词条 | Viralytics |
释义 |
| name = Viralytics Ltd | type = Public company | traded_as = {{asx|VLA}} | foundation = 2006 | location = Sydney | key_people = Paul A. Hopper Non-Executive chairman) Malcolm McColl (chief executive officer) Darren Shafren (Chief Scientific Officer) | industry = Biotechnology | products = Cavatak, an oncylytic virus | homepage = {{URL|www.viralytics.com}} }}Viralytics Ltd is an Australian biotechnology company working in the field of oncolytic viruses, that is, viruses that preferentially infect and kill cancer cells. The company's oncolytic virus product, called Cavatak, is currently in clinical trials in metastatic melanoma and other cancers. The drug was granted Orphan Drug status in advanced melanoma in December 2005.[1] In February 2018, Merck & Co. announced it would acquire Viralytics for AUD$502 million ($394 million).[2] Corporate historyAround 1999 a team led by the virologist Professor Darren Shafren at the University of Newcastle in Australia established that a Coxsackievirus called Coxsackievirus A21 was an oncolytic virus, in addition to being a common-cold virus causing mild upper respiratory tract infections.[3] Shafren filed for patent protection over the use of the virus in oncology[4] and the University of Newcastle subsequently formed a spin-out company called ViroTarg Pty Ltd. An ASX-listed biotech company called Psiron began to fund development of the ViroTarg project in June 2004[5] and in December 2006 acquired the Virotarg intellectual property. Psiron changed its name in the process to Viralytics to reflect the fact that oncolytic viruses were now its core focus.[6] Shafren's wild-type Coxsackievirus A21, which Viralytics called Cavatak, was trialled in a Phase I in melanoma between 2007 and 2010 and in 2012 the product entered a Phase II trial in advanced melanoma called 'CALM', short for '{{underline|CA}}vatak in {{underline|L}}ate Stage {{underline|M}}elanoma'. This trial took place under an Investigational New Drug application. The trial completed in 2015 with favourable results and multiple trials are now underway to establish various indications for Cavatak. Viralytics stock is publicly traded on the ASX under the code VLA. In the US its ADRs have traded OTC since October 2006[7] and on OTCQX under the code VRACY since August 2013.[8] The ratio of ADRs to the ordinary shares is 30:1. Board of DirectorsViralytics' Non-Executive chairman is Paul Hopper, an Australian bioentrepreneur based in Sydney who has been a director since September 2008[9] and chairman since November 2008.[10] The company's CEO is Dr Malcolm McColl, a former executive of the major Australian pharmaceutical company CSL and the biotech company Starpharma who joined the company in January 2013.[11] LocationsViralytics' is headquartered in the City Mutual Building, an art deco icon in the Sydney CBD located at 66 Hunter Street. Darren Shafren has a laboratory in Newcastle. CavatakCavatak is the trade name for a preparation of wild-type Coxsackievirus A21, as manufactured by Viralytics. Within the Picornaviradae family of viruses, Coxsackievirus A21 is a member of the Human enterovirus C species. The virus consists of a single positive-stranded RNA genome within a capsid of approximately 28 nm in diameter. The virus is known to utilise the viral entry receptor ICAM-1 as its primary entry receptor, with DAF as a co-receptor to infect host cells.[12] Mechanism of actionThe firm argues that Cavatak has a dual mechanism of action. As well as oncolysis through the preferential targeting of cells that over-express the molecules ICAM-1 and/or DAF compared to normal cells, there is also an immunological involvement in which the infection promotes tumour inflammation, which in turn prompts the patient's immune system to attack the infected cancer cells.[13] Pre-clinical evidence of efficacyShafren et al. first published data showing that Cavatak could destroy malignant melanoma cells in the journal Clinical Cancer Research in January 2004.[14] A June 2005 paper in the International Journal of Oncology showed that this effect worked as well for melanoma exhibiting a highly vascular phenotype.[15] In April 2007, in a paper in the British Journal of Haematology, the Shafren lab showed that Cavatak could work in multiple myeloma[16] and over the next two years papers in The Prostate (May 2008)[17] and Breast Cancer Research and Treatment (January 2009)[18] suggested similar pre-clinical efficacy in prostate and breast cancer respectively. What these cancers have in common is that they all have high levels of ICAM-1 expression. 2007–2011: Early clinical workIn January 2010 Viralytics reported favourable results from a nine patient Phase I trial of Cavatak in Stage IV melanoma patients (ClinicalTrials.gov identifier NCT00438009) where the virus was administered intratumourally. In this trial, which was initiated in May 2007[19] but was not completed until 2009, all patients were given two Cavatak doses of the same size 48 hours apart into a single cutaneous melanoma lesion. Three patients received a low dose, three a middle dose and three a high dose.
These results were presented at the May 2011 Annual Meeting of the American Society of Clinical Oncology, held that year in Chicago. 2012–2015: The CALM studyThe Phase II CALM study (ClinicalTrials.gov identifier NCT01227551) took a considerable period of time for Viralytics to initiate – the pre-IND meeting with the FDA was held in June 2010[22] and Viralytics lodged its IND in November 2010,[23] however the trial wasn't cleared until June 2011.[24] This meant that the study didn't dose its first patient until after January 2012.[25] However this open-label trial was eventually able to evaluate 57 patients with stage IIIc or stage IV melanoma. Each evaluated patient received 10 intratumoural injections of Cavatak over 18 weeks. The dose level was 3x108 TCID50 virus with the investigators measuring response rates as well as Progression Free Survival at 6 months, and tracking the immune response of the patient. The trial was one of the first in the world to make use of the new Immune-Related Response Criteria.
Current clinical trials
See also
References1. ^{{cite news|title=Psiron's Cavatak received Orphan Drug Designation from the FDA|url=http://www.asx.com.au/asxpdf/20051221/pdf/3tv5gzx4nrrjx.pdf|accessdate=4 December 2015|agency=asx.com.au|date=21 December 2015}} 2. ^https://uk.reuters.com/article/us-viralytics-m-a-merck-co/merck-to-buy-virus-based-cancer-drug-firm-viralytics-for-394-million-idUKKCN1G50ZN 3. ^{{cite journal|author1=Magee WE |author2=Miller OV. |title=Individual variability in antibody response of human volunteers to infection of the upper respiratory tract by coxsackie A21 virus. |journal=J Infect Dis |volume=122 |issue=3 |pages=127–38. |date=1 September 1970 |doi= 10.1093/infdis/122.3.127 |pmid=4317757}} 4. ^{{ cite patent |country=WO |number=2001037866 |status= application |title=A method of treating a malignancy in a subject and a pharmaceutical composition for use in same |pubdate=2001-05-31 |fdate=2000-11-27 |pridate=1999-11-25 |invent1=Darren Shafren |assign1= The University of Newcastle}} 5. ^{{cite news|title=Psiron signs MOU and moves to a cancer therapy focus|url=http://www.asx.com.au/asxpdf/20040622/pdf/3lxr775b152fy.pdf|accessdate=4 December 2015|agency=asx.com.au|date=22 June 2004}} 6. ^{{cite news|title=Change of Name to Viralytic Ltd|url=http://www.asx.com.au/asxpdf/20061221/pdf/310885vn0wwcv3.pdf|accessdate=4 December 2015|agency=asx.com.au|date=21 December 2006}} 7. ^{{cite news|title=Commencement of ADR trading|url=http://www.asx.com.au/asxpdf/20061013/pdf/3yz7tmlkb3l28.pdf|accessdate=4 December 2015|agency=asx.com.au|date=13 October 2006}} 8. ^{{cite news|title=Viralytics commences trading on US OTCQX marketplace|url=http://www.asx.com.au/asxpdf/20130805/pdf/42hh32cck2xdqn.pdf|accessdate=4 December 2015|agency=asx.com.au|date=5 August 2013}} 9. ^{{cite news|title=Appointment of Paul Hopper as Non-Executive Director|url=http://www.asx.com.au/asxpdf/20080904/pdf/31c4cw8r48kdmk.pdf|accessdate=3 December 2015|agency=asx.com.au|date=4 September 2008}} 10. ^{{cite news|title=Viralytics restructures Board and Management|url=http://www.asx.com.au/asxpdf/20081023/pdf/31d25k02pzy493.pdf|accessdate=3 December 2015|agency=asx.com.au|date=23 October 2008}} 11. ^{{cite news|title=Dr Malcolm McColl commences as Chief Executive Officer|url=http://www.asx.com.au/asxpdf/20130121/pdf/42cj5hspcrt76n.pdf|accessdate=3 December 2015|agency=asx.com.au|date=23 January 2013}} 12. ^{{cite journal|vauthors=Shafren DR, Dorahy DJ, Ingham RA, Burns GF, Barry RD | title=Coxsackievirus A21 binds to decay-accelerating factor but requires intercellular adhesion molecule 1 for cell entry. | journal=J Virol | year= 1997 | volume= 71 | issue= 6 | pages= 4736–43 | pmid=9151867 | doi= | pmc=191695 }} 13. ^{{cite journal |vauthors=Shafren D, Quah M, Wong Y, Andtbacka R, Kaufman H, Au G |title=Combination of a novel oncolytic immunotherapeutic agent, CAVATAK (coxsackievirus A21) and immune-checkpoint blockade significantly reduces tumor growth and improves survival in an immune competent mouse melanoma model |journal=J Immunother Cancer. |volume=2 |issue=Suppl 3 |pages= |date=1 June 2005 |pmid= |doi=10.1186/2051-1426-2-S3-P125 |pmc=4288429 |page=P125}} 14. ^{{cite journal |vauthors=Shafren DR, Au GG, Nguyen T, Newcombe NG, Haley ES, Beagley L, etal | title=Systemic therapy of malignant human melanoma tumors by a common cold-producing enterovirus, coxsackievirus a21. | journal=Clin Cancer Res | year= 2004 | volume= 10 | issue= 1 Pt 1 | pages= 53–60 | pmid=14734451 | doi= 10.1158/1078-0432.ccr-0690-3| pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14734451 }} 15. ^{{cite journal |author1=Au GG |author2=Lindberg AM |author3=Barry RD |author4=Shafren DR. |title=Oncolysis of vascular malignant human melanoma tumors by Coxsackievirus A21 |journal=Int J Oncol |volume=26 |issue=6 |pages=1471–6 |date=1 June 2005 |doi= |pmid=15870858}} 16. ^{{cite journal|vauthors=Au GG, Lincz LF, Enno A, Shafren DR | title=Oncolytic Coxsackievirus A21 as a novel therapy for multiple myeloma. | journal=Br J Haematol | year= 2007 | volume= 137 | issue= 2 | pages= 133–41 | pmid=17391493 | doi=10.1111/j.1365-2141.2007.06550.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17391493 }} 17. ^{{cite journal|vauthors=Berry LJ, Au GG, Barry RD, Shafren DR | title=Potent oncolytic activity of human enteroviruses against human prostate cancer. | journal=Prostate | year= 2008 | volume= 68 | issue= 6 | pages= 577–87 | pmid=18288643 | doi=10.1002/pros.20741 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18288643}} 18. ^{{cite journal|vauthors=Skelding KA, Barry RD, Shafren DR | title=Systemic targeting of metastatic human breast tumor xenografts by Coxsackievirus A21. | journal=Breast Cancer Res Treat | year= 2009 | volume= 113 | issue= 1 | pages= 21–30 | pmid=18256929 | doi=10.1007/s10549-008-9899-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18256929}} 19. ^{{cite news|title=First Patient Enrolled in Viralytics' Phase I Melanoma Cancer Trial With Cavatak|url=http://www.asx.com.au/asxpdf/20070524/pdf/312ly6drpjd2tm.pdf|accessdate=4 December 2015|agency=asx.com.au|date=24 May 2007}} 20. ^{{cite news|title=Melanoma Phase I Clinical Trial Report Completed|url=http://www.asx.com.au/asxpdf/20100119/pdf/31n76qgzblyb5v.pdf|accessdate=4 December 2015|agency=asx.com.au|date=19 January 2010}} 21. ^{{cite news|title=Chief Scientific Officer's Presentation at the International Melanoma Conference|url=http://www.asx.com.au/asxpdf/20101105/pdf/31tq2j1ykqg4pb.pdf|accessdate=4 December 2015|agency=asx.com.au|date=4 November 2010}} 22. ^{{cite news|title=US FDA Pre-IND Meeting Update|url=http://www.asx.com.au/asxpdf/20100625/pdf/31r0bc8k41zt6v.pdf|accessdate=4 December 2015|agency=asx.com.au|date=25 June 2010}} 23. ^{{cite news|title=Investigational New Drug Application Lodged With the FDA|url=http://www.asx.com.au/asxpdf/20101103/pdf/31tn3878kqdb35.pdf|accessdate=4 December 2015|agency=asx.com.au|date=3 November 2010}} 24. ^{{cite news|title=Allowance of FDA Investigational New Drug (IND) Application for Cavatak Phase II Melanoma Trial|url=http://www.asx.com.au/asxpdf/20110627/pdf/41zfbjfzr2zl66.pdf|accessdate=4 December 2015|agency=asx.com.au|date=27 June 2011}} 25. ^{{cite news|title=First Patients Commence Cavatak Injections in Phase II Clinical Trial|url=http://www.asx.com.au/asxpdf/20120119/pdf/423v46n6ggv71s.pdf|accessdate=4 December 2015|agency=asx.com.au|date=19 January 2012}} 26. ^{{cite news|title=Primary Endpoint Achieved in Cavatak Phase II Melanoma Trial|url=http://www.asx.com.au/asxpdf/20130918/pdf/42jfgyp6t2wwxc.pdf|accessdate=4 December 2015|agency=asx.com.au|date=18 September 2013}} 27. ^{{cite news|title=Updated positive data from Phase 2 trial of Cavatak in late stage melanoma|url=http://www.asx.com.au/asxpdf/20140929/pdf/42sj256mrsxfnj.pdf|accessdate=3 December 2015|agency=asx.com.au|date=29 September 2014}} 28. ^1 {{cite news|title=Viralytics Reports Positive Final Results from Cavatak Phase II melanoma trial|url=http://www.asx.com.au/asxpdf/20150602/pdf/42yy9ntnfyw9vy.pdf|accessdate=4 December 2015|agency=asx.com.au|date=2 June 2015}} 29. ^{{cite news|title=Viralytics commences STORM phase 1/2 clinical trial|url=http://www.asx.com.au/asxpdf/20140306/pdf/42n6g8bhwdbhx3.pdf|accessdate=4 December 2015|agency=asx.com.au|date=6 March 2014}} 30. ^{{cite news|title=Viralytics and Merck & Co., Inc., Kenilworth, New Jersey, U.S.A. to Collaborate on Combination Clinical Trial of Cavatak and Keytruda in Lung and Bladder Cancer|url=http://www.asx.com.au/asxpdf/20151106/pdf/432shq5h1fpx3d.pdf|accessdate=4 December 2015|agency=asx.com.au|date=6 November 2015}} 31. ^{{cite news|title=Viralytics Commences Clinical Trial of Cavatak in Bladder Cancer|url=http://www.asx.com.au/asxpdf/20150127/pdf/42w5l8ymj1mdvf.pdf|accessdate=4 December 2015|agency=asx.com.au|date=27 January 2015}} 32. ^{{cite news|title=Viralytics to Commence Clinical Trial of Cavatak Immunotherapy Combination|url=http://www.asx.com.au/asxpdf/20141204/pdf/42v80l2s83b8dn.pdf|accessdate=4 December 2015|agency=asx.com.au|date=4 December 2014}} 33. ^{{cite news|title=Viralytics Initiates Clinical Trial of Cavatak in Combination with PD-1 Blocker Keytruda|url=http://www.asx.com.au/asxpdf/20150928/pdf/431mp2lwg56vpy.pdf|accessdate=4 December 2015|agency=asx.com.au|date=28 September 2015}} 5 : Biotechnology companies|Cancer research|Health care companies of Australia|2018 mergers and acquisitions|Merck & Co. |
随便看 |
|
开放百科全书收录14589846条英语、德语、日语等多语种百科知识,基本涵盖了大多数领域的百科知识,是一部内容自由、开放的电子版国际百科全书。