On Febuary 27, 2017 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, received Fast Track designation from the U.S. Food and Drug Administration (FDA) for its ImmunoPulse IL-12, a potentially first-in-class, Intratumoral anti-cancer gene therapy that expresses interleukin-12 (IL-12) for the treatment of metastatic melanoma, following progression on pembrolizumab or nivolumab (Press release, OncoSec Medical, FEB 27, 2017, View Source [SID1234517850]).

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"With the number of melanoma patients now being treated with either pembrolizumab or nivolumab in either the first- or second-line settings, there will be an increasing number of patients who will not respond to therapy. Thus, there is a clear need for treatments that can rescue these patients and help them benefit from these immunotherapies," said Punit Dhillon, OncoSec President and CEO. "With the recent presentation of our interim data from our ongoing combination study with pembrolizumab in patients predicted not to respond to single-agent anti-PD-1 therapy, we are increasingly confident in ImmunoPulse IL-12 to potentially convert ‘cold’ tumors to ‘hot’ tumors to effectively and safely improve the response rates of these patients."

"This Fast Track designation by the FDA serves as an additional validation for OncoSec’s clinical development program," said Sharron Gargosky, Ph.D., Chief Clinical and Regulatory Officer. "As we launch our upcoming Phase 2b PISCES clinical trial, we look forward to collaborating closely with the FDA at this important stage of our clinical program."

The PISCES (Anti-PD-1 IL-12 Stage III/IV Combination Electroporation Study) will be a Phase 2b, Simon 2-stage, non-comparative, open-label, single-arm, multicenter study of ImmunoPulse IL-12 (intratumoral pIL-12 plus electroporation) in combination with an intravenous anti-PD-1 antibody in patients with histological diagnosis of melanoma with progressive locally advanced or metastatic disease defined as Stage III or Stage IV. Eligible patients will be those with Stage III/IV metastatic melanoma who are progressing or have progressed according to RECIST v1.1 guidelines on, or within, 24 weeks of receiving approved anti-PD-1 antibodies on either pembrolizumab or nivolumab treatment (either as monotherapy or in combination with another approved checkpoint inhibitor). The primary endpoint for this registration-directed trial will be overall response rate (ORR) at 24 weeks with secondary endpoints of best overall response rate (BORR), duration of response (DOR), median progression-free survival (PFS) and overall survival (OS). This clinical trial is planned to initiate in the first half of 2017.

The FDA established the Fast Track program to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening conditions, and demonstrate the potential to address unmet medical needs. Drugs that receive this designation benefit from more frequent communications and meetings with the FDA, to review the drug’s development plan including the design of the proposed clinical trials, use of biomarkers, and the extent of data needed for approval. Fast Track designated drugs may qualify for expedited FDA review, and a rolling Biologics License Application (BLA), if certain criteria are met.

On Feb. 27, 2017 (GLOBE NEWSWIRE) — Celsion Corporation (NASDAQ:CLSN) reported that Khursheed Anwer, Ph.D., Celsion’s executive vice president and chief science officer, presented two posters on February 23, 2017 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) – Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Clinical Immuno-Oncology Symposium held from February 23 – 25, 2017 in Orlando, FL (Press release, Celsion, FEB 27, 2017, View Source [SID1234517847]). The ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium focused on the latest clinical and translational research in immuno-oncology and the implications for clinical care.
The first poster (#155) entitled “Phase I study and activity of formulated IL-12 plasmid administered intraperitoneally in combination with standard neoadjuvant chemotherapy in patients with newly diagnosed advanced stage ovarian cancer” reported the latest clinical results from the Phase Ib dose escalating clinical trial (the OVATION Study) combining GEN-1, the Company’s IL-12 gene-mediated immunotherapy, with the standard of care for the treatment of newly-diagnosed patients with Stage III and IV ovarian cancer who will undergo neoadjuvant chemotherapy followed by interval debulking surgery.
In the first twelve patients dosed in the OVATION Study, GEN-1 plus standard chemotherapy produced impressive clinical results, with no dose limiting toxicities and highly promising efficacy signals in this difficult to treat cancer.
Of the first twelve patients dosed, one patient (8%) demonstrated a complete response (CR), eight patients (67%) demonstrated a partial response (PR) and three patients (25%) demonstrated stable disease (SD), as measured by RECIST criteria. This translates to a 100% disease control rate (DCR), and 75% objective response rate (ORR).

Eleven of twelve patients had successful resections of their tumors, with six patients having an optimal R0 resection, which indicates a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed, and four patients with a R1 resection, indicating microscopic residual tumor. One patient had an R2, indicating macroscopic residual tumor. One patient in the second cohort was ineligible for debulking surgery due to a medical complication unrelated to the study or the study drug.

Of the eleven surgically treated and evaluable patients, one patient demonstrated a complete pathological response (cPR), five patients demonstrated a micro pathological response (microPR), and five patients demonstrated a macroPR. These data compare favorably to historical data, which indicate that cPRs are typically seen in less than 7% of patients receiving neoadjuvant chemotherapy followed by surgical resection. cPRs have been associated with a median overall survival of 72 months, which is more than three years longer than those who do not experience a cPR. In addition, microPRs are seen in approximately 30% of patients, and are associated with a median overall survival of 38 months¹.

All eleven patients who completed treatment follow-up experienced a dramatic (greater than 90%) drop in their CA-125 protein levels as of their most recent study visit. CA-125 is used to monitor certain cancers during and after treatment. CA-125 is present in greater concentrations in ovarian cancer cells than in other cells. A 50% reduction in CA-125 levels is considered meaningful.
The second poster (#156) entitled “Immunological changes following intraperitoneal administration of a formulated IL-12 plasmid in combination with standard neoadjuvant chemotherapy in patients with newly diagnosed advanced stage ovarian cancer” reported preliminary translational data from the OVATION Study focusing primarily on the treatment-related changes in immune activating and immune suppressive T-cell populations in tumor tissue and in the levels of relevant cytokines in tumor ascites.
GEN-1 plus neoadjuvant chemotherapy resulted in dose-dependent increases in IFN-g levels and decreases in VEGF levels in peritoneal fluid, which is consistent with the results obtained from recurrent ovarian cancer patient population treated with GEN-1 in combination with standard chemotherapy in a previous clinical trial or in preclinical models of ovarian cancer.

Immuno-histochemical analysis of tumor tissue for various T-cell populations showed reduction in immunosuppressive T-cell phenotypes in most patients. The ratio of cytotoxic CD8+ T cells to immunosuppressive FoxP3, IDO1 and PD-1 expressing cells was also increased in a majority of patients.
“Our hypothesis is that GEN-1 plus neoadjuvant chemotherapy treatment will reprogram the tumor immune microenvironment towards a potent antitumor immune response,” said Dr. Anwer. “The available data demonstrate highly relevant immunological changes in the tumor immune environment, which supports the immune activating role of GEN-1 in this patient population. We are currently analyzing the tissue samples for additional immune cell populations and immune cytokines, and look forward to sharing a complete set of the clinical and translational results with the scientific and medical community.”
The OVATION Study is designed to enroll three to six patients per dose cohort with the goal of identifying a safe, tolerable and immunologically active dose of GEN-1 by recruiting and maximizing an immune response. Enrollment in the fourth and final cohort is ongoing with the final three patients currently on study. Celsion expects to complete the enrollment and treatment phase of the OVATION Study early in the second quarter and report final data, including translational data for all patients, by the end of the second quarter of 2017.
“We are very encouraged, as have been our Investigators, by the findings to-date in this difficult-to-treat patient population,” said Michael H. Tardugno, Celsion’s chairman, president and CEO. “Over the past year, we have demonstrated the potential of our GEN-1 program, in both first and second-line ovarian cancer, and we look forward to reporting final clinical and translational data from this important study in the second quarter of 2017.”
The two poster presentations will be available on Celsion’s website under “News & Investors – Scientific Presentations.”

On Feb. 27, 2017 (GLOBE NEWSWIRE) — Celsion Corporation (NASDAQ:CLSN) reported that Khursheed Anwer, Ph.D., Celsion’s executive vice president and chief science officer, presented two posters on February 23, 2017 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) – Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Clinical Immuno-Oncology Symposium held from February 23 – 25, 2017 in Orlando, FL (Press release, Celsion, FEB 27, 2017, View Source [SID1234517847]). The ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium focused on the latest clinical and translational research in immuno-oncology and the implications for clinical care.

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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

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The first poster (#155) entitled "Phase I study and activity of formulated IL-12 plasmid administered intraperitoneally in combination with standard neoadjuvant chemotherapy in patients with newly diagnosed advanced stage ovarian cancer" reported the latest clinical results from the Phase Ib dose escalating clinical trial (the OVATION Study) combining GEN-1, the Company’s IL-12 gene-mediated immunotherapy, with the standard of care for the treatment of newly-diagnosed patients with Stage III and IV ovarian cancer who will undergo neoadjuvant chemotherapy followed by interval debulking surgery.
In the first twelve patients dosed in the OVATION Study, GEN-1 plus standard chemotherapy produced impressive clinical results, with no dose limiting toxicities and highly promising efficacy signals in this difficult to treat cancer.
Of the first twelve patients dosed, one patient (8%) demonstrated a complete response (CR), eight patients (67%) demonstrated a partial response (PR) and three patients (25%) demonstrated stable disease (SD), as measured by RECIST criteria. This translates to a 100% disease control rate (DCR), and 75% objective response rate (ORR).

Eleven of twelve patients had successful resections of their tumors, with six patients having an optimal R0 resection, which indicates a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed, and four patients with a R1 resection, indicating microscopic residual tumor. One patient had an R2, indicating macroscopic residual tumor. One patient in the second cohort was ineligible for debulking surgery due to a medical complication unrelated to the study or the study drug.

Of the eleven surgically treated and evaluable patients, one patient demonstrated a complete pathological response (cPR), five patients demonstrated a micro pathological response (microPR), and five patients demonstrated a macroPR. These data compare favorably to historical data, which indicate that cPRs are typically seen in less than 7% of patients receiving neoadjuvant chemotherapy followed by surgical resection. cPRs have been associated with a median overall survival of 72 months, which is more than three years longer than those who do not experience a cPR. In addition, microPRs are seen in approximately 30% of patients, and are associated with a median overall survival of 38 months&supl;.

All eleven patients who completed treatment follow-up experienced a dramatic (greater than 90%) drop in their CA-125 protein levels as of their most recent study visit. CA-125 is used to monitor certain cancers during and after treatment. CA-125 is present in greater concentrations in ovarian cancer cells than in other cells. A 50% reduction in CA-125 levels is considered meaningful.
The second poster (#156) entitled "Immunological changes following intraperitoneal administration of a formulated IL-12 plasmid in combination with standard neoadjuvant chemotherapy in patients with newly diagnosed advanced stage ovarian cancer" reported preliminary translational data from the OVATION Study focusing primarily on the treatment-related changes in immune activating and immune suppressive T-cell populations in tumor tissue and in the levels of relevant cytokines in tumor ascites.
GEN-1 plus neoadjuvant chemotherapy resulted in dose-dependent increases in IFN-g levels and decreases in VEGF levels in peritoneal fluid, which is consistent with the results obtained from recurrent ovarian cancer patient population treated with GEN-1 in combination with standard chemotherapy in a previous clinical trial or in preclinical models of ovarian cancer.

Immuno-histochemical analysis of tumor tissue for various T-cell populations showed reduction in immunosuppressive T-cell phenotypes in most patients. The ratio of cytotoxic CD8+ T cells to immunosuppressive FoxP3, IDO1 and PD-1 expressing cells was also increased in a majority of patients.
"Our hypothesis is that GEN-1 plus neoadjuvant chemotherapy treatment will reprogram the tumor immune microenvironment towards a potent antitumor immune response," said Dr. Anwer. "The available data demonstrate highly relevant immunological changes in the tumor immune environment, which supports the immune activating role of GEN-1 in this patient population. We are currently analyzing the tissue samples for additional immune cell populations and immune cytokines, and look forward to sharing a complete set of the clinical and translational results with the scientific and medical community."
The OVATION Study is designed to enroll three to six patients per dose cohort with the goal of identifying a safe, tolerable and immunologically active dose of GEN-1 by recruiting and maximizing an immune response. Enrollment in the fourth and final cohort is ongoing with the final three patients currently on study. Celsion expects to complete the enrollment and treatment phase of the OVATION Study early in the second quarter and report final data, including translational data for all patients, by the end of the second quarter of 2017.
"We are very encouraged, as have been our Investigators, by the findings to-date in this difficult-to-treat patient population," said Michael H. Tardugno, Celsion’s chairman, president and CEO. "Over the past year, we have demonstrated the potential of our GEN-1 program, in both first and second-line ovarian cancer, and we look forward to reporting final clinical and translational data from this important study in the second quarter of 2017."
The two poster presentations will be available on Celsion’s website under "News & Investors – Scientific Presentations."

On February 27, 2017 BioCryst Pharmaceuticals, Inc. (NASDAQ:BCRX) reported financial results for the fourth quarter and full year ended December 31, 2016 (Press release, BioCryst Pharmaceuticalsa, FEB 27, 2017, View Source [SID1234517846]). In a separate press release issued earlier today, BioCryst announced positive results from an interim analysis of its APeX-1 clinical trial of BCX7353 for the treatment of HAE attacks.

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Fourth Quarter Financial Results

For the three months ended December 31, 2016, total revenues increased to $9.0 million from $4.6 million in the fourth quarter of 2015. This increase, compared to the fourth quarter of 2015, resulted from higher peramivir royalty revenue and inventory sales to Seqirus, and was slightly offset by lower collaborative revenue in the fourth quarter of 2016.

Research and Development (R&D) expenses of $12.2 million decreased in the fourth quarter of 2016, as compared to R&D expense of $19.0 million in the fourth quarter of 2015. The decrease was due primarily to lower spending on the Company’s HAE portfolio of compounds associated with the discontinuation of avoralstat development in 2016.

Selling, general and administrative (SG&A) expenses of $2.6 million in the fourth quarter of 2016 decreased slightly from the $2.7 million in the fourth quarter of 2015.

Interest expense was $2.1 million for the fourth quarter of 2016 and $1.3 million in the fourth quarter of 2015. Also, a $5.7 million mark-to-market gain on the Company’s foreign currency hedge was recognized in the fourth quarter of 2016, compared to a $229,000 mark-to-market gain in the fourth quarter of 2015. These gains result from periodic changes in the U.S. dollar/Japanese yen exchange rate and the related mark-to-market valuation of our underlying hedge arrangement.

The net loss for the fourth quarter of 2016 was $4 .5 million, or $0.06 per share, compared to a net loss of $18.1 million, or $0.25 per share for the fourth quarter of 2015.

2016 Financial Results

For the year ended December 31, 2016, total revenues decreased to $26.4 million from $48.3 million in 2015. The decrease in 2016 revenues, as compared to 2015, was primarily due to the RAPIVAB out-licensing transaction to Seqirus, which resulted in the recognition of $21.8 million of collaborative revenue in 2015 and a $4.0 million decrease in 2016 RAPIVAB product sales, as well as a reduction in collaboration revenue associated with lower galidesivir development activity in 2016. All of these decreases were slightly offset by a $7.3 million increase in 2016 peramivir royalty revenue derived from BioCryst’s commercial partners. A component of the peramivir royalty revenue was $5.7 million of Japanese government stockpiling revenue that is available for general corporate use. Although these orders provided a significant cash infusion, stockpiling royalty revenues may not recur on an annual basis as they are subject to the Japanese government’s appropriation and stockpiling process, which is difficult to predict.

R&D expenses decreased to $61.0 million for 2016 from $72.8 million for 2015. This decrease was primarily due to lower spending on the Company’s HAE portfolio of compounds associated with the discontinuation of avoralstat development in 2016.

SG&A expenses decreased to $11.3 million in 2016 from $13 .0 million in 2015, due primarily to lower unrestricted grants awarded to HAE patient advocacy groups, as well as a general reduction of administrative expenses.

Interest expense was $6.5 million in 2016 and $5.2 million in 2015. In addition, a $1.7 million mark-to-market loss on the Company’s foreign currency hedge was recognized in 2016, compared to a $564,000 million mark-to-market loss in 2015. These gains result from periodic changes in the U.S. dollar/Japanese yen exchange rate and the related mark-to-market valuation of our underlying hedge arrangement. During 2016 and 2015, the Company also realized currency hedge gains of $811,000 in 2016 and $1.7 million in 2015 from the exercise of a U.S. Dollar/Japanese yen currency option.

The Company’s 2016 net loss increased to $55.1 million, or $0.75 per share, compared to a net loss of $43.0 million, or $0.59 per share for 2015.

Cash, cash equivalents and investments totaled $65.1 million at December 31, 2016 and represented a $35.8 million decrease from $100.9 million at December 31, 2015. Net operating cash use for 2016 was $61.9 million. In September 2016, the Company closed a $23 million senior credit facility that allowed it to extend its forecasted cash runway into 2018.

Clinical Development Update

On February 27th, the Company reported statistically significant and clinically meaningful reductions in attack frequency from an interim analysis of its ongoing APeX-1 clinical trial in patients with HAE.

On January 30th, the Company announced that the European Medicines Agency (EMA) accepted the Company’s filing of its peramivir Marketing Authorization Application (MAA) for treatment of symptoms typical of influenza in adults 18 years and older. The acceptance of the MAA begins the review process by the EMA under the centralized licensing procedure for all 28 member states of the European Union, Norway and Iceland.

On January 8th, the Company announced that Health Canada approved RAPIVAB (peramivir injection), for intravenous (I.V.) treatment of acute, uncomplicated influenza. Peramivir is being commercialized by Seqirus on a worldwide basis, excluding Japan, Taiwan, Korea and Israel.

On October 26, 2016, the Company announced positive results from a study of galidesivir (formerly BCX4430) administered to Rhesus monkeys infected with the Zika virus at a late-breaker oral presentation at IDWeek 2016 in New Orleans.
Financial Outlook for 2017

Based upon development plans and our awarded government contracts, BioCryst expects its 2017 net operating cash use to be in the range of $30 to $50 million, and its 2017 operating expenses to be in the range of $53 to $73 million. Our operating expense range excludes equity-based compensation expense due to the difficulty in reliably projecting this expense, as it is impacted by the volatility and price of the Company’s stock, as well as by vesting of the Company’s outstanding performance-based stock options.

On February 27, 2017 Kura Oncology, Inc. (Nasdaq:KURA), a clinical stage biopharmaceutical company, reported an oral presentation for its lead product candidate, tipifarnib, at the 15th International Congress on Targeted Anticancer Therapies (TAT 2017), taking place March 6-8, 2017 in Paris, France (Press release, Kura Oncology, FEB 27, 2017, View Source [SID1234517845]). The presentation will feature clinical data from the first stage of Kura Oncology’s tipifarnib Phase 2 program in HRAS mutant tumors.

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Presentation:
Date & Time: March 6, 2017, 2:45 p.m. – 3:00 p.m. CET
Title of Presentation: Preliminary evidence of clinical activity with tipifarnib in squamous cell carcinomas of the head & neck (SCCHN) with HRAS mutations
Presenter: Alan L. Ho, M.D., Ph.D., Memorial Sloan Kettering Cancer Center
Session: Plenary Session 3: Phase 1 Studies – Completed or in progress (miscellaneous drugs & targets)