On November 13, 2017 RXi Pharmaceuticals Corporation (NASDAQ: RXII) a clinical-stage company developing a new class of RNAi-based therapeutics, and Gustave Roussy, a leading Comprehensive Cancer Centre in Europe, reported that they have entered into a collaborative research agreement to evaluate the potential of RXi’s novel sd-rxRNA technology platform for use in cancer treatments (Press release, RXi Pharmaceuticals, NOV 13, 2017, View Source [SID1234521983]). The agreement covers research to design and evaluate sd-rxRNA compounds in a human tumor xenograft model. Positive results may lead to further development of these compounds for treatment of cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are excited to be working with Gustave Roussy on this research effort," said Dr. Geert Cauwenbergh, President and CEO of RXi Pharmaceuticals. He further added, "We believe that our sd-rxRNA technology platform is broadly applicable to many therapeutic areas, including cancer. Considering our sd-rxRNA development for immuno-oncology applications, we look forward to working with the exceptional team at this prominent cancer center to leverage their expertise in this area."

Professor Caroline Robert, MD, PhD, head of the Dermatology Unit at the Gustave Roussy Institute which focuses on skin cancer research, said that "the innovative technology developed by RXi will allow us to address several critical questions in the field of cancer research and to explore future potential use of siRNAs in the clinic."

About Gustave Roussy

Gustave Roussy, the largest comprehensive cancer center in Europe, is a pole of expertise dedicated to the comprehensive care of patients, employing 3,100 health professionals for health care, research and teaching. – www.gustaveroussy.fr/en

On November 13, 2017 Immunocore Limited, the world’s leading TCR company developing biological drugs to treat cancer and infectious diseases, reported durable tumour responses and strong overall survival data from two Phase I clinical trials of its wholly owned, lead programme, IMCgp100, in metastatic uveal melanoma (Press release, Immunocore, NOV 13, 2017, View Source [SID1234521949]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The data, which show a near doubling in the average rate of overall survival compared with studies of other agents, was presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 32nd Annual Meeting on Saturday 11th November 2017, at the Gaylord National Resort & Convention Center in National Harbor, Maryland, USA.

Immunocore’s intra-patient dose escalation Phase I IMCgp100 study in metastatic uveal melanoma patients demonstrates a one-year overall survival (OS) rate of 73% (95% confidence interval [46, 88]) and a one-year progression-free-survival (PFS) rate of 62% based on the irRC criteria as of the data cut-off in October 2017. Median OS has not been reached with median follow-up of 12.8 months in this cohort. The overall survival data from this study compare very favourably to studies with other agents, which show one-year OS rates of approximately 25-45%*.

Pharmacodynamic analysis demonstrated evidence of T cell infiltration and immune activation in tumours after IMCgp100 administration, with persistence of T cell infiltration in the setting of resistance, underpinning confidence in the efficacy observed with the T cell redirection technology of IMCgp100.

Commenting on the results, Dr Richard Carvajal, Head of Experimental Therapeutics at Columbia University, said: "Metastatic uveal melanoma is a condition with exceptionally high unmet medical need with no current standard of care in this setting. No therapies to date have shown survival benefits in trials. The exciting one year overall survival and progression-free survival data we have observed with IMCgp100 have given us confidence to move into pivotal trials measuring survival in this disease setting."

Christina Coughlin, Chief Medical Officer at Immunocore, said: "We believe this therapy has the potential to be a game-changer for medical practice in this devastating condition. At Immunocore, we’re optimistic that the exceptionally strong data we have seen with IMCgp100 in metastatic uveal melanoma have the potential to read across to other ImmTAC programmes, especially when addressing ‘cold’ tumours which are challenging for checkpoint inhibitors and other novel immuno-oncology agents to address. We believe that this underscores the broader applicability of Immunocore’s soluble TCR technology in cancer and beyond."

The details of the clinical trial can be found on clinicaltrials.gov.

Poster Presentation Information

Title: Safety, efficacy and biology of the gp100 TCR-based bispecific T cell redirector, IMCgp100 in advanced uveal melanoma in two Phase 1 trials

Authors: Richard Carvajal, Takami Sato, Alexander N. Shoushtari, Joseph Sacco, Paul Nathan, Marlana Orloff, Pippa Corrie, Neil Steven, Jeff Evans, Jeffrey Infante, Mario Sznol, Clive Mulatero, Omid Hamid, Leonel Hernandez-Aya, Nicola Little, Cheryl McAlpine, David Krige, Namir J. Hassan, Sanjay Patel, Ann-Marie Hulstine, Christina M. Coughlin, Mark R. Middleton

Category: Clinical Trials (Completed)

Date: Saturday 11 November 2017

Time: 12:30 – 14:00 & 18:30 – 20:00

Abstract Number: P208

To view the abstract, please visit the SITC (Free SITC Whitepaper) website at View Source

Phase I, First-in-Human, Open-Label, Multiple-Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of M4112 an IDO1/TDO2 Inhibitor as Single Agent and Sequentially in Combinations with Avelumab or M7824 (TGFß Trap) in Subjects with Metastatic or Locally Advanced Unresectable Solid Tumors

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

There are 2 parts to this study: Part 1 and Part 2. This consent form is for Part 1 only. In Part 1, there are 3 sub-groups: Part 1A, 1B, and 1C. The goal of this clinical research study is to find the highest tolerable dose of M4112 that can be given to patients with advanced or metastatic (have spread) solid tumors that are unresectable (cannot be removed with surgery). In this study, M4112 will be studied alone (Part 1A) or in combination with either avelumab (Part 1B) or M7824 (Part 1C). This is the first study using M4112 in humans. The safety of M4112 and the drug combinations will also be studied.

General Information

Disease Group: Malignant neoplasms of ill-defined secondary and unspecified sites,Malignant neoplasms of independent (primary) multiple sites

Treatment Agent: Avelumab,M4112,MSB0011359C

Treatment Location: Both at MDACC & and Other Sites

Sponsor: EMD Serono

Study Objectives/Outcome

Primary Objectives Part IA (Dose Escalation – M4112 as Single Agent) To determine safety and tolerability or, if observed, the maximum tolerated dose (MTD), and to define the recommended phase 2 dose (RP2D) of M4112 as single agent in subjects with solid tumors. Part IB (Dose Escalation – M4112 in Combination with Avelumab) To determine safety and tolerability or, if observed, the MTD, and to define the RP2D of M4112 in combination with avelumab in subjects with solid tumors. Part IC (Dose Escalation – M4112 in Combination with M7824) To determine safety and tolerability or, if observed, the MTD, and to define the RP2D of M4112 in combination with M7824 in subjects with solid tumors. Secondary Objectives Part IA (Dose Escalation – M4112 as Single Agent) To characterize the pharmacokinetic (PK) parameters of M4112 as single agent. To assess QT prolongation potential by central tendency, outlier analysis and the slope of exposure-QT corrected interval (QTc) analysis to evaluate preliminary clinical activity parameters using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. To evaluate preliminary clinical activity parameters using RECIST 1.1. Part IB (Dose Escalation – M4112 in Combination with Avelumab) To characterize the PK parameters of M4112 and avelumab exposure in combination. To evaluate the immunogenicity of avelumab when given in combination with M4112. To evaluate preliminary clinical activity parameters using RECIST 1.1. Part IC (Dose Escalation – M4112 in Combination with M7824) To characterize the PK parameters of M4112 and M7824 exposure in combination. To evaluate the immunogenicity of M7824 when given in combination with M4112. To evaluate preliminary clinical activity parameters using RECIST 1.1. Exploratory Objectives Part IA (Dose Escalation – M4112 as Single Agent) To evaluate the effect of M4112 on kynurenine (Kyn) and tryptophan (Trp) in plasma of subjects. To evaluate the effect of M4112 on indoleamine-2,3-dioxygenase 1 (IDO1) activity in ex vivo stimulated whole blood of subjects. To study genetic variations that may affect the safety and tolerability, PK and pharmacodynamics (PD) profiles of M4112. To evaluate the effects of M4112 on changes in immune phenotype and cytokines in relation to treatment-related adverse events (TRAE) and clinical outcomes. To assess effects of M4112 as single agent on 4B-hydroxycholesterol and cholesterol activity. Part IB (Dose Escalation – M4112 in Combination with Avelumab) To evaluate the effect of M4112 in combination with avelumab on Kyn and Trp in plasma of subjects. To evaluate the effect of M4112 on IDO1 activity in ex vivo stimulated whole blood of subjects. To study genetic variations that may affect the safety and tolerability, PK and PD profiles of M4112 in combination with avelumab. To evaluate the effects of M4112 in combination with avelumab on changes in immune phenotype and cytokines in relation to TRAE and clinical outcomes. Part IC (Dose Escalation – M4112 in Combination with M7824) To evaluate the effect of M4112 in combination with M7824 on Kyn and Trp in plasma of subjects. To evaluate the effect of M4112 on IDO1 activity in ex vivo stimulated whole blood of subjects. To study genetic variations that may affect the safety and tolerability, PK and PD profiles of M4112 in combination with M7824. To evaluate the effects of M4112 in combination with M7824 on changes in immune phenotype and cytokines in relation to TRAE and clinical outcomes.

IRB Review and Approval Date: 12/11/2017

Recruitment Status: Open

Projected Accrual: 60

Enrollment Eligibility
Eligibility:

1) Signed written informed consent form (ICF) before any study-related procedure is undertaken that is not part of the standard subject management.
2) Male or female subjects >/= 18 years of age.
3) Subject population: a. In the dose escalation cohorts (Part IA to Part IC): Histologically or cytologically proven advanced or metastatic solid malignancies for whom no effective standard therapy exists or has failed or subjects who are intolerant to established therapy known to provide clinical benefit for their condition.
4) Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at Screening.
5) Subjects who have been treated previously with a checkpoint inhibitor may enroll.
6) Adequate hematological function as defined below: a. Absolute neutrophil count >/= 1,500/mm^3 or >/= 1.5 × 10^9/L; b. Platelet count >/= 100,000/mm^3 or >/= 100 × 10^9/L; c. Hemoglobin >/= 9 g/dL.
7) Adequate hepatic function defined: by a total bilirubin level 1.5 × ULN but < 3 × ULN; b. Subjects with tumor involvement in their liver: AST < 3.0 × ULN, ALT < 3.0 × ULN, with normal bilirubin 8) Adequate renal function defined by an estimated glomerular filtration rate > 50 mL/min according to the Cockcroft-Gault formula or normal creatinine laboratory values. (Glomerular filtration rate [mL/min/1.73 m^2] = 175 × serum creatinine (Scr)-1.154 × age – 0.203 × 1.212 [if African American] × 0.742 [if female]).
9) Male participants must agree to use and to have their female partners use a highly effective contraception (i.e., methods with a failure rate of less than 1 % per year) as detailed in protocol 30 days before first dose of study treatment (as appropriate), during the treatment period and for at least 60 days after the last dose of study treatment of M4112 as single agent or in combination with avelumab and for at least 120 days after the last dose of M7824 and must refrain from donating sperm during this period.
10) Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a. Not a woman of childbearing potential (WOCBP) as defined in protocol, OR b. A WOCBP who agrees to use a highly effective contraception (i.e., methods with a failure rate of less than 1 % per year) as detailed in protocol 30 days before start of first dose of study treatment (as appropriate), during the treatment period and for at least 60 days after the last dose of study treatment of M4112 as single agent or in combination with avelumab and for at least 120 days after the last dose of M7824. Since the effect of potential of M4112 to induce/inhibit CYP3A4 is unknown at this time, WOCBP that are currently using hormonal contraception that is a substrate for CYP3A4 should also use double barrier contraception.
11) Women of childbearing potential must have a negative plasma pregnancy test at the Screening Visit and a negative urine pregnancy test on Day 1 before enrollment and dosing.
Exclusion:

1) Prior therapy with: In combination with avelumab or M7824 in the dose escalation only cohorts (Part 1B and Part 1C): Intolerance to immune checkpoint inhibitor therapy as defined by the occurrence of an adverse drug reaction (ADR) requiring drug discontinuation.
2) Persisting toxicity related to prior therapy Grade > 1 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 4.03, however sensory neuropathy Grade 3) Prior organ transplantation including allogeneic stem cell transplantation.
4) All subjects with known brain metastases, except those meeting the following criteria: a. Brain metastases that have been treated locally and are clinically stable for at least 4 weeks prior to the start of treatment. b. No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable). c. Subjects must be either off steroids or on a stable or decreasing dose of < 10 mg daily prednisone (or equivalent).
5) Concurrent treatment with a non-permitted drug/intervention: a. Strong inhibitors or inducers of CYP3A4, and drugs with a narrow therapeutic index, which are predominantly metabolized by CYP3A4 should be discontinued 7 days prior to treatment and avoided during treatment. b. Drugs known to have a high risk of prolonging QTc as per label. c. Drugs that are known to increase gastric pH should be stopped at least 1 week before the start of study treatment.
6) Continued from #5: d. Anticancer treatment (eg, cytoreductive therapy, radiotherapy, immune therapy, cytokine therapy, monoclonal antibody, targeted small molecule therapy) or any investigational drug within 4 weeks prior to start of study treatment, or not recovered from adverse event (AE) related to such therapies, with the following exceptions: i. Palliative bone-directed radiotherapy is permitted (concurrently or within pretreatment period). ii. Hormonal therapies acting on the hypothalamic-pituitary-gonadal axis are permitted (ie, luteinizing hormone-releasing hormone agonist/antagonists). No other hormonal anticancer therapy is permitted. e. Major surgery (as deemed by the Investigator) for any reason, except diagnostic biopsy, within 4 weeks of the study treatment and/or if the subject has not fully recovered from the surgery within 4 weeks of the study treatment.
7) Continued from #5: f. Subjects receiving immunosuppressive agents (such as steroids), for any reason, should be tapered off these drugs before start of study treatment, with the following exceptions: i. Subjects with adrenal insufficiency, may continue corticosteroids at physiologic replacement dose, equivalent to < 10 mg prednisone daily. ii. Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation). iii. Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the dose after 14 days will be equivalent to 8) Current significant cardiac conduction abnormalities, including corrected QT interval (QTc) prolongation of > 450 milliseconds or impaired cardiovascular function, ventricular tachycardia, hypokalemia or a history of paroxysmal atrial fibrillation, serious cardiac arrhythmia and family history of sudden death or long QT syndrome.
9) A history of cardiovascular/cerebrovascular disease as follows: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina or congestive heart failure (New York Heart Association Classification Class >/= II).
10) Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent: a. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible. b. Autoimmune diseases: eg, inflammatory bowel diseases, interstitial lung disease or pulmonary fibrosis.
11) Pneumonitis and history of pneumonitis.
12) A history of difficulty of swallowing, gastric or small bowel surgery with history of malabsorption or other chronic gastro-intestinal disease or conditions that may hamper compliance and/or absorption of the M4112.
13) Any psychiatric condition that would prohibit the understanding or rendering of Informed Consent, or interfere with compliance to study requirements and procedures in the opinion of Investigator and/or Sponsor.
14) Known current alcohol and drug abuse as determined by the Investigator if no consent by legal representative.
15) Hepatocellular carcinoma.
16) Legal incapacity or limited legal capacity.
17) Significant acute or chronic infections requiring systemic therapy including, among others: a. History of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. b. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (defined as, HBV surface antigen positive and HBV core antibody positive with reflex to positive HBV DNA or HBV core antibody positive alone with reflex to positive HBV DNA or positive HCV antibody with reflex to positive HCV RNA). Subjects with a history of infection must have polymerase chain reaction documentation that infection has cleared. c. Active tuberculosis (history of exposure or history of positive TB test with presence of clinical symptoms, physical, or radiographic findings).
18) Known hypersensitivity to the investigational medicinal products (IMPs) or to one or more of the excipients of M4112, avelumab or M7824.
19) Known severe hypersensitivity reactions to monoclonal antibodies (Grade >/= 3 NCI-CTCAE 4.03), or uncontrolled asthma (ie, 3 or more features of partially controlled asthma).
20) Pregnancy or lactation.
21) Administration of a live vaccine within 28 days prior to study entry.
For Enrollment:

713-563-1930

On November 13, 2017 argenx (Euronext & Nasdaq: ARGX) a clinical-stage biotechnology company developing a deep pipeline of differentiated antibody-based therapies for the treatment of severe autoimmune diseases and cancer, reported that management will present at several upcoming investor conferences in November (Press release, argenx, NOV 12, 2017, View Source;p=RssLanding&cat=news&id=2316341 [SID1234521948]):

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Stifel 2017 Healthcare Conference. Chief Scientific Officer, Hans de Haard, will present on Wednesday, November 15, 2017 at 2:45 p.m. ET in New York City.
Jefferies 2017 London Healthcare Conference. Chief Executive Officer, Tim Van Hauwermeiren, will present on Thursday, November 16, 2017 at 11:20 a.m. UTC in London.
Piper Jaffray 29th Annual Healthcare Conference. Chief Executive Officer, Tim Van Hauwermeiren, will present on Wednesday, November 29, 2017 at 2:30 p.m. ET in New York City.
Live webcasts of the presentations will be available on the Company’s website at www.argenx.com. Replays of the webcasts will be availalbe for 90 days following the presentation.

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.