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Curriculum Vitae

Michael Anthony Whelan BSc PhD FSB

Key Skills

Senior biotech professional (>fifteen years industrial experience)

Eight years academic experience (PhD)

Experienced project and team manager

Fundraising and budget management

Company Director

Managed both pre-clinical and clinical research (Phase I & II)

Regulatory affairs experience

Excellent communication skills

BSc Biochemist PhD Immunologist

Synopsis

An experienced biotech executive, with a considerable portfolio of skills including project, budget and research management. Experience as both Company Secretary and Director. Worked in two biotech companies and also considerable postdoctoral scientific experience. Particular expertise in vaccine development from both a research and development perspective, although skills are not limited to this area. Experience in regulatory affairs further complements portfolio, with both clinical trial and MA experience.

mike@whelan.org.uk +7710 385105

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Industrial Experience 2013- Director Research & Development (iQur Ltd.) iQur is a biotechnology company, spun out of University of Southampton. It has relocated to University College London and again to the London Bioscience Innovation Centre (Royal Veterinary College). It is focused on the development of a novel vaccine platform with a lead candidate for influenza. Previous projects with the company have also included the development of a novel ribavirin analogue and application for a generic ribavirin marketing authorisation (MA).

Job title changed to reflect increased responsibility and in recognition of funds raised through grant applications Board level position with associated voting rights Responsible for development of new products as well as project management of existing portfolio.

2009-2013 Head Research & Development (iQur Ltd.)

Attend at all Board meetings and present results/plans directly. Act as Company Secretary and also responsible for direct financial control of company and interface with investors. Wrote and was awarded an EU Framework 7 grant (total value €4.6M to develop a universal influenza vaccine. The consortium comprises seven partners and I chair and project-manage to the group. Wrote and was awarded a TSB BioCatalyst grant with the Jenner Institute (total value £200,000) to develop a novel malaria vaccine. Subcontracted by Mologic to take part in a grant consortium led by DTRA (US Military) to develop a vaccine to Burkholderia. Total value £200,000 over four years. Made Company Secretary in 2010

2006-2009 Head of Scientific Operations (iQur Ltd.) Senior member of the executive team coordinating all aspects of therapeutic development reporting directly to the CEO and Board. Deputy to Chief Scientific Officer, running all R&D functions. Responsible for entire research portfolio. On joining the company, due to reservations about the breadth of topics undertaken, I redesigned the programmes to be more focused on product development. As a result of my strategic review, several small projects were put into hibernation and, more recently, the entire focus of the company has been reallocated into therapeutics. The vaccine portfolio was particularly attractive, but was suffering from a lack of direction. Wrote and submitted a successful grant to the TSB (formerly DTI) to lead a consortium of companies worth over £1.1m. Of this, some £450k was spent by iQur. Part of this plan involved finding and negotiating with a CMO, which was successfully achieved, leading to our current programme of product development. The role played in refocusing this project has been critical in the allocation of funds and direction of the company. Wrote and was awarded a second TSB grant in May 2009 for a consortium worth £1.2m. Members include UCL and Mologic Ltd. Responsible for the scientific development of our vaccine platform and its commercial development, including manufacture. Ran team based in Leeds University, where we had a satellite laboratory. This was managed both locally and remotely. Moved them from a shared University lab into a Bioincubator on site. Responsible for all negotiation and set up of this facility. Moved the Therapeutics division to London and successfully opened another facility in UCL. Again, was responsible for sourcing, negotiating and equipping this unit. Recently relocated the group again to LBIC due to the closure of UCL's Windeyer building. Again, was responsible for all aspects of this. Wrote, and was granted, a Home Office project licence to allow us to carry out in vivo work within the company. This was a major cost saving and has massively improved

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throughput. Running a generic drug application to the EMEA in concert with a US manufacturer. Using regulatory skills developed at Onyvax, project managed this application for nearly two years. This included multiple interactions with regulatory authorities and two visits to EMEA. Unfortunately, our application was ultimately unsuccessful, for a number of technical reasons, however the experience was invaluable. Ran a project for the development of a novel NCE for hepatitis, based on a glycosylation of ribavirin. This project was run entirely virtually and used both chemical synthesis companies and CROs to carry out the work. The project was put into hibernation at the pre-clinical stage due to lack of funding. Project managed budgets for each therapeutic projects and been responsible for design, ensuring results are produced on time/budget, negotiation with outsource suppliers and filing patents as a matter of course. Responsible for the entire patent portfolio of the company. Carry out the majority of business development functions within the company by presenting and meeting with third parties.

2003-2006 Head of Research (Onyvax Ltd.)

Onyvax was a biotechnology company based at St. George’s Hospital Medical School.

The company is developing a whole-cell allogeneic vaccine against prostate cancer, as well as several other common cancers. Completed both Phase I and Phase II human trials in prostate cancer with encouraging clinical responses.

Member of the executive team Responsible for entire research budget. Main fundraising in 2000 was £10m. Budget for research was approximately £250K pa, plus a further £150K for immunological monitoring. Developed all in vivo models. Wrote, and was granted, a Home Office project licence to allow us to carry out in vivo work within the company, thereby saving considerable amounts of outsourced money. Intimately involved with regulatory filings to MHRA and FDA for clinical trials. Attended scientific advice meeting at EMEA and designed and wrote a reply to scientific questions asked after our CTA filing. This was instrumental in ensuring that clinical Phase II began successfully. Also participated in FDA pre-IND meeting. My group developed and ran all of the immunological testing used in both the Phase IIa and IIb clinical trial of ONYY-P1. Experience included liaison with clinical colleagues and regulators. Lead company participant in one Framework V EU grant (approx value €1m) and a Framework V EU programme grant (approx value €10m). All research activities were presented to the Scientific Advisory Board (SAB) on an annual and ad hoc basis. I led these meetings and was responsible for regular liaison with the SAB. Experience of running a large group. My research group had twelve active scientists at its height. Developed a new method for screening cancer patients' immune responses in collaboration with Nottingham Trent University. Published and presented extensively Carried out preliminary due diligence on several potential opportunities. Reason for leaving was due to financial constraints on the research budget. In close collaboration with the CEO, we developed a strategy to move the entire company over to product development, reallocate/let go my staff and then move on myself. After leaving, I remained a consultant for Onyvax and fully supported the reallocation of resources plan. This was clearly the correct business decision at the time.

1999-2003 Head of Immunology (Onyvax Ltd.)

Development of the vaccine by using both animal models and clinical samples. Our studies included both clinical and preclinical projects. My immunology group ranged in ability, from technicians to post-doctoral scientists. We had to manage our resources such

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that we could carry out both fundamental research and clinical trials. This work was to be extremely focused in order to ensure that we can bring a product to market as quickly as possible. Member of the Research & Development committee and gave presentations to investors and collaborators. Presented at several international conferences and was actively engaged in a publication program, thus raising the profile of the company. Role in business development, in which I acted as an expert reviewing due diligence packages and meeting potential collaborators. In the course of the company development I have was been instrumental in implementing complete documentation and moving towards GLP/GMP. Furthermore, I gained valuable skills when we successfully applied for a phase II CTX trial. This involved writing complete documentation for our product and compiling reports to answer specific questions posed by the regulators. My group played a fundamental role in running trials by both designing and deploying the vast majority of assays that we employed. Integral in defining the product by devising and developing analysis and potency assays for use in regulatory submissions.

Business skills Project management: extensive knowledge of writing and implementing project plans (MS Project). Regularly use these to build company budgets by extracting costs directly from the plan. Ran projects with several CRO and CMOs. These included GMP manufacture with Eden Biodesign and 3P Pharmaceuticals. Budget management: intimately linked with project planning is ensuring that budgets are adhered to and forecasts accurate. Worked in close collaboration with the CFO to maintain a tight control of corporate spend. Latterly, took on the role of financial modeling personally. People management: I have managed a large 10+ research team and also smaller units. Interaction with external parties is also a critical skill since this allows for successful negotiation and acts as the public face of the company. Presentations: From both academic and commercial backgrounds I have extensive presentation skills. Negotiation: I have played a role in a number of major negotiations for both of my companies. At Onyvax this included developing partnerships, whilst at iQur this included successful sale of our generic drug business to an American independent. Scientific assessment/due diligence: My experience has often been called upon to examine the commercial opportunities which arise from time to time. Examples of this include patent assessment, development potential and market assessment for a variety of new molecules and first pass due diligence on potential partners. Market assessment: I keep myself informed of major developments in the bio/pharma space by scanning websites and reading professional publications. Using such tools, I developed and implemented iQur’s tandem-core technology within the hepatitis sphere. Business development: Regular attendance at a variety of business partnering events ensures that our company name is well known and we are actively searching for partners. In particular, I have been active in both the BIA and BioProcessUK. R&D management: My broad level of experience has allowed me to be Research Director for Onyvax and also to manage both R&D for iQur. My academic and industrial experience is particularly relevant for research management, however, my industrial experience has allowed me to build development strategies for both companies. Regulatory affairs: Closely involved in EMEA application for Onyvax Phase II clinical trial, specifically defined and developed immunological testing and answered regulatory questions relating to vaccine safety. Participated in meetings with regulators in several countries. Ran iQur's application for a generic MA, using Denmark as rapporteur and five other countries as applicants. Application was discussed at both CMDh and CHMP (twice). Part of the team for all meetings. Product development: Development is a skill that can only really be gained with

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industrial experience and I have carried out this role at Onyvax and, more latterly, at iQur. This has included designing a viable development pathway, finding external contractors (for GxP), negotiation and implementation of plans. Grant writing: Throughout my career I have been involved in grant writing and partnerships. At Onyvax his included co-writing and joining two EU FP5 grants. At iQur I wrote and led two TSB collaborative research grants with an overall value of £2.3 million, as well as writing and chairing the FLUTCORE FP7 programme worth €4.6m. Fund raising: I have played a pivotal role in both writing and designing presentations for fund-raising proposals for both companies. My budgets have been the basis of such presentations at iQur and I have met and presented to our existing investors. Ran several internal funding rounds including issue of convertible notes and shares. As Company Secretary was responsible for the issue of these.

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Academic Experience 1996-1998 Postdoctoral Scientist (Edward Jenner Institute for Vaccine Research)

The Edward Jenner Institute for Vaccine Research (Compton, Nr. Newbury, Berkshire)

was set up as a collaborative initiative between UK government and GSK to fund basic research into novel mechanisms of vaccine development. It was built in the grounds of Institute of Animal Health in 1997.

Post-doctoral position of senior scientist, examining the role of dendritic cells in the initiation of the immune response. The dendritic cell has been shown to be a potent initiator of immune responses and our work focused on the potential interaction between the innate and adaptive immune responses. We demonstrated the ability to mature dendritic cells, via innate immune molecules, to yield a variety of phenotypes and consequently to alter the outcome of the resulting immune response. This has obvious implications for vaccine development. The Jenner Institute itself was relatively new organisation when I joined, with core funding from GSK. This allowed us to equip ourselves with outstanding hardware and has given me the opportunity to gain experience in a wide variety of techniques. Furthermore, the nascent nature of the laboratories made it necessary for me to become involved in lab design, IT provision and management. At the Jenner Institute, my role diversified from simply working as a bench scientist, to one of a junior manager. Given the unique nature of the Institute, I had to help design and specify our laboratories and equipment, and had to adapt my skills to a number of challenging new roles. Some of these projects included the design and deployment of a new computer network, which employed a number of different techniques, including, negotiation, time management and management of change.

1993-1996 Postdoctoral Scientist (Institute for Animal Health)

The Institute for Animal Health (Compton, Nr. Newbury, Berkshire) was originally a

government funded establishment which became part of the BBSRC portfolio in 1994. Research is primarily aimed at food production animals, although some studies into sporting animals were also carried out.

Post-doctoral position (Higher Scientific Officer) investigating the cytotoxic T-lymphocyte response present in horses to Equine Herpes Virus I (EHV-I). Development of a cytotoxic T-cell (CTL) assay to detect the cellular immune response after experimental challenge. We progressed to examining the class I MHC restriction of this killing by making use of a specially in-bred line of ponies. Furthermore, class I genes were isolated in the laboratory and transfected into mouse cells in an attempt to identify the exact class I restricting elements involved in the mediation of killing. Some work was done to examine the possibility of cloning T-cells by use of limiting dilution. Initial experiments indicated that this was possible since T-cells were generated that kill for up to three weeks in culture. In conjunction with peptide motif studies we hoped to identify antigenic positions in the EHV-1 genome which could be used to develop a novel vaccine. Responsibilities included developing the CTL assay, examining restimulation protocols and to help in the peptide elution studies. Furthermore, managed the equine in-breeding program and developed infection strategies for our animals. Played a small role in supervision of technicians and Ph.D. students. As an additional project spent some time examining class I MHC levels in infected cells and postulated that these levels decreased during infection and may lead to evasion of immunity.

1992-1993 Postdoctoral Scientist (BJRU)

Bone & Joint Research Unit (Royal London Hospital) was an Arthritis and Rheumatism

(ARC) funded establishment focused on the development of novel therapies for a variety of arthritic

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conditions. Post-doctoral appointment to continue studies begun during Ph.D. study. In particular, the prevalence of free thiol in patients with AS was assessed, as was the effect of thiol derivatisation on peptide restriction. The latter experiments involved peptide assembly assays using the T2-B27 transfectant and peptide derived from HIV.

Education 1975-1985 Regent House Grammar School (Co.Down, N.Ireland) 1983 9 GCE O-Levels 1984 1 GCE O-Level 1985-1986 Belfast College of Technology 1986 3 GCE A-Levels 1986-1989 Queen Mary College (University of London) 1989 Upper second class Honours degree in Biochemistry.

1989-1992 Bone and Joint Research Unit (London Hospital)

Study for Ph.D. in Biochemistry/Immunology concentrating on the association of the class I histocompatibility antigen B27 with several arthropathies, most notably ankylosing spondylitis (AS).

Work included isolation of HLA-B27 by immunoprecipitation, followed by isoelectric focusing and the demonstration of the presence of a reactive thiol in the antigen binding cleft. This was accomplished by the addition of the charged thiol binding reagent monobromotrimethylammonium bimane which produced extra bands in the presence of free thiol. Hence, we proposed that the function of HLA-B27 may be altered either as a result of altered peptide restriction or T-cell recognition.

Led to the proposition that the chemical reactivity of HLA-B27 may be attributed to an exceptionally reactive thiol located at cysteine 67. Interestingly, these data have subsequently been validated by more recent authors.

Majority of this project was carried out on established cell lines and from a bank of AS patient samples collected from both at the London Hospital and Winchester General Infirmary by clinical colleagues.

Responsibilities included the development of new assay protocols for B27 related diseases, routine tissue culture, ordering and maintaining chemical and consumable stocks for the group and laboratory supervision of project students from Queen Mary and Westfield College.

1993 Ph.D. in Immunology (University of London)

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Interests I enjoy cycling and cross-country walking in the Oxfordshire countryside. This also has the added advantage of allowing me to enjoy some of the excellent eating and drinking establishments in the area. I enjoy cooking and socialising with friends. I spend a considerable amount of time travelling and hence my spare time is extremely precious. I particularly enjoy spending as much time as possible with my young family. My extensive knowledge of computer technology has allowed be to build my own machines and repair some for friends; a pastime which I find both rewarding and useful. Professional Societies British Society of Immunology Fellow of Royal Society of Biology

Editorships & Lectureships Visiting Research Lecturer University of Surrey (2007-2012) Honorary Lecturer UCL (2006-2016) Honorary Lecturer Royal Veterinary College (2014-) Section Editor for Current Opinion in Molecular Therapeutics (2007-2010) Lecturer on Oxford University’s Human and Veterinary Vaccinology course (2009-)

Personal Details

Date of Birth: 20th November 1966 Nationality: British Sex: Male Marital Status: Married Place of Birth: Belfast Children: 3 Address: 1 Drayton Road,

Sutton Courtenay, OXON,

OX14 4AJ. Telephone: +44 1235-848-102 (home) +44 7710-385-105 (mobile) E-mail: mike@whelan.org.uk (home)

Referees On request

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Appendix I

Scientific Publications

1. McLean IL, Macey M, Lowdell M, Badakere S, Whelan M, Perrett D, Archer J (1992) Sulphydryl reactivity of the HLA-B27 epitope: accessibility of the free cysteine studied by flow cytometry.

Annals of Rheumatic Diseases 51: 456-460.

2. Archer JR, Whelan MA, Badakere SS, McLean IL, Archer IVJ, Winrow VR (1990) Effect of a free sulphydryl group on the expression of HLA-B27 specificity.

Scand. J. Rheumatol. Supple. 87: 44-50

3. Grootveld MG, Claxson WD, Naughton D, Whelan MA, Furst A & Blake DR (1991) Influence of an intravenous dose of aurothiomalate on the status of low-molecular-mass endogenous metabolites in blood plasma: A proton nuclear magnetic resonance (NMR) study.

Agents and Actions Suppl. 32: 65-69

4. McLean IL, Archer JR & Whelan MA (1991) HLA-B27 subtypes. Lancet 337: 927

5. Whelan MA & Archer JR (1993) Chemical reactivity of an HLA-B27 thiol group. Eur. J. Immunol. 23: 3278-3285

6. Naughton D, Whelan M, Smith EC, Williams R, Blake DR & Grootveld M (1993) An investigation of the abnormal metabolic status of synovial fluid from patients with rheumatoid arthritis by high field proton nuclear magnetic resonance spectrosopy.

FEBS letters 317: 135-138

7. Archer JR & Whelan MA (1993) HLA-B27 and effector T cells: arthritogenic peptide or arthritogenic antigen?

Lancet 342: 1307

8. Siedek EM, Whelan M, Edington N and Hamblin A. (1999) Equine herpesvirus type 1 infects dendritic cells in vitro: stimulation of T lymphocyte proliferation and cytotoxicity by infected dendritic cells.

Veterinary Immunology and Immunopathology 67: 17-32.

9. Whelan M, Harnett MM, Houston KM, Patel V, Harnett W & Rigley KP (2000) A filarial nematode-secreted product signals dendritic cells to acquire a phenotype that drives development of Th2 cells.

J Immunol. 164(12): 6453-60

10. Eaton JD, Perry MJA, Nicholson S Guckian M, Russell N, Whelan M & Kirby RS (2002) Allogeneic whole cell cancer vaccine: a phase I/II study in men with hormone refractory prostate cancer.

BJU International 89: 19-26

11. Ward S, Casey D, Labarthe M-C, Whelan M, Dalgleish A, Pandha H & Todryk S. (2002) Immunotherapeutic potential of whole tumour cells

Cancer Immunology and Immunotherapy 51: 351-357

12. Havranek E, Pandha H, Greenhalge R, Whelan M & Dalgleish A. (2002) Advances in prostate cancer immunotherapy.

Surgical Oncology 1-2: 35-45

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13. Whelan JA, Russell N & Whelan MA. (2003) A method for the absolute quantification of cDNA using real-time PCR.

Journal of Immunological Methods 278(1-2): 261-269.

14. Whelan M, Whelan J, Russell N & Dalgleish A. (2003) Cancer immunotherapy: an embarrassment of riches?

Drug Discovery Today. 8(6): 253-258.

15. Angus Dalgleish & Mike Whelan (2002) Tumor cells- poacher turned gamekeeper? Current Drug Discovery Nov: 25-28.

16. Rollier C, Depla E, Drexhage JAR, Verschoor EJ, Verstrepen BE, Fatmi A, Brinster C, Fournillier A, Whelan JA, Whelan M, Jacobs D, Maertens G, Inshauspe G & Heeney JL (2004). Control of heterologous Hepatitis C virus infection in chimpanzees correlates with the quality of vaccine-induced peripheral T-helper immune response

Journal of Virology. 78(1): 187-196.

17. Zal B, Kaski JC, Arno G, Akiyu JP, Xu Q, Cole D, Whelan M, Russell N, Madrigal A, Dodi IA, Baboonian C (2004). Heat shock protein 60 reactive CD4+ CD28 null T cells in patients with acute coronary syndromes.

Circulation. 109(10): 1230-1235.

18. Charoenvit Y, Goal N, Whelan M, Rosenthal KS & Zimmerman DH (2004). CEL-1000- a peptide with adjuvant activity for Th1 immune responses.

Vaccine 22(19): 2368-2373.

19. Whelan MA (2004). Immunotherapy in anticancer responses. Current Opinion in Molecular Therapeutics. 6(1): 8-9.

20. Lundqvist A, Palmborg A, Bidla G, Whelan M & Pisa P (2004) Allogeneic tumor/dendritic cell vaccines for generation of broad prostate cancer T-cell responses.

Medical Oncology. 21(2): 155-165

21. Pandha HS, John RJ, Hutchinson J, James N, Whelan M, Corbishley C & Dalgleish AG (2004). Dendritic cell immunotherapy for urological cancers using cryopreserved allogeneic tumour lysate-pulsed cells: a phase I/II study.

BJU Int. 94(3): 412-418.

22. Havranek E, Howell WM, Fussell HM, Whelan JA, Whelan MA, Pandha HS. An interleukin-10 promoter polymorphism may influence tumor development in renal cell carcinoma.

J Urol. 2005 173(3): 709-12.

23. Dalgleish AG & Whelan MA (2005). Novel immunotherapeutic approaches to prostate cancer. Current Opinion in Molecular Therapeutics 7(1): 30-34.

24. Michael A, Ball GR, Quatan N, Wushishi F, Russell N, Whelan J, Chakraborty P, Leader D, Whelan MA & Pandha H (2005). A prostate cancer allogeneic cell vaccine (ONY-P1) induces delayed disease progression in hormone resistant patients and correlates with immunological parameters.

Clincal Cancer Research 11(12): 4469-4478.

25. Labarthe M-C, Halanek N, Birchall L, Russell N, Desel C, Todryk S, Peters MJ, Lucas A, Falkenberg FW, Dalgleish AG, Whelan MA & Ward SJ (2006). The biological effects of syngeneic and allogeneic cytokine-expressing prophylactic whole cell vaccines and the influence of irradiation in a murine melanoma model.

Cancer Immunology & Immunotherapy 55(3): 277-288.

26. Dalgleish AG & Whelan MA. (2006) Cancer vaccines as a therapeutic modality; the long trek.

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Cancer Immunology & Immunotherapy 55(8):1025-1032.

27. Whelan M, Balls G, Beattie C & Dalgleish A. (2006) Biomarkers for the development of cancer vaccines.

Personalized Medicine 3(1): 79-88.

28. Copier J, Whelan M & Dalgleish A. (2006) Biomarkers for the development of cancer vaccines. Molecular Diagnostics & Therapeutics 10(6): 337-343.

29. Rollier CS, Paranhos-Baccala G, Verschoor EJ, Verstrepen BE, Drexhage JA, Fagrouch Z, Berland JL, Komurian-Pradel F, Duverger B, Himoudi N, Staib C, Meyr M, Whelan M, Whelan JA, Adams VA, Larrea E, Riezu JI, Lasarte JJ, Bartosch B, Cosset FL, Spaan WJ, Diepolder HM, Pape GR, Sutter G, Inchauspe G, Heeney JL (2007) Vaccine-induced early control of hepatitis C virus infection in chimpanzees fails to impact on hepatic PD-1 and chronicity.

Hepatology 45(3): 602-613.

30. Morse MA & Whelan M (2007). Learning from each other: Applying lessons from anti-tumor, anti-pathogen and anti-toxin immunotherapy.

Current Opinion in Molecular Therapeutics. 9(1): 10-11.

31. Labarthe MC, Theocharous P, Russell N, Todryk S, Bangma C, Thraves P, Dalgleish AG, Whelan MA (2008). A novel murine model of allogeneic vaccination against prostate cancer. Cancer Immunol Immunother. 57(4): 453-65.

32. Havranek EG, Labarthe M-C, Ward S, Anderson CJ , Whelan MA & Pandha H (2008). A novel

murine model of allogeneic vaccination against renal cancer. BJU International 101(9):1165-9.

33. Whelan M & Morse M (2008). When is an adjuvant not an adjuvant? Current Opinion in Molecular Therapeutics. 10(1): 8-9.

34. MacDonald AJ, Libri NA, Lustigman S, Barker SJ, Whelan MA, Semper AE, Rosenberg WM. (2008). A novel, helminth-derived immunostimulant enhances human recall responses to hepatitis C virus and tetanus toxoid and is dependent on CD56+ cells for its action. Clin Exp Immunol. 152(2): 265-73.

35. Michael A Morse & Michael Whelan (2009). Turning lemons into lemonade: learning from negative studies in cancer immunotherapy.

Current Opinion in Molecular Therapeutics. 11(1): 10-12.

36. Michael A Morse & Michael Whelan (2010). A year of successful cancer vaccines points to a way forward.

Current Opinion in Molecular Therapeutics. 12(1): 10-12.

37. Macdonald DC, Singh H, Whelan MA, Escors D, Arce F, Bottoms SE, Barclay WS, Maini M, Collins MK, Rosenberg WM (2014). Harnessing alveolar macrophages for sustained mucosal T-cell recall confers long-term protection to mice against lethal influenza challenge without clinical disease. Mucosal Immunol. 7(1): 89-100.

38. Peyret, H, Gehin A, Thuenemann EC, Blond D, El-Turabi A, Beales L, Clarke D, Gilbert RJ, Fry EE, Stuart DI, Holmes K, Stonehouse NJ, Whelan M, Rosenberg W, Lomonossoff GP & Rowlands, D. (2015). Tandem fusion of hepatitis B core antigen allows assembly of virus-like particles in bacteria and plants with enhanced capacity to accommodate foreign proteins. PLoS ONE 10(4):e0120751. doi: 10.1371/journal.pone.0120751

39. Holmes K, Shepherd DA, Ashcroft AE, Whelan M, Rowlands DJ & Stonehouse NJ. (2015) Assembly pathway of hepatitis B core virus-like particles from genetically fused dimers.

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Journal of Biological Chemistry. doi: 10.1074/jbc.M114.622035.

Patents EP1495136A2: Nucleic Acid Quantification Quantifying a target nucleic acid in a sample comprises accurately quantifying the total amount of nucleic acid in the sample using fluorescence Application number EP2003000704733 EP1485466A2: Methods for treating diseases or conditions with peptide constructs. Use of peptide G or derG directing a CD4-related T helper cell response, for treating cancer, autoimmune or transplant conditions, infectious conditions or allergies caused by foreign eukaryotic organisms or parasitic organisms Application number EP2003000732026 US2013171182 (A1): Influenza vaccine. A novel influenza vaccine based on tandem core technology Application number US201013503317 WO2015124919 (A1): Vaccines based on hepatitis B core antigens. Conjugate vaccines based on tandem core VLP Application number WO2015GB50460

Meeting Abstracts The use of thiol blocking agents on B27 positive cells. Whelan MA, Badakere SS & Archer JR European Federation Of Immunological Societies, Edinburgh, September 1990 Utilisation of 500MHz NMR spectroscopy to elucidate lymphocyte metabolism. Whelan MA, Grootveld M, Naughton D & Archer JR European Federation Of Immunological Societies, Edinburgh, September 1990 Lymphocyte metabolism as examined by 500MHz NMR spectroscopy. Whelan MA, Grootveld M, Naughton D & Archer JR Int. J. Microcirc: Clin. & Exp. 9(1) 36 XVI European conference on microcirculation, Zurich, August 1990 Modifications in the metabolic profile of synovial fluid (SF) from patients with inflammatory synovitis by excercise of the inflamed joint: a proton NMR study. Grootveld M, Whelan M, Farrell A, Smith E, Henderson E, Blake DR British Society for Rheumatology, London, September 1990 Anaerobic metabolism: Elucidation of its role in rheumatoid and osteo-arthritis by high field nuclear magnetic resonance (NMR) spectroscopy. Naughton D, Whelan M, Grootveld M, Parkes H & Blake DR British J. Rheumatol. 30 32 British Society for Rheumatology, London, September 1991 New metabolic markers for arthritic disease etiology. Naughton DP, Whelan MA, Grootveld M & Blake DR Arthritis and Rheumatism 34(9) S143 2 American College of Rheumatology, Boston, November 1991 Demonstration of a reactive thiol on the surface of HLA-B27 positive cells. Whelan MA & Archer JR British Society for Immunology, London, October 1991

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Alteration of the tertiary structure of HLA-B27 affects the reactivity of cysteine 67. Michael A. Whelan & James R. Archer International Conference on Immunology, Budapest, August 1992 Chemical reactivity of the HLA-B27 molecule. Michael A. Whelan & James R. Archer 56th meeting American College of Rheumatology, Atlanta, October 1992. Immunoprecipitation of HLA-B27 with W6/32 reveals the presence of a unique reactive thiol moiety on a closely associated protein. MA Whelan & JR Archer European Journal of Immunogenetics 20(6) 472 British Society of Histocompatibility and Immunogenetics, Belfast, January 1994. Use of lucifer yellow iodoacetamide with flow cytometry to measure cell surface thiol. JR Archer, MA Whelan, MM Macey & SS Badakere. Biochemical Society Meeting (652), University of Kent, Canterbury, September 1994. Thiol reactions of maturing HLA-B27 molecules. JR Archer & MA Whelan. Biochemical Society Meeting (652), University of Kent, Canterbury, September 1994. MHC downregulation by equine herpes virus. MA Whelan, SA Ellis & WI Morrison. European Journal of Immunogenetics 23(1) 77. British Society of Histocompatibility and Immunogenetics, Liverpool, January 1996. Modulation of T cell function by dendritic cells. Mike Whelan, Clair Brammer & Kevin Rigley. British Society of Immunology, Brighton, December 1997. Reactivity of HLA-B27 thiol in controls and patients with ankylosing spondylitis or psoriasis. VS Naik, MA Whelan, JR Archer British Society for Rheumatology, Brighton, April 1998 Br J Rheumatol Supplement 1; 37 (1998) 41 Comparison of thiol reactivity of HLA-B27 in cells from diseased and healthy individuals V. S. Naik, M. A. Whelan and J. R. Archer British Society of Histocompatibility and Immunogenetics, City University, London March 25-27, 1998 Eur. J. Immunogenetics 25 49. Ex vivo labelling of chicken spleen lymphocytes with fluorescent dyes for studying cell migration in vivo. B. Baaten, CJ Rothwell, L Vervelde, M Whelan, TF Davison. Avian Immunology Research Group, Turku, Finland, August 1998. Caveolae mediated uptake of Respiratory Syncytial Virus by dendritic cells. D Werling, RA Collins, M Whelan and CJ Howard. Veterinary Immunology meeting, Dehli, India, November 1998. Measurement of antigen-specific proliferation in cancer patients Russell N Labarthe M-C & Whelan MA EFIS 2000, 14th European Immunology Meeting, Poznan, Poland 23-27 September 2000 Immunology Letters 73:2,3 125 An in vivo model of allogeneic vaccine kinetics Labarthe M-C, Thraves P & Whelan MA EFIS 2000, 14th European Immunology Meeting, Poznan, Poland 23-27 September 2000 Immunology Letters 73:2,3 279

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An in vivo model of allogeneic vaccine kinetics Labarthe M-C, Thraves P Dalgleish AG & Whelan MA Cancer Vaccines, Cancer Research Institute, New York, USA 2-4th October 2000 Dissection of the immune response to an allogeneic melanoma model in mice Labarthe M-C, Dalgleish AG & Whelan MA Cancer Vaccines, Cancer Research Institute, New York, USA 2-4th October 2000 Allogeneic Whole Cell Vaccine Trial; a Phase I/II Study in Men with Hormone Refractory Prostate Cancer Eaton JD, Perry MJA, Kirby RS, Whelan MA,Russell N, Guckain M, Labarthe M-C & Dalgleish AG Cancer Vaccines, Cancer Research Institute, New York, USA 2-4th October 2000 Cross-protective CTL are generated after allogeneic vaccination in vivo in two models of mouse melanoma Labathe M-C, Dalgleish AG & Whelan MA British Society of Immunology, Harrogate, UK 5-8th December 2000 A novel murine model of allogeneic vaccination against prostate cancer Labarthe M-C, Thraves P, Theocharous P, Dalgleish AG & Whelan MA American Association Of Immunology, New Orleans, USA 21-24th April 2002 Examination of the immune response in murine model of allogeneic vaccination against prostate cancer Labarthe M-C, Thraves P, Theocharous P, Dalgleish AG & Whelan MA PIVAC 2, Nottingham, UK 18-21st July 2002 Preliminary results of a Phase I/II study to determine the safety, tolerability and efficacy of the allogeneic whole cell vaccine in patients with hormone refractory prostate cancer. Michael A, Quatan N, Whelan MA, Kendall A. & Pandha H American Association of Clinical Oncologists, Chicago, USA 31st May-3rd June 2003 A histopathological review of renal cell cancer. Havranek EG, Corbishley C, Shah D, Whelan M, Pandha H & Anderson C British Association of Urological Surgeons, Manchester, UK 3rd March 2003 Interleukin 10 polymorphism may influence renal cell cancer development. Havranek EG, Whelan M, Whelan J, Dalgleish A, Anderson C & Pandha H British Association of Urological Surgeons, Manchester, UK 3rd March 2003 Interleukin 10 polymorphism may be associated with renal cell cancer. Havranek EG, Whelan M, Whelan J, Dalgleish A, Anderson C & Pandha H American Urology Association, Chicago, USA 21st April 2003 Allogeneic whole tumor cell vaccination for prostate cancer: a clinical trial using real-time cytokine analysis and correlation with clinical parameters. Whelan M.A., Russell N., Whelan J., Wushishi F. Michael A. & Pandha H American Association of Immunology, Denver, USA 1st-5th May 2003

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In vivo kinetics of whole cell anti-cancer vaccine in a murine melanoma model Labarthe M-C, Dalgleish AG & Whelan MA ISCT, Phoenix, USA 28th-31st May 2003 A novel murine C57 protection model as an allogeneic whole cell vaccine against renal cell carcinoma. Havranek E, Desel C, Pandha H, Dalgeish A, Anderson C & Whelan M. Progress in vaccines against cancer (PIVAC), Oxford, UK. 30th August-1st September 2003. Whole cell allogeneic vaccination in hormone-relapsed prostate cancer leads to significant slowing of PSA release and immunological responses. Pandha H, Michael A, Quatan N, Russelll N, Whelan J, Wushishi F & Whelan MA. World Urology Congress, London, UK 24th-26th September 2003 Evidence of immune system activation after administration of a whole cell allogeneic vaccine: a phase

II trial in prostate cancer Whelan MA, Michael A, Quatan N, Russell N, Whelan J, Wushishi F & Pandha H Cancer Vaccines, Cancer Research Institute, New York, USA 1st-3rd October 2003 Use of Artificial Neural Network analysis to predict responders versus non-responders in a clinical trial using a whole cell allogeneic vaccine for hormone-relapsed prostate cancer. Balls G., Michael A., Quatan N., Wushishi F., Russell N., Whelan J., Whelan M.A. & Pandha H. AACR, Florida, USA 27th-31st March 2004 Allogeneic whole cell vaccination significantly delays disease progression in hormone-relapsed prostate cancer: final data from a Phase II study Michael A., Quatan N., Wushishi F., Russell N., Whelan J., Whelan M.A. & Pandha H. EORTC, Geneva, Switzerland 28th September-1st October 2004. Multi-parametric immunological data analysis correlates with clinical response in a whole cell allogeneic vaccine trial for prostate cancer Balls G, Michael A., Quatan N., Wushishi F., Russell N., Whelan J., Pandha H. & Whelan M.A. PIVAC 4, Freudenstadt-Lauterbad, Germany 22nd-25th September 2004 Artificial Neural Network analysis correlates immunological profile and clinical outcome in a Phase II trial using a whole cell allogeneic vaccine for hormone-relapsed prostate cancer. Balls G., Michael A., Quatan N., Wushishi F., Russell N., Whelan J., Pandha H. & Whelan M.A. Prostate Cancer Foundation, Lake Tahoe, Nevada, USA 8th-11th July 2004. Clinical and immunological responses differ in metastatic and non-metastatic hormone resistant prostate cancer patients vaccinated with ONYVAX-P Balls G., Michael A., Wushishi F, Beattie C, Whelan MA & Pandha HS NCI Molecular Markers, Washington, USA. 20th-21st September 2005 A dual insert Hepatitis B tandem core vaccine elicits strong HBV immune responses and simultaneously confers protective immunity in an influenza model. Mike Whelan, Aadil El-Turabi, Lucy Beales, Sophie Maucourant & William M. Rosenberg AASLD, Boston, USA 30th October 2010

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Lentiviral vectors co-expressing hepatitis B core and vFLIP induce potent CD8 T-cell and antibody responses in HLA-A2 transgenic mice Doug MacDonald, Mike Whelan & William M. Rosenberg AASLD, Boston, USA 30th October 2010

Oral Presentations Syntex rheumatology competition March 5th 1991 HLA-B27, thiols and arthritis East London Rheumatology Club September 12th 1991 Chemical modifications to HLA-B27 and their possible role in arthritis British Society for Immunology October 16th 1991 Demonstration of a reactive thiol on the surface of HLA-B27 positive cells 8th International Congress on Immunology August 28th 1992 Alteration of the tertiary structure of HLA-B27 affects the reactivity of cysteine 67. British Society for Histocompatibility and Immunogenetics January 6th 1994 Chemical reactivity of HLA-B27 and associated molecules. Equine Virology Research Foundation 19th October 1994 Cellular responses to Equine Herpes Virus-1 (EHV-1) Equine Virology Research Foundation 17th October 1995 Examination of the cytotoxic T-lymphocyte response to Equine Herpes Virus-1 in an MHC-defined herd of Welsh mountain ponies. Equine Virology Research Foundation 21st October 1996 Further studies on the CTL response to EHV-1. British Society for Histocompatibility and Immunogenetics January 9th 1996 MHC downregulation by equine herpes virus. Institute for Animal Health Annual Science Review 26th November 1997 Taqman chemistry and applications. TaqMan users group, Cambridge 4th March 1998 TaqMan probe and primer design for cytokine detection TaqMan Science Review, London 29th September 1998 TaqMan chemistry and cytokine measurement EFIS 2000, 14th European Immunology Meeting, Poznan, Poland

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23-27 September 2000 Measurement of antigen-specific proliferation in cancer patients Becton-Dickinson Users Group, Oxford, UK 1st-2nd October 2002 Examination of immunological responses in a clinical trial of whole cell vaccine to prostate cancer. Cancer Vaccines, Boston, USA 14th-15th April 2003 Monitoring immunological responses in an allogeneic whole cell vaccine clinical trial. New Technologies in Cytokine Detection 27th June 2003, London, UK Cytokine detection by quantitative PCR and cytometric bead array. British Society for Cancer Research 3rd July 2003, Bournemouth, UK Monitoring of immunological changes after administration of a whole cell allogeneic prostate cancer vaccine. British Association: Festival of Science 8th September 2003, University of Salford, UK. Using the immune system to combat cancer. Progress in vaccines against cancer (PIVAC) 1st September 2003, Oxford, UK. Measuring immunological activation after whole cell allogeneic vaccination in a phase II clinical trial for prostate cancer. Royal Society of Medicine, Tumour Immunotherapy. 10th May 2004, London, UK Update on Onyvax ONY-P1 clinical trial Robert Baldwin Tumour Immunology Symposium 30th June 2005, Nottingham, UK Cancer vaccines: the long trek. Progress in vaccines against cancer (PIVAC) 20th-21st September 2005, Athens Greece Immunological monitoring for cancer vaccines. BioTrinity 28th March 2007, Oxford UK Development of tandem-core based vaccines BioProcess UK 28th November 2007, Cardiff UK Commercial development of tandem-core based vaccines Vaccines Europe 17th November 2009, Brussels Belgium Development and production of tandem core virus like particles Vaccines Europe 20th October 2011, Berlin, Germany Bioprocessing of tandem core virus like particles One Nucleus: Infectious Diseases & Vaccines 17th May 2012, Clare College, Cambridge, UK Utilising Tandem Core constructs to enhance immune responses.

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MRC Vaccine Meeting 5th February 2015, Dept. Business, Whitehall, London, UK Tandem core based vaccines and their development.

Grants Named postgraduate worker on Arthritis and Rheumatism grant to investigate the chemical changes in HLA-B27 associated with inflammation. Grant holders: Archer JR, Grootveld MG & Blake DR Grant no A039 1990. Named postdoctoral worker on Arthritis and Rheumatism grant to further investigate the chemical changes in HLA-B27. Grant holder: Archer JR Grant no A039 1993. Named postdoctoral worker on Horserace Betting Levy Board grant investigating the role of cytotoxic T-cells in Equine Herpes Virus-1 infections. Onyvax co-ordinator for LCVAC. This is a Framework 6 EU grant examining the feasibility of development for a whole cell vaccine for lung cancer. Commenced November 2004. Onyvax co-ordinator for ENACT. This is a Framework 6 EU Network of Excellence, focused on developing a central database of immunological responses to cancer vaccines. Commenced March 2005. Department of Trade & Industry Grant. Author and Project Manager for “Commercial development of tandem-core based vaccines for hepatitis”. This was a collaborative proposal between University of Leeds and three commercial companies, with a total value of £1.1 million. Technology Strategy Board Grant. Author and Project Manager for “Commercial manufacture of a novel dual hepatitis vaccine (hepatacore)”. This consortium was comprised of iQur, UCL Engineering and Mologic Ltd with a total value of £1.2 million. Technology Strategy Board Biocatalyst Fund. Author and Project Manager for “Development of a novel tandem core based malaria vaccine”. In collaboration with the Jenner Institute, the grant was worth £200,000. EU Framework 7 (FLUTCORE). Author, Project Manager and coordinator for “Development of a universal influenza vaccine based on the tandem vaccine platform”. This large, multicentre grant is worth a combined €4.6 million and has partners in Latvia, Spain, Luxembourg and the UK. All of the intellectual property comes to iQur.

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Appendix II

Scientific Techniques Flow-cytometry: Operation of a variety of flow cytometers, including the

Coulter EPICS-C, EPICS-MCL, Becton-Dickinson FACScan and FACScalibur. These machines use a variety of software including Consort-30, Lysis I/II and CellQuest. Developed a number of novel assays using FACS, including a whole blood proliferation assay for use in clinical trials. Use of fully quantitative flow cytometry. Involved in UK deployment of CBA assay and MAS automated system for BD-UK. Fully trained in cell sorting using the Cytomation MoFlo system.

Radioisotopes: 3H-thymidine cell proliferation assays, 35S-methionine protein labeling, 51Cr cytotoxicity tests.

Tissue culture: Routine culture of EBV-transformed B-cells, T2 transfectants, T/B-cell lines, 3T3 fibroblast lines, L-cell transfectants, human fibroblast lines, hybridomas, equine lines and tumour lines. Separation protocols from fresh patient samples and primary culture of both human and animal cells. Transformation and development of cels lines. Isolation and growth of human and murine dendritic cells.

Animal models: Home Office personal and project licence holder. Familiarity with a variety of tumour models including, melanomas in mice and prostate models in mice and rats. Developed several novel allogeneic tumour models. Use and development of novel transgenic models. Preparation of antisera to various antigens and the ultimate construction of a monoclonal antibody. Developed protocols for viral infection of equids. Influenza models in mice. Vaccine efficacy studies.

Cellular Immunology: Cytotoxic T-cell (CTL) assays and proliferation assays. Induction of CTL's by in vitro stimulation. Development of restimulation protocols. Extensive knowledge of dendritic cell culture from a variety of sources, including mouse, horse and human. Familiar with many cell separation protocols including Ficoll gradients and MACS cell sorting.

ELISA: Familiar with both standard ELISA technology and CELISA, in which cells are immobilised as the target antigen. Developed a number of assays for particular antigens as required. Use of ELISPOT for specific antigens, in particular ifn and IL10 production.

Confocal microscopy: Using the Leica TCS-NT system familiar with a variety of techniques, including Z-series, quantitation and filter optimisation, which allows the use of multiple simultaneous colours.

Molecular Biology: Preparation of DNA/RNA samples. Experience in mRNA preparation by use of Trizol and magnetic bead separation. Purification using DNAse I and assessing the quality of the product by gel, spectrophotometry and a novel fluormetric assay. Use of PCR for semi-quantitative mRNA levels and in TOPO cloning strategies. Running of both DNA and RNA gels in agarose and polyacrylamide. Conventional PCR and use of the Perkin-Elmer TaqMan 7700 system. Much of my experience has been in developing and selecting primer-probe sets and have

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been asked by Perkin-Elmer to act as a technical consultant on occasion. Developed unique absolute quantitation method for cytokine transcripts.

Electrophoresis: One dimensional isoelectric focusing of HLA, H2 and ELA antigens. Two-dimensional gels. SDS-PAGE and native-PAGE. Western blotting in both wet and semi-dry systems. Enhanced chemiluminescent detection on Western blots. Agarose immunodiffusion. Immunoprecipitation using Staphylococcus aureus and protein A or protein G.

Virology: Culture, infection and purification of Equine Herpes Virus (EHV-1). Use of plaque assay, immunohistochemistry PCR and FACS as methods of infectivity measurement. Infection protocols for a variety of cell types. Use of EBV to produce B-cell lines.

Image Analysis: Use of the STORM Phosphorimager for radioactive and fluorescent quantitation. Extensive knownledge of other image analysis packages, employing both scanning and CCD technology.

Affinity Chromatography: Used for routine purification of antibodies and antisera. Also used for the isolation of peptide pools from class I MHC molecules prior to HPLC separation and Edman degradation. Extensive use of FPLC (SEC and AEX) for VLP purification. HPLC assay development.

Spectrophotometry: Spectrophotometry and fluorimetry used for protein assays and for the development of novel cell surface thiol assays. Use in quantitation of mRNA samples before use in PCR.

NMR: Used to examine the metabolic status of rheumatoid joints and tissue culture cells.

Information Technology: Highly proficient using a variety of systems, including DOS, Windows 3.1, Windows95/98, WindowsNT/2000/XP/Vista/7/8/10, Macintosh and Linux systems. Excellent Microsoft Office skills, including Project. Some knowledge of Bioinformatics. Successfully deployed and managed the installation of a LAN at the Bone & Joint Research Unit, based on Novell Netware 4.0. Responsible of purchase of all hardware, its installation and the day to day management of users. Designed and deployed a WindowsNT based network at the Jenner Institute. Responsible for all software and hardware procurement, specifying network infrastructure and was acting network manager. Significant role in managing Onyvax network, in particular, building and servicing hardware. Developed database solution for iQur and designed an independent network. Webdesign for several internal projects including iqur.com and flutcore.eu. iQur network administrator.

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Appendix III

Courses Introduction to Management. BBSRC approved course September 12-14th 1995. Theory and Methods in PCR Perkin-Elmer course 9th December 1997. Module V Project Licence Holders Course Home Office, London 12-15th December 2000 MoFlo advanced users course DakoCytomation, Ely, Cambridgeshire 26th-28th October 2004 Good Clinical Laboratory Practice Madingley House Cambridge 4th-5th October 2005