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| Item 7.01 | Regulation FD Disclosure. |
On January 10, 2022, CytomX Therapeutics, Inc. (the “Company”) posted its corporate presentation relating to its research and development programs to be presented at the 40th Annual J.P. Morgan Healthcare Conference to the investor section of the Company’s website at: https://ir.cytomx.com/events-and-presentations. The Company’s corporate presentation is attached hereto as Exhibit 99.1.
The furnishing of the attached presentation is not an admission as to the materiality of any information therein. The information contained in the slides is summary information that is intended to be considered in the context of more complete information included in the Company’s filings with the U.S. Securities and Exchange Commission (the “SEC”) and other public announcements that the Company has made and may make from time to time by press release or otherwise. The Company undertakes no duty or obligation to update or revise the information contained in this report, although it may do so from time to time as its management believes is appropriate. Any such updating may be made through the filing of other reports or documents with the SEC, through press releases or through other public disclosures. For important information about forward looking statements, see the slide titled “Forward-Looking Statements” in Exhibit 99.1 attached hereto.
The information in this Item 7.01 of this Current Report on Form 8-K and Exhibit 99.1 attached hereto shall not be deemed “filed” for purposes of Section 18 of the Exchange Act or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act. The information contained in this Item 7.01 and in the presentation attached as Exhibit 99.1 to this Current Report shall not be incorporated by reference into any filing with the SEC made by the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing.
| Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits
| Exhibit No. |
Description | |
| 99.1 | Corporate Presentation of CytomX Therapeutics, Inc. dated January 10, 2022. | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| CYTOMX THERAPEUTICS, INC. | ||||||
| Date: January 10, 2022 | By: | /s/ Lloyd Rowland | ||||
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Lloyd Rowland Senior Vice President, General Counsel | ||||||
Exhibit 99.1
© 2022 CytomX Therapeutics, Inc. 40 th Annual J.P. Morgan Healthcare Conference Sean McCarthy, D.Phil. President, Chief Executive Officer, and Chairman January 12, 2022
Forward - Looking Statements This presentation may contain projections and other forward - looking statements regarding future events. All statements other tha n statements of historical facts contained in this presentation, including statements regarding our future financial condition, technology pl atf orm, development strategy, prospective products, preclinical and clinical pipeline and milestones, regulatory objectives, expected payments fr om and outcomes of collaborations, and likelihood of success, are forward - looking statements. Such statements are predictions only and involve know n and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materia lly different from any future results, performance or achievements expressed or implied by the forward - looking statements. These risks and uncertai nties include, among others, the costs, timing and results of preclinical studies and clinical trials and other development activities; the un certainties inherent in the initiation and enrollment of clinical trials; the uncertainties associated with the COVD - 19 pandemic; expectations of expand ing on - going clinical trials; availability and timing of data from clinical trials; the unpredictability of the duration and results of re gul atory review; market acceptance for approved products and innovative therapeutic treatments; competition; the potential not to receive partnership mi lestone, profit sharing or royalty payments; the possible impairment of, inability to obtain and costs of obtaining intellectual property rig hts ; and possible safety or efficacy concerns, general business, financial and accounting risks and litigation. Because forward - looking statements are in herently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you sho uld not rely on these forward - looking statements as predictions of future events. More information concerning us and such risks and uncertainti es is available on our website and in our press releases and in our public filings with the U.S. Securities and Exchange Commission. We are p rov iding this information as of its date and do not undertake any obligation to update or revise it, whether as a result of new information , f uture events or circumstances or otherwise. Additional information may be available in press releases or other public announcements and publi c f ilings made after the date of this presentation. This presentation concerns products that have not yet been approved for marketing by the U.S. Food and Drug Administration (F DA) . No representation is made as to their safety or effectiveness for the purposes for which they are being investigated. 2
© 2022 CytomX Therapeutics, Inc. Destroying Cancer. Differently.
CD3 EGFR CytomX has Pioneered a Multi - Modality Platform for Conditional Activation and Tissue Localization of Potent Biologic Drug Candidates Cytokines Antibodies Antibody - Drug Conjugates T - cell Bispecifics Our Value Proposition The Leading Paradigm of Biologics Localization, Opening Unparalleled Opportunity for More Effective and Safer Cancer Therapeutics 4 Substrate linkers Linker payload M asks
The Probody ® Therapeutic Platform – Exploiting Cancer’s Achilles’ Heel 5 More Binding in Tumors Less Binding in Normal Tissues Protease Mask Substrate linker Protease T arget PROBODY is a U.S. registered trademark of CytomX Therapeutics, Inc. All other brands and trademarks referenced herein are th e p roperty of their respective owners. Adapted from Santi et al., Proteomics 2018 Upregulated protease activity is a hallmark of cancer “Masking” limits ability of Probody therapeutics to bind to healthy tissues Proteases in tumor microenvironment “ unmask” Probody therapeutics, allowing more binding to tumor cells
Integrated Business Model for Long - Term Value Creation 6 • 4 global partnerships • 3 partnered programs in clinic • Raised >$500M non - dilutive capital to date • Robust & diverse portfolio • 6 INDs • 4 Phase 2 assets in 9 cancer types • Leader in conditional activation • Tunable platform • Multi - modality • Strong balance sheet • $336M end Q3 2021 • >450 issued and pending patents worldwide Robust Financing and IP Deep Pipeline Probody ® Platform Strong Partners
Experienced Leadership Team 7 Sean A. McCarthy, D. Phil. President, Chief Executive Officer and Chairman >20 years of experience in biotech with roles in R&D, business development, financing and general management Amy C. Peterson, M.D. EVP, Chief Development Officer >15 years of leadership experience in oncology drug development Carlos Campoy SVP, Chief Financial Officer >30 years of financial and leadership experience, mostly with publicly - held healthcare and biopharmaceutical companies Marcia P. Belvin, Ph.D. SVP, Head of Research >20 years of experience in preclinical pipeline discovery and development in oncology Alison L. Hannah, M.D. SVP, Chief Medical Officer >30 years of experience in investigational cancer therapy development Jeff Landau SVP, Head of Strategy and Chief Business Officer >20 years of biopharmaceutical experience in corporate development, corporate strategy and new product strategy/planning
Strong Track Record of Execution Towards Our Vision Becoming a Sustainable, Commercial Stage Oncology Leader 8 Financials Clinical Alliance $125M public equity offering 2014 2016 2017 2018 2019 2020 2008 2021 2015 2022 CX - 2009 Ph1 data at AACR CX - 904 IND $80M upfront $100M public equity offering $40M upfront + $20M equity $30M upfront IPO $70M Series D financing $50M upfront $20M Series C financing founded $200M upfront extension CX - 072 Ph1 combo data at ESMO CX - 2029 Ph2 preliminary results CX - 072 Ph1 data at ASCO CX - 2009, CX - 072 & CX - 2029 Ph1 data at ASCO CX - 072 Ph1 data at ASCO
CytomX Leadership has Established Conditional Activation as a Highly Strategic Area of Biologics Research and Development 9 2016 2019 2020 2015 2021 2022 Public Companies Recent M&A
Modality Product Candidate Target - Payload Indication Preclinical Phase 1 Phase 2 Commercial Rights Antibody - Drug Conjugate Praluzatamab ravtansine (CX - 2009) CD166 - DM4 HR+/HER2 - non - amp BC TNBC CX - 2029 CD71 - MMAE Squamous NSCLC HNSCC Esophageal/GEJ DLBCL CX - 2043 EpCAM - DM21 Solid tumors Immuno - Oncology BMS - 986249 CTLA - 4 1L Melanoma TNBC, HCC, CRPC BMS - 986288 CTLA - 4 (a - fucosylated ) Solid tumors TCB CX - 904 EGFRxCD3 TBD Cytokine TBD IFN - a2b TBD Leading Platform, Deepest Pipeline, Broadest Clinical Experience 4 Assets in 11 Phase 2 Studies in 9 Cancer Types 10 IND filed + pacmilimab (CX - 072) + nivolumab vs. ipi + nivo + nivolumab +/ - nivolumab
Praluzatamab Ravtansine (CX - 2009) First - in - Class Antibody - Drug Conjugate (ADC) Directed Toward CD166 for HER2 - non - Amplified Advanced Breast Cancer DM4 PAYLOAD
CD166 Expression (H - Score) in Breast Cancer Patients CD166 is a Novel ADC Target with High Tumor Expression Undruggable Using Conventional ADC Because of High Expression on Normal Tissue 12 log 2 normalized expression High Expression on Tumors High CD166 Expression by IHC Source: Lui J. et al SABCS 2020; PS 11 - 07
Praluzatamab Ravtansine Demonstrated Meaningful Clinical Benefit in Breast Cancer in Phase 1 13 Heavily pretreated patients with measurable disease who received ≥ 4 mg/kg CX - 2009 Source: Lui J. et al SABCS 2020; PS 11 - 07 CBR= clinical benefit rate (CR, PR or SD for 16 or 24 wks ); cPR = confirmed partial response; uPR = unconfirmed Partial Response Parameter Evaluable* Breast Cancer Patients Overall (n=32) HR+/HER2‒ (n=22) TNBC (n=10) CBR16 13 (41%) 9 4 CBR24 9 (28%) 5 (2 cPR ) 4 (3 uPR ) * Includes those with non - measurable but evaluable (e.g. bone - only) disease * * Percent Change in Tumor Burden from Baseline (%) Weeks Since Treatment Initiation Other Key Takeaways from Phase 1 Study • Recommended Phase 2 dose ‒ 7 mg/kg Q3W • Toxicity profile consistent with DM4 payload ‒ Ocular, neuropathic and hepatic CR in target lesions
Ongoing Multi - Arm Breast Cancer Phase 2 Study Initial Data Readout Expected in 2022 14 Ocular prophylaxis required HR+/HER2 non - amplified • 0 – 2 prior cytotoxics for advanced disease • Measurable disease required • No active corneal disease TNBC • CD166 High • ≥ 1 and ≤ 3 priors for advanced disease • Measurable disease required • Treated/stable brain metastases allowed • No active corneal disease • Arm C exclusion criteria: – PD - L1 negative/unknown – I/O refractory – History of or active autoimmune condition Arm A HR+/HER2 non - amp (n~40*) CX - 2009 *Efficacy evaluable, ** Naing, A. et al. J Immunother Cancer 2021;9:e002447 Arm B TNBC (n~40*) CX - 2009 Arm C TNBC (n~40*) CX - 2009 + CX - 072** Primary: Overall Response Rate (ORR) by central review Secondary : ORR (Inv), PFS, DCR, CBR24, DoR, OS, Safety, PK, ADA Exploratory: Biomarker correlation with outcome Endpoints Key Eligibility Breast Cancer SubType Monotherapy and Combination with Pacmilimab (CX - 072; anti - PD - L1) In Advanced, HER2 - non - Amplified Breast Cancer
PARPi (Olaparib, Talazoparib ) +/ - Hormone therapy, Praluzatamab Ravtansine Has Broad Potential in Current HR+/HER2‒ Treatment Paradigm 15 First Line (82K patients) Hormone Therapy Eligible (2021 US and EU5 patients) Chemotherapy Eligible (2021 US and EU5 patients) Second Line ( 53K patients) Chemo - Naïve* (88K patients) Post One Line Chemo (78K patients) Post Two Lines Chemo (63K patients) Hormone therapy +/ - mTOR ( Everolimus ) Hormone therapy +/ - PI3K ( Alpelisib ) Hormone therapy +/ - CDK4/6 ( Abemaciclib , ribociclib , Palbociclib) CX - 2009 monotherapy 0 - 2 prior lines of chemotherapy, post - endocrine therapy Sources: NCCN Breast Cancer Guidelines, 2021; DRG Breast Cancer Treatment 2021; GlobalData HER2 - Epidemiology and Forecast 2020; CytomX analysis
Praluzatamab Ravtansine Has Broad Potential in Current TNBC Treatment Paradigm 16 First Line (17K patients) Second Line (12K patients) Third Line (8K patients) Chemotherapy Sources: NCCN Breast Cancer Guidelines, 2021; DRG Breast Cancer Treatment 2021; DRG Breast Cancer Epidemiology 2021; CytomX a nal ysis Chemo +/ - Pembrolizumab (PDL1+) PARPi (Olaparib, Talazoparib ), BRCA+ Sacituzumab govitecan CX - 2009 Monotherapy 2/3L Post - Chemotherapy Chemotherapy Eligible (2021 US and EU5 patients)
CX - 2029 First - in - Class Antibody - Drug Conjugate (ADC) Directed Toward CD71 (Transferrin Receptor) for Multiple Cancer Types MMAE PAYLOAD
CD71 is a High Potential ADC Target With High Tumor Expression • Undruggable target with conventional ADC due to central role in iron metabolism • CX - 2029 is a CD71 - directed MMAE conjugated conditionally activated ADC • Anti - cancer agent with first - in - class potential HNSCC LYMPHOMA ESOPHAGEAL CD71 Expression by IHC LUNG 18 Data generated by CytomX
CX - 2029 Phase 1 Clinical Activity in Squamous Cancers 19 sqNSCLC or HNSCC patients with measurable disease who received ≥ 2 mg/kg CX - 2029 Percent Change in Tumor Burden from Baseline (%) Weeks Since Treatment Initiation 2 mg/kg 3 mg/kg 5 mg/kg Dose Level: SD PR Response: PD HNSCC HNSCC HNSCC sqNSCLC HNSCC HNSCC HNSCC sqNSCLC sqNSCLC HNSCC *Denotes patients still on treatment • > 90% masking maintained in circulation • Most frequent Grade 3+ AE was anemia – Managed with red blood cell transfusions, growth factor support and/or dose delays/reductions – Likely multi - factorial including CD71 biology and MMAE payload • 3 mg/kg Q3W selected as Phase 2 dose Source: Johnson M. et al Clin Cancer Res . 2021; 1078 - 0432.CCR - 21 - 0194
Ongoing Multi - Cohort CX - 2029 Phase 2 Expansion Study 20 sqNSCLC, HNSCC and esophageal/GEJ • Prior platinum and checkpoint inhibitor required • Documented progression after at least one prior systemic regimen for advanced disease DLBCL • ≥2 prior regimens (including anti - CD20 based therapy); not a candidate for stem cell transplant sqNSCLC n~25* *Efficacy evaluable HNSCC n~25* Esophageal/GEJ n~25* Primary: Overall Response Rate (ORR) by local investigator Secondary : PFS, DCR, CBR24, DoR , OS, Safety, PK, ADA, TTR Exploratory: Biomarker correlation with outcome Readout: Preliminary data for sqNSCLC and HNSCC reported Dec 2021 Endpoints Key Eligibility Cancer Type DLBCL n~25* Monotherapy at 3 mg/kg Every Three Weeks (Q3W)
No Current Standard - of - Care in 3L+ Post - Checkpoint Inhibitor Setting CX - 2029 Interim Phase 2 ORR of 18.8% in 3L+ SqNSCLC Enrollment Continues 21 Interim Takeaways from Ongoing Phase 2 Expansion Study • Heavily - pretreated and unselected sqNSCLC patients (n=16*) ‒ Medium # prior therapies = 2 ‒ All received prior checkpoint inhibition ‒ Response durability: 5.6 months for 1 PR and two PRs still on therapy** • HNSCC cohort fully enrolled (n=25*) ‒ 4% ORR • Safety profile consistent with Phase 1 observations ‒ No new safety signals identified ‒ Anemia most common Grade 3+ adverse event (67%) ‒ Low TRAE discontinuation rate, all due to anemia (5.8%) * Efficacy Evaluable; ** As of data cut off on October 29, 2021 Study Treatment Phase Line N Sq NSCLC ORR (%) CX - 2029 CX - 2029 2 3 rd 16 18.8 CheckMate 063 1 Nivolumab 2 3 rd 117 14.5 REVEL 2 Docetaxel 3 2 nd 171 10.5 CheckMate 017 3 Nivolumab 3 2 nd 135 20.0 Docetaxel 137 8.8 OAK 4,5 Atezolizumab 3 2 nd 112 11.6 Docetaxel 110 8.2 Sources: 1) Rizvi NA, Lancet Oncol 2015 ; 2) Garon EB, Lancet 2014; 3) Brahmer J, NEJM 2015; 4) Rittmeyer A, Lancet 2017 ; 5) Cortinovis D, Annals Oncol 2017 Supplement 2, ii32
Emerging Opportunity for CX - 2029 in 3L+ SqNSCLC 22 Sources: NCCN NSCLC Guidelines, 2021; DRG NSCLC Treatment 2021; DRG Breast Cancer Epidemiology 2021; CytomX analysis First Line (81K patients) Second Line (49K patients) Third Line (20K patients) Chemotherapy Nivolumab + ipilimumab +/ - chemotherapy Chemotherapy Physician’s choice / salvage PD - (L)1 inhibitors +/ - chemotherapy T argeted therapies +/ - chemotherapy CX - 2029 Monotherapy 3L Metastatic SqNSCLC Treatment ( 2021 US and EU5 Patients) PD - (L)1 monotherapy
EGFR CX - 904 Conditionally Activated EGFR x CD3 T - Cell - Engaging Bispecific Antibody (TCB) CD3
Conditionally Activated TCBs Open Target Landscape for Solid Tumors 24 Normal Tissue Source: Image adapted from Middelburg et al. Cancers. 2021 Conventional TCB Conditionally Activated TCB CD3+ T cell • Conventional TCBs are highly potent, however toxicity is a challenge due to high EGFR expression on normal tissues • Limited TCB targets and narrow therapeutic window Tumor • Conditionally activated TCBs designed to retain potent anti - tumor activity while having less systemic toxicities by avoiding T - cell engagement outside of tumor • Potentially expands TCB target landscape and widens therapeutic window Tumor Proteases Tumor Proteases Key: = EGFR = Normal cells = CD3+ T cells = Tumor cells = Proteases CD3+ T cell
EGFR: A High Potential Target for Conditionally Activated TCB Modality • Epidermal Growth Factor Receptor (EGFR) – EGFR is a tyrosine kinase receptor involved in homeostatic regulation of normal cells and carcinogenesis of epithelial malignacies 1,2 – EGFR plays a crucial role in cancer, and is one of the most frequently altered oncogenes in solid tumors 1 – Multiple EGFR mAbs approved (cetuximab, panitumumab, nimotuzumab, and necitumumab) • Prevalent EGFR expression – EGFR x CD3 conditionally activated TCB has opportunity in both high - and low - expressing cancers • Conditionally activated TCBs designed to unlock EGFR potential – Mechanism of action does not rely on EGFR signaling blockade – Less impacted by acquired resistance, e.g., activating mutations in NSCLC, KRAS/BRAF mutations in CRC – Opportunity to combine with IO agents 25 Sources: 1) Thomas and Weihua . Front Oncol. 2019; 2) Cai et al. Front. Oncol. 2020
Conditionally Activated EGFRxCD3 TCB Induces Tumor Regressions and Increases MTD in Preclinical Studies 26 * Act - TCB: Protease activated, unmasked TCB; Pb - TCB: Conditionally activated, masked TCB Increases MTD Extends PK Single Agent Efficacy in Human PBMCs engrafted into HCT116 and HT29 Tumor - bearing NSG mice Initiating First - in - Human Phase 1 Dose - Escalation Study of CX - 904 in 2022 Source: Boustany L. et al AACR - NCI - EORTC International Conference on Molecular Targets 2017 Masking markedly extends PK relative to the unmasked TCB (no TMDD) MTD increases by >60 - fold with conditionally activated TCB (Pb - TCB) Conditionally Activated EGFRxCD3 TCB Demonstrates Efficacy in Animal Models
Summary and Milestones
Modality Product Candidate Target - Payload Indication Preclinical Phase 1 Phase 2 Commercial Rights Antibody - Drug Conjugate Praluzatamab ravtansine (CX - 2009) CD166 - DM4 HR+/HER2 - non - amp BC TNBC CX - 2029 CD71 - MMAE Squamous NSCLC HNSCC Esophageal/GEJ DLBCL CX - 2043 EpCAM - DM21 Solid tumors Immuno - Oncology BMS - 986249 CTLA - 4 1L Melanoma TNBC, HCC, CRPC BMS - 986288 CTLA - 4 (a - fucosylated ) Solid tumors TCB CX - 904 EGFRxCD3 TBD Cytokine TBD IFN - a2b TBD Leading Platform, Deepest Pipeline, Broadest Clinical Experience 4 Assets in 11 Phase 2 Studies in 9 Cancer Types 28 IND filed + pacmilimab (CX - 072) + nivolumab vs. ipi + nivo + nivolumab +/ - nivolumab
Continued Leadership and Execution in 2022 29 • Initial CX - 2009 Phase 2 data in breast cancer (Arms A & B) • Expansion phase completion for CX - 2029 and new data updates • CX - 904 Phase 1 study initiation • Early - stage pipeline progress including cytokine program 2022 Outlook
©
2022 CytomX Therapeutics, Inc. Questions and Answers 30