Phase 1a multiple ascending dose studies for enriched AML and specific solid tumor indications. Lastly, phase 1b/2a studies will be performed as a multiple dose study in selected patient populations expanded from completion of the Phase 1a studies.
In total, these studies are anticipated to provide sufficient evidence for Ruga-S6 to pursue both FDA Orphan Drug and Breakthrough designation, and further, to validate the use of Ruga’s companion diagnostic for stratification of patients for targeted therapy with Ruga-S6.
Ares Immunotherapy Inc., an early-stage biopharma company founded in 2019, is located in Cartersville, Georgia with plans to move to Houston, Texas. In this SEED application, Ares is preparing for a first -in-human clinical trial in mesothelioma, a rare and deadly cancer most frequently associated with exposure to asbestos in the past. Ares' lead candidate, called Ares meso-CAR, is a mesothelin-specific chimeric antigen receptor (CAR) T cell therapy. CAR T-cell therapy is a form of immunotherapy that uses specially altered T cells - a part of the immune system - to fight cancer. In research studies, The Ares meso-CAR has been shown to be highly effective against solid tumors in cell studies and in mouse studies, where it has the ability to completely heal even large established tumors. Ares meso-CAR T also shows promise as a therapy for cancers that contain mesothelin including pancreas, lung and ovarian, as well as others. If Ares is successful in its clinical goals, it has the potential to make a major impact for patients with mesothelioma and perhaps other cancers. In moving to Texas as part of the CPRIT programs, Ares will be creating employment opportunities and expanding the Texas biotech ecosystem.
We propose to establish targeted next generation sequencing (NGS) assays that enable accurate, sensitive, and cost-effective detection of “actionable” mutations in clinically relevant, cancer-related genes. The existing armament of anticancer drugs includes ~100 approved therapies, and an additional 800 drugs in development. The NGS assays will interrogate mutations in key cancer pathways relevant to these medicines, and both improve the diagnostic yield of “real world” clinical biopsies and help steer drugs to those patients that are most likely to benefit. The funding for this proposal will help bridge the gap between the identified clinical utility of mutations and the need for clinical tests that are manufactured under best practices and that can be validated with confirmatory tests. The availability of robust, reliable, rapid and scalable assays will have a significant impact on clinical research and on improving treatment selection for patients with cancer.
Many patients with leukemia are cured by a stem cell transplant after intense chemotherapy. However, cancer relapse, infection, and graft versus host (GvHD) are common in the months after a transplant. The problem is that harmful T cells in the transplant cannot be separated from essential, helpful T cells that kill residual cancer and help stem cells become established. Harmful T cells attack the skin, intestines, and the liver, which they see as foreign. For these reasons, many cancer patients without a matched donor cannot receive a transplant, and those that do risk severe, often fatal complications.
Bellicum Pharmaceuticals has developed a revolutionary new T-cell therapy (BPX-501) to solve the critical problems associated with non-matched transplants. Bellicum inserts a “safety switch” into donor T-cells, which allows the physician to kill harmful T cells while preserving those helpful T-cells that protect from infection, assist the new stem cells, and kill residual cancer.
This project will test a new combination therapy consisting of BPX-501 along with donor stem cells that have been specially prepared to maintain certain beneficial cells that can work together with BPX-501. Bellicum will treat adults and children with a very serious form of leukemia called AML, who have failed conventional therapy and have little chance for cure. The results of this trial could revolutionize cancer treatment and provide hope to many patients with no current alternatives.
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.
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.
Formation Biologics is developing an innovative pipeline of anti-cancer biotherapeutics called antibody-drug conjugates (ADCs). These next-generation treatments are designed to kill cancer cells while sparing healthy cells. Formation’s lead ADC product, AVID100, has been extensively studied and has demonstrated excellent safety and efficacy. It efficiently kills cells from many deadly cancer types including breast, ovarian, head and neck, glioma, pancreatic, gastric and lung. AVID100 is now in early clinical trials in San Antonio exhibiting a good safety profile.
Formation seeks CPRIT funding to expand testing of AVID100 in clinical trials allowing us to evaluate the anti-cancer activity of AVID100 in patients selected based on a test that predicts their likelihood of responding. It is expected that AVID100 will continue to exhibit superior efficacy relative to currently available drugs and could help address significant unmet cancer needs.
To achieve this goal, Formation will grow its operations in Austin, creating high-quality jobs and training staff in drug development and clinical trial operations. Formation is committed to the State of Texas and will ensure that funds are spent in Texas wherever possible. Cancer patients in Texas will have the potential to be among the first to benefit from treatment with AVID100.
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.
Hummingbird Bioscience, a highly innovative biotech company, with facilities in Singapore and South San Francisco, is applying for a CPRIT Relocation grant to move to Texas. The company has developed a new cancer therapy, HMBD-002-V4, for patients who are resistant to cancer immuno-oncology (IO) drugs.
FDA-approved IO drugs that harness the power of the body’s immune system to fight cancer have made rapid advances in treating patients with cancers who previously had very few options. This includes patients with melanoma, non-small cell lung cancer, kidney and bladder cancer and several others. However, as many as 70% of these patients develop resistance and their cancer progresses, and they are again without options.
HMBD-002-V4 is designed to treat one of the most important causes of resistance – a branch of the immune system called MDSC cells that can switch-off the cancer killing cells that were turned on by the IO drugs. In preclinical studies, HMBD-002-V4 showed the ability to reverse resistance to IO therapies and completely cure the cancer in some cases.
This CPRIT project aims to bring this exciting new cancer therapy to patients. The team will manufacture clinical-grade material and apply to the FDA for an Investigational New Drug application that will allow HMBD-002-V4 to begin a Phase IA/B study in Texas to confirm the drug is safe and start looking for responses among patients who have become resistant to approved IO therapies and whose cancers have progressed.
While cure rates for several cancers have significantly improved over the last decades, the outcome for patients with advanced solid tumors remains grimly unchanged, underscoring the need for new therapies. Oncolytic (cancer destroying) vaccinia virus (VV) is an appealing addition to the current cancer therapies due to its preference for infecting and killing tumor cells and a potential for activating the immune system component called T-cells that can travel to distant sites and kill any tumor cells they find, even those not infected by the virus.
At present, a desirable systemic intravenous administration of the virus is not feasible due to the strong immune response against it. In addition, virus spread within the tumor as well as the activation of T-cells is suboptimal. In our proposal we will engineer a VV by (i) making the necessary modifications within the VV proteins to mask it against immune system, making it suitable for systemic delivery, and (ii) secreting a new molecule called a T-cell engager that couples T cells to the tumor cells increasing the effectiveness of the T cells and their activation.
Our therapy will target solid tumors in humans, including melanoma, breast cancer, colorectal cancer, pancreatic adenocarcinoma, and ovarian cancer and is expected to have a major impact on the treatment of advanced, metastatic tumors, which are often incurable with current treatment strategies.
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.
An improved capacity to isolate and characterize circulating tumor cells (CTCs) would have a significant impact on the early detection, treatment, and scientific understanding of many types of cancer. Despite considerable progress in diagnosing and treating solid tumors, metastatic disease remains the foremost cause of cancer-related death.
With current diagnostic approaches, the spread of tumor cells in most patients is undetected until after metastatic disease is well-established, and early, potentially effective, intervention is not an option. Introduction of a facile means for the early detection and continual systemic monitoring of circulating tumor cells would enable timely administration of a wider range of treatment options that are more appropriately tailored to a patient’s specific disease.
We propose to build a novel, compact system to detect, isolate, and characterize circulating tumor cells originating from primary solid tumors or their metastases. Specifically, we will develop two key technologies to demonstrate a portable system that comprises the following elements: 1) a self-assembled biofilter for specific capture, concentration, and recovery of circulating tumor cells from whole blood samples, and 2) a low-cost contact imaging cytometer for subsequent cell quantification and molecular analysis.
Both the size selectivity and capture probe functionalization of the enrichment filter will be optimized to selectively trap CTCs from blood samples; dissolution of the filter will then yield a CTC-enriched sample for cell enumeration and further analysis. Employment of imaging cytometry will enable CTC analysis without a need for bench or lab-scale equipment, making the unit much more appropriate for bedside or clinic use compared to current CTC detection systems.
Our ultimate aim is to combine these two core technologies into a system that will rival or surpass the sensitivity of current CTC detection technologies, interface with current medical sample handling techniques, and be easy for caregivers to use.
Seven million biopsy procedures are performed annually to diagnose cancer or collect tumor tissue for personalized therapy. Yet, due to inadequate biopsy tumor content, 1 in 5 biopsy procedures have to be repeated to confirm diagnosis, and thousands of patients can’t receive potentially life-saving therapies because of downstream test failures. If doctors can quickly test that a sample is insufficient they can collect more tissue immediately, but currently available tests are too slow and destructive and require dedicated personnel.
We will develop technology that re-envisions the way this testing is done by developing an Automated Digital Pathology Lab (ADPL) imaging system that updates the traditional histology workflow, for the first time enabling users to go from the fresh sample directly to the histology image automatically and quickly. By making tissue adequacy testing fast, non-destructive, and fully automated, doctors can verify sample adequacy in less time with fewer personnel during the procedure, while there is still time to collect more tissue if needed.
By producing images that can be reviewed remotely, the ADPL system could be transformative for the 92.52% of Texas counties that contain medically-underserved rural institutions without on-site pathologists. The ADPL system would allow for remote assessment and guidance of biopsy procedures, empowering hospital systems in underserved communities to provide higher quality of care with limited personnel resources.
Invectys S.A. is a French biopharmaceutical company developing innovative anti-cancer products in immunotherapy based on leading technology from the Institut Pasteur in Paris. The Company is applying for a CPRIT relocation grant to advance its novel CAR-T platform to be able to conduct early stage clinical studies in Texas.
Invectys research is focused on the HLA-G molecule, a powerful modulator of the human immune system. It is the only cancer immunotherapy company focused on HLA-G: a highly significant and novel approach. HLA-G protects the fetus from the mother's immune system. However, in cancer tumors, cells are selected that express HLA-G to protect the tumor from attacks of the immune system. There are very few cell surface molecules that are so specific, and by comparison, current targets in immunotherapy are far less specific.
Cellular immunotherapy is a powerful new weapon in the anti-cancer arsenal, and progress is fast. However, only a small percentage of patients respond. Invectys approach is to reprograms immune cells to become killer cells for any tumor cells that is HLA-G. This would potentially increase responsiveness to immunotherapy in many cancer patients.
Invectys relocation proposal fulfills multiple CPRIT priorities: to address large unmet needs in cancer therapy; to attract experienced and innovative companies to Texas that will create jobs; and to provide CPRIT with a high potential return on its investment.
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.
Iterion Therapeutics is a clinical stage biotechnology company headquartered in the Texas Medical Center. Our first drug product, tegavivint, targets the protein TBL1 which interacts with multiple signaling pathways that control cancer cell growth. One of these is the Wnt/beta-catenin pathway which is frequently overactive in cancer. Tegavivint is currently being investigated in a clinical trial for a rare type of sarcoma, desmoid tumors. Early results from this study indicate that the drug is very well tolerated and shows signs of efficacy. Given these promising early results, tegavivint will be investigated in other types of cancer. However, the current formulation of tegavivint requires intravenous delivery, limiting its potential use in cancers where the standard of care prefers an oral agent. Therefore, we propose to develop a second-generation TBL1 inhibitor that leverages our current chemistry and understanding of TBL1 as a target to achieve novel, structurally distinct drug candidates with improved pharmaceutical properties, including oral absorption. We anticipate that learnings from this development process will also enhance our understanding of the structural and functional role that TBL1 plays in cancer, how our new compounds affect TBL1-mediated pathways, and how this data can be used to select targeted patient populations.
Chemotherapy is frontline treatment for millions of cancer patients, but it can cause devastating side effects. Some side effects, like nausea, are managed by medicine. But the most common serious side effect, the burning pain, tingling, and loss of sensation in hands and feet, has no effective treatment. This condition, known as chemotherapy induced peripheral neuropathy (CIPN), is the main reason why patients fail to complete their treatments. Currently, there are no medicines to prevent CIPN.
Chemotherapy may also damage the brain, causing problems with memory and higher cognitive function. This troubling mental fog is called chemo brain, and in some patients, may cause permanent disability. According to estimates there will be more Americans living with chemo brain than Alzheimer's by 2024. And, again, there are no medicines to treat this condition.
Korysso Therapeutics is a Houston-based biotechnology startup that has a single mission: to deliver medicines that prevent these side effects and allow patients to complete their chemotherapy and become healthy survivors. Based on technology invented at MD Anderson Cancer Center, Korysso is starting clinical trials with its first drug candidate, KOR-8287, this year.
With CPRIT's support, we aim to prove our medicine is effective at preventing CIPN and chemo brain from developing in patients by 2020, then to commercialize this breakthrough so that it is available for physicians and patients worldwide.
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.
In 2015, there were approximately 27,000 new cases of multiple myeloma diagnosed in the US making it the second most prevalent blood cancer. The five-year survival rate for multiple myeloma is 45% and the median survival is approximately 4 years. CD38 is a protein expressed on the surface of myeloma cells.
Recently, daratumumab, an antibody that specifically targets CD38, was approved for the treatment of patients with multiple myeloma. Daratumumab works primarily by binding myeloma cells and recruiting an immune response to them. Most patients’ immune system will ultimately stop responding to daratumumab allowing the disease to progress.
Molecular Templates, a venture-backed biopharmaceutical company in Georgetown, TX, has developed a novel multiple myeloma drug that targets CD38 but works in a different way from daratumumab. MT-4019ND is a fusion of an antibody fragment that binds CD38 with a highly toxic bacterial protein. MT-4019ND binds CD38 on the surface of myeloma cells but instead of recruiting an immune response, it directly kills the myeloma cell through its toxin component. MT-4019ND has shown a potent ability to kill myeloma cell lines in the laboratory and in animal models of myeloma.
Molecular Templates has a similar compound in the clinic for lymphoma that appears safe and effective in patients. Molecular Templates seeks $15.3M in CPRIT financing to move MT-4019ND through clinical studies in patients with refractory multiple myeloma.
Rules-Based Medicine® (RBM), the world’s leading multiplexed biomarker testing laboratory, provides comprehensive protein biomarker products and services based on its Multi-Analyte Profiling (MAP) technology platform. RBM’s biomarker testing service provides pre-clinical and clinical researchers with reproducible, quantitative, multiplexed immunoassay data for hundreds of proteins in a cost-effective manner, from a small sample volume and from multiple species. RBM is CLIA certified and supports GLP studies.
Most diseases and drug effects manifest themselves in abnormal levels of specific biomarkers found in the peripheral blood. By providing multiplexed, quantitative, and reproducible tests for hundreds of biomarkers, RBM enables research that historically was not available due to sample volume requirements and associated costs. Use of our testing services can help determine the sources of both the positive and negative effects of drugs during pre-clinical research and clinical trials. Biomarker testing results identify patients most likely to respond to a given therapy and the biochemical reason for that response, making clinical trials more successful and effective.
RBM’s OncologyMAP™ program is the result of our collaboration with the Proteomics Initiative of the National Cancer Institute. The first version of OncologyMAP, released in the fall of 2010, contains 102 quantitative immunoassays for “cancer-related” blood-based biomarkers. It is the only available method to quickly, accurately, and cost-effectively quantify all of these important oncology biomarkers from a small amount of biological material.
Biomarker patterns discovered in the blood or tissue can serve as diagnostic tests for early detection of tumors when therapeutic intervention is more successful or as prognostic tests that provide physicians with information to design treatment protocols. Biomarker patterns can also serve as companion diagnostics, distinguishing those who will benefit most from a specific therapy regimen.
Over the next few years, RBM will use funding from the Cancer Prevention and Research Initiative of Texas (CPRIT) to expand OncologyMAP by over 150 new cancer-related biomarker assays. RBM also performs custom assay development, participates in co-sponsored research programs, and pursues in-licensing of novel high-value assays.
RBM employs over 145 people at three facilities: • Austin, TX: Corporate headquarters and CLIA-certified biomarker testing laboratory • Lake Placid, NY: Multiplex assay development and manufacturing • Reutlingen, Germany: TruCulture® manufacturing and custom cell culture services.
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.
Cancer immunotherapy, heralded as “Breakthrough of the Year” by the journal Science in 2013, has enormous potential to improve survival, and even cure, patients with many types of cancer. Pelican Therapeutics is developing PTX-25 as an immunotherapy agent for cancer patients. Studies indicate that PTX-25 is a best-in-class product due to specific activation of killer T cells, the strongest predictor of survival benefit in cancer immunotherapy.
Pelican is applying for a CPRIT New Company Product Development Award to transition to a bricks-and-mortar company in the State of Texas. Under the CPRIT award, Pelican will finalize development of PTX-25 and complete a three-part phase I clinical trial to examine the benefits that PTX-25 provides to patients with several types of cancer, including lymphoma, lung, prostate, pancreatic and ovarian cancer.
Pelican’s growth in Texas will require hiring full-time employees to support manufacturing, regulatory filings, clinical development, and clinical trial execution. The expanded staff will manage critical development tasks, including (1) manufacturing PTX-25 in Texas-based facilities, (2) toxicity testing of PTX-25 using Texas-based contract research organizations, and (3) phase I clinical trial development primarily among patients in Texas-based hospitals and clinics. Pelican’s development of PTX-25 will stimulate economic development in Texas, with the overall goal of improving outcomes for everyone with deadly cancers.
Peloton Therapeutics aims to become a leading oncology company through the discovery and development of superior therapeutics, delivering extraordinary value to its employees, investors, and ultimately, cancer patients. The Company will initiate efforts with three cutting edge small molecule discovery programs, sourced from top investigators at The University of Texas Southwestern Medical Center (UTSWMC), including Dr. Steven McKnight, a world-recognized leader in the area of gene regulation.
Each of these programs represents a unique approach to cancer therapy, from blocking the tumor's critical need for adaptation to a limited oxygen supply to poisoning its ability to self-renew and proliferate by shutting off key metabolic pathways and cancer stem cell compartments. Despite the promise of these approaches, the challenge of drug discovery necessitates a multiple shots-on-goal" approach.
To that end, Peloton Therapeutics will continually replenish its discovery pipeline by in-licensing one or more compelling new programs each year from UTSWMC and other leading institutions. This approach enables pipeline building and diversification without the delay, cost, and technology risk associated with more "conventional" biotech platforms. Furthermore, the Company will focus its resources on medicinal chemistry, rigorous pharmacology, IND-enabling pre-clinical toxicology, and eventual clinical development, leveraging the expertise in biology and HTS capabilities of academic scientists.
Peloton Therapeutics plans to initiate research efforts in 2011 with 2 or more "founding" programs in oncology. Current program candidates include: (1) Inhibitors of Hypoxia-inducible Factor; (2) Wnt and Hedgehog (Hh) pathway antagonists; (3) a platform for the identification of novel drug-target combinations aimed at unique molecular vulnerabilities in non-small cell lung cancer. Several additional programs at an earlier stage of discovery are also being evaluated, comprising a project "bullpen" for the Company. Peloton Therapeutics, Inc. was formerly known as Damascus Pharmaceuticals, Inc.
Working closely with partners at M. D. Anderson Cancer Center, Texas A&M, and Baylor College of Medicine, Pulmotect is developing a novel, protectable technology to reduce the incidence of pneumonia in immunosuppressed cancer patients and significantly improve how cancer patients are treated. Our therapeutic product, PUL-042, is a combination of two stimulants that boost the lung's own defense mechanisms to create a broad protection against invading pathogens thereby reducing and preventing lung infection. Both cellular and live animal preclinical proof-of-concept experiments have been completed that validate this technology and support moving it forward into the clinic. It is in the most at-risk cancer patients where clinical proof-of-concept can be captured and support development for additional patient populations (additional cancers, transplant, ICU, bioterror, pandemic, and asthma). The purpose of this proposal is to accomplish three key developmental milestones that will advance this technology into an available therapy for patient care where it can help save lives. The three primary milestones are: 1) Complete final three milestones of IND-enabling studies. 2) Phase I clinical trial in healthy normal subjects. 3) 3Phase II clinical trial in leukemia patients
Salarius specializes in developing novel drugs for rare pediatric cancers and other cancers by focusing on treatments that interrupt the final steps of the signaling cascade. Our first drug, SP-2577, targets the Lysine Specific Histone Demethylase 1 pathway (LSD1), a cellular control protein that is overactive in a range of cancers. Salarius has developed a first-in-class highly specific LSD1 inhibitor that we will test in Ewing’s Sarcoma and other undifferentiated sarcomas, in addition to late stage prostate cancer.
We plan to file an IND in early 2016 and initiate phase 1 clinical studies in Ewing’s and prostate cancer in June 2016. Ewing’s is a rare devastating pediatric, adolescent and young adult bone cancer with no approved treatment. Roughly 50% of Ewing’s patients fail to respond to chemotherapy, radiation and surgical treatment and face 70%-80% mortality. If successful, a treatment for Ewing’s Sarcoma represents hope for thousands of patients and their families where current treatments are often woefully inadequate. Successful phase 1/2 studies could support an accelerated regulatory process with a Ewing’s orphan drug indication approved by Q3’19.
Salarius plans to relocate to Texas and set up a collaborative research effort to discover new drugs in its quest to become an integrated pharmaceutical company. Our business model is based on tight integration with academia and creating win-win environments between Salarius and academic cancer centers.
Many patients with cancer are cured by a stem cell transplant from a donor's bone marrow, umbilical cord blood, or peripheral blood. However, because these patients must endure a period of months before their immune system recovers, severe viral infections afflict over 70% of patients following transplant. These viral infections cause pain, organ damage, prolonged hospitalization, and even death. In fact, viral infections are now the most common severe complication related to stem cell transplantation. Because of the risk of infection, many other cancer patients cannot receive a transplant, and thus lose their best hope for cure.
ViraCyte has developed revolutionary new T-cell therapies that safely treat severe viral infections in cancer patients after stem cell transplants. In this CPRIT project, ViraCyte will perform an advanced clinical trial to establish the safety and effectiveness of our lead product, Viralym-M, in adults and children with a common, very severe virus infection (BK Virus) after stem cell transplant. BK causes debilitating abdominal pain, bleeding, kidney failure, and even death. Unfortunately, there are no FDA-approved treatments, or even effective experimental treatments, for this cancer complication. Therefore, the results of this project could revolutionize cancer supportive care, and fill a critical unmet need for patients. ViraCyte's ultimate goal is to assure that no patient who is cured of cancer will ever die from a viral infection.
The primary treatment for prostate cancer has long been radical prostatectomy (surgical removal of the prostate) or whole gland radiation. However, because prostate cancer presents in broadly varying degrees of aggressiveness, recent data show that 42 men who would not otherwise die from the disease must have their prostates removed in order to save one life.
Because the complications of prostatectomy (incontinence, erectile dysfunction) are common and devastating regardless of technique used (manual or robotic surgery), it is clear that prostate cancer is being dramatically over-treated. There is growing evidence that patients with low-risk disease may benefit significantly from a minimally invasive focal therapy (treatment of only the cancerous tumor) and avoid complications associated with prostatectomy and other “whole gland” therapies such as radiation.
In this CPRIT funded project we plan to complete product development tasks and gain early clinical experience using magnetic resonance imaging (MRI) guided laser therapy for targeted focal (tumor specific) destruction of localized prostate cancer. The Visualase laser technology is fully developed, FDA-cleared, and currently being employed clinically in the thermal destruction of brain tumors.
In this project we will develop the accessories required to extend this technique to localized prostate cancer, modify the current software for treatment planning specific to prostate cancer, and perform multi-center clinical studies in collaboration with renowned clinicians at M.D. Anderson Cancer Center and other leading institutions.
During these studies patients with both low risk and MRI visible disease, will undergo MRI-guided laser therapy of only the cancerous areas in their prostate. Patients will be monitored for any complications and followed-up over time to evaluate the control of their disease. Upon completion of this project, we will have determined if focal laser therapy of low-risk prostate cancer is an effective treatment approach which helps avoid more invasive surgery and related complications.