On November 9, 2016 Nektar Therapeutics (Nasdaq: NKTR) reported that new Phase 1 clinical data for Nektar’s lead immuno-oncology agent, NKTR-214, were presented at the SITC (Free SITC Whitepaper) 2016 Annual Meeting (Press release, Nektar Therapeutics, NOV 9, 2016, View Source [SID1234516469]). NKTR-214 is an investigational immuno-stimulatory therapy designed to expand specific cancer-fighting T cells and Natural Killer (NK) cell abundance directly in the tumor micro-environment and increase expression of PD-1 on these immune cells. The results were presented by Adi Diab, MD, Assistant Professor, Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center in an oral presentation during today’s session entitled "New Cancer Immunotherapy Agents in Development."

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Interim results presented were from the ongoing Phase 1 dose-escalation, first-in-human, trial of single-agent NKTR-214 in patients with locally advanced or metastatic solid tumors, including melanoma, renal cell carcinoma (RCC), bladder, colorectal and other solid tumor cancers. A total of 20 patients were treated in four separate every three-week (q3w) dose cohorts (ranging from 0.003 mg/kg q3w to 0.012 mg/kg q3w) with 18 of these patients evaluable for anti-tumor activity. Based upon encouraging anti-tumor activity and tolerability of NKTR-214 observed at the 0.006 mg/kg q3w dose, an every two week (q2w) cohort of the 0.006 mg/kg dose began enrolling in September 2016 with an additional 5 patients enrolled to this cohort, all of which are continuing on therapy.

"NKTR-214 resulted in robust activation of the immune system and encouraging anti-tumor activity, including a partial response observed in a patient who continues to be treated with NKTR-214," said Dr. Ivan Gergel, Senior Vice President, Drug Development & Chief Medical Officer of Nektar. "NKTR-214 was also well tolerated in patients when administered as an every two-week or every three-week outpatient therapy. We are very encouraged by the clinical profile emerging for NKTR-214 and the totality of the data from this ongoing single-agent trial of NKTR-214."

Preliminary encouraging evidence of anti-tumor activity has been observed to date in the ongoing study:

12/18 (67%) evaluable patients had stable disease at the initial 8 week scan
7/18 (39%) evaluable patients had radiographic reductions in tumor size per RECIST 1.1 on NKTR-214
One patient with metastatic melanoma (prior treatment with ipilimumab and a BRAF inhibitor) has received 13 cycles of treatment (0.003 mg/kg q3w) with stable disease and continues on therapy with NKTR-214
In the 18 evaluable patients, a total of 5 patients with metastatic RCC who had progressed on 1 prior tyrosine kinase inhibitor (TKI) were treated with NKTR-214 at the 0.006 mg/kg q3w dose level:
1/5 (20%) of these RCC patients had a uPR per RECIST 1.1 (at 16 week scan) and treatment with NKTR-214 is ongoing
2/5 of these RCC patients had additional tumor reductions of 6% and 10% per RECIST 1.1 while on NKTR-214
NKTR-214 also demonstrated a favorable safety and tolerability profile with convenient, outpatient q2w or q3w administration in 25 patients evaluable for safety to-date:

No immune-related AEs were observed (e.g. colitis, dermatitis, hepatitis pneumonitis, adrenal insufficiency)
No deaths or grade 4 AEs related to NKTR-214
No capillary leak syndrome was observed at any dose
One patient experienced a dose-limiting toxicity (DLT) of hypotension/syncope at 0.012 mg/kg q3w and continued on treatment at 0.006 mg/kg q3w
3/25 patients experienced grade 3 hypotension, which was rapidly reversed with fluid administration and all patients continued on treatment with NKTR-214
Most common grade 1-2 adverse events were fatigue, pruritis, cough, decreased appetite, pyrexia, and hypotension
Immune pheno-typing was conducted and biomarkers of immune activation were measured in patients with evaluable tumor biopsies and blood samples. Treatment with NKTR-214 produced a robust elevation in immune cell frequency and activation, including:

Increase in total and newly proliferating (Ki67+) CD4+ T cells, CD8+ T cells, and Natural Killer (NK) cells in 9/9 patients with blood samples evaluated in the trial to-date, with increases of up to 30-fold observed
Increase in frequency of PD-1+ T cell subsets of up to 9-fold in the blood
Increase in CD8+ T cells and Natural Killer (NK) cells of up to 10-fold in the tumor micro-environment in patients with evaluable tumor biopsies (pre-dose and post-dose at week 3), with minimal intratumoral changes to T regulatory cells
Increase in expression of cell-surface PD-1 on T cell subsets of up to 2-fold in the tumor micro-environment
Induction of an activation gene signature in the tumor micro-environment, including increases of 5-fold or greater in expression of interferon γ, perforin and granzyme B genes
Changes in T cell repertoire (TCR), which is a measure of T cell clonality, in the tumor micro-environment
"We are extremely pleased with the single-agent activity of NKTR-214 and the potential of NKTR-214 to transform the immuno-oncology landscape," said Howard W. Robin, President & CEO of Nektar Therapeutics. "As the first I-O agent to demonstrate that it can increase tumor-infiltrating lymphocytes (TILs) and increase PD-1 expression on immune cells in humans, NKTR-214 complements not only existing checkpoint inhibitors, such as nivolumab, but also other I-O mechanisms in development."

In September 2016, Nektar entered into a clinical collaboration with Bristol-Myers Squibb to evaluate NKTR-214 as a potential combination treatment regimen with Bristol-Myers Squibb’s Opdivo (nivolumab) in five tumor types and seven potential indications. The Phase 1/2 clinical trials will enroll up to 260 patients and will evaluate the potential for the combination of Opdivo (nivolumab) and NKTR-214 to show improved and sustained efficacy and tolerability above the current standard of care in melanoma, kidney, triple-negative breast cancer, bladder and non-small cell lung cancer patients. The initial dose-escalation trial is underway with Opdivo (nivolumab) and NKTR-214.

NKTR-214 is an experimental therapy designed to stimulate cancer-killing immune cells in the body by targeting CD122 specific receptors found on the surface of these immune cells, known as CD8+ effector T cells and Natural Killer (NK) cells. In preclinical studies, treatment with NKTR-214 resulted in a rapid expansion of these cells and mobilization into the tumor micro-environment.1 NKTR-214 has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines. A Phase 1/2 clinical study is ongoing to evaluate single-agent NKTR-214 in cancer patients.

On November 9, 2016 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical-stage pharmaceutical company focused on discovering and developing novel small molecule drugs directed against tumor and tumor immune cell metabolism targets for the treatment of cancer, reported its financial results for the third quarter ended September 30, 2016 (Press release, Calithera Biosciences, NOV 9, 2016, View Source;p=RssLanding&cat=news&id=2221119 [SID1234516512]). As of September 30, 2016, cash, cash equivalents and investments totaled $56.3 million.

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"During the third quarter, we continued enrolling the two cohorts evaluating our glutaminase inhibitor CB-839 in triple negative breast cancer and in renal cell carcinoma. We expect to be in a position to provide additional updates at medical meetings in the fourth quarter," said Susan Molineaux, Ph.D., President and Chief Executive Officer of Calithera. "In addition, we opened two new immuno-oncology trials in the quarter, both of which should have an initial read out in 2017."

Third Quarter 2016 and Recent Highlights

CB-839: First patient enrolled and dosed in combination with checkpoint modulator. In August 2016, we enrolled the first patient in a Phase 1/2 clinical trial assessing the safety and efficacy of CB-839, in combination with Opdivo for the treatment of renal cell carcinoma (RCC), malignant melanoma and non-small cell lung cancer. The Phase 1/2 study will assess the safety, pharmacokinetics and pharmacodynamics of CB-839 and Opdivo. The study will enroll patients with clear cell RCC who are naïve to checkpoint inhibitors, as well as clear cell RCC, melanoma, and non-small cell lung cancer patients who are receiving anti-PD-1 monotherapy as their current therapy without having a tumor response.
CB-839: Data in renal cell carcinoma selected for oral presentation. In September, we announced that clinical data for CB-839 will be presented in a plenary session at the 28th Annual EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics, November 29 to December 2, 2016 in Munich, Germany. The clinical presentation will be focused on data from Calithera’s CB-839 Phase I RCC combination trial with everolimus.
CB-839: Data in triple negative breast cancer selected for presentation. Clinical data for CB-839 will be presented at the San Antonio Breast Cancer Symposium in San Antonio, December 6 to 10, 2016 in San Antonio, Texas. The clinical presentation will be focused on data from Calithera’s CB-839 Phase I triple negative breast cancer combination trial with paclitaxel.
CB-1158: First patient dosed in a phase 1 study of our first-in-class inhibitor of the immuno-oncology target arginase. In September 2016, we announced dosing of the first patient in a Phase I clinical trial assessing the safety and efficacy of our drug candidate as a treatment for advanced solid tumors. Arginase is an enzyme in myeloid-derived suppressor cells (MDSCs), which prevents T-cell and natural killer (NK) cell activation in tumors.
Board of Directors. In August 2016, Suzy Jones was appointed to our Board of Directors, and added to the Audit committee. Ms. Jones is currently Founder and Managing Partner of DNA Ink, a boutique life sciences advisory firm.
Selected Third Quarter 2016 Financial Results

Research and development expenses were $6.3 million for the three months ended September 30, 2016, compared with $6.8 million for the same period in the prior year. The decrease of $0.5 million was primarily due to the timing of manufacturing clinical supply to support our CB-839 and CB-1158 clinical trials, partially offset by increased personnel-related costs primarily due to higher headcount, salary increases and stock-based compensation expense, and costs associated with our licensing arrangements.

General and administrative expenses were $2.3 million for the three months ended September 30, 2016, compared with $2.2 million for the same period in the prior year. The increase of $0.1 million was primarily due to higher personnel-related costs as a result of higher headcount, salary increases and stock-based compensation expense.

Net loss for the three months ended September 30, 2016 was $8.5 million, or $0.44 per share.

Based on the results for the first nine months of 2016 and our current expectations for the remainder of the year, we are raising our guidance and expect cash, cash equivalents and investments will be at least $50 million at the end of 2016.

On November 9, 2016 Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company, reported financial results for the third quarter ended September 30, 2016 (Press release, Puma Biotechnology, NOV 9, 2016, View Source [SID1234516720]).

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Unless otherwise stated, all comparisons are for the third quarter and nine months ended September 30, 2016, compared to the third quarter and nine months ended September 30, 2015.

Based on accounting principles generally accepted in the United States (GAAP), Puma reported a net loss applicable to common stock of $65.8 million, or $2.02 per share, for the third quarter of 2016, compared to a net loss of $60.4 million, or $1.87 per share, for the third quarter of 2015. Net loss applicable to common stock for the nine months ended September 30, 2016 was $203.4 million, or $6.26 per share, compared to $177.6 million, or $5.55 per share, for the nine months ended September 30, 2015.

Non-GAAP adjusted net loss was $36.0 million, or $1.11 per share, for the third quarter of 2016, compared to non-GAAP adjusted net loss of $35.5 million, or $1.10 per share, for the third quarter of 2015. Non-GAAP adjusted net loss for the nine months ended September 30, 2016 was $115.4 million, or $3.55 per share, compared to $104.3 million, or $3.26 per share, for the nine months ended September 30, 2015. Non-GAAP adjusted net loss excludes stock-based compensation expense, which represents a significant portion of overall expense and has no impact on the cash position of the Company. For a reconciliation of GAAP net loss to non-GAAP adjusted net loss and GAAP net loss per share to non-GAAP adjusted net loss per share, please see the financial tables at the end of this news release.

Net cash used in operating activities for the third quarter of 2016 was $34.9 million. Net cash used in operating activities for the nine months ended September 30, 2016 was $100.7 million. At September 30, 2016, Puma had cash and cash equivalents of $52.5 million and marketable securities of $56.4 million, compared to cash and cash equivalents of $31.6 million and marketable securities of $184.3 million at December 31, 2015. The Company’s balance of cash, cash equivalents and marketable securities at the end of the quarter does not include the net proceeds of approximately $162 million received from the Company’s public offering in October 2016.

"During the third quarter, we achieved several key milestones, including the European Medicines Agency’s (EMA) validation of the Marketing Authorization Application (MAA) for neratinib as an extended adjuvant treatment of HER2-positive early stage breast cancer in Europe, and the U.S. Food and Drug Administration’s (FDA) acceptance of the New Drug Application (NDA) for neratinib as an extended adjuvant treatment for patients with early stage HER2-overexpressed/amplified breast cancer who have received prior adjuvant trastuzumab (Herceptin)-based therapy," said Alan H. Auerbach, Chairman, Chief Executive Officer and President of Puma.

"We anticipate a number of additional milestones through the end of 2016 and first half of 2017," Mr. Auerbach added. "These include: (i) reporting additional data in the fourth quarter of 2016 from the Phase II trial of neratinib as an extended adjuvant treatment in HER2-positive early stage breast cancer using loperamide and budesonide prophylaxis; (ii) reporting additional Phase II data in the fourth quarter of 2016 from the FB-7 neoadjuvant HER2-positive breast cancer trial in the subgroup of patients who are MammaPrint High; (iii) reporting data in the fourth quarter of 2016 from the Phase II trial of neratinib plus fulvestrant in patients with HER2 non-amplified breast cancer that has a HER2 mutation; (iv) reporting data in the first half of 2017 from the Phase III trial of neratinib in third-line HER2-positive metastatic breast cancer patients; and (v) reporting data during the first half of 2017 from the Phase II trial of neratinib in HER2-positive metastatic breast cancer patients with brain metastases."

Operating Expenses

Operating expenses were $66.0 million for the third quarter of 2016, compared to $60.7 million for the third quarter of 2015. Operating expenses for the nine months ended September 30, 2016 were $203.7 million, compared to $178.2 million for the nine months ended September 30, 2015.

General and Administrative Expenses:

General and administrative expenses were $14.0 million for the third quarter of 2016, compared to $8.8 million for the third quarter of 2015. General and administrative expenses for the nine months ended September 30, 2016 were $37.3 million, compared to $22.2 million for the nine months ended September 30, 2015. The increase of approximately $15.1 million during the nine months ended September 30, 2016 compared to the same period in 2015 resulted primarily from increases of approximately $7.5 million in stock-based compensation, $1.9 million in payroll and related costs, $3.7 million in professional fees and expenses, and $1.6 million in facility and equipment costs. These increases reflect higher legal and compliance expenses, as well as overall corporate growth.

Research and Development Expenses:

Research and development expenses were $52.0 million for the third quarter of 2016, compared to $51.9 million for the third quarter of 2015. Research and development expenses for the nine months ended September 30, 2016 were $166.4 million, compared to $156.0 million for the nine months ended September 30, 2015. The increase of approximately $10.4 million during the nine months ended September 30, 2016 compared to the same period in 2015 resulted primarily from increases of approximately $7.2 million in stock-based compensation, $3.7 million for internal clinical development, regulatory affairs and quality assurance and internal chemical manufacturing expenses, and $2.7 million in consultants and contractors related expenses, offset by a $3.3 million decrease in clinical trial expenses.

Ariad has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Ariad, NOV 8, 2016, View Source [SID1234516412]).

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

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

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

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

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

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

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

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

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