On November 13, 2017 Novartis reported that it has had a strong year in innovation with several key approvals and positive trial readouts (Press release, Novartis, NOV 12, 2017, View Source [SID1234521950]). Novartis holds an R&D and investor update in London, which will provide deeper insights into key late-stage pipeline projects. In the Oncology business unit, Novartis is pursuing multiple indications for Kymriah, the first-in-class CAR-T therapy, and could further strengthen the oncology pipeline if the proposed acquisition of Advanced Accelerator Applications is closed. In the Pharmaceuticals business unit, Novartis continues to strengthen its position in Multiple Sclerosis through BAF312 (siponimod), OMB157 (ofatumumab) and the recent pediatric findings for Gilenya. During the investor event Novartis will provide a deep dive on the four selected programs below.

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In Ophthalmology, RTH258 (brolucizumab) data presented at the American Academy of Ophthalmology showed superiority versus aflibercept in key secondary endpoints reflective of disease activity in patients with nAMD. Patients treated with RTH258 showed fewer signs of specific disease activity than patients treated with aflibercept. RTH258 patients showed less retinal fluids, less fluid in the deepest part of the retina and superior reductions in retinal thickness. Novartis expects to file for the nAMD indication by Q4 2018 and expects to start clinical trials in DME and RVO during 2018. Additionally, RTH258 creates the potential opportunity for Novartis to enter the attractive growing US retina market.

In Neuroscience, AMG 334 (erenumab) is being developed to deliver an effective and safe prophylactic treatment for patients suffering from chronic or episodic migraine. This debilitating disease affects more than 10% of adults, mainly in their prime working years. AMG 334 has shown encouraging results in reducing monthly migraine days, even in difficult to treat patients. AMG 334 is a fully human, potent, selective CGRP antagonist targeting the receptor and it was the first CGRP antagonist to be filed in the US and EU, on track for a potential first-in-class launch in 2018.

In Immunology, Cosentyx continues to build on its best-in-class profile, which has demonstrated sustained control of signs and symptoms in PSO, PsA and AS. Cosentyx has strong differentiation based on its unique biology which has shown a high level of enthesitis resolution and no radiographic progression in psoriatic arthritis and ankylosing spondylitis. By targeting the IL-17A pathway, the cornerstone cytokine of enthesitis, Cosentyx has the potential to change the course of disease in AS and PsA. Cosentyx is uniquely positioned to continue growth in all indications, particularly in spondyloarthritis, where the segment opportunity is larger than psoriasis.

In Cardiology, ACZ885 (canakinumab) data showed there was a significant reduction in major adverse cardiac events, in a subpopulation of patients who achieved hsCRP<2mg/L three months after the initial treatment. This well defined target population is critical to establishing the product’s value proposition and commercial uptake. Feedback from FDA and EU regulators supports moving forward with regulatory submissions for cardiovascular risk reduction, which are planned for Q4 and onwards. The novelty of approach to reduce CV risk is recognized by the regulators and there is interest in understanding the relationship between hsCRP and patient response.

For background slides and webcast (audio only) please refer to the following link: View Source
The background slide decks will be available on Monday November 13th, 2017.

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "pipeline," "on track," "moving forward," "will," "pursuing," "could," "continues," "expects," "by Q4 2018," "during 2018," "potential," "growing," "being developed," "encouraging," "launch," "to build," "positioned," "opportunity," "planned," "for Q4 and onwards," "interest in," or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational and approved products described in this press release, including RTH258, AMG 334, ACZ885, BAF312, OMB157, Cosentyx, Kymriah and Gilenya, or regarding potential future revenues from such investigational and approved products, or by express or implied discussions regarding the potential outcome of the tender offer for Advanced Accelerator Applications, and the potential impact on Novartis of the proposed acquisition, including express or implied discussions regarding potential future sales or earnings of Novartis, and any potential strategic benefits, synergies or opportunities expected as a result of the proposed acquisition. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that any new products will be approved for sale in any market, or that any new indications will be approved for any existing products in any market, or that any approvals which are obtained will be obtained at any particular time, or that any such products will achieve any particular revenue levels. Neither can there be any guarantee that the investigational or approved products described in this press release will be commercially successful in the future. Nor can there be any guarantee that the proposed acquisition described in this press release will be completed, or that it will be completed as currently proposed, or at any particular time. Neither can there be any guarantee that Novartis will achieve any particular future financial results as a result of the proposed acquisition, or that Novartis will be able to realize any potential strategic benefits, synergies or opportunities as a result of the proposed acquisition. Nor can there be any guarantee that shareholders will achieve any particular level of shareholder returns. Neither can there be any guarantee that the Group, or any of its divisions, will be commercially successful in the future, or achieve any particular credit rating or financial results. In particular, our expectations could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally, including potential regulatory actions or delays relating to the completion of the potential acquisition described in this press release, as well as potential regulatory actions or delays with respect to the development of the products described in this press release; the potential that the strategic benefits, synergies or opportunities expected from the proposed acquisition may not be realized or may take longer to realize than expected; uncertainties regarding actual or potential legal proceedings, including, among others, potential legal proceedings with respect to the proposed acquisition; our ability to obtain or maintain proprietary intellectual property protection, including the ultimate extent of the impact on Novartis of the loss of patent protection and exclusivity on key products which commenced in prior years and will continue this year; the particular prescribing preferences of physicians and patients; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures, such as from increased publicity on pharmaceuticals pricing, including in certain large markets; general economic and industry conditions, including the effects of the persistently weak economic and financial environment in many countries; uncertainties regarding future demand for our products; safety, quality or manufacturing issues, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

Additional Information
Novartis announced October 30, 2017, that it had entered a memorandum of understanding with Advanced Accelerator Applications (AAA) under which Novartis intends to commence a tender offer for 100% of the share capital of AAA. The transaction is subject to certain closing conditions. Novartis will commence a tender offer upon completion of works council consultation and AAA’s Board of Directors recommending the tender offer to AAA shareholders. The senior management and Directors of AAA have, in their capacity as shareholders of AAA, undertaken to tender their shares into the proposed tender offer. The transaction is additionally subject to (i) the valid tender pursuant to the tender offer of ordinary shares (including ordinary shares in the form of American Depositary Shares) of AAA representing at least 80% of the outstanding ordinary shares on a fully diluted basis and (ii) receipt of customary transactional regulatory approvals and other customary closing conditions. Until such time as the closing conditions are satisfied, Lutathera remains under the custody and control of AAA. Novartis does not currently own or control these projects and will not have the ability to influence them until closing of the proposed acquisition of AAA which is subject to certain closing conditions and regulatory approvals.

Lutathera is a registered trademark of Advanced Accelerator Applications.

On November 11, 2017 Heat Biologics, Inc. ("Heat") (Nasdaq: HTBX), a biopharmaceutical company developing drugs designed to activate a patient’s immune system against cancer, reported updated pre-clinical data evaluating its Combination Pan-antigen Cytotoxic Therapy (ComPACT) platform in combination with a checkpoint inhibitor and T-cell co-stimulators as a potential immunotherapy cocktail approach to treat cancer (Press release, Heat Biologics, NOV 11, 2017, View Source [SID1234521945]). Data from the follow-up study build upon previous pre-clinical results utilizing Heat’s ComPACT platform, which generated positive synergies with checkpoint inhibitors and the T-cell co-stimulator, OX40.

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The poster presentation, Gp96-IG/costimulatory Combination Vaccine Improves T-cell Priming and Enhances Immunity, Memory, and Tumor Elimination, was presented at the 32nd annual meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper).

The follow-up study was designed to further assess ComPACT combined with a checkpoint inhibitor and OX40, but now with the addition of the cell-secreted, T-cell costimulatory, TL1A. ComPACT is Heat’s next generation, T-cell activation platform (TCAP). It combines T-cell activation and co-stimulation in a single therapy by both delivering the gp96 heat shock protein and a T-cell co-stimulatory fusion proteins in a single compound.

Results in pre-clinical trials show that this combination approach effectively synergizes with antagonist antibody therapies that amplify antigen-specific T-cells; program a memory response; and eliminate tumors. Heat subsidiary Pelican Therapeutics is currently manufacturing a TL1A drug for anticipated human clinical trials that is partially funded through a $15 million grant provided by the Cancer Prevention Research Institute of Texas (CPRIT).

"Our follow-up study on our ComPACT T-cell activation platform provides us with robust data demonstrating a potentially efficacious approach to treating human cancers," said Louis E. Gonzalez, chief scientist at Heat. "The addition of TL1A in combination with OX40 has been found to improve T-cell priming which is an important of any immunotherapy cocktail to treat patients with cancer."

On November 11, 2017 Corvus Pharmaceuticals, Inc. (NASDAQ:CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of novel immuno-oncology therapies, reported updated clinical data from the renal cell carcinoma (RCC) expansion cohorts of its ongoing Phase 1/1b study of CPI-444 as a single agent and in combination with atezolizumab (TECENTRIQ) (Press release, Corvus Pharmaceuticals, NOV 11, 2017, View Source;p=RssLanding&cat=news&id=2316328 [SID1234521944]). Results showed a response rate of 14 percent (two partial responses, one of which was unconfirmed) with single agent CPI-444 and 13 percent (two confirmed partial responses) for the combination therapy, and a disease control rate of 29 percent and 69 percent for single agent and combination therapy, respectively, in 30 response-evaluable patients. Additionally, biomarker data from the trial showed an association between adenosine pathway gene expression and response to therapy, and resistance to prior anti-PD-(L)1 treatment. The clinical and biomarker data were presented today in an oral session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 32ND Annual Meeting in National Harbor, Md., by Jason J. Luke, M.D., a medical oncologist and assistant professor of medicine at the University of Chicago Medicine.

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CPI-444 is a selective and potent inhibitor of the adenosine A2A receptor. Atezolizumab, developed by Genentech, a member of the Roche Group, is a monoclonal antibody designed to target and bind to a protein called PD-L1 (programmed death ligand-1).

"These data provide new information on the importance of the adenosine pathway and its value as a target for cancer immunotherapy," said Dr. Luke. "We are seeing clinical activity in patients with RCC and other tumors, including patients who are resistant to prior anti-PD-(L)1 therapy and have few treatment options. The early biomarker data show that prior exposure to anti-PD-(L)1 increases expression of adenosine pathway genes, supporting earlier research indicating that the adenosine pathway is a resistance mechanism to anti-PD-(L)1 therapy. The data suggest that it may be possible to use biomarkers, specifically tumor expression of the A2A receptor and CD73, to identify patients with RCC and other tumors who are most likely to respond to treatment with CPI-444 or other forms of adenosine blockade."

The ongoing Phase 1/1b clinical trial has enrolled more than 225 patients with several tumor types including RCC, non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), melanoma and other tumors. To date, RCC (single agent and combination) and NSCLC (single agent and combination) cohorts have met the protocol-defined criteria for expansion from 14 to 26 patients. For both the RCC single agent and combination cohorts, criteria for expansion to 48 patients per cohort have been reached. Of 51 patients with RCC enrolled in the study, 69 percent were resistant or refractory to prior anti-PD-(L)1 therapy, having failed those therapies within a median time of 1.6 months prior to enrollment. The RCC patients had several adverse prognostic features including visceral metastases (88 percent), hepatic metastases (20 percent), anemia (45 percent) and elevated serum lactate dehydrogenase (21 percent).

"Our Phase 1/1b study continues to generate important clinical and biologic data that is helping us identify mechanisms of resistance to anti-PD-(L)1 therapies. With that data, we may be able to identify clinical characteristics and biomarkers associated with a clinical response, optimize treatment regimens and improve patient outcomes," said Richard A. Miller, an oncologist and co-founder, president and chief executive officer of Corvus. "In 2018, we anticipate initiating a pivotal trial of CPI-444 in RCC and, utilizing the information we have learned to date, selecting patients most likely to benefit from treatment. We also intend to initiate a clinical trial of our anti-CD73 antibody in the first half of 2018, which is another approach to blockade of the adenosine pathway in RCC and other cancers."

KEY CLINICAL RESULTS PRESENTED AT SITC (Free SITC Whitepaper)
Updated efficacy and safety data from the single agent and combination RCC cohorts were presented at SITC (Free SITC Whitepaper). 51 patients with RCC have been enrolled to date. Data from 14 patients receiving CPI-444 single agent therapy and 16 receiving combination therapy who were evaluable for response showed:

Four patients experienced a partial response (one confirmed and one unconfirmed with single agent therapy and two confirmed partial responses with combination). Both single agent responses occurred in patients resistant or refractory to prior treatment with anti-PD-(L)1.
Disease control (stable disease and partial responses) was achieved in 29 percent and 69 percent of patients receiving single agent and combination therapy, respectively.
CPI-444 continues to be well tolerated to date, with observed adverse events similar to previous reports. In both the single-agent and combination arms for the entire safety data set (N=210), Grade 1 and 2 adverse events occurring in 5 or more percent of patients included fatigue, nausea, pruritis, pyrexia, decreased appetite, diarrhea and anemia. One patient had Grade 3 nausea, vomiting and diarrhea in the single agent arm. Four patients had a serious Grade 3 toxicity in the combination arm, one with hepatitis, one with pneumonitis, one with hemolytic anemia, and one with hepatitis, mucositis, pneumonitis and dermatitis. One other patient in the combination arm had both Grade 4 encephalitis and Grade 3 thrombocytopenia.
KEY BIOMARKER RESULTS PRESENTED AT SITC (Free SITC Whitepaper)
Biomarker analysis, performed on blood and tumor tissues from the RCC and NSCLC cohorts, showed:

Tumor expression of the A2A receptor, CD73 and CD39 was increased in patients resistant to prior treatment with anti-PD-(L)1.
Patients with RCC and NSCLC had high tumor expression of the A2A receptor, CD73 and CD39 in screening, pre-treatment biopsies compared to patients with other tumors.
Biopsies showed that treatment with CPI-444 increased CD8 positive cell infiltration in tumors and induced expression of genes consistent with Th1 activation.
For patients enrolled in the study with all tumor histologies and for whom screening biopsies were available for analysis, tumor expression of the A2A receptor and CD73 was associated with a response to CPI-444, as follows:

Patients with high expression of the A2A receptor had a disease control rate of 29 percent (10 of 34) compared with 10 percent (four of 39) for those with low expression.
Patients with high expression of CD73 had a disease control rate of 24 percent (12 of 51) compared with 9 percent (two of 22) for those with low expression.
Patients with high expression of both the A2A receptor and CD73, referred to as double positive, had a disease control rate of 42 percent (10 of 24) compared to 8 percent for those without double positive tumors (four of 47), p<0.0007.
All four of the patients with a partial response were double positive (two RCC patients, one NSCLC patient and one MSI-H colon cancer patient). Tissue was not available for all patients with a partial response.
PHASE 1/1B TRIAL DESIGN
The Phase 1/1b trial is designed to select the dose, assess the safety and examine the activity of CPI-444 as a single agent and in combination with Genentech’s atezolizumab, an anti-PD-L1 antibody, in multiple histologies known to be sensitive to immuno-oncology agents. Patients with non-small cell lung cancer, melanoma, renal cell cancer, triple-negative breast cancer, MSI-H colorectal cancer, head and neck cancer, bladder cancer and prostate cancer who have failed standard therapies are eligible. The efficacy endpoints of the study are response rate and disease control rate, which is defined as complete response, partial response (reduction of >30 percent tumor volume) or stable disease (change in tumor volume of between 20 percent growth of tumor and 30 percent reduction of tumor volume). Patients with minor tumor regressions are those with changes in tumor volume of 0 to ≤30 percent reduction in tumor volume. Patients are treated until disease progression or evidence of Grade 3 or 4 toxicity.

The dose-selection part of the study included four cohorts of 12 patients each (N=48) – three cohorts treated with single agent CPI-444 (100 mg twice daily for 14 days; 100 mg twice daily for 28 days; 200 mg once daily for 14 days) and one cohort treated with the combination (CPI-444 50 mg or 100 mg twice daily for 14 days combined with atezolizumab). A treatment cycle is 28 days. Based on biomarker analyses showing sustained, complete blockade of the adenosine A2A receptor in peripheral blood lymphocytes, and evidence of immune activation in circulating lymphocytes, an optimum single agent and combination dose of 100 mg twice a day for 28 days was selected for the second part of the study. As defined in the protocol, patients in the dose-selection stage of the trial receiving the dose and schedule selected for evaluation in the second part of the study are included in the disease-specific cohort efficacy analysis.

The second part of the study is evaluating CPI-444 as a single agent in five disease-specific cohorts (NSCLC, melanoma, RCC, TNBC and a category of "other" that includes MSI-H colorectal cancer, bladder cancer and prostate cancer) and CPI-444 in combination with atezolizumab in five additional matched disease-specific cohorts. Each of the 10 cohorts is initially enrolling 14 patients, but may be expanded based on efficacy.

ABOUT CPI-444
CPI-444 is a small molecule, oral, checkpoint inhibitor designed to disable a tumor’s ability to subvert attack by the immune system by blocking the binding of adenosine in the tumor microenvironment to the A2A receptor. Adenosine, a metabolite of ATP (adenosine tri-phosphate), is produced within the tumor microenvironment where it may bind to the adenosine A2A receptor present on immune cells and block their activity. CD39 and CD73 are enzymes on the surface of tumor cells and immune cells. These enzymes work in concert to convert ATP to adenosine.

On November 11, 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 an update on the immunology data from the February 2017 interim analysis of data from the ongoing Phase 3 ADAPT clinical trial evaluating Rocapuldencel-T for the treatment of metastatic renal cell carcinoma (mRCC) presented in the poster session at the 32nd Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in National Harbor, Maryland(Press release, Argos Therapeutics, NOV 11, 2017, View Source [SID1234521943]). The presentation is focused primarily upon immunology data from the ADAPT clinical trial and includes both new data and an update to data that was previously presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Conference in September 2017 that now includes additional patients.

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As background, a total of 462 patients were enrolled in the ADAPT study and randomized 2:1 between combination treatment with Rocapuldencel-T and sunitinib (combination arm) vs. sunitinib monotherapy (control arm).

Immunology data from the February 2017 interim analysis of the data from the ADAPT study reported at the SITC (Free SITC Whitepaper) Conference were pre-specified and include correlations between survival and (i) the change from baseline in antigen-specific memory T-cells, (ii) the amount of IL-12 secreted by each patient’s specific Rocapuldencel-T immunotherapy, and (iii) the percentage of regulatory T-cells at baseline, which was observed in both arms of the study. Of note, data for antigen-specific memory T-cells and regulatory T-cells were available only for patients enrolled at North American sites.

Increase from Baseline in Antigen-Specific Memory T-Cells

In subjects for whom immune response data were analyzed (n=146), the number of antigen-specific memory T-cells was found to increase only after administration of Rocapuldencel-T. In those subjects who received at least seven doses of Rocapuldencel-T (n=100), the average number of antigen-specific memory T-cells after the seventh dose was approximately double the number observed before treatment. This increase was found to be statistically significant (p<0.0001). Similar data on a smaller number of patients were presented at the European Society for Medical Oncology Conference in September 2017.

Additionally, for those subjects who received at least seven doses of Rocapuldencel-T, there was a statistically significant correlation between survival and the change in the number of antigen-specific memory T-cells from baseline (Spearman’s Rho = 0.40; p<0.0001). For those 25 patients with the greatest increase in the number of antigen-specific memory T-cells from baseline, no patient deaths had been recorded as of the time of the February 2017 interim analysis.

IL-12 Secretion by Each Patient’s Specific Rocapuldencel-T Immunotherapy

An analysis was conducted to evaluate the relationship between the amount of IL-12 secreted by each patient’s specific immunotherapy and that patient’s survival. Samples from patients treated with Rocapuldencel-T as of February 2017 (n=179) were divided into two groups: those with above the median amount of IL-12, and those with below the median amount of IL-12. Comparison of the Kaplan-Meier curves for these two groups revealed that those with higher than median levels of IL-12 demonstrated improved survival. Additionally, there was a statistically significant correlation between the level of IL-12 and survival (Spearman’s Rho = 0.27; p<0.0002). There was also a statistically significant correlation between the level of IL-12 and the change from baseline in antigen-specific memory T-cells for patients who received at least seven doses of Rocapuldencel-T (n=95; Spearman’s Rho = 0.43; p<0.0001).

Regulatory T-Cells

An analysis was conducted to evaluate the relationship between the percentage of regulatory T-cells at baseline and survival for patients in both arms of the trial. Samples from patients in the combination arm (n=176) were divided into two groups: those with above median percentage of regulatory T-cells at baseline, and those with below median percentage of regulatory T-cells at baseline. Comparison of the Kaplan-Meier curves for these two groups revealed that those with higher than median percentage of regulatory T-cells at baseline demonstrated improved survival. This finding was in contrast to the control arm (n=79), where a greater percentage of regulatory T-cells at baseline was associated with poorer survival. One hypothesis that could potentially explain this result is that Rocapuldencel-T may be acting to convert regulatory T-cells to effector T-cells.

Commenting on the additional immunology data, Charles Nicolette, Chief Scientific Officer of Argos Therapeutics, noted, "As we have conducted additional analyses of the immunology data from the February 2017 interim analysis, we have been pleased to see that the data are generally supportive of our hypothesis regarding the intended mechanism of action of Rocapuldencel-T to induce an immune response against the tumor in patients with metastatic renal cell carcinoma. While we await further data from the next planned interim data analysis that we expect to be conducted during the first half of 2018, pending agreement with the FDA on a revised protocol that we plan to submit, we are encouraged to see these positive indicators of activity."

As previously reported, the February 2017 interim analysis was conducted by the ADAPT trial’s Independent Data Monitoring Committee (IDMC) after 75% of the originally targeted number of 290 events (deaths) for the analysis of the primary endpoint of overall survival had occurred. At the time of the analysis, with more than half of the patients still alive in each arm and a median follow-up time of ~20 months, the IDMC concluded that the trial was unlikely to demonstrate a statistically significant improvement in median overall survival in the combination arm and recommended that the trial be discontinued for futility. However, the ADAPT trial principal investigators and Argos considered the data too immature to observe the delayed effects typically associated with immunotherapy and decided to continue the trial pending further review and analysis of the data and discussions with the U.S. Food and Drug Administration (FDA). In making this determination, Argos considered, among other factors, the degree of maturity of the data set, the mechanism of action of Rocapuldencel-T, which involves the induction of a long-term memory immune response, and the IDMC’s assessment of the safety profile of Rocapuldencel-T. This determination was subsequently further supported by the extended durability of tumor responses in the combination arm, as previously reported.

Following the IDMC’s interim analysis, the Company met with the FDA to discuss the ADAPT trial and the future direction of the Rocapuldencel-T program in April 2017. The FDA agreed with the Company’s decision to continue the ADAPT trial, and further agreed to review a protocol amendment to extend the trial beyond the originally targeted 290 events and a revised statistical analysis plan that the Company plans to submit.

Conference Call Information

Argos will hold a conference call to discuss the data presented at the 32nd Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) on Monday, November 13th at 8:30am ET. 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 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.

On November 11, 2017 Nektar Therapeutics (Nasdaq: NKTR) and Bristol-Myers Squibb (NYSE: BMY) reported the first presentation of data from the PIVOT-02 Phase 1/2 Study, which is designed to evaluate the combination of Bristol-Myers Squibb’s Opdivo (nivolumab) with Nektar’s investigational medicine, NKTR-214. The initial results presented at the 2017 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting reported both safety and efficacy data for patients enrolled in the dose-escalation phase of the trial (Press release, Nektar Therapeutics, NOV 11, 2017, View Source [SID1234521946]).

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"These initial findings underscore the potential benefit of the combination of Opdivo and NKTR-214 across several tumor types," said Fouad Namouni, M.D., Head of Oncology Development, Bristol-Myers Squibb. "We believe that a combination regimen which utilizes two different, complementary, and non-overlapping mechanisms designed to harness the body’s own immune system to fight cancer has the potential to benefit patients and should be the subject of additional research."

Opdivo is a PD-1 immune checkpoint inhibitor designed to overcome immune suppression. NKTR-214 is an investigational immuno-stimulatory therapy designed to expand and activate specific cancer-fighting T cells and natural killer (NK) cells directly in the tumor micro-environment and increase expression of cell-surface PD-1 on these immune cells.

"In the dose-escalation stage of the PIVOT trial, we’ve observed important response rates across all three tumor types – melanoma, renal cell carcinoma and non-small lung cancer – in both PD-L1 positive and PD-L1 negative patients," said Mary Tagliaferri, M.D., Senior Vice President of Clinical Development at Nektar Therapeutics. "All patients with responses in the trial continue on treatment. Of note, we observed responses in 3 of 4 Stage IV non-small cell lung cancer patients whose tumors did not express PD-L1 and who had progressed on prior chemotherapy, including one patient who experienced a complete response. In the combination treatment, there were no Grade 3 or higher immune-mediated adverse events at the recommended Phase 2 dose or below. Nektar and Bristol are now actively enrolling patients in the Phase 2 expansion part of the PIVOT study in 5 different tumor types."

A copy of the full data presentation from Dr. Diab’s oral session is available on Nektar’s corporate website at View Source

A total of 38 patients were enrolled in the dose-escalation phase of the ongoing PIVOT study in a number of dose cohorts. Responses were measured per RECIST 1.1 for efficacy-evaluable ( > 1 on treatment scan) patients as of November 2, 2017.

Highlights from the oral presentation include:

Advanced Treatment-Naïve 1L Melanoma Patients (Stage IV):
Responses were observed in 7/11 (63%) efficacy-evaluable patients (2 CR and 5 PR) ◊. Median time to response was 1.7 months. DCR, also known as disease control rate (CR + PR + 3 SD), was 91%. All 7 patients with responses continue on treatment in the trial.
Advanced Treatment-Naïve 1L Renal Cell Carcinoma Patients (Stage IV):
For patients with one or more baseline scans, responses were observed in 6/13 patients (46%) (1 CR+ and 5 PR). DCR (CR + PR + 5 SD) was 85%. Median time to response in these patients was 1.9 months. For patients with two or more scans available, responses were observed in 6/10 patients (60%) (1 CR, 5 PR, 2 SD). All 11 patients with disease control (CR, PR or SD) continue on treatment in the trial.
Advanced 2L Renal Cell Carcinoma Patients (Stage IV, I-O Naïve)
For patients with one or more baseline scans, responses were observed in 1/7 patients (14%) (1 PR). DCR (CR + PR + 6 SD) was 100%. Median time to response was 3.5 months. All 7 patients with disease control (PR or SD) continue on treatment in the trial.
Advanced 2L PD-L1 Negative Non-Small Cell Lung Cancer Patients (Stage IV, I-O Naïve)
Responses were observed in 3/4 patients (75%) (1 CR± and 2 PR). DCR (CR + PR) was 75%. Median time to response was 1.7 months. All 3 patients with responses continue on treatment in the trial.
Robust expansion of ICOS+ CD4 and CD8+ T cells in the blood and increased ICOS gene expression in the tumor were both observed with the combination of NKTR-214 and nivolumab.
The most common grade 1-2 adverse events were fatigue (74%), flu-like symptoms (68%), rash (60%) and pruritus (42%). There were no treatment discontinuations due to adverse events (AEs) or study deaths.
There were no grade 3 or higher immune-mediated AEs (such as colitis, dermatitis, hepatitis, pneumonitis or endocrinopathies) at the recommended Phase 2 dose or below
A recommended Phase 2 dose of NKTR-214 0.006 mg/kg q3w + nivolumab 360 mg q3w was established and is being evaluated in expansion cohorts in over 10 patient populations with melanoma, renal cell carcinoma, non-small cell lung cancer, bladder, and triple-negative breast cancers (n=~330).
Nektar and Bristol-Myers Squibb entered into a clinical collaboration in September of 2016 to evaluate the potential for the combination of Opdivo and NKTR-214 to show improved and sustained efficacy and tolerability above the current standard of care. Bristol-Myers Squibb and Nektar are equally sharing costs of the combined therapy trials. Nektar maintains its global commercial rights to NKTR-214.

NKTR-214 preferentially binds to the CD122 receptor on the surface of cancer-fighting immune cells in order to stimulate their proliferation. In clinical and preclinical studies, treatment with NKTR-214 resulted in expansion of these cells and mobilization into the tumor micro-environment.1,2,3 NKTR-214 has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines.

◊ One patient with confirmed PR at last scan experienced an unconfirmed CR, there was one additional patient with unconfirmed PR in the melanoma cohort as of Nov 2, 2017.
+ Complete response is unconfirmed, patient has confirmed PR.