CYCLACEL PHARMACEUTICALS, INC. Translating cancer biology into medicines
Cyclacel Pharmaceuticals, Inc. (CYCC) APRIL 2024
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 forward- looking statements. Such forward-looking statements include statements regarding, among other things, the efficacy, safety and intended utilization of Cyclacel's product candidates, the conduct and results of future clinical trials, plans regarding regulatory filings, future research and clinical trials and plans regarding partnering activities. Factors that may cause actual results to differ materially include the risk that product candidates that appeared promising in early research and clinical trials do not demonstrate safety and/or efficacy in larger-scale or later clinical trials, trials may have difficulty enrolling patients, Cyclacel may not obtain approval to market its product candidates, the risks associated with reliance on outside financing to meet capital requirements, and the risks associated with reliance on collaborative partners for further clinical trials, development and commercialization of product candidates. You are urged to consider statements that include the words "may," "will," "would," "could," "should," "believes," "estimates," "projects," "potential," "expects," "plans," "anticipates," "intends," "continues," "forecast," "designed," "goal," or the negative of those words or other comparable words to be uncertain and forward-looking. 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 other filings we file with the Securities and Exchange Commission and are available at www.sec.gov. Such forward-looking statements are current only as of the date they are made, and we assume no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.
© 2024 Cyclacel Pharmaceuticals, Inc. Rel. APR2024 | 2 |
Cyclacel Opportunity
Discovered and developing fadraciclib & plogosertib cell cycle, drug portfolio Fadra potentially best-in-class, next generation CDK inhibitor
Unique Ph 2 precision medicine strategy: patients with CDKN2A/CDKN2B mutationsSingle-agent anticancer activity (CR, PR, SD) with good tolerability including:
- GYN (incl. breast/endometrial/ovarian), hepatobiliary, NSCLC, pancreatic, testicular and lymphoma
Enroll two Phase 2 cohorts with readouts in Q4 '24 - Q1 '25; potentially supporting registration pathways
© 2024 Cyclacel Pharmaceuticals, Inc. Rel. APR2024 | 3 |
Fadra Patient Groups
- Two dose escalation studies:
- 065-01IV (n=52)
- 20/52 had sequencing data
- 6/20 had CDKN2A and/or CDKN2B alterations
- 065-101oral (n=47)
- 21/47 had sequencing data
- 5/21 had CDKN2A and/or CDKN2B alterations
Data on file. | © 2024 Cyclacel Pharmaceuticals, Inc. Rel. APR2024 | 4 |
Responder Profiles: CDKN2A/B Alterations (retrospective review)
Patient | Histology | Best Response (sum | Dose Level | Schedule | Mutation |
Study | of target lesions) | ||||
38 iv | Endometrial | CR (-100%) | 213mg QD | 2d/wk 2/3 wks | CDKN2A, CDKN2B, MTAP loss, |
065-01 | MCL1 amp | ||||
14 iv | Ovarian | SD (-2.5%) | 192mg/m2 | 1d/3 wks | CDKN2A, CCNE1, MYC gain |
065-01 | |||||
11 iv | Salivary gland | SD (0.8%) | 128mg/m2 | 1d/3 wks | CDKN2A mutation & gain |
065-01 | CDKN2B gain | ||||
51 oral | NSCLC squamous | SD (-22%) | 125mg BID | 5d/wk 4/4 wks | CDKN2B loss |
065-101 | |||||
16 oral | Cholangio- | SD (-5%) | 75mg BID | 5d/wk 4/4 wks | CDKN2A mutation |
065-101 | carcinoma | ||||
55 oral | Pancreatic | SD (4%) | 125mg BID | 5d/wk 4/4 wks | CDKN2A loss |
065-101 | |||||
62 oral | Sertoli germ cell | SD (-12%) | 150mg QD | 7d/wk 4/4 wks | CDKN2A, CDKN2B, MTAP loss |
065-101 | testicular | ||||
Data on file. Pt 62 unmonitored data. Mutational status with CDKN2A/B alterations: in oral study: 5/21, | © 2024 Cyclacel Pharmaceuticals, Inc. Rel. APR2024 | 5 |
in IV study: 6/20 patients. Pt 20 i.v. pancreaticobiliary; 192 mg/m2; 1 C only) CDKN2A loss. | ||
Fadra - Novel and Potent CDK2 and CDK9 inhibitor
Kinase Profile | CDK9 inhibition | CDK2 inhibition |
EOL-1(KTM2A-PTD, CDKN2A/B Loss) AML xenograft
Mean T/C (%) Day 19 40 mg/kg CYC065: 4% 29 mg/kg CYC065: 7%
Depletion of MCL1 level and Rb phosphorylation (pRB) in vivo following fadraciclib treatment of lung cancer PDX models
Vehicle | Fadraciclib | Vehicle | Fadraciclib |
MCL1 | pRB |
Frame, PLoS One 2020, 15:e0234103; Kawakami, Mol Cancer Ther 2021, 20:477 | © 2024 Cyclacel Pharmaceuticals, Inc. Rel. APR2024 | 6 |
CDKN2A/B and Fadra MoA
CDKN2A encodes p16INK4a, CDKN2B p15INK4b which inhibit D-type cyclin complexes w/ CDK4 & CDK6
- Dysregulated CDK4/6 drive cancer progression and proliferation in G1, suggesting a role for CDK4/6 inhibition
- Abemaciclib (CDK4/6i) activity in CDKN2A mutant cells is limited by CDK2 bypass of CDK4/6 inhibition 1
CDKN2A also encodes p14ARF, which disrupts MDM2-directed degradation of p53; suppression of MDM2 expression by CDK9i may compensate for loss of this activity
No approved drugs for patients harboring CDKN2A/ CDKN2B
1 Gong, Cancer Cell 2017, 32, 761. | © 2024 Cyclacel Pharmaceuticals, Inc. Rel. APR2024 | 7 |
CDKN2A Alterations
Solid tumors >10%: GBM, H&N, pancreas, esophagus, lung, bladder, HCC/BTC, breast, melanoma, sarcoma
Lymphoma: CDKN2A deletions in 46% of PTCL-NOS patients.
cBioportal, dl 23OCT23. Maura F et al Haematologica. 2021 Nov 1 106 11 2918 | © 2024 Cyclacel Pharmaceuticals, Inc. Rel. APR2024 | 8 |
CDKN2B Alterations
>10%: glioma, lung, bladder, H&N, pancreas, melanoma, esophagus, sarcoma, HCC/BTC, breast, ovarian
cBioportal, dl 23OCT23. | © 2024 Cyclacel Pharmaceuticals, Inc. Rel. APR2024 | 9 |
Fadra Oral 065-101 Ph 1/2 Solid Tumors & Lymphoma (ongoing, unselected, late line)
Enrolled n=47 as of March 26, 2024. No DLT in cohorts 1-5 (n=22). DL5=RP2D. PoC part to start next.
(3+3; unselected,
all comer, late line; DL= dose level)
DL6B (n=10)
150mg qd tabs 7d (4/4 wk)
DL6A (n=13)
125mg bid tabs M to F (4/4 wk)
DL6 (n=2)
150mg bid caps M to F (4/4 wk)
DL5 (n=9)
100mg bid caps M to F (4/4 wk)
DL4 (n=3)
100mg bid caps M to F (3/4 wk)
DL3 (n=3)
75mg bid caps M to F (3/4 wk)
DL2 (n=4)
50mg bid caps M to F (3/4 wk)
Starting DL (n=3)
50mg bid caps MWF (3/4 wk)
Proof of Concept (PoC)**
(Simon 2-stage; 2nd /3rd line)
- Cohort 1: Endometrial, Ovarian
- Cohort 2: Biliary / cholangiocarcinoma
-
Cohort 3: Hepatocellular Carcinoma
Cohort 4: Breast (post-CDK4/6i, TNBC, HER-2 - refractory)
Cohorts 5, 6: Lymphoma (T-cell; B-cell)
Cohort 7: mCRC (including KRAS mutated)
- Cohort 8 Basket: biomarker selected
(related MoA suspected; expand if PR seen)
Pivotal
(if randomized study not needed)
Single-arm, open label, study for n=TBD cancer patients in a histology from PoC
Pivotal indication to be determined based on clinical data from PoC
*Single agent.**Single agent; followed by combination. ClinicalTrials.gov Identifier: NCT04983810. | © 2024 Cyclacel Pharmaceuticals, Inc. Rel. APR2024 | 10 |
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Cyclacel Pharmaceuticals Inc. published this content on 02 April 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 02 April 2024 17:39:07 UTC.
