Core Viewpoint - Achilles Therapeutics plc has announced its intention to voluntarily delist its American Depositary Shares (ADSs) from Nasdaq and deregister from the SEC as part of a planned liquidation process [1][2]. Group 1: Delisting and Deregistration - The company will file a Form 25 with the SEC on March 10, 2025, with the last trading day on Nasdaq expected to be March 20, 2025 [2]. - Following the delisting, trading of the company's ADSs will only occur in privately negotiated sales or potentially on an over-the-counter market, with no guarantee of continued trading [2]. - The company plans to file a Form 15 with the SEC around March 20, 2025, which will suspend its obligation to file periodic reports immediately and terminate it 90 days after the Form 15 is filed [3].

Core Viewpoint - Achilles Therapeutics has transferred the commercial license of data and samples from the TRACERx Non-Small Cell Lung Cancer study to AstraZeneca, marking a significant strategic move for both companies [1][2]. Group 1: Transaction Details - AstraZeneca will pay Achilles Therapeutics a total of $12 million for the assets, which include proprietary data and samples from the TRACERx study and the Material Acquisition Platform (MAP) [2]. - The transaction also includes AstraZeneca taking over as the sponsor of the MAP, which has collected tumor tissue and blood from nearly 300 cancer patients across various solid tumor types [1]. Group 2: TRACERx Study Insights - TRACERx is one of the largest tumor evolution studies, generating deep sequencing multi-region and multi-time-point genetic data from over 3,200 tumor samples from more than 800 lung cancer patients [1][9]. - The study has significantly advanced the understanding of tumor evolution, demonstrating that tumors originate from a single cell and evolve in a Darwinian manner, preserving early mutations in all subsequent tumor cells [9]. Group 3: Company Strategy and Future Plans - The completion of this transaction signals the conclusion of Achilles' strategic review, which was initiated in September 2024, and the company plans to implement further measures, including a reduction in employee headcount and Board size [7]. - Achilles Therapeutics focuses on developing AI-powered precision T cell therapies targeting clonal neoantigens, which are unique protein markers expressed on cancer cells [8].

Core Viewpoint - Achilles Therapeutics plc reported its financial results for Q3 2024, highlighting a significant decrease in cash reserves and ongoing strategic evaluations following the discontinuation of certain clinical programs [1][2][3]. Financial Highlights - Cash and cash equivalents stood at $86.1 million as of September 30, 2024, down from $131.5 million as of December 31, 2023. The company received a cash R&D tax credit of $12.8 million in October 2024 [3][6]. - Research and development (R&D) expenses for Q3 2024 were $16.4 million, an increase from $14.7 million in Q3 2023 [3][8]. - General and administrative (G&A) expenses decreased to $4.0 million in Q3 2024 from $4.4 million in Q3 2023 [3][8]. - The net loss for Q3 2024 was $19.6 million, or $0.48 per share, compared to a net loss of $16.7 million, or $0.42 per share, in Q3 2023 [3][8]. Corporate Updates - The company has discontinued its TIL-based cNeT program and closed the Phase I/IIa CHIRON and THETIS clinical trials. It has engaged BofA Securities as a financial advisor to explore strategic options [2][3]. - Chief Scientific Officer Sergio Quezada presented insights from the cNeT clinical trials at the 6th Annual TIL Therapies Summit on October 23, 2024 [2]. Company Overview - Achilles Therapeutics is a clinical-stage biopharmaceutical company focused on developing AI-powered precision T cell therapies targeting clonal neoantigens, which are unique protein markers expressed on cancer cells [4]. - The company utilizes DNA sequencing data and its proprietary PELEUSTM bioinformatics platform to identify patient-specific clonal neoantigens for targeted therapy development [4].

Group 1 - Achilles Therapeutics PLC Sponsored ADR (ACHL) is currently ranked 5 in the Zacks Sector Rank among 1016 companies in the Medical group, indicating strong performance relative to peers [1] - The Zacks Rank for ACHL is 2 (Buy), suggesting a favorable outlook based on earnings estimate revisions and improving earnings outlooks [1] - Year-to-date, ACHL has increased by approximately 17%, outperforming the Medical sector's average return of 10.8% [2] Group 2 - ACHL belongs to the Medical - Biomedical and Genetics industry, which has 495 stocks and is currently ranked 79 in the Zacks Industry Rank, indicating better performance compared to the industry average gain of 2.2% [3] - In contrast, Butterfly Network, Inc. (BFLY), which is in the Medical Info Systems industry ranked 67, has seen its industry decline by 7.7% since the beginning of the year [3] - Both ACHL and BFLY are highlighted as stocks to watch for maintaining solid performance in the Medical sector [3]

Core Insights - Achilles Therapeutics announced a research collaboration with Arcturus Therapeutics to develop second-generation mRNA cancer vaccines utilizing AI-powered tumor-targeting technology [1][4] - The company provided an interim update on its Phase I/IIa clinical trials for clonal neoantigen reactive T cells (cNeT) in advanced non-small cell lung cancer (NSCLC) and melanoma, highlighting improved persistence and engraftment in patients with enhanced host conditioning (EHC) [2][4] - As of June 30, 2024, the company reported a cash position of $95.1 million, which is expected to support operations through 2025 [3][5] Clinical and Business Updates - The collaboration with Arcturus Therapeutics aims to combine Achilles' AI technology with Arcturus' self-amplifying mRNA platform, potentially leading to strong T cell responses in preclinical studies [4] - Interim data from the CHIRON and THETIS trials indicated that the first three EHC patients showed improved cNeT persistence and engraftment [4] - The company has delivered over 100 million cNeT in 10 products and over one billion cNeT in five products [4] Financial Highlights - Cash and cash equivalents decreased to $95.1 million as of June 30, 2024, from $131.5 million as of December 31, 2023 [5] - Research and development (R&D) expenses for Q2 2024 were $13.6 million, slightly down from $13.8 million in Q2 2023, primarily due to reduced activity in the THETIS trial [5] - General and administrative (G&A) expenses were $4.2 million for Q2 2024, compared to $4.3 million in Q2 2023, reflecting lower personnel costs [5] - The net loss for Q2 2024 was $16.4 million, or $0.41 per share, compared to a net loss of $16.8 million, or $0.42 per share, in Q2 2023 [5][6] 2024 Focus - The company plans to report clinical activity and translational science data from the CHIRON and THETIS trials, with significant updates expected in the second half of 2024 [6] - Ongoing evaluation of self-amplifying mRNA personalized cancer vaccines targeting clonal neoantigens is a priority [6] - Development of the VELOS™ and PELEUS™ platforms will continue to optimize cNeT dose and functionality [6] Company Overview - Achilles Therapeutics is a clinical-stage biopharmaceutical company focused on developing AI-powered precision T cell therapies targeting clonal neoantigens unique to individual cancer cells [7] - The company is conducting two ongoing Phase I/IIa trials: the CHIRON trial for advanced NSCLC and the THETIS trial for recurrent or metastatic melanoma [7]

Core Viewpoint - Achilles Therapeutics and Arcturus Therapeutics have announced a research collaboration to develop personalized cancer vaccines using AI-driven tumor-targeting technology and self-amplifying mRNA platforms, aiming to enhance T cell responses against solid tumors [1][2]. Company Overview - Achilles Therapeutics is a clinical-stage biopharmaceutical company focused on AI-powered precision T cell therapies targeting clonal neoantigens, with ongoing Phase I/IIa trials for advanced non-small cell lung cancer and metastatic melanoma [4]. - Arcturus Therapeutics is a global mRNA medicines company known for its self-amplifying mRNA technology and has developed the first approved sa-mRNA COVID vaccine [8][10]. Technology and Innovation - The collaboration will utilize Achilles' PELEUS platform, which employs AI to select highly immunogenic clonal neoantigens, and Arcturus' STARR platform, which combines self-replicating RNA with a nanoparticle delivery system to enhance immune responses [2][9]. - PELEUS identifies clonal neoantigens that are present on all cancer cells but absent from healthy tissue, making them ideal targets for immunotherapy [5][7]. Clinical Development - The collaboration aims to generate IND-enabling data demonstrating the ability to select multiple immunogenic clonal neoantigens for effective T cell responses, with any subsequent clinical development to be jointly agreed upon by both companies [2][3]. - Achilles is advancing its TIL-based clonal neoantigen reactive T cells programs while exploring new modalities for earlier-stage patients through this collaboration [2]. Research Background - The TRACERx study, which provides foundational data for Achilles, has significantly advanced the understanding of tumor evolution and identified clonal neoantigens as promising targets for cancer therapies [6][7].

Core Viewpoint - Achilles Therapeutics and Arcturus Therapeutics have announced a research collaboration to develop personalized cancer vaccines using AI-driven tumor-targeting technology and self-amplifying mRNA platforms, aiming to enhance T cell responses against solid tumors [1][2]. Company Overview - Achilles Therapeutics is a clinical-stage biopharmaceutical company focused on AI-powered precision T cell therapies targeting clonal neoantigens, with ongoing Phase I/IIa trials for advanced non-small cell lung cancer and recurrent melanoma [4]. - Arcturus Therapeutics is a global mRNA medicines company known for its self-amplifying mRNA technology and has developed the first approved sa-mRNA COVID vaccine [8][10]. Technology and Innovation - The collaboration will utilize Achilles' PELEUS platform, which employs AI to select highly immunogenic clonal neoantigens, and Arcturus' STARR platform, which combines self-replicating RNA with a nanoparticle delivery system to enhance immune responses [2][9]. - PELEUS identifies clonal neoantigens that are present on all cancer cells but absent from healthy tissue, making them ideal targets for immunotherapy [5][7]. Clinical Development - The collaboration aims to generate IND-enabling data demonstrating the ability to select multiple immunogenic clonal neoantigens for effective T cell responses, with future clinical development to be jointly agreed upon by both companies [2][3]. - Achilles is advancing its TIL-based clonal neoantigen reactive T cells programs while exploring new modalities for earlier-stage patients through this collaboration [2]. Research Background - The TRACERx study, which provides foundational data for Achilles, has significantly advanced the understanding of tumor evolution and identified clonal neoantigens as promising targets for cancer therapies [6][7].

Nasdaq Compliance and Regulatory Issues - The company received a deficiency letter from Nasdaq on September 20, 2023, indicating that the closing bid price for its ADSs had been below the minimum $1.00 per ADS for 30 consecutive business days[346]. - The company was given until March 18, 2024, to regain compliance with Nasdaq Listing Rule 5550(a)(2) and successfully reestablished price compliance on March 4, 2024[346]. - The company may face challenges in maintaining compliance with Nasdaq listing requirements, which could lead to potential delisting of its ADSs[347]. - The company may incur significant regulatory and compliance costs as a result of operating as a U.S. listed company, which includes legal, accounting, and other expenses not previously incurred as a private entity[348]. - The company is subject to U.S. federal securities laws, and any claims arising under these laws must be brought in federal court in New York[366]. - The company has limited choice of forum for legal actions, which may discourage lawsuits against it[365]. Shareholder Rights and Corporate Governance - The company has not paid dividends on its ADSs and does not intend to do so, limiting returns to shareholders to potential appreciation of their shares[354]. - The company may not provide voting materials to ADS holders in time for them to exercise their voting rights, potentially limiting their ability to participate in corporate governance[356]. - Shareholder approval is required for certain capital structure decisions, which may limit the company's flexibility[367]. - The company has a five-year authorization from shareholders to allot additional shares, which will need to be renewed upon expiration[368]. - Shareholder rights differ under English law compared to U.S. law, including preemptive rights and requirements for shareholder approval on certain corporate actions[396]. - The company is not currently subject to the UK Takeover Code, which affects shareholder protections in takeover situations[392]. - The company’s Articles of Association stipulate that the courts of England and Wales are the exclusive forum for resolving most shareholder complaints[398]. Financial Performance and Operating Results - The company anticipates fluctuations in operating results due to various factors, including research and development costs and clinical trial outcomes, making future results difficult to predict[388]. - The company may face significant fluctuations in quarterly and annual operating results, which could lead to a decline in the price of its American Depositary Shares (ADSs) if expectations are not met[390]. - Total operating expenses for the year ended December 31, 2023, were $75.3 million, a decrease of $3.1 million compared to $78.4 million in 2022[692]. - Research and development expenses increased by $1.0 million to $58.2 million in 2023, primarily due to a $4.7 million increase in the NSCLC program and a $3.2 million increase in the melanoma program[693]. - General and administrative expenses decreased by $4.1 million to $17.0 million in 2023, attributed to a reduction in facilities expenses and lower personnel costs[695]. - Other income (expense), net was $6.1 million for 2023, down from $7.3 million in 2022, mainly due to a decrease in foreign exchange gains[696]. - The provision for income taxes was $0.5 million for 2023, compared to $0.1 million in 2022, related to U.S. income tax obligations[697]. - The net loss for the year ended December 31, 2022, was $71.2 million, compared to a net loss of $61.1 million in 2021[699]. - As of December 31, 2023, the company had cash and cash equivalents of $131.5 million, with net cash proceeds of $230.9 million from preferred shares and $160.6 million from IPO sales[705]. - Net cash used in operating activities for 2023 was $48.4 million, primarily due to a net loss of $69.7 million[708]. - The company expects to fund its operating expenses and capital requirements through 2025 with its current cash reserves, focusing on ongoing clinical trials[715]. Taxation and Financial Obligations - As of December 31, 2023, the company had cumulative United Kingdom carryforward tax losses of $121.7 million[409]. - The company expects to be classified as a Passive Foreign Investment Company (PFIC) for the taxable year ending December 31, 2024[404]. - The UK research and development tax credit regime allows the company to surrender some trading losses for a cash rebate of 33.35% of qualifying R&D expenditure incurred prior to April 1, 2023, decreasing to 18.6% thereafter[410]. - Changes to the R&D tax relief legislation effective from April 2024 may restrict the relief that can be claimed for subcontracted R&D activity[411]. - The company has not paid any UK corporation tax due to generating losses since inception[409]. - The company is subject to increased scrutiny from HMRC regarding claims for R&D tax credits[414]. - The determination of whether the company is a Controlled Foreign Corporation (CFC) is complex and may have adverse tax consequences for U.S. Holders[407]. - The company may incur additional costs if the U.S. Federal Forum Provision is found to be inapplicable or unenforceable[400]. Cybersecurity and Operational Risks - The company has not experienced any material cybersecurity incidents to date, but acknowledges the increasing risk of cyber-attacks that could disrupt operations and compromise sensitive data[373]. - The company relies on third-party providers for manufacturing and clinical trials, which could be adversely affected by cybersecurity incidents or operational disruptions[374]. - The company has implemented security measures to protect its information systems, but acknowledges that cyber-attacks are becoming more sophisticated and frequent[379]. - The company is exposed to significant risks related to cybersecurity incidents, which could lead to litigation, fines, and reputational damage[381]. - The company is predominantly self-insured against various business disruptions, which could significantly harm its financial condition[374]. Environmental and Social Governance (ESG) Concerns - Environmental, social, and governance (ESG) concerns are increasingly impacting the company's operations, potentially leading to increased costs and reduced demand for products if expectations are not met[382]. - Climate change poses physical risks to the company's facilities and supply chain, which could result in increased operational costs and business interruptions[385]. - The company may face new legal or regulatory requirements related to climate change, which could increase compliance costs and operational expenses[387].

Core Insights - Achilles Therapeutics has made significant advancements in its VELOS™ manufacturing process, achieving a ~10-fold improvement in the median clonal neoantigen reactive T cell (cNeT) dose delivered to patients [3][4] - The company is focusing on evaluating the benefits of enhanced host conditioning in its ongoing Phase I/IIa trials for advanced non-small cell lung cancer (NSCLC) and melanoma, with meaningful data updates expected in the second half of 2024 [2][7] - Financially, Achilles Therapeutics maintains a strong cash position of $131.5 million, which is projected to support operations through 2025 [5][6] Clinical Highlights - An interim update on the Phase I/IIa trials revealed improved tolerability profiles and enhanced cNeT doses from the VELOS™ process, with 10 products exceeding 100 million cNeT and five exceeding one billion cNeT [3] - The first patients have been dosed in the CHIRON and THETIS trials, which are assessing the impact of increased lymphodepletion intensity and IL-2 dosing [3] - The company continues to develop its PELEUS™ clonal neoantigen prediction platform, which is crucial for identifying patient-specific neoantigens [3][4] Corporate Highlights - A publication in Nature Cancer highlighted the potential of neoantigen immunogenicity prediction, showcasing the capabilities of the company's neoRanker™ module [4] - Achilles Therapeutics regained compliance with Nasdaq's minimum bid price requirement as of March 1, 2024 [4] - The company has been granted a U.S. patent covering immunotherapy targeting neoantigens presented by HLA alleles that have not been lost in tumors [4] Financial Highlights - Cash and cash equivalents decreased from $173.3 million in 2022 to $131.5 million in 2023, but are still sufficient to fund operations through 2025 [5] - Research and development expenses for Q4 2023 were $15.9 million, down from $18.9 million in Q4 2022, while total R&D expenses for the year increased slightly to $58.2 million [6] - The net loss for Q4 2023 was $18.6 million, or $0.46 per share, an improvement from a net loss of $24.1 million, or $0.61 per share, in Q4 2022 [6][15] 2024 Focus and Upcoming Events - The company plans to report clinical activity and translational science data from the CHIRON and THETIS trials in the second half of 2024 [7] - Upcoming conferences include the Immuno-Oncology Summit Europe and LSX World Congress, where the company will present its advancements [7]

Core Insights - Achilles Therapeutics has reported interim Phase I/IIa data on clonal neoantigen reactive T cells (cNeT) for treating advanced non-small cell lung cancer (NSCLC) and malignant melanoma, showing improved manufacturing processes and patient outcomes [1][3] Manufacturing Process - The VELOS™ manufacturing process has been enhanced, achieving a median of 172 million cNeT doses across 18 patients, a significant increase from 18 million cNeT in the previous update [2][4] - Ten products delivered over 100 million cNeT, with five exceeding one billion cNeT [2][4] Clinical Trials and Patient Data - The update includes data from 18 patients (12 in CHIRON and 6 in THETIS), with a median of two prior lines of therapy [3][4] - Enhanced host conditioning has been introduced in Cohort C, with initial results showing improved cNeT persistence and engraftment [1][4] - No new objective responses were observed, attributed to limited cNeT persistence with previous conditioning regimens [4] Safety and Tolerability - The tolerability profiles for cNeT remain favorable and comparable to standard TIL therapy, with lymphopenia and neutropenia as the most common adverse events [2][3] - No dose-limiting high-grade toxicities were reported [2][4] Future Directions - The company plans to evaluate cNeT persistence and clinical activity in patients with enhanced host conditioning, with a meaningful data update expected in the second half of 2024 [1][3]