UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

 

FORM 8-K

 

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): October 22, 2018

 

CYTOMX THERAPEUTICS, INC.

(Exact name of Registrant as Specified in Its Charter)

 

 

 

151 Oyster Point Blvd.

Suite 400

South San Francisco, CA 94080

(Address of principal executive offices, including Zip Code)

Registrant’s telephone number, including area code: (650) 515-3185

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instructions A.2. below):

 

 

 

 

 

---

 

Item 7.01Regulation FD Disclosure

Representatives of CytomX Therapeutics, Inc. are hosting an investor conference call to present the information in the presentation slides, attached hereto as Exhibit 99.1, to the investor community during the European Society for Medical Oncology (“ESMO”) 2018 Congress on October 22, 2018. A copy of the presentation slides, including a slide setting forth certain cautionary language intended to qualify the forward-looking statements included in the presentation, is furnished as Exhibit 99.1 to this Current Report and is incorporated herein by reference.

The information in this Item 7.01, including Exhibit 99.1, shall not be deemed “filed” for purposes of Section 18 of the Security Exchange Act of 1934, as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.

 

Item 9.01.Financial Information and Exhibits

(d) Exhibits

 

 

 

---

 

 

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.

 

 

 

 

 

 

 

 

 

 

 

 

PROCLAIM CX-072 ESMO 2018 Clinical Presentations October 22, 2018 Exhibit 99.1

Forward Looking Statements Special Note Regarding Forward-Looking Statements This presentation may contain projections and other forward-looking statements regarding future events. All statements other than statements of historical facts contained in this presentation, including statements regarding our future financial condition, technology platform, development strategy, prospective products, preclinical and clinical pipeline and milestones, regulatory objectives, expected payments from and outcomes of collaborations, and likelihood of success, are forward-looking statements. Such statements are predictions only and involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These risks and uncertainties include, among others, the costs, timing and results of preclinical studies and clinical trials and other development activities; the uncertainties inherent in the initiation and enrollment of clinical trials; expectations of expanding on-going clinical trials; availability and timing of data from clinical trials; the unpredictability of the duration and results of regulatory review; market acceptance for approved products and innovative therapeutic treatments; competition; the potential not to receive partnership milestone, profit sharing or royalty payments; the possible impairment of, inability to obtain and costs of obtaining intellectual property rights; and possible safety or efficacy concerns, general business, financial and accounting risks and litigation. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. More information concerning us and such risks and uncertainties 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 providing this information as of its date and do not undertake any obligation to update or revise it, whether as a result of new information, future events or circumstances or otherwise. Additional information may be available in press releases or other public announcements and public filings 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 (FDA). No representation is made as to their safety or effectiveness for the purposes for which they are being investigated.

Introduction Sean McCarthy, D. Phil. President and Chief Executive Officer

Reinventing Therapeutic Antibodies Imaging of Active Protease1 Normal Colon Primary Colon Cancer Metastatic Colon Cancer 1. Matriptase: LeBeau, et al., PNAS 2012 Probody™ Therapeutics: Activated in Tumor Tissue Proteases: Active in Tumor Tissue Antibodies are a very successful therapeutic class in many disease areas 2017: Half of the top 10 selling drugs were mAbs Major opportunity to target antibodies to disease tissue Enable new targets/mechanisms Reduce toxicities Maximize efficacy CytomX is targeting cancer tissue using Probody™ Therapeutics A versatile platform Leverages intrinsic protease activity in tumors PROBODY is a trademark of CytomX Therapeutics, Inc. All other brands and trademarks referenced herein are the property of their respective owners.

Deep and Differentiated Probody Pipeline Immunotherapies Probody Drug Conjugates Pb T Cell Engaging Bispecifics Multiple Programs PRODUCT CANDIDATE LEAD OPTIMIZATION IND-ENABLING PHASE 1/2 COMMERCIAL RIGHTS CX-072 CX-2009 BMS-986249 CX-2029 CX-188 Probody Drug Conjugate Pb T Cell Bispecific Additional PDCs, IO, TCBs CD166 Probody Drug Conjugate PD-L1 Probody Immunotherapy EGFR-CD3 PbTCB PD-1 Probody Immunotherapy CTLA-4 Probody Immunotherapy CD71 Probody Drug Conjugate EpCAM PDC $335.1M in cash end of Q218; $135.5M Follow-On Financing July 2018

CX-072 as a Potentially Differentiated Centerpiece of Combination Cancer Therapy CX-072 PD-L1 PROBODY THERAPEUTIC Checkpoint Inhibitors E.g. Yervoy® Probody Tx PDCs Pb-TCBs Other Cancer Immuno- therapies Kinase Inhibitors E.g. Zelboraf® ADCs Validated target Well-established efficacy & safety for class

PROCLAIM-CX-072 Design: Exploratory Studies 2018-2019, Expansion Studies 2019-2020 Initiation: Q3 2017 Inclusion: Unselected cancer types Data Presentations: ESMO 2018 A1: DOSE ESCALATION Initiation: January 2017 Inclusion: PD naïve, unselected cancer types Data Presentations: ESMO 2018 A2: MANDATORY BIOPSY D: 8 UNDISCLOSED TUMOR TYPES Initiation: Q2 2018 Inclusion: Selected for PD-L1 positivity Data Presentations: ESMO 2018, SITC 2018 Initiation: 2Q 2018 B: IPILIMUMAB COMBO C: VEMURAFENIB COMBO Initiation: Q3 2017 Inclusion: V600E BRAF mutated melanoma, PD-naïve Data Presentation: 2019 Enrollment completed Enrollment ongoing Initiation: 2019 SELECTED CANCER TYPES Trial not initiated EXPLORATORY EXPANSION D: 8 UNDISCLOSED TUMOR TYPES

CX-072 Clinical Data Presentations 2018 ESMO Annual Meeting Poster #435 Preliminary Results of the First-In-Human, Dose-Finding PROCLAIM-072 Trial of PD-L1 Probody Therapeutic CX-072 as Monotherapy in Patients with Advanced Solid Tumors Presenter:Valentina Boni, M.D., Ph.D., TART Madrid CIOCC Hospital Universitario Sanchinarro Date/Time:Monday, October 22, 12:45 – 1:45 p.m. CEST _______________________ Poster #436 Preliminary Interim Results of the First-In-Human, Dose-Finding PROCLAIM-072 Trial Evaluating the PD-L1 Probody Therapeutic CX-072 in Combination with Ipilimumab in Patients with Advanced Solid Tumors Presenter:Ruth Plummer, M.D., Northern Institute for Cancer Research, Newcastle University Date/Time:Monday, October 22, 12:45 – 1:45 p.m. CEST _______________________

Summary of CX-072 Updates Provided at ESMO CX-072 Monotherapy (PROCLAIM-CX-072 Part A1, A2) Part A1 follow up largely complete (22 patients; 0.03 – 30mg/kg) Well tolerated 3 PRs, including 1 confirmed PR TNBC (on treatment for 48 weeks as of data cutoff) Snapshot of Part A2; mandatory biopsy arm (0.3 – 10mg/kg) Additional safety data, follow up ongoing for efficacy at therapeutic doses Biopsy data to be presented at SITC CX-072 + 3 mg/kg ipilimumab (PROCLAIM-CX-072 Part B) Well tolerated Emerging, potentially differentiated safety profile Toxicity profile similar to 3 mg/kg ipilimumab monotherapy Clinical activity continues to be encouraging with longer term follow up Confirmation of responses presented at ASCO (1 CR, 2 PR) Ongoing durability

CX-072 Anti PD-L1 Probody Therapeutic: Monotherapy and Ipilimumab Combination Clinical Results Presented at 2018 ESMO Rachel Humphrey, M.D. Chief Medical Officer

PROCLAIM-CX-072 Monotherapy Dose Escalation Design Patients heavily pre-treated and PD-L1 positive a CX-072 monotherapy was administered intravenously every 14 days. One patient each was enrolled in the 0.03, 0.1, and 0.3 mg/kg dosing cohorts, and subsequent dose levels follow a 3+3 design, which is also used for all other dose-escalation groups. b After successful completion of the monotherapy dose level in Part A, Part A2 has enrolled 6 additional patients with PD-L1–positive cancer at each indicated dose to refine the maximum tolerated dose/multiple ascending dose and to evaluate the relationship between dose/exposure and safety, efficacy, and pharmacodynamic biomarkers.

PROCLAIM-CX-072 Monotherapy Dose Escalation: CX-072 Well Tolerated in Heavily Pre-treated Patients 46 evaluable patients MTD not reached Most treatment-related AEs (TRAEs) were Grade 1/2 5 patients (11%) experienced a Grade 3-4 TRAE 3 patients (7%) experienced an irAE AE, adverse event; irAE, immune-related adverse event; IRR, infusion-related reaction; SAE, serious adverse event; TEAE, treatment-emergent adverse event; TRAE, treatment-related adverse event. Deaths due to disease progression were excluded from all safety analyses. AEs were coded using MedDRA v19.1. Safety Summary, Patients Experiencing Event, n (%)

PROCLAIM-CX-072 Monotherapy Dose Escalation: Encouraging Anti-tumor Activity Observed in Heavily Pre-Treated Patients 38 evaluable patients with no available PD-1, PD-L1 inhibitors for their disease 3 PR: TNBC (confirmed PR 10 mg/kg); thymoma (unconfirmed PR (uPR) 3 mg/kg); cervical (uPR 10 mg/kg) 15 SD (39%); DCR 47% 38% (14/37) decrease in target lesions from baseline (per RECIST v1.1) 59% (10/17) decrease in target lesions from baseline at ≥ 3 mg/kg RECIST, Response Evaluation Criteria in Solid Tumors. Disease control rate is equal to the number of patients with complete response, partial response, or stable disease. a Evaluable patients are those with ≥1 postbaseline tumor assessment. b Includes 2 patients with unconfirmed partial response. c One patient with nonmeasurable disease at baseline in the 3 mg/kg cohort had a best overall response of noncomplete response/nonprogressive disease and was grouped under stable disease. d Disease control rate = partial response + stable disease. e Two patients each had a single postbaseline assessment that was stable disease but was assessed earlier than the protocol-defined minimum duration on study drug (7 weeks).. Best Tumor Response in Evaluable Patients a

PROCLAIM-CX-072 Monotherapy Dose Escalation: Waterfall Plot Among patients with measurable target lesions at baseline (n = 37), target lesions decreased from baseline in 14 (38%) patients and at dose levels ≥3 mg/kg in 10/17 (59%) patients per RECIST v1.1. CCC, cholangiocellular carcinoma; ER+ BC, breast (ER+) carcinoma; HNSCC, head and neck squamous cell carcinoma; RECIST, Response Evaluation Criteria in Solid Tumors; TNBC, triple-negative breast cancer. * Patient is still receiving treatment. a As evaluated per RECIST v1.1. Plots include evaluable patients with measurable disease at baseline. Comprised of Part A1 Follow-Up Patients and Part A2 New Patients at Lower Doses

PROCLAIM-CX-072 Monotherapy Dose Escalation: Spider Plot TNBC

Reduction of Tumor Burden Patient Profile 39 years old, Microsatellite Stable, TMB low, PD-L1 negative Initial CX-072 Case Study: Confirmed Partial Response in Triple Negative Breast Cancer Patient Three prior lines of therapy Post mastectomy and left reconstruction with radiotherapy Received CX-072 10 mg/kg Confirmed Partial Response Continues to receive CX-072 10mg/kg as of data cutoff; on treatment for 48 weeks Treatment History Aug 30, 2017 Baseline Sept 25, 2017 After 2 doses Oct 9, 2017 After 4 doses Nov 7, 2017 After 6 doses Jan 2, 2018 After 9 doses Reduction of Skin Lesion August 14, 2017 Baseline Scan December 5, 2017 Partial Response

PROCLAIM-CX-072 Dose Escalation: Single Dose PK Supports Platform MoA Single-dose CX-072 PK data suggests that CX-072 circulates predominantly as the intact prodrug species Clearance is minimally influenced by target mediated drug disposition Figure B is reprinted by permission from Springer Nature. Herbst RS et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515:563-567. Copyright © 2014.

CX-072 is Well-Tolerated MTD not reached in escalation through 30 mg/kg cohort Probody therapeutic well tolerated No differences in toxicity observed across all dose cohorts 5/46 (11%) patients experiencing a Grade 3/4 TRAE 3/46 (7%) patients experienced a Grade 3/4 irAE PROCLAIM-CX-072 Dose Escalation: Key Takeaways Predominant circulation as the intact (masked) prodrug species Minimal influence of target-mediated drug disposition at low doses Favorable safety profile CX-072 Remains Masked in Circulation CX-072 is Demonstrating Antitumor Activity as Monotherapy Demonstration of antitumor activity across a range of tumor types 3 objective responses in 38 evaluable patients (17%), including those with negative PD-L1 expression includes 1 confirmed PR in a TNBC patient, who has been on CX-072 for 11 months as of data cut-off Objective responses in heavily pre-treated patients with a variety of generally non-immunogenic tumors

Full Potential for Combination Immunotherapy is Limited by Immune-Related Toxicities 1. Larkin et al., NEJM, July 2015. Nivo + Ipi toxicity 64 patients with advanced or unresectable melanoma Nivolumab + Ipilimumab 38 (59%) Grade 3/4 irAE 46 (72%) required steroids 91% irAE leading to emergency department visits, hospitalizations and systemic immunosuppression 1. Larkin et al., NEJM, July 2015. Nivolumab Mono melanoma Ipilimumab Mono melanoma Nivo + Ipi Combo1 melanoma 3mg/kg every 2 weeks 3mg/kg every 3 weeks nivo 1mg/kg + ipi 3mg/kg every 3 weeks ORR 44% 19% 58% Treatment related Grade 3/4 AEs 16% 27% 55% Discontinued Drug 8% 15% 36% 2. Shoushtari AN, et al.JAMA Oncol. 2018; 4(1):98-101. doi:101001/jamaoncol.2017.2391 Historical Data Shows Combination Toxicities Results from MSKCC Expanded Access Program2

PROCLAIM-CX-072 Ipilimumab Combination Safety Summary: Initial Observations Supported with Further Follow Up 20 evaluable patients Weakly immunogenic tumors MTD not reached irAEs occurred in 3 of 20 patients (15%); Grade 3 irAEs occurred in 2 patients (10%) Most treatment-related AEs (TRAEs) were Grade 1/2, Grade 3/4 TRAEs occurred in 20% (4/20) patients: 2 (colitis and dyspnea/pneumonitis) (Grade 3) 0.3 mg/kg CX-072 + 3 mg/kg ipilimumab 1 (headache and hyponatremia) (Grade 3) 1 mg/kg CX-072+ 3 mg/kg ipilimumab 1 patient (amylase) (Grade 3) and (lipase increase) (Grade 4) 10 mg/kg CX-072 + 3 mg/kg ipilimumab AE, adverse event; irAE, immune-related adverse event; IRR, infusion-related reaction; SAE, serious adverse event; TEAE, treatment-emergent adverse event; TRAE, treatment-related (to any study drug) adverse event. Deaths due to disease progression were excluded from all safety analyses. AEs were coded using MedDRA v19.1. Safety Summary by Dose, Patients Experiencing Event, n (%)

PROCLAIM-CX-072 Ipilimumab Combination: irAE Safety Summary irAE, immune-related adverse event. a Dyspnea and pneumonitis occurred in the same patient. irAEs were defined as treatment-related AEs that were on a predefined list of >300 preferred terms, and that required treatment with systemic steroids within 30 days of the onset of the relevant AE. Patients were grouped according to the most severe grade experienced for a particular AE. AEs were coded using MedDRA v19.1.

PROCLAIM-CX-072 Ipilimumab Combination Dose Escalation: Initial Encouraging Anti-tumor Activity Observed in Ongoing Study Best Tumor Response in Evaluable Patients a per RECIST v1.1, n (%) 14 evaluable patients with no available PD-1, PD-L1 inhibitors for their disease 1 confirmed complete response Anal SCC (0.3 mg/kg CX-072 + 3 mg/kg ipi) PD-L1 negative, microsatellite-stable, intermediate tumor mutational burden, HPV-positive 2 confirmed partial responses (testis:1 mg/kg CX-072 + 3 mg/kg ipi; cancer unknown primary: 3 mg/kg CX-072 + 3 mg/kg ipi) 3 SD; DCR 43% 31% (4/13) Target lesion reduction from baseline (per RECIST v1.1) RANO, Response Assessment in Neuro-Oncology; RECIST, Response Evaluation Criteria in Solid Tumors. a Evaluable patients are those with ≥1 postbaseline tumor assessment. No patients in the 10 + 10 cohort were evaluable. b Objective response rate is the proportion of patients with complete response or partial response on 2 consecutive tumor assessments at least 4 weeks apart. c Disease control rate = complete response + partial response + stable disease. d One patient with glioblastoma assessed per RANO criteria.

PROCLAIM-CX-072 Ipilimumab Combination: Waterfall Plot ER+ BC, breast (ER+) carcinoma; HNSCC, head and neck squamous cell carcinoma; SCC, squamous cell carcinoma; SCLC, small cell lung cancer; TNBC, triple-negative breast cancer; RECIST, Response Evaluation Criteria in Solid Tumors * Patient is still receiving treatment. One patient (glioblastoma) had increases up to 392.6%, which have been omitted from this plot (with annotated values) in order to maintain readability. One evaluable patient had PD, as evidenced by a new lesion, and did not have a postbaseline target lesion assessment. As evaluated per RECIST v1.1. Plots include evaluable patients with measurable disease at baseline.6 Anal SCC* Cancer of unknown primary*

CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease; RECIST, Response Evaluation Criteria in Solid Tumors * Patient is still receiving treatment. One patient (glioblastoma) had increases up to 392.6%, which have been omitted from this plot (with annotated values) in order to maintain readability. One evaluable patient had PD, as evidenced by a new lesion, and did not have a postbaseline target lesion assessment. As evaluated per RECIST v1.1. Plots include evaluable patients with measurable disease at baseline.6 PROCLAIM-CX-072 Ipilimumab Combination: Spider Plot Deepening Responses Observed Since ASCO 2018

Well-Tolerated Ipilimumab (3 mg/kg) combination: favorable safety profile 20% Grade 3/4 rate trending below the level reported for other PD-1 pathway inhibitors in combination with ipilimumab1 15% overall irAE rate No new safety signals beyond those expected for other anti-PD-1 pathway inhibitors or ipilimumab PROCLAIM-CX-072 Ipilimumab Combination: Key Takeaways Observed Antitumor Activity 21% (3/14) confirmed objective responses, including 1 confirmed complete response (cCR) cCR: Anal carcinoma confirmed PR (cPR): Testicular cancer cPR: Cancer of unknown primary 1. Larkin et al., NEJM, July 2015.

Summary Sean McCarthy, D. Phil. President and Chief Executive Officer

PROCLAIM-CX-072 Next Steps: Clinical Proof of Concept Supports Program Expansion D: 8 UNDISCLOSED TUMOR TYPES Initiation: 2Q 2018 Enrollment ongoing EXPANSION Initiation: 2019 SELECTED CANCER TYPES Trial not initiated CX-072 MONOTHERAPY CX-072 COMBINATION WITH IPILUMIMAB Potential to advance one or more indications into registrational trials Ongoing CX-072 10 mg/kg + 6 mg/kg ipi Expansion plans in 2019 NEXT STEPS

November Presentations Provide Clinical Program Updates Society for Immunotherapy of Cancer Annual Meeting November 9-11, 2018 – Washington, DC Poster: “Preliminary Evidence of Intratumoral Activation and Immunomodulatory Effect of CX-072, a Probody Therapeutic Antibody Prodrug Targeting PD-L1, in a Phase 1/2a Trial” Analyst and Investor Event: Saturday, November 10th 12:30-2:00pm EDT Webcast Review SITC Presentation of CX-072 Part A2 Biopsy Data CytomX Therapeutics Third Quarter 2018 Financial Results Early November Corporate and clinical updates including a status update on CX-2009 Probody Drug Conjugate program targeting CD166

Thank you

Question and Answer Session