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OncoSec Announces Positive Phase II Data Demonstrating Company’s ImmunoPulse® IL-12 in Combination with Pembrolizumab Increased Response Rates in Anti-PD-1 Non-Responder Melanoma Patients

On February 23, 2017 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported new positive clinical data from a Phase II Investigator Sponsored Trial assessing the combination of OncoSec’s investigational intratumoral therapy, ImmunoPulse IL-12, and the approved anti-PD- 1 therapy (pembrolizumab), in patients with unresectable metastatic melanoma (Press release, OncoSec Medical, FEB 23, 2017, View Source [SID1234517814]). The results of this single-arm, open-label trial, which was led by the University of California, San Francisco (UCSF), indicated that ImmunoPulse IL-12 can increase response rates in patients who are not expected to respond to anti-PD-1 therapy alone.

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The trial is evaluating the following key endpoints: best overall response rate (BORR) by 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 (PFS); median PFS; and overall survival (OS). The study results showed an overall response rate (ORR) at 24 weeks of 43% (9/21), and BORR of 48% by RECIST v1.1. There were 24% (5/21) complete responders (CR), 19% (4/22) partial responders (PR), and 9% (2/21) stable disease (SD) for a total disease control rate of 52% (11/21). These data are consistent with, and expand upon, previously reported preclinical and clinical data that provide a strong rationale for combining ImmunoPulse IL-12 with anti-PD-1 blockade.

"Collectively, these data suggest that intratumoral IL-12 DNA with electroporation in combination with pembrolizumab can effectively alter the tumor microenvironment by triggering adaptive resistance," said Alain Algazi, M.D., the study’s lead investigator, and skin cancer specialist in the Melanoma Center at the UCSF Helen Diller Family Comprehensive Cancer Center. "This increases the substrate for a therapeutic PD-1/PD-L1 blockade while driving systemic anti-tumor immunity and concordant clinical responses in patients unlikely to benefit from anti-PD-1 monotherapy."

Dr. Algazi presented the study findings today in an oral presentation titled, "Immune monitoring outcomes of patients with stage III/IV melanoma treated with a combination of pembrolizumab and intratumoral plasmid interleukin 12 (pIL-12)" (Abstract #78), at the ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium in Orlando, FL.

In this trial, a biomarker that has previously been shown to be predictive of response to checkpoint inhibitor therapy was used to enroll 22 patients who have a low likelihood of responding to an anti-PD-1 therapy. These patients were treated with the combination of intravenous pembrolizumab and ImmunoPulse IL-12 for more than 24 weeks.

The combination therapy continued to demonstrate a favorable safety profile and was well tolerated. Importantly, of the 22 patients enrolled, nine had previous checkpoint inhibitor therapy; ORR for this subset of patients was 33% (3/9).

Comprehensive immune monitoring of blood and tissue samples showed that the combination of ImmunoPulse IL-12 with pembrolizumab produces a safe and powerful systemic immune response. This response leads to an increase in tumor-specific CD8+ T-cells and an "adaptive immune resistance" that broadly supports an immune-directed mechanism that is differentiated between responders and non-responders. Analysis of the biomarker data suggests that the combination of ImmunoPulse IL-12 with pembrolizumab is transforming "cold" tumors, which would be predicted to not respond to anti-PD-1 therapy, into "hot" tumors, thus increasing the potential for a meaningful clinical response to the checkpoint inhibitor therapy. Moreover, an analysis of pre-treatment samples using various analytical methods that have also been demonstrated to predict response to anti-PD-1 therapy, including immunohistochemistry (IHC) and RNA expression of critical immune-related genes by NanoString, correlate with the predictive biomarker used to enroll patients for this study.

"OncoSec’s vision to bring intratumoral gene therapies to the oncology market continues to advance with these positive, impactful data, which hold immense promise for cancer patients who are unlikely to benefit from immunotherapy," said Punit Dhillon, OncoSec President and CEO. "These results provide a strong foundation for our planned Phase II registration trial, which will evaluate the combination of ImmunoPulse IL-12 and an anti-PD-1 therapy in melanoma patients who have previously failed an approved anti-PD-1 therapy alone. We expect to initiate this study later in 2017."

The full-text abstract is available and can be viewed on ASCO (Free ASCO Whitepaper)-SITC’s website at www.immunosym.org. The presentation is available in the Publications section of OncoSec’s website.

About the ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium
The ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium is a three-day meeting focused on clinical and translational research in immuno-oncology and the implications for clinical care. This is a new meeting, one that will address the high level of need for clinical education in a field where all aspects of care are fundamentally different from traditional therapies. For more information, please visit www.immunosym.org.

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Insmed Reports Fourth Quarter 2016 Financial Results and Provides Business Update

On February 23, 2017 Insmed Incorporated (Nasdaq:INSM), a global biopharmaceutical company focused on the unmet needs of patients with rare diseases, reported financial results for the fourth quarter and year ended December 31, 2016 and provided a business update (Press release, Insmed, FEB 23, 2017, View Source [SID1234517842]).

Business Update

Achieved enrollment objective in global phase 3 study of ARIKAYCE. In November 2016, the company announced that it has achieved its patient enrollment objective in the phase 3 study of ARIKAYCE (liposomal amikacin for inhalation). The study, which is known as CONVERT or INS-212, is evaluating ARIKAYCE in treatment refractory nontuberculous mycobacteria (NTM) lung disease caused by Mycobacterium avium complex (MAC). The primary efficacy endpoint is the proportion of subjects who achieve culture conversion at Month 6 in the ARIKAYCE plus multi-drug regimen arm compared to the multi-drug regimen without ARIKAYCE arm. The Company expects to report the top-line data in the second half of 2017.
Granted U.S. Patent for ARIKAYCE, extending patent protection by more than five years into 2034. U.S. Patent 9,566,234 was issued to Insmed on February 14, 2017. The claims of the patent relate in part to systems and methods for treating pulmonary infections, including NTM infections, comprised of an aqueous dispersion of liposomal complexed aminoglycoside, which can be amikacin sulfate, with a nebulizer.
Advancing INS1007 toward Phase 2 trial. In October, the company exclusively licensed global rights to INS1007 (previously AZD7986) from AstraZeneca. INS1007 is a small molecule, oral reversible inhibitor of dipeptidyl peptidase I (DPP1), an enzyme responsible for activating neutrophil serine proteases (NSPs) in neutrophils when they are formed in the bone marrow. In chronic inflammatory lung diseases, neutrophils accumulate in the airways and result in excessive active NSPs that cause lung destruction and inflammation. The company expects to begin a phase 2 dose-ranging study of INS1007 in non-cystic fibrosis (non-CF) bronchiectasis in 2017. Non-CF bronchiectasis is a rare, progressive, neutrophil-driven pulmonary disorder with no approved therapies. Insmed is also evaluating the potential of INS1007 in other indications and expects to announce plans for phase 2 studies in additional disease states by the end of 2017.
“2017 represents a pivotal year for Insmed, with the potential to set the company on a new growth trajectory supported by a portfolio of novel products that address rare diseases,” said Will Lewis, president and chief executive officer of Insmed. “We anticipate announcing top-line results from our ongoing phase 3 CONVERT study of ARIKAYCE for the treatment of NTM lung disease which, if positive, may provide the basis for accelerated approval in the U.S. and potentially other parts of the world. We are also focused on advancing our pre-regulatory activities to support a timely filing and continuing to build NTM lung disease awareness among physicians. We plan to manage our clinical, pre-commercial and operational priorities while maintaining our commitment to efficient use of capital.”

Fourth Quarter Financial Results

For the fourth quarter of 2016, Insmed posted a net loss of $68.4 million, or $1.10 per share, compared with a net loss of $31.2 million, or $0.51 per share, for the fourth quarter of 2015. The fourth quarter 2016 results include $30.0 million of expense related to an upfront payment to AstraZeneca for INS1007.

Research and development expenses were $54.9 million for the fourth quarter of 2016, compared with $19.6 million for the fourth quarter of 2015. The increase was primarily due to the $30.0 million upfront payment related to INS1007, as well as the advancement of the company’s global phase 3 CONVERT study of ARIKAYCE in NTM lung disease and an increase in headcount and related expenses.

General and administrative expenses for the fourth quarter of 2016 were $12.2 million, compared with $12.9 million for the fourth quarter of 2015. The expenses in the fourth quarter of 2016 were relatively flat compared to the prior year and included $3.7 million of expenses related to pre-commercial activities for ARIKAYCE.

Balance Sheet Highlights and Cash Guidance

As of December 31, 2016, Insmed had cash and cash equivalents of approximately $163 million. The company’s cash operating expenses for the second half of 2016 were $64 million, not including the $30 million upfront payment related to INS1007 and excluding depreciation and stock-based compensation expense. Insmed ended the fourth quarter of 2016 with $55 million in debt.

The company is investing in the following activities in 2017: (i) clinical development of ARIKAYCE, (ii) regulatory and pre-commercial initiatives for ARIKAYCE, and (iii) preclinical and clinical activities for its earlier-stage development candidate INS1007. As a result of these activities, Insmed expects its cash-based operating expenses to be in the range of $67 million to $77 million for the first half of 2017. This range primarily reflects spending for the CONVERT study, the follow on 312 study for those NTM patients that do not convert, and continued regulatory and commercial development of ARIKAYCE. The estimates also include expenses related to INS1007, including inventory purchases as well as preclinical and clinical start-up activities.

Heron Therapeutics Announces Fourth Quarter and Full Year 2016 Financial Results and Recent Corporate Progress

On February 23, 2017 Heron Therapeutics, Inc. (NASDAQ: HRTX) (the Company or Heron), a commercial-stage biotechnology company focused on developing novel best-in-class treatment solutions to address some of the biggest unmet patient needs, reported fourth quarter and full year 2016 financial results and highlighted recent corporate progress (Press release, Heron Therapeutics, FEB 23, 2017, View Source [SID1234517840]).

Recent Corporate Progress

Pain Franchise
Advanced HTX-011 through Four Positive Phase 2 Studies. HTX-011 is Heron’s investigational, long-acting formulation of the local anesthetic bupivacaine in a fixed-dose combination with the anti-inflammatory meloxicam for the prevention of post-operative pain. In four Phase 2 studies, HTX-011 produced statistically significant reductions in both pain intensity and the need for opioids compared to saline placebo following procedures with incisions ranging from very large (abdominoplasty) to very small (hernia repair and bunionectomy surgeries). Statistically significant reductions in pain and opioid use were also demonstrated when compared against bupivacaine solution, the current standard-of-care. Heron anticipates initiating Phase 3 studies in 2017 and filing a New Drug Application (NDA) in 2018.

Established Synergy of Heron’s Novel Formulation of Bupivacaine and Meloxicam. HTX-011 demonstrated a statistically significant benefit over each individual component of the product alone, providing evidence of the synergistic activity of bupivacaine and meloxicam in the HTX-011 formulation.

CINV Franchise
Launched First Commercial Product, SUSTOL. SUSTOL (granisetron) extended-release injection 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. Heron launched SUSTOL in October 2016, and we anticipate net sales of SUSTOL in 2017 to range from $15 to $25 million.

Submitted NDA for CINVANTITM (HTX-019). CINVANTI is the first surfactant-free, intravenous formulation of aprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV). If approved by the FDA, CINVANTI will strengthen Heron’s CINV portfolio by adding a second, complementary therapeutic agent. In January 2017, Heron submitted an NDA with the FDA for CINVANTI and expects to receive approval in the fourth quarter of 2017.

"2016 was an exciting and transformational year for Heron, highlighted by the release of our best-in-class Phase 2 data for HTX-011 and our FDA approval and commercial launch of SUSTOL," said Barry D. Quart, Pharm.D., Chief Executive Officer of Heron. "2017 is off to a promising start as well, highlighted by our submission of an NDA for CINVANTI, our second, complementary therapeutic agent in the CINV category, and the release of strong Phase 2 results of HTX-011 in abdominoplasty."

Financial Results
As of December 31, 2016, we had cash, cash equivalents and short-term investments of $51.1 million. In January 2017, we completed an underwritten public offering of 14.1 million shares of our common stock for net proceeds of $163.7 million. As of December 31, 2016, our pro-forma cash, cash equivalents and short-term investments, adjusting for the January 2017 public offering, was $214.8 million. This compares to $131.2 million in cash, cash equivalents and short-term investments as of December 31, 2015.

For the quarter and year ended December 31, 2016, we recognized net product sales of $1.3 million related to sales of SUSTOL. Due to the recent launch, we have recognized revenue only when our specialty distributors have resold SUSTOL to healthcare providers, the end users. We have deferred an additional $1.1 million in SUSTOL sales to the specialty distributors.

Our net loss for the quarter and year ended December 31, 2016 was $48.0 million and $173.1 million, or $1.22 per share and $4.56 per share, respectively, compared to a net loss of $31.2 million and $97.6 million, or $0.87 per share and $2.95 per share, respectively, for the same periods in 2015. Net loss for the quarter and year ended December 31, 2016, included non-cash, stock-based compensation expense of $7.3 million and $26.0 million, respectively, compared to $5.8 million and $14.4 million for the same periods in 2015.

Our net cash used for operating activities for the quarter and year ended December 31, 2016 was $38.5 million and $134.1 million, respectively, compared to net cash used for operating activities of $23.2 million and $78.5 million, respectively, for the same periods in 2015.

The increases in net loss and net cash used for operating activities 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 CINVANTI and HTX-011.

Five Prime Announces Fourth Quarter and Full Year 2016 Financial Results

On February 23, 2017 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported a corporate update and reported financial results for the fourth quarter and full year ending December 31, 2016 (Press release, Five Prime Therapeutics, FEB 23, 2017, View Source [SID1234517836]).

"2016 was a year of tremendous progress in Five Prime’s clinical and preclinical pipeline," said Lewis T. "Rusty" Williams, M.D., Ph.D., president and chief executive officer of Five Prime. "We advanced our three clinical-stage programs and look forward to announcing data from each of these programs this year. With a concerted focus on building out our pipeline, we also unveiled three preclinical programs that we advanced into IND-enabling activities. We are on track to meet our goal of filing at least one IND application for a new molecule each year for the foreseeable future, beginning this year."

2016 Business Highlights and Recent Developments

Clinical Pipeline:

Cabiralizumab (FPA008): an investigational antibody that inhibits CSF1R and has been shown to block the activation and survival of monocytes and macrophages. In the setting of advanced cancer, tumor-associated macrophages can inhibit the immune system’s ability to eradicate the disease. In pigmented villonodular synovitis (PVNS), a CSF-1-driven tumor, the bulk of the tumor mass in joints is formed by the macrophages themselves. Five Prime and Bristol-Myers Squibb (BMS) have an exclusive worldwide collaboration agreement for the development and commercialization of cabiralizumab for these and potentially additional indications.
– Initiated Phase 1b portion of cabiralizumab/OPDIVO trial.
In October 2016, Five Prime initiated the Phase 1b portion of the clinical trial evaluating the immunotherapy combination of cabiralizumab with the PD- 1 immune checkpoint inhibitor OPDIVO (nivolumab) in multiple tumor types. Five Prime and BMS are evaluating the safety, tolerability and preliminary efficacy of the combination in advanced solid tumors, including non-small cell lung cancer, squamous cell carcinoma of the head and neck, pancreatic cancer, glioblastoma, renal cell carcinoma and ovarian cancer. Five Prime expects to complete enrollment in the current Phase 1b trial cohorts in the second half of 2017.

– Advanced the Phase 2 trial of cabiralizumab in patients with tenosynovial giant cell tumor (TGCT), also known as pigmented villonodular synovitis (PVNS).
Five Prime expects to complete enrollment of the Phase 2 trial of cabiralizumab in PVNS in the first half of 2017. Five Prime is evaluating clinical measures, including response rate, pain and range of motion in approximately 30 PVNS patients.

– Five Prime plans to seek regulatory guidance on a pivotal trial in diffuse PVNS.

– Five Prime plans to disclose clinical data from the cabiralizumab PVNS trial at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2017 Annual Meeting and from the cabiralizumab immuno-oncology trial in the second half of 2017.

FPA144: an isoform-selective antibody in development as a targeted immuno-therapy for tumors that overexpress FGFR2b, a splice variant of a receptor for some members of the fibroblast growth factor (FGF) family. FPA144 has been engineered for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) to increase direct tumor cell killing by recruiting natural killer (NK) cells. Five Prime retains global development and commercialization rights to FPA144.
– Opened new gastric cancer cohorts and added a bladder cancer cohort in Phase 1 monotherapy trial of FPA144. Enrollment continues in the expansion portion of the trial, evaluating the safety, PK and efficacy of biweekly 15 mg/kg infusions of FPA144 in patients with gastric cancer whose tumors highly overexpress FGFR2b. During the third quarter of 2016, Five Prime added cohorts to evaluate FPA144 in patients with bladder cancer whose tumors overexpress FGFR2b and in patients with gastric cancer whose tumors express moderate or low levels of FGFR2b. Five Prime reported initial single-agent efficacy and safety data at the ASCO (Free ASCO Whitepaper) 2016 Annual Meeting and at the ASCO (Free ASCO Whitepaper) 2016 Gastrointestinal Cancers Symposium.

– Five Prime plans to seek regulatory guidance on a registrational path for FPA144 in combination with chemotherapy as an early-line gastric cancer therapy.

– Five Prime plans to disclose updated clinical data from the FPA144 program at the ASCO (Free ASCO Whitepaper) 2017 Annual Meeting.

FP-1039: a protein drug designed to block FGF signaling. As a ligand trap, FP-1039 binds to and neutralizes a subset of FGF ligands (such as FGF2), preventing these growth-promoting and angiogenic proteins from reaching FGFR1 on the surface of tumor cells.
– Five Prime plans to make decisions on potential future development of FP-1039 in mesothelioma after data on objective response rate, disease control rate and progression-free survival are mature. Five Prime regained full rights to FP-1039 from GlaxoSmithKline (GSK) in September 2016. GSK is completing the ongoing Phase 1b trial combining FP-1039 with 1st-line pemetrexed and cisplatin in untreated, unresectable mesothelioma. GSK concluded trial recruitment with 25 patients enrolled at the 15 mg/kg dose in June 2016, and continues to dose and follow patients.

– Five Prime plans to disclose clinical data from this program at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress.

Preclinical Research and Development:

Five Prime unveiled three preclinical development candidates in IND-enabling studies at its R&D Day in New York City in December 2016.
– FPA150 (anti-B7-H4)

— An antibody designed for two mechanisms of action: to block an inhibitory T cell checkpoint pathway and to enhance killing of B7-H4-expressing tumors by ADCC.
— Investigational New Drug (IND) application planned for the fourth quarter of 2017.

– FPA154 (GITR agonist antibody)

— A tetravalent agonist antibody designed for greater GITR activation versus conventional antibodies. Conventional GITR agonist antibodies have two GITR binding sites while FPA154 has four.
— IND application planned for the fourth quarter of 2017.

– FPT155 (CD80)

— A natural, multi-targeting immune modulator that stimulates T cell responses through three critical pathways: CTLA4 blockade, CD28 agonism (without superagonism) and PD-L1 blockade that removes a potent inhibitory checkpoint.
— IND planned in 2018.

Progress in pre-clinical and research programs is on track for the company to achieve the goal of filing at least one IND application for a new molecule each year for the foreseeable future, beginning this year.

Completed multiple immuno-oncology research screens to identify new targets and drug candidates. Five Prime’s research team completed functional screens on CD8 T cells and regulatory T cells, as well as a comprehensive screen of all extracellular binding interactions in the "immunome," a defined subset of 700 extracellular proteins enriched for potential immune cell modulators. Five Prime conducted the screens to identify new immuno-oncology targets, which the company is prioritizing for further development as targets for new drug candidates or drug candidates themselves, either as monotherapies or as part of rational combination regimens.

Five Prime will feature three preclinical research poster presentations during the 2017 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, April 1 – 5, 2017, in Washington, D.C.
Summary of Financial Results and Guidance:

Cash Position. Cash, cash equivalents and marketable securities totaled $421.7 million on December 31, 2016 compared to $517.5 million on December 31, 2015. The decrease in year-end cash in 2016 was primarily attributable to net cash used in operations to advance the company’s clinical and preclinical pipeline.
Revenue. Collaboration and license revenue for the fourth quarter of 2016 was $8.3 million compared to $363.3 million for the fourth quarter of 2015. During the fourth quarter of 2015, the company recognized the entire upfront payment of $350 million as revenue under the cabiralizumab license and collaboration agreement with BMS. Collaboration and license revenue for the full year 2016 was $30.7 million compared to $379.8 million for the full year 2015.
R&D Expenses. Research and development expenses for the fourth quarter of 2016 increased by $8.2 million, or 39%, to $29.1 million from $21.0 million in the fourth quarter of 2015. Full year 2016 research and development expenses increased by $23.9 million, or 34%, to $94.1 million in 2016 from $70.2 million in 2015. These increases were primarily related to advancing the FPA144 program in a phase 1 clinical trial, advancing the cabiralizumab program in immuno-oncology and PVNS, and advancing our internal immuno-oncology preclinical and research activities.
G&A Expenses. General and administrative expenses for the fourth quarter of 2016 increased by $1.9 million, or 22%, to $10.5 million from $8.6 million in the fourth quarter of 2015. Full year 2016 general and administrative expenses were $35.8 million, an increase of $13.2 million, or 58%, from $22.6 million in 2015. This increase was primarily due to increases in personnel related expenses, including stock-based compensation.
Net Income (Loss). Net loss for the fourth quarter of 2016 was $20.1 million, or $0.73 per basic share and diluted share, compared to net income of $296.1 million, or $11.37 per basic share and $10.63 per diluted share, for the fourth quarter of 2015. Full year 2016 net loss was $65.7 million, or $2.44 per basic share and diluted share, compared to net income of $249.6 million, or $9.73 per basic share and $9.23 per diluted share. These decreases in net income were primarily related to recognizing the 2015 upfront payment of $350 million as revenue under the cabiralizumab license and collaboration agreement with BMS.
Cash Guidance. Five Prime expects full-year 2017 net cash used in operating activities to be less than $120 million. The company estimates ending 2017 with approximately $300 million in cash, cash equivalents and marketable securities.