On February 11, 2019 Precigen, Inc., a wholly-owned subsidiary of Intrexon Corporation (NASDAQ: XON) and a biopharmaceutical company specializing in the development of innovative gene and cellular therapies to improve the lives of patients, reported that the US Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for Precigen’s PRGN-3005, a first-in-class investigational therapy using autologous chimeric antigen receptor T (CAR-T) cells to treat advanced-stage platinum-resistant ovarian cancer patients (Press release, Intrexon, FEB 11, 2019, View Source [SID1234533229]).

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PRGN-3005 is the second candidate to clear IND utilizing Precigen’s transformative UltraCAR‑T platform that reduces manufacturing time to less than two days following non-viral gene transfer. PRGN-3005 UltraCAR-T is a multigenic CAR-T cell treatment utilizing Precigen’s clinically-validated Sleeping Beauty system to co-express a chimeric antigen receptor, membrane-bound interleukin‐15 (mbIL15), and a kill switch for better precision and control in targeting advanced ovarian cancer. This is an open-label, first-in-human Phase 1 dose escalation study to evaluate the safety and maximal tolerated dose of PRGN‐3005 UltraCAR-T.

"This patient population has limited treatment options and ovarian cancer remains one of the most challenging with minimal advances in long-term survival for patients with advanced disease," said Mary L. (Nora) Disis, MD, professor of medicine at the University of Washington and lead investigator for the PRGN-3005 study. "Clinical advancements and new research, including the PRGN-3005 UltraCAR-T study, are needed to make progress in fighting this intractable disease."

Precigen’s UltraCAR-T platform has the potential to disrupt the CAR-T treatment landscape by increasing patient access through shortening manufacturing time, decreasing manufacturing-related costs, and improving outcomes using advanced approaches for precise tumor targeting and control of the immune system. The platform brings several key advancements:

Non-viral gene transfer using multigenic vectors for expression of multiple effector genes leads to better precision and control of tumor targeting and eliminates the need for virus;
Sustained persistence and desired phenotype of infused UltraCAR-T helps address T-cell exhaustion, a common issue with current CAR-T therapies;
T-cell control by incorporation of kill switch technology to potentially improve the safety profile; and
Rapid manufacturing of UltraCAR-T cells using our proprietary non-viral gene transfer process, eliminates the need for ex vivo propagation, thus dramatically reducing wait times for patients from weeks to less than two days.
"We are pleased our PRGN-3005 UltraCAR-T investigational therapy received clearance from the FDA to advance into the clinic. This is an exciting milestone as it represents the first UltraCAR-T to enter the clinic targeting solid tumors," said Helen Sabzevari, PhD, President of Precigen. "This is an important step for patients and our dedicated employees who continue to work with urgency to execute our important mission of creating innovative medicines with meaningful benefit for patients."

About Ovarian Cancer
Worldwide, nearly 300,000 women are diagnosed with ovarian cancer every year1 and around 22,000 are diagnosed in the US2. Five-year survival rates depend on stage and type of ovarian cancer; however, stage IV survival can drop to as low as 20 percent.3.

Precigen : Advancing Medicine with Precision
Precigen is a dedicated discovery and clinical stage biopharmaceutical company advancing the next generation of gene and cellular therapies using precision technology to target the most urgent and intractable diseases in immuno-oncology, autoimmune disorders, and infectious diseases. Precigen also follows the science opportunistically in pursuit of promising programs in emerging therapeutics. Our technologies enable us to find innovative solutions for affordable biotherapeutics in a controlled manner. Precigen operates as an innovation engine progressing a preclinical and clinical pipeline of well-differentiated unique therapies toward clinical proof-of-concept and commercialization. Precigen was founded as a wholly-owned subsidiary of Intrexon Corporation (NASDAQ: XON) and leverages Intrexon’s proprietary technology platforms to advance human health. For more information about Precigen, visit www.precigen.com.

1World Health Organization, International Agency for Research on Cancer, Global Cancer Observatory. Cancer Today, Estimated number of new cases in 2018, worldwide, both sexes, all ages. Accessed December 2018 via WHO IARC GCO website.
2American Cancer Society Ovarian Cancer Special Section. Access December 2018 via ACS website.
3American Cancer Society. Survival Rates for Ovarian Cancer, by Stage. Accessed December 2018 via ACS website.

Safe Harbor Statement
Some of the statements made in this press release are forward-looking statements. These forward-looking statements are based upon our current expectations and projections about future events and generally relate to plans, objectives and expectations for the development of our business, including the timing and progress of preclinical and clinical trials and discovery programs. Although management believes that the plans and objectives reflected in or suggested by these forward-looking statements are reasonable, all forward-looking statements involve risks and uncertainties and actual future results may be materially different from the plans, objectives and expectations expressed in this press release.

On February 11, 2019 Enzo Biochem, Inc. (the "Company"), along with its subsidiary Enzo Life Sciences, Inc. reported that it has entered into a Settlement Agreement as of February 5, 2019 (the "Agreement") with Roche Diagnostics GmbH and Roche Molecular Systems, Inc. (together, "Roche") with respect to an action between the Company and Roche before the U.S. District Court, Southern District of New York, Case No 04-CV-4046. Roche has agreed to pay $21,000,000 in settlement pursuant to the Agreement (Press release, Enzo Biochem, FEB 11, 2019, View Source [SID1234533206]). This settlement does not affect Enzo’s civil action for patent infringement against Roche in the U.S. District Court for the State of Delaware, Enzo Life Sciences Inc. v. Roche Molecular Systems Inc., et al., civil action no. 12-cv-00106, which remains pending on appeal. The Agreement is filed with this current report as Exhibit 10.1 and incorporated herein by reference.

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On February 11, 2019 Hemispherx Biopharma, Inc. (NYSE American: HEB), an immuno-pharma company focused on unmet medical needs in immunology and oncology, reported the start at the UPMC Hillman Cancer Center in Pittsburgh, PA of a new clinical study supported by Merck that will combine the company’s Ampligen with Merck’s Keytruda for the treatment of recurrent, platinum-sensitive, ovarian cancer (Press release, Hemispherx Biopharma, FEB 11, 2019, View Source [SID1234533230]). The study will enroll up to 45 participants and be conducted at UPMC, which is sponsoring the study, by Robert Edwards, MD, director of the Ovarian Cancer Program at UPMC Magee Womens Hospital. The overall funding and support for the clinical trial and the supply of Keytruda is based upon a collaboration between Merck and UPMC. Hemispherx is not funding the clinical trial and its collaboration obligation relates to supplying the Ampligen needed for the clinical trial. Over the past year, Hemispherx has produced 16,000 vials of Ampligen, including all of the supply of Ampligen needed for this clinical trial. Hemispherx shipped Ampligen for the clinical trial to UPMC on January 29, 2019 and the first subject was enrolled. The company believes the study will be an important and more extensive test of Ampligen as an immune system primer that can convert "cold" tumors into "hot" tumors, thereby making the formerly "cold" tumors more responsive to Keytruda. View Source;cond=Ovarian+Cancer&cntry=US&state=US%3APA&city=Pittsburgh&rank=1

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This clinical trial will study how well Ampligen-based combination therapy works when given with Cisplatin and Keytruda in treating participants with recurrent ovarian cancer compared to historical controls. Drugs used in this combination therapy work by either direct antitumor activity, or by unleashing or enhancing the cancer immune responses that already exist. So called "checkpoint inhibitors" such as Merck’s Keytruda interfere with the ability of tumor cells to grow and spread when present in a "hot" tumor microenvironment. The clinical trial tests whether the combination therapy will work better than Keytruda alone in treating participants with ovarian cancer. Studies from UPMC and the Roswell Park Comprehensive Cancer Center, in human tumor explants, have demonstrated that Ampligen is a TLR3 restricted and targeted immune modulator that can facilitate the transformation of some "cold" tumor microenvironments into "hot" tumor microenvironments (Cancer Res. 2018 Aug 1;78(15):4292-4302).

"At Hemispherx we are determined to pursue a comprehensive R&D program focused on improved immune therapies for lethal malignancies such as recurrent ovarian cancer. We at Hemispherx are deeply grateful for the attention and support we are getting from Merck and the world-class ovarian cancer team at UPMC in this important major clinical trial," said Hemispherx CEO Thomas K. Equels. "We believe this clinical study at UPMC is an important step in Hemispherx’ overall clinical plan in immuno-oncology and just one of the major milestones we have recently announced. We believe that the clinical trials that are now underway are very important to our company. We have seen a clear synergistic effect in our animal laboratory studies in several different solid tumors. Data from human tumor explants indicate this phenomenon may extend to humans. In addition to the already existing large IV safety profile, we have established that Ampligen is generally well tolerated intraperitoneally. To the extent this follows through in vivo with humans in these clinical trials, we believe the expected synergy with the checkpoint inhibitors in humans has the potential to position Ampligen as a medical translational breakthrough in immuno-oncology. We believe the Ampligen clinical data are important first and foremost to those in need of such enhanced immuno-therapeutic response in recurrent cancers as well as a long-term driver for stockholder value. "

Cautionary Statement

Some of the statements included in this press release may be forward-looking statements that involve a number of risks and uncertainties. Among other things, for those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Any forward-looking statements set forth in this press release speak only as of the date of this press release. Among other things, no assurance can be given as to whether the trial at UPMC or other ongoing or planned trials will be successful or yield favorable data and the trials are subject to many factors including lack of regulatory approval(s), lack of study drug, or a change in priorities at the sponsoring Universities or Cancer Centers. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. This press release and prior releases are available at www.hemispherx.net. The information found on our website is not incorporated by reference into this press release and is included for reference purposes only.

On February 11, 2019 Immunomedics, Inc., (NASDAQ: IMMU) ("Immunomedics" or the "Company"), a leading biopharmaceutical company in the area of antibody-drug conjugates (ADC), reported that updated data with longer follow-up on sacituzumab govitecan, its lead investigational ADC, in patients with metastatic urothelial cancer (mUC) who have relapsed or are refractory to chemotherapies and immune checkpoint inhibitors (CPIs), have been accepted for an oral presentation at this year’s Genitourinary Cancers Symposium (ASCO-GU) (Press release, Immunomedics, FEB 11, 2019, View Source [SID1234533208]).

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As reported in the abstract released online, sacituzumab govitecan produced an overall response rate (ORR) of 31 percent in 45 heavily-pretreated mUC patients, with an encouraging median duration of response of 12.6 months and median progression-free survival of 7.3 months. Consistent with prior reports, the updated safety profile demonstrates that sacituzumab govitecan is generally well tolerated and manageable relative to other available therapies. Further data on subgroups will be presented at the meeting.

"Despite the late-stage setting, sacituzumab govitecan continues to show promising activity in patients who failed current standard of care for mUC," said Dr. Robert Iannone, Head of Research & Development and Chief Medical Officer of Immunomedics. "We believe these results support further investigation in a pivotal Phase 2 TROPHY U-01 study.

The trial design of TROPHY U-01 is the subject of the second presentation at ASCO (Free ASCO Whitepaper)-GU. Details of the two presentations are listed below (all times are in Pacific Time):

Friday, February 15, 2019

Sacituzumab govitecan (IMMU-132) in patients with previously treated metastatic urothelial cancer (mUC): Results from a Phase I/II study (Tagawa, et al.)

Oral Abstract Session B: Urothelial Carcinoma & Penile, Urethral, Testicular, & Adrenal Cancer

Abstract # 354

1:45 pm – 1:55 pm

Level 3 – Ballroom

Poster Session B: Prostate Cancer, Urothelial Carcinoma, and Penile, Urethral, Testicular, and Adrenal Cancers

Board B5

12:15 pm -1:45 pm and 5:15 pm – 6:15 pm

Level 1 – West Hall

TROPHY U-01: A Phase II open-label study of sacituzumab govitecan (IMMU-132) in patients with advanced urothelial cancer after progression on platinum-based chemotherapy and/or anti-PD-1/PD-L1 checkpoint inhibitor therapy (Tagawa, et al.)

Trials in Progress Poster Session B: Prostate Cancer, Urothelial Carcinoma, and Penile, Urethral, Testicular, and Adrenal

Abstract TPS495

Board N5

12:15 pm -1:45 pm and 5:15 pm – 6:15 pm

Level 1 – West Hall

On February 11, 2019 Aduro Biotech, Inc. (NASDAQ: ADRO) reported that the first patient has been dosed in a Phase 1 trial of ADU-S100 (MIW815), a novel stimulator of interferon genes (STING) pathway activator, in combination with YERVOY (ipilimumab), an approved anti-CTLA-4 antibody for the treatment of relapsed and refractory melanoma (Press release, Aduro Biotech, FEB 11, 2019, View Source;p=RssLanding&cat=news&id=2386898 [SID1234533231]). The multicenter trial (see www.clinicaltrials.gov, identifier: NCT02675439), which is part of an ongoing research and development collaboration with Novartis, will enroll advanced melanoma patients who have relapsed after or are refractory to treatment with anti-PD-1 antibodies, nivolumab or pembrolizumab.

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"We are pleased to initiate this study evaluating ADU-S100 with ipilimumab in a homogeneous patient population. Despite recent advancements in treating earlier stages of melanoma, the relapsed and refractory patient segment remains underserved due to a lack of therapeutic options. Based on their potential synergistic activity, ADU-S100 in combination with an anti-CTLA-4 antibody could generate a systemic adaptive immune response in patients with late-stage melanoma," commented Stephen Isaacs, chairman, president and chief executive officer of Aduro Biotech. "As demonstrated leaders in the STING pathway, we are committed to build upon the growing body of data we’ve generated thus far, including encouraging clinical signals demonstrated by ADU-S100 as a single agent and in combination with spartalizumab, an investigational anti-PD-1 antibody."

The protocol for investigation of ADU-S100 as a single agent was amended to include evaluation of ADU-S100 in combination with ipilimumab. During the ongoing dose escalation phase of the trial, ipilimumab will be administered at its approved dose and schedule, while the dose of ADU-S100 will be escalated. The dose expansion phase of the trial will evaluate the optimized dose of ADU-S100 in combination with ipilimumab in two expansion cohorts that will enroll patients with cutaneously and viscerally accessible melanoma.

As previously presented at the 2018 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, target engagement of ADU-S100 and activation of the STING pathway was demonstrated in the ongoing Phase 1 dose escalation of ADU-S100 alone through increases in key systemic cytokines, IL-6, MCP-1 and IFN- β after administration. Partial responses were observed in 4.9 percent of patients (n=2/41), including one patient with parotid gland cancer who received prior anti-PD-1 therapy. Stable disease (SD) was achieved in 26.8 percent of patients (n=11/41), including five patients who had received prior checkpoint inhibitor therapy. In the ongoing study of ADU-S100 in combination with spartalizumab, clinical responses were observed in several tumor types, including two patients who had previously demonstrated responses to checkpoint inhibitor therapy alone.

In preclinical models, activation of the STING pathway has been shown to rapidly invoke an innate immune response, which subsequently leads to a systemic and sustained adaptive immune response through tumor-specific-CD8+ T cells. Ipilimumab may further augment such immunity, by blocking the activity of the checkpoint protein, CTLA-4, resulting in enhanced activity of T cells that attack melanoma cells in the body, supported by the demonstration of combined activity of ADU-S100 and anti-CTLA-4 in preclinical models.

About STING Pathway Activator Technology
The Aduro-proprietary STING pathway activator product candidates, including ADU-S100 (MIW815), are synthetic small molecule immune modulators that are designed to target and activate human STING. STING is generally expressed at high levels in immune cells, including dendritic cells. Natural activation of STING is not always sufficient to prevent the growth and spread of cancer cells. In preclinical models, ADU-S100 directly activates STING to further amplify the natural anti-tumor response. Once activated, the STING receptor initiates a profound innate immune response through multiple pathways, inducing the expression of a broad profile of cytokines, including interferons and chemokines. This subsequently leads to the development of a systemic tumor antigen-specific T cell adaptive immune response.

Aduro’s lead molecule, ADU-S100, is the first therapeutic in development specifically targeting STING. In collaboration with Novartis, it is being tested in a Phase 1 clinical trial as a single agent and in combination with ipilimumab, and in a Phase 1b combination trial with spartalizumab (PDR001), an investigational anti-PD-1 monoclonal antibody. These studies are enrolling patients with cutaneously accessible, advanced/metastatic solid tumors or lymphomas. The trials are evaluating the ability of ADU-S100 to activate the immune system and recruit specialized immune cells to attack the injected tumor, leading to a broad immune response that seeks out and kills distant metastases.