On November 9, 2017 Bristol-Myers Squibb Company (NYSE:BMY) and Five Prime Therapeutics, Inc. (NASDAQ:FPRX) reported preliminary results from a dose escalation and expansion study evaluating the safety, pharmacokinetics and pharmacodynamics of cabiralizumab in combination with Opdivo (nivolumab) in patients with advanced solid tumors (Press release, Bristol-Myers Squibb, NOV 9, 2017, View Source [SID1234521857]). This is the first disclosure of a clinical experience evaluating an anti-CSF-1 receptor antibody, which depletes immunosuppressive tumor associated macrophages (TAMs), in combination with an anti-PD-1 antibody. Preliminary results show that the safety profile of cabiralizumab plus Opdivo was generally consistent with that of Opdivo monotherapy, and that the combination results in dose-related decreases in circulating monocytes. In a cohort of heavily pre-treated patients with advanced pancreatic cancer (n=31 evaluable patients), a patient population that is generally insensitive to immunotherapy, durable clinical benefit was observed in five patients (16%), including confirmed objective responses in three patients with microsatellite-stable (MSS) disease (objective response rate 10%). The data will be presented Saturday, November 11 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 32nd Annual Meeting in a late-breaking oral presentation (abstract #O42) during Clinical Trials: Novel Combinations from 4:30 – 4:45 p.m. ET.

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More cancer patients are being treated with immunotherapy, but most patients with advanced pancreatic cancer remain resistant to anti-PD-1/PD-L1 therapy and typically have poor outcomes, with an average one-year survival rate of only 16 percent and five-year survival of less than 3 percent.1-3 Pancreatic cancer is known to be associated with TAM infiltration and higher TAM infiltration is in turn associated with worse prognosis, suggesting that suppressed immune response contributes to tumor progression in this patient population. These data show for the first time that combining an anti-CSF-1 receptor antibody with Opdivo may help restore T cell function by a simultaneous reduction of TAMs and inhibition of PD-1 signaling.

"In our robust Immuno-Oncology clinical program, we are focused on discovering ways to leverage the complex tumor microenvironment to help restore the body’s natural ability to fight cancer," said Fouad Namouni, M.D., head of development, Oncology, Bristol-Myers Squibb. "These preliminary results support our additional evaluation of the combination of cabiralizumab and Opdivo in patients with advanced pancreatic cancer."

"Cabiralizumab depletes immunosuppressive TAMs that regulate T cells in the tumor microenvironment. TAM depletion may be synergistic to PD-1 blockade," said Helen Collins, chief medical officer, Five Prime Therapeutics. "While early, we are encouraged by these results, which are supportive of continued development of this combination in pancreatic cancer."

About the Study

NCT02526017 is a Phase 1a/1b open-label study to evaluate safety, tolerability, pharmacokinetics (PK), and clinical benefit of cabiralizumab in combination with Opdivo in patients with advanced cancers in single-arm cohorts. In the expansion cohorts, patients received cabiralizumab 4mg/kg plus Opdivo 3mg/kg intravenous (IV) once every two weeks in a 3+3+3 design.

As of data cut-off, 229 patients have been treated, including 205 patients in the combination dose expansion cohorts in advanced solid tumors, of which 33 were pancreatic cancer patients. Cabiralizumab PK activity appears similar as a monotherapy and in combination with Opdivo. The PK of cabiralizumab ≥ 4 mg/kg Q2W approaches the linear dose range, suggesting saturation of target-mediated clearance. Cabiralizumab alone or in combination with Opdivo results in dose-related decreases in circulating monocytes. Treatment-related adverse events (TRAEs) of any grade occurred in 90 percent (n=184) of patients treated with cabiralizumab and Opdivo, with 49 percent (n=100) of patients experiencing Grade 3/4 adverse events. Of the 24 patients in the monotherapy group, 63 percent (n=15) experienced TRAEs of any grade, and 54 percent (n=13) experienced Grade 3/4 adverse events. The most common TRAEs were elevations in creatine kinase and serum liver enzymes.

The efficacy data reported at SITC (Free SITC Whitepaper) pertain to an expansion cohort in pancreatic cancer. The ongoing Phase 1a/1b trial has started to enroll and treat an additional 30 pancreatic cancer patients to further evaluate the combination in this patient population in a total of 60 patients. Further, Bristol-Myers Squibb is launching a new study of cabiralizumab plus Opdivo to provide additional insight into the potential benefit of the combination in pancreatic cancer. Additional details on this trial are available on clinicaltrials.gov.

About CSF1R and Cabiralizumab

Colony-stimulating factor 1 receptor (CSF1R) is a cell-surface tyrosine kinase receptor expressed by macrophages and other cells of the myeloid lineage. The CSF1R tyrosine kinase is activated when bound by its ligands, CSF-1 and IL-34. High levels of CSF1 in tumors stimulate more M2-like macrophages, which further tumor progression through suppressing effector T cell functions. High levels of TAMs in tumors are associated with poor prognostic outcomes, and preclinical research suggests that a blockade of CSF1R or inhibition of kinase activity may reduce the tumor burden, with a net effect of promotion of antitumor immunologic effects. Preclinical studies suggest that targeting the CSF1R pathway in combination with other potentially complementary immune pathways, like PD-1, may be a key strategy to more effectively activate the antitumor immune response.

Bristol-Myers Squibb and Five Prime are evaluating cabiralizumab in combination with Opdivo in a variety of advanced solid tumors. In 2015, Bristol-Myers Squibb and Five Prime entered into an exclusive worldwide license and collaboration agreement for the development and commercialization of Five Prime’s CSF1R antibody program, which includes cabiralizumab. Five Prime will continue to conduct the current Phase 1a/1b trial evaluating the combination of Opdivo and cabiralizumab in six tumor types, which was announced as part of the Companies’ initial clinical collaboration in November 2014, through to completion. Bristol-Myers Squibb will be responsible for subsequent development studies and for global commercialization, and Five Prime will retain rights to a U.S. co-promotion option.

Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research

At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines for hard-to-treat cancers that could potentially improve outcomes for these patients.

We are leading the scientific understanding of I-O through our extensive portfolio of investigational compounds and approved agents. Our differentiated clinical development program is studying broad patient populations across more than 50 types of cancers with more than 15 clinical-stage programs designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs position us to advance I-O/I-O, I-O/chemotherapy, I-O/targeted therapies and I-O/radiation therapies across multiple tumors and potentially deliver the next wave of therapies with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and how patients’ tumor biology can be used as a guide for treatment decisions throughout their journey.

We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

U.S. FDA-APPROVED INDICATIONS FOR OPDIVO

OPDIVO (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. OPDIVO (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

OPDIVO (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

IMPORTANT SAFETY INFORMATION

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.

Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy and evaluate clinical chemistries including liver function tests (LFTs), adrenocorticotropic hormone (ACTH) level, and thyroid function tests at baseline and before each dose.

Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions.

Immune-Mediated Pneumonitis

OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated pneumonitis occurred in 6% (25/407) of patients.

In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 6.0% (16/266) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 4.9% (13/266) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=12).

Immune-Mediated Colitis

OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. When administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated colitis occurred in 26% (107/407) of patients including three fatal cases.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal (diarrhea of ≥7 stools above baseline, fever, ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis occurred in 34 (7%) patients. Across all YERVOY-treated patients in that study (n=511), 5 (1%) developed intestinal perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were hospitalized for severe enterocolitis.

Immune-Mediated Hepatitis

OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. For patients without HCC, withhold OPDIVO for Grade 2 and permanently discontinue OPDIVO for Grade 3 or 4. For patients with HCC, withhold OPDIVO and administer corticosteroids if AST/ALT is within normal limits at baseline and increases to >3 and up to 5 times the upper limit of normal (ULN), if AST/ALT is >1 and up to 3 times ULN at baseline and increases to >5 and up to 10 times the ULN, and if AST/ALT is >3 and up to 5 times ULN at baseline and increases to >8 and up to 10 times the ULN. Permanently discontinue OPDIVO and administer corticosteroids if AST or ALT increases to >10 times the ULN or total bilirubin increases >3 times the ULN. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated hepatitis occurred in 13% (51/407) of patients.

In Checkmate 040, immune-mediated hepatitis requiring systemic corticosteroids occurred in 5% (8/154) of patients receiving OPDIVO.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5x the ULN or total bilirubin elevations >3x the ULN; Grade 3-5) occurred in 8 (2%) patients, with fatal hepatic failure in 0.2% and hospitalization in 0.4%.

Immune-Mediated Neuropathies

In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral motor neuropathy were reported.

Immune-Mediated Endocrinopathies

OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency, autoimmune thyroid disorders, and Type 1 diabetes mellitus. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency, thyroid function prior to and periodically during treatment, and hyperglycemia. Administer hormone replacement as clinically indicated and corticosteroids for Grade 2 or greater hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients. In patients receiving OPDIVO with YERVOY, hypophysitis occurred in 9% (36/407) of patients. In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994) of patients. In patients receiving OPDIVO with YERVOY, adrenal insufficiency occurred in 5% (21/407) of patients. In patients receiving OPDIVO monotherapy, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 9% (171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In patients receiving OPDIVO with YERVOY, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 22% (89/407) of patients. Hyperthyroidism occurred in 8% (34/407) of patients receiving OPDIVO with YERVOY. In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients. In patients receiving OPDIVO with YERVOY, diabetes occurred in 1.5% (6/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe to life-threatening immune-mediated endocrinopathies (requiring hospitalization, urgent medical intervention, or interfering with activities of daily living; Grade 3-4) occurred in 9 (1.8%) patients. All 9 patients had hypopituitarism, and some had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism. 6 of the 9 patients were hospitalized for severe endocrinopathies.

Immune-Mediated Nephritis and Renal Dysfunction

OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grades 2-4 increased serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 increased serum creatinine. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated nephritis and renal dysfunction occurred in 2.2% (9/407) of patients.

Immune-Mediated Skin Adverse Reactions and Dermatitis

OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with fatal outcome. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care for assessment and treatment; if confirmed, permanently discontinue. In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated rash occurred in 22.6% (92/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal immune-mediated dermatitis (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13 (2.5%) patients. 1 (0.2%) patient died as a result of toxic epidermal necrolysis. 1 additional patient required hospitalization for severe dermatitis.

Immune-Mediated Encephalitis

OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis. In patients receiving OPDIVO monotherapy, encephalitis occurred in 0.2% (3/1994) of patients. Fatal limbic encephalitis occurred in one patient after 7.2 months of exposure despite discontinuation of OPDIVO and administration of corticosteroids. Encephalitis occurred in one patient receiving OPDIVO with YERVOY (0.2%) after 1.7 months of exposure.

Other Immune-Mediated Adverse Reactions

Based on the severity of the adverse reaction, permanently discontinue or withhold OPDIVO, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO monotherapy or in combination with YERVOY, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1.0% of patients receiving OPDIVO: myocarditis, rhabdomyolysis, myositis, uveitis, iritis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism, systemic inflammatory response syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), motor dysfunction, vasculitis, and myasthenic syndrome.

Infusion Reactions

OPDIVO can cause severe infusion reactions, which have been reported in <1.0% of patients in clinical trials. Discontinue OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2. In patients receiving OPDIVO monotherapy, infusion-related reactions occurred in 6.4% (127/1994) of patients. In patients receiving OPDIVO with YERVOY, infusion-related reactions occurred in 2.5% (10/407) of patients.

Complications of Allogeneic HSCT after OPDIVO

Complications, including fatal events, occurred in patients who received allogeneic HSCT after OPDIVO. Outcomes were evaluated in 17 patients from Checkmate 205 and 039, who underwent allogeneic HSCT after discontinuing OPDIVO (15 with reduced-intensity conditioning, 2 with myeloablative conditioning). Thirty-five percent (6/17) of patients died from complications of allogeneic HSCT after OPDIVO. Five deaths occurred in the setting of severe or refractory GVHD. Grade 3 or higher acute GVHD was reported in 29% (5/17) of patients. Hyperacute GVHD was reported in 20% (n=2) of patients. A steroid-requiring febrile syndrome, without an identified infectious cause, was reported in 35% (n=6) of patients. Two cases of encephalitis were reported: Grade 3 (n=1) lymphocytic encephalitis without an identified infectious cause, and Grade 3 (n=1) suspected viral encephalitis. Hepatic veno-occlusive disease (VOD) occurred in one patient, who received reduced-intensity conditioned allogeneic HSCT and died of GVHD and multi-organ failure. Other cases of hepatic VOD after reduced-intensity conditioned allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor blocking antibody before transplantation. Cases of fatal hyperacute GVHD have also been reported. These complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT.

Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, severe (Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other immune-mediated adverse reactions, and intervene promptly.

Embryo-Fetal Toxicity

Based on their mechanisms of action, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with an OPDIVO- or YERVOY- containing regimen and for at least 5 months after the last dose of OPDIVO.

Lactation

It is not known whether OPDIVO or YERVOY is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from an OPDIVO-containing regimen, advise women to discontinue breastfeeding during treatment. Advise women to discontinue nursing during treatment with YERVOY and for 3 months following the final dose.

Serious Adverse Reactions

In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO . The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions (73% and 37%), adverse reactions leading to permanent discontinuation (43% and 14%) or to dosing delays (55% and 28%), and Grade 3 or 4 adverse reactions (72% and 44%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.6%), colitis (10% and 1.6%), and pyrexia (10% and 0.6%). In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 205 and 039, adverse reactions leading to discontinuation occurred in 7% and dose delays due to adverse reactions occurred in 34% of patients (n=266). Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions reported in ≥1% of patients were pneumonia, infusion-related reaction, pyrexia, colitis or diarrhea, pleural effusion, pneumonitis, and rash. Eleven patients died from causes other than disease progression: 3 from adverse reactions within 30 days of the last OPDIVO dose, 2 from infection 8 to 9 months after completing OPDIVO, and 6 from complications of allogeneic HSCT. In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO. The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis. In Checkmate 275, serious adverse reactions occurred in 54% of patients receiving OPDIVO (n=270). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were urinary tract infection, sepsis, diarrhea, small intestine obstruction, and general physical health deterioration. In Checkmate 040, serious adverse reactions occurred in 49% of patients (n=154). The most frequent serious adverse reactions reported in at least 2% of patients were pyrexia, ascites, back pain, general physical health deterioration, abdominal pain, and pneumonia.

Common Adverse Reactions

In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (59%), rash (53%), diarrhea (52%), nausea (40%), pyrexia (37%), vomiting (28%), and dyspnea (20%). The most common (≥20%) adverse reactions in the OPDIVO (n=313) arm were fatigue (53%), rash (40%), diarrhea (31%), and nausea (28%). In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were asthenic conditions (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 205 and 039, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=266) were upper respiratory tract infection (44%), fatigue (39%), cough (36%), diarrhea (33%), pyrexia (29%), musculoskeletal pain (26%), rash (24%), nausea (20%) and pruritus (20%). In Checkmate 141, the most common adverse reactions (≥10%) in patients receiving OPDIVO were cough and dyspnea at a higher incidence than investigator’s choice. In Checkmate 275, the most common adverse reactions (≥ 20%) reported in patients receiving OPDIVO (n=270) were fatigue (46%), musculoskeletal pain (30%), nausea (22%), and decreased appetite (22%).. In Checkmate 040, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=154) were fatigue (38%), musculoskeletal pain (36%), abdominal pain (34%), pruritus (27%), diarrhea (27%), rash (26%), cough (23%), and decreased appetite (22%). The most common adverse reactions (≥20%) in patients who received OPDIVO as a single agent were fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, and pyrexia.

In a separate Phase 3 study of YERVOY 3 mg/kg, the most common adverse reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%).

Please see U.S. Full Prescribing Information for OPDIVO and YERVOY, including Boxed WARNING regarding immune-mediated adverse reactions for YERVOY.

Checkmate 067 – advanced melanoma alone or in combination with YERVOY; Checkmate 037 and 066 – advanced melanoma; Checkmate 017 – squamous non-small cell lung cancer (NSCLC); Checkmate 057 – non-squamous NSCLC; Checkmate 025 – renal cell carcinoma; Checkmate 205/039 – classical Hodgkin lymphoma; Checkmate 141 – squamous cell carcinoma of the head and neck; Checkmate 275 – urothelial carcinoma; Checkmate 040 – hepatocellular carcinoma.

On November 9, 2017 BioTime, Inc. (NYSE American: BTX), a late stage clinical biotechnology company developing and commercializing products addressing degenerative diseases, reported financial results for the third quarter ended September 30, 2017 (Press release, BioTime, NOV 9, 2017, View Source;p=RssLanding&cat=news&id=2316015 [SID1234521856]).

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"BioTime achieved several significant milestones during the third quarter, both in its clinical programs and in the execution of its corporate strategy," said Adi Mohanty, Co-Chief Executive Officer. "With the additional positive long-term data from our EU Renevia trial, and the expansion of the OpRegen trial into the U.S., physicians and patients that may benefit from these products are one step closer to approved therapies."

"BioTime successfully secured over $40 million in funding including a public equity offering, which will enable the advancement of our clinical programs into the middle of 2019," continued Mr. Mohanty.

Corporate Highlights

AgeX completed a $10 million financing, which is expected to fund its operations well into 2019.
BioTime Board of Directors approved a distribution of some or all of the shares of AgeX Therapeutics, Inc. owned by BioTime to BioTime’s shareholders. The Board also authorized management to work with investment banks and other financial institutions to finalize and implement the strategy for taking AgeX public, which may include a tax-free distribution.
BioTime successfully completed a public equity offering raising net proceeds of approximately $26.7 million. The raise was completed on attractive terms and included both new and existing investors.
BioTime was awarded two grants, one from the Israel Innovation Authority and one from the National Institutes of Health, totaling approximately $3.6 million.
Clinical Progress

Renevia

BioTime announced positive secondary and additional positive long-term data from the Renevia pivotal trial. Treated patients retained an average 70% of the transplanted volume at 12 months and 64% at 18 months. The results thus far are encouraging and the long-term performance exceeded management expectations. All Renevia transplants were shown to be well tolerated and there were no device-related serious adverse events noted during this trial.
BioTime announced that an investigator-led clinical trial successfully treated its first patient in a study of Premvia, in combination with stromal vascular fraction cells, for the treatment of volume loss in the face, as was done in the Renevia pivotal trial. This clinical trial is studying Premvia in a cosmetic application. Premvia has 510(k) clearance in the U.S. for wound management. BioTime expects to file for CE Mark in Europe under the name Renevia for the treatment of facial lipoatrophy in HIV patients early next year.
OpRegen (dry-AMD)

Awarded a $2 million grant from the Israel Innovation Authority (IIA) for further development of OpRegen for Dry age-related macular degeneration. To date the IIA has provided grants totaling approximately $12 million.
Successful defense of two key patents providing protection to OpRegen. The patents were upheld during an opposition proceeding in March. In September, we announced the successful conclusion of the appeals. The two European patents (EP2554661 and EP2147094), cover the proprietary directed differentiation methods to produce pluripotent stem cell-derived cell replacement therapies being developed to treat retinal degenerative diseases, such as age-related macular degeneration.
Vision Restoration Program

Awarded a grant of up to $1.6 million from the Small Business Innovation Research program of the National Institutes of Health. The grant provides funding to further develop BioTime’s innovative, next generation vision restoration program for more advanced retinal diseases and injuries, which severely impact the quality of life for millions of people with no treatment option. This initiative aims at improving vision in people affected by blindness, whether caused by retinal injuries, age-related macular degeneration, retinitis pigmentosa or other causes.
AST-OPC1 (oligodendrocyte progenitor cells)

Asterias Biotherapeutics announced new 12-month data from the first efficacy cohort in the company’s ongoing Phase 1/2a SCiStar study designated to evaluate safety and efficacy of AST-OPC1 in spinal cord injury. The 12-month data showed 67% of Cohort 2 subjects have recovered 2 or more motor levels on at least one side through 12 months, which is more than double the rates of recovery seen in both matched historical controls and published data in a similar population. Also, the FDA granted the company’s request for AST-OPC1 to be designated a Regenerative Medicine Advanced Therapy under the 21st Century Cures Act.
AST-VAC2 (patient specific cancer vaccine)

Asterias Biotherapeutics announced that the Medicines and Healthcare Products Regulatory Agency and the NHS Research Ethics Committee have provided the necessary approvals to initiate the first-in-human clinical trial of AST-VAC2 in the United Kingdom. The trial, which is being sponsored and managed by Cancer Research UK, will examine the safety, tolerability, immunogenicity and activity of AST-VAC2 in non-small cell lung cancer patients and is expected to be initiated later this year.
Liquid Biopsy (lung cancer confirmatory blood test)

OncoCyte received Clinical Laboratory Improvements Amendments (CLIA) certification of registration from the Centers for Medicare and Medicaid Services. In addition, OncoCyte’s laboratory has passed inspection by the California Department of Public Health and is now fully licensed and operational. Clinical validation study initiated.
OncoCyte announced positive results from the Analytical Validation Study of its liquid biopsy lung cancer diagnostic test, DetermaVU.
Simplification and Unlocking Value

New Subsidiary AgeX Therapeutics, Inc.

BioTime Board of Directors approved a distribution of some or all of the shares of AgeX Therapeutics, Inc. owned by BioTime to BioTime’s shareholders. The Board also authorized management to work with investment banks and other financial institutions to finalize and implement the strategy for taking AgeX public, which may include a tax-free distribution.
Third Quarter Financial Results

Cash Position and Marketable Securities: Cash, cash equivalents and available for sale securities totaled $18.2 million as of September 30, 2017, compared to $15.8 million as of June 30, 2017. On October 17, 2017, we completed a public offering of our common stock in which we issued 11,057,693 shares of our common stock for aggregate net cash proceeds of $26.7 million, after deducting commissions, discounts and estimated offering expenses.

Value of Holdings in Public Affiliates: At September 30, 2017, BioTime held common stock in publicly-traded affiliates valued at $184.7 million. This amount was the market value of BioTime’s 21.7 million shares in Asterias Biotherapeutics (NYSE American: AST) and 14.7 million shares in OncoCyte (NYSE American: OCX).

Revenues: BioTime’s revenue is generated primarily from research grants, licensing fees and royalties, and subscription and advertising from the marketing of online database products. Total revenue was $1.7 million for the third quarter of 2017, compared to $1.5 million in the third quarter of 2016.

Operating Expenses: Operating expenses for the third quarter of 2017 were $11.1 million. On an adjusted basis, operating expenses were $8.6 million, of which $6.5 million was mainly attributable to our clinical programs, while $2.1 million in expenses were related to AgeX.

Our operating expenses for the nine months ended September 30, 2017 were $33.4 million. Adjusted operating expenses were $26.8 million for this period, including $18.3 million spent on our clinical and early stage programs.

The reconciliation between GAAP and non-GAAP operating expenses by entity, is provided in the financial tables included with this earnings release.

R&D Expenses: Research and development expenses were $6.6 million for the third quarter of 2017, compared to $6.4 million for the comparable period in 2016, a decrease of $0.2 million.

G&A Expenses: General and administrative expenses were $4.6 million for the third quarter of 2017 compared to $4.6 million for the comparable period in 2016.

Net Income or loss attributable to BioTime: Net income attributable to BioTime was $14.3 million, or $0.12 per basic and diluted common share for the three months ended September 30, 2017, compared to net income of $31.2 million, or $0.30 per basic and diluted common share for the three months ended September 30, 2016. For the nine months ended September 30, 2017, net income attributable to BioTime was $52.0 million, or $0.47 per diluted common share, compared to $38.6 million, or $0.39 per share for the nine months ended September 30, 2016. Results in each period were primarily driven by noncash deconsolidation gains and noncash gains and losses in the changes in share prices of our public affiliate investments in Asterias and OncoCyte common stock.

Conference Call and Webcast Details

BioTime is hosting a conference call and webcast today, Thursday, November 9, at 4:30 p.m. Eastern Time / 1:30 p.m. Pacific Time to discuss the results and recent corporate developments. The conference call dial-in number in the U.S./Canada is 1-877-407-0784. For international participants outside the U.S./Canada, the dial-in number is 1-201-689-8560. For all callers, please refer to the "BioTime, Inc. Conference Call." The live webcast can be accessed on the "Events & Presentations" page of the "Investors & Media" section on the company’s website at View Source;p=irol-calendar.

A replay of the conference call will be available for seven business days beginning about two hours after the conclusion of the live call, by calling toll-free from U.S./Canada: 1-844-512-2921; international callers dial 1-412-317-6671. Use the Conference ID 13671848. Additionally, the archived webcast will be available on the "Events & Presentations" page of the "Investors & Media" section on the company’s website at View Source;p=irol-calendar.

About Renevia

Renevia is an investigational medical device that is being developed as an alternative for whole adipose tissue transfer (fat grafting) procedures. Renevia’s hydrogel polymer network provides the requisite amino acid sequences for adipose stromal vascular cell attachment and may support proliferation, localization and adipogenic differentiation. Renevia is part of the Hystem hydrogel family of proprietary injectable matrices, which are designed to facilitate the survival and growth of transplanted cells.

About OpRegen

OpRegen, which is being studied for the treatment of the dry form of AMD, consists of a suspension of Retinal Pigment Epithelial (RPE) cells that are delivered subretinally during a simple intraocular injection. RPE cells are essential components of the back lining of the retina, and function to help nourish the retina including photoreceptors. A proprietary process that drives the differentiation of human pluripotent stem cells is used to generate high purity OpRegen RPE cells. OpRegen RPE cells are also "xeno-free," meaning that no animal products are used at any point in the derivation and production process. The avoidance of the use of animal products eliminates some potential safety concerns. Preclinical studies in rats have shown that following a single subretinal injection of OpRegen, the cells can rapidly organize into its natural monolayer structure in the subretinal space and survive throughout the lifetime of the animal. OpRegen is designed to be an "off-the-shelf" allogeneic (non-patient specific) product. Unlike treatments that require multiple, frequent injections into the eye, it is expected that OpRegen would be administered in a single procedure. OpRegen was granted Fast Track designation from the FDA, which allows more frequent interactions with the agency, and eligibility for accelerated approval and priority review. OpRegen is a registered trademark of Cell Cure Neurosciences Ltd., a majority-owned subsidiary of BioTime, Inc.

About Premvia

Approved Uses

Premvia is indicated for the management of wounds including: partial-thickness, full-thickness, tunneling wounds, pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, donor skin graft sites, post-Moh’s surgery, post-laser surgery, podiatric wounds, wound dehiscence, abrasions, lacerations, second degree burns, skin tears, and draining wounds.

Contraindications

Premvia is contraindicated for patients with severe allergies, indicated by a history of anaphylaxis or presence of multiple severe allergies.
Premvia is specifically contraindicated for patients with known allergies to products containing either hyaluronan or collagen derivatives.
Premvia is not indicated for use in third degree burns.
Important Safety Information

Complications that may arise from wound management products may include: infection, chronic inflammation, allergic reaction, excessive redness, pain, or swelling. If any of these complications are present, product should be removed from the wound area.
Federal law restricts this device to sale by or on the order of a physician or practitioner.
Only the vial contents are sterile – outside of vials are not sterile.
Do not add additional components or additives to Premvia.

On November 9, 2017 Bio-Path Holdings, Inc. (NASDAQ: BPTH), a biotechnology company leveraging its proprietary DNAbilize antisense RNAi nanoparticle technology to develop a portfolio of targeted nucleic acid cancer drugs, reported its financial results for the third quarter ended September 30, 2017 and provided an update on recent corporate developments (Press release, Bio-Path Holdings, NOV 9, 2017, View Source [SID1234521855]).

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"The third quarter was marked by growth and progress as we continue to advance our clinical and preclinical pipeline candidates. Following our recent financing, we are well-positioned to achieve several important milestones, including an interim update from our Phase 2 clinical trial of prexigebersen for the treatment of acute myeloid leukemia," said Peter Nielsen, President and CEO of Bio-Path Holdings. "In addition, the selection of BP1003 as a new drug candidate for the treatment of pancreatic cancer highlights the exciting and expansive potential of our DNAbilize technology platform to produce targeted drug candidates that can address many different diseases with high unmet need."

Recent Corporate Highlights

· Completed Registered Direct Public Offering. On November 3, 2017, Bio-Path agreed to the sale and issuance of 13,333,332 shares of common stock and warrants to purchase up to 6,666,666 shares of common stock to healthcare focused institutional investors in a registered direct offering with gross proceeds of approximately $4.0 million. The offering closed on November 6, 2017.

· Selected Third Drug Candidate, BP1003, for Treatment of Pancreatic Cancer. In November, Bio-Path announced that BP1003, which targets the Stat3 protein, has been moved into preclinical development for the treatment of pancreatic cancer. The candidate is currently being studied in a patient-derived tumor model, and previous models have shown it to successfully penetrate pancreatic tumors and enhance the efficacy of standard frontline treatments.

· Demonstrated Promising Preclinical Results for Prexigebersen in Solid Tumors. In November, Bio-Path announced that prexigebersen, targeting the Grb2 protein, showed ovarian tumor penetration in recently completed preclinical studies. Bio-Path plans to initiate a Phase 1 trial of prexigebersen in several solid tumor types in 2018. Prexigebersen is currently in Phase 2 development for the treatment of blood cancers and has demonstrated clinical benefit as a monotherapy and in combination with standard frontline treatments in both acute myeloid leukemia and chronic myeloid leukemia.

· Announced Encouraging Preclinical Results for BP1002. In November, Bio-Path announced that, BP1002, targeting the Bcl2 protein, demonstrated strong anti-non-Hodgkin’s lymphoma activity in cell lines and in an animal model. The Company intends to initiate a Phase 1 trial of BP1002 in lymphoma in 2018.

Financial Results for the Third Quarter Ended September 30, 2017

The Company reported a net loss attributable to common stockholders of $2.5 million, or $0.02 per share, for the three months ended September 30, 2017, compared to a net loss attributable to common stockholders of $1.6 million, or $0.02 per share, for the three months ended September 30, 2016. The increase was primarily due to the benefit received from the change in fair value of the warrant liability in 2016. The Company reported a net loss attributable to common stockholders of $5.9 million, or $0.06 per share, for the nine months ended September 30, 2017, compared to a net loss attributable to common stockholders of $5.4 million, or $0.06 per share, for the nine months ended September 30, 2016. The increase was primarily due to the deemed dividend related to the warrant conversion of $1.0 million during the period.

Research and development expenses for the three months ended September 30, 2017 decreased to $1.6 million, compared to $2.3 million for the three months ended September 30, 2016. For the nine months ended September 30, 2017, research and development expenses decreased to $4.1 million, compared to $4.5 million for the nine months ended September 30, 2016. The decreases were primarily due to the release of drug material for our Phase 2 clinical trial for prexigebersen in AML in 2016.

General and administrative expenses for the three months ended September 30, 2017 increased to $0.9 million, compared to $0.7 million for the three months ended September 30, 2016. For the nine months ended September 30, 2017, general and administrative expenses increased to $2.7 million, compared to $2.3 million for the nine months ended September 30, 2016.

As of September 30, 2017, the Company had cash of $4.6 million, compared to $9.4 million at December 31, 2016. Net cash used in operating activities for the nine months ended September 30, 2017 was $5.7 million compared to $6.5 million for the comparable period in 2016. Net cash used in investing activities for the nine months ended September 30, 2017 was $0.5 million. Net cash provided by financing activities for the nine months ended September 30, 2017 was $1.5 million.

Conference Call and Webcast Information

Bio-Path Holdings will host a conference call tomorrow to review these third quarter 2017 financial results, as well as to provide a general update on the Company, via a webcast and conference call at 8:30 a.m. ET. To access the conference call please dial (844) 815-4963 (domestic) or (210) 229- 8838 (international) and refer to the conference ID number 3166609. A live audio webcast of the call and the archived webcast will be available in the Media section of the Company’s website at www.biopathholdings.com.

On November 9, 2017 ArQule, Inc. (Nasdaq: ARQL) reported its financial results for the third quarter of 2017 (Press release, ArQule, NOV 9, 2017, View Source [SID1234521854]).

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For the quarter ended September 30, 2017, the Company reported a net loss of $6,666,000 or $0.09 per share, compared with a net loss of $5,817,000 or $0.08 per share, for the third quarter of 2016. For the nine-month period ended September 30, 2017, the Company reported a net loss of $21,443,000 or $0.30 per share, compared with a net loss of $15,898,000 or $0.23 per share, for the nine-month period ended September 30, 2016.

At September 30, 2017, the Company had a total of approximately $27,603,000 in cash, equivalents and marketable securities. In October and November 2017, the Company raised approximately $25 million in net proceeds from two equity offerings.

Key Highlights

· Miransertib (ARQ 092), lead AKT inhibitor, has met its primary endpoint of determining a biologically active dose in a phase 1 trial for Proteus syndrome lead by the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH). The NIH presented preliminary data from the ongoing phase 1 clinical trial for Proteus syndrome at the Proteus Syndrome Foundation Family Conference in September 2017. In five of the six patients, a reduction of a least 50% of phospho-AKT levels was reported. This met the primary objective of the study. Most significantly the NIH observed disease modification in the cerebriform connective tissue nevus (CCTN) lesions which are considered one of the hallmarks of the disease.

· Miransertib was granted by the U.S. Food and Drug Administration (FDA) Rare Pediatric Disease Designation. Under the FDA’s rare pediatric disease priority review voucher program, the sponsor may be eligible for a voucher that can be used to obtain a priority review for a subsequent human drug application.

· Miransertib continues to dose in the phase 1/2 trial for Overgrowth Diseases driven by PI3K and AKT mutations and opened its first U.S. clinical trial site. This trial is part of the company’s continued progress towards expanding its rare disease strategy in Overgrowth Diseases.

· ARQ 531, an orally bioavailable, potent and reversible BTK inhibitor, continues dosing as planned in a phase 1a/b trial. The trial is enrolling patients with B-cell malignancies, including B-cell lymphomas, chronic lymphocytic leukemia, and Waldenstrom’s macroglobulinemia, who are refractory to other therapeutic options, including ibrutinib. Up to 120 patients can be enrolled in the trial.

· Derazantinib (ARQ 087), a pan-FGFR inhibitor, in a registrational trial in FGFR2 fusion positive second-line intrahepatic cholangiocarcinoma (iCCA) is recruiting with six active sites in the U.S. The trial is planned to enroll up to 100 iCCA patients and provides an opportunity for a conditional approval as part of a fast-to-market strategy and includes an interim analysis that will be performed after the first 40 patients have been enrolled and evaluated for response.

· Company raised approximately $29 million in capital through a private placement of $15.7 million of common stock, a private placement of $9.5 million of convertible preferred stock and an additional $4 million through unrelated business development activities and other sources. Net proceeds will be used to advance ArQule’s proprietary pipeline and for general business purposes, including working capital.

"The ArQule clinical pipeline is the strongest it has ever been, and the most recent positive developments are the compelling clinical data in Proteus syndrome and the granting of Rare Pediatric Disease Designation for miransertib in this indication," said Paolo Pucci, Chief Executive Officer of ArQule. "We are now well capitalized to see our pipeline assets through major inflection points."

"Based on the preliminary results from the phase 1 NIH-sponsored Proteus syndrome trial, miransertib is the first drug to demonstrate activity and achieve clinical proof of concept in this indication," said Dr. Brian Schwartz, M.D., Head of Research and Development and Chief Medical Officer at ArQule. "We are thankful to the NIH for their work in identifying the mutation driving the disease, conducting the first clinical trial and ultimately identifying potential clinical endpoints. We plan to engage regulatory authorities to define a clinical path to registration in this indication. In parallel and consistent with the regulatory interactions we will continue to enroll in our ongoing phase 1/2 trial in Overgrowth Diseases driven by mutations in the PI3K or AKT pathway, including Proteus syndrome, and provide the drug under compassionate policy."

Revenues and Expenses

Revenues for the quarter ended September 30, 2017, were zero compared with revenues of $1,223,000 for the quarter ended September 30, 2016. Revenues in the nine-months ended September 30, 2017 were zero compared with revenues of $3,522,000 in the nine-months ended September 30, 2016. Revenue in the three and nine-month periods of 2016 is comprised of revenue from the Daiichi Sankyo tivantinib development agreement and the Kyowa Hakko Kirin exclusive license agreement. No further revenue is anticipated from these agreements.

Research and development expense in the third quarter of 2017 was $4,570,000, compared with $5,265,000 for the third quarter of 2016. Research and development expense decreased $0.7 million in the third quarter of 2017 primarily due to lower outsourced preclinical, clinical and product development costs.

Research and development expense in the nine-months ended September 30, 2017 was $14,747,000 compared with $13,800,000 in the nine-months ended September 30, 2016. The $0.9 million increase in research and development expense in the nine-months ended September 30, 2017 was primarily due to higher outsourced clinical and product development costs.

General and administrative expense was $1,762,000 in the third quarter of 2017 compared with $1,824,000 in the third quarter 2016.

General and administrative expense was $5,702,000 in the nine-months ended September 30, 2017 compared with $5,755,000 in the nine-months ended September 30, 2016.

2017 Financial Guidance

As a result of ArQule’s recent stock offerings and business development activities the company is updating 2017 guidance. For 2017, ArQule expects net use of cash to range between $25 and $27 million. Net loss is expected to range between $28 and $30 million, net loss per share is expected to range between $(0.38) and $(0.40) for the year. ArQule expects to end 2017 with between $47 and $49 million in cash and marketable securities.

Conference Call and Webcast

ArQule will hold its third quarter 2017 financial results call today, November 9, 2017 at 9:00 a.m. ET. The live webcast can be accessed in the "Investors & Media" section of our website, www.arqule.com, under "Events & Presentations." You may also listen to the call by dialing (877) 868-1831 within the U.S. or (914) 495-8595 outside the U.S. A replay will be available two hours after the completion of the call and can be accessed in the "Investor and Media" section of our website, www.arqule.com, under "Events & Presentations."

On November 9, 2017 Argos Therapeutics Inc. (NASDAQ:ARGS), an immuno-oncology company focused on the development and commercialization of individualized immunotherapies based on the Arcelis precision immunotherapy technology platform, reported financial results and operational highlights for the third quarter of 2017 (Press release, Argos Therapeutics, NOV 9, 2017, View Source [SID1234521853]).

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"We are pleased with the progress we have made since the second quarter, both with regard to our financial position as well as in our two clinical programs," Jeff Abbey, CEO of Argos Therapeutics, noted. "First, from a financial perspective, we are pleased to have raised approximately $10 million through our ATM facility between June and November, and to have received a $1.5 million milestone payment from our partner in China and certain other Asian territories, Lummy (Hong Kong) Ltd. In addition, as previously reported, we were pleased to reach a satisfactory resolution with one of our important vendors regarding the deferred fees that we owed them, thereby significantly extending the payment term."

Mr. Abbey continued, "From an operational perspective, we are continuing the ADAPT clinical trial, and look forward to the next interim analysis, which we expect to occur during the first half of 2018, subject to agreement with the FDA on an amended protocol. In addition, we were encouraged by the updated immunology data from the ADAPT clinical trial indicating that Rocapuldencel-T stimulated an immune response in patients with metastatic renal cell carcinoma in the trial, and by the data from the trial related to the duration of tumor response, that were presented at the European Society for Medical Oncology 2017 Congress in September. Additionally, we are continuing our study of AGS-004 in combination with the latency-reversing agent vorinostat in adult HIV patients."

Operational Highlights

During the third quarter, the Company announced the following progress:

In July 2017, the Company reported positive immunogenicity data from the AGS-004 program for the treatment of HIV
In September 2017, additional data from the Phase 3 ADAPT clinical trial was presented by Robert Figlin, MD, principal investigator, at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Conference
In September 2017, the Company announced the first dosing of an HIV patient with AGS-004 derived from the latent viral reservoir
Financial Results

Revenue for the three months ended September 30, 2017 was $53,000 compared to $147,000 for the same period in 2016. The decrease in revenue for the third quarter of 2017 compared with the third quarter of 2016 resulted from lower reimbursement under the Company’s contract with the NIH and NIAID primarily related to the achievement of certain specified development milestones under the Company’s AGS-004 program during 2016.

Research and development expense for the three months ended September 30, 2017 was $4.6 million compared to $9.3 million for the same period in 2016. The decrease in research and development expense for the third quarter of 2017 compared with the third quarter of 2016 was due to reduced expenses associated with the Phase 3 ADAPT trial, and the Company’s decision not to proceed with the development of commercial manufacturing capabilities and to significantly reduce the size of its workforce engaged in research and development activities following the recommendation of the IDMC to discontinue the ADAPT trial for futility.

General and administrative expense for the three months ended September 30, 2017 was $2.9 million compared to $3.0 million for the same period in 2016. The decrease in general and administrative expense for the third quarter of 2017 compared with the third quarter of 2016 was primarily due to reduced consulting and personnel costs.

Additionally, the Company incurred restructuring charges of $679,000 during the three months ended September 30, 2017 related to the Company’s decision to discontinue preparation for commercial manufacturing and reduce the size of its workforce, which amount was offset by a non-cash gain due to the decrease in the value of the warrant liability of $502,000 and a gain on the early extinguishment of debt of $1.5 million associated with the satisfaction and release of all of the Company’s payment obligations to Invetech, Pty Ltd.

Interest expense for the three months ended September 30, 2017 was $67,000 compared to $448,000 for the same period in 2016. The decrease in interest expense for the first three months of 2017 compared with the first three months of 2016 was primarily due to a lower average balance of debt outstanding.

Reflecting the factors noted above, net loss for the three months ended September 30, 2017 was $6.1 million compared to a net loss of $12.2 million for the same period in 2016.

Revenue for the nine months ended September 30, 2017 was $228,000 compared to $782,000 for the same period in 2016. The decrease in revenue for the first nine months of 2017 compared with the first nine months of 2016 resulted from lower reimbursement under the Company’s contract with the NIH and NIAID primarily related to the achievement of certain specified development milestones under the Company’s AGS-004 program during 2016.

Research and development expense for the nine months ended September 30, 2017 was $17.6 million compared to $28.0 million for the same period in 2016. The decrease in research and development expense for the first nine months of 2017 compared with the first nine months of 2016 was due to reduced expenses associated with the Phase 3 ADAPT trial, and the Company’s decision not to proceed with the development of commercial manufacturing capabilities and to significantly reduce the size of its workforce engaged in research and development activities following the recommendation of the IDMC to discontinue the ADAPT trial for futility.

General and administrative expense for the nine months ended September 30, 2017 was $9.5 million compared to $9.4 million for the same period in 2016. The increase in general and administrative expense for the first nine months of 2017 compared with the first nine months of 2016 was primarily due to increased personnel costs.

Additionally, the Company incurred impairment charges of $27.2 million and restructuring charges of $6.0 million during the nine months ended September 30, 2017 related to the Company’s decision to discontinue preparation for commercial manufacturing and reduce the size of its workforce, which amounts were partially offset by a non-cash gain due to the decrease in the value of the warrant liability of $20.7 million and a gain on the early extinguishment of debt of $1.8 million.

Interest expense for the nine months ended September 30, 2017 was $1.1 million compared to $1.5 million for the same period in 2016. The decrease in interest expense for the first nine months of 2017 compared with the first nine months of 2016 was primarily due to a lower average balance of debt outstanding, partially offset by the decision to no longer capitalize the interest related to construction of the Centerpoint facility following the decision not to proceed with plans to develop this facility.

Reflecting the factors noted above, net loss for the nine months ended September 30, 2017 was $38.7 million compared to a net loss of $37.7 million for the same period in 2016.

As of September 30, 2017, cash and cash equivalents totaled $9.4 million.

Upcoming Conference Call and Webcast

Argos will be presenting updated immunology data in the poster session at the 32nd Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Conference to be held this weekend in National Harbor, Maryland. Argos will hold a conference call to discuss this data on Monday, November 13th at 8:30am ET (rescheduled from today at 4:30pm). To participate by telephone, please dial (855) 433-0930 (Domestic) or (484) 756-4271 (International). The conference ID number is 9396519. Slides setting forth the data to be presented at the SITC (Free SITC Whitepaper) 2017 Annual Meeting, and a live and archived audio webcast, will be accessible through the Investors section of the Company’s website at www.argostherapeutics.com. The archived webcast will remain available on the Company’s website for twelve (12) months following the call.