On September 3, 2019 Puma Biotechnology, Inc. (Nasdaq: PBYI) reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to NERLYNX (neratinib) for the treatment of breast cancer patients with brain metastases (Press release, Puma Biotechnology, SEP 3, 2019, View Source [SID1234539244]).

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"Receiving Orphan Drug Designation from the FDA signifies our continued progress and commitment to developing treatments for patients with HER2-positive breast cancer," said Alan H. Auerbach, Chairman, Chief Executive Officer and President of Puma. "Despite expanded treatment options for HER2-positive breast cancer, brain metastases in these patients represent a significant clinical challenge, as well as sources of morbidity and mortality for most of these patients. The blood-tumor penetrability of NERLYNX represents a potential treatment option for these underserved patients."

The FDA Orphan Drug Designation program grants orphan designation to investigational drugs designed to treat, prevent, or diagnose rare medical diseases or conditions that affect fewer than 200,000 individuals in the United States. Orphan designation qualifies sponsors for several key benefits and incentives, including opportunities for grant funding towards clinical trial costs, tax credits, user fee waivers, and the potential for a seven-year period of marketing exclusivity upon FDA approval of the investigational drug for the indication for which it has orphan designation.

About HER2-Positive Breast Cancer

Approximately 20 to 25 percent of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.

On September 3, 2019 Bio-Path Holdings, Inc., (NASDAQ: BPTH), a biotechnology company leveraging its proprietary DNAbilize antisense RNAi nanoparticle technology to develop a portfolio of targeted nucleic acid cancer drugs, reported that Peter H. Nielsen, Chief Executive Officer, will present a corporate overview at the upcoming H.C. Wainwright 21st Annual Global Investment Conference on Monday, September 9, 2019 at 3:25 p.m. ET in New York.

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A live webcast of the presentation can be accessed under "Events" in the Media section of the Company’s website at www.biopathholdings.com.

On September 3, 2019 Inhibrx, Inc. (Inhibrx), a clinical-stage biotechnology company focused on developing a broad pipeline of novel biologic therapeutic candidates, reported the completion of the dose escalation portion of its Phase 1 clinical trial of INBRX-109 (Press release, Inhibrx, SEP 3, 2019, View Source [SID1234539195]). INBRX-109 is a multivalent agonist of death receptor 5 (DR5) in development for the treatment of solid tumors. The dose expansion portion of the trial will now begin enrollment, with planned 20 patient cohorts in each of gastric and colorectal adenocarcinomas as well as mesothelioma.

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Twenty patients were enrolled in the dose escalation portion of the Phase 1 trial, in which INBRX-109 was well-tolerated with no significant liver toxicities observed at doses up to and including the maximum administered dose of 30 mg/kg. Additionally, INBRX-109 demonstrated a PK profile similar to conventional antibodies, providing potential validation of Inhibrx’s proprietary single domain antibody platform (sdAb).

Initial signs of disease control were demonstrated in five out of eight (5/8) patients with the tumor types chosen for inclusion in the expansion cohorts. The duration of disease control observed was ongoing in four out of five (4/5) patients and is now greater than five months in the first patient.

"We believe the favorable safety and efficacy profile demonstrated by INBRX-109 in heavily pre-treated patients in the dose escalation portion of the Phase 1 trial is encouraging, particularly given that these tumor types have historically not been well served by immune checkpoint inhibitors," said Klaus Wagner, Chief Medical Officer of Inhibrx. "Expansion cohorts are now enrolling in colorectal and gastric adenocarcinomas as well as mesothelioma, and efficacy and safety data from these cohorts is expected to be reported in the second quarter of 2020."

About INBRX-109
INBRX-109 is a multivalent agonist of DR5 in Phase 1 clinical development. It was built with the proprietary Inhibrx single domain antibody platform (sdAb). Activation of the DR5 receptor can lead to tumor biased cell death. DR5 activation requires higher-order clustering of receptors to initiate cell death but clustering of too many DR5 receptors can lead to cell death in normal tissues, most notably the liver. INBRX-109 was designed to maximize the therapeutic index of DR5 activation. A tetravalent format, INBRX-109 clusters four receptors and in preclinical studies led to tumor, but not liver, cell death. Preclinical data demonstrated the potential of DR5 activating agents to induce cell death in a variety of tumors with limited treatment options – colorectal adenocarcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma, mesothelioma and certain sarcomas.

About the Inhibrx sdAb Platform
Inhibrx utilizes diverse methods of protein engineering to address the specific requirements of complex target and disease biology. Our sdAb platform is designed to enable the development of therapeutic candidates with unique mechanisms of action and attributes superior to current monoclonal antibody and fusion protein approaches. sdAbs are highly modular and can be combined to create therapeutic candidates with defined valencies and multiple specificities, enabling enhanced cell signaling and conditional activation. Inhibrx’s sdAb-based therapeutic candidates are manufactured by established processes used to produce therapeutic proteins.

Initially, Inhibrx is utilizing its sdAb platform to pursue therapeutic candidates directed to validated targets, which the Company believes its protein engineering technologies can overcome prior therapeutic limitations.

On September 3, 2019 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported that the U.S. Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) application for FT596, the Company’s first off-the-shelf chimeric antigen receptor (CAR) natural killer (NK) cell cancer immunotherapy which targets multiple tumor-associated antigens (Press release, Fate Therapeutics, SEP 3, 2019, View Source [SID1234539212]). FT596 is derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three functional modalities designed to optimize anti-tumor activity: a proprietary CAR targeting B-cell antigen CD19; a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor; and an interleukin-15 receptor fusion (IL-15RF). The Company plans to initiate clinical investigation of FT596 as a monotherapy and in combination with CD20-directed monoclonal antibodies for the treatment of B-cell lymphoma and chronic lymphocytic leukemia.

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"FT596 is a ground-breaking product candidate with the potential to supplant current-generation patient-specific and allogeneic CAR19 T-cell immunotherapies, which recognize only one antigen and fail to address the significant risk of relapse due to antigen escape," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "Our robust clinical development strategy for FT596 is designed to target multiple tumor-associated antigens for the treatment of B-cell lymphomas and leukemias. We believe the product candidate’s engineered functionality, coupled with its ability to be cost-effectively administered on-demand in multiple treatment cycles, will deliver a deeper and more durable response to patients compared to single-antigen targeted CAR19 T cells."

While CAR19 T-cell therapies have demonstrated profound initial responses, not all patients respond to therapy and, even for those who initially respond, durability of response remains a significant limitation. Downregulation of target antigen CD19 from the tumor cell surface has been clinically demonstrated to be an important mechanism of resistance.

FT596, which is the first cellular immunotherapy engineered with three active anti-tumor components cleared for clinical investigation by the FDA, is uniquely designed to overcome CD19 antigen escape. In addition to a proprietary CAR targeting CD19, FT596 expresses a novel hnCD16 Fc receptor that has been modified to augment antibody-dependent cellular cytotoxicity, enabling coincident targeting of CD19 and additional antigens such as CD20. FT596 also expresses IL-15RF, a potent cytokine complex that promotes survival, proliferation and trans-activation of NK cells and CD8 T cells without the need for systemic cytokine support. Together, these features of FT596 are intended to maximize potency and minimize toxicity in treated patients.

FT596 is the third off-the-shelf, iPSC-derived NK cell product candidate from the Company’s proprietary iPSC product platform cleared for clinical investigation by the FDA in less than one year. The Company is conducting first-in-human clinical trials of FT516, an off-the-shelf NK cell cancer immunotherapy engineered to express hnCD16, for the treatment of acute myeloid leukemia and B-cell lymphoma, and FT500, an off-the-shelf NK cell cancer immunotherapy, for the treatment of advanced solid tumors.

About FT596
FT596 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three anti-tumor functional modalities: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology, which contains a NKG2D transmembrane domain, a 2B4 co-stimulatory domain and a CD3-zeta signaling domain, that targets B-cell antigen CD19; a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor that has been modified to augment antibody-dependent cellular cytotoxicity by preventing CD16 down-regulation and enhancing CD16 binding to tumor-targeting antibodies; and an IL-15 receptor fusion (IL-15RF) that promotes enhanced NK cell activity. In preclinical studies of FT596, the Company has demonstrated that the concurrent activation of the CAR and hnCD16 targeting modalities, in combination with IL-15RF signaling, convey synergistic anti-tumor activity. Increased degranulation and cytokine release were observed upon concurrent receptor activation in lymphoma cancer cells as compared to activation of each receptor alone, indicating that dual-antigen engagement may elicit a deeper and more durable response. Additionally, in a mixed cellular composition cytotoxicity assay comprised of CD19+ and CD19- tumor cells, FT596 combined with rituximab effectively eliminated the heterogeneous population of tumor cells, a result that was not observed with single-antigen targeted CAR19 T cells.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered in repeat doses to mediate more effective pharmacologic activity, including in combination with cycles of other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is fraught with batch-to-batch and cell-to-cell variability that can affect safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 250 issued patents and 150 pending patent applications.

On September 3, 2019 OBI Pharma, a Taiwan biopharma company (TPEx: 4174), reported that the U.S. Food and Drug Administration (FDA) has cleared an investigational new drug (IND) application for OBI-999 to conduct a Phase 1/2 study of its antibody drug conjugate (ADC) cancer therapy targeting Globo H, a glycolipid antigen (Press release, OBI Pharma, SEP 3, 2019, View Source [SID1234539229]).

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OBI plans to enroll patients with advanced solid tumors including pancreatic, gastric, colorectal and esophageal cancers. OBI Pharma’s Chief Medical Advisor, Tillman Pearce, M.D. noted, "This clinical trial intends to verify the safety and preliminary efficacy profile of OBI-999, a novel first-in-class antibody-drug conjugate that selectively targets Globo H. We are delighted to conduct this first-in-human clinical trial at the University of Texas M.D. Anderson Cancer Center, one of America’s leading academic oncology research institutions."

Michael Chang, Ph.D., OBI Pharma Chairman and CEO, added, "OBI Pharma is excited to commence the Phase 1/2 safety and efficacy study of OBI-999, our unique anti-Globo H ADC glycolipid cancer therapy. We strive to develop and validate our novel anti-Globo H immuno-oncology pipeline to fulfill unmet medical needs of cancer patients."

About OBI-999

OBI-999 is a novel first-in-class Antibody Drug Conjugate (ADC) with a proprietary linker technology that provides a consistent Drug-to-Antibody ratio (DAR) for cancer treatment that is based on Globo H, an antigen expressed in up to 15 epithelial cancers. OBI-999 uses a Globo H antibody to target cancer cells of high Globo H expression. By releasing a small molecule chemotherapeutic drug through the specificity of the antibody, it directly deploys cytotoxic therapy at the targeted cancer cells. This Globo H targeting antibody, OBI-888, is currently in a Phase ½ clinical trial (ClinicalTrials.gov Identifier: NCT03573544) to test its safety and efficacy as an immune-oncology therapy. In pre-clinical xenograft animal models in multiple tumor types (pancreatic, lung, gastric, and breast), OBI-999 has demonstrated profound tumor shrinkage at various doses. In pre-clinical single and repeated dose toxicology studies, OBI-999 was well-tolerated, and achieved a favorable safety margin which warrants further clinical development. OBI Pharma owns global rights to OBI-999.