On October 02, 2017 Spring Bank Pharmaceuticals, Inc. (NASDAQ:SBPH), a clinical-stage biopharmaceutical company developing novel therapeutics for the treatment of viral infections, inflammatory diseases and certain cancers, reported that it will present a poster (#A25) at 5:30 p.m. to 7:30 p.m. today, October 2, 2017, entitled “Pharmacodynamic and preclinical studies of SB 11285, a highly potent, and systemically bioavailable STING agonist as a novel immunotherapeutic agent,” at the AACR (Free AACR Whitepaper) Conference on Tumor Immunology and Immunotherapy, taking place in Boston, MA, October 1-4, 2017 (Press release, Spring Bank Pharmaceuticals, OCT 2, 2017, View Source [SID1234520749]). The data shows that Spring Bank Pharmaceuticals’ next-generation, proprietary STING (STimulator of INterferon Genes) agonist compound, SB 11285, has highly potent anti-tumor activity along with a durable anti-tumor response when administered by multiple routes in several tumor models.

“Data from multiple tumor models in preclinical studies of SB 11285 demonstrated durable antitumor activity and support continued development of SB 11285, either alone or in combination with other agents, with different routes of administration,” said Radhakrishnan (Kris) Iyer, Ph.D., Chief Scientific Officer of Spring Bank Pharmaceuticals. “We are conducting additional preclinical and IND-enabling studies to support the initiation of the SB 11285 clinical program in mid-2018.”

SB 11285 was evaluated in several syngeneic mouse models, including A20 lymphoma, CT26 colon carcinoma, B16 melanoma, and orthotopic 4T1 breast cancer models, for tumor growth inhibition (TGI) and tumor growth delay (TGD). SB 11285 was administered by intravenous (i.v.), intraperitoneal (i.p.), and intra-tumoral (i.t.) routes. The results are summarized here:

A20 Lymphoma Model: When SB 11285 was administered by i.t. route, 9 out of 10 animals achieved complete regression with 86% tumor growth inhibition (TGI) and 73% tumor growth delay (TGD). Furthermore, all tumor-free survivors rejected the tumors when re-challenged with A20 cells indicating the induction of immune memory.
CT26 Colon Carcinoma Model: Dose-ranging studies of SB 11285 were performed using i.t. doses (10 to 100µg on days 1,2,4,6,8), i.p. (1 to 9 mg/kg) and i.v. (1 to 9mg/kg, days 1,3,5,8). Highly durable anti-tumoral responses were seen in the CT26 models with i.t. (94% TGI & 207% TGD), i.p. (62% TGI & 49% TGD), and i.v. (80% TGI & 85% TGD). SB 11285 administered i.t. also showed a significant abscopal effect (a shrinkage of tumors beyond the scope of the localized treatment) in this model.

B16 Melanoma Model: Administration of SB 11285 resulted in 77% and 56% reductions in mean tumor volumes, when administered i.v. and i.p., respectively, by day 11 post-treatment.

4T1 Breast Cancer Model: SB 11285 administered i.p. resulted in 78% reduction in primary tumor volume and showed potent inhibition of tumor metastasis.

The anti-tumor activity observed in these models correlated with anti-tumoral immune response. Immuno-histochemistry combined with flow cytometric analysis of tissues and blood from SB 11285-treated groups revealed the presence of activated immune cells, including CD8+ T cells, natural killer (NK) cells and macrophages critical for anti-tumor effects.

About the AACR (Free AACR Whitepaper) Special Conference on Tumor Immunology and Immunotherapy

The AACR (Free AACR Whitepaper) Special Conference on Tumor Immunology and Immunotherapy is focusing on recent advances in understanding the range of immune responses towards cancer and how these can be modified and harnessed for prevention and therapeutics. The conference features the world’s premier oncologists who will present their latest research on current immunotherapies, engineered cells, checkpoints, and combinations. In addition, highly acclaimed basic researchers and immunologists will present data that bridge the gap between the cutting-edge advances that are under way in the lab, such as single-cell analysis, neoantigens, systems and synthetic biology, and their application to clinical practice.

On October 2, 2017 Sophiris Bio Inc. (NASDAQ: SPHS) (the “Company” or “Sophiris”) today provided an update on clinical trial enrollment of its Phase 2b study of topsalysin as a treatment for men with clinically significant localized prostate cancer (Press release, Sophiris Bio, OCT 2, 2017, View Source [SID1234520748]). Patient enrollment is near completion, and the remaining patients are being scheduled to receive treatment within the next few weeks. Sophiris expects the study will be fully enrolled by the end of October. The Company expects biopsy data from all patients dosed with the first administration of topsalysin to be available late in the first quarter of 2018.

“Interest in this study has been strong, and the remaining patients are being scheduled for treatment in the next few weeks,” said Randall E. Woods, president and CEO of Sophiris. “We look forward to completing enrollment, and, assuming enrollment is completed as expected, initial biopsy results will be available toward the end of the first quarter of 2018.”

On October 2, 2017 Rigel Pharmaceuticals, Inc. (Nasdaq:RIGL) reported that during the company’s mid-cycle meeting with the U.S. Food and Drug Administration (FDA) the FDA indicated that, at this point, it is not planning to hold an Oncology Drugs Advisory Committee (ODAC) meeting to discuss the New Drug Application (NDA) for fostamatinib in patients with chronic or persistent immune thrombocytopenia (ITP) (Press release, Rigel, OCT 2, 2017, View Source [SID1234520747]). Additionally, the FDA indicated that it anticipates meeting the Prescription Drug User Fee Act (PDUFA) action date for the application review, which is April 17, 2018. In an earlier communication, the FDA had conditionally approved the proprietary name TavalisseTM.

“Since we submitted our NDA this spring, we have worked collaboratively with the FDA to answer routine questions as they arise,” said Anne-Marie Duliege, MD, executive vice president and chief medical officer of Rigel. “Our positive interactions with the FDA, including their customary biomedical monitoring (BIMO) inspections at our facilities and clinical sites, are in-line with our expectations and have progressed well. We will continue to work closely with the agency and remain committed to bringing fostamatinib to patients with ITP who are in need of new treatment options.”

About ITP
In patients with ITP, the immune system attacks and destroys the body’s own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP are excessive bruising and bleeding. People suffering with chronic ITP may live with increased risk of severe bleeding events that can result in serious medical complication, or even death. Currently approved therapies for ITP include steroids, blood platelet production boosters (TPO-RAs) and splenectomy. However, not all patients derive a benefit from existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP.

On October 2, 2017 Pieris Pharmaceuticals, Inc. (NASDAQ: PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform for cancer, respiratory and other diseases, reported that the first patient has been dosed in the Company’s Phase I clinical trial of PRS-343, its lead proprietary immuno-oncology drug candidate. PRS-343 is a first-in-class bispecific antibody-Anticalin fusion protein and functions as a tumor-targeted immune costimulatory 4-1BB agonist (Press release, Pieris Pharmaceuticals, OCT 2, 2017, View Source [SID1234520746]). The trial, a multicenter, open-label, Phase I dose escalation study that will include expansion cohorts, is designed to determine the safety, tolerability and potential anti-cancer activity of PRS-343 in patients with advanced or metastatic HER2-positive solid tumors for which standard treatment options are not available, are no longer effective, are not tolerated, or the patient has refused standard therapy. Elevated HER2 expression is associated with multiple cancers, including gastroesophageal, bladder, breast and a range of other tumor types.

“We are very pleased to have commenced dosing PRS-343 in this Phase I trial,” said Louis Matis, M.D., Senior Vice President and Chief Development Officer of Pieris. “PRS-343 has been designed to selectively activate 4-1BB-expressing T cells within the tumor microenvironment, thus diminishing the likelihood of toxicity from systemic immune activation. PRS-343 has also exhibited HER2 inhibitory activity in preclinical studies, thereby demonstrating the potential to mediate dual anti-tumor effects.”

About PRS-343:
PRS-343 is a bispecific monoclonal antibody-Anticalin fusion protein comprised of a HER2 tumor-targeting antibody genetically linked to a potent Anticalin specific for the immune costimulatory TNF family receptor 4-1BB (CD137). PRS-343 is being developed as the first 4-1BB based bispecific therapeutic to mediate the activation of tumor-specific T lymphocytes selectively within the tumor microenvironment (TME). 4-1BB is a potent costimulatory immunoreceptor and an established marker for tumor-specific infiltrating T lymphocytes, and is, therefore, an attractive target for cancer immunotherapy. In in vivo preclinical tumor models, PRS-343 has demonstrated potent T lymphocyte activation localized to the TME of established HER2-positive tumors, indicating the potential for both enhanced safety and efficacy.

About HER2-Positive Malignancies:
HER2 is a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells and is associated with aggressive disease progression. Multiple tumor types can express HER2 including breast, gastroesophageal, bladder, biliary (cholangiocarcinoma), colorectal, endometrial, ovarian, non-small cell lung, pancreatic, head and neck, and other cancers.

On October 2, 2017 NantKwest Inc. (Nasdaq:NK), a pioneering, next-generation, clinical-stage immunotherapy company focused on harnessing the unique power of the immune system using natural killer (NK) cells to treat cancer reported the clinical implementation of the company’s haNK cell therapy program to human clinical trials with the first participants treated in the first-in-human, Phase I haNK cell therapy clinical trial targeting a wide range of cancer types (Press release, NantKwest, OCT 2, 2017, http://ir.nantkwest.com/phoenix.zhtml?c=254059&p=RssLanding&cat=news&id=2303927 [SID1234520745]).

“Only about 10% of individuals are born with a high affinity Natural Killer cell type needed for the maximum killing effect when combined with monoclonal antibodies widely used in clinical practice today such as Trastuzamab, Rituxan and Avulamab. To maximize tumor cell death by this mechanism known as ADCC we have engineered our off the shelf natural killer cell line with a high affinity CD16 receptor. The potential for this haNK cell therapy is to improve patient outcomes for a significant percentage of the other 90% of individuals being treated with antibody therapy in a broad range of tumor types that can now be explored,” said Patrick Soon-Shiong, MD, Chairman and CEO of NantKwest.

Dr. Soon-Shiong added, “Our haNK cell therapy program was designed to optimize the unique properties of two immunotherapeutics (a cell based platform with a monoclonal antibody) used as a combination therapy. Multiple published preclinical studies have demonstrated the potential for haNK/antibody combinations to synergistically enhance antibody-dependent cell-mediated cytotoxicity (ADCC) activity, providing a sound scientific rationale for the transition of the haNK program into human clinical trials,” said Patrick Soon-Shiong, MD, Chairman and CEO of NantKwest.

haNK Cell Therapy Platform

NantKwest’s haNK cell therapy platform, an allogeneic, off-the-shelf therapy, was developed to optimize the key role of natural killer cells in mediating innate immunity, enhancing adaptive immune responses, and, specifically in the case of haNK, improve anti-tumor responses via antibody-dependent cell-mediated cytotoxicity (ADCC). ADCC is an important part of the human immune system associated with the synergistic interaction of natural killer cells with antibodies to directly kill a target cell that has been identified by an antigen-specific antibody. ADCC represents one of the key mechanisms that antibodies utilize to target and kill cancer cells.

Engineered to express the high-affinity variant of the CD16, high affinity Fc receptor (V158 FcγRIIIa), in multiple published preclinical studies, the combination of haNK cells with a variety of therapeutic antibodies has led to enhanced tumor cell killing when compared to use of the antibody as a single therapeutic agent, providing strong support for this novel combination immunotherapeutic approach.

haNK Phase I Study Background

The primary objective of the Phase I clinical study is to determine the safety of haNK cell therapy administered once per week in up to 16 patients with metastatic or locally advanced solid tumors. Secondary objectives include the determination of objective response rate, progression-free survival, overall survival, and any correlations between tumor molecular profiles (based on genomics, transcriptomics, and quantitative proteomics) and patient outcomes.