On November 23, 2020 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted cancer therapeutics and utilizing a cost efficient, CRO-independent product development platform to partner with ex-U.S. companies to develop and commercialize innovative products in the U.S., reported the publication of clinical data that provides molecular insight into TRC102’s mechanism of action and patient populations most likely to respond to treatment (Press release, Tracon Pharmaceuticals, NOV 23, 2020, View Source [SID1234571567]). The article, entitled, "Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment," highlights the clinical features and tumor biology of an exceptional responder patient treated with TRC102 at the National Cancer Institute (NCI): View Source

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The patient was diagnosed with metastatic and highly refractory colorectal cancer and received temozolomide (Temodar) and TRC102. Following treatment, the patient was considered an exceptional responder through the achievement of a near compete response lasting 45 months at the most recent follow-up. Detailed molecular analyses of the patient’s tumor showed silencing of DNA repair pathways that may have resulted in sensitivity to the inhibition of DNA base excision repair pathway by TRC102. Specifically, MGMT expression was silenced by promoter methylation, and RAD50, a mediator of DNA double strand break repair, was silenced by genetic mutation and loss of heterozygosity. The publication authors hypothesized that the combination of Temodar and TRC102 was effective because all necessary DNA repair pathways were compromised genetically or through the activity of TRC102. MGMT expression was also assessed in biopsies from 11 colorectal patients who subsequently enrolled in an expansion cohort, one of which demonstrated a partial response. The tumor associated with the partial response did not express MGMT, whereas each of the 10 tumors that did not respond to therapy expressed this enzyme robustly.

TRC102 is being studied in multiple Phase 1 and Phase 2 clinical trials sponsored by the NCI through a Cooperative Research and Development Agreement. TRC102 was also evaluated in a Phase 2 trial in combination with Temodar chemotherapy in 19 patients with progressive or recurrent glioblastoma who progressed following Temodar and external beam radiotherapy. Extended survival was observed in two patients for more than two years, both of whom demonstrated activation of the DNA base excision repair pathway and showed hyperactivation of DNA damage response genes prior to treatment with TRC102.

"The Cancer Cell publication supports our belief that patients whose cancers are dependent on the DNA base excision repair pathway to repair DNA damage from chemotherapy may be particularly sensitive to the pharmacologic effects of TRC102," said James Freddo, M.D., Chief Medical Officer of TRACON. "The NCI data are also consistent with the results from the Phase 2 trial of Temodar and TRC102 in refractory glioblastoma. We remain committed to developing TRC102 in collaboration with the NCI and believe that the data generated to date provide strong rationale for studying TRC102 in combination with Temodar and radiotherapy in newly diagnosed patients with malignant glioma."

About TRC102

TRC102 (methoxyamine) is a novel, clinical-stage small molecule inhibitor of the DNA base excision repair pathway, which is a pathway that causes resistance to alkylating and antimetabolite chemotherapeutics. TRC102 is currently being studied in multiple Phase 1 and Phase 2 clinical trials sponsored by the National Cancer Institute through a Cooperative Research and Development Agreement (CRADA). TRC102 was granted orphan drug designation by the US FDA for the treatment of malignant glioma in 2020. For more information about the clinical trials, please visit TRACON’s website at www.traconpharma.com/clinical-trials.

About Malignant Glioma and GBM

GBM (also called glioblastoma) is a fast-growing malignant glioma that develops from star-shaped glial cells (astrocytes and oligodendrocytes) that support the health of the nerve cells within the brain. GBM is the most invasive type of glial tumors, rapidly growing and commonly spreading into nearby brain tissue. The National Cancer Institute estimates that approximately 22,850 adults (12,630 men and 10,280 women) are diagnosed with brain and other nervous system cancer annually in the U.S. and approximately 15,320 of these diagnoses will result in death. GBM has an incidence of two to three per 100,000 adults per year in the U.S., and accounts for 52 percent of all primary brain tumors.

On November 23, 2020 RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported that it will present and participate at the following virtual conferences in December (Press release, RedHill Biopharma, NOV 23, 2020, View Source [SID1234571566]):

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Evercore ISI 3rd Annual HealthCONx Conference
Fireside chat and an open Q&A: Thursday, December 3, 2020, 8 a.m. EST
Moderator: Umer Raffat, Equity Research – Biotech-large, Pharma-major, Specialty Pharma
Speaker: Dror Ben-Asher, CEO & Gilead Raday, Chief Operating Officer

Piper Sandler 32nd Annual Virtual Healthcare Conference
Fireside chat: Available on-demand from November 23, 2020
Moderator: David Amsellem, Managing Director, Sr. Research Analyst, Specialty Pharma
Speaker: Guy Goldberg, Chief Business Officer

The webcasts will be available for replay for 30 days on the Company’s website: View Source

On November 23, 2020 Silicon Therapeutics, a privately-held, integrated therapeutics company with a pioneering platform based on physics-driven molecular simulations, reported treatment of the first patient with its therapeutic candidate SNX281 in a Phase 1 clinical trial in patients with advanced solid tumors or lymphoma (Press release, Silicon Therapeutics, NOV 23, 2020, View Source [SID1234571564]). Wholly owned by Silicon Therapeutics, SNX281 is a small molecule Stimulator of Interferon Genes (STING) agonist with systemic exposure that was designed using unique insights and capabilities provided by the Silicon Therapeutics proprietary physics-driven drug discovery platform.

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This Phase 1 open-label, multicenter, multidose, first-in-human clinical trial of SNX281 will evaluate the safety and tolerability of SNX281 alone and in combination with the PD-1 inhibitor pembrolizumab in subjects with relapsed or refractory solid tumors or lymphomas. The trial is designed to enroll up to 128 patients.

"The initiation of this study is a significant milestone for Silicon Therapeutics, as it marks the entry of our lead therapeutic into clinical development. The speed with which we have arrived at this milestone from our foundation in 2016 is a testament to Silicon Therapeutics’ unique platform. Computational physics-driven drug discovery has truly come to fruition with our delivery of this new experimental medicine," said Lanny Sun, co-founder and chief executive officer. "As we navigate the unprecedented COVID-19 pandemic, we are leveraging virtual capabilities to initiate clinical trial sites, while ensuring patient and clinician safety is our top priority. We are incredibly grateful to the patients and their families, investigators and their clinical study sites, and our employees for advancing a program with the potential to treat patients suffering from challenging and life-threatening cancers."

The company’s proprietary platform is being used to design additional first-in-class small molecules targeting key drivers of disease in cancer that have proven difficult to treat with prior approaches and thus previously considered undruggable. The discovery platform is fully integrated with Silicon Therapeutics’ internal laboratories using cutting edge experimental capabilities in biophysics, biology and chemistry.

"There have been important advancements in immunotherapy treatments for cancer in recent years, but many patients do not benefit and therefore new approaches to stimulate effective anti-tumor responses are needed in the clinic," said Humphrey Gardner, M.D., F.C.A.P, chief medical officer. "We are excited about the potential of SNX281 to treat a broad array of cancers given its strong pre-clinical activity both as a single agent and in combination with a PD-1 inhibitor. We look forward to sharing the near- and long-term data as it becomes available."

About the SNX281 Clinical Trial
The purpose of this Phase 1 multi-center, open-label study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical activity of SNX281 as a monotherapy and in combination with pembrolizumab, a monoclonal antibody immunotherapy for the treatment of cancers. Dose escalation in monotherapy and combination will be explored in patients with advanced solid tumors or lymphoma. After determination of the optimal dose of SNX281 as a single-agent and in combination with pembrolizumab, expansion cohorts to further evaluate safety and efficacy in specific populations will be examined, including colorectal and ovarian carcinoma in the monotherapy arm, and tumors refractory to or relapsed on checkpoint inhibitors in the combination arm.

For more information about the SNX281 clinical trial (NCT04609579), please visit: View Source

About SNX281
Activation of STING provides two critical anti-tumor responses: the "spark" for initiating a robust innate immune response as well as the priming and induction of a robust tumor directed T cell response, providing sustained antitumor immunity. First generation clinical compounds are structural mimetics of endogenous cyclic dinucleotides (CDNs) STING agonists and cannot be delivered systemically, thus limiting use to local delivery via intra-tumoral injection.

To address these limitations, the Silicon Therapeutics team has designed and developed the small molecule STING agonist SNX281 with unique drug properties permitting systemic delivery. SNX281 is potent, specific and active against all prevalent human isoforms of STING, rapidly activating downstream signaling and induction type I interferon (IFN). Treatment of primary immune cells from human donors results in the maturation and activation of antigen presenting cells. In vivo, SNX281 stimulates cross-presentation, antigen-specific T cell response and rapid multi-lineage anti-tumor immunity.

In preclinical disease models, treatment with SNX281 results in complete regression of tumors in mice harboring colorectal tumors (CT26) with a single intravenous dose. This anti-tumor activity was shown to be immune-mediated, as it did not occur in immunocompromised mice. Further, the combination of an anti-PD-1 antibody with SNX281 demonstrated both enhanced anti-tumor activity as well as increased survival in a variety of additional tumor models.

SNX281 drug characteristics and STING pharmacology allow for a unique dosing paradigm with robust tumor regression after a short duration of exposure, and durable anti-tumor immunity.

On November 23, 2020 ImmunityBio, a privately-held immunotherapy company, reported the publication in Cancer Immunology, Immunotherapy of preclinical data demonstrating that ImmunityBio’s AnktivaÔ (IL-15 superagonist also known as N-803) improves interferon-gamma (IFN-g) production and killing of tumor of cells in vitro and in vivo by CD34+ progenitor-derived natural killer (NK) cells (Press release, Altor BioScience, NOV 23, 2020, View Source [SID1234571563]). Anktiva is currently being evaluated in late-stage clinical trials in combination with NantKwest’s (NASDAQ: NK) NK cell therapies for multiple indications including metastatic pancreatic cancer, triple negative breast cancer (TNBC), bladder cancer and lung cancer.

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"While allogeneic NK cell therapy is a promising and potentially paradigm-shifting approach for cancer immunotherapy, there are still considerable challenges remaining in the field," said Patrick Soon-Shiong, M.D., Chairman and CEO of ImmunityBio. "One way to boost NK cell function is through the use of IL-15, however, its short in vivo half-life limits its utility in the clinic. Anktiva was developed to overcome the limitations of IL-15 to fully unleash the potential of NK cell immunotherapy. These preclinical data are an important step forward in demonstrating the potential of Anktiva to boost NK cell functionality by increasing the production of key cytokines and improving killing properties across diverse in vitro and in vivo cancer models. Importantly, these data provide validating proof-of-mechanism that support the encouraging clinical data observed to date when combining Anktiva with NantKwest’s NK cell therapies across a range of challenging solid tumors with poor prognoses. We look forward to the continued evaluation of Anktiva as a promising IL-15 superagonist, which may be broadly applied to improve NK cell-based immunotherapies."

Key findings from the study performed under the guidance of Prof. Harry Dolstra at the Radboud Institute for Molecular Life Sciences in The Netherlands, reported in the publication titled, "IL‐15 superagonist N‐803 improves IFN-g production and killing of leukemia and ovarian cancer cells by CD34+ progenitor‐derived NK cells" include:

Anktiva induces HPC-NK cell proliferation in a dose-dependent manner;
Treatment with Anktiva increases IFN-g production in CD34+ hematopoietic progenitor-derived NK cells (HPC-NK) stimulated with leukemia cells lines and improves killing of primary AML samples from patients;
Anktiva improves serial killing properties of HPC-NK cells against leukemia as measured by live cell imaging with single cell resolution;
Anktiva increases CXCL10 production and improves long-term HPC-NK cell-mediated killing in ovarian cancer spheroids, an ovarian cancer model which mimics three-dimensional growth of ovarian cancer in vivo;
HPC-NK cells combined with Anktiva and nanogam (human immunoglobulins) show anti-tumor effects in a human ovarian cancer mouse model;
Together, these data point to the clear potential of AnktivaÔ to improve efficacy of NK cell-based immunotherapies by promoting HPC-NK cell expansion and functionality.

On November 23, 2020 Anixa Biosciences, Inc. (NASDAQ: ANIX), a biotechnology company focused on the treatment and prevention of cancer and infectious diseases, reported that an IND (Investigational New Drug) application for its prophylactic breast cancer vaccine has been filed with the U.S. Food and Drug Administration (Press release, Anixa Biosciences, NOV 23, 2020, View Source [SID1234571562]).

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This vaccine technology was invented by a research team from Cleveland Clinic, led by Dr. Vincent Tuohy, the Mort and Iris November Distinguished Chair in Innovative Breast Cancer Research in the Department of Inflammation and Immunity at Cleveland Clinic’s Lerner Research Institute. Anixa has a worldwide, exclusive license to this technology.

The technology takes advantage of self-proteins that have a function at certain times in life, but then become "retired" and disappear from the body. One such protein, alpha-lactalbumin, is expressed only in the mammary glands during lactation and then disappears once lactation ceases. Dr. Tuohy discovered that this protein is abnormally expressed again when a woman contracts breast cancer, especially Triple Negative Breast Cancer (TNBC), the most deadly form of this disease. Dr. Tuohy postulated that if women could be immunized against this protein after their childbearing years, the immune system could be trained to destroy cancer cells as they arise while ignoring normal cells that no longer express this protein, thus making it difficult for the cancer to gain critical mass. Early studies to test this theory demonstrated highly significant prevention of breast cancer in animal models.

The technology is being developed at Cleveland Clinic with funding from the U.S. Department of Defense. The funding is expected to enable completion of two Phase 1 clinical trials.

"This has the potential to be a paradigm-shifting clinical study," said Dr. Tuohy. "If our data demonstrate results similar to the pre-clinical studies, this vaccine could have a significant impact on breast cancer, the most common malignancy in women. Furthermore, the way we think about controlling breast cancer may completely change."

"We look forward to moving this novel technology into the clinical stage of development," stated Dr. Amit Kumar, President and CEO of Anixa Biosciences. "If the data in humans is comparable to the data in animals, Dr. Tuohy’s ‘retired’ protein hypothesis will usher in a new way to prevent breast cancer, as well as other types of tumors."

"This initial clinical trial will be with women who have been diagnosed with high-risk early stage TNBC and are receiving standard of care at Cleveland Clinic," said Dr. G. Thomas Budd, Department of Medical Oncology at the Taussig Cancer Center at Cleveland Clinic, and the Clinical Investigator who will be conducting the trial. "We look forward to commencing the Phase 1 clinical trial and evaluating these patients."