Innovative Medicines for Cancer and Other Proliferative Diseases Using Cell Cycle Biology

CYC 682

Innovative medicines for cancer and other proliferative diseases using cell cycle biology

Rodman & Renshaw Global Investment Conference 2015 September 10, 2015 Disclaimer

This presentation contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995 about financial results and estimates, business strategy, clinical trial plans and research and development programs of Cyclacel Pharmaceuticals, Inc. By their nature, forward-looking statements and forecasts involve risks and uncertainties because they relate to events and depend on circumstances that will occur in the future. For a further list and description of the risks and uncertainties the Company faces, please refer to our most recent Annual Report on Form 10- K and other periodic and current filings that have been filed with the Securities and Exchange Commission and are available at www.sec.gov . The information in this presentation is current as of this date. Cyclacel does not take any responsibility to update such information.

Sapacitabine oral capsules – Approaching Phase 3 readout front-line elderly AML – “Impressive” Phase 2 median survival in 2/3 line MDS

CDK 2/9 inhibitor program – Seliciclib & sapacitabine oral combination: durable clinical benefit seen in Phase 1 patients with BRCA mutations – CYC065 2nd gen CDK Inhibitor (iv & oral; IND cleared by FDA)

Strong financial position – Est. capital beyond Phase 3 AML data readout to early 2018

Source: Cyclacel press releases and data on file.

AML = acute myeloid leukemia. MDS = myelodysplastic syndromes. CLL = chronic lymphocytic leukemia. IND = investigational new drug.

Profs David Lane (p53 ) & David Glover (Polo & Aurora kinases ) – Exploit cell cycle biology to disrupt cancer cell immortality: • Modulating DNA repair in cancer cells • Breaking cancer cell addiction to oncogenes Drug portfolio strategy – Small molecules, enzyme targets ( DNA pol-α, CDK, PLK ) – Phase 1 through Phase 3 trials completed – Target profile: orally available, chronic treatments – Low intensity treatment experience & patient QoL – High value therapeutics

Source: Cyclacel data on file.

sapacitabine

Oral nucleoside analog interfering with cancer cell DNA repair via HR pathway; active in: – Hematological malignancies (AML, MDS) – BRCA /HRD +ve solid tumors (combination with seliciclib) Therapeutic strategy: disease control vs. toxic cure attempt – Well-tolerated; administered over multiple cycles – Low intensity therapy Significant market opportunity & unmet medical needs Exclusivity to 2027-30; Orphan Drug Status for AML/MDS

• Newly diagnosed AML: multigenetic, heterogeneous disease

• Old age, frailty and comorbid conditions

Options: • 45-year old intensive chemotherapy regimen • Investigational agent(s) in a clinical trial • Hospice or terminal care at home

• Expected median survival of 3 - 6 months • 60-day mortality of ~ 20 - 36%

In consultation with FDA under SPA Fully enrolled at 110 US & European hospitals

≥27.5% reduction in risk of death Median OS of: – 8 months for experimental arm – 6 months for control arm Final analysis after 424 events

Events Remaining until Mature Data as of September 2015: 12%

SEP15 * Source: Cyclacel data on file.

All Patients (n=46) CYC682-11 Pilot (25) CYC682-12 Lead-in (21)

Median O.S. (n=46) ~ 8 months 72% > 75 yrs (n=33) ~ 9 months

No. at risk 3M 6M 12M 18M 24M 38 (83%) 30 (65%) 16 (35%) 12 (26%) not reached

* Source: Ravandi F, et al, American Society of Hematology Annual Meeting Dec. 2012, Abstract #2630.

Superior

Equivalent

Inferior

© 1997-2015 Cyclacel Pharmaceuticals, Inc. Released JUN 2015 13 SEAMLESS DSMB Recommendations * After 247 events • No safety concerns; futility cross • 173/247 events (70%) occurred in first 6 months • Complete follow-up so that any treatment effect beyond 6 months is not missed • Saw no reasons to discontinue treatment and recommended that recruited patients stay on treatment • Similar response rates between arms; no adverse outcomes for experimental arm “…Formulaic Interpretations of Interim Analyses for Futility may be Misleading…” #

* Source: Cyclacel press release December 16, 2014. # Source: Herson J, Buyse M, Wittes J, On stopping a randomized trial for futility, Design for Clinical Trials Perspectives on Current Issues, Harrington D ed., 109-138 , 2011.

• Already failed 1 st line hypomethylating agents (HMAs): azacitidine (Vidaza®) and/or decitabine (Dacogen®)

• Higher risk from infections; transformation into AML

• Multigenetic, heterogeneous disease

Options: • Investigational agent(s) in a clinical trial • Hospice or terminal care at home

• Expected median survival of 4.3 - 5.6 months †

† Source: Prebet T, Gore S, et al, JCO 2011; Jabbour E, Garcia-Manero G, et al, Cancer 2010.

1 year Treatment m OS survival

Azacitidine 2nd line ~ 6 months † - †

Decitabine 2nd line ~ 4 months † - †

Best Supportive Care ~ 4 months † 17% †

Sapacitabine: Phase 2 study 2 nd , 3 rd , 4 th line ~ 9 months @ 38% @

† Prebet T, Gore S, et al, JCO 2011 (95% CI, 14% to 26% on best supportive care; 29% on investigational agents). @ Garcia- Manero G et al, American Society of Hematology Annual Meeting Dec. 2013, Abstract #2752 (Arm G 1-year survival).

• First CDK inhibitor approved in 2015 for breast cancer

• Translating the 2001 Nobel Prize for Physiology & Medicine into treatments

• Cyclacel’s portfolio of CDK2/9 inhibitors:

• Seliciclib (Phase 2)

• CYC065 (entering Phase 1)

Cancer cells evolve after sublethal exposure to therapy eventually becoming immortal by: • Blocking DNA repair circuits • Expressing pro-survival proteins (i.e. MCL-1)

CDK inhibitor-based Strategies: • Modulate DNA repair (via HR, NHEJ pathways) • Suppress pro-survival proteins to resensitize cells to therapy

Clinical Utility: • Single agent treatment in sensitive cancers • Combinations with drugs encountering resistance

All-oral combination of seliciclib + sapacitabine:

– durable clinical benefit (PRs & prolonged SD) in patients

with BRCA +ve breast, ovarian, pancreatic cancers

– 55% ORR in BRCA +ve patients with excellent durability

…Opening new opportunities for line extensions…

* Source: Shapiro et al, AACR Proceedings, 2013, LB-202. HR=homologous recombination.

Best Total Cancer Diagnosis Prior Treatment Response cycles BRCA mutation carriers (n=16) Breast* PR adriamycin, cyclophosphamide, paclitaxel, cisplatin >66 Ovary* SD paclitaxel, carboplatin, gemcitabine 21 Ovary* PR paclitaxel, carboplatin, gemcitabine, topotecan, iniparib 18 Breast* PR adriamycin, cyclophosphamide, paclitaxel, carboplatin 31 tamoxifen, raloxifene, anastrozole, adriamycin, Breast* SD 7 cyclophosphamide, paclitaxel, carboplatin, vinorelbine Pancreas* PR gemcitabine, 5-FU, oxaliplatin 7 Others (n=22) Uterine leiomyosarcoma SD gemcitabine, flavopiridol 9 Sigmoid colon SD 5-FU, folfox, irinotecan, cetuximab, bevacizumab 7 Non-small cell lung paclitaxel, carboplatin, pemetrexed, vinorelbine, SD 6 (poorly differentiated) erlotinib, cetuximab Nasopharyngeal docetaxel, paclitaxel, cisplatin, carboplatin, 5-FU, SD 6 (squamous) pemetrexed, cetuximab, SCH727965 doxorubicin, ifosfamide, dacarbazine, vinorelbine, LE sarcoma SD 4 trabectedin, ALB-109564, Ro4929097, PF-04554878 Pancreas SD folfox, gemcitabine, erlotinib, nab-paclitaxel, 5-FU 4

* By investigator assessment. Source: Shapiro et al, AACR Proceedings, 2013, LB-202 and Cyclacel data on file (as of May 2015).

* Source: Shapiro et al, AACR Proceedings, 2013, LB-202. * Prior PARP Inhibitor.

Intravenous or oral, potent & selective CDK2/9 inhibitor

Active in:

– Hematological malignancies (AML, MLL-r)

– BRCA /HRD +ve solid tumors; sapacitabine combination

– HER2 +ve solid tumors; trastuzumab combination

Therapeutic strategy: modulation of resistance

Significant market opportunity & unmet medical needs

Source: Cyclacel press releases and data on file.

Cancer propagated by:

• Inactivation of tumor suppressor genes (i.e. p27, p53);

• Activation of continuously expressed oncogenes required for cancer maintenance (i.e. KRAS, MYC):

ONCOGENE ADDICTION

• Pharmacologic inhibition of oncogenes → apoptosis or senescence & innate immune response → cell death

Source: Weinstein I, Science 2002:297:63. Pelengaris S, et al, Cell 2002:109:321. Xue Lowe et al Nature 2007 doi:10.1038/nature05529. Cyclacel data on file.

Control Trastuzumab CDK2i.CYC065 T+CDK2i.CYC065

1200 1000 800 600 400

Tumor volume (mm3) volume Tumor 200 0 5 10 15 20 Days of treatment

CYC065 single agent and in combination with trastuzumab in vivo tumor growth inhibition & regression (combination) of BT474R trastuzumab resistant HER2 + BC cell line .

Source: Scaltriti et al 2011 PNAS 108 3761

CDK4/6 isoforms CDK2/9 isoforms - palbociclib (PFE) - seliciclib (CYCC) P2 Approved in combination with - CYC065 (CYCC) IND letrozole for ER +ve Her2 -ve advanced BC - abemaciclib (LLY ; also - dinaciclib (pan CDK, MRK) P3 CDK9 ) P3 - BAY1143572 (CDK9, BAY) P1 - ribociclib (NVS) P3

* Source: Cyclacel data on file.

Q2 2015 cash & cash equivalents: ~$26.9m 1

Operating cash burn (excludes non-cash items)

2013: ~ $18.2m annual 1

2014: ~ $19.3m annual 1

2015 Est.: ~ $15.5m annual (~$3.9m / quarter) 2 Fully diluted shares: ~ 37.2 million 3

No debt

1. 10-K, 10-Q 2. Est.= estimated. Co. guidance. 3. 10-Q June 30, 2015. Common stock outstanding: 34.7m. Includes 0.9m warrants and options with an exercise price higher than $10 per share.

√ Sapacitabine SEAMLESS: complete enrollment

– Sapacitabine SEAMLESS: topline data readout

– Sapacitabine MDS: Phase 2b after HMA failure

– Sapacitabine & seliciclib solid tumors update Phase 1

– CYC065 (CDK) Initiate First-in-Human Phase 1 study

– CYC140 (PLK1) IND-directed development

Cell cycle pioneers

Improving patient lives

With orally-available

Innovative medicines