Slide 1: Phase 3 trial of CAN-2409+prodrug with EBRT for localized prostate cancer
Phase 3, randomized, placebo-controlled clinical trial of CAN-2409+prodrug in combination with standard of care external beam radiation (EBRT) for newly diagnosed localized prostate cancer Theodore DeWeese, Thomas Wheeler, John Sylvester, Thomas Schroeder, Glen Gejerman, Gregory Chesnut, Thomas Face
Slide 2: Key Takeaways
2 Key Takeaways CAN-2409 + prodrug significantly reduces the risk of disease recurrence or death by 30% (HR 0.7, p-value 0.0155) compared with placebo when added to SoC EBRT in patients with intermediate-to-high-risk, localized prostate cancer CAN-2409 could offer a potential paradigm shift in the t
Slide 3: Unmet need in localized prostate cancer
Unmet need in localized prostate cancer Global concern: approximately 1.4 million new cases of prostate cancer in 20201 Incidence in US2 INTERMEDIATE HIGH LOW RISK RISK RISK 65K 108K 43K Patients Currently Receiving Radiotherapy ~65K (~43%) 1 WHO cancer fact sheet. February 3, 2022 2 Globe Life Scie
Slide 4: CAN-2409 + prodrug: multimodal immunotherapy synergistic with radiotherapy
CAN-2409 + prodrug: multimodal immunotherapy synergistic with radiotherapy CAN-2409 induces formation of Valacyclovir Inflammatory Tumor CD8+ cytotoxic T cells mediators antigens Dendritic cell B-cell CAN-2409 locally administered Macrophage Fibroblast combined with oral prodrug Cytotoxic metabolite
Slide 5: Phase 3 clinical trial of CAN-2409 in intermediate / high risk localized prostate cancer
5 Phase 3 clinical trial of CAN-2409 in patients with newly diagnosed, intermediate / high risk, localized prostate cancer NCT01436968 Primary Endpoints CAN-2409 + Valacyclovir N=745 (3 injection courses + radiotherapy, • Disease-free survival (time to cancer recurrence or death due to with or witho
Slide 6: CAN-2409 is delivered in a routine and well-tolerated outpatient procedure
CAN-2409 is delivered in a routine and well-tolerated 6 outpatient procedure Standard urologic injection procedure CAN-2409 biodistribution analysis Bladder Prostate Images of fluorescently labeled adenoviral vector in freshly resected prostate, demonstrating homogeneous distribution throughout the
Slide 7: CONSORT diagram
CONSORT diagram 7 Randomized 2:1 to CAN-2409 vs. placebo Reasons for incomplete treatment: Reasons for incomplete AE or complications 26 (5.2%), treatment: Lost to follow-up 1 (0.2%), AE or complications 15 (6%), Patient choice 7 (1.4%), Lost to follow-up 0 (0%), Physician choice 4 (0.8%) Patient ch
Slide 8: Baseline characteristics of randomized patients
Baseline characteristics of randomized patients 8 CAN-2409 + prodrug Placebo + prodrug Total ITT population (N=745) (N=496) (N=249) (N=745) Median age (yrs) 69 68 69 Race, n(%) White/Caucasian 385 (77.6) 206 (82.7) 591 (79.3) Black/African American 93 (18.8) 28 (11.2) 121 (16.2) Asian 3 (0.6) 1 (0.4
Slide 9: CAN-2409 in combination with SoC radiation +/-ADT was generally well tolerated
CAN-2409 in combination with SoC radiation +/-ADT was 9 generally well tolerated Treatment related AEs >5% in either arm Preferred term CAN-2409+prodrug Placebo+prodrug Total (N=479) (N=232) (N=711) Chills 160 (33.4) 20 (8.6) 180 (25.3) • Chills, fever, flu-like symptoms were Influenza-like illness
Slide 10: CAN-2409 significantly improves disease-free survival (DFS)
CAN-2409 significantly improves disease-free survival (DFS) 10 in newly diagnosed, intermediate / high-risk prostate cancer Hazard ratio (95% CI): 0.70 (0.52, 0.94), P=0.0155 Median follow-up 50.3 months (CI 45.37, 51.29) CAN-2409 results in 30% improvement in DFS (includes death from anyNote:cause)
Slide 11: DFS outcomes stratified by use of short-term ADT
11 DFS outcomes stratified by use of short-term androgen deprivation therapy (ADT) Distribution of ADT use in intermediate risk category and outcomes Intermediate N events/ Use of ADT DFS HR with CAN-2409 Risk Category patients No Androgen HR = 0.56 - 104/349 deprivation therapy 95% CI 0.38 – 0.83 H
Slide 12: CAN-2409 significantly improves prostate cancer-specific DFS
CAN-2409 significantly improves prostate cancer-specific DFS 12 Hazard ratio (95% CI): 0.62 (0.44, 0.87) P=0.0046 Highly significant 38% reduction in risk for prostate cancer recurrence or prostate cancer-related death (ITT, N=745) Note: Disease-free survival (DFS) represents time to cancer recurren
Slide 13: CAN-2409: other key secondary endpoints
13 CAN-2409: other key secondary endpoints • Significant increase in the proportion of patients achieving a prostate-specific antigen (PSA) nadir of <0.2 ng/ml in the treatment arm compared with placebo o 67.1% vs. 58.6%, respectively (p=0.0164) • As expected*, overall survival was similar by treatm
Slide 14: CAN-2409 significantly improves pathological complete response in 2-year biopsies
CAN-2409 significantly improves the rate of pathological 14 complete response in 2-year biopsies compared with the placebo control arm Pathological complete response was observed in 80.4% of the biopsies available at 2 years in the CAN-2409 arm compared with 63.6% in the placebo arm CAN-2409 Placebo
Slide 15: Positive biopsies ≥2 years after radiotherapy predict metastases and mortality
Positive biopsies ≥ 2 years after radiotherapy are predictive of 15 metastases and cancer-related mortality after long-term follow up Patients with a positive prostate biopsy ≥ 2 years after radiotherapy because of localized cancer had: • 10-fold higher odds of developing biochemical failure (P < 0.
Slide 16: Concluding remarks
16 Concluding remarks • Compared with standard of care alone, the addition of CAN-2409: • Significantly reduced the risk of disease recurrence or death by 30% (HR 0.70; p=0.0155) • Significantly reduced the risk of prostate cancer recurrence or prostate cancer-related death by 38% (HR 0.62; p=0.0046
Slide 17: Acknowledgements
17 Acknowledgements Patients and their families, study site personnel, Dr. Peter Scardino for co-designing the trial. Investigators: Drs. Joshua Meeks, Nilay Gandhi, Steven Sukin, Daniel Song, Michael Liss, Steven Kester, Maximiliano Sorbellini, Bryan Mehlhaff, Paul Kim, Shawn Zimberg, Stephen Savag
Slide 18: Lay Summary
18 Lay Summary For patients with localized prostate cancer (meaning the cancer has not spread), the experimental treatment CAN-2409 has been shown to reduce the risk of the cancer coming back or leading to death by 30% when added to standard radiation therapy. This experimental treatment could repre