Revenues - Revenues for the three and nine months ended September 30, 2021 and 2022 were $0, with no anticipated revenues for the foreseeable future[124][125] Research and Development Expenses - Research and development expenses increased by $2.7 million from $10.9 million for the nine months ended September 30, 2021 to $13.6 million for the same period in 2022[130] - Total research and development expenses for the three months ended September 30, 2022 were $4.4 million, representing a 5% increase compared to $4.2 million in the same period of 2021[129] - The transcriptional regulation program (fadraciclib) incurred $2.5 million in expenses for the three months ended September 30, 2022, a decrease of 25% from $3.3 million in the same period of 2021[129] - CYC140 research and development expenses increased by 157% to $1.7 million for the three months ended September 30, 2022, compared to $664,000 in the same period of 2021[129] - The company anticipates an increase in overall research and development expenses for the year ended December 31, 2022 compared to 2021 as it progresses its clinical development programs[133] General and Administrative Expenses - General and administrative expenses for the three months ended September 30, 2022 were $2.1 million, a 15% increase from $1.8 million in the same period of 2021[134] Income and Other Financial Metrics - Total other income increased by $1.7 million from $0.2 million for the nine months ended September 30, 2021 to $1.9 million for the same period in 2022[137] - Foreign exchange gains increased by $0.5 million, from $5,000 for the nine months ended September 30, 2021, to $0.5 million for the nine months ended September 30, 2022[140] - Total income tax benefit increased by approximately $0.5 million from $2.6 million for the nine months ended September 30, 2021, to $3.1 million for the nine months ended September 30, 2022, representing an 18% increase[143] Cash and Cash Equivalents - Cash and cash equivalents decreased from $40.2 million as of September 30, 2021, to $23.7 million as of September 30, 2022[145] - Net cash used in operating activities increased by $1.7 million, from $14.0 million for the nine months ended September 30, 2021, to $15.7 million for the nine months ended September 30, 2022[150] - Net cash provided by financing activities was $2.9 million for the nine months ended September 30, 2022, compared to $20.9 million for the same period in 2021[152][153] Accumulated Deficit and Future Outlook - The accumulated deficit as of September 30, 2022, was $398.7 million[147] - The company expects to incur substantial operating losses in the future and does not guarantee significant product revenues until FDA or EMA approval[156] - Future funding requirements will depend on various factors, including clinical trial costs and the impact of COVID-19 on operations[158] Strategic Plans - The company plans to evaluate in-licensing and acquisition opportunities to access new drugs or drug targets[157] Impact of COVID-19 - The COVID-19 pandemic has negatively impacted clinical trials and the availability of materials, affecting the company's operations[162] - The company will not pursue further development of sapacitabine and has notified the licensor of the termination of the license agreement effective March 23, 2023[127]

Corporate Presentation September 2022 Translating cancer biology into medicines Disclaimer This presentation contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forwardlooking statements. Such forward-looking statements include statements regarding, among other things, the efficacy, safety and intended utilization of Cyclacel's product candid ...

Financial Data and Key Metrics Changes - As of June 30, 2022, cash and cash equivalents totaled $29.1 million, down from $36.6 million as of December 31, 2021, with available cash resources expected to fund planned programs into the second half of 2023 [31] - Research and development (R&D) expenses were $4.2 million for Q2 2022, slightly up from $4.1 million in Q2 2021 [31] - Net loss for Q2 2022 was $4.6 million, compared to $5.1 million for the same period in 2021 [34] Business Line Data and Key Metrics Changes - R&D expenses related to the lead product candidate, oral fadraciclib (fadra), were $2.6 million for Q2 2022, down from $2.8 million in Q2 2021, attributed to increased clinical trial costs [32] - R&D expenses for CYC140 were $1.5 million for Q2 2022, compared to $1.1 million in Q2 2021, due to the initiation of the CYC140 Phase 1/2 study [33] Market Data and Key Metrics Changes - The 065-101 study of oral fadra is enrolling well at four sites in the US, South Korea, and Spain, with 17 patients enrolled in the dosage escalation part of the study [9][10] - The company is also testing oral fadra for leukemia and myelodysplastic syndromes in study 065-102, which is currently enrolling patients [23] Company Strategy and Development Direction - The company aims to establish oral fadra as a best-in-class CDK inhibitor, focusing on its dual targeting of CDK2 and CDK9, good tolerability, and preliminary anti-cancer activity [11][12] - The company plans to hold an R&D day in the fall to provide updates on clinical programs and preclinical work [29] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the safety and anti-cancer activity of oral fadra, noting the encouraging results in heavily pretreated patients [7][8] - The company anticipates building momentum as the fadra solid tumor trial progresses, along with other clinical stage programs [48] Other Important Information - The company has made progress in advancing its novel PLK1 inhibitor, CYC140, into a Phase 1/2 study for solid tumors and lymphomas, with no dose-limiting toxicities observed so far [27][28] Q&A Session Summary Question: Plans for R&D Day and safety data from fadra program - Management confirmed that updates, including safety data, will be presented during the R&D Day event in Q3 [35][36] Question: Synergistic toxicity of inhibiting CDK2 and CDK9 - Management indicated that no toxicity has been observed in the study so far [37] Question: Indications for CYC140 and enrollment rates - Management discussed ongoing dose escalation and indicated that solid tumors and lymphomas are currently the focus, with plans to activate the leukemia part of the study later [41][42] Question: Upcoming conferences and data presentations - Management mentioned that an abstract has been submitted for an upcoming oncology conference, with expectations for data updates in the second half of the year [43][45]

Revenue and Income - Revenues for the three and six months ended June 30, 2021 and 2022 were $0, with no anticipated revenues for the foreseeable future[124][125]. - Total other income increased by $1.4 million from $0.1 million for the six months ended June 30, 2021 to $1.5 million for the six months ended June 30, 2022[136]. - Total income tax benefit increased by approximately $0.5 million from $1.6 million for the six months ended June 30, 2021 to $2.1 million for the six months ended June 30, 2022, representing a 29% increase[141]. Research and Development Expenses - Research and development expenses increased by $2.5 million from $6.7 million for the six months ended June 30, 2021 to $9.2 million for the six months ended June 30, 2022[129]. - Expenditure for the transcriptional regulation program increased by $1.8 million for the six months ended June 30, 2022, primarily due to a $2.2 million increase in clinical trial costs[129]. - Total research and development expenses represented 73% and 74% of operating expenses for the three and six months ended June 30, 2022, respectively[128]. - The company anticipates an increase in overall research and development expenses for the year ended December 31, 2022 compared to the previous year[131]. - The company expects eligible expenses for research and development to be higher in the fiscal year ended December 31, 2022, leading to an anticipated increase in tax credits recoverable[142]. Cash Flow and Financial Position - Cash and cash equivalents decreased from $43.6 million as of June 30, 2021 to $29.1 million as of June 30, 2022[143]. - Net cash used in operating activities increased by $0.9 million, from $7.8 million for the six months ended June 30, 2021 to $8.7 million for the six months ended June 30, 2022[146]. - Net cash provided by financing activities was $1.4 million for the six months ended June 30, 2022, compared to $17.9 million for the same period in 2021[148][149]. - The accumulated deficit as of June 30, 2022, was $393.6 million, indicating significant losses since inception[143]. Clinical Trials and Drug Development - The ongoing Phase 1/2 studies for fadraciclib and CYC140 aim to assess safety and identify signals of clinical activity[118][122]. - The COVID-19 pandemic has adversely affected clinical trials, particularly in patient enrollment and resource allocation[155]. - The company does not currently have sufficient funds to complete the development and commercialization of any drug candidates[151]. Future Funding and Opportunities - Future funding requirements will depend on various factors, including clinical trial costs and the impact of COVID-19 on operations[153][155]. - The company plans to evaluate in-licensing and acquisition opportunities to access new drugs or drug targets, which may increase future funding needs[151]. General and Administrative Expenses - General and administrative expenses decreased by 21% to $1.58 million for the three months ended June 30, 2022 compared to $1.99 million for the same period in 2021[133]. Marketing Rights - The company retains virtually all marketing rights worldwide to the compounds associated with its drug programs[123].

Financial Data and Key Metrics Changes - As of March 31, 2022, cash and cash equivalents totaled $29.6 million, down from $36.6 million as of December 31, 2021. After receiving $3.6 million in UK research and development tax credits and $1.3 million in royalty receipts post-quarter, cash and cash equivalents increased to $34.5 million [19] - Research and development (R&D) expenses were $5 million for Q1 2022, compared to $2.6 million for the same period in 2021, reflecting increased clinical trial costs [20] - The net loss for Q1 2022 was $4.1 million, compared to $3.5 million for the same period in 2021 [23] Business Line Data and Key Metrics Changes - R&D expenses related to fadraciclib were $3.6 million for Q1 2022, up from $1.7 million in Q1 2021, due to increased clinical trial costs [20] - R&D expenses for CYC140 were $1.1 million for Q1 2022, compared to $0.7 million in Q1 2021, attributed to costs associated with opening clinical trial sites [21] Market Data and Key Metrics Changes - The company is currently enrolling patients in three separate registration-directed Phase I/II clinical trials for its drug candidates fadraciclib and CYC140, despite challenges in patient enrollment faced by many biotechnology companies [5][6] Company Strategy and Development Direction - The company aims to meet key milestones for its drug candidates in 2022, including initial data for oral fadraciclib, and believes it has sufficient resources to fund operations through mid-2023 [7] - The clinical development plan for CYC140 will explore its potential for single-agent activity across various solid tumor types and hematological malignancies [15] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's competitive position and the potential for recovery in the biopharma market, emphasizing the importance of their clinical assets [7] - The management team highlighted the importance of continuous daily dosing for their drugs, which they believe provides a competitive advantage [14] Other Important Information - The company has established strong relationships with leading cancer centers in the U.S. and abroad, which is crucial for their clinical development efforts [6] - The company anticipates completing analyses related to fadraciclib in the coming weeks and remains on track to initiate the Phase II part of the study in the second half of 2022 [10] Q&A Session Summary Question: Update on oral fadraciclib cohort 5 and DLTs - Management confirmed that a patient has been dosed in cohort 5 and is doing well [25] Question: Timeline for updates on oral fadraciclib - Management expects to hold an R&D Day in early summer to provide updates [27] Question: Dosing strategy for the hematologic malignancy study - Management indicated that the dosing strategy for the leukemia trial is aligned with the solid tumor trial [29] Question: Active sites and dosing schedule for CYC140 - Management stated that they are starting with two initial sites for CYC140 and will proceed cautiously [31] Question: Differentiating factors of CYC140 compared to other PLK1 inhibitors - Management highlighted that CYC140 has a shorter half-life and is designed for oral administration, which may provide advantages over other PLK1 inhibitors [37] Question: Rationale behind indication selection for CYC140 - Management explained that all selected cohorts have a PLK1-related mechanism, supported by preclinical data [39] Question: Expectations for success across different tissue types in trials - Management noted that the trial design allows for flexibility to adapt based on emerging data from various tumor types [43]

[Part I. Financial Information](index=3&type=section&id=Part%20I.%20Financial%20Information) [Item 1. Financial Statements (Unaudited)](index=3&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) Cyclacel Pharmaceuticals reported no revenue and a net loss of $4.1 million for Q1 2022, with cash decreasing to $29.6 million due to increased R&D expenses [Consolidated Balance Sheets](index=3&type=section&id=Consolidated%20Balance%20Sheets) Total assets decreased to $39.6 million as of March 31, 2022, primarily due to a reduction in cash and cash equivalents | Financial Metric | March 31, 2022 ($000s) | December 31, 2021 ($000s) | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | 29,639 | 36,559 | | Total current assets | 36,577 | 40,942 | | Total assets | 39,629 | 42,587 | | **Liabilities & Equity** | | | | Total current liabilities | 6,204 | 5,294 | | Total liabilities | 6,219 | 5,324 | | Total stockholders' equity | 33,410 | 37,263 | | Total liabilities and stockholders' equity | 39,629 | 42,587 | [Consolidated Statements of Operations](index=4&type=section&id=Consolidated%20Statements%20of%20Operations) The company reported no revenue and an increased net loss of $4.1 million for Q1 2022, driven by higher research and development expenses | Metric | Three Months Ended March 31, 2022 ($000s) | Three Months Ended March 31, 2021 ($000s) | | :--- | :--- | :--- | | Revenues | 0 | 0 | | Research and development | 4,954 | 2,566 | | General and administrative | 1,605 | 1,739 | | Total operating expenses | 6,559 | 4,305 | | Operating loss | (6,559) | (4,305) | | Net loss | (4,108) | (3,478) | | Net loss applicable to common shareholders | (4,158) | (3,528) | | Net loss per share – basic and diluted | $(0.42) | $(0.50) | [Consolidated Statements of Cash Flows](index=7&type=section&id=Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operating activities increased to $6.8 million in Q1 2022, resulting in a $6.9 million net decrease in cash and cash equivalents | Cash Flow Activity ($000s) | Three Months Ended March 31, 2022 | Three Months Ended March 31, 2021 | | :--- | :--- | :--- | | Net cash used in operating activities | (6,775) | (3,566) | | Net cash used in investing activities | (4) | (78) | | Net cash (used in) provided by financing activities | (50) | 17,997 | | Net (decrease) increase in cash and cash equivalents | (6,920) | 14,371 | | Cash and cash equivalents, end of period | 29,639 | 47,777 | [Notes to Unaudited Consolidated Financial Statements](index=8&type=section&id=Notes%20to%20Unaudited%20Consolidated%20Financial%20Statements) The company, a clinical-stage biopharmaceutical firm, has $29.6 million in cash, sufficient to fund operations through June 2023, and recognized $1.3 million in other income - The company is a clinical-stage biopharmaceutical firm focused on developing cancer medicines based on cell cycle, transcriptional regulation, and mitosis control biology[26](index=26&type=chunk) - Management asserts that the company's cash of approximately **$29.6 million** as of March 31, 2022, is sufficient to fund operations and capital expenditures through June 30, 2023, with future viability dependent on raising additional capital[29](index=29&type=chunk)[32](index=32&type=chunk) - The company recognized **$1.3 million** of other income during Q1 2022 related to royalty payments receivable under a December 2005 Asset Purchase Agreement with Thermo Fisher Scientific Company[56](index=56&type=chunk) - As of March 31, 2022, the company had sold **752,425 shares** for gross proceeds of approximately **$4.0 million** under its August 2021 Controlled Equity Offering Sales Agreement[75](index=75&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=30&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the company's clinical-stage programs, fadraciclib and CYC140, highlighting a 93% increase in R&D expenses and the need for future capital [Overview](index=30&type=section&id=Overview) Cyclacel, a clinical-stage biopharmaceutical company, focuses on fadraciclib and CYC140, with the first patient in the CYC140 study dosed in April 2022 - The company's primary focus is on its transcriptional regulation program evaluating fadraciclib (CDK2/9 inhibitor) and its anti-mitotic program evaluating CYC140 (PLK1 inhibitor)[114](index=114&type=chunk) - Fadraciclib is in ongoing Phase 1/2 studies for advanced solid tumors/lymphomas (065-101) and hematological malignancies (065-102)[115](index=115&type=chunk)[117](index=117&type=chunk) - The first patient was dosed in the CYC140 Phase 1/2 study for hematological malignancies (140-101) in April 2022[118](index=118&type=chunk) [Results of Operations](index=32&type=section&id=Results%20of%20Operations) For Q1 2022, the company reported no revenue, a 93% increase in R&D expenses, and a significant rise in other income from royalty payments | R&D Expense Breakdown ($000s) | Q1 2022 | Q1 2021 | Change (%) | | :--- | :--- | :--- | :--- | | Transcriptional Regulation (fadraciclib) | 3,645 | 1,662 | 119% | | Anti-mitotic (CYC140) | 1,122 | 679 | 65% | | **Total R&D Expenses** | **4,954** | **2,566** | **93%** | - The increase in R&D expenses was driven by a **$1.7 million** rise in clinical trial costs for fadraciclib and a **$0.4 million** increase for CYC140 trial site openings[125](index=125&type=chunk) - General and administrative expenses decreased by **8%** to **$1.6 million** in Q1 2022 from **$1.7 million** in Q1 2021, due to lower professional and recruitment costs[128](index=128&type=chunk) - Total other income increased to **$1.3 million** in Q1 2022 from **$140,000** in Q1 2021, mainly due to **$1.3 million** in royalty income from a 2005 asset sale agreement[130](index=130&type=chunk) [Liquidity and Capital Resources](index=37&type=section&id=Liquidity%20and%20Capital%20Resources) As of March 31, 2022, the company had $29.6 million in cash, sufficient through June 2023, but acknowledges the need for additional future funding | Liquidity Metric ($000s) | March 31, 2022 | March 31, 2021 | | :--- | :--- | :--- | | Cash and cash equivalents | 29,639 | 47,777 | | Total working capital | 30,373 | 47,691 | - Net cash used in operating activities increased to **$6.8 million** in Q1 2022 from **$3.6 million** in Q1 2021, primarily due to increased clinical activities[140](index=140&type=chunk) - Existing funds are expected to be sufficient to satisfy working capital and capital expenditure needs through June 30, 2023[144](index=144&type=chunk) - The company will require additional funding to complete the development and commercialization of any of its drug candidates, which it may seek through equity offerings, debt financings, or strategic collaborations[148](index=148&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=43&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a smaller reporting company, Cyclacel is exempt from providing quantitative and qualitative disclosures about market risk - As a smaller reporting company, Cyclacel is not required to provide quantitative and qualitative disclosures about market risk[153](index=153&type=chunk) [Item 4. Controls and Procedures](index=43&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of March 31, 2022, with no significant changes in internal control over financial reporting - The company's management, including the CEO and principal financial officer, concluded that disclosure controls and procedures were effective as of March 31, 2022[154](index=154&type=chunk) - There were no significant changes in the company's internal controls over financial reporting during the quarter ended March 31, 2022[155](index=155&type=chunk) [Part II. Other Information](index=43&type=section&id=Part%20II.%20Other%20Information) [Item 1. Legal Proceedings](index=43&type=section&id=Item%201.%20Legal%20Proceedings) The company reported no legal proceedings during the period - There are no legal proceedings to report[157](index=157&type=chunk) [Item 1A. Risk Factors](index=43&type=section&id=Item%201A.%20Risk%20Factors) No material changes have occurred in the company's risk factors since its Annual Report on Form 10-K for the year ended December 31, 2021 - No material changes have occurred in the company's risk factors since its Annual Report on Form 10-K for the year ended December 31, 2021[158](index=158&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=43&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company reported no unregistered sales of equity securities during the period - None[160](index=160&type=chunk) [Item 3. Defaults Upon Senior Securities](index=45&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) The company reported no defaults upon senior securities - None[161](index=161&type=chunk) [Item 4. Mine Safety Disclosures](index=45&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to the company - Not applicable[162](index=162&type=chunk) [Item 5. Other Information](index=45&type=section&id=Item%205.%20Other%20Information) The company reported no other information - None[163](index=163&type=chunk) [Item 6. Exhibits](index=45&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the Form 10-Q, including certifications by the Principal Executive Officer and Principal Financial Officer and iXBRL financial statements - Exhibits filed include CEO and CFO certifications (31.1, 31.2, 32.1, 32.2) and iXBRL formatted financial data (101, 104)[164](index=164&type=chunk)

[PART I](index=6&type=section&id=PART%20I) - The company is a clinical-stage biopharmaceutical firm developing cancer medicines based on cell cycle, transcriptional regulation, and mitosis control biology[14](index=14&type=chunk) - The main clinical programs are evaluating fadraciclib (CDK2/9 inhibitor) and CYC140 (PLK1 inhibitor) in various cancers[15](index=15&type=chunk) - Cyclacel's strategy involves building a diversified pipeline, retaining commercialization rights, and entering into selective partnerships[16](index=16&type=chunk) [Business](index=6&type=section&id=Item%201.%20Business) Cyclacel is a clinical-stage biopharmaceutical company developing cancer medicines focused on cell cycle, transcriptional regulation, and mitosis control biology [Clinical Development Pipeline](index=8&type=section&id=Clinical%20Development%20Pipeline) The company's pipeline focuses on oral formulations of fadraciclib and CYC140 in Phase 1/2 studies for various cancers Clinical Development Pipeline Summary | Program | Drug Candidate | Indication | Phase | | :--- | :--- | :--- | :--- | | Transcriptional Regulation | Fadraciclib (oral) | Solid tumors | Phase 1/2 (in progress) | | | Fadraciclib (oral) | Leukemias | Phase 1/2 (in progress) | | Mitosis Regulation | CYC140 (oral) | Solid tumors | Phase 1/2 (in progress) | | | CYC140 (oral) | Leukemias | Phase 1/2 (in planning) | | DNA Damage Response | Sapacitabine (oral) | AML/MDS with venetoclax | Phase 1/2 (recruitment completed) | - The company has transitioned its lead drug candidates, fadraciclib and CYC140, from intravenous to oral administration for current and planned Phase 1/2 clinical studies[24](index=24&type=chunk) - Cyclacel **retains all global marketing rights** for its clinical-stage compounds, with the exception of sapacitabine in Japan[26](index=26&type=chunk) [Transcriptional Regulation Program - Fadraciclib](index=8&type=section&id=Transcriptional%20Regulation%20Program%20-%20Fadraciclib) Fadraciclib is a selective CDK2/9 inhibitor targeting cancer pathways, with two oral Phase 1/2 trials underway for solid tumors and leukemias - Fadraciclib is a **selective CDK2/9 inhibitor** that causes apoptotic death in cancer cells by suppressing the MCL1-mediated survival pathway and can reverse drug resistance associated with cyclin E addiction[38](index=38&type=chunk) - A Phase 1/2 trial (CYC065-101) is evaluating oral fadraciclib in patients with various solid tumors and lymphomas, including breast, colorectal, and ovarian cancers, with a basket cohort for patients with specific biomarkers (MCL1, MYC, cyclin E)[41](index=41&type=chunk) - A separate Phase 1/2 trial (CYC065-102) is evaluating oral fadraciclib in patients with leukemias (AML, CLL) and MDS, both as a single agent and in combination with other therapies[50](index=50&type=chunk)[51](index=51&type=chunk)[53](index=53&type=chunk) - Preclinical data indicate fadraciclib may be effective against KRAS-mutated cancers (colorectal, lung, pancreatic) and can synergize with venetoclax in leukemia models[58](index=58&type=chunk)[61](index=61&type=chunk) [Mitosis Regulation Program - CYC140](index=17&type=section&id=Mitosis%20Regulation%20Program%20-%20CYC140) CYC140 is a novel, selective PLK1 inhibitor with potent anti-cancer activity, currently in a Phase 1/2 trial for solid tumors - CYC140 is a novel, **selective PLK1 inhibitor** with potent anti-cancer activity demonstrated in preclinical models[66](index=66&type=chunk) - A Phase 1/2 registration-directed trial (CYC140-101) is underway to evaluate oral CYC140 in advanced solid tumors and lymphomas, with plans for a subsequent study in hematological malignancies[68](index=68&type=chunk)[69](index=69&type=chunk) - Preclinical data show CYC140 preferentially induces growth inhibition and cell death in malignant cells compared to non-malignant cells[71](index=71&type=chunk)[72](index=72&type=chunk) [DNA Damage Response Program - Sapacitabine](index=19&type=section&id=DNA%20Damage%20Response%20Program%20-%20Sapacitabine) Sapacitabine is an orally available nucleoside analog, with a Phase 3 trial not meeting its primary endpoint but showing subgroup potential, and a Phase 1/2 combination study completed - The randomized **Phase 3 SEAMLESS trial** of sapacitabine in elderly AML patients did not meet its primary endpoint of overall survival, but showed a trend toward improvement in a subgroup with low baseline white blood cell counts[81](index=81&type=chunk) - The company has received consistent scientific advice from three European regulatory authorities regarding a potential approval pathway for sapacitabine based on subgroup analyses from the SEAMLESS trial[83](index=83&type=chunk) - A Phase 1/2 study evaluating an oral combination of sapacitabine with venetoclax in patients with relapsed or refractory AML or MDS has dosed 13 patients[77](index=77&type=chunk) [Competition](index=33&type=section&id=Competition) The company faces intense competition from large pharmaceutical and biotech firms with greater resources in the highly competitive biopharmaceutical industry - The company faces **intense competition** from commercial, pharmaceutical, and biotechnology companies, many of which have significantly greater financial and development resources[128](index=128&type=chunk) - Competitors with CDK or MCL1 inhibitors include Amgen, AstraZeneca, Eli Lilly, Pfizer, and Novartis. Cardiff Oncology has a competing PLK1 inhibitor in trials[129](index=129&type=chunk) [Risk Factors](index=37&type=section&id=Item%201A.Risk%20Factors) The company faces significant risks including uncertain clinical trial outcomes, reliance on third parties, extensive regulation, financial losses, and intellectual property challenges [Risks Associated with Development and Commercialization of Our Drug Candidates](index=37&type=section&id=Risks%20Associated%20with%20Development%20and%20Commercialization%20of%20Our%20Drug%20Candidates) Success depends on clinical trial outcomes, third-party reliance, regulatory approvals, market acceptance, and intense competition, all posing significant risks - Clinical trials are expensive, time-consuming, and subject to delays and uncertain outcomes. The SEAMLESS Phase 3 study failing to meet its primary endpoint is cited as an example of negative results[142](index=142&type=chunk) - The company has no manufacturing capacity and relies on third-party manufacturers for clinical and potential commercial supply, creating dependence and risk of delays or shortages[148](index=148&type=chunk) - Drug candidates are subject to extensive, costly, and time-consuming regulation by the FDA and EMA, with no guarantee of approval[151](index=151&type=chunk) - The company faces **intense competition** from numerous companies with greater resources, and its drug candidates may be rendered obsolete or noncompetitive[155](index=155&type=chunk) [Risks Related to Our Business and Financial Condition](index=59&type=section&id=Risks%20Related%20to%20Our%20Business%20and%20Financial%20Condition) The company has a history of operating losses, requires substantial additional funding, and faces risks from economic conditions and the COVID-19 pandemic - The company has a history of operating losses, with an accumulated deficit of **$385.0 million** as of December 31, 2021, and may never become profitable[179](index=179&type=chunk) - Substantial additional capital will be required to complete drug development. Future financing may not be available on reasonable terms and could cause significant stockholder dilution[173](index=173&type=chunk) - The COVID-19 pandemic has adversely affected clinical trials by delaying operations and impacting patient recruitment and enrollment[188](index=188&type=chunk) - The United Kingdom's withdrawal from the European Union (Brexit) could disrupt markets, change tax benefits, and lead to legal uncertainty and increased regulatory complexity[176](index=176&type=chunk) [Risks Related to our Intellectual Property](index=67&type=section&id=Risks%20Related%20to%20our%20Intellectual%20Property) Commercial success relies on obtaining and defending patent and trade secret protection, but faces risks of invalidation, infringement claims, and difficulty protecting proprietary information - Commercial success depends on obtaining and maintaining patent and trade secret protection, but legal protections are limited and may not provide a competitive advantage[191](index=191&type=chunk)[193](index=193&type=chunk) - The company may be subject to costly litigation or other proceedings relating to intellectual property rights, which could result in substantial damages or prevent commercialization of products[197](index=197&type=chunk) - Third-party intellectual property rights could increase costs or prevent the commercialization of drug candidates, potentially requiring the company to obtain licenses or redesign products[195](index=195&type=chunk) [Properties](index=84&type=section&id=Item%202.%20Properties) The company leases its corporate headquarters in Berkeley Heights, New Jersey, and considers its current facilities adequate for business needs - The company **leases its corporate headquarters** in Berkeley Heights, New Jersey, and considers its current facilities adequate[222](index=222&type=chunk) [Legal Proceedings](index=84&type=section&id=Item%203.%20Legal%20Proceedings) As of December 31, 2021, Cyclacel Pharmaceuticals, Inc. was not a party to any material legal proceedings - As of December 31, 2021, the company was **not party to any material legal proceedings**[223](index=223&type=chunk) [PART II](index=84&type=section&id=PART%20II) [Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities](index=84&type=section&id=Item%205.%20Market%20for%20Registrant's%20Common%20Equity%2C%20Related%20Stockholder%20Matters%20and%20Issuer%20Purchases%20of%20Equity%20Securities) The company's common stock trades on Nasdaq under 'CYCC', with no anticipated common stock dividends, but required preferred stock dividends - Common stock is traded on The **Nasdaq Capital Market** under the symbol "**CYCC**"; preferred stock trades under "**CYCCP**"[226](index=226&type=chunk) - As of March 24, 2022, there were **9,993,135 shares** of common stock outstanding[227](index=227&type=chunk) - The company has **never paid cash dividends on common stock** and does not plan to in the foreseeable future, but is required to pay dividends on its Preferred Stock[229](index=229&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=85&type=section&id=Item%207.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) The company reported a net loss of **$18.9 million** in 2021 due to increased R&D and G&A expenses, with existing cash sufficient into mid-2023 [Results of Operations](index=88&type=section&id=Results%20of%20Operations) In 2021, the company reported no revenues, a **225%** surge in R&D expenses, a **27%** rise in G&A expenses, and a significant increase in income tax benefit - There were **no revenues** for the years ended December 31, 2020 and 2021[246](index=246&type=chunk) Research and Development Expenses (in thousands) | Program | 2020 | 2021 | Change ($) | Change (%) | | :--- | :--- | :--- | :--- | :--- | | Transcriptional Regulation (fadraciclib) | $3,665 | $11,105 | $7,440 | 203% | | Anti-mitotic (CYC140) | $579 | $3,579 | $3,000 | 518% | | DNA Damage Response (sapacitabine) | $203 | $301 | $98 | 48% | | Other R&D | $312 | $492 | $180 | 58% | | **Total R&D Expenses** | **$4,759** | **$15,477** | **$10,718** | **225%** | General and Administrative Expenses (in thousands) | Period | Amount | Change ($) | Change (%) | | :--- | :--- | :--- | :--- | | Year ended Dec 31, 2020 | $5,877 | | | | Year ended Dec 31, 2021 | $7,461 | $1,584 | 27% | Income Tax Benefit (in thousands) | Period | Amount | Change ($) | Change (%) | | :--- | :--- | :--- | :--- | | Year ended Dec 31, 2020 | $1,236 | | | | Year ended Dec 31, 2021 | $3,847 | $2,611 | 211% | [Liquidity and Capital Resources](index=93&type=section&id=Liquidity%20and%20Capital%20Resources) As of December 31, 2021, the company had **$36.6 million** in cash, with net cash used in operations increasing, and believes existing funds are **sufficient through mid-2023** but not for full development Key Liquidity Measures (in thousands) | Measure | Dec 31, 2020 | Dec 31, 2021 | | :--- | :--- | :--- | | Cash and cash equivalents | $33,406 | $36,559 | | Total working capital | $32,983 | $35,648 | Summary of Cash Flows (in thousands) | Activity | 2020 | 2021 | | :--- | :--- | :--- | | Net cash used in operating activities | $(7,934) | $(18,540) | | Net cash used in investing activities | $(96) | $(27) | | Net cash provided by financing activities | $29,504 | $21,737 | - Management believes existing funds are **sufficient to finance operations through mid-2023**, but are not sufficient to complete development and commercialization of any drug candidates[275](index=275&type=chunk) [Critical Accounting Policies and Estimates](index=97&type=section&id=Critical%20Accounting%20Policies%20and%20Estimates) Key accounting policies include **Accrued Research and Development Costs** and **Stock-based Compensation**, both requiring significant estimates and judgments - **Accrued Research and Development Costs** are a critical estimate, involving judgments about the level of services performed by CROs and other vendors before invoices are received. The accrual was $2.3 million as of Dec 31, 2021[284](index=284&type=chunk)[288](index=288&type=chunk)[289](index=289&type=chunk) - **Stock-based Compensation** is another critical policy, requiring the use of the Black-Scholes model to estimate the fair value of stock options, which involves assumptions for volatility, term, interest rates, and dividend yields[290](index=290&type=chunk) [Financial Statements and Supplementary Data](index=99&type=section&id=Item%208.%20Financial%20Statements%20and%20Supplementary%20Data) This section presents the company's audited consolidated financial statements and the independent auditor's **unqualified opinion**, highlighting clinical trial accrual as a **critical audit matter** Consolidated Balance Sheet Data (in thousands) | | Dec 31, 2020 | Dec 31, 2021 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $33,406 | $36,559 | | Total current assets | $35,469 | $40,942 | | Total assets | $36,802 | $42,587 | | **Liabilities & Equity** | | | | Total current liabilities | $2,486 | $5,294 | | Total liabilities | $3,543 | $5,324 | | Total stockholders' equity | $33,259 | $37,263 | Consolidated Statement of Operations Data (in thousands) | | Year Ended Dec 31, 2020 | Year Ended Dec 31, 2021 | | :--- | :--- | :--- | | Research and development | $4,759 | $15,477 | | General and administrative | $5,877 | $7,461 | | Operating loss | $(10,636) | $(22,938) | | Net loss | $(8,445) | $(18,887) | | Net loss per share | $(3.42) | $(2.14) | - The independent auditor, RSM US LLP, issued an **unqualified opinion**, stating the financial statements are fairly presented. The auditor identified 'Clinical Trial Accrual and Expenses' as a **critical audit matter**[299](index=299&type=chunk)[303](index=303&type=chunk)[304](index=304&type=chunk) [Controls and Procedures](index=139&type=section&id=Item%209A.Controls%20and%20Procedures) Management concluded that disclosure controls and internal control over financial reporting were **effective as of December 31, 2021**, with no material changes reported - Management, including the CEO and CFO, concluded that the company's disclosure controls and procedures were **effective as of December 31, 2021**[487](index=487&type=chunk) - Based on an assessment using the COSO framework, management determined that the company's internal control over financial reporting was **effective as of December 31, 2021**[493](index=493&type=chunk) - This annual report does not include an attestation report from the independent public accounting firm regarding internal control over financial reporting, as permitted for smaller reporting companies[494](index=494&type=chunk) [PART III](index=140&type=section&id=PART%20III) [Directors, Executive Officers, Corporate Governance, Compensation, Security Ownership, and Accountant Fees](index=140&type=section&id=Items%2010-14) Information for these items is **incorporated by reference** from the company's definitive Proxy Statement for the 2022 Annual Meeting of Stockholders - Information for Items 10, 11, 12, 13, and 14 is **incorporated by reference** from the company's Proxy Statement for the 2022 Annual Meeting of Stockholders[499](index=499&type=chunk)[500](index=500&type=chunk)[502](index=502&type=chunk) [PART IV](index=142&type=section&id=PART%20IV) [Exhibits and Financial Statement Schedules](index=142&type=section&id=Item%2015.%20Exhibits%20and%20Financial%20Statement%20Schedules) This section lists **all exhibits filed with the Form 10-K**, including financial statements, corporate governance documents, material contracts, and executive certifications - This section provides a list of **all exhibits filed with the Form 10-K**, including financial statements, corporate governance documents, material contracts, and executive certifications[508](index=508&type=chunk)[509](index=509&type=chunk)

Cyclacel Pharmaceuticals, Inc. (NASDAQ:CYCC) Q4 2021 Results Conference Call March 28, 2022 4:30 PM ET Company Participants Spiro Rombotis - President and CEO Paul McBarron - EVP, Finance and COO Dr. Mark Kirschbaum - SVP and Chief Medical Officer Conference Call Participants Kevin DeGeeter - Oppenheimer Ahu Demir - Ladenburg Jonathan Aschoff - ROTH Capital Kumar Raja - Brookline Operator Good afternoon, and welcome to the Cyclacel Pharmaceuticals Fourth Quarter and Full Year 2021 Results Conference Call an ...

Company Overview - Cyclacel is focused on converting cell cycle control biology into innovative oncology medicines[4] - The company has assets in mid-stage development targeting CDK2/9 and PLK1[4] - Cyclacel held a cash position of $40.2 million as of September 30, 2021, expected to finance operations through early 2023[4, 10] Clinical Programs - Fadraciclib (CYC065) is an oral CDK2/9 inhibitor with ongoing Phase 1/2 studies in solid tumors and leukemias, with data expected in 1H 2022 and 2H 2022 respectively[4] - CYC140 is an oral PLK1 inhibitor with IND cleared and Phase 1/2 in solid tumors to initiate in 1H 2022, with data expected in 1H 2023[4] - Fadraciclib has shown durable MCL1 suppression and anticancer activity in patients[7] Therapeutic Strategy - The company's therapeutic strategy involves suppressing multiple redundant mechanisms with a single drug to durably suppress cancer-promoting proteins/genes, enabling apoptosis[6] - Fadraciclib's mechanism of action includes durable suppression of anti-apoptotic proteins like MCL1, MYC, cyclin E, and KRAS mutant[12] - CYC140 has shown compelling preclinical data in liquid and solid cancers, including KRAS mutated cancers[7] Market Potential - Fadraciclib potentially addresses large markets, such as high-grade serous ovarian cancer where CCNE1 is amplified in over 20% of patients[28] - CCNE1 is amplified in 20% of high-grade serous endometrial/uterine cancers, which represents approximately 5,000 US incidence and 77,000 prevalence[28] - In breast cancer, CCNE1 is amplified in 30% of HR+ cases (56,000 US incidence, 735,000 prevalence) and 40% of BRCA1/2+ cases (18,000 US incidence, 238,000 prevalence)[28]

Table of Contents Title of each class Trading Symbol(s) Name of each exchange on which registered Common Stock, par value $0.001 per share CYCC The Nasdaq Stock Market LLC Preferred Stock, $0.001 par value CYCCP The Nasdaq Stock Market LLC UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2021 OR ☐ TRANSITION REPORT PURSUANT TO SECT ...