Novartis 重金佈署 Aduro’s STING (Stimulator of Interferon Genes)癌症免疫治療($200 million upfront)

Novartis, Aduro: Up-to-$750M Cancer Immunotherapy Collaboration Mon, 03/30/2015 - 12:52pm Stephanie Guzowski, Editor Novartis is planning to boost its cancer immunotherapy pipeline with a collaboration with California-based Aduro Biotech worth up to $750 million. The partnership is focused on the development of cancer immunotherapies based on Aduro's STING (Stimulator of Interferon Genes) technology, a next-generation method to harness the body's immune system to fight cancer. Novartis will pay $200 million upfront for rights to the program, along with an initial equity investment of $25 million. Aduro could receive up to an additional $500 million in payments tied to development milestones from Novartis, as well as a commitment for another $25 million investment from Novartis at a future date. Aduro's agreement with Novartis covers research, development and commercialization of cyclic dinucleotide (CDN)-based oncology therapies. Novartis will lead worldwide commercialization for any drug projects developed, while Aduro will focus on U.S. commercialization. "We are delighted to collaborate with Aduro," Novartis' Mark C. Fishman, M.D., president of the Novartis Institutes for BioMedical Research, said in a statement. "We believe this target is among the most exciting in oncology today, the drug candidate to be of the highest quality, and the talent of our new colleagues from Aduro to be fantastic. We anticipate many clinical opportunities will be explored with the CDN approach, both directly and in combination with other agents." Novartis has been active in the development of cancer immunotherapies, including chimeric antigen receptor T-cell (CART) drug CTL019, which is in mid-stage Phase 2 clinical trials. Said Aduro Chief Scientific Officer Thomas W. Dubensky, Jr., Ph.D. in a statement, "We look forward to collaborating with Novartis to begin a Phase 1 clinical trial with our first novel immune-oncology candidate."

荷蘭癌症中心(NKI) 目標成為歐洲T 細胞基因治療龍頭!

Kite Pharma Acquires T-Cell Factory for $21M UpFront Mar 18, 2015 Kite Pharma has acquired privately held T-Cell Factory (TCF) for €21 million ($21 million) upfront, and renamed it Kite Pharma EU, in a deal designed to establish a European presence for the buyer and strengthen its T Cell Receptor (TCR) gene therapy product platform. TCF has focused on discovery and development of tumor-specific TCRs for broad use in cancer treatment based on its TCR-GENErator? platform. TCRs allow targeting of tumor antigens found inside cancer cells, as well as surface antigens. Kite agreed to make the upfront payment, of which €3.8M (about $4 million) will be paid in Kite stock—as well as an undisclosed sum in payments tied to achieving clinical, regulatory, and sales milestones relating to TCR-based product candidates. By acquiring TCF, Kite said, it has obtained license agreements with IBA GmbH, Sanquin Blood Supply Foundation, and the Netherlands Cancer Institute (NKI) that include rights to new TCR-related intellectual property in the TCR space developed by a co-founder of TCF, professor Ton N. M. Schumacher, Ph.D., deputy director of the NKI. Dr. Schumacher will become CSO of Kite Pharma EU, while maintaining his position at NKI. "NKI's goal is to become the leader in T cell gene therapy in Europe, and we are expanding our clinical and manufacturing capacities. We are excited about partnering with Kite and potential future R&D collaborations with the company," professor Rene Medema, director of NKI, said in a statement. Dr. Schumacher co-founded TCF with professor Dirk H. Busch, M.D., director of the Institute for Medical Microbiology, Immunology and Hygiene (MIH) at Technische Universitat Munchen (TUM) School of Medicine; Lothar Germeroth, Ph.D., former TCF senior advisor, CEO of IBA GmbH and COO of Stage Cell Therapeutics; Carsten Linnemann, Ph.D., senior scientist with Kite Pharma EU; and Georg Dossinger, Ph.D., a scientist at MIH. Kite also said the acquisition provides access to European clinical manufacturing facilities, launching a base for Kite to build its global presence and initiate clinical programs in the EU. Kite has developed the engineered Autologous cell therapy (eACT?), a platform technology encompassing T cells manufactured ex vivo, that are genetically re-directed against cancerous cells. TCR is one category of eACT; the other consists of Chimeric Antigen Receptor (CAR) T cells genetically re-directed against cancerous cells through receptors comprising a target recognition domain linked to T cell activating domains. In January, Kite launched a partnership with Amgen to develop and commercialize CAR T cell immunotherapies, in a deal that could generate a combined billion-plus dollars for both companies. Kite's pipeline includes clinical-stage programs advancing multiple TCR-based product candidates: NY-ESO-1 against various tumors; HPV-16 E6 antigens against cervical and head and neck cancers, and MAGE antigens against various tumors. "The acquisition of TCF and its novel discovery and development platform provides Kite with a strong position in TCR gene therapy for cancer," Arie Belldegrun, M.D., FACS, Kite's president and CEO, said in a statement. "In addition, with our strategic plans for expanding clinical operations to ex-US sites, Kite's relationship with NKI, an internationally renowned research and clinical institution, provides an important operational platform and potential access to investigators, clinical sites and manufacturing facilities in Amsterdam." Added David Chang, M.D., Ph.D., Kite Pharma's evp, research and development and CMO: "In addition to expanding our capabilities in TCR, this acquisition is an important first step in our goal of global clinical expansion outside the US, applying our leadership and in-house clinical expertise in both CAR and TCR therapies." Kite's acquisition of TCF follows the announcement earlier this month of Kite's expanded Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) to develop new TCR candidates, including against tumor neo-antigens, truly tumor-specific antigens generated as tumors accumulate genetic mutations.

BMS 重押 癌症疫苗 失敗再投資!! (PD-1 ab, Opdivo+ GVAX)

Bristol-Myers forges a billion-dollar cancer vaccine deal with Bavarian Nordic March 4, 2015 | By John Carroll Determined to stay ahead of the growing pack of rivals in immuno-oncology, Bristol-Myers Squibb ($BMY) has swooped in with $60 million upfront to gain an option on Bavarian Nordic's Phase III therapeutic prostate cancer vaccine Prostvac, ready to shell out an additional $915 million-plus in milestones if it takes the next step to license and ultimately commercialize the therapy. In the meantime, Bristol-Myers--which has now committed up to $2.6 billion in three new cancer R&D deals over the past two weeks--and its new partner are hatching plans for a slate of combination studies. If Bristol-Myers does take the next step, it will be on the hook for another $80 million payment, more than $230 million in development milestones if the therapy tops its Phase II efficacy results, $110 million in regulatory milestones and $495 in sales milestones. The Danish biotech will manufacture Prostvac and also stands to earn a double-digit royalty. Bristol-Myers' deal today could go a long way toward reviving expectations for cancer vaccines, which have experienced a multitude of setbacks in the clinic at Merck KGaA and elsewhere. The pioneering cancer vaccines just haven't had the efficacy punch needed to prove their value. But with checkpoint inhibitors like Bristol-Myers' leading program for Opdivo stealing the limelight in cancer R&D, leaders in the field are demonstrating a renewed interest in matching a therapy that can jump-start an immune attack on specific cancer cells with new therapies that are taking the brakes off an immune system assault. "Obviously, we've been looking for a partner for some time," Bavarian Nordic CEO Paul Chaplin tells FierceBiotech. In the early days the field's risky profile had an effect. But with the arrival of checkpoint inhibitors and the booming market for collaborations, the pendulum swung in Bavarian Nordic's favor, particularly as new data rolled in on Prostvac's efficacy. "The world has changed," adds Chaplin, pointing to the large percentage of cancer patients who don't respond to the checkpoint drugs and could well benefit substantially by adding a cancer vaccine. "I think we became quite popular in the last 18 months." Bavarian Nordic ended 2014 with its Phase III program for Prostvac fully enrolled with 1,200 patients. The final readout is expected 18 to 24 months after full enrollment with three interim analyses along the way that might possibly trigger the option deal. Bristol-Myers already has a mid-stage combination study underway with Prostvac and Yervoy to test that theory. More combo studies are being planned, according to today's announcement. And just days ago Bristol-Myers and Aduro noted that they had begun a midstage study of a combination therapy that includes Opdivo and GVAX, one of the failed cancer vaccines that has now come back into the spotlight. Last week Bristol-Myers and Bavarian Nordic rolled out some promising data from an early-stage study combining Prostvac and Yervoy. Investigators from the National Cancer Institute say that the overall survival benefit in one cohort hit 37.2 months with an average median OS of 31.3 months. That stacks up against an "expected" OS rate of 18.5 months. Researchers enrolled 30 patients in that study. The deal today marks the latest step in a multibillion-dollar deal spree in cancer R&D for Bristol-Myers. In late February the company bought Flexus in a $1.25 billion acquisition, and added a $339 million pact with Rigel. "Our agreement with Bavarian Nordic reflects our commitment to following the emerging science in immuno-oncology and supports our strategy to transform the treatment of cancer across multiple tumor types, lines of therapy and stages of disease," says Michael Giordano, who runs oncology R&D for Bristol-Myers.

 

VAX  is a granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transfected tumor cell vaccine. Original work with GM-CSF as a recombinant DNA protein (Leukine) involved proliferative stimulation of macrophages and neutrophils for the purpose of reducing hematopoietic toxicity related to dose-intensive chemotherapy. Following US Food and Drug Administration approval of Leukine several years ago, extensive preclinical results have demonstrated an immunostimulatory effect related to GM-CSF gene when transfected into tumor cells and used as a vaccine (GVAX). Tumor regression and prolonged survival was demonstrated in animal models. Toxicology with GVAX indicated no adverse effects, which enabled further testing in cancer patients. A small number of responses were demonstrated in Phase I trials in immunosensitive cancer patients (renal cell carcinoma and melanoma). However, a series of dramatic complete and durable responses in advanced non-small cell lung cancer patients, demonstrated in recent clinical trials, have generated interest in further development of this vaccine in nontraditional cancer disease types. The rationale of GVAX development and a summary of clinical results are reviewed.

 

PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) is a cancer immunotherapy candidate in clinical development by Bavarian Nordic for the treatment of metastatic castration-resistant prostate cancer (mCRPC). PROSTVAC is designed to enable the immune system to recognize and attack prostate cancer cells by triggering a specific and targeted T cell immune response to cancer cells that express the tumor-associated antigen prostate-specific antigen (PSA). PROSTVAC utilizes recombinant poxviruses to express PSA, along with 3 immune-enhancing costimulatory molecules collectively designated as TRICOM (LFA-3, ICAM-1, and B7.1). Treatment is initiated by subcutaneous administration of a priming dose of vaccinia encoding PSA-TRICOM, followed by 6 subsequent boosting doses of fowlpox encoding the same PSA-TRICOM cassette. Using this heterologous prime-boost dosing regimen, the immune system becomes focused on inducing PSA-specific T cell responses, designed to kill tumor cells expressing PSA.

 

The PD-1/PD-L1 axis and antibodies in development. T cells interact with tumor cells in peripheral tissues. Tumor cells can present antigen to the T-cell receptor, resulting in a stimulatory signal to the T cell (+). Tumor cells may also express PD-L1, which interacts with PD-1 on activated T cells, and results in inhibition (−) of the antitumor T-cell response.

默克/ GSK 癌症疫苗失敗 期待後繼勝出(CureVac)?! (肺癌疫苗- MERCK: tecemotide (BLP25 liposomal vaccine/ GSK: MAGE-A3)

Boehringer pairs its lung cancer drug with a vaccine in $600M tie-up with CureVac September 17, 2014 | By John Carroll  A little more than two months after inking a licensing deal with Sanofi ($SNY), CureVac has completed another tie-up, banking a $45 million upfront from Boehringer Ingelheim and partnering its therapeutic vaccine aimed at lung cancer. The deal also includes up to about $556 million in prospective milestones for the German biotech. In exchange for the cash, Boehringer gains the global commercial rights to CV9202, a cancer vaccine. The private German pharma company plans to match it with Gilotrif (afatanib) for non-small cell lung cancer, with added plans to pair CV9202 with chemo/radiation therapy for unresectable--or inoperable--stage III NSCLC. While cancer vaccines have had a bleak history in the clinic in recent years, Boehringer believes that CureVac's mRNA approach has the potential to kick up a powerful immune response which could succeed where others have failed. Tubingen, Germany-based CureVac has been working on both therapeutic cancer vaccines as well as the more traditional prophylactic vaccines used to fight the spread of a virus--which is what attracted Sanofi Pasteur. On the cancer side, it's pursuing the vision of company founder and CEO Ingmar Hoerr, who believes that RNA can be injected into humans to illicit a specific immune response targeting cancer cells. Its most advanced program is in a Phase IIb study for prostate cancer, using a slate of 6 mRNA-based molecules encoding specific antigens that are overexpressed in prostate cancer cells. CV9202 is built the same way, only targeting NSCLC. CureVac is backed by Dietmar Hopp, the German billionaire who orchestrates his biotech investing through dievini Hopp BioTech. In addition to funding CureVac, Hopp--who clearly loves supporting companies with a complex technology--also finances immatics, another cancer vaccine company, as well as Switzerland's AC Immune, which is focused on Alzheimer's. Boehringer won an approval for Gilotrif (afatanib) for lung cancer a little more than a year ago. The drug is a tyrosine kinase inhibitor which is most likely to work in patients whose tumors express EGFR exon 19 deletions or exon 21 L858R substitution gene mutations. Patients taking the drug had an average rate of progression-free survival of 11.1 months compared to 6.9 months for the standard therapy arm. Clearly, Boehringer believes it can do better in fighting lung cancer. Like a lot of cancer drug developers, its researchers back the notion that a cancer vaccine could well act as a booster to an existing therapy. And they intend to test that theory with CureVac. The deal marks a significant new outreach for Boehringer, which has been very focused up to now on its own homegrown pipeline of cancer drugs. The company was attracted to evidence that the cancer vaccine has produced a "very, very strong immune response" involving CD8-positive T cells, Hoerr tells FierceBiotech. Boehringer's combination approach is quite similar to many other cancer drug development programs that are mixing a variety of therapies to obtain the most potent, targeted cancer cell killer. And the cancer vaccine strategy reminds Hoerr of the early days in HIV research, when a eries of failures was followed by the success of new cocktail therapies. Other R&D teams in the cancer vaccine field have been bitterly disappointed in recent months. Stimuvax, renamed tecemotide, was recently scrapped (for the second time) by Merck KGaA after a new clinical setback in Japan. GlaxoSmithKline's MAGE A-3 has experienced a full slate of late-stage failures. Vical's Allovectin flunked out and the pioneering Provenge from Dendreon failed to succeed against the competition in prostate cancer. CureVac, though, intends to be the exception to a harsh rule, gambling that its multi-antigen technology will provide the therapeutic punch that's needed. The sizable upfront provides CureVac, which has a staff of 140, with some additional capital as it ponders its evolving business plan. Hoerr says he's planning more such partnerships with Big Pharma to provide liquidity for the biotech. Eventually, CureVac could file for an IPO if the timing was right. In the meantime, there's a very rough estimated timeline on its Phase IIb trial, with data coming in around 2017--give or take a year--which would provide key efficacy data relevant to all of its programs.

 

Tecemotide    On August 18, 2014, Oncothyreon and finally on September 12, 2014, also Merck KGaA informed that a randomized Phase 1/2 study, EMR 63325-009, of tecemotide compared to placebo in Japanese patients with Stage III non-small cell lung cancer did not meet its primary endpoint of an improvement in overall survival, and no treatment effect was seen in any of the secondary endpoints (progression free survival, time to progression or time to failure). Merck made the recommendation to stop the investigational treatment of patients in the EMR 63325-009 study in Japan. Furthermore, Merck KGaA announced its decision to discontinue the Phase III START2 and INSPIRE studies, and all other Merck-sponsored clinical trials with tecemotide in NSCLC worldwide. Merck will continue to supply tecemotide for ongoing investigator-sponsored trials in other indications in accordance with their agreements with the sponsors of these studies.

 

MAGE-A3   is a tumor-specific protein, and has been identified on many tumors including melanoma, non-small cell lung cancer, hematologic malignancies, among others. MAGE-A3 Lung Cancer Vaccine Provides No Benefit Over Placebo News | October 13, 2014 | Lung Cancer, ESMO 2014 By Dave Levitan  With these results, the future of lung cancer vaccines is very much in...The future of lung cancer vaccines is very much in doubt as results of the large, randomized MAGRIT trial have been presented. The trial showed no benefit with the recMAGE-A3 + AS15 cancer immunotherapeutic (MAGE-A3 CI) compared with placebo in completely resected, MAGE-A3-positive non–small-cell lung cancer (NSCLC). Lung cancer immunotherapeutics are intended to improve poor outcomes in stage II and IIIA NSCLC; the current standard of care is adjuvant chemotherapy, but the 5-year disease-free survival remains below 50%. The MAGRIT trial, which was stopped earlier this year due to futility, randomized 2,272 MAGE-A3-positive patients to either MAGE-A3 CI or placebo and followed them for a median of 38.8 months. Final results were presented at the European Society of Medical Oncology (ESMO) 2014 Congress in Madrid.

 

CV9202  A non-small cell lung cancer (NSCLC) vaccine containing six modified mRNAs, which encode six different NSCLC associated antigens, with potential antitumor and immunomodulatory activities. Upon intradermal administration, mRNA-derived lung cancer vaccine CV9202 may stimulate the immune system to mount both humoral and cellular responses against NSCLC cells. The six tumor-associated antigens (TAAs) encoded by these mRNAs are frequently expressed by NSCLC cells and are minimally expressed or absent in normal, healthy cells. CV9202 is a self-adjuvanting mRNA vaccine that targets six antigens commonly expressed in NSCLC (NY-ESO-1, MAGEC1, MAGEC2, 5 T4, survivin, and MUC1).

 

南六(醫療衣布) 2014年全年營收53.44億元

南六去年業績亮麗EPS達5.79元 決配發2.8元股息 鉅亨網記者張欽發 台北2015-03-1709:08上市不織布及其應用美妝、衛生產品廠商南六(6504-TW)在2014年第4季以來的訂單強勁，去年11月、12月的營收陸續改寫歷史新高，南六2014年全年財報出爐稅後盈餘4.2億元，每股稅後盈餘5.79元，南六經董事會決議對於去年股利配發2.8元現金股息。 南六2014年全年營收53.44億元，年營收成長率16.98%，而2014年財報顯示其營業毛利10.39億元，營業淨利5.99億元，稅前盈餘5.96億元，稅後盈餘4.2億元，每股稅後盈餘5.79元。南六董事會所決議對於去年股利配發2.8元現金股息，明顯優於上一配發的1.5元現金股息。去年盈餘配發率為48.36%。2015年1月營收以5.28億元改寫單月歷史次高紀錄，同時，在南六接單全滿且加上自動化生產的有利條件之下，2月也有3.97億元的營收，累計1-2月營收為9.26億元，年增率達19.19%。南六主管強調，今年以的四大產品線訂單爆滿，即使連2月的春節假期期間，生產線仍加班生產，而在春節連續假期結束之後，出貨狀況也恢復正常。同時，南六企業自2014年第4季以來接單強勁，在產、銷兩方面南六已獲高能見度的經營環境之下，2015年不分淡旺季的月平均營收都可望維持在5億元以上的高水準。而2015年的營收水準南六也期望將較2014年至少成長20%。名列亞洲不織布業十強的南六企業成立於1978年，南六目前四大產品線包括水針不織布，其應用已發展到醫療用途的醫療手術衣布、無塵擦拭布及面膜用布，同時，南六的醫療用途的醫療手術衣布也是與美國杜邦同時獲得認證的供應商。而南六並生產柔濕巾等嬰兒及成人清潔用品、熱風熱壓不織布，使用於嬰兒、成人紙尿布表材及婦女生理用衛生棉表材。南六在2014年以來除本身在產品的產能完成大幅度的擴充之外，其對外拓展高階新產品也獲明確回報，其中如日本市場的醫療用手術衣並已獲得了訂單入袋。