7 Hills Pharma is a Texas-based company developing novel therapies for cancer. Our drug, 7HP349, could benefit melanoma and other solid tumor patients resistant to immune checkpoint inhibitor (ICI) therapy. ICIs use the immune system to fight tumors, and have made rapid strides in treating melanoma, non-small cell lung, renal, bladder and other cancers. However, 43% of melanoma patients develop ICI drug resistance and are left with limited treatment options. 7HP349 addresses a primary cause of ICI resistance, the inability of T cells to infiltrate tumors, and has shown the ability in preclinical studies to reverse ICI drug resistance and reduce or eliminate tumors. This proposal aligns with CPRIT's mission to bring accessible treatment options to cancer patients, in particular to those in Texas. We have Orphan Drug Designation, Fast Track status, and an active IND for this indication with the FDA and have completed a Phase I clinical trial to show that 7HP349 is safe and well tolerated in humans. CPRIT funds will enable a Phase Ia/IIb study to confirm drug safety and positive responses with 7HP349 in ICI-resistant melanoma patients with progressive disease. If successful, this study will represent a new treatment paradigm for ICI-resistant cancers. 7 Hills will expand operations in Houston, creating high-quality jobs in drug development and clinical operations. 7 Hills is committed to Texas and will ensure that CPRIT funds are spent in Texas, whenever possible.

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.

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.

Houston-based Allterum Therapeutics is developing a novel drug to treat acute lymphoblastic leukemia (ALL). ALL is the most common childhood cancer though it can also occur in adults. Current treatments are effective for many patients, although the treatment can take years and have severe side effects. However, there is still a major unmet medical need since mortality is high for patients who recur and who lack effective options. Our drug is a monoclonal antibody that targets and kills ALL cancer cells without the broader side-effects typically observed with conventional chemotherapies. We will initially focus on treating patients who have failed other treatments with the goal of getting them to a potentially curative stem-cell transplant. Over time, we will expand our drug's use, adding it to the initial treatments that patients receive, to increase the treatment's effectiveness and potentially decrease its toxicity. Our CPRIT Seed Grant allowed us to manufacture pharma-grade drug, do initial safety tests in animals, and get feedback from FDA on our planned clinical trial. This grant will allow us to enter clinical testing and, if successful, demonstrate that our drug can help patients with ALL. Our program fits well with CPRIT's product development mission: funding a novel therapeutic program that addresses a major unmet medical need, that is being developed by an early-stage Texas-based company that will also grow the pool of experienced drug developers in Houston.

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.

Antibody-drug conjugates (ADCs) are an expanding class of highly effective cancer medicines. In ADCs, a toxic payload is conjugated to an antibody that recognizes a specific protein target selectively expressed on the surface of cancer cells. This results in the high concentration of toxin in tumors, while reducing toxicity to normal tissues. A long-sought goal has been to identify targets that are selectively expressed on the surface of a broad range of cancer but not normal cells. The scientific founders of Asylia discovered that the surface of many cancer cell types, but not normal cells, is decorated by Heat Shock Protein 70 (HSP70), where it can be targeted by antibodies loaded with cancer-killing toxins. The goal of this proposal is the development of an ADC based on antibody 239-87, that recognizes the cell surface form of HSP70. Strikingly, 239-87 treatment resulted in prolonged eradication (cures) of several cancer types in mice transplanted with human cancer cells. We plan to convert this promising antibody into an ADC conjugate that can then be tested for safety and efficacy in cancer patients who are failing current therapies in cancers, beginning with T-cell lymphoma. Encouraging initial trial results will support the broader testing in other tumor types with high cell surface HSP70 expression such as Myeloma and Breast Cancer. This work will be performed at Houston-based Asylia labs, together with our state's world renowned medical and research institutions.

Magnetically Activated and Guided Isotope Separation ('MAGIS") technology will enable production of the stable isotope Ytterbium-176 (176Yb) needed to make the radio-isotope Lutetium-177 (177Lu). 177Lu is an effective beta-therapy agent approved for certain neuroendocrine cancers and soon to be approved for prostate cancer, the second leading cause of cancer death in men, with clinical trials underway for a range of cancers. 177Lu can be used to target small tumors and dispersed, inoperable metastatic cancer using precise delivery molecules. 176Yb is currently only available in small quantities from Russia and that supply is uncertain due to geopolitics and competition for limited production capacity. We have already produced small quantities of medical-grade (99.5%) 176Yb and have secured a funded distribution partnership with Eckert & Ziegler. Development of this isotope production capability will also enable future production of diagnostic isotopes and of other beta and alpha emitting radioisotopes, effective in targeting cancer cells with minimal damage to adjacent healthy cells. Early access to these isotopes will put cancer treatment and medical research institutes in Texas at the forefront of these therapies with opportunities for development and trials of a range of related co?products. MAGIS offers a scalable, reliable, domestic source of 176Yb for 177Lu production to make 177Lu-based therapies readily available in Texas and to the global medical community.

Over 1.8 million people are estimated to be stricken with colorectal cancer (CRC) every year (3rd most common cancer), and over 880,000 will die (2nd most common cancer). While improvements in prevention and screening have led to increased survival over the past several decades, metastatic cancer still has a poor prognosis (11% 5-year survival) despite best available therapies. Treatment for CRC relies heavily on non-specific chemotherapy drugs with harsh side effects. Under prior CPRIT research awards, scientists at the University of Texas Southwestern (UTSW) identified a class of highly specific drugs for CRC, referred to as TASINs, that selectively inhibit a mutated gene (adenomatous polyposis coli, or APC) present in greater than 80% of CRC patients. Mutations in APC are one of the earliest and critical events responsible for initiation and progression of CRC. In animal studies, TASINs significantly reduced tumor growth without harming normal cells. Barricade has selected the TASIN molecule that will move forward into human studies in 2020, with the goal of improving the survival of CRC patients diagnosed. The selective nature of TASINs combined with the prevalence of its target in CRC makes Barricade’s drug an attractive candidate for treating millions of people suffering from CRC worldwide. Barricade’s experienced Texas-based drug development team plans to bring TASIN to market by 2026.

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.

CerRx is developing drugs to trick cancer cells into overproducing toxic waxes, called ceramides. When the ceramides increase to a certain level, cancer cells die. CerRx has a pipeline of such drugs, including fenretinide and safingol, which work synergistically against many cancer types in laboratory testing. Human testing already shows fenretinide eliminates the cancers of some patients with relapsed lymphomas.

CerRx needs funding to advance these drugs to market, specifically for the following clinical trials to be conducted in Texas-based consortia: 1) a larger trial of fenretinide in advanced Peripheral T-cell lymphoma, 2) a larger trial in advanced Cutaneous T-cell lymphoma, and 3) a trial combining fenretinide and safingol in advanced solid tumors like colon and small cell lung cancer.

If patient responses in these trials confirm the activity observed in early testing, CerRx will have sufficient data to justify expanding these trials, ideally including CTNet, for accelerated FDA product approval for T-cell lymphoma patients in need. If fenretinide + safingol is as tolerable and active as expected, CerRx drugs will lead a revolutionary new treatment approach based on ceramides that is likely effective against many types of cancer resistant to current therapies. These goals are consistent with the CPRIT mission to improve the lives of cancer patients in Texas by supporting innovative, potentially breakthrough therapies, and to create high-quality new jobs in Texas.

Cellular therapies have shifted the goalpost from treating cancer to curing it. Cellular therapies, in various cancer indications, provide options in the refractory setting where there is high unmet medical need. Though there has been progress on allogenic or "off-the-shelf" cellular therapies, most early phase therapies are autologous processes, with a dedicated manufacturing run for each patient. These personalized immunotherapies start with the collection of the patient's own cells or tumor samples, which is modified or re-engineered depending on the therapeutic modality and indication, then stimulated for growth to expand the cell number, and infused back into the patient. Cell therapy is particularly challenging to develop and manufacture since every donor is unique, necessitating a robust process that can support modification and expansion for each patient and cells requiring additional support for growth and expansion ex-vivo. Additionally, viral vectors utilized in the modification/engineering of the cells are critical raw materials that require their own manufacturing process. Our proposal intends to build platforms and bolster expertise at our site in Houston that reduce manufacturing time, variability, and cost to reach patients, who often have no other options, faster and more efficiently. This proposal will also support innovation, scientific career growth, and research knowledge here in 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.

Dialectic Therapeutics (DT) is a biotech start up dedicated to the development of impactful and unique anti-cancer drugs to effectively treat cancers with few to no other options. Founded by three respected cancer scientists and two successful biotech investors, DT is located in Dallas and has research facilities/partners at UT Health in San Antonio (UTHSA) and the University of Florida. DT’s lead candidate, DT2216, is a unique programmed protein degradation compound that selectively induces cancer cells to degrade BCL-XL, stimulating the cells to commit suicide on their own, or become more susceptible to chemotherapy. Cancer cells are less likely to develop resistance to DT2216 because of its unique mechanism of action. Preliminary studies show that DT2216 destroys T-cell lymphoma / T-cell leukemia as a single agent. It is effective against small cell lung cancer and breast cancer when combined with traditional chemotherapy. The toxicity profile is favorable showing only a dose dependent decrease in platelets. This novel approach to cancer therapy will fill a significant need in current cancer treatment regimens. The clinical studies can all be performed at Texas institutions. The work supported by the CPRIT TXCO grant will enable DT to perform clinical phase trials for DT2216 in the treatment of T-cell lymphoma and small cell lung cancer. When successful, we will relieve the suffering of patients with cancer, give them hope and prolong their productive 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.

Emtora Biosciences is a San Antonio, TX company that has developed eRapa, a novel form of the FDA-approved active ingredient rapamycin. Rapamycin has previously shown promise in treating gastrointestinal diseases and in cancer prevention, but is limited by toxicity. eRapa is targeted to the colon and is delivered at lower doses, resulting in lower toxicity. eRapa is being evaluated to prevent colorectal cancer in patients with Familial Adenomatous Polyposis (FAP). FAP is a rare genetic disease that results in 100's to 1000's of benign polyps forming in the colon as early as the teen years. It is an orphan indication. In mice, eRapa decreased the occurrence of polyps based on dosage levels, with the highest dose resulting in no polyps. FAP is ideal for a cancer prevention drug because 100% of FAP patients will develop cancer without prophylactic surgical bowel resection, and no approved therapy exists. In 2019, Emtora received a CPRIT Product Development (SEED) award for a Phase IIa study of eRapa in FAP, which is currently underway. Emtora is also developing a final dosage form of eRapa that will be more stable at room temperatures. Emtora seeks to expand the Phase IIa trial to evaluate comparability of the final formulation to the current formulation. At the conclusion of the Phase IIa trial, Emtora plans to initiate a randomized controlled trial (RCT) to study the efficacy of eRapa in preventing or delaying the onset of colorectal cancer in patients with FAP.

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.

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.

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.

ImmuneSensor Therapeutics Inc. is a Dallas, Texas-based clinical stage biotechnology company founded on Dr. Zhijian Chen's CPRIT funded research at UTSW. The company is developing a new class of drug called STING agonist that activates the patient's immune system to fight cancers. Immunotherapy has revolutionized cancer therapy; however, inadequacy remains due to insufficiency in mobilizing and coordinating the immune system against the cancer. STING agonist can help overcome such insufficiency. ImmuneSensor's lead STING agonist, IMSA101 has shown in Phase 1 trial an excellent clinical safety profile and encouraging immune stimulatory activity. It is ready to advance into Phase 2 trials. ImmuneSensor is proposing a Phase 2 program to evaluate adding IMSA101 to an existing therapy in metastatic solid tumor cancer. The proposed IMSA101 combination could result in greater disease control, delay in disease progression leading to improvement in survival and quality of life. Execution of this project will significantly advance IMSA101 development and commercialization in the billion-dollar immunotherapy market and provide a novel therapy for metastatic cancer. New clinical staff will be hired in or relocated to Texas to support the project. Texas-based clinical investigators including ones at UTSW and MD Anderson will be recruited into the project. This project provides an opportunity for UTSW and Texas to further establish itself as a leading immunotherapy cancer center.

ImmunoGenesis is a Houston, Texas-based company developing novel drugs with technology spun out of MD Anderson Cancer Center (MDACC). In the last decade, immunotherapy drugs, called checkpoint inhibitors, have revolutionized therapy for many cancers, and new combination therapies continue to evolve. However, only a minority (~45%) of cancer patients are eligible to receive these drugs and among those less than 20% achieve a complete or even partial response. ImmunoGenesis' IMGS-001 is a new type of immunotherapy that for the first time can both benefit the majority (55%) of patients ineligible to receive current drugs, and also has the potential to improve responses in existing indications. In pre-clinical studies, IMGS-001 out-performed the most potent existing drug in freeing the immune system to reject established cancers. In this CPRIT Product Development Grant application, ImmunoGenesis will take its innovative, first-in-class immunotherapy drug, IMGS-001, to the FDA to request approval to open a clinical trial at MDACC and other Texas clinics. The company is also developing a biomarker test to identify the patients most likely to benefit from IMGS-001.

Radiation therapy is a critical part of combinatorial cancer care. The dose must be sufficient enough to kill the targeted tumor, but also minimal enough to ensure that the radiation does not cause collateral damage to nearby healthy tissues and organs. These treatments are very precise and individualized. Each person's unique medical history and needs factors in. For example, a patient who has both bladder cancer and failing kidneys will have a specific radiation plan to avoid further kidney damage. Cancer doctors (oncologists) have an extensive team that helps create these radiation plans, called directives, but estimating the dose is tedious, iterative, time-consuming and inaccurate. A doctor can spend 10+ hours creating a single patient's directive and the clinical team could take 24-48 hrs too finalize a plan. Our team is building RadOnc-AI, a software that uses a form of artificial intelligence (AI) called deep learning to fully automate this directive planning. The AI uses the person's medical data and tumor images to predict the optimal radiation dose. Cancer patients treated at larger hospitals with specialized doctors tend to have better outcomes than those treated at small clinics, who have a reduced survival rate of 20%. We are asking for CPRIT funding to build out our software so that patients across Texas and the country can receive the same equitable quality treatment plans.

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.

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.

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.

Marker Therapeutics, a Texas-based company, focuses on novel cell-based therapies for a variety of cancer indications. Marker proposes MT-401 for the treatment of acute myeloid leukemia (AML), supporting CPRIT’s mission for novel cancer treatments. AML is a deadly cancer, treated with chemotherapy, often followed by stem cell transplant (SCT). However, relapse after SCT remains a major cause of death, with poor 1-year survival. Limited treatments are available for patients who fail chemotherapy and SCT. MT-401 is a novel T cell-based therapy that targets multiple tumor-associated antigens (mTAAs) highly expressed in AML cancer cells (with absent / low expression in healthy tissue), minimizing the chance of tumor cells escaping treatment. MT-401 can recognize and kill target cancer cells, and leads to activation of other immune cells and recognition of additional cancer cells. mTAA T cells have shown safety and efficacy in preclinical and early phase clinical testing in a multiple cancer types, including AML. In this CPRIT proposal, Marker will conduct a Phase 2 clinical trial of MT-401 in AML patients post-SCT in the adjuvant setting (in remission, at risk of relapse). 60 AML patients will be treated with MT-401 and compared with patients treated with standard of care to assess safety, efficacy, and immune effects. Completion of this trial will advance MT-401 towards market approval and provide a safe, effective treatment option where none currently exists on the market.

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.

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.

OmniNano Pharmaceuticals is a pharmaceutical technology startup located in Missouri City, TX. Omninano is developing nano-codelivery formulations with two drugs of distinct mechanisms of action for treating solid tumors. The foundational work has been done at the University of Texas MD Anderson Cancer Center and the University of Houston. Our lead product, ONP-001 is designed to treat pancreatic cancer. In 2022, 62,210 new pancreatic cases will be diagnosed in the US, with 49,830 deaths and a 5-year survival rate of only 11.5%. Extant drug therapies have very limited efficacy, with more than half of all pancreatic cancer patients dying within 12 months of diagnosis. Furthermore, current treatments can cause serious adverse effects that require costly mitigation. Pancreatic cancer is a difficult-to-treat disease with critical unmet needs. ONP-001, even administrated at a small fraction of conventional drug dosages, is shown to overcome drug resistance by depleting cancer stem cells and killing proliferating tumor cells. In animal studies, ONP-001 displays remarkable anti-tumor efficacy with minimal toxicity. To bring this novel drug to the clinic, OmniNano will conduct preclinical studies that will enable an Investigative New Drug (IND) application to the US Food and Drug Administration. Successful realization of the proposed project will enable clinical testing of ONP-001, an important milestone towards use in treating patients with pancreatic cancer.

OncoNano Medicine, Inc., a spinout of UT Southwestern headquartered in Southlake, TX, developed its first product, ONM-100, for imaging cancer with the help of a $6 million CPRIT NEWCO award in 2014. ONM-100 was granted a Fast Track designation and is currently in Phase 2 trials. These initial clinical trials continue to successfully demonstrate the use of ONM-100 in imaging cancer tumors. OncoNano has discovered that ONM-100 can also be used to image and stage metastatic disease in the peritoneum, lymph nodes and pleura resulting from gastric, colorectal, prostate, ovarian, lung, and breast cancers. This important and valuable advance meets a critical unmet need for cancer patients. Today, there are very few tools or technologies that allow doctors to see small tumors that have metastasized, and ONM-100 does this very well. This important use of ONM-100 to help doctors visualize tumors they might have otherwise missed is the subject of this grant application. Since its first funding from CPRIT, OncoNano has grown to 20 employees and the company works with Texas-based thought leaders as advisors and continues to support the vision of CPRIT. Through a $15.4 million grant in 2019, OncoNano�s technology is being used in the development of another important cancer nanovaccine (ONM-500) for human papilloma virus (HPV)-associated cancers. OncoNano is an example of how CPRIT funds are being used to create valuable drugs to save lives in Texas and the rest of the world.

The modern treatment of cancer activates the body's own immune system to attack cancer. These treatments, called immunotherapy, may not be successful if the cancer can recruit bad-acting cells, such as tumor associated macrophages, or TAMs, that create barriers preventing immunotherapies from activating the body's own defenses against the cancer. To find drugs that may help counteract these TAMs, OncoResponse looked to patients who had responded very well to immunotherapy to see if their bodies made factors to block TAMs and helped them fight their cancers. Along with MD Anderson Cancer Center, and using a unique, high-throughput platform, OncoResponse has discovered several factors that may help conquer cancer and fulfill CPRIT's mission. One such factor, OR502, is an antibody that binds a protein, LILRB2, that is expressed by TAMs. OR502 blocks TAMs from shutting down the body's response to cancer, restoring tumor-killing immune activity. OncoResponse has persuasive data in laboratory assays and mouse models that demonstrate OR502 can reverse the suppressive activity of TAMs and reactivate tumor killing by the immune system. This CPRIT grant will support a clinical study to understand how OR502 works in humans and develop it into a powerful new medicine. This will spur innovation and development in Texas and provide cancer cures for patients. Our goal is to develop a drug that will help patients fight cancer with their most powerful ally: their own immune system.

Pancreatic cancer is a highly lethal disease and the third leading cause of cancer death. The only chance for cure remains complete surgical removal, but this is impossible for most patients due to advanced local growth or metastatic spread. For inoperable patients, multiple approaches have been attempted to shrink tumor and allow for subsequent resection. Multiagent chemotherapy is utilized in this "neoadjuvant" approach but has met with limited success due to modest activity and significant side effects. By directly targeting tumors, PanTher's novel approach looks to significantly increase drug accumulation at the site, while dramatically reducing systemic side effects to improve antitumor activity, preserve quality of life and lower overall healthcare costs. In animal models, this technology has demonstrated a 12-fold greater efficacy in controlling progression compared to the same agent given intravenously. PanTher has previously partnered with surgical oncologists at MD Anderson Cancer Center to complete large animal studies and demonstrate the platform to be easily implantable, well tolerated, and able to deliver chemotherapy only to the tumor with no systemic exposure. This work has led to the ongoing first-in-human trial of PTM-101 to assess feasibility and safety in patients with locally advanced disease. Further optimization of the dosing and expansion to phase 1b/2 is the focus of this proposal to assess antitumor activity of PTM-101 in this devastating disease.

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.

Pancreatic cancer is a highly lethal disease and the third leading cause of cancer death. The only chance for cure remains complete surgical removal, but this is impossible for most patients due to advanced local growth or metastatic spread. For inoperable patients, multiple approaches have been attempted to shrink tumor and allow for subsequent resection. Multiagent chemotherapy is utilized in this "neoadjuvant" approach but has met with limited success due to modest activity and significant side effects. By directly targeting tumors, PanTher's novel approach looks to significantly increase drug accumulation at the site, while dramatically reducing systemic side effects to improve antitumor activity, preserve quality of life and lower overall healthcare costs. In animal models, this technology has demonstrated a 12-fold greater efficacy in controlling progression compared to the same agent given intravenously. PanTher has previously partnered with surgical oncologists at MD Anderson Cancer Center to complete large animal studies and demonstrate the platform to be easily implantable, well tolerated, and able to deliver chemotherapy only to the tumor with no systemic exposure. This work has led to the ongoing first-in-human trial of PTM-101 to assess feasibility and safety in patients with locally advanced disease. Further optimization of the dosing and expansion to phase 1b/2 is the focus of this proposal to assess antitumor activity of PTM-101 in this devastating disease.

PLUS Therapeutics’ Rhenium-186 NanoLiposome (186RNL) is a novel radiotherapeutic being developed to combat rare and difficult-to-treat cancers. Currently in clinical development for recurrent glioblastoma, 186RNL is safe and well-tolerated while delivering a radiation dose to the tumor that is up to 15 times higher than typically achievable with standard radiation therapy. PLUS now plans to develop 186RNL to treat leptomeningeal metastases (LM), a rare but typically fatal complication of advanced cancer affecting the fluid-lined structures surrounding the brain and spinal cord. LM affects over 110,000 people in the U.S. every year and, even with the best available care, is rapidly fatal with a 1-year survival rate of only 7%. To treat LM, 186RNL will circulate throughout the fluid surrounding the brain and spinal cord, targeting the cancer cells with high doses of radiation while minimizing exposure to normal tissues. The goals are to improve the patient's quality of life and extend their survival. 186RNL is being developed and manufactured in Texas. Support for development of 186RNL fits with CPRIT's mission to expedite innovation in new product development and to promote cancer research in Texas. Whenever possible, PLUS will utilize Texas-based businesses that conduct clinical research. In line with CPRIT's priorities, the Award will allow PLUS to continue to provide high paying jobs in Texas and develop a therapy that addresses a very challenging unmet medical need.

Nucore Inc. is a Houston-based medical device company resulting from a multi-year collaboration between J&J's Center for Medical Device Innovation @ The Texas Medical Center and California-based Precision Thoracic to innovate novel technologies focused on the early interception, diagnosis, and treatment of lung cancer. The American Cancer Society notes that "Lung cancer is by far the leading cause of cancer death among both men and women, making up almost 25% of all cancer deaths. More people die of lung cancer than of colon, breast, and prostate cancers combined." One reason that lung cancer is so lethal is that it is usually diagnosed late when it has already spread. There is a desperate need to develop technologies to more effectively facilitate diagnosis and treatment of lung cancer at much earlier stages. Nucore has developed Minimally-invasive Targeted Resection (MiTR-core™), the first medical device designed to safely remove lung nodules in a simple, quick, and minimally invasive procedure. The MiTR-core procedure will enable clinicians to remove suspicious nodules upon initial detection, will provide a definitive diagnosis of the nodule, spare healthy lung tissue, and in the event of cancer, provide direct access to the site of the nodule for further targeted therapy. This CPRIT grant will significantly accelerate the commercialization of MiTR-core by the Houston-based Nucore team working in collaboration with clinical experts at MD Anderson Cancer Center.

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

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.

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.

Novel therapies are urgently needed for pancreatic cancer (PDAC) and triple negative breast cancer (TNBC), two of the most aggressive cancers with no effective cure. For PDAC, 4420 Texans and 60,000 Americans are diagnosed each year and only 7% are expected to survive 5 years. TNBC is also aggressive, affecting 3000 women in Texas and 42,000 in the US annually, with a disproportionate impact on African American and Hispanic women. Stellanova's co-founders have demonstrated that cells in the tumor microenvironment of PDAC and TNBC produce Dickkopf-3 (DKK3) that acts on neighboring cancer cells to stimulate their growth, metastasis and resistance to standard therapy. We have developed novel antibodies to block DKK3 (anti-DKK3 mAb) which inhibited tumor growth in mice and produced long-term survival with no toxicity. For TNBC, treatment also reduced lung and brain metastases. Anti-DKK3 mAb is effective either alone or in combination with immunotherapy, thus avoiding chemotherapy and its toxicities. Stellanova has assembled a team of experts who have a proven track record in cancer drug development and fundraising. Completion of this project is critical to achieving our overall goal of developing a DKK3-targeted antibody for a first-in-human clinical trial for patients with PDAC, TNBC and potentially other cancers. Given the lack of effective therapies for these diseases, the successful development of DKK3-targeted therapy has the potential to be practice-changing for the field.

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.

Pancreatic cancer is almost always fatal and is the third leading cause of cancer-related death in the United States. Pancreatic cancer is difficult to treat because it often cannot be removed by surgery and shrinking the tumors by conventional radiation is significantly limited because the pancreas is next to the intestines (specifically duodenum), which can be easily damaged during radiation treatment. Xerient is a startup dedicated to the development of an orally administered tablet that releases very efficient radioprotectant molecule in the duodenum. Xerient demonstrated that it is possible to repurpose an FDA-approved radioprotectant, and reformulate it in a tablet with a targeted-delivery and in-body-monitoring functionalities, to allow very efficacious radiation therapy.