Notice of General Meeting

21st April 2020

Clinical pipeline update, resolutions seeking shareholder authority to issue new ordinary shares for cash and approval of proposed option grant

London, New York 21 April 2020 – Tiziana Life Sciences plc (Nasdaq: TLSA / AIM: TILS) (the “Company” or “Tiziana”), the U.S. and U.K. biotechnology company that focuses on the discovery and development of novel molecules to treat human disease in oncology and immunology, today announces that it has convened a general meeting (the “GM”) to consider proposals to take increased authorities to allot shares; consider the replacement of share option awards and to adopt new articles of association. The GM will be held on Wednesday 6 May 2020, at 11:00 a.m.

Please note that arrangements for the GM are different from those of previous years. As we expect significant restrictions on personal movement to still be in place due to Covid-19, we are utilising provisions in our articles of association, and certain associated discretionary powers for the orderly conduct of meetings, to facilitate the holding of the meeting on an electronic platform. Accordingly, the GM will be an electronic meeting only. All voting at the resolutions at the GM will be conducted on a poll which means that you should submit your proxy (by post, email or online voting) as soon as possible. We ask that all question which shareholders wish to raise be submitted to in advance.

The platform that we will be using will allow shareholders the option to submit a separate poll card as they “exit” the electronic meeting but, to ease administration, we request that proxies be lodged in advance wherever possible.

Full details of the operation and arrangements for the GM are set out in the Notice of GM.

We are also taking the opportunity to adopt new articles of association to allow semi-virtual or hybrid meetings as we believe this may be a way to facilitate and enhance shareholder engagement at future meetings.

The full text of the Chairman’s letter is set out below:

Dear Shareholder,

I look forward to welcoming you at the Tiziana Life Sciences plc (the “Company” or “Tiziana“) General Meeting (“GM“), on 6 May 2020. The GM will start at 11.00 a.m.

About the Meeting process

In light of the ongoing Coronavirus pandemic and with a view to taking appropriate measures to safeguard its shareholders health and make this GM as safe and efficient as possible, the Company is invoking certain of the meetings provisions in the Companies Act 2006 and its articles of association (the “Articles“). These provisions allow the Company to establish satellite meetings if necessary, and for the Company to make arrangements for the safety and security of shareholders. Whilst it was never envisaged that these provisions would be used for this purpose (in fact provisions of this nature are rarely invoked), they can be used, in combination, to facilitate a shareholder meeting where it is necessary, on grounds of the personal safety of all concerned, to avoid the need for persons to be in the same physical location. For the purposes of the satellite meeting provisions of the Articles, we are designating the location of the meeting to be the place where the Chairman is located, and all other shareholders and “attendees” will be deemed to be at their own individual satellite location. The requirement that all satellite locations be connected by at least audio means is satisfied by use of the meeting platform.

Accordingly, we appreciate that the Company has not done this before, and so I will explain the impact on the operation of this GM and the voting process in some detail.

1. Before the GM

In the usual way we ask and encourage shareholders to vote for the GM resolutions by appointing the Chairman as a shareholder’s proxy. Accordingly, shareholders are encouraged to complete the enclosed form of proxy (the “Form of Proxy“) and return it by email to or by post to Link Asset Services (the “Registrar“), as soon as possible. To be valid, the Form of Proxy provided or other instrument appointing a proxy must be received by 11.00 a.m. on 4 May 2020, or in the case of shares held through CREST, via the CREST system.

In accordance with article 63.1 of the Articles, as Chairman, I am formally requiring that all of the voting at the meeting will be conducted on a poll and there will be no show of hands. This means that your votes will all be counted for all the shares that you have.

Please remember to submit any questions in advance in accordance with the instructions on pages 15 and 16 by email to with the subject line “GM Question”.

If you wish to appoint a corporate representative, please contact the Registrar in the usual way.

2. On the Day of the Meeting

The meeting takes place at 11.00 a.m. on 6 May 2020.

To join the meeting type (or paste) the following web address into your web browser:

You will be asked to enter a password to gain access to the meeting. This code can be found on the bottom section of your proxy form. Please detach and keep this portion of the proxy form before returning the proxy form.

When the meeting opens at the appointed time, you will be able to see and hear the Chairman. The Chairman will open the meeting and address any questions that have been submitted in advance. There will then be a short opportunity to put any additional questions. Shareholders should indicate if they would like to ask a question using the electronic “raise your hand” feature or by typing their question into the Q&A box in the meeting. All attendees will remain muted by the host unless and until they are invited to ask a question.

The Chairman will then formally put the resolutions to the meeting and advise of the proxy votes received in advance.

The meeting will then formally close.

As shareholders exit the meeting, they will have the option to submit an electronic poll card to record their vote. If you (a) have already submitted a proxy instruction and do not wish to change your vote; or (b) do not wish to vote, you can click on the button to skip this step.

The voting facility will switch off 30 minutes after the close of the meeting.

The results of the meeting will be announced by RNS and posted to the Company’s website on the day of the meeting. The full poll results will also be published on this website at the same time.

The Business of the Meeting

The business of the GM comprises resolutions (each, a “Resolution” and together, the “Resolutions“), the purpose of which is to seek certain additional authorities to issue shares, disapply statutory pre-emption rights and to approve certain incentive awards proposed to made to certain members of the Company’s leadership team (the “Option Grants).

Introduction and Background

The Directors recently announced on 16 March 2020 the closing of a placing of ADSs (each representing 5 ordinary shares), raising US$10,000,000 (before expenses) of new capital to develop its clinical programs. Following this fundrise the Company was able to enter into an “At the Market” sales agreement (the “ATM Facilty”) to sell its ADSs to new investors, with a value of up to US$20,000,000 on a continuing basis to further enhance liquidity. The ATM Facility is now active.

The Company has also been taking rapid steps to develop the potential of TZLS-501 to treat COVID-19 infections, using investigational new technology, consisting of direct delivery of anti-IL-6 receptor (anti-IL-6R) monoclonal antibodies (mAbs) into the lungs using a handheld inhaler or nebulizer. Development of this novel technology is a step forward toward expediting development of TZLS-501, a fully-human anti-interleukin-6 receptor (anti-IL6R) monoclonal antibody (mAb) for treatment of patients infected with COVID-19 (SARS-CoV-2) coronavirus. The Company believes the technology could also be applicable for use with other FDA approved mAbs and drugs. The Company reported on 9 April 2020 that it had submitted a provisional patent application for the delivery technology.

This new program, and the Company’s current pipeline of clinical activity requires significant amounts of capital, which was one of the main drivers for the Company seeking to dual list on NASDAQ in 2018.

The Company’s clinical pipeline now consists of the following programs:

(i) Foralumab (TZLS-401)

The Company’s lead product candidate in immunology is Foralumab (TZLS-401), which the Company believes is the only fully human anti-cluster of differentiation 3, or anti-CD3, monoclonal antibody, or mAb, in clinical development. The Company believes that based on the concepts of mucosal tolerance, oral or intranasal administration of Foralumab has the potential to reduce inflammation while minimizing the toxicity and related side effects. The Company believes the switch from intravenous administration to oral and nasal administration is a ‘game changer’ for treatment with mAbs as it could improve patient’s compliance and safety. MAbs represent a single pure antibody produced by single clones and are an important class of human therapeutics for treating cancers and autoimmune diseases. The global market opportunity for mAb therapeutics is greater than $86 billion. Generation of antibodies for use in humans developed in animals, lead to strong immune responses limiting their effectiveness and potentially leading to severe side effects. A process known as “humanization” removes most of the animal components of the antibody thereby lowering the immune response from the human immune system. The entire omission of other animal material, as in fully human antibodies, is the optimal goal to avoid incompatibility with the human immune system.

The Company is also developing Foralumab, for which intellectual property was in-licensed from Novimmune SA, in December 2014, as a potential treatment for non-alcoholic steatohepatitis, or NASH, and Crohn’s disease as well as neurodegenerative diseases such as multiple sclerosis, or MS. The Company has now developed and filed patent applications with respect to oral and nasal administration formulation of Foralumab for treatment of human diseases. These patent applications may be applicable to all mAbs for nasal and oral administration. To date, Foralumab has been studied in one Phase 1 and two Phase 2a clinical trials conducted by Novimmune in 68 patients dosed by the intravenous route of administration. In these trials, Foralumab was observed to be well-tolerated with a maximum tolerated dose (MTD) of 1 mg/dose and produced immunologic effects consistent with potential clinical benefit while demonstrating mild to moderate infusion related reactions, or IRR.

The Company initially investigated orally and nasally administered Foralumab for its safety and immunomodulatory activity in healthy volunteers in separate Phase 1 clinical trials. A Phase I single site, double-blind, placebo-controlled, dose-ranging clinical study dosed intranasally in healthy volunteers was initiated in November 2018 to evaluate safety and biomarkers of immunomodulation of clinical responses in healthy volunteers to dose Foralumab intranasally in collaboration with Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. This clinical trial was completed in July 2019 in which 18 subjects received Foralumab treatment and 9 patients received placebo. All nasal doses were well tolerated, and no drug related safety issues were reported at any of the doses. Biomarker analysis showed significant positive immune effects, that were most prominent in the 50 µg cohort with minimal immunomodulatory effects at the 10 µg and 250 µg doses. In addition, we submitted an IND on March 18, 2019 for the oral formulation, to the FDA. The FDA requested safety data from the phase 1 trial with nasal administration of Foralumab to justify the proposed dose-range for the phase 1 trial with oral administration of enteric-coated capsules of Foralumab in healthy volunteers. The Company withdrew the IND on April 17, 2019. A third IND was submitted to the FDA on July 23, 2019 for a Phase I trial in healthy volunteers using orally administered Foralumab with an intent to treat progressive multiple sclerosis, or pMS. On September 9, 2019, the FDA granted approval to initiate the Phase I clinical trials to evaluate the safety and pharmacokinetics of oral Foralumab at 1.25, 2.5 and 5.0 mg/day as a single ascending dose study. The study was completed in December 2019 at Brigham and Women’s Hospital (Boston, MA USA) and the formulated Foralumab powder encapsulated in enteric-coated capsule was well-tolerated at all doses tested and there were no drug-related safety issues observed even at the highest dose of 5 mg in this trial. We intend to conduct a Phase 2 study using Crohn’s Disease patients starting in the second half of 2020 and file an IND for a Phase 2 trial using NASH patients. In addition, we intend to initiate a Phase 2 study with nasally administered Foralumab in pMS patients in the second half of 2020.

(ii) Milciclib (TZLS-201)

The Company’s lead product candidate in oncology is Milciclib (TZLS-201), which is an orally bioavailable, small molecule broad spectrum inhibitor of cyclin-dependent kinases, or CDKs, and Sarcoma, or Src, family kinases. CDKs are a highly conserved family of enzymes that phosphorylate a specific group of proteins that are involved in regulating the cell cycle. The cell cycle is a series of events that takes place in cells leading to division and duplication of its DNA to produce two daughter cells. Src family kinases are non-receptor tyrosine kinase proteins encoded by the Src gene also involved in regulating cell growth and potential transformation of normal cells to cancer cells. The Company now has a drug discovery pipeline of small molecule new chemical entities, or NCEs, and biologics. Milciclib has Orphan Drug Designation (ODD) in the U.S. and EU for thymic cancer (thymic epithelial tumor or TET) such as thymic carcinoma and thymoma.

The Company is developing Milciclib, for which the intellectual property was in-licensed from Nerviano Medical Sciences S.r.l., or Nerviano, in January 2015, as a potential treatment for hepatocellular carcinoma, or HCC. A novel feature of Milciclib is its ability to reduce levels of microRNAs, miR-221 and miR-222. MicroRNAs are small RNA molecules that play a significant role in the regulation of gene expression. miR-221 and miR-222 are believed to be linked to the development of blood supply (angiogenesis) in cancer tumors. Levels of these microRNAs are consistently elevated in HCC patients and may contribute towards resistance to treatment with Sorafenib, a multikinase inhibitor (a drug which may inhibit the cellular division and proliferation associated with certain cancers) often prescribed to HCC patients as the Standard of Care (SOC). To date, Milciclib has been studied in a total of eight Phase 1 and Phase 2 clinical trials in 316 patients. In these trials, Milciclib was well-tolerated with minimal adverse events. We initiated a Phase 2a trial for Milciclib as a monotherapy in patients with HCC in the third quarter of 2017. This trial is a single-arm, repeated-dose (100 mg once daily; 4 days on/3 days off every 4 weeks defining each cycle), 6-month duration study to evaluate the safety, tolerability and anti-tumor activity of Milciclib in Sorafenib-refractory or intolerant patients with unresectable or metastatic advanced HCC, the most common form of liver cancer. Enrollment of 31 patients in Italy, Greece, and Israel was completed in November 2018

In March 2019, the Independent Monitoring Committee, or IDMC, reviewed safety data from patients as of February 26, 2019 and concluded that the administration of Milciclib to patients with advanced HCC was not associated with unexpected signs or signals of toxicity. 28 out of 31 treated patients were evaluable, 14 completed the 6-month duration study. The most frequent adverse events such as diarrhea, ascites, nausea, fatigue, asthenia, fever, ataxia, headache, and rash were manageable. No drug-related deaths were recorded.

  • 9 out of 14 patients (64.2%) were approved by their respective ethical committees to continue the treatment.
  • 15 of the 9 patients on compassionate use had received Milciclib for a total of 9, 9, 11, 13 and 16 months.
  • As of January 17, 2020, the remaining 2 patients continuing the compassionate use treatment are in their 15th month.
  • Both median TTP and PFS were 5.9 months (95% Confidence Interval (“CI”) 1.5-6.7 months) out of the 6-months duration of the trial.
  • 17 of 28 (60.7%) evaluable patients showed “Stable Disease” (SD; met at least once in an 8-week interval).
  • One patient (3.6%) showed “Partial Response” (PR, unconfirmed).
  • 18 of 28 (64.3%) evaluable patients showed “Clinical Benefit Rate” defined as CBR=CR+PR+SD (with CR representing Complete Remission).

Since overexpression of CDKs and dysregulation in pRB pathway (regulates transcription factors critical for cell cycle progression) are prominently associated with tumor cell resistance to certain chemotherapeutic drugs, inhibition of multiple CDKs is an appealing approach to improve clinical responses in cancer patient’s refractory to existing treatment options. A Phase 1 dose-escalation study of Milciclib in combination with gemcitabine in patients with refractory solid tumors exhibited clinical activity in patients including those refractory to gemcitabine. We plan to explore a combination approach in patients with HCC.

(iii) IL-6R

In addition, the Company is developing a fully human mAb targeting the IL-6R (TZLS-501) for the treatment of inflammatory and autoimmune diseases. The Company licensed the intellectual property from Novimmune in January 2017. This fully human mAb has a novel mechanism of action, binding to both the membrane-bound and soluble forms of the IL-6R as well as depleting circulating levels of the IL-6 in the blood. IL-6 is a major determinant in the priming of pathogenic T cells producing an inflammatory response and binding to its receptor subunit IL-6Rα on the cell membrane. The receptor IL-6Rα can be shed as a soluble, sIL6Rα, which binds to circulating IL-6 cytokine in the blood. The downstream signaling, for which soluble IL-6R is implicated, mediates the pro-inflammatory effect underlying inflammatory diseases such as rheumatoid arthritis (RA), acute respiratory distress syndrome (ARDS) and other autoimmune diseases. We believe that the novel features of TZLS-501 consisting of its dual mechanism of action to inhibit signaling by the membrane-bound and soluble IL-6 receptor and the rapid depletion of circulating IL-6 cytokines, which is the major cause of lung damage, provides this mAb with distinct advantages for treatment of COVD-19.

Recently it was reported that certain patients infected with COVID-19 may develop an uncontrolled immune response (“cytokine storm”) resulting in severe damage to lung tissue which could lead to respiratory failure (Chaolin Huang, et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet, volume 395, pages 497-506. 2020. Published online January 24, 2020). Early clinical studies conducted by doctors in China suggest that anti-IL6R mAbs may be used in clinical practice for treatment of COVID-19. Consequently, China’s National Health Commission has recommended the use of Roche’s blockbuster drug, Actemra® for treatment of patients infected with COVID-19, with serious lung damage and elevated IL-6 levels. Actemra was first approved by the FDA in 2010 for rheumatoid arthritis. Besides Actemra®, Sanofi and Regeneron are currently exploring Kevzara®, an FDA-approved anti-IL-6 receptor therapy for rheumatoid arthritis, for treatment of severe COVID-19. We are expediting development of TZLS-501, which is in pre-clinical development, for treatment of patients infected with coronavirus COVID-19 (SARS-CoV-2). The Company currently plans to administer TZLS-501 using a proprietary formulation employing targeted delivery technology.

In preclinical studies, TZLS-501 demonstrated the potential for overcoming the limitations of other IL-6 blocking pathway drugs. Compared to tocilizumab and sarilumab, while binding to the membrane-bound IL-6R complex, TZLS-501 has been observed to have a higher affinity for the soluble IL-6 receptor from antibody binding studies conducted in cell culture. TZLS-501 also demonstrated the potential to block or reduce IL-6 signaling in mouse models of inflammation. The soluble form of IL-6 has been implicated to have a larger role in disease progression compared to the membrane-bound form (Kallen, K.J. (2002). “The role of trans-signaling via the agonistic soluble IL-6 receptor in human diseases.” Biochimica et Biophysica Acta. 1592 (3): 323–343.)

Resolution 1 – Authority to a allot shares

On 15 April 2020 the Company announced that it had entered into an “at the market” sales agreement to raise up to an additional US$20,000,000 to finance and currently intends to use the net proceeds from the sale of the ADSs to (i) advance the clinical development of Foralumab, (ii) manufacture antibodies and preclinical safety and toxicology studies for COVID-19 and (iii) conduct other research and development programs, working capital and other general corporate purposes. The Company may also use a portion of the net proceeds from this offering to in-license, acquire or invest in complementary businesses, technologies, products or assets. However, the Company currently has no commitments or obligations to do so

The Company sought to finance its short-term working capital requirements in late 2019 and early 2020 through the issue of convertible loan notes with warrants attached. The Company now wishes to retire those convertible loan notes by accelerating conversion to become debt free. This will involve the issue of an additional 3,798,386 ordinary shares at a conversion price of 42p (including accrued interest) and the potential for the note holders to exercise up to 3,798,386 warrants at a price of 35p per share. This will substantially erode our existing ability to issue ordinary shares to raise additional capital.

The proposal is accordingly that the Company seeks an authority to allot Ordinary Shares up to a further third of the current issued share capital, in addition to that approved by shareholders at the general meeting held on 20 February 2020.

Assuming the passing of this Resolution, the new authorities will expire 12 months from the date of the passing of this Resolution or until the conclusion of the next annual general meeting, if earlier, and will be in addition to all previous authorities to the extent that they have not already been utilised (apart from other specific authorities taken in respect of outstanding warrants and options which will continue unaffected).

Resolution 2 (disapplication of pre-emption rights)

Section 561 of the 2006 Act contains pre-emption rights that require all equity shares which it is proposed to allot for cash to be offered to existing shareholders (the “Shareholders”) in proportion to existing shareholdings, unless a special resolution is passed to disapply such rights. Such rights do not apply to an issue otherwise than for cash, such as an issue in consideration of an acquisition. However as many of the participants in the Company’s long term incentive scheme are based in the USA and hence participate in the US Sub-Plan of the long term incentive plan, any shares falling to be issued on the exercise of options may also require a specific disapplication of pre-emption rights.

Subject to the passing of Resolution 1 and as noted therein, the proposed Resolution provides for the dis-application of statutory pre-emption rights for allotments of equity securities for cash, but limits this authority to the allotment of equity securities up to an aggregate nominal value of £1,533,200 (representing approximately one third of the Company’s share capital) and up to an aggregate amount of £640,000 in respect of the share option awards that are being put to shareholders for approval at the GM.

Further, the Directors believe that the statutory requirements are too restrictive and, it is proposed that, subject to the passing of Resolution 1, the Directors should be able to allot shares for cash otherwise than pursuant to rights issues, open offers or other pre-emptive issues etc. amounting to no more than an aggregate nominal amount of £1,533,200 representing 30 per cent. of the Company’s share capital, in addition to the authority granted at the annual general meeting held on 31 May 2019 and the general meeting held on 20 February 2020.

The Resolution to include all pre-emptive issues for cash at this level is a departure from the strict wording of the IMA guidelines (which is limited to rights issues), which the Directors regard as too restrictive, particularly given the Company’s nexus with US markets and its sector of operation. The above departures in Resolutions 1 and 2 from the IMA guidelines should not be taken to indicate that they are being disregarded, but rather that the proposed Resolutions are designed to provide greater flexibility for the Directors to determine the form of any future pre-emptive issues in the light of market conditions and practice and potential opportunities to secure equity finance, at the time such an issue may be proposed. At the current time the Company has generated investor interest and the Directors are mindful that the Company’s strategy must be to raise additional working capital if the opportunity exists to do so without significant dilution for existing shareholders.

Resolutions 3 and 4 – Replacement Option Grants

The Company has a long-term incentive plan, with a US Sub-plan, to facilitate grants of options over ordinary shares of 0.03 pence each in the capital of the Company (“Ordinary Shares“) to incentivise an reward the creation of long-term shareholder value and to align the interests of the Company’s executive directors with those of its shareholders (the “Shareholders“). Historic options were granted at prices at which render those awards no longer meaningful incentives and do not reflect the efforts of the staff and management team over the last year in delivering on the clinical program and upon new opportunities.

The Remuneration Committee, comprising the two independent non-executive directors were asked by the Board to review the current awards outstanding and make recommendations to the Board in January 2020. Those recommendations and timing of implementation have been hindered and delayed by the timing of the announcement of significant events, which have led to extended close periods. The Remuneration Committee recommenced its work in the weeks following the fundraise in March 2020. The Company’s share price has seen some significant spikes reflecting investor reaction to the work of the staff and executive team in identifying new opportunities and the Remuneration Committee was keen that, given the original timing of its remit, that it was able to take the “undisturbed” share price into account in reaching a fair result.

The conclusions of the Remuneration Committee were that the only sensible way in which to address the situation was that (i) all existing options held by the relevant individuals (including all non-managerial staff staff members) be surrendered and new options be granted; (ii) the new options to reflect an immediate vesting percentage equal to the vested element of the old awards; but (iii) the new options to be subject to strict criteria on any sale of shares arising from awards for two years post the relevant vesting dates; and (iv) all vested element of such awards to be subject to claw-back in the event that the recipient ceased to be a director or employee within two years of the award being made. The same terms to be applied to all directors and employees holding option awards. The Remuneration Committee selected an exercise price of 35p per share (which was above the average prevailing share price in January 2020, February 2020 and early March 2020 and above the actual share price in late March following the fundraise. The Remuneration Committee believes that the replacement option grant proposal is fair and reasonable to Shareholders and that such proposals are within the normal remuneration parameters for an early stage life science company.

The following new options over Ordinary Shares are proposed to be granted:

(a) options over 9,000,000 Ordinary Shares to Dr Kunwar Shailubhai, the Company’s Chief Executive Officer and Chief Scientific Officer, at an exercise price of 35p per share, split into two component parts:

(i) 7,200,000 options are time vesting awards, with 2,500,000 options the subject of immediate vesting and the balance of 4,700,000 options vesting at the rate of 1,175,000 per annum over four years. Shares resulting from the exercise of the options are subject to disposal restrictions. These options have a life of 8 years, after which any unvested or unexercised element will lapse; and

(ii) 1,800,000 options vest subject to clinical performance conditions relating to the Company’s lead drug candidates. These options have a life of 10 years, after which any unvested or unexercised element will lapse.

Dr Shailubhai will surrender all 7,200,000 existing options held by him. The 2,500,000 options which vest immediately are subject to the 2 year “no-sale” and “claw-back” provisions.

(b) options over 400,000 Ordinary Shares to Tiziano Lazzaretti, the Company’s Chief Financial Officer, at an exercise price of 35p, split into two component parts:

(i) 300,000 options are the subject of immediate vesting and the balance of 100,000 options vesting at the rate of 25% per annum over four years; and

(ii) shares resulting from the exercise of the options are subject to disposal restrictions. These options have a life of 8 years, after which any unvested or unexercised element will lapse.

Mr Lazzaretti will surrender all 300,000 existing options held by him. The 300,000 options which vest immediately are subject to the 2 year “no-sale” and “claw-back” provisions.

(c) options over 3,809,403 Ordinary Shares, at an exercise price of 35p, to Gabriele Cerrone, the Company’s Executive Chairman, split into two component parts:

(i) 3,259,703 options vest if the volume weighted share price of the ordinary shares exceeds £3.00 (or if the ADS price exceeds the US$ equivalent of £15.00) for 120 consecutive trading days. These options have a life of 8 years, after which any unvested or unexercised element will lapse; and

(ii) 550,000 options vest if the volume weighted share price of the ordinary shares exceeds £1.635 (or if the ADS price exceeds the US$ equivalent of £8.175) for 5 consecutive trading days. These options have a life of 8 years, after which any unvested or unexercised element will lapse.

Mr Cerrone will surrender 3,809,403 existing options held by him.

In conjunction with the Option Grants, all current options held by Dr Shailubhai, Mr Lazzaretti and Mr Cerrone and all the options held by other employees were surrendered by mutual agreement, resulting in the surrender of a total of 11,409,403 existing share option