News Article | December 1, 2016
Munich, Germany: Researchers working to find effective treatments for soft tissue sarcomas have discovered that combining a new anti-cancer drug with an existing one kills cancer cells not only in the laboratory but also in the first two patients treated with it, leading to unusually long-lasting periods without the disease progressing. Soft tissue sarcomas - cancers of soft tissues such as fat, muscles, blood vessels, nerves, tendons and ligaments - are rare but difficult to treat successfully if they are advanced and have spread to other parts of the body (metastasised). In a late-breaking presentation at the 28th EORTC-NCI-AACR  Symposium on Molecular Targets and Cancer Therapeutics in Munich, Germany, today (Friday), Professor Antoine Italiano, head of the Early Phase Trials and Sarcoma Units at Institut Bergonié, Bordeaux, France, described how a new drug, GDC-0575, inhibits a molecule called Checkpoint kinase 1 (CHK1) that regulates the response of cancer cells to DNA damage. By inhibiting CHK1, the drug prevents tumour cells recovering from DNA damage and they die. Combining GDC-0575 with gemcitabine, a cancer-killing drug that is already used for treating sarcomas, proved remarkably effective. "Soft tissue sarcomas represent a rare group of malignant tumours. Despite the use of surgery, radiotherapy and chemotherapy to treat the tumour in the localised region in which it started, up to 40% of patients will develop recurrence with cancer cells spreading to other parts of the body," he said. "The number of drugs approved to manage patients with advanced sarcoma is very low and patients in this setting have a very poor outcome with a median [average] overall survival of only 12-18 months. Gemcitabine is one of the drugs used in patients with advanced soft tissue sarcoma. "We did this study in order to assess if combining a CHK1 inhibitor with gemcitabine can improve the anti-tumour efficacy in pre-clinical models of the disease. We observed a very strong synergy between the CHK1 inhibitor GDC-0575 and gemcitabine in sarcoma cells in the lab, but also in mice. The combination of the two drugs significantly reduced tumour growth rate in comparison to treatment with just one drug both in the lab and in the mice. "Interestingly, two patients, who were treated with such a combination in a phase I clinical trial  had a meaningful response, which is quite unusual in this setting. Despite a significantly lower dose of gemcitabine than is used routinely, the tumours in these patients shrank rapidly and substantially for an unusually long-lasting time. The first patient who had a leiomyosarcoma  with extensive metastases in the peritoneum had a partial response, in which the tumour shrank, that lasted for one year. The second patient, who had lung metastases, had a complete response, in which the cancer completely disappeared, that is still ongoing nine months after the start of treatment." The patients had been given 250mg/m3 a week of gemcitabine instead of the more usual 660 mg/m3. Gemcitabine was given intravenously and GDC-0575 was given orally with a range of different doses. The researchers analysed tumour samples taken from the first patient at the start of treatment and when the cancer started to grow again to identify genes that might play a role in the patient's eventual resistance to the treatment. "We have identified 16 potential genes and these data now have to be validated by further studies," said Prof Italiano. The study is no longer enrolling new patients but Prof Italiano said: "Based on these pre-clinical and preliminary clinical data we will try to set up a phase II clinical trial to assess the safety and efficacy of gemcitabine plus a CHK1 inhibitor in soft-tissue sarcoma." Chair of the scientific committee for the Symposium, Professor Jean Charles Soria from the Institut Gustave Roussy (France), commented: "Exceptional responders in the clinical setting represent unique opportunities to better understand the biological basis underlying tumour shrinkage. This is very well exemplified in this work, where not only the basis of response is analysed by sequencing all the active genes in the tumour samples, but also the basis of acquired secondary resistance."  EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].  Leiomyosarcoma is one of the more common types of soft tissue sarcomas to develop in adults.  Clinical trial no: NCT01564251. "A study of GDC-0575 alone and in combination with gemcitabine in patients with refractory solid tumours or lymphoma".
News Article | November 29, 2016
Munich, Germany: The first drug to target a key enzyme that cancer cells need to keep them alive has shown that it is effective in controlling disease in patients with advanced kidney cancer when it is used in combination with another anti-cancer drug, everolimus. Dr Funda Meric-Bernstam told the 28th EORTC-NCI-AACR  Symposium on Molecular Targets and Cancer Therapeutics in Munich, Germany, today (Wednesday) that out of 15 patients with clear cell and papillary renal cell cancer who had been given the new drug CB-839 together with everolimus in a phase I clinical trial and for whom data were available to analyse, 93% had their tumour controlled by the regimen: the tumour shrank by more than 30% in one patient (called a partial response), was stable in 13 other patients (stable disease), and grew by more than 20% in the last patient (called progressive disease). Clear cell is the most common form of kidney cancer, accounting for 75% of cases, and in this study all the patients with this form of the disease (12) had their disease controlled. Papillary renal cell cancer is the next most common form of the disease and accounts for 10% of cases. CB-839 targets glutaminase, an enzyme involved in the conversion of glutamine to glutamate, which is an important nutrient for cancer cells - without it they die. Dr Meric-Bernstam, who is chair of the Department of Investigational Cancer Therapeutics and Medical Director of the Institute of Personalized Cancer Therapy at the University of Texas MD Anderson Cancer Centre (USA), said: "Glutaminase is a very interesting target and previous work in the lab has shown that CB-839 is effective at inhibiting it in renal cell cancers and that it enhances the anti-tumour efficacy of everolimus. "To date, tumours in 93% of patients with clear cell and papillary renal cell cancers have had tumour control from the regimen, with a median [average] time without their cancer growing of 8.5 months. For more than half of these patients their time on this treatment has been longer than the time they remained on their prior treatment, which is considered to be a good sign." The median number of previous treatments the patients had received was two, some of which included inhibitors of the mTOR cell signalling pathways, and checkpoint inhibitors that reactivate the body's immune system to attack the cancer. All had advanced or metastatic disease (cancer that has started to spread to other parts of the body). They were given CB-839 in oral doses that ranged from 400-800 mg twice a day in combination with a fixed oral dose of everolimus at 10 mg once a day. The patients tolerated the treatment well, with most adverse side effects being no more severe than was consistent with everolimus and advanced cancer. "These results suggest that CB-839 is a very tolerable drug with significant potential in combination therapy for kidney cancer patients," said Dr Meric-Bernstam. The researchers continue to enrol and treat patients in this trial, and they plan to evaluate CB-839 in combination with everolimus in a randomised controlled trial in the future. "In the current trial, we are also assessing the efficacy of CB-839 in kidney cancer in combination with another drug, cabozantinib. In another trial, we are evaluating the efficacy of CB-839 in combination with immunotherapy in kidney cancer, lung cancer and melanoma patients," she concluded. Chair of the scientific committee for the Symposium, Professor Jean Charles Soria from the Institut Gustave Roussy (France), commented: "Compounds able to modulate cancer metabolism represent a new and innovative area for cancer drug development."  EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].
News Article | December 1, 2016
Munich, Germany: A new anti-cancer drug that inhibits a key cell signalling process involved in many different cancers has shown that it is capable of stopping the progression of cancer and shrinking tumours. Importantly, it has been able to do this in rare cancers that are less well-studied such as adenoid cystic carcinoma. Dr Christophe Massard, a senior medical oncology consultant and chair of the Early Drug Development programme at the Institut Gustave Roussy Cancer Campus (Villejuif, France) told the 28th EORTC-NCI-AACR  Symposium on Molecular Targets and Cancer Therapeutics in Munich, Germany, today (Friday) that results from a phase I clinical trial in 103 patients showed that the drug LY3039478 was successful in inhibiting the Notch signalling pathway in patients with alterations in the Notch protein. Patients in the trial had a range of cancers, including breast, colon, parotid (salivary gland) and sarcoma, which were all advanced or had started to spread to other parts of the body (metastasise). After treatment with LY3039478, the tumour shrank in one patient with breast cancer and the disease stabilised and did not progress in another 29 patients. In addition, using PET scanning, researchers found two more cases where the tumours had shrunk: in a patient with adenoid cystic carcinoma and a patient with testicular cancer. Dr Massard said: "Research suggests that the Notch signalling pathway plays a role in helping cancer cells to grow, divide and spread around the body; it is also involved in angiogenesis, the process by which tumours grow new blood vessels, and it may contribute to tumours becoming resistant to chemotherapy. Notch signalling that is unregulated due to mutations in the Notch protein is implicated in a number of cancers. The Notch signalling pathway involves four Notch receptors (NOTCH1, 2, 3 and 4) - proteins that sit on the membranes of cells, including cancer cells, and transfer messages across the cell membrane. LY3039478 is able to inhibit all four receptors. The results from this phase I trial prove that LY3039478 has the effect on tumours that was expected, by inhibiting the Notch signalling and thereby preventing cancer cell growth and proliferation. "Notch was evaluated as a target for anti-cancer drugs several years ago, with promising results in lymphoma and rare cancers. However, because of gastrointestinal toxicity, the development of several Notch-inhibition compounds was stopped," said Dr Massard. "In this trial we have worked closely with gastrointestinal specialists to manage the toxic effects of the drug." Side effects from the drug were manageable, the most common being diarrhoea (in 48% of patients), vomiting (40%), nausea (38%), loss of strength (25%) and decreased appetite (21%). Other, less common side effects included weight loss, dry skin and mouth, and hair loss. The clinical trial also established that the recommended dose for a phase II clinical trial as 50 mg three times a week for 28 days, repeated until the disease starts to progress. The drug is taken orally. "This was a proof of concept trial that has shown that LY3039478 is successful in inhibiting unregulated Notch signalling, resulting in encouraging signs of preliminary clinical activity in several advanced and metastatic cancers. One of the interesting results with implications for some patients is that the drug was active against rare cancers such as adenoid cystic carcinoma," concluded Dr Massard. The phase I trial is continuing and there are plans for a further trial in advanced and metastatic cancers to test the drug in combination with other anti-cancer drugs such as taladegib (in breast cancer), abemaciclib (colon cancer), cisplatin (cholangiocarcinoma) and gemcitabine and carboplatin (soft tissue sarcoma). Dr Kapil Dhingra, a member of the executive committee for the Symposium and managing member of KAPital Consulting LLC (USA), commented: "Notch signalling is an important contributor to the development of a variety of cancers. However, successful development of drugs against this pathway has been challenging, in part due to unacceptable side effects. While preliminary, the results of the phase I study of LY3039478 show evidence of anti-tumour activity in a number of different tumour types with a manageable safety profile. These results warrant further investigation of this drug in clinical trials."  EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].
News Article | November 30, 2016
Munich, Germany: An experimental drug called TAS-114, which has the potential to increase the anti-cancer effects of chemotherapy without increasing adverse side effects, has shown promising results in patients with hard-to-treat cancers in a phase I clinical trial. In a presentation at the 28th EORTC-NCI-AACR  Symposium on Molecular Targets and Cancer Therapeutics in Munich, Germany, today (Thursday) Dr Takekazu Aoyama, a surgeon and vice president of clinical development at Taiho Oncology Inc, Princeton, USA, described how TAS-114 in combination with another chemotherapy caused tumours to shrink in patients with advanced non-small cell lung cancer, pancreatic cancer, colorectal cancer and breast cancer. In addition, some patients whose cancer had failed to respond to other therapies were able to continue with the treatment and their disease remained stable without progressing for more than six months. TAS-114 inhibits deoxyuridine triphosphatase (dUTPase) -- a 'gatekeeper' protein that acts on FdUTP, a metabolite of the anti-cancer drug 5-fluorouracil (5-FU), and restricts its incorporation into the DNA of cancer cells, thereby enabling the cells to continue living and proliferating. Research has already shown that tumours with high levels of dUTPase are resistant to 5-FU chemotherapy, and so successful inhibition of dUTPase may be an important step in enhancing the activity of 5-FU. In the study presented today, researchers from Italy, Switzerland, France and Belgium, enrolled 92 patients into a phase I trial in which TAS-114 was given to patients together with a chemotherapy called S-1, which is a fixed-dose combination of tegafur, gimeracil and oteracil. Tegafur is the active anti-cancer agent, which, after administration, is converted by the body into the active form of 5-FU ; gimeracil inhibits the degradation of 5-FU, leading to higher 5-FU levels in the body for longer; and oteracil inhibits activation of 5-FU in the gut, resulting in lower toxic side effects there, such as diarrhoea. TAS-114 and S-1 were given orally twice a day for 14 days before food, followed by seven days rest before repeating. The doses ranged from a starting dose of 5 mg/m2 (TAS-114) and 25 mg/m2 (S-1) up to 240 mg/m2 and 36 mg/m2 respectively. The trial aimed to determine the maximum tolerated dose and the recommended dose, while also looking at how well the drugs worked against the tumours and how they interacted with the body (pharmacokinetics and pharmacodynamics). In addition to the cancers already mentioned, patients with cancers of the liver, biliary tract, endometrium and stomach were included. The most recent data from the trial presented at the Symposium showed that 15 of the patients were able to continue receiving the treatment for more than six months without their disease progressing. In addition, tumour responses were observed in three of the patients with non-small cell lung cancer, one with pancreatic cancer, one with breast cancer and one with colorectal cancer.  Dr Aoyama said: "These results show favourable responses across all the tumour types and they were particularly outstanding in patients with non-small cell lung cancer where we saw robust partial tumour responses  and good disease control rates. We consider that to be able to control disease for a period as long as six months and beyond provides a significant clinical benefit to patients who had all been previously heavily treated. "In addition, we saw no additional toxic side effects in patients who were given the drug combination above what is expected with S-1 alone. Patients tolerated the treatment well and the side effects were manageable. These findings warrant further investigation of the drug combination in a phase II clinical trial." An international phase II trial for patients with non-small cell lung cancer in Japanese patients was started in August 2016; investigators are preparing to start the Europe / USA part of the trial in November 2016.  EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].  These figures were correct as of the beginning of November 2016. However, the trial continues with several more patients remaining on the treatment, so more may have continued beyond six months by the time the Symposium takes place at the end of November.  Partial response is when the tumour shrinks by more than 30%.
News Article | December 1, 2016
SOUTH SAN FRANCISCO, Calif., Dec. 01, 2016 (GLOBE NEWSWIRE) -- Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, announced that a poster featuring data related to FPA144 in urothelial cancer (UC), also known as bladder cancer, was presented today at 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Munich, Germany. The Poster titled “FGFR2b Represents a Novel Target for Treatment of Urothelial Cancer,” is available at http://www.fiveprime.com/news-media/publications-presentations. "This translational data suggest that FGFR2b protein is expressed in a subset of bladder cancers," said Robert Sikorski, M.D., Ph.D., senior vice president and chief medical officer of Five Prime. "In our Phase 1 clinical trial, a patient with bladder cancer that expressed FGFR2b achieved a complete response after treatment with FPA144. We are actively investigating FPA144 as a treatment for gastric cancer and are now exploring its clinical potential in bladder cancer.” FPA144 is an isoform-selective antibody in development as a targeted immuno-therapy for tumors that overexpress FGFR2b, a splice variant of a receptor for some members of the fibroblast growth factor (FGF) family. FPA144 has been engineered for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) to increase direct tumor cell killing by recruiting natural killer (NK) cells. As reported at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, in the dose escalation phase of the Phase 1 clinical trial, a 76-year-old patient diagnosed with stage 4 bladder cancer received FPA144 at the 3 mg/kg dose level. That patient achieved a durable complete response, suggesting potential efficacy for FPA144 in bladder cancer. As of the November 4, 2016 cutoff, the patient has remained on treatment with FPA144 for 571 days. The poster presented today includes data showing positive FGFR2b immunohistochemistry (IHC) staining in 11.6% of 387 archival primary bladder cancer tumor samples tested. Five Prime believes bladder cancer patients could be selected for treatment with FPA144 using an IHC molecular diagnostic test, similar to what is being used to identify gastric cancer patients for treatment with FPA144. FivePrime has completed dose escalation testing in the ongoing Phase 1 study of single-agent FPA144 in patients with solid tumors including gastric cancer, and the drug was well tolerated with no dose limiting toxicities, and no maximum tolerated dose was reached. Enrollment continues in the expansion portion of the trial evaluating the safety, pharmacokinetics (PK) and efficacy of biweekly 15 mg/kg infusions of FPA144 in patients with gastric cancer whose tumors overexpress FGFR2b as well as in a new cohort to evaluate FPA144 in patients with bladder cancer whose tumors overexpress FGFR2b. About FPA144 FPA144 is an anti-FGF receptor 2b (FGFR2b) humanized monoclonal antibody in clinical development as a targeted immune therapy for tumors that over-express FGFR2b, as determined by a proprietary immunohistochemistry (IHC) diagnostic assay. FGFR2 gene over-expression is found in a number of tumors, including in approximately 5% of gastric cancer patients, and is associated with poor prognosis. FPA144 is designed to block tumor growth through two distinct mechanisms. First, it has been engineered to drive immune-based killing of tumor cells by antibody-dependent cell-mediated cytotoxicity (ADCC) and the recruitment of natural killer (NK) cells and T cells. Second, it binds specifically to FGFR2b and prevents the binding of certain fibroblast growth factors that promote tumor growth. When combined with PD-1 blockade, FPA144 has shown an additive effect in tumor growth inhibition in preclinical models. Five Prime retains global development and commercialization rights to FPA144. About Five Prime Five Prime Therapeutics, Inc. discovers and develops innovative therapeutics to improve the lives of patients with serious diseases. Five Prime's comprehensive discovery platform, which encompasses virtually every medically relevant extracellular protein, positions it to explore pathways in cancer, inflammation and their intersection in immuno-oncology, an area with significant therapeutic potential and a growing focus of the company's R&D activities. Five Prime has entered into strategic collaborations with leading global pharmaceutical companies and has promising product candidates in clinical and late preclinical development. For more information, please visit www.fiveprime.com. Cautionary Note on Forward-looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "plan," "anticipate," "estimate," "intend" and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Five Prime's expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from these forward-looking statements. Forward-looking statements contained in this press release include statements regarding Five Prime's potential receipt of upfront and milestone payments and royalties. Factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Five Prime's filings with the U.S. Securities and Exchange Commission, including the "Risk Factors" contained therein. Except as required by law, Five Prime assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.
News Article | November 30, 2016
Marseille, France, Nov. 30, 2016 (GLOBE NEWSWIRE) -- FIRST CLINICAL DATA FOR MONALIZUMAB as a single agent in cancer patients show favorable SAFETY PROFILE Innate Pharma SA (the "Company" - Euronext Paris: FR0010331421 - IPH) today announces preliminary safety results from the dose-ranging part of a Phase I/II trial investigating monalizumab as a single agent in patients with advanced gynecologic malignancies. The data are presented today as a poster at the EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium (Munich, Germany) 10:15 a.m. - 5:00 p.m. CET and will be discussed by Dr Anna Tinker, Medical Oncologist (British Columbia Cancer Agency, Vancouver) on behalf of CCTG during the Spotlight session at 1:10 - 1:20 p.m. CET. Monalizumab is Innate Pharma's first-in-class anti-NKG2A antibody partnered with AstraZeneca. The trial is sponsored and conducted by the Canadian Cancer Trials Group (CCTG). In this dose-ranging part of the study, 18 patients with advanced, heavily pretreated ovarian cancer were randomized to receive three dose levels of monalizumab (1, 4 and 10mg/kg, every two weeks - six patients at each dose level). The data showed that monalizumab was well tolerated in this patient population, with no dose-limiting toxicities observed. No major differences in terms of safety were observed across the different dose levels. The most common adverse events (AEs) reported include fatigue and headaches. AEs were mostly low grade and rarely resulted in treatment delays. Preliminary efficacy data showed short-term disease stabilization in 41% of patients, including one patient with a mixed response. Lesley Seymour, MD, PhD, Professor in Oncology at Queen's University in Kingston, Ontario and Director of the Investigational New Drug Program at CCTG, said: "Monalizumab was well tolerated in this patient population with advanced gynecologic malignancies. These refractory tumors are an area of unmet need, and are typically treated with cytotoxic chemotherapy which is often poorly tolerated. Building on these initial results, further investigation of monalizumab in these patients is warranted and we are therefore continuing to enroll patients with relapsed and refractory gynecologic malignancies into the expansion phase of the study." Pierre Dodion, Chief Medical Officer of Innate Pharma, said: "These are the first clinical data reported with monalizumab in cancer patients and they suggest a favorable safety profile. Preliminary results support the continuation of the ongoing cohort expansion part of this study and we look forward to its results. A comprehensive exploratory clinical plan investigating monalizumab in several indications, as both a monotherapy and combination treatment, is underway. We look forward to reporting further data as we move into 2017." The cohort expansion part of this trial (up to 98 patients) is ongoing at the recommended Phase II dose (10 mg/kg) in patients with platinum sensitive ovarian cancer, platinum-resistant ovarian cancer, epithelial endometrial cancer and squamous cell carcinoma of the cervix. The poster #296 is available on Innate Pharma's website. This is an open-label Phase I/II dose escalation trial to evaluate monalizumab as a single agent in patients with gynecologic malignancies. The primary objective is to confirm the recommended Phase II dose of monalizumab as a single agent in patients with gynecologic malignancies. The secondary objectives include assessing the safety, pharmacokinetics, pharmacodynamics and immunogenicity of monalizumab. The first patient in the trial was treated in September 2015. In the first part of the trial, patients will receive 1, 4, or 10 mg/kg of monalizumab every two weeks. In the second part of the trial, patients will receive the recommended phase II dose (RP2D). Sponsored by the Canadian Cancer Trials Group, the trial will enroll up to 98 patients. Gynecologic malignancies encompass ovarian, fallopian tube, peritoneal, cervical and endometrial cancer. Vulval and vaginal cancers are sometimes also included within this diverse group of tumors affecting the female reproductive system. With the exception of cervical cancer, most occur in women aged 50 and over. According to the National Cancer Institute and Cancer Research UK, cervical cancer is the fourth most common cancer in women, representing 5% of all female cancers, with 5-year survival reported as approximately 67.5%. Ovarian cancer is the sixth most common, representing 4% of all cancers in women, with 5-year survival at approximately 46%. Endometrial cancer is the most common gynecological cancer affecting 25.4 per 100,000 women per year with 5-year survival at approximately 81.7%. The U.S. Department of Health has stated that the incidence of these cancers is likely to increase in the near future due to a number of driving factors including the improvement of diagnosis, ageing population and increased oncogenic HPV infections, among others. Across all gynecologic malignancies, a substantial fraction of patients are diagnosed with advanced or metastatic disease at initial presentation or experience relapse following primary local therapy. Standard treatment varies according to the exact origin of the cancer. Most gynecologic malignancies treatments are limited to surgery, radiotherapy and platinum-based chemotherapy. Endometrial cancer can also be treated with hormone therapy. No highly effective or curative therapies are available and platinum-based chemotherapy is considered as the mainstay systemic therapy. Overall, gynecologic malignancies refractory to prior systemic therapies remain an area of a significant unmet medical need. Monalizumab is a first-in-class immune checkpoint inhibitor targeting NKG2A receptors expressed on tumor infiltrating cytotoxic CD8 T lymphocytes and NK cells. NKG2A is an inhibitory receptor binding HLA-E. By expressing HLA-E, cancer cells can protect themselves from killing by NKG2A+ immune cells. HLA-E is frequently up-regulated and widely expressed on cancer cells of many solid tumors or hematological malignancies. In some cancers, HLA-E expression is associated with poor prognosis. Monalizumab, a humanized IgG4, blocks the binding of NKG2A to HLA-E allowing activation of NK and cytotoxic T cell responses. By blocking the inhibitory NKG2A receptors, monalizumab may re-establish a broad anti-tumor response mediated by NK and T cells. Monalizumab may also enhance the cytotoxic potential of other therapeutic antibodies. Monalizumab is partnered with AstraZeneca and MedImmune, AstraZeneca's global biologics research and development arm, through a co-development and commercialization agreement. The initial development plan includes a combination trial with durvalumab in solid tumors conducted by AstraZeneca as well as multiple Phase II trials conducted by Innate Pharma, to study monalizumab efficacy as a monotherapy and in combinations with currently approved treatments in several cancer indications. As previously announced, under the terms of this agreement, Innate Pharma is eligible to cash payments of up to $1.275 billion as well as double digit royalties on sales. In addition to the initial payment of $250 million, AstraZeneca will pay Innate Pharma a further $100 million at the decision to go into Phase III development, as well as additional regulatory and sales-related milestones of up to $925 million. AstraZeneca will book all sales and will pay Innate Pharma double-digit royalties on net sales. The arrangement includes the right for Innate Pharma to co-promote in Europe for a 50% profit share in the territory. The Canadian Cancer Trials Group is a cooperative oncology group which carries out clinical trials in cancer therapy, supportive care and prevention across Canada and internationally. It is one of the national programmes and networks of the Canadian Cancer Society Research Institute (CCSRI), and is supported by the Canadian Cancer Society (CCS). Its Central Operations and Statistics Centre is located at Queen's University in Kingston, Ontario, Canada. Innate Pharma S.A. is a clinical-stage biotechnology company with a focus on discovering and developing first-in-class therapeutic antibodies that harness the innate immune system to improve cancer treatment and clinical outcomes for patients. Innate Pharma specializes in immuno-oncology, a new therapeutic field that is changing cancer treatment by mobilizing the power of the body's immune system to recognize and kill cancer cells. The Company's aim is to become a commercial stage biopharmaceutical company in the area of immunotherapy and focused on serious unmet medical needs in cancer. Innate Pharma has pioneered the discovery and development of checkpoint inhibitors to activate the innate immune system. Innate Pharma's innovative approach has resulted in three first-in-class, clinical-stage antibodies targeting natural killer cell receptors that may address a broad range of solid and hematological cancer indications as well as additional preclinical product candidates and technologies. Targeting receptors involved in innate immunity also creates opportunities for the Company to develop therapies for inflammatory diseases. The Company's expertise and understanding of natural killer cell biology have enabled it to enter into major alliances with leaders in the biopharmaceutical industry including AstraZeneca, Bristol-Myers Squibb and Sanofi. Based in Marseille, France, Innate Pharma has more than 140 employees and is listed on Euronext Paris. Learn more about Innate Pharma at www.innate-pharma.com. This press release contains certain forward-looking statements. Although the company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. For a discussion of risks and uncertainties which could cause the company's actual results, financial condition, performance or achievements to differ from those contained in the forward-looking statements, please refer to the Risk Factors ("Facteurs de Risque") section of the Document de Reference prospectus filed with the AMF, which is available on the AMF website (http://www.amf-france.org) or on Innate Pharma's website. This press release and the information contained herein do not constitute an offer to sell or a solicitation of an offer to buy or subscribe to shares in Innate Pharma in any country.
News Article | November 15, 2016
REDWOOD CITY, Calif., Nov. 15, 2016 (GLOBE NEWSWIRE) -- OncoMed Pharmaceuticals Inc. (NASDAQ:OMED) announced today it will present first-in-human data from its Phase 1 clinical trials of anti-RSPO3 (OMP-131R10) and anti-DLL4/VEGF bispecific antibody (OMP-305B83) at the upcoming 28th EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium being held November 28 – December 2, 2016 in Munich, Germany. Abstracts for the presentations have been posted to www.ecco-org.eu/ENA. Data will be presented on Tuesday, November 29, 2016: The posters will be available on OncoMed’s website following the presentation at www.oncomed.com. About Anti-RSPO3 OncoMed is currently enrolling patients in an ongoing Phase 1a/b clinical trial of anti-RSPO3 that was started in July 2015. The Phase 1a/b trial initially enrolled patients with advanced refractory solid tumors and includes an expansion arm for biomarker-selected patients to receive single-agent therapy. The Phase 1b portion, which began enrollment in January 2016, is testing anti-RSPO3 with FOLFIRI in patients with second-line metastatic colorectal cancer. Anti-RSPO3 is believed to be the first drug candidate in its class to target the R-spondin-LGR pathway, an important cancer stem cell pathway identified by OncoMed researchers. About Anti-DLL4/VEGF OncoMed initiated a single-agent study of its anti-DLL4/VEGF bispecific in January 2015 in patients with advanced refractory solid tumors. Dose escalation is completed in the Phase 1a trial and enrollment in an expansion cohort is ongoing. The anti-DLL4/VEGF bispecific antibody is designed to combine the anti-cancer stem cell, dysangiogenic and immunotherapy mechanisms of anti-DLL4 with the anti-angiogenic activity of an anti-VEGF agent. The bispecific antibody was discovered using OncoMed's proprietary MAbTrap™ antibody display technology, which enables the rapid identification of monoclonal antibodies that bind targets with high affinity and specificity. The antibody is the first program based on OncoMed's BiMAb™ bispecific platform technology to enter clinical testing. About OncoMed Pharmaceuticals OncoMed Pharmaceuticals is a clinical-stage company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology therapeutics. OncoMed has seven anti-cancer therapeutic candidates in clinical development, including demcizumab (anti-DLL4, OMP-21M18), tarextumab (anti-Notch2/3, OMP-59R5), brontictuzumab (anti-Notch1, OMP-52M51), anti-DLL4/VEGF bispecific antibody (OMP-305B83), vantictumab (anti-FZD7, OMP-18R5), ipafricept (FZD8-Fc, OMP-54F28), and anti-RSPO3 (OMP-131R10), which each target key cancer stem cell signaling pathways including Notch, Wnt and R-spondin LGR. OncoMed is advancing its wholly owned GITRL-Fc candidate and an undisclosed immuno-oncology candidate (IO#2) toward clinical trials in the 2016-2017 timeframe. OncoMed has formed strategic alliances with Celgene Corporation, Bayer Pharma AG and GlaxoSmithKline (GSK). Additional information can be found at the company's website: www.oncomed.com.
News Article | December 21, 2016
BEIJING, Dec. 21, 2016 (GLOBE NEWSWIRE) -- BeiGene, Ltd. (NASDAQ:BGNE), a clinical-stage biopharmaceutical company developing molecularly-targeted and immuno-oncology drugs for the treatment of cancer, today announced the dosing of the first patient in a Phase I clinical trial of BGB-290, a potent and selective PARP inhibitor, in Chinese patients with advanced solid tumors. “We are pleased to announce the start of clinical development for BGB-290 in China, and we look forward to its rapid development following this Phase I study. BGB-290 entered clinical evaluation in Australia in July 2014, and proof of principle data were presented at the AACR-NCI-EORTC meeting in 2015. We look forward to developing BGB-290 for patients in China, where this class of agents is still not available,” commented John V. Oyler, Founder, Chief Executive Officer, and Chairman. The Phase I open-label, multi-center dose escalation and expansion study of BGB-290 is designed to investigate the safety, pharmacokinetics, and antitumor activity of BGB-290 in Chinese patients with advanced solid tumors and to determine the recommended Phase II dose in these patients. Professor Binghe Xu from The Chinese Academy of Medical Sciences Cancer Hospital is the principal investigator of the study. BGB-290 is a potent and highly selective inhibitor of PARP1 and PARP2. BGB-290 is being developed as a monotherapy and in combination with other therapies for the treatment of several cancers including ovarian cancer, prostate cancer, breast cancer, glioblastoma multiforme, small cell lung cancer, and gastric cancer. BeiGene is a global, clinical-stage, research-based biotechnology company focused on molecularly targeted and immuno-oncology cancer therapeutics. With a team of over 300 scientists, clinicians and staff in mainland China, the United States, Australia and Taiwan, BeiGene is advancing a pipeline consisting of novel oral small molecules and monoclonal antibodies for cancer. BeiGene is working to create combination solutions aimed to have both a meaningful and lasting impact on cancer patients. This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the encouraging clinical data of BGB-290, the potential implications of these data for the future development of BGB-290, and BeiGene’s advancement of, and anticipated clinical development and regulatory milestones and plans related to BGB-290. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeiGene's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials; BeiGene's ability to achieve market acceptance in the medical community necessary for commercial success; BeiGene's ability to obtain and maintain protection of intellectual property for its technology and drugs; BeiGene's reliance on third parties to conduct preclinical studies and clinical trials; BeiGene’s limited operating history and BeiGene's ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates, as well as those risks more fully discussed in the section entitled “Risk Factors” in BeiGene’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeiGene undertakes no duty to update such information unless required by law.
News Article | December 13, 2016
HOUSTON, TX--(Marketwired - December 13, 2016) - Moleculin Biotech, Inc., ( : MBRX) ("Moleculin" or the "Company"), a preclinical pharmaceutical company focused on the development of anti-cancer drug candidates, many of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, today announced its scientific presentation at the 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics. Waldemar Priebe, PhD, Moleculin's Founder, Founding Scientist, and Chair of the Scientific Advisory Board presented the Abstract on November 30th at the Symposium in Munich, Germany. Wally Klemp, Chairman and CEO stated, "This presentation shows proof of concept data for our WP1122 portfolio, including data demonstrating increased survival of animals with human brain tumors treated with WP1122, as well as its biodistribution and pharmacokinetics. In non-optimal doses and treatment regimens, our lead inhibitor WP1122 performed equal to or better than the current market leader, cytotoxic drug temozolomide and significantly improved survival in animals treated with WP1122 in combination with temozolomide." The following is an overview of the presentation, titled "Latentiation of 2-deoxy-D-glucose". No curative therapy exists for patients with high-grade malignant gliomas (GBMs). New approaches to the treatment of this disease are currently being evaluated with mixed results. One approach, that deserves to be therapeutically exploited, is targeting brain tumor metabolism. 2-Deoxy-D-glucose (2-DG), a known effective inhibitor of glycolysis, has been clinically tested but results did not meet expectations due to poor drug-like characteristics and inability to achieve therapeutic concentrations of 2-DG in the brain. Dr. Waldemar Priebe stated, "We proposed to use latentiation of 2-DG to overcome this problem by chemically modifying biologically active 2-DG to form prodrugs with increased brain uptake that will be able to liberate in vivo the parent compound 2-DG in the brain. In our approach, we synthesized a series of differentially acetylated derivatives of 2-DG. Preliminary in vivo studies in mice of selected diacetates of 2-DG demonstrated >9 fold increased levels of 2-DG in the brain when compared with levels of 2-DG after administration of equimolar amount of 2-DG itself. Ultimately, our studies focused on a single compound 3,6-di-O-acetyl-2-deoxy-D-glucose (WP1122)." Compound WP1122 was administered in vivo without toxic death up to the highest feasible dose of 3.0 g/kg intravenously and orally up to 6.0 g/kg. Significantly increased survival, comparable to or better than that of temozolomide, was observed for orally administered WP1122 in a U87 orthotopic glioma model at a dose of 1.25 g/kg. These promising results prompted continuation of preclinical toxicology evaluation of WP1122 aimed at the initiation of formal IND enabling studies. In addition, the proof of concept delivered by WP1122 has provided not only an effective approach to develop novel agents able to effectively cross the blood brain barrier but also a method to create a new class of dual function prodrugs by exploring biologically active acids. Moleculin's Chairman and CEO, Walter Klemp, concluded, "We are excited to present our results at this prestigious symposium. Clearly, the significantly increased survival data is key, especially as no curative therapy exists for patients with high-grade malignant gliomas today. We look forward to presenting additional data as we progress toward our clinical timeline." For more information on the Symposium click: http://www.ecco-org.eu/ENA2016 Moleculin Biotech, Inc. is a preclinical pharmaceutical company focused on the development of anti-cancer drug candidates, some of which are based on discoveries made at M.D. Anderson Cancer Center. Our lead product candidate is Annamycin, a Phase II clinical stage anthracycline for the treatment of relapsed or refractory acute myeloid leukemia, more commonly referred to as AML. We also have two pre-clinical small molecule portfolios, one of which is focused on the modulation of hard-to-target tumor cell signaling mechanisms and recruitment of the patient's own immune system, the other targeting tumor specific metabolism. For more information about Moleculin, please visit: http://www.moleculin.com Some of the statements in this release are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995, which involve risks and uncertainties. Forward-looking statements in this press release include, without limitation, the ability to achieve future promising results of preclinical toxicology evaluation of WP1122 sufficient to initiate formal IND enabling studies and the acceptance of the patent application filed. These statements relate to future events, future expectations, plans and prospects. Although Moleculin Biotech believes that the expectations reflected in such forward-looking statements are reasonable as of the date made, expectations may prove to have been materially different from the results expressed or implied by such forward-looking statements. Moleculin Biotech has attempted to identify forward-looking statements by terminology including "believes," "estimates," "anticipates," "expects," "plans," "projects," "intends," "potential," "may," "could," "might," "will," "should," "approximately" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. These statements are only predictions and involve known and unknown risks, uncertainties, and other factors, including those discussed under the heading "Risk Factors" in our Registration Statement on Form S-1 originally filed with the Securities and Exchange Commission on February 1, 2016, as amended (Registration No. 333-209323). Any forward-looking statements contained in this release speak only as of its date. We undertake no obligation to update any forward-looking statements contained in this release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events.
Expert Opinion on Investigational Drugs | Year: 2012
Introduction: Drug development is a complex and risky enterprise. Clinical development must be a thoroughly paced process sequenced by clinical and developmental questions logically ordered. Drug development parameters are changing due to better insights in system biology and mechanisms of actions. Therefore, there is a need to revisit how clinical trials are designed and sequenced. Areas covered: In the context of this paper, the development of glufosfamide is placed in perspective of possible new trends for more optimal drug development. Glufosfamide is an alkylating agent with a favorable safety profile as its metabolic activation does not lead to the release of toxic metabolites such as acrolein. In addition, its cellular uptake mediated through the transmembrane receptors of glucose makes it an attractive agent for the treatment of highly proliferative tumors cells. These observations have served the rationale to bring this agent to the clinic from Phase I up to Phase III with a focus on pancreatic cancer. The pathways for its development have been challenging due in part to the fact that there is no proof of mechanism-based study for any alkylating agent, even those used in the clinic. Expert opinion: Solid mechanism and translational research-based clinical trials providing evidence on the mechanism of action and how the agent interacts with the biology of the targeted disease are today an absolute requirement for the development of new agents. Optimal clinical trial design must complement system biology understanding so that 'trials designed to learn' may give robust grounds to 'clinical trials designed to conclude'. © 2012 Informa UK, Ltd.