ONCTERNAL THERAPEUTICS, INC. TA R G E T I N G
C A N C E R
N e w S c i e n c e . N e w C a n c e r T h e r a p i e s . N e w H o p e .
Company Overview - May 2024
ONCT Corporate Presentation May 2024
FORWARD-LOOKING STATEMENTS
This presentation contains forward-looking statements (including within the meaning of §21E of the U.S. Securities Exchange Act of 1934, as amended, and § 27A of the U.S. Securities Act of 1933, as amended). Forward-looking statements, which generally include statements regarding goals, plans, intentions and expectations, are based upon current beliefs and assumptions of Oncternal Therapeutics, Inc. ("Oncternal") and are not guarantees of future performance. Statements that are not historical facts are forward-looking statements, and include statements regarding the expected timing for achieving key milestones, the timing of regulatory communications and completing and announcing results of clinical trials of Oncternal's product candidates, the anticipated market potential, duration of patent coverage, ability to obtain and maintain favorable regulatory designations, potential accelerated approval pathways for Oncternal's product candidates and preclinical programs, and Oncternal's anticipated cash runway.
All forward-looking statements are subject to risks and uncertainties, including risks and uncertainties inherent in Oncternal's business, including risks associated with the clinical development and process for obtaining regulatory approval of Oncternal's product candidates such as potential delays in the commencement, enrollment and completion of clinical trials; the risk that results seen in a case study of one patient likely will not predict the results seen in other patients in the clinical trial; the risk that interim results of a clinical trial do not predict final results and that one or more of the clinical outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data, as follow-up on the outcome of any particular patient continues, and as more patient data become available; and other risks described in Oncternal's filings with the U.S. Securities and Exchange Commission ("SEC"). Except as required by applicable law, Oncternal undertakes no obligation to revise or update any forward-looking statement. All forward-looking statements in this presentation are current only as of the date on which the statements were made. Additional factors that could cause actual results to differ materially from those expressed in the forward-looking statements are discussed in Oncternal's filings with the SEC.
ONCT-534,ONCT-808 and zilovertamab are investigational product candidates that have not been approved by the U.S. Food and Drug Administration for any indication.
This presentation includes certain information obtained from trade and statistical services, third-party publications, and other sources. Oncternal has not independently verified such information and there can be no assurance as to its accuracy.
ONCT Corporate Presentation May 2024 | 2 |
Corporate Highlights
ONCT-534: DUAL-ACTION ANDROGEN RECEPTOR INHIBITOR (DAARI)
- Fourth cohort (300mg once daily) fully enrolled in Phase 1/2 dose escalation study in R/R mCRPC
- Received Fast-Track designation from U.S. FDA
- Activity in preclinical prostate cancer models of androgen receptor inhibitor resistance, including LBD mutations, AR overexpression and AR splice variants such as AR-V7
ONCT-808: AUTOLOGOUS CAR T CELL THERAPY TARGETING ROR1
- Encouraging clinical activity in Phase 1/2 clinical study in aggressive B-cell NHL, including CD19 CAR T treatment failures
- Study is open and enrolling with protocol amendments
- Robust and scalable manufacturing process using closed system
ZILOVERTAMAB: POTENTIALLY FIRST-IN-CLASS MONOCLONAL ANTIBODY TARGETING ROR1 | |
• Encouraging 100% PFS for patients with CLL and TP53 aberrations being further investigated | |
• Discussions ongoing with BTK inhibitor developers | |
MULTIPLE CATALYSTS WITHIN CASH RUNWAY PERIOD | |
• ONCT-534 Phase 1/2 dose escalation study in R/R mCRPC initial data in 2Q 2024 | |
• ONCT-808 clinical data update in aggressive B-cell NHL in mid 2024 | |
• Cash and short-term investments of $27.0M as of March 31, 2023, cash runway into Q1 2025 | 3 |
ONCT Corporate Presentation May 2024 |
Experienced Team
James Breitmeyer, MD, PhD | Richard Vincent | Salim Yazji, MD | Raj Krishnan, PhD | Chase Leavitt | Pablo Urbaneja |
CEO, Founder, Director | CFO | CMO | CTO/CSO | General Counsel | SVP, Corporate Development |
Tang Capital | |||||
Management |
±7
David Hale | Michael Carter, MB | Jill DeSimone | Daniel Kisner, MD | Rosemary Mazanet, MD, PhD | Bill LaRue | Xin Nakanishi, PhD Charles Theuer, MD, PhD | Robert Wills, PhD | |
Co-founder | Director | Director | Director | Director | Director | Director | Director | Director |
Board Chairman
ONCT Corporate Presentation May 2024 | 4 |
Robust Pipeline - Novel Product Candidates in Multiple Indications
Modality | Product Candidate | Indication | Preclinical | Phase 1 | Phase 2 | Phase 3 |
Dual-Action | ONCT-534 | Prostate Cancer | Patients | |||
AR Inhibitor | ||||||
Treated | ||||||
ROR1 | ONCT-808 | Aggressive B-cell NHL | Patients | |||
Cell Therapy | (Autologous CAR T) | |||||
Treated | ||||||
ROR1 mAb | Zilovertamab | Hematological Malignancies | Seeking | |||
and Solid Tumors (ISTs) | ||||||
Partnership |
ONCT Corporate Presentation May 2024 | 5 |
Table of Contents
ONCT-534:DUAL-ACTION ANDROGEN RECEPTOR INHIBITOR (DAARI)
ONCT-808: ROR1 TARGETED CELL THERAPY
ZILOVERTAMAB: MONOCLONAL ANTIBODY TARGETING ROR1 FINANCIAL INFO AND UPCOMING MILESTONES
ONCT Corporate Presentation May 2024 | 6 |
ONCT-534Dual-Action Androgen Receptor Inhibitor (DAARI)
Differentiated Mechanism of Action
- ONCT-534acts on both the N-terminal domain (NTD) and the ligand-binding domain (LBD) of the androgen receptor (AR) and induces AR protein degradation
- NTD binding essential for activity against splice-variants
- Current standard of care treatments, such as enzalutamide or apalutamide, bind to LBD only
N-terminal Domain (NTD) DNA-binding Domain (DBD) | Ligand-binding Domain (LBD) |
Hinge
Potential to address unmet needs in prostate cancer
- Potential next-generation treatment option for patients with R/R metastatic prostate cancer
- Compelling preclinical efficacy in vitro and in vivo
- Activity against enzalutamide-sensitive and resistant models, including AR overexpression, LBD mutants, splice variants tumors
- Dose escalation portion of Phase 1/2 Study ONCT- 534-101 in patients with mCRPC ongoing; received Fast Track designation by U.S. FDA in October 2023
- Potential in other AR-driven disease, including luminal AR-triple negative breast cancer (LAR- TNBC) and non-oncology rare disease indication
ONCT Corporate Presentation May 2024 | 7 |
Oncternal Prostate Cancer Scientific Advisory Board
Johann de Bono, M.D., Ph.D. | Evan Yu, M.D. | Matthew Smith, M.D., Ph.D. | |||||||
Regius Professor of Cancer Research at | Professor and Section Head of Medical | Director of the Genitourinary | |||||||
The Institute of Cancer Research, London | Oncology at the Fred Hutch Cancer Center | Oncology Program at Mass General | |||||||
• | Director of the joint Drug Development | • | Medical Director of Clinical Research | • | Internationally recognized expert | ||||
Unit at The ICR and The Royal Marsden | Support for the Fred Hutch Children's | in prostate cancer and authored | |||||||
NHS Foundation Trust, London | Cancer Consortium | >150 peer-reviewed articles | |||||||
• | Lead trials of abiraterone, cabazitaxel, | • | Focused on personalized-medicine | • | Lead investigator in | ||||
enzalutamide and multiple PARPi | approach and the discovery of unique | darolutamide pivotal study | |||||||
prostate cancer biomarkers | |||||||||
Scott Dehm, Ph.D. | Howard Soule, Ph.D. - pro-bonoadvisor | Gunnar Kaufmann, Ph.D. | |||||||
Professor in Cancer Research at the | Executive Vice President & Chief Science | SVP and CSO and Head of Open | |||||||
University Minnesota | Officer at the Prostate Cancer Foundation | Innovation at Kyowa Kirin, Inc. | |||||||
• | Research focused on the role of AR and | • | Senior fellow of the Milken Institute, | • | Former CSO at Oncternal, and | ||||
alterations in AR signaling in prostate | and member of the DoD Prostate | Adjunct Assistant Professor at | |||||||
cancer development and progression | Cancer Research Program | The Scripps Research Institute | |||||||
and re-activation the androgen/AR | • | Vice president and managing director | • | Led ONCT-534 preclinical | |||||
pathway | of CaP CURE | development | |||||||
ONCT Corporate Presentation May 2024 | 8 |
ONCT-534 Differentiated vs other AR-targeting Therapeutic Agents
AR antagonist | PROTAC | ANITEN | DAARI | |
Examples | Enzalutamide (Pfizer) | ONCT-534 | ||
Apalutamide (J&J) | ARV-110 (Arvinas) | EPI-7386 (ESSA) | ||
Darolutamide (Bayer) | ||||
First-in-class Molecule | X | √ | √ | √ |
AR Degradation | X | √ | X | √ |
N-terminal domain Binding | X | X | √ | √ |
Active against AR LBD Mutants | certain mutants1,2 | certain mutants3 | ? | √ |
Active in ENZA-resistant in vivo models | darolutamide | √ | √ | √ |
Active in AR-overexpressing in vivo models | √ | √ | √ | √ |
Active in AR-SV expressing in vivo models | X | X | ? | √ |
Active in CRPC models using intact rodents | apalutamide4 | √ | ? | √ |
√ = Yes, X = No, ? = Unknown
ONCT Corporate Presentation May 2024
1) Joseph Cancer Discov 2013; 2) Moilanen Sci Rep 2015; 3) Cancer Discov 2022; 4) Clegg Cancer Res 2012 | 9 |
ONCT-534 Positioning within the Evolving Prostate Cancer Landscape
Prostate Cancer Treatment Paradigm
LocalizedSystemic
1st line
AR-dependent
mCRPC
2nd line | 3rd line |
AR Independent |
- Active surveillance
- Surgical / chemical castration (LHRH analogues)
Development Programs (not exhaustive)
AR Pathway Inhibitors | Chemotherapy | PARP Inhibitors | RLTs | ||
• | XTANDI (enzalutamide) - Pfizer/Astellas | • | LYNPARZA - AZ | • PLUVITCO | |
• | NUBEQA (darolutamide) - Bayer | • | TALZENNA - Pfizer | - Novartis |
- ERLEADA (apalutamide) - J&J
- ZYTIGA (abiraterone acetate) - J&J
NTD-Inhibitor | AR degraders | Other MoA | RLTs | ADCs/Bispecifics | Other MoA | ||||
• Masofaniten - | • Bavdegalutamide | • | ODM-208 (CYP11A1 | • | 177Lu- | • | ARX517 (PSMA | • | Gedatolisib |
ESSA | - Arvinas | inhibitor) - Merck | PNT2002 - | ADC) - Ambrx/J&J | (PI3K/mTOR | ||||
• BMS-986365 - | • | PF-06821497 (EZH2 | Point/Lilly | • | JANX007 (PSMA- | inhibitor) - | |||
BMS | inhibitor) - Pfizer | • | RYZ101 - | CD3 TCE) - Janux | • | Celcuity | |||
RayzeBio/ | • | JNJ-8081 (PSMA- | Afuresertib (AKT | ||||||
BMS | CD3 TCE) - J&J | inhibitor) - Laekna |
ONCT-534 future
positioning
ONCT Corporate Presentation May 2024
ONCT-534 initial
positioning
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Oncternal Therapeutics Inc. published this content on 11 May 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 11 May 2024 00:15:05 UTC.
