On November 8, 2016 Heron Therapeutics, Inc. (NASDAQ:HRTX) (the Company or Heron), a biotechnology company focused on improving the lives of patients by developing best-in-class medicines that address major unmet medical needs, reported financial results for the three and nine months ended September 30, 2016 and highlighted recent corporate progress (Press release, Heron Therapeutics, NOV 8, 2016, View Source;p=RssLanding&cat=news&id=2220688 [SID1234516540]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Recent Corporate Progress:
Heron commenced U.S. commercial sales of SUSTOL (granisetron) extended-release injection in October 2016. SUSTOL was approved by the U.S. Food and Drug Administration in August 2016. SUSTOL is indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens.
Positive results from the Company’s Phase 2 clinical study of HTX-011, its lead product candidate for the management of post-operative pain, in patients undergoing inguinal hernia repair (Study 202) were presented at PAINWeek 2016. The primary and important secondary endpoints were achieved, and HTX-011 was generally well tolerated. Furthermore, HTX-011 administered via instillation was shown to be equally effective to administration via injection.

Heron reported positive, top-line results from the Company’s second Phase 2 clinical study of HTX-011 in patients undergoing bunionectomy (Study 208). The primary and important secondary endpoints were achieved, and HTX-011 was generally well tolerated.

"The second half of 2016 is off to an exciting start for Heron, highlighted by the FDA approval and commercial launch of SUSTOL," commented Barry D. Quart, Pharm.D., Chief Executive Officer of Heron. "We are progressing toward our NDA submission for HTX-019, the approval of which could position Heron as the first company to address both mechanisms of action for the prophylaxis of CINV with injectable products. Furthermore, we are excited about the impressive clinical profile of HTX-011 emerging from our broad-based Phase 2 program and look forward to providing a further update on the HTX-011 program in early 2017."

Results of Operations
As of September 30, 2016, Heron had $88.9 million in cash, cash equivalents and short-term investments, compared to $131.2 million in cash, cash equivalents and short-term investments as of December 31, 2015.

Heron’s net cash used for operating activities for the three and nine months ended September 30, 2016 was $36.1 million and $95.6 million, respectively, compared to net cash used for operating activities of $19.9 million and $55.4 million, respectively, for the same periods in 2015.

Heron’s net loss for the three and nine months ended September 30, 2016 was $48.5 million and $125.2 million, or $1.24 per share and $3.34 per share, respectively, compared to a net loss of $22.7 million and $66.3 million, or $0.63 per share and $2.07 per share, respectively, for the same periods in 2015.

The increases in net cash used for operating activities and net loss in the 2016 periods as compared to the 2015 periods were primarily due to costs incurred in preparation for the commercial launch of SUSTOL, as well as clinical and manufacturing costs related to the development of HTX-019 and HTX-011.

On November 8, 2016 FibroGen, Inc. (NASDAQ:FGEN), a research-based biopharmaceutical company, reported financial results for the quarter ended September 30, 2016 and provided an update on the company’s recent developments (Press release, FibroGen, NOV 8, 2016, View Source;p=RssLanding&cat=news&id=2220698 [SID1234516521]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The completion of enrollment in our Phase 3 roxadustat studies in China is a significant milestone for FibroGen and our first-in-class small molecule treatment for anemia. We are gratified to be able to advance this promising new therapeutic for patients with chronic kidney disease," said Thomas B. Neff, FibroGen’s Chief Executive Officer. "In collaboration with our world-class partners, AstraZeneca and Astellas, we have substantially expanded the reach of our global development programs, while efficiently managing use of our resources."

Recent Developments

Roxadustat (FG-4592)

Anemia in Chronic Kidney Disease (CKD):

Completed enrollment of Phase 3 clinical development program in China for treatment of anemia in dialysis and non-dialysis chronic kidney disease patients
Initiating new drug application process in China in 2016, and expect to announce topline Phase 3 data in early 2017
In August, the independent data safety monitoring board reviewing the China Phase 3 data recommended that these studies continue without modification to current protocols
In October, the independent data safety monitoring board reviewing Phase 3 studies to support U.S. and European regulatory submissions recommended these studies continue without modification to current protocols
Achieved initial target enrollment objectives for all three FibroGen-sponsored Phase 3 clinical trials supporting U.S. and European approval, and are continuing to enroll Global Phase 3 program focused on U.S. incident dialysis and non-dialysis patients
Results from the Japan Phase 2 study in CKD non-dialysis-dependent patients will be presented at the American Society of Nephrology’s Kidney Week in November 2016
Remain on track for an NDA submission for roxadustat in the United States in 2018
Other Anemia Program Highlights

The U.S. FDA accepted the company’s investigational new drug application for a Phase 3 trial evaluating roxadustat for the treatment of anemia in myelodysplastic syndrome (MDS) patients
Pamrevlumab (FG-3019)

Fibrosis and Other Fibroproliferative Diseases

Data presented from the open-label extension of the 049 study in idiopathic pulmonary fibrosis (IPF) at the 19th International Colloquium on Lung and Airway Fibrosis in September showed no safety issues during prolonged treatment with pamrevlumab
Trends toward improved or stable pulmonary function and stable fibrosis observed in the initial one-year study (049) have continued among patients participating in the extension study
Anticipate topline results for 067 IPF placebo-controlled study and combination therapy sub-study in summer 2017
Continue to enroll locally advanced pancreatic cancer patients in open-label, randomized Phase 2 trial
Expect to present updated, interim results from open-label, randomized Phase 2 pancreatic cancer study in January 2017
Continue to enroll in the company’s open-label study of pamrevlumab in non-ambulatory Duchenne muscular dystrophy patients
Financial Highlights

Net loss per basic and diluted share for the quarter ended September 30, 2016, was $0.38, as compared to $0.74 a year ago.
At September 30, 2016, FibroGen had $356.8 million of cash, cash equivalents, investments, receivables, and restricted cash.

On November 8, 2016 XOMA Corporation (Nasdaq:XOMA), a leader in the discovery and development of therapeutic antibodies, reported its interleukin-2 (IL-2) monoclonal antibody program, a series of novel agents from its scientific discovery research unit, and announced the advancement of its parathyroid hormone receptor 1 (PTH1R) antibody antagonists program. (Press release, Xoma, NOV 8, 2016, View Source [SID1234516483]). These novel monoclonal antibodies are further examples of the capability of XOMA’s antibody platform and its expertise in the identification of novel oncology and oncology-related candidates with potential to positively affect outcomes in cancer patients.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"With our strategic focus on advancing our endocrine programs, we continue to seek ways to support and fund these efforts through discovery and licensing of our non-endocrine assets. For our oncology antibodies, we seek partners who have a deep commitment to and expertise in oncology drug development. An example of this is the TGF-beta antibody program that we licensed to Novartis last year, which we believe is advancing rapidly to initiation of clinical studies in the near future," said John Varian, Chief Executive Officer of XOMA. "We have unique expertise in creating new antibodies to treat a variety of cancers and the side effects associated with currently marketed therapies. As with our TGF-beta antibody program, we plan to out-license our IL-2 and PTH1R antibody programs to organizations that can rapidly advance them into clinical development."

IL-2 Monoclonal Antibodies Program
Immune checkpoint inhibitors are transforming cancer treatment and revitalizing interest in immunotherapies. While efficacy has been observed in patients with advanced metastatic disease treated with checkpoint inhibitors, not all patients respond, and most responses are incomplete. Preclinical studies suggest that combining additional modalities with checkpoint inhibitors will provide opportunities to improve patient outcomes.

"IL-2 has long been recognized as an effective therapy for metastatic melanoma and renal cell carcinoma, but it has serious dose-limiting toxicities that prevent broad clinical use. We generated novel antibodies that, when given with IL-2, are intended to steer IL-2 to enhance its positive impact with less toxicity, potentially improving the therapeutic index over standard IL-2 therapy," commented Paul Rubin, M.D., Senior Vice President, Research and Development, and Chief Medical Officer of XOMA.

A poster highlighting preclinical data from the IL-2 monoclonal antibodies program will be presented at The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 31st Annual Meeting & Associated Programs. The meeting will take place November 9-13 at the Gaylord National Hotel and Convention Center in National Harbor, Maryland.

Poster Presentation Details
Title: Novel IL-2/mAb complexes mediate potent anti-tumor immunity which is augmented with anti-PD-1 mAb therapy
Poster Topic: Combinations: Immunotherapy/Immunotherapy
Abstract Number: 454
Poster Session Date: Saturday, November 12, 2016
Poster Session Time: 11:45 a.m. — 1:00 p.m. ET

The abstract can be viewed on the SITC (Free SITC Whitepaper) website at www.sitcancer.org/2016.

PTH1R Monoclonal Antibodies Program
XOMA has developed several unique functional antibody antagonists targeting PTH1R, a G-protein-coupled receptor involved in the regulation of calcium metabolism. These antibodies have shown promising efficacy in in vivo studies and could potentially address high unmet medical needs, including primary hyperparathyroidism (PHPT) and humoral hypercalcemia of malignancy (HHM). The Company plans to present preclinical data at a scientific conference later this year.

"Our PTH1R program began as an endocrine program, but its mechanism-of-action is potentially also beneficial to patients suffering from HHM. HHM is present in many advanced cancers and is caused by high serum calcium due to increased levels of the PTH1R ligand PTH-related peptide (PTHrP). Since current HHM treatments often fall short and many cancer patients die from ‘metabolic death’, XOMA’s PTH1R antibodies could be very beneficial for the treatment of HHM," stated Patrick Scannon, M.D., Ph.D., Executive Vice President and Chief Scientific Officer of XOMA.

On November 8, 2016 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported that new clinical data are being presented from a Phase II Investigator Sponsored Trial led by the University of California, San Francisco (UCSF) (Press release, OncoSec Medical, NOV 8, 2016, View Source [SID1234516470]). This single-arm, open-label trial assessed the combination of OncoSec’s investigational intratumoral therapy, ImmunoPulse IL-12, and Merck’s KEYTRUDA (pembrolizumab) in patients with unresectable metastatic melanoma. A predictive biomarker was used to enroll patients that have a low likelihood of response to an anti-PD1 agent alone, and the purpose of the trial is to assess whether the addition of ImmunoPulse IL-12 can increase response rates in these patients. The data will be presented at an oral poster presentation (#466) by Dr. Alain Algazi at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) ("SITC") Annual Meeting in National Harbor, MD on November 11, 2016 at 12:50 PM EST.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In August 2016, OncoSec announced the publication of a research assay in the Journal of Clinical Investigation that might be used as a predicative biomarker in melanoma patients. The assay shows that patients with a low frequency of a certain phenotype of CD8 T cells, pre-disposes them to low response rates to PD-1 inhibitor therapy alone. The Company is using this biomarker assay to select patients considered to be PD-1 non responders for this ongoing combination study. The key endpoints of the study include: best overall response rate by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune-related Response Criteria; safety and tolerability; duration of response; 24-week landmark progression-free survival; median progression-free survival; and overall survival.

Results
Interim efficacy and safety data are available on 15 patients. In patients considered unable to respond to PD-1 we measured an overall response rate of 40% (6 /15), consisting of 4 complete responses and 2 partial responses by RECISTv1.1 criteria. Additionally, the therapy has an acceptable safety profile and was well tolerated. Analysis of tumor biopsies and blood correlated with patients’ responsiveness and demonstrated correlative immunological changes including an increased number of CD8+ tumor-infiltrating lymphocytes, tumoral RNA signatures and concordant immune phenotypes in the periphery. Investigators concluded that the combination of ImmunoPulse IL-12 with pembrolizumab in patients with an anti-PD-1 non-responsive phenotype enables an effective anti-PD-1 response.

Punit Dhillon, CEO of OncoSec, stated: "These results validate our therapeutic hypothesis for the ability of ImmunoPulse IL-12 to improve response rates in advanced melanoma. We wish to thank the investigators and patients for their continued participation in this study. We are working diligently to advance this agent towards registration-enabling studies, and we look forward to providing additional details regarding the Company’s operations and strategy at our upcoming Investor and Analyst Day on November 17, 2016."

Alain Algazi, M.D., Principal Investigator from UCSF, stated: "Although this open-label study is still ongoing and data are maturing, I am encouraged by the meaningful interim response rates that the combination of ImmunoPulse IL-12 and pembrolizumab has been able to achieve in a patient population otherwise expected to respond poorly to pembrolizumab alone. While checkpoint inhibition has conferred meaningful clinical benefit for advanced melanoma patients, there remains an urgent need to increase these agents’ efficacy through the rational combination with other immunotherapies. I look forward to the continued maturation of this data and to further reporting on the trial’s progress."

For more information about this trial, please visit: View Source;rank=3

On November 8 Lion Biotechnologies, Inc. (NASDAQ: LBIO), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte technology (TIL), reported encouraging data in four poster presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 31st Annual Meeting & Associated Programs in National Harbor, Maryland taking place November 9-13, 2016.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The data to be presented at SITC (Free SITC Whitepaper) is reflective of our progress in two main directions at Lion; process optimization and expansion of utilization of the TIL technology in new indications. In one abstract, data is provided demonstrating successful culturing of TIL cells from non-melanoma solid tumors, potentially expanding application of the Lion TIL technology in new indications. Additionally, we show progress in process optimization including development of cryopreservation methodology and a more efficient assay to assess potency of TIL cells," said Maria Fardis, PhD, MBA, Lion Biotechnologies President and Chief Executive Officer.

Poster Presentation: "Successful Expansion and Characterization of Tumor Infiltrating Lymphocytes (TILs) from Non-melanoma Tumors"

This study demonstrated the feasibility of culturing and expanding TILs isolated from non-melanoma tumors including bladder, cervical, head and neck, lung and triple negative breast cancer (TNBC).
TILs were harvested to assess cell count and viability, followed by immunophenotyping and cryopreservation for future studies.
Phenotypic characterization of TIL from bladder, cervical and lung cancer were > 60-70% CD8+ T cells whereas TILs from head and neck demonstrated variable distribution of CD8+ and CD4+ T cells. TIL propagated from TNBC were > 80% CD4+ T cells. Regardless of the tumors, most cultures had < 20% CD56+ NK cells.
Based on the successful culturing of TILs, clinical feasibility of adoptive cellular therapy for patients with non-melanoma solid tumors will be investigated.
Poster Presentation: "Artificial Antigen Presenting Cells Promote Expansion of Tumor Infiltrating Lymphocytes (TILs)"

The study evaluated artificial antigen presenting cells (aAPC) as a potential substitute for allogeneic peripheral blood mononuclear cells (PBMC) which are currently required for the expansion of TIL. The benefit of using aAPC is to reduce the price of the manufacturing process as well to turn the process into a more reproducible and scalable one.
A novel aAPC was developed from the CD64+ MOLM-14 human leukemia cell line, genetically engineered to express recombinant CD86 (B7-2) and CD137-L (41BBL) (MOLM14-86/137).
The study showed that co-culture of TILs with MOLM-14-86/137 aAPC resulted in expansion, metabolic activity and cytotoxicity that were sufficiently similar to that obtained with PBMC.
TIL differentiation, cellular respiration (OXPHOS) and redirected cytotoxicity were also within the range expected via co-culture with PBMC.
This data suggests that the expansion protocol using the novel MOLM14-86/137 aAPC can be tested in a clinical setting.
Poster Presentation: "Bioluminescent Redirected Lysis Assay (BRLA) as an Efficient Potency Assay to Assess Tumor-Infiltrating Lymphocytes (TILs) for Immunotherapy"

TIL therapy involves culturing and expanding T cells isolated from a patient’s tumor and then reinfusing them into the patient. TIL antitumor activity is commonly measured using tumor cells from the patient’s tumor, when available.
In order to test the potency of TILs, a BRLA assay was developed using an engineered P815 cell line. It requires no radionuclides and is more efficient than traditional cytotoxicity assays.
The assay was shown to measure TIL cytotoxicity in a highly sensitive dose dependent manner.
Poster Presentation: "Stable Tumor-Infiltrating Lymphocytes (TIL) Phenotype Following Cryopreservation"

Cryopreservation is a beneficial process which allows cell products to be shipped in a safe manner with less time constraints. In this study, the data show that cryopreservation did not affect the measured phenotypic characteristics of TIL, enabling Lion to further investigate the possibility of using cryopreserved TIL in a clinical setting.
Clinical studies using cryopreserved TIL have not been conducted so far.
In this study, fresh versus frozen/thawed TIL samples were tested to evaluate the expression of phenotypic markers.
Cryopreservation did not affect the measured phenotypic characteristics of TIL, with the exception of some regulatory molecules. Lion will further investigate the possibility of using cryopreserved TIL in a clinical setting.