Pepper Bio Emerges from Stealth with ‘Waze for Drug Discovery’ Technology

On October 15, 2021 Pepper Bio, the world’s first transomics drug discovery company, reported the company emerges from stealth to leverage its proprietary transomics — including phosphoproteomics — data translation technology to discover new drugs, rediscover new uses for existing therapeutics, and rescue drugs that may be on a course toward failing (Press release, Pepper Bio, OCT 15, 2021, View Source [SID1234638709]).

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Drug discovery is often a bad bet for pharma. Pepper Bio significantly reduces that risk.
Currently, the successful development of a new therapy is estimated to cost around $2.6 billion on average and last over a decade through a variety of failed and successful trials. Because of the high cost and risks involved, many diseases will go untreated because of their low expected return on investment in drugs that may work. With hundreds of thousands of therapeutics candidates being evaluated each year, 86 percent of clinical trials of drug candidates fail to earn FDA approval, according to a new study from the MIT Sloan School of Management. More than 30 percent of drugs entering Phase II clinical trials fail to progress, and 58 percent of drugs fail in Phase III. These end-stage studies commonly cost upward of hundreds of millions of dollars for manufacturing, clinical trial design, implementation, and data analysis.

"From my experience as a drug development strategist, many therapeutic programs were killed simply because they would have cost too much with an inadequate return on investment," said Jon Hu, co-founder and CEO, Pepper Bio. "These are very difficult decisions because they are made with the understanding that many people who may benefit from these potential new drugs would never have that opportunity. We founded Pepper Bio in order to significantly improve the volume, quality, and accuracy of the data analysis used to evaluate opportunities for novel new therapeutics. We empower our drug discovery partners with a much higher level of informed confidence. Ultimately, our work will result in many more drug development initiatives going forward to help people around the world struggling with diseases that are left untreated today."

A first in drug discovery, Pepper Bio and their partners make significantly more informed strategic decisions by relying on more accurately analyzed data. This allows them to develop therapeutics that treat diseases at their root cause, have less toxicity and higher response rates with patients exhibiting fewer symptoms. Already, Pepper Bio has demonstrated proof of concept of the company’s proprietary platform across three therapeutic areas: Neurodegenerative, Oncology, and Inflammatory.

Pepper Bio’s proprietary capability to translate multiple levels of complex transomic data unlocks a new level of sophistication in drug discovery, much like Waze leverages multiple layers of data to direct travelers on the optimal and safe road to their destination. Pepper Bio identifies how and why novel drug candidates may or may not be effective in specific patient populations and diseases, directing drug discovery initiatives toward the most promising disease targets and patients who will be helped most with reduced side effects.

The success of Pepper Bio is rooted in the company’s proprietary capacity to access and analyze transomic data leveraging three pillars of the field: Global (1), comprehensive data from the entire biological system are analyzed to determine functional (2) characteristics of intercellular biologic activity. Multiple omic layers, including phosphoproteomics, the layer at the top of the biotech stack, are analyzed. By analyzing all layers combined, Pepper Bio empowers drug developers to identify and reach accurate, much more informed causal (3) inferences.

"Pepper Bio is working to ensure that the right therapeutics and combinations of drugs are developed in a precise, effective, efficient, and safe manner. Our proprietary capacity to translate complex transomic data into meaningful, evidence-based guidance for drug discovery programs significantly improves the likelihood of success for clinical trials. This promises to conserve many millions of dollars that may otherwise be funneled into traditional methods of research and development," said Samantha Dale Strasser, Ph.D., Co-Founder and Chief Scientific Officer, Pepper Bio.

The industry moving towards transomics is inevitable and Pepper Bio is leading the way." said Omri Amirav Drory, General Partner at NFX, an investor in Pepper Bio. NFX was an early backer of biotech companies such as Mammoth Biosciences and c2i genomics.

CEO Jon Hu is experienced in pharmaceutical research and development (Shire Pharmaceuticals), corporate strategic consulting (Bain & Company), and venture capital (Guild Capital). Hu earned his Bachelor’s degrees in biomedical engineering and economics, and earned his MBA from Harvard Business School. CSO Samantha Dale Strasser, Ph.D., developed the foundation of Peppe Bio’s technology during her time as a National Science Foundation Graduate Research Fellow at the Massachusetts Institute of Technology, where she earned her Doctorate in Electrical Engineering and Computer Science. She earned her Master’s Degree in M.Phil in Physics at the University of Cambridge as a Churchill Scholar and her Bachelor’s degrees in Biomedical Engineering and Applied Mathematics from Northwestern University.

Mr. Hu and Dr. Strasser are joined by Christopher Nicholson, Ph.D., Head of Biology, and Caitlin Brown, Ph.D., Head of Business Development. Dr. Nicholson earned his doctorate from Newcastle University and was a Senior Research Fellow at Harvard Medical School and MGH. Dr. Brown earned her doctorate from Brown University.

Pepper Bio announced its scientific and strategic advisory board members today: Douglas Lauffenberger, Ph.D., Professor, MIT; Founder, Biological Engineering, MIT.; Dean Felsher, MD, Ph.D., Professor, Oncology, Stanford; Director, Translational Research, Stanford. Imran Nasrullah, JD, VP & Head, Open Innovation Center, North America – East, Bayer; Former Director, Strategic Partnering & Business Development & Licensing, Boehringer-Ingelheim. Tom Rush, Ph.D., Chief R&D Officer, Variant Bio; Former US Lead, Functional Genomics, GlaxoSmithKline. Jerome Windsor, PharmD, SVP, Corporate Development & Product Strategy, GNS Healthcare; Former VP, Strategy & Business Development, Median Technologies. Peter Hornbeck, Ph.D., Director, Cell Signaling Technology; Founder, PhosphoSitePlus.

Hervolution receives 2.5M EUR in funding through the European Innovation Council Accelerator

On October 15, 2021 Hervolution Therapeutics reported that Hervolution is one of just 65 European companies to receive funding through the European Innovation Council Accelerator of 2.5M EUR (Press release, Hervolution Therapeutics, OCT 15, 2021, View Source [SID1234637208]).

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Silence Announces Proposed Cancellation of Admission of its Ordinary Shares to Trading on AIM and Transition of its Primary Trading Venue to the Nasdaq Global Market

On October 15, 2021 Silence Therapeutics plc, AIM:SLN and Nasdaq:SLN ("Silence" or "the Company"), a leader in the discovery, development and delivery of novel short interfering ribonucleic acid (siRNA) therapeutics for the treatment of diseases with significant unmet medical need, reported the Company’s intention to cancel the admission of its ordinary shares of nominal value £0.05 each (the "Ordinary Shares") to trading on AIM (the "AIM Delisting"), subject to shareholder approval, with effect from 30 November 2021 (Press release, Silence Therapeutics, OCT 15, 2021, View Source [SID1234591430]). Subject to shareholder approval, the Company’s last day of trading on AIM will be 29 November 2021. Silence will retain the listing on the Nasdaq Global Market ("Nasdaq") of American Depositary Shares, each representing three Ordinary Shares (the "ADSs"), under ticker symbol "SLN". The Company expects Nasdaq to become the primary trading venue for its equity securities. Existing holders of ADSs not also holding Ordinary Shares do not need to take any action in relation to the AIM Delisting; and

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the posting of a circular to shareholders (the "Circular") which contains further information on the AIM Delisting and the process to deposit Ordinary Shares for delivery of ADSs and notice of a general meeting to be held on 1 November 2021 at 72 Hammersmith Road, London W14 8TH at 2.00 p.m. (London time) (the "General Meeting") at which shareholder approval will be sought, inter alia, for the AIM Delisting

The Proposed AIM Delisting and the General Meeting

Highlights

Following the AIM Delisting, the Company’s ADSs will remain listed on Nasdaq, which will become the primary trading venue for its equity securities, and securities in the Company will only be publicly tradeable in the form of Nasdaq-listed ADSs.

The board of directors of the Company (the "Board" and the "Directors") believes that the AIM Delisting should enhance the liquidity of trading in the Company’s ADSs as all such trading will be concentrated in a single venue.

The Company is providing an opportunity for shareholders to deposit their Ordinary Shares with the Company’s ADS depositary in exchange for delivery of ADSs, without cost, in connection with the AIM Delisting whether prior, on, or subsequent to 30 November 2021 (being the date on which the AIM Delisting takes effect), except that the Depositary has not agreed to waive that fee with respect to more than 81,831,467 Ordinary Shares, which is the number of Ordinary Shares that were in issue but not represented by ADSs on 15 October 2021 and has not agreed to waive fees on any deposit made by the Company.

Mark Rothera, President and Chief Executive Officer of Silence Therapeutics, said: "This marks a very important step in the evolution of our company and positions Silence as a global RNAi leader. With our mRNAi GOLD platform advancing in the clinic, we see substantial opportunity to build value over the next 12 months and longer term. We are grateful to have the continued support of our loyal shareholders and look forward to this exciting new chapter of growth."

Craig Tooman, Chief Financial Officer of Silence Therapeutics, said: "A key priority for us has been to create a more attractive and efficient trading mechanism for our shareholders and to support increasing interest from new investors. We believe the move to trade exclusively on the Nasdaq – a top global exchange – accomplishes that objective. This is an exciting time for Silence and we look forward to continuing to expand our global shareholder base."

The Company will today be posting the Circular to shareholders which will set out further information on the process to deposit Ordinary Shares for delivery of ADSs, including personalised forms for those holders of certificated Ordinary Shares who wish to deposit their Ordinary Shares for delivery of ADSs, as well as containing the notice of General Meeting. Copies will also be available on Silence’s website at www.silence-therapeutics.com.

Background to the AIM Delisting

The Company was incorporated in 1994 and its Ordinary Shares have been admitted to trading on AIM since 1995. In September 2020, the Company undertook a direct listing of ADSs representing its Ordinary Shares on the Nasdaq Capital Market. In February 2021, the Company announced an oversubscribed private placement of ADSs for gross proceeds of approximately $45 million. In June 2021, the Company moved its Nasdaq listing from the Nasdaq Capital Market tier to the Nasdaq Global Market tier.

As at 13 October 2021, being the last practicable date prior to the date of this announcement, approximately 8.9 per cent. of the Company’s Ordinary Shares are represented by ADSs tradeable on Nasdaq. All shareholders who have not already deposited their Ordinary Shares for delivery of ADSs are currently able to do so at any time. Affiliates of the Company who deposit their ordinary shares may be subject to limitations on resale of ADSs under U.S. securities law. The Company intends to convert an existing secondary resale shelf registration statement on Form F-1 to a short-form registration statement on Form F-3, which will, upon effectiveness, continue to grant such affiliates the ability to freely resell such restricted securities without restriction.

The AIM Rules for Companies published by London Stock Exchange plc (the "London Stock Exchange") (the "AIM Rules for Companies") require that, unless the London Stock Exchange otherwise agrees, the cancellation of a company’s shares from trading on AIM requires the consent of not less than 75 per cent. of votes cast by its shareholders given in a general meeting. Notwithstanding that the Company may be able to seek the agreement of the London Stock Exchange that shareholder consent in general meeting is not required due to the listing of ADSs on Nasdaq, the Board has determined to seek shareholder approval for the proposed AIM Delisting.

Reasons for the AIM Delisting

The Board has decided to implement the AIM Delisting for the following reasons:

The AIM Delisting is expected to further enhance the liquidity of trading in the Company’s securities by combining on Nasdaq the volume of transactions from both Nasdaq and AIM.

Having securities solely listed on Nasdaq, rather than dual-listed on Nasdaq and AIM as is the case at present, is expected to increase the willingness of US-based investors to invest in the Company’s securities.

A Nasdaq-only listing structure provides for a streamlined operation that showcases the global nature of the Company’s scope and places it more clearly within the ranks of international biotechnology companies that are its true peers.

The cost of complying with the AIM Rules for Companies is incremental to that for complying with the Nasdaq market rules and the Company sees advantages in reducing its cost base as it progresses its clinical programmes and commercial strategy.

Internal financial and legal staff time spent on compliance with the AIM Rules for Companies is incremental to that required for compliance with the Nasdaq market rules.

ADSs representing the Company’s Ordinary Shares will remain tradeable on Nasdaq.

Accordingly, the Directors believe that it is no longer in the best interests of the Company or its shareholders as a whole for the Company to retain admission of its Ordinary Shares to trading on AIM. However, the Company is providing an opportunity for shareholders to deposit their Ordinary Shares with the Company’s ADS depositary in exchange for delivery of ADSs, without cost, in connection with the AIM Delisting whether prior, on, or subsequent to 30 November 2021 (being the date on which the AIM Delisting takes effect), except that the Depositary has not agreed to waive that fee with respect to more than 81,831,467 Ordinary Shares, which is the number of Ordinary Shares that were in issue but not represented by ADSs on 15 October 2021 and has not agreed to waive fees on any deposit made by the Company.

Effect of the AIM Delisting

If the resolutions are passed at the General Meeting, Shareholders will no longer be able to buy and sell Ordinary Shares on AIM after 29 November 2021. Holders of Ordinary Shares should read "Information for holders of Ordinary Shares" below which explains in more detail the process of depositing Ordinary Shares for delivery of ADSs.

As a company incorporated in England and Wales, the Company will continue to be subject to the requirements of the Companies Act 2006.

Following the AIM Delisting taking effect, the Company will no longer be subject to the AIM Rules for Companies or be required to retain the services of an independent nominated adviser. The Company will also no longer be subject to the QCA Corporate Governance Code or be required to comply with the continuing obligations set out in the Disclosure Guidance and Transparency Rules (the "DTRs") of the Financial Conduct Authority (the "FCA") or, provided the Company’s securities remain outside the scope of the regulation, UK MAR. In addition, the Company and its shareholders will no longer be subject to the provisions of the DTRs relating to the disclosure of changes in significant shareholdings in the Company. The Company intends to continue to comply with all regulatory requirements for the Nasdaq listing of ADSs, including all applicable rules and regulations of the SEC.

Shareholders who continue to hold Ordinary Shares following the AIM Delisting will continue to be notified of the availability of key documents on the Company’s website, including publication of annual reports and annual general meeting documentation. Holders of ADSs will be able to continue to access all such information via the Silence website. Holders of Ordinary Shares and ADSs will remain entitled to receive any future dividends that may be declared thereon, which dividends will also accrue to ADS holders in accordance with the terms of the Deposit Agreement.

Application of the City Code following the AIM Delisting

Following the AIM Delisting, as the Company will remain a public limited company incorporated in England and Wales but its securities will not be admitted to trading on a regulated market or multilateral trading facility in the United Kingdom (or a stock exchange in the Channel Islands or the Isle of Man), the City Code on Takeovers and Mergers (the "City Code") will only apply to the Company if it is considered by the Panel on Takeovers and Mergers (the "Panel") to have its place of central management and control in the United Kingdom (or the Channel Islands or the Isle of Man). This is known as the "residency test". The way in which the test for central management and control is applied for the purposes of the City Code may be different from the way in which it is applied by the United Kingdom tax authorities, Her Majesty’s Revenue & Customs ("HMRC"). Under the City Code, the Panel looks to where the majority of the directors of the Company are resident, amongst other factors, for the purposes of determining where the Company has its place of central management and control.

The Panel has confirmed to the Company that following the AIM Delisting, based on the current composition of the Board, the City Code will continue to apply to the Company. However, the City Code could cease to apply to the Company in the future if any changes to the Board composition result in the majority of the Directors not being resident in the United Kingdom, Channel Islands and Isle of Man.

Further details of the Panel, the City Code and the protections given by the City Code are set out in the Circular. Shareholders are encouraged to read this information carefully as it outlines certain important protections which they will be giving up if they agree to the AIM Delisting and the Company subsequently ceases to be subject to the City Code.

The Board is seeking shareholder approval to an amendment to the Company’s articles of association (the "Articles") which would apply in the event that the City Code ceased to apply to the Company. This amendment would insert a new article 159 into the Articles which would apply in the event that the City Code were no longer to apply to the Company. Article 159 includes certain takeover protections so that the Company is able to defend itself and its shareholders from hostile takeovers. An ordinary resolution will be put to shareholders at each annual general meeting, starting with the annual general meeting in 2022, as to whether article 159 should continue to apply for the period until the next following annual general meeting. The full text of article 159 is set out in Appendix B to the Circular.

Information for holders of Ordinary Shares

If the resolutions are passed at the General Meeting, the Company’s Ordinary Shares will continue to be traded on AIM until market close (4.30 p.m. London time) on 29 November 2021. Thereafter, holders of Ordinary Shares can still hold the Ordinary Shares, but there will be no public market in the United Kingdom on which the Ordinary Shares can be traded, and the Ordinary Shares will not be tradeable on Nasdaq in this form.

To sell Ordinary Shares on a public market following the AIM Delisting, shareholders will need to deposit their Ordinary Shares for delivery of ADSs. Each ADS represents three Ordinary Shares. This deposit can be made at any time, including before the AIM Delisting, subject in all cases to the provisions of, and the limitations set forth in, the New York law governed deposit agreement dated 4 September 2020 between the Company, the Bank of New York Mellon (the "Depositary") and all holders and beneficial owners of ADSs issued thereunder (the "Deposit Agreement").

The Board considers that shareholders should consider depositing their Ordinary Shares for delivery of ADSs prior to the AIM Delisting on 30 November 2021 for the following reasons:

For those shareholders who hold their Ordinary Shares in certificated form and wish to deposit their Ordinary Shares for delivery of ADSs, the Company’s Receiving Agent, Link Group, will facilitate, on the Company’s behalf, a block transfer process. Shareholders who hold their Ordinary Shares in certificated form will find enclosed with the Circular a personalised block transfer participation request form for use if they wish to deposit their Ordinary Shares for delivery of ADSs. Subject to the requisite documents being returned to Link Group by the required deadline (being 1.00 p.m. on 3 November 2021), Link Group will arrange for the relevant Ordinary Shares to be transferred to and through Link Group’s CREST account to the CREST account of the Custodian, which has been appointed by the Depositary, The Bank of New York Mellon, to safe keep the Ordinary Shares upon deposit, so that the Depositary can arrange to deliver the corresponding number of ADSs. The Custodian, on behalf of the Depositary, will hold all deposited Ordinary Shares in a custody account for the benefit of the holders and beneficial owners of ADSs.

Shareholders who elect to deposit their Ordinary Shares for delivery of ADSs prior to the AIM Delisting will not incur a UK stamp duty, or SDRT, charge. However, it is expected that shareholders who elect to deposit their Ordinary Shares for delivery of ADSs following the AIM Delisting will incur a stamp duty, or SDRT, charge, at a rate of 1.5 per cent. of the market value of the Ordinary Shares being deposited, to the UK taxation authority, HMRC.

Ordinarily, shareholders who deposit their Ordinary Shares for delivery of ADSs are charged an ADS issuance fee, by the Depositary, of up to $5.00 per 100 ADSs or portion thereof. However, no ADS issuance fees will be charged to shareholders who elect to deposit their Ordinary Shares in connection with the AIM Delisting whether prior, on, or subsequent to 30 November 2021 (being the date on which the AIM Delisting takes effect), except that the Depositary has not agreed to waive that fee with respect to more than 81,831,467 Ordinary Shares, which is the number of Ordinary Shares that were in issue but not represented by ADSs on 15 October 2021 and has not agreed to waive fees on any deposit made by the Company.

Otherwise than in connection with the AIM Delisting, ADS issuance fees of up to $5.00 per 100 ADSs or portion thereof will be charged by the Depositary in connection with any future deposits of Ordinary Shares.

Ordinary Shares may be deposited for delivery of ADSs only in multiples of three Ordinary Shares. It is not possible to receive a fraction of an ADS, so in the event that the deposit is completed after the AIM Delisting, there is a risk that shareholders will be left with a small number of Ordinary Shares (up to a maximum of two shares) which cannot be deposited for delivery of ADSs. If the deposit is made before the AIM Delisting has taken effect, any residual Ordinary Shares can be sold by shareholders on AIM prior to, and including, 29 November 2021 so long as those Ordinary Shares are in uncertificated form. Shareholders who hold their Ordinary Shares in certificated form may elect to donate their residual shares to the charity Share Gift by making that election on their personalised block transfer participation request form.

Shareholders who do not elect to participate in the block transfer process can utilise the services of a broker who is able to facilitate deposits of Ordinary Shares at the shareholder’s convenience.

Shareholders whose Ordinary Shares are held in uncertificated form in CREST and who wish to deposit their Ordinary Shares for delivery of ADSs, should contact their broker without delay to request that their Ordinary Shares are deposited.

Silence advises holders of Ordinary Shares to seek independent financial advice regarding the AIM Delisting and the deposit of their Ordinary Shares for delivery ADSs.

Information on the process to deposit Ordinary Shares for delivery of ADSs and the forms to be completed accompany the Circular. The information and forms, and contacts at the Company’s Receiving Agent, Link Group, in respect of completion of the block transfer participation request form for certificated holders, and the Depositary, The Bank of New York Mellon, are included on Silence’s website at www.silence-therapeutics.com.

If the Resolutions are not passed at the General Meeting, all documents provided to Link Group and/or The Bank of New York Mellon in relation to the deposit of Ordinary Shares for delivery of ADSs shall be of no effect and all original share certificates will be returned to shareholders by Link Group.

UK tax treatment

Many investors purchase AIM-quoted shares because they are classed as unlisted/unquoted securities which may qualify individuals who are UK tax resident and UK domiciled for relief from inheritance taxation and certain other preferential tax benefits. Silence cannot and does not provide any form of taxation advice to shareholders and therefore shareholders are strongly advised to seek their own taxation advice to confirm the consequences of continuing to hold unlisted Ordinary Shares or depositing Ordinary Shares for delivery of ADSs.

The following summary does not constitute legal or tax advice and is not exhaustive. The Company’s understanding of the current position for UK individuals who are UK domiciled for relevant tax purposes is as follows but it should be noted that the position on certain points is not free from uncertainty and that the Company has not taken steps to confirm the current position with HMRC. Therefore, the following should not be relied upon by shareholders without taking further advice (and the Company accepts no liability in respect of any such reliance on any information provided herein on taxation matters):

The AIM Delisting should not prevent the Ordinary Shares from qualifying as unlisted/unquoted securities for the purposes of certain specific UK tax rules (notably, the UK inheritance tax business property relief rules). Accordingly, it is expected that HMRC should accept that those shareholders who elect to continue to hold unlisted Ordinary Shares should continue to be regarded as holding unlisted/unquoted securities under those same rules.

Under HMRC’s stated practice those shareholders who elect to deposit their holdings of Ordinary Shares for delivery of Nasdaq-listed ADSs should not be considered as disposing of the Ordinary Shares for UK capital gains tax purposes when transferring the shares to the Depositary, The Bank of New York Mellon, in exchange for issue of ADSs on the basis that the shareholder retains beneficial ownership of the Ordinary Shares.

Shareholders who elect to deposit their holdings of Ordinary Shares for delivery of Nasdaq-listed ADSs prior to the AIM Delisting should not incur a stamp duty, or SDRT, charge. It is expected that shareholders who elect to deposit their holdings of Ordinary Shares for delivery of Nasdaq-listed ADSs following the AIM Delisting may incur a stamp duty, or SDRT, charge at the rate of 1.5 per cent. of the market value of the Ordinary Shares being deposited.

It is strongly recommended that shareholders obtain appropriate professional advice in respect of these and other taxes.

Further information in relation to the AIM Delisting

The Board believes that the proposed AIM Delisting is an appropriate next step for the Company and is in the best interests of shareholders as a whole. Further information about the process required to deposit Ordinary Shares for delivery of ADSs tradeable on Nasdaq, together with a set of Frequently Asked Questions, accompany the Circular.

Details of the General Meeting and action to be taken in respect of the General Meeting

A notice convening the General Meeting, which is to be held at 72 Hammersmith Road, London W14 8TH at 2.00 p.m. (London time) on 1 November 2021 is set out in the Circular.

At the time of publication of the notice of General Meeting, it is anticipated that the General Meeting will proceed as an open meeting. However, given ongoing uncertainty, and bearing in mind the broader public health considerations and for the safety of others, the Board will continue to monitor government guidance in relation to the COVID-19 pandemic, and if any changes to the arrangements set out in the notice of General Meeting are required, this will be communicated via a regulatory information service and the Company’s website.

Expected timetable for the AIM Delisting

Dispatch of the Circular and the enclosed documents 15 October 2021

Latest date for receipt of proxy voting instructions and (if applicable) hard copy forms of proxy 2.00 p.m. on 28 October 2021


General Meeting 2.00 p.m. on 1 November 2021

Last date for receipt by Link Group from certificated shareholders of duly completed block transfer participation request forms and original share certificates 3 November 2021 at 1.00 p.m.

Last date for receipt by The Bank of New York Mellon from CREST holders of duly completed issuance forms 17 November 2021 at 3.00 p.m.

Expected date of issuance of ADSs to block transfer participants 24 November 2021

Expected date of posting of ADS confirmations to shareholders by The Bank of New York Mellon 24 November 2021

Last day of dealings in the Ordinary Shares on AIM 29 November 2021

Cancellation of admission to trading on AIM of the Ordinary Shares 30 November 2021 at 7.00 a.m.
Notes

(1) References to time in this announcement are to London time unless otherwise stated.

(2) Each of the times and dates in the above timetable are subject to change. If any of the above times and/or dates change, the revised times and/or dates will be notified to shareholders by announcement through a Regulatory Information Service.

(3) All steps after the General Meeting are dependent on the resolutions being passed at the General Meeting. If the resolutions are not passed at the General Meeting, all documents provided to Link Group and/or The Bank of New York Mellon in relation to the deposit of Ordinary Shares for delivery of ADSs shall be of no effect and all original share certificates will be returned to shareholders by Link Group.

EORTC Completes Patient Recruitment to Study of Treatment for Rare Cancer High-Grade Uterine Sarcoma

On October 15, 2021 The European Organisation for Research and Treatment of Cancer (EORTC) reported that it has finished patient recruitment for the EORTC-62113-55115 trial in patients with the very rare tumour High-Grade Uterine Sarcoma (HGUtS) (Press release, EORTC, OCT 15, 2021, View Source [SID1234591427]). The randomised trial will study the effect of giving maintenance treatment* with cabozantinib after response or stabilisation further to adjuvant chemotherapy in cases of advanced stage disease, and as first-line treatment of metastatic disease (where the cancer has spread). Uterine sarcomas are aggressive tumours that occur mainly in postmenopausal women. They account for less than 1% of all gynaecological cancers and about 3-7% of all uterine malignancies, with an incidence of approximately 0.4 per 100,000 women.[1]

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The most common type of HGUtS is leiomyosarcoma (LMS), followed by endometrial stromal sarcoma (ESS), and even rarer subtypes such as undifferentiated uterine sarcoma.[2] This diversity of subtypes has led to a lack of consensus on risk factors and optimal treatment and this, combined with the rarity of the disease, has meant that outcomes for patients remain poor; there is a high risk of recurrence and most die within two years of their diagnosis.

Current treatments can include chemotherapy given after surgery for patients with a good performance status and poorly differentiated** early-stage sarcoma or in patients with advanced disease.[3] Different approaches for management of metastatic uterine sarcoma more generally include systemic chemotherapy with doxorubicin alone or in combination.[4] ‘To date, no prospective dedicated research has been conducted in uterine sarcoma, and therefore the treatment options remain limited. Considering the poor prognosis for these patients, the need to investigate new agents in this and in other rare cancers is imperative. We hope that our research will be able to improve outcomes, and also ensure that existing treatments can be used as effectively as possible’, says Prof. Isabelle Ray-Coquard of the Centre Leon Bérard in Lyon and Coordinator of this trial for the EORTC Sarcoma Group,

‘This study exemplifies the importance of multidisciplinary international collaboration, especially in the field of rare cancers, and here in particular the role of the International Rare Cancer Initiative (IRCI)’, says Prof. Nicholas Reed of the NHS Greater Glasgow & Clyde Beatson West of Scotland Cancer Centre, Co-coordinator of the trial for the EORTC Gynecological Group.

Recruitment to the trial started in February 2015 – initially dedicated to undifferentiated uterine sarcoma only, then expanded to also include High Grade LMS and High Grade adenosarcoma from 2017. As in the case of all rare cancers, enlisting the number of patients needed for the results to have the statistical power required to be reliable has been challenging. Now, more than six years later, the trial has passed its target recruitment with 58 patients (from six countries) randomised, as opposed to the 54 originally deemed to be necessary to meet the purpose of the study. This marks a crucial milestone for the trial. More broadly, this is an important step in advancing treatment optimisation, which relies on research to ensure that the right patients with rare cancers get the right medicine at the right time, thus improving safety and reducing waste.

First results from the trial are expected early 2023.

*Maintenance treatment is used to prevent or delay the cancer’s return if the cancer is in complete remission after the initial treatment. **Poorly differentiated tumours are made up of cancer cells that look very abnormal compared to normal cells.

References:

Hosh M, Antar S, Nazzal A, et al. Uterine sarcoma: analysis of 13,089 cases based on surveillance, epidemiology, and end results database. Int J Gynecol Cancer. 2016. July; 26(6): 1098-104.
Benson C & Miah AB. Uterine sarcoma – current perspectives. Int J Womens Health. 2017; 9: 597–606.
Tropé CG, Abeler VM, Kristensen GB. Diagnosis and treatment of sarcoma of the uterus. A review. 2012. Acta Oncol. 2012;51:694-705.
Giuntoli RL, Metzinger DS, DiMarco CS, et al. Retrospective review of 208 patients with leiomyosarcoma of the uterus: Prognostic indicators, surgical management, and adjuvant therapy. Gynecol Oncol. 2003;89:460-9.
About the study

The EORTC-62113-55115 trial was initiated as a collaboration between EORTC’s Soft Tissue & Bone Sarcoma Group (STBSG) and Gynaecological Cancer Group (GCG), with a protocol developed through the International Rare Cancers Initiative (IRCI) platform.

This randomised phase II double blinded trial aims to evaluate the role of maintenance therapy with cabozantinib in HGUtS, after stabilisation of the disease or response to chemotherapy following surgery, or in metastatic first-line treatment.

Cabozantinib is an oral tyrosine kinase inhibitor approved for the treatment of metastatic medullary thyroid cancer and is also being investigated in several other cancers. It is thought that this pharmaceutical could also be a beneficial maintenance treatment after chemotherapy for patients with sarcoma, as it blocks important pathways in the tumour growth process.

The primary objective of the trial is to assess – in different subtypes of HGUtS – the efficacy (measured by progression-free survival (PFS) at 4 months) of maintenance treatment with cabozantinib as compared with placebo, after clinical benefit to standard chemotherapy (doxorubicin +/- ifosfamide) (given as an adjuvant treatment after surgery, or for locally advanced or metastatic disease). Secondary endpoints include overall survival (OS), response rate (RR) and duration of response, as well as describing the safety profile of cabozantinib in the patient population studied.

Dosage of cabozantinib or placebo is set to 60 mg per day, based on results from preclinical and clinical studies. Treatment will be continued until trial completion (2 years) or occurrence of a criterion for withdrawal. Patients in the control arm (receiving placebo) will be permitted to receive cabozantinib at the time of relapse (disease progression), at the discretion of the investigators. Of note, such cross-over will not affect the selected primary endpoint (PFS).

A total of 54 patients randomised to receive either cabozantinib or placebo were required in order to detect an increase from 50% to 80% in PFS rate after 4 months.

This is an academic trial supported by the EORTC STBSG, the EORTC GCG, and a restricted educational grant from Exelixis, who supply cabozantinib for the whole duration of the trial.

About IRCI

IRCI is a joint initiative between Cancer Research UK (CRUK), the National Institute of Health Research Clinical Research Network: Cancer (NIHR CRN:Cancer), the National Cancer Institute (NCI), the European Organisation for Research and Treatment of Cancer (EORTC), the Institut National Du Cancer (INCa), Clinical Oncology Society of Australia (COSA), Japan Clinical Oncology Group (JCOG) and Canadian Cancer Trials Group. The aim of this initiative is to facilitate the development of international clinical trials for patients with rare cancers in order to boost the progress of new treatments for these patients. The initiative hopes to encourage the use of innovative methodologies to maximise the potential for answering research questions and to identify and overcome barriers to international trials to allow international collaborative trials to run smoothly.

Leading Researchers Present 24-Plex Digital PCR Assay and Novel Multiplex Applications Uniquely Enabled by Stilla’s 6-Color naica® system

On October 15, 2021 Stilla Technologies, the multiplex digital PCR company, reported that researchers from SAGA Diagnostics in presenting a 24-plex digital PCR assay generated on Stilla’s six-color naica system (Press release, Stilla Technologies, OCT 15, 2021, View Source [SID1234591401]). To mark the platform’s global commercial launch at the American Society of Human Genetics (ASHG) 2021 Virtual Meeting, Stilla’s Cofounder and Chief Technology Officer Rémi Dangla, PhD, and researchers from SAGA Diagnostics, Fred Hutchinson Cancer Research Center, and University of Athens highlighted the new data during a discussion on how highly sensitive, multiplex digital PCR technology is transforming complex genomic data into actionable insights across a breadth of research and clinical applications.

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The six-color naica system is the industry’s first digital PCR system featuring six fluorescent channels, providing biomedical researchers and clinicians the highest multiplexing and detection capacity available on the market. Scientists are already using Stilla’s technology to advance their research and discovery across wide applications including cell and gene therapies, cancer and liquid biopsy studies, infectious disease detection including SARS-CoV-2 variant detection in wastewater, and food and environmental testing. Additional information on six-color digital PCR can be found here: www.stillatechnologies.com/6-color-dpcr.

"Modern genetics increasingly relies on more complex signatures from scarce samples to inform on a variety of biological events such as early and residual disease detection, drug mechanism of action and efficiency in patients or full characterization of products for use in gene and cell therapy. Building upon the well-established three-color naica system’s ease-of use and transparency of data delivered, our six-color naica system is democratizing digital PCR and enabling the world’s most powerful platform of its kind," said Dr. Dangla. "From quantifying circulating tumor cells (CTCs) and cell-free DNA (cfDNA) in liquid biopsies for oncology, to detecting low-level genetic variants in infectious diseases, multiplex digital PCR is allowing researchers to parse complex genomics data to gain real-world, clinical insights at both the patient and the population level."

Registered ASH (Free ASH Whitepaper)G 2021 attendees are encouraged to tune in here to join Dr. Dangla and other scientists from Stilla Technologies at the following upcoming sessions:

Presenter: Rémi Dangla, PhD, Cofounder and Chief Technology Officer
Topic: Democratizing digital PCR to bridge the gap between genomics data and genetics insights
Time: October 20, 2021, at 9 AM EDT

Presenter: Kimberley Gutierrez, PhD, Field Applications and Scientific Support Manager
Topic: User-friendly high-plex digital PCR for absolute quantitation of genetic targets
Time: October 21, 2021, at noon EDT