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TESARO Announces Six Data Presentations at the 2016 European Society for Medical Oncology (ESMO) Annual Meeting

On September 6, 2016 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported that data from six abstracts will be presented at the 2016 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) annual meeting, October 7 to October 11, 2016, in Copenhagen (Press release, TESARO, SEP 6, 2016, View Source [SID:1234514953]). In addition, TESARO will webcast an investor and analyst briefing from Copenhagen on Saturday, October 8 at 7:00 PM local time in conjunction with the ESMO (Free ESMO Whitepaper) annual meeting.

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Please plan to visit TESARO at Booth #415 for information about our pipeline.

Presentation Details (all times local):

Niraparib

Saturday, October 8, 2016, 4:30 PM to 6:00 PM — Presidential Symposium 1
A randomized, double-blind phase 3 trial of maintenance therapy with niraparib vs placebo in patients with platinum-sensitive recurrent ovarian cancer (ENGOT-OV16/NOVA trial)
Presentation: LBA3_PR, Presidential Symposium 1, Location: Copenhagen Room, Time: 5:30 PM
Results selected for inclusion in the ESMO (Free ESMO Whitepaper) Press Programme

Sunday, October 9, 2016, 1:00 PM to 2:00 PM
Modeling maintenance therapy in ovarian cancer
Poster: 1043P, Location: Hall E

Niraparib is an investigational product candidate that has not been approved by any regulatory agencies.

Rolapitant

Sunday, October 9, 2016, 1:00 PM to 2:00 PM
Efficacy and safety of rolapitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) in elderly patients
Poster: 1441P, Location: Hall E

Sunday, October 9, 2016, 1:00 PM to 2:00 PM
Efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with gastrointestinal and colorectal cancers
Poster: 1440P, Location: Hall E

Sunday, October 9, 2016, 1:00 PM to 2:00 PM
Safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving Breast Cancer Resistant Protein (BCRP) substrate chemotherapy agents
Poster: 1442P, Location: Hall E

Sunday, October 9, 2016, 1:00 PM to 2:00 PM
Systematic review of the efficacy and safety of neurokinin-1 receptor antagonists for chemotherapy-induced nausea and vomiting: identification of the relevant clinical trials
Poster: 1443P, Location: Hall E

Rolapitant is marketed in the United States under trade name VARUBI. Rolapitant has not been approved by any regulatory agencies outside of the United States.

Investor Briefing and Webcast
TESARO will webcast an investor and analyst briefing in Copenhagen on Saturday, October 8 at 7:00 PM local time in conjunction with the ESMO (Free ESMO Whitepaper) annual meeting. At this briefing, TESARO management will review the niraparib development program and data presented at ESMO (Free ESMO Whitepaper) and answer questions from investors and analysts. This event will be webcast live and archived for 30 days, and may be accessed from the TESARO Investor Events and Presentations webpage at www.tesarobio.com.

About Niraparib
Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in four ongoing pivotal trials. TESARO is building a robust niraparib franchise by assessing activity across multiple tumor types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development program for niraparib includes the Phase 3 trial in patients with recurrent ovarian cancer (the NOVA trial); a registrational Phase 2 treatment trial in patients with ovarian cancer (the QUADRA trial); a Phase 3 trial for the treatment of patients with BRCA-positive breast cancer (the BRAVO trial); and a Phase 3 trial in patients with first-line ovarian cancer (the PRIMA trial). Several collaborator-sponsored studies are also underway, including combination trials of niraparib plus pembrolizumab and bevacizumab. Janssen Biotech has licensed rights to develop and commercialize niraparib specifically for patients with prostate cancer worldwide, except in Japan.

About VARUBI (Rolapitant)
Rolapitant is marketed in the United States under trade name VARUBI. VARUBI is a substance P/neurokinin-1 (NK-1) receptor antagonist indicated in the U.S. in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. VARUBI is contraindicated in patients receiving thioridazine, a CYP2D6 substrate. The inhibitory effect of a single dose of VARUBI on CYP2D6 lasts at least seven days and may last longer. Avoid use of pimozide; monitor for adverse events if concomitant use with other CYP2D6 substrates with a narrow therapeutic index cannot be avoided. Please see full prescribing information, including additional important safety information, available at www.varubirx.com.

An intravenous formulation of rolapitant is also being developed. TESARO licensed exclusive rights for the development, manufacture, commercialization, and distribution of VARUBI (rolapitant) from OPKO Health, Inc.

Infinity Announces Presentations On IPI-549 At Upcoming Immuno-Oncology Meeting

On September 6, 2016 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported that new preclinical data as well as early clinical data from an ongoing Phase 1 study will be presented for IPI-549, an immuno-oncology development candidate that selectively inhibits PI3K-gamma, during the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper): Translating Science into Survival taking place September 25-28, 2016, in New York City (Press release, Infinity Pharmaceuticals, SEP 6, 2016, View Source;p=RssLanding&cat=news&id=2199662 [SID:1234514950]).

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The following two presentations will take place during the poster session being held on Monday, September 26, from 5:15 p.m. – 7:45 p.m. ET:

Title: IPI-549-01: A Phase 1/1b first-in-human study of IPI-549, a PI3K-gamma inhibitor, as monotherapy and in combination with an anti-PD1 antibody in subjects with advanced solid tumors
Poster Board: B070
Presentation Time: Monday, September 26, 6:15 p.m. – 7:15 p.m. ET

Title: The PI3K-gamma inhibitor, IPI-549, increases antitumor immunity by targeting tumor-associated myeloid cells and remodeling the immune-suppressive tumor microenvironment
Poster Board: B032
Presentation Time: Monday, September 26, 6:15 p.m. – 7:15 p.m. ET

About IPI-549
IPI-549 is an orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. In preclinical studies, IPI-549 inhibits immune-suppressive macrophages within the tumor microenvironment, whereas other immunotherapies such as checkpoint modulators more directly target immune effector cell function. As such, IPI-549 may have the potential to treat a broad range of solid tumors and represents a potentially complementary approach to restoring anti-tumor immunity in combination with other immunotherapies such as checkpoint inhibitors.

IPI-549 is an investigational compound and its safety and efficacy has not been evaluated by the U.S. Food and Drug Administration or any other health authority.

Cyclacel’s CYC065 Demonstrates Promising Activity in MYCN-Addicted Neuroblastoma in Preclinical Data Presented at Childhood Cancer 2016

On September 6, 2016 (GLOBE NEWSWIRE) Cyclacel Pharmaceuticals, Inc. (Nasdaq:CYCC) (Nasdaq:CYCCP) ("Cyclacel" or the "Company"), a biopharmaceutical company developing oral therapies that target various phases of cell cycle control for the treatment of cancer and other serious disorders, reported the presentation of preclinical data demonstrating that both Cyclacel’s CYC065, a clinical stage, second generation, cyclin-dependent kinase CDK2/9 inhibitor, and CCT68127, a preclinical stage CDK2/9 inhibitor, prolong survival in MYCN-addicted neuroblastoma models (Press release, Cyclacel, SEP 6, 2016, View Source [SID:1234514936]). The data were presented at the Childhood Cancer Meeting, September 5 — 7th in London, UK.

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"This study adds to the growing evidence of the value of CDK inhibition as an approach to treating cancer. MYCN is an important therapeutic target in oncology and a major oncogenic driver of neuroblastoma, a childhood cancer. There are no approved drugs that act against MYCN or MYC proteins," said Spiro Rombotis, President and Chief Executive Officer of Cyclacel. "We are encouraged by the preclinical data, which extend and support earlier findings, showing that CYC065 and CCT68127 reduce MYCN transcription and protein levels and have antitumor activity in neuroblastoma models. Additionally, we have demonstrated in other preclinical studies, that our transcriptional CDK2/9 inhibitors target key molecular features of cancers with poor prognosis, such as MLL-r leukemias or MYC-driven lymphomas. Furthermore, evidence from early clinical trials show that CDK2/9 inhibitors can have a synergistic effect with other anticancer agents. We look forward to reporting data from our ongoing Phase 1 study of CYC065 in patients with solid tumors."

In this preclinical study, an international group of researchers led by Prof. Louis Chesler from The Institute of Cancer Research, London, explored in vitro and in vivo the sensitivity of neuroblastoma cells to CYC065 and CCT68127. Neuroblastoma cells with MYCN amplification and overexpression were found to be particularly sensitive to both CDK2/9 inhibitors. The mechanism of action of CYC065 and CCT68127 included inhibition of MYCN transcription, downregulation of N-MYC protein, blocking neuroblastoma cell proliferation and induction of apoptosis. Treatment with either CYC065 or CCT68127 significantly reduced tumor burden and prolonged survival in several neuroblastoma models in vivo.

Citation

Poon E, Jamin Y, Walz S, Hakkert S, Kwok C, Hallsworth A, Thway K, Barker K, Sbirkov Y, Pickard L, Urban Z, Tardif N, Webber H, Box G, Valenti M, De Haven Brandon A, Petrie K, Ebus M, Molenaar J, Eccles S, Robinson SP, Zheleva D, Eilers M, Workman P, Chesler L. The small molecule CDK2 and CDK9 inhibitors CYC065 and CCT68127 are potent inhibitors of MYCN via transcriptional repression. Childhood Cancer Meeting 2016, September 5 — 7th, London, UK, Abs. 1-19.

About MYCN

The MYCN gene encodes a transcription factor that is expressed in fetal brain and neural crest and is critical for normal development of the brain and nerves. The MYCN oncogene is over-expressed in a number of different types of cancer, most notably neuroblastoma, and also rhabdomyosarcoma, medulloblastoma, astrocytoma, Wilms’ tumor and small cell lung cancer. Amplification of the MYCN oncogene is the most common genomic alteration in aggressive neuroblastomas and is associated with poor clinical outcome. There are no approved drugs that directly target MYCN prompting the investigation of indirect approaches such as exploitation of a synthetic lethal relationship between MYCN amplification/overexpression and inhibition of CDK2.

About Neuroblastoma

According to the American Cancer Society, neuroblastoma is the most common cancer in infants less than one year old and it accounts for about six percent of all pediatric cancers or about 700 cases per year. The disease has a fatal outcome in one out of every seven children diagnosed with it. Preclinical data from an international investigator group demonstrated that Cyclacel’s CYC065 and CCT68127 target MYCN gene expression and have potent in vitro and in vivo anti-tumor activities, suggesting therapeutic potential in neuroblastoma, including high-risk patients with MYCN amplification.

About CYC065

CYC065 is a highly-selective, orally- and intravenously-available, second generation inhibitor of CDK2 and CDK9 and causes apoptotic death of cancer cells at sub-micromolar concentrations. Antitumor efficacy has been achieved in vivo with once a day oral dosing at well tolerated doses. Evidence from published nonclinical studies show that CYC065 may benefit patients with adult and pediatric hematological malignancies, including certain Acute Myeloid Leukemias (AML), Acute Lymphocytic Leukemias (ALL), Chronic Lymphocytic Leukemias (CLL), B-cell lymphomas, multiple myelomas, and certain solid tumors, including breast and uterine cancers. Independent investigators published nonclinical evidence that CYC065 induced regression or tumor growth inhibition in a model of HER2-positive breast cancer addicted to cyclin E that is resistant to trastuzumab, reduced tumor growth in models of CCNE1-amplified uterine serous carcinoma and reduced tumor burden and prolonged survival in several neuroblastoma models in vivo.

CYC065 is mechanistically similar but has much higher dose potency, in vitro and in vivo, improved metabolic stability and longer patent protection than seliciclib, Cyclacel’s first generation CDK inhibitor. Translational biology data support development of CYC065 as a stratified medicine for solid and liquid cancers. CYC065 has been shown to reverse drug resistance associated with the addiction of cancer cells to cyclin E and may inhibit CDK9-dependent oncogenic and leukemogenic pathways, including malignancies driven by certain oncogenes and mixed lineage leukemia rearrangements (MLL-r). CYC065 causes prolonged down regulation of the Mcl-1-mediated pro-survival pathway in cancer cells.

OGD2 Pharma and Syndivia launch collaboration to develop an ADC targeting the O-acetyl-GD2 cancer antigen

On September 6, 2016 (GLOBE NEWSWIRE) — OGD2 Pharma SAS, a biotechnology company developing innovative anti-cancer therapies targeting the O-acetylated form of the GD2 ganglioside (OAcGD2), reported a collaboration with Syndivia SAS, a biotechnology company that provides best-in-class bioconjugation technologies for the development of Antibody-Drug Conjugates (ADC) (Press release, OGD2 Pharma, SEP 6, 2016, View Source [SID1234519567]).

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This collaboration agreement will explore the potential of targeting chemotherapeutic drugs using anti-OAcGD2 ADCs in the treatment of difficult-to-treat solid tumors. The ADCs will be designed to release the cytotoxic drug both within tumor cells and in the tumor microenvironment.

"Thanks to this collaboration, OGD2 Pharma accelerates the development of its anti-OAcGD2 ADC platform. Syndivia’s versatile linker technology will allow depicting the best way to specifically deliver ADC payloads to tumors using the unique cellular biology of the OAcGD2 membrane glycolipid" said Jean-Marc Le Doussal, President at OGD2 Pharma. "Syndivia’s technology should result in ADCs that are highly stable in patient’s blood, in line with our strategy to develop safer anti-cancer therapies leveraging the highly tumor-specific tissue distribution of the OAcGD2 antigen. OGD2 Pharma will continue building such strategic partnerships with academic groups and private companies in other ADC technologies." he added.

Oleksandr Koniev, Chief Executive Officer of Syndivia commented "We are excited by this synergy between Syndivia’s stable payloads for intracellular and tumor microenvironment specific drug release and OGD2 Pharma’s innovative immunotherapy agents targeting OAcGD2 antigen. We believe this collaboration will result in the development and future commercialization of a brand-new class of efficient ADC for unmet clinical needs in both pediatric and adult cancers".

About Syndivia: www.syndivia.com

Syndivia SAS, headquartered in Illkirch, France, is a biotechnology company providing best-in-class bioconjugation technologies for the development of Antibody-Drug Conjugates (ADC). With a strong portfolio of patented ADC payloads and know-how in ADC preparation and characterization Syndivia is building up a strong partnered pipeline of ADCs for a broad range of oncology indications.

About OGD2 Pharma: www.ogd2pharma.com

OGD2 Pharma SAS, headquartered in Nantes, France, is a pre-clinical stage privately-held biotechnology company. Our mission is to research, develop and commercialize, with pharmaceutical partners, safe and efficacious cancer immunotherapies targeting the O-acetylated form of the GD2 ganglioside (OAcGD2). Pipeline includes OGD201 humanized monoclonal antibody (EMA Orphan Drug Designation for neuroblastoma), chimeric antigen receptors (CAR), antibody drug conjugates and companion diagnostic products.

About O-acetylated-GD2

As its first cousin GD2, the OAcGD2 glycolipid is expressed at high copy numbers in the membrane of tumor cells in many types of pediatric cancers (such as neuroblastoma) and adult cancers (such as glioblastoma, melanoma, sarcoma, breast cancer, etc.) and on cancer stem cells. Remarkably, and by contrast to GD2, OAcGD2 is not expressed by normal nerves and brain tissues.

About APN and C&R Technology

Syndivia’s APN technology enable the preparation of ADCs having increased stability in blood circulation. This stability is of crucial importance for oncology applications as it widens the therapeutic index of the conjugates. The C&R technology allows for tumor-specific release of the cytotoxic payload both inside cancer cells and in tumor microenvironment. This tumor-specific release contributes further to the improvement of the efficacy and toxicity profile of Syndivia’s ADCs.

Peloton Therapeutics, Inc. Announces Dual Publications of HIF-2α Antagonism in Kidney Cancer in the Journal Nature

On September 6, 2016 Peloton Therapeutics, Inc., a drug discovery and development company focused on advancing first-in-class, small molecule cancer therapies targeting unexploited molecular vulnerabilities, reported two publications in the journal Nature that describe the application of Peloton-invented antagonists to advance the understanding of hypoxia-inducible factor-2α (HIF-2α) and its role in kidney cancer (Press release, Peloton Therapeutics, SEP 6, 2016, View Source [SID:1234514959]).

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The first paper titled "On-target efficacy of a HIF2α antagonist in preclinical kidney cancer models" (Cho et al., Nature, Advanced Online Publication, September 2016, View Source) characterizes PT2399, an analogue of PT2385, Peloton’s first-in-class small molecule antagonist of HIF-2α that is in clinical development for the treatment of clear cell renal cell carcinoma (ccRCC). Using multiple techniques, the researchers demonstrated the high specificity of PT2399 for HIF-2α and its efficacy in orthotopic, metastatic, and patient-derived models of ccRCC. Their work also raises the possibility that sensitivity of ccRCC tumors to HIF-2α antagonism may depend on the status of the tumor suppressor protein p53.

In the second paper titled "Targeting renal cell carcinoma with a HIF-2 antagonist (Chen et al., Nature, Advanced Online Publication, September 2016, View Source), PT2399 was found to be more potent, active in a greater number of models, and less toxic than sunitinib in a large panel of patient-derived ccRCC xenografts. Additionally, a number of tumors that were completely insensitive to sunitinib regressed when transferred to PT2399. Importantly, genetic biomarkers that correlated with sensitivity to Peloton’s HIF-2α antagonists were identified.

"The work reported demonstrates the exquisite selectivity of Peloton’s antagonists that then enabled the further elucidation of the role of HIF-2α in kidney cancer and the potential value of our compounds in treating this disease," said John A. Josey, Ph.D., Peloton’s Chief Executive Officer. "By causing regression in tumors that are resistant to standard-of-care drugs while minimizing cardiovascular and other toxicities, our hope is to provide patients with more attractive drug treatment options. Genetic biomarker development may also enable identification of patients best able to benefit from treatment with our HIF-2α antagonists. These biomarkers may also be particularly important as we expand indications beyond kidney cancer."

About PT2385
PT2385 is a first-in-class small molecule antagonist of hypoxia-inducible factor-2α (HIF-2α), a transcription factor implicated in the development and progression of kidney cancer. It is currently being investigated in a Phase 1 clinical trial for the treatment of advanced or metastatic clear cell renal cell carcinoma (ccRCC) as monotherapy and in combination with the immuno-oncology agent nivolumab. Loss of the von Hippel-Lindau tumor suppressor (VHL) is the key oncogenic event in up to 95 percent of patients with ccRCC. With the loss of the VHL protein (pVHL), the transcription factor HIF-2α accumulates and drives the unbalanced expression of numerous gene products. Preclinical data indicate that orally bioavailable PT2385 disrupts HIF-2α activity in ccRCC and thereby blocks the expression of multiple tumorigenic factors. Clinical data in patients with advanced ccRCC has shown PT2385 to have encouraging efficacy, including a number of responses and a favorable tolerability profile, with no dose-limiting toxicities nor evidence of cardiovascular adverse events.

About Kidney Cancer
The American Cancer Society estimates that more than 62,000 new cases of kidney cancer will be diagnosed and more than 14,000 people will die from this disease this year. The National Cancer Institute reports that the prognosis for any treated renal cell cancer patient with progressing, recurring, or relapsing disease is poor, regardless of cell type or stage.