On May 20, 2024 OmniAb, Inc. reported that management will be participating at the Jefferies Global Healthcare Conference, being held June 4-6, 2024 at the Marriott Marquis in New York City. Management will be presenting a corporate overview on Wednesday, June 5th at 8:00 a.m. Eastern time and will be holding one-on-one meetings with investors (Press release, OmniAb, MAY 20, 2024, View Source [SID1234643464]).

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A live and archived webcast of the presentation will be available in the Investors section of OmniAb’s website.

On May 20, 2024 Alpha Tau Medical Ltd. ("Alpha Tau", or the "Company") (NASDAQ: DRTS, DRTSW), the developer of the innovative alpha-radiation cancer therapy Alpha DaRT, reported first quarter 2024 financial results and provided a corporate update (Press release, Alpha Tau Medical, MAY 20, 2024, View Source [SID1234643463]).

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"This year we remain focused on advancing our ReSTART U.S. multi-center pivotal trial in recurrent cutaneous squamous cell carcinoma, but in parallel we have seen very encouraging initial results from our internal organ trials over the past quarter, which remind us of the broader opportunity set ahead of us," stated Alpha Tau CEO Uzi Sofer. "Alongside our focus on completing our pivotal trial and feasibility programs, we also continue to make good progress in preparing for potential future product launches by advancing our commercial planning activities and solidifying our supply chain, with a focus on building out our new planned manufacturing facility in Hudson, New Hampshire. Alpha Tau anticipates remaining adequately capitalized to support all of these programs over the coming years," he concluded.

Recent Corporate Highlights:

● In May, preclinical data demonstrating an abscopal immune effect in pancreatic murine tumor models was presented at ESTRO 2024 Congress in Glasgow. Initial data demonstrates significant reduction in distant pancreatic cancer tumor growth rate starting from three weeks after first tumor is treated with Alpha DaRT alone. The effect was seen across both Panc02 and KPC tumor models.

● In May, the first patient with liver cancer metastases was treated in a feasibility and safety study of Alpha DaRT at McGill University Health Center in Montreal, Canada. The trial aims to recruit up to 10 patients who are eligible for a two-staged hepatectomy to resect liver metastases of colorectal cancer. For more information, please refer to View Source

● In May, the first patient was treated in a clinical trial at the Rambam Health Care Campus in Haifa, Israel examining the use of Alpha DaRT for focal treatment of recurrent prostate cancer tumors. The trial aims to recruit up to 10 patients with recurrent, non-metastatic prostate adenocarcinoma. For more information, please refer to View Source

Upcoming 2024 Milestones

● Planning treatment of the first patient in the Israeli recurrent lung cancer safety and feasibility trial in Q2 2024. The trial is currently open for recruitment; for more information please see here: View Source

● Targeting first brain cancer treatment in H2 2024.

● Targeting completion of patient recruitment in the ReSTART U.S. multi-center pivotal trial in recurrent cutaneous squamous cell carcinoma in H2 2024. The trial is currently open for recruitment; for more information please see here: View Source

● Targeting completion of patient recruitment in the Canadian advanced inoperable pancreatic cancer study in Montreal in H2 2024. The trial is currently open for recruitment; for more information please see here: View Source

● Anticipating response from PMDA in Japan by year-end 2024 for pre-market approval for Alpha DaRT in patients with recurrent head and neck cancer.

Financial results for quarter ended March 31, 2024

R&D expenses for the quarter ended March 31, 2024 were $6.4 million, compared to $6.3 million for the same period in 2023, due to increased employee compensation and benefits, including share-based compensation, and increased preclinical study and clinical trial expenses, particularly as related to its ReSTART U.S. multi-center pivotal trial, offset by increased government grants.

Marketing expenses for the quarter ended March 31, 2024 were $0.5 million, compared to $0.4 million for the same period in 2023, due to increased employee compensation and benefits and increased marketing expenses.

G&A expenses for the quarter ended March 31, 2024 were $1.4 million, compared to $1.9 million for the same period in 2023, due primarily to a reduction in D&O insurance costs.

Financial income, net, for the quarter ended March 31, 2024 was $0.4 million, compared to $0.4 million for the same period in 2023, as an increase in interest from bank deposits was offset by a higher expense from remeasurement of warrants.

For the quarter ended March 31, 2024, the Company had a net loss of $8.0 million, or $0.11 per share, compared to a net loss of $8.2 million, or $0.12 per share, in the first quarter of 2023.

Balance Sheet Highlights

As of March 31, 2024, the Company had cash and cash equivalents, deposits and restricted deposits in the amount of $80.7 million, compared to $84.9 million at December 31, 2023. The Company expects that this cash balance will be sufficient to fund anticipated operations for at least two years.

About Alpha DaRT

Alpha DaRT (Diffusing Alpha-emitters Radiation Therapy) is designed to enable highly potent and conformal alpha-irradiation of solid tumors by intratumoral delivery of radium-224 impregnated sources. When the radium decays, its short-lived daughters are released from the sources and disperse while emitting high-energy alpha particles with the goal of destroying the tumor. Since the alpha-emitting atoms diffuse only a short distance, Alpha DaRT aims to mainly affect the tumor, and to spare the healthy tissue around it.

On May 20, 2024 Wugen, Inc., a clinical-stage biotechnology company developing allogeneic, off-the-shelf cell therapies for the treatment of hematological and solid tumor malignancies, reported receipt of two new regulatory designations for its investigational CAR-T cell therapy, WU-CART-007, that it anticipates will expedite regulatory reviews on two continents (Press release, Wugen, MAY 20, 2024, View Source [SID1234643462]).

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Specifically, Wugen received Regenerative Medicine Advanced Therapy (RMAT) designation in the United States and PRIME ("Priority Medicines") designation in the European Union for WU-CART-007 for the treatment of relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL). Both designations provide increased agency support to expedite the development and review of promising therapies for patients in need.

Regulators granted Wugen these designations following their reviews of data including results from the global Phase 1/2 clinical trial for the treatment of R/R T-ALL/LBL. Additional information is available on clinicaltrials.gov, identifier NCT# 04984356. The newest data from the Phase 1/2 study will be presented by Ibrahim Aldoss, M.D., City of Hope, on June 14 during the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress in Madrid, Spain.

"Our goal is to bring this investigational off-the-shelf allogeneic CAR-T treatment to patients as soon as possible," said Kumar Srinivasan, Ph.D., M.B.A., Wugen president and chief executive officer. "These designations represent a significant opportunity to accelerate regulatory reviews for WU-CART-007 as we conclude Phase 1/2 trials and begin pivotal studies later this year."

"The FDA and EMA granted these designations for WU-CART-007 based on the rigor of our data and the potential of WU-CART-007 in addressing serious unmet needs of patients suffering from resistant blood cancers following treatment with current therapies," said Jan Davidson-Moncada, M.D., Ph.D., chief medical officer of Wugen.

About RMAT and PRIME Designations

The U.S. Food and Drug Administration’s Center for Biologic Research and Evaluation grants RMAT designation for regenerative medicine therapies intended to treat, modify, reverse, or cure a serious condition as well as having preliminary clinical evidence indicating their potential to address unmet medical needs for a serious condition. EMA’s PRIME scheme is designed for medicines that demonstrate the potential to address an unmet medical need.

WU-CART-007 previously received Orphan Drug, Fast Track, and Rare Pediatric Disease Designations from the U.S. Food and Drug Administration for the treatment of R/R T-ALL/LBL.

Wugen Presentations at EHA (Free EHA Whitepaper)

These abstracts will be presented at the hybrid EHA (Free EHA Whitepaper) 2024 meeting:

Oral Presentation

Title: WU-CART-007, an Allogeneic CAR-T Cell Targeting CD7, is Highly Effective Against Relapsed/Refractory (R/R) T-Cell Acute Lymphoblastic Leukemia/Lymphoma (T-ALL/LBL)

Presenter: Ibrahim Aldoss, M.D., City of Hope, Duarte, CA

Abstract/Presentation ID: S110

Date/time: Friday, June 14, 14:45-15:00 CEST (8:45-9:00 a.m. U.S. ET)

Poster Presentations

Title: Preliminary Effect of Enhanced Lymphodepletion (ELD) on WU-CART-007 in T-ALL/LBL

Presenters: Ouiam Bakkacha M.D. and Ben Capoccia Ph.D., Wugen, St. Louis, MO

Abstract: P408

Title: WU-NK-101 is an Off-The-Shelf memory NK Cell with a Time-Resilient, Anti-Tumor Phenotype that can be Detected in R/R AML Patient PBMC After Infusion

Presenter: Laura Arthur, Ph.D., Wugen, St. Louis, MO

Abstract: P1422

About WU-CART-007

WU-CART-007 is an allogeneic, off-the-shelf, fratricide-resistant CD7-targeted CAR-T cell therapy engineered to overcome the technological challenges of harnessing CAR-T cells to treat CD7+ hematological malignancies. Wugen is deploying CRISPR/Cas9 gene editing technology to delete CD7 and the T-cell receptor alpha constant (TRAC), preventing CAR-T cell fratricide and mitigating the risk of graft-versus-host-disease (GvHD). WU-CART-007 is manufactured using healthy donor-derived T-cells to eliminate the risk of malignant cell contamination historically observed in the autologous CAR-T setting. WU-CART-007 is currently being evaluated in a global Phase 1/2 clinical trial for the treatment of relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (LBL). Additional information is available on clinicaltrials.gov, identifier NCT# 04984356. WU-CART-007 has received Orphan Drug, Fast Track, and Rare Pediatric Disease Designations from the U.S. Food and Drug Administration for the treatment of R/R T-ALL/LBL.

About WU-NK-101

WU-NK-101 is a novel immunotherapy harnessing the power of memory natural killer (NK) cells to treat liquid and solid tumors. Memory NK cells are hyper-functional, long-lasting immune cells that exhibit enhanced anti-tumor activity and a cytokine-induced memory-like (CIML) phenotype. This cell population has a superior phenotype, proliferation capacity, and metabolic fitness, making it better suited for cancer therapy than other NK cell therapies. Wugen is applying its proprietary MonetaTM platform to advance WU-NK-101 as a commercially scalable, off-the-shelf cell therapy for cancer. WU-NK-101 is currently in development for acute myelogenous leukemia (AML). Wugen is planning to initiate solid tumor studies of WU-NK-101 in combination with cetuximab. Studies of WU-NK-101 to date have shown promising robust in vivo activity in various tumor indications, retention of anti-cancer activity in TME, resistance to immune suppression, and enhanced activity with checkpoint inhibitors. WU-NK-101 has received Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of AML.

On May 20, 2024 Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) (the "Company" or "Sonnet"), a clinical-stage company developing targeted immunotherapeutic drugs, reported that the safety of SON-1010 dosing has been formally reviewed in both of the current Phase 1 clinical trials and the Company is now increasing the target dose of SON-1010 during dose escalation (Press release, Sonnet BioTherapeutics, MAY 20, 2024, View Source [SID1234643461]). SON-1010 is a proprietary version of recombinant human interleukin-12 (rhIL-12), configured using Sonnet’s Fully Human Albumin Binding (FHAB) platform, which extends the half-life and activity of the IL-12 component due to binding native albumin in the serum and targets the tumor microenvironment (TME) by strongly binding gp60 and Secreted Protein Acidic and Rich in Cysteine (SPARC). SB101 is a Phase 1 multiple-ascending dose (MAD) trial in adult patients with advanced solid tumors (NCT05352750) that commenced in Q2 2022 and is currently enrolling the sixth dose cohort. SB221 is a Phase 1b/2a dose-escalation and proof-of-concept study of the combination of SON-1010 with atezolizumab (in collaboration with Genentech, a member of the Roche Group), in a study focused on platinum-resistant ovarian cancer (PROC) (NCT05756907) that started in Q4 2023, now enrolling the fourth dose cohort. In addition, SON-1010 was studied in SB102, which was a Phase 1 single-ascending dose (SAD) trial in healthy volunteers (NCT05408572) that started in Q3 2022; the results were recently published (Kenney, et al, Frontiers in Immunology, 2024).

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Safety in both of the active cancer trials has been reviewed by their respective Safety Review Committees at each step during dose escalation. Both trials use a ‘desensitizing’ first dose to take advantage of the known tachyphylaxis with rhIL-12, which minimizes toxicity and allows higher maintenance doses. No dose-limiting toxicities or related serious adverse events have occurred to date. The safety and toxicity profile that has developed is typical for a Phase 1 oncology trial, with the majority of adverse events (AEs) being reported as mild. All have been transient, with no evidence of cytokine release syndrome. Of the 25 cancer patients dosed to date and evaluable for follow-up at this latest cutoff, 15 (60%) had stable disease at their first follow-up scan, 8 of whom were progressing at study entry. At four months follow-up, 8 of 23 evaluable patients remained stable at the second CT scan, suggesting clinical benefit of SON-1010 in 35% of the patients.

"We have now dosed 18 cancer patients at increasing SON-1010 drug levels in the SB101 study, completed dosing in 31 healthy volunteers in SB102, and are rapidly filling the dose-escalation cohorts with 12 subjects enrolled in the first four cohorts of the SB221 combination study," said Richard Kenney, M.D., Sonnet’s Chief Medical Officer. "The overall safety and toxicity profile for SON-1010, primarily including local reactions, headache, myalgia, and fatigue, mimics the published experience with rhIL-12, which prompted us to raise the target dose to enhance potential efficacy. The SB102 study allowed us to generate clean data for the pharmacokinetic (PK) and pharmacodynamic (PD) analyses, enabling simulation of the effect of multiple doses with the help of a continual reassessment model of PK and PD. This modeling suggests target-mediated drug disposition (TMDD), which supports the mechanism of the FHAB being directed to tumor tissue. The combination of SON-1010 with atezolizumab may benefit from the ability of IL-12 to turn ‘cold’ tumors ‘hot’, which upregulates the amount of PD-L1 in the TME."

One patient with progressive endometrial sarcoma receiving SON-1010 monotherapy in SB101 had stable disease (SD) for almost 2 years before progressing – her ascites had resolved and tumors had shrunk at one point but she never reached a partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) rules. Cytokine analysis following each dose in that study revealed controlled and prolonged induction of interferon gamma (IFNγ) that peaked at 24 to 48 hours and returned to baseline within 2 to 4 weeks. A small increase in IL-10 was observed with each dose as expected in response to IFNγ. There was either a minimal or no signal for IL-1β, IL-6, IL-8, and TNFα, and there was no indication of any potential for cytokine release syndrome (CRS) at these doses. One patient in Part 1 of SB221 with uterine sarcomas received 8 cycles of the SON-1010/atezolizumab combination therapy every 3 weeks before progressing; another two have received 8 and 10 cycles, respectively, and are continuing on the study. The stable AE profiles despite dose escalation led us to reevaluate the target dose, so the Company has added groups in both studies to evaluate 1200 ng/kg SON-1010 as a maintenance dose (the molar equivalent of 800 ng/kg rhIL-12). Finally, Part 2 of the SB221 combination study has been trimmed to remove the monotherapy arm.

"The findings to date in these two trials represent significant progress for the SON-1010 molecule", said Robert Wenham, M.D., Chair, Department of GYN Oncology at Moffitt Cancer Center and the Lead Principal Investigator for SB221. "Multiple strategies to present IL-12 safely have been tried over the past two decades with little evidence of improved tolerability in humans, yet the preclinical models continue to suggest that induction of IFNγ in the TME can activate an effective anti-tumor response. This also results in the local induction of PD-L1. Adding a cohort to increase the target MTD of SON-1010, an extended PK molecule that is concentrated in the TME, is the right approach at this stage. This will provide a chance to study the safety of SON-1010 monotherapy in SB101, and then in combination with atezolizumab in SB221, along with the clinical effect of the combination on PROC in a limited set of subjects in the expansion cohort later this year. Defining the best dose for SON-1010 is required to allow a direct randomized comparison of the strategy with the standard of care therapy in Part 2."

"We are very pleased with the data we are seeing at these higher dose levels of SON-1010, with safety and tolerability being well within expected levels, as well as displaying SON-1010 extended PK/PD, tumor targeting, and clinical activity during treatment," said Pankaj Mohan, Ph.D., Sonnet Founder and Chief Executive Officer. "Research on rhIL-12 in humans has been hindered by toxicity for decades. We believe that the IL-12 component in SON-1010 is presented in a way that is safer, due to the longer half-life, and it is concentrated in the tumor, due to the recurrent binding of the FHAB-associated albumin to SPARC in the TME. It is important to note that many of these patients have been fighting their cancers for a very long time and have exhausted all approved treatment regimens available to them, so seeing tumor shrinkage at any dose is both difficult to achieve and encouraging for future results. We are excited to continue testing the impact of SON-1010 in combination with atezolizumab at these higher dose levels in patients with PROC, who represent a significant unmet medical need, and we expect to have a further update early next year."

About SON-1010

SON-1010 is a candidate immunotherapeutic recombinant drug that links unmodified single-chain human IL-12 with the albumin-binding domain of the single-chain antibody fragment A10m3. This was selected to bind both at normal pH, as well as at the acidic pH typically found in the TME. The FHAB technology targets tumor and lymphatic tissue, providing a mechanism for dose sparing and an opportunity to improve the safety and efficacy profile of not only IL-12, but a variety of potent immunomodulators that can be added using the platform. Interleukin-12 can orchestrate a robust immune response to many cancers and pathogens. Given the types of proteins induced in the TME, such as the Secreted Protein and Rich in Cysteine (SPARC) and glycoprotein 60 (GP60), several types of cancer such as non-small cell lung cancer, melanoma, head and neck cancer, sarcoma, and some gynecological cancers are particularly relevant for this approach. SON-1010 is designed to deliver IL-12 to local tumor tissue, turning ‘cold’ tumors ‘hot’ by stimulating IFNγ, which activates innate and adaptive immune cell responses and increases the production of Programed Death Ligand 1 (PD-L1) on tumor cells.

About the SB101 Phase 1 Trial

This first-in-human study is primarily designed to evaluate the safety of multiple ascending doses of SON-1010 in cancer patients and will be conducted at several sites across the United States. While the optimal dose is unknown at this stage, the potential to target tumors, the extended PK mechanism and our preclinical data suggest the therapeutic dose may be lower compared to native human IL-12. The study, utilizing a standard 3+3 oncology design in at least five cohorts, should establish the MTD and the recommended Phase 2 dose (RP2D) using monthly subcutaneous injections of SON-1010. The primary endpoint explores the safety and tolerability of SON-1010, with key secondary endpoints intended to measure pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and anti-tumor activity. This study will form the basis for potential combinations with other types of immunotherapies and the future development of bispecific candidates using the FHAB platform.

About the SB221 Phase 1b/2a Trial

SB221 is a global Phase 1b/2a multicenter, dose-escalation and randomized proof-of-concept study to assess the safety, tolerability, PK, PD, and efficacy of SON-1010 administered subcutaneously (SC), either alone or in combination with atezolizumab given intravenously (IV). The study is designed in Part 1 to rapidly establish the maximum tolerated dose (MTD) of the combination in patients with advanced solid tumors at the lower dose levels. The focus shifts to PROC at higher dose levels using small dose-escalation groups with expansion of the dataset at the recommended Phase 2 dose (RP2D). This would be followed in Part 2 by an assessment in patients with PROC of the potential for improved efficacy of the combination versus the standard of care. Both companies look forward to this collaboration as an opportunity to improve outcomes for patients with ovarian cancer.

On May 20, 2024 PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to changing the lives of patients with devastating diseases, reported the opening of its proposed $100 million tender offer (the "Tender Offer") (Press release, PureTech Health, MAY 20, 2024, View Source [SID1234643460]).

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Tender Offer Highlights

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The Tender Offer opens today 20 May 2024. Subject to the terms and conditions of the Tender Offer, the Company will purchase for cash a maximum of $100 million in value of ordinary shares of one pence each in the capital of the Company ("Ordinary Shares") (including Ordinary Shares represented by the Company’s American Depositary Shares each representing 10 Ordinary Shares ("ADSs")).

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The Tender Offer for the Company’s Ordinary Shares will close at 1:00 p.m. London time on Thursday 20 June 2024 (the "Ordinary Share Closing Date"), and the Tender Offer for the Company’s ADSs will close at 5:00 p.m. New York City time on Tuesday 18 June 2024 (the "ADS Closing Date"), unless the Tender Offer is extended.

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The Company is offering to purchase up to 33,500,000 Ordinary Shares (including Ordinary Shares represented by ADSs) representing approximately 12 percent of the Company’s issued ordinary share capital as at 16 May 2024 (being the latest practicable date before publication of this announcement ("Latest Practicable Date")) at a fixed price of 250 pence per Ordinary Share (equivalent to £25.00 per ADS) (the "Tender Price") up to a maximum aggregate amount of $100 million. The maximum amount of $100 million will be translated into a pounds sterling amount on the Ordinary Share Closing Date, and that pounds sterling amount shall determine the maximum number of shares to be accepted for payment in the Tender Offer.

•
The Tender Price represents a premium of 25 percent to PureTech’s trailing volume weighted average price per Ordinary Share over the three days prior to 19 March 2024, the date of the Company’s initial announcement of the Tender Offer proposals and a premium of 12.6 percent to the closing price of 222 pence per Ordinary Share on the Latest Practicable Date.

•
If the full $100 million is not returned through the Tender Offer, then, if there is sufficient surplus, the Company’s board of directors ("Board") intends to return such surplus by way of a special dividend following completion of the Tender Offer, without interest, less any applicable withholding taxes and subject to market and industry conditions at the time and any relevant legal restrictions (the "Special Dividend").

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Completion of the Tender Offer will be conditional, among other things, on shareholder approval at a general meeting of the Company to be held at 11:00 a.m. New York City time (4:00 p.m. London time) on 6 June 2024 at the Company’s offices at 6 Tide Street, Boston, Massachusetts, 02210, United States (the "General Meeting").

•
Full details of the Tender Offer are included in a circular to the Company’s Shareholders (the "Circular") which will be mailed to Shareholders and ADS Holders today and available on a website set up by the Company for the purposes of the Tender Offer. The website is available at View Source Copies of the Circular will be submitted to the National Storage Mechanism and will be available for inspection at View Source The Circular will also be included as an exhibit to the Schedule TO to be filed with the Securities and Exchange Commission and will be available for inspection at View Source

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SHAREHOLDERS AND ADS HOLDERS ARE ADVISED TO CONSULT WITH THEIR PROFESSIONAL TAX ADVISORS IN CONNECTION WITH CERTAIN US FEDERAL WITHHOLDING TAX CONSIDERATIONS DESCRIBED IN FURTHER DETAIL BELOW (SEE "Certain US Federal Income Tax Considerations with Respect to the Tender Offer").

Structure of the Tender Offer

The Tender Offer will be implemented on the basis of Jefferies International Limited ("Jefferies") acquiring, as principal, the successfully tendered Ordinary Shares (including Ordinary Shares represented by ADSs) at the Tender Price. In turn, Jefferies has the right to require the Company to purchase such Ordinary Shares (including Ordinary Shares represented by ADSs) from it at the same Tender Price pursuant to an option agreement entered into between the Company and Jefferies (the "Option Agreement"). If Jefferies does not exercise its right to require the Company to purchase such Ordinary Shares (including Ordinary Shares represented by ADSs), the Company has the right to require Jefferies to sell such Ordinary Shares (including Ordinary Shares represented by ADSs) to it at the same price. The Company intends to cancel the Ordinary Shares (including Ordinary Shares represented by ADSs) purchased by it pursuant to the Tender Offer.

Shareholders can decide whether they want to tender all, some or none of their Ordinary Shares or ADSs in the Tender Offer.

If the aggregate value at the Tender Price of all validly tendered Ordinary Shares (including Ordinary Shares represented by ADSs) exceeds $100 million (based on the applicable exchange rate of US dollars to pounds sterling on the Ordinary Share Closing Date) or the number of validly tendered Ordinary Shares (including Ordinary Shares represented by ADSs) exceeds 33,500,000 Ordinary Shares, then not all of the Ordinary Shares (including Ordinary Shares represented by ADSs) validly tendered will be accepted and purchased. In these circumstances, tenders will be scaled down pro-rata to the total number of Ordinary Shares (including Ordinary Shares represented by ADSs) so tendered by that shareholder, such that the total cost of Ordinary Shares (including Ordinary Shares represented by ADSs) purchased pursuant to the Tender Offer does not exceed $100 million or the total number of validly tendered Ordinary Shares (including Ordinary Shares represented by ADSs) does not exceed 33,500,000 Ordinary Shares.

Certain US Federal Income Tax Considerations with Respect to the Tender Offer

Shareholders and ADS Holders should consult their professional tax advisors in connection with the Tender Offer.

Shareholders and ADS Holders should note that, due to the circumstances of its formation and the application of Section 7874 of the United States Internal Revenue Code of 1986, as amended ("Code"), the Company is treated as a US domestic corporation for US federal income tax purposes. Accordingly, the Company is subject to US federal income tax as if it were a US corporation, and distributions made by the Company (including certain payments in respect of the Tender Offer that are treated as distributions for US federal income tax purposes) are generally treated as US-source dividends, as if the Company were incorporated in the US. As a result, both US Holders and Non-US Holders (each as defined in the Circular) may be subject to US federal income tax withholding on receipt of cash proceeds from any tendered Ordinary Shares or ADSs accepted in the Tender Offer and the Special Dividend (if any).

The attention of Shareholders and ADS Holders is drawn to Part VI of the Circular, which provides a summary of certain material UK tax and US federal income tax consequences for Shareholders and ADS Holders of accepting the Tender Offer or receipt of the Special Dividend (if any).

All Shareholders and ADS Holders should receive a Section 302 Certification. Copies of the Section 302 Certification, IRS Form W-9, and IRS Forms W-8, as well the IRS instructions with respect to such IRS Forms, are also available on the Microsite set up by the Company for the purposes of the Tender Offer. The Microsite is available at View Source

In consultation with their professional tax advisors regarding their individual circumstances, Shareholders and ADS Holders should complete the Section 302 Certification and an IRS Form W-9 or applicable IRS Form W-8, as applicable, in accordance with the instructions thereon. Shareholders and ADS Holders should return the properly completed Section 302 Certification and the IRS Form W-9 or applicable IRS Form W-8, as applicable, in accordance with the instructions set forth the Circular, the Tender Form, the Letter of Transmittal and the Section 302 Certification, as applicable. Part VI of the Circular also provides additional information to Shareholders and ADS Holders on the process for returning a Section 302 Certifications and an IRS Form W-9 or applicable IRS Forms W-8, as applicable.

The appropriate IRS Form W-9 or Form W-8 should be returned whether or not a Shareholder plans to participate in the Tender Offer, if not previously provided. IRS Form W-9 and IRS Form W-8 will also be relevant in connection with the Special Dividend (if any).

This information is not tax advice, and the Company cannot advise you with respect to taxes. Shareholders and ADS Holders should consult their professional tax advisors, in particular regarding their individual tax position and the exemptions or reductions of US withholding tax that may be available to them. For more information, Shareholders and ADS Holders should read the full text of this announcement of the Tender Offer, the Circular, the Tender Form, and the Letter of Transmittal.

General Meeting

Implementation of the Tender Offer is conditional upon, amongst other things, the approval of the shareholders of the resolution necessary to implement the Tender Offer (the "Resolution"). For this purpose, the Company is convening the General Meeting for 11 a.m. New York City time (4 p.m. London time) on 6 June 2024 to be held at 6 Tide Street, Boston, Massachusetts, 02210, United States to consider and, if thought fit, pass the Resolution to approve the terms on which the Tender Offer will be effected. A notice convening the General Meeting is set out at the end of the Circular.

Participating in the Tender Offer

If you are a Shareholder and hold your Ordinary Shares in Certificated Form and you wish to tender all or any of your Ordinary Shares, you should complete the Tender Form in accordance with the instructions printed on it and in Part V of the Circular and return it by post in the accompanying reply-paid envelope (for use in the UK only) to the Receiving Agent, at the Pavilions, Bridgewater Road, Bristol, BS99 6AH so as to be received by no later than 1:00 p.m. (London time) on Thursday 20 June 2024, together with your share certificate(s) in respect of the Ordinary Shares tendered.

If you are a Shareholder and hold your Ordinary Shares in Uncertificated Form and you wish to tender all or any of your Ordinary Shares, you should send the TTE Instruction through CREST so as to settle by no later than 1:00 p.m. (London time) on Thursday 20 June 2024.

Any ADS Holder who holds ADSs on the books of the Depositary who wishes to tender pursuant to the Tender Offer should properly complete and duly execute a Letter of Transmittal (or facsimile thereof), together with any required signature guarantees and any other required documents, and deliver such documents to the tender agent for the ADSs, Citibank, N.A. (the "Tender Agent"), at the appropriate address set forth in the Letter of Transmittal so as to be received no later than 5:00 p.m. (New York City time) on the ADS Closing Date (unless the Tender Offer is extended). In addition, the ADRs evidencing the tendered ADSs must be received by the Tender Agent at the appropriate address or be delivered pursuant to the procedures for book-entry transfer set forth below (and a confirmation of receipt of such transfer must be received by the Tender Agent) so as to be received no later than 5:00 p.m. (New York City time) on the ADS Closing Date.

If the ADSs are held through a broker, dealer, commercial bank, trust company or other securities intermediary and the ADS Holder wishes to participate in the Tender Offer, such ADS Holder should provide tender instructions in accordance with the instructions provided by such intermediary in sufficient time so as to ensure that such intermediary can provide such instructions to the Tender Agent so as to be received no later than 5:00 p.m. (New York City time) on the ADS Closing Date (unless the Tender Offer is extended).

Timetable

A summary expected timetable of principal events is set out in Appendix I to this announcement.