Candel Therapeutics, Inc. · NASDAQ:CADL
Candel Therapeutics — Rotterdam IOVC 2024
32 slides from Candel Therapeutics's conference presentation, Oct 28, 2024
Slide 1: Oncolytic immuno-activation Clinical Trial in Glioblastoma: Preliminary Safety and Feasibility
10/28/2024 Oncolytic immuno-activation Clinical Trial in Glioblastoma: Preliminary Safety and Feasibility from Longitudinal Injections E.A. Chiocca, MD PhD
Slide 2: Disclosures and Financial Support
Disclosures and Financial Support Current Advisor to Insightec, Inc., DNAtrix Inc, Bionaut Therapeutics, Theriva, Inc Equity interest in DNAtrix, Seneca Therapeutics, Ternalys Therapeutics Royalties/ Milestones to MassGeneral Brigham from Candel Therapeutics Research support from NIH, US Department
Slide 3: Glioblastoma clinical timeline (2024)
Glioblastoma clinical timeline (2024) Recurrence 2nd Recurrence (6-9 months) (a few months) Surgical +/- Clinical Resection Chemoradiation Trial (6 weeks) and +/- Surgery +/- off label then TMZ chemo +/- Optune Median survival time from initial dx = 15-20 months (but this varies based on genetic and
Slide 4: The Problem Glioblastoma (GBM)
The Problem Glioblastoma (GBM) For GBM, novel therapies (Immunotherapies) have not been Successful. Why? Immunological “coldness” Immune-deserted tumor
Slide 5: Glioblastoma immune microenvironment
Glioblastoma wit - Less immunosuppressive Myeloid cells - More immunoreactive T cells Gliobla - More immunosuppressive Myeloid cells - Less immunoreactive T cells in @ In situ administration of e Myeloid-derived Tumor cell / suppressor cells/MDSCs
Slide 6: CAN-3110 HSV-1 engineered for immunogenic potency and specificity
CAN-3110 (formerly known as rQNestin34.5v.2, Nakashima et al, 2020 Kambara et al, 2005) HSV-1 engineered for immunogenic potency and specificity ⎼ ICP34.5-null viruses have shown safety but replicate poorly ⎼ CAN-3110: ICP34.5 expression under control of Nestin promoter ⎼ Nestin overexpressed in gli
Slide 7: Steps towards clinical trial (rQnestin34.5v.2, now CAN-3110)
Steps towards clinical trial (rQnestin34.5v.2, now CAN-3110) 1999: Initial paper/IP on use of tumor-specific promoters to drive expression of ICP34.5 in oHSV 2000: Licensed to newCO/ oHSV GMP sub-contracted to Magenta, Inc. 2000-2001: Magenta “experts” cannot grow oHSV to required titers/ lose MVB 2
Slide 8: Slide 8
Slide 9: Patients with recurrent high-grade glioma: dose escalation and expansion
Dose escalation Single stereotactic injection of CAN-3110 Completed 3+3 dose escalation Nature 1x106 to 1x1010 PFU in half-log increments Completed: 30 patients dosed No dose-limiting toxicity observed Maximum administered dose: 1x1010 PFU Patients with Completed Dose expansion recurrent 1x109 PFU h
Slide 10: Summary of Arm A from Ling et al, 2023
Summary of Arm A from Ling et al, 2023 1. Well tolerated. No DLT up to 10e10 PFUs or with single timepoint injection in up TO 5 regions in tumor 2. Unexpected post-hoc analysis shows that mOS significantly linked to HSV1 serology, which was also a significant independent predictor of response 3. OS
Slide 11: How do we measure responses in clinical trials of GBM?
How do we measure responses in clinical trials of cancers like glioblastoma (GBM) ? • The only accepted “biomarker” of response is imaging by MRI
Slide 12: Manual 2D measurement in operator-selected MRI slice
Manual 2D measurement in operator-selected MRI slice Yang et al, 2015
Slide 13: Limitations of gadolinium contrast MRI as biomarker
Limitations of current methods of using gadolinium contrast extravasation in MRI as “biomarker” of response in GBM clinical trials: BBB disruption can occur after radiation Kebir et al, 2020
Slide 14: Limitations of MRI in oncolytic virus trials: inflammation
Limitations of current methods of using gadolinium contrast extravasation in MRI as “biomarker” of response in GBM oncolytic virus trials: BBB disruption occurs also during inflammation! (Frederick et al, 2022)
Slide 15: Why are so many GBM clinical trials failing?
Why are so many GBM clinical trials failing? What is the problem? We never know if the promising therapy actually does what it is supposed to do in patients because we use MRI as the biomarker of response SOC surgery/ Radiochemotx Clinical Trial 1 Clinical Trial 2 Surgery and Clinical Trial 3
Slide 16: Longitudinal Sampling Platform to Accelerate Development of Therapeutics for GBM
Longitudinal Sampling Platform to Accelerate Development of Therapeutics for Glioblastoma (GBM) A new clinical trial approach: G B M Te a m L a b ( M I T, D F C I , B W H , M S KCC, JH U, M DA ) R A D I C A L C O L L A B O R AT I O N
Slide 17: Longitudinal Sampling Clinical Trial for GBM
Longitudinal Sampling Clinical Trial for GBM
Slide 18: Biopsy size
Biopsy size Stereotactic needle has cut window ~ 10 mm x 3 mm. Stereotactic needle GBM biopsy Needle image from: https://www.semanticscholar.org/paper/A-Sequential-Comparison-on-the-Risk-of-Haemorrhage-Yuen-Zhu/a2cc1379e4b1a0bc36564eb
Slide 19: What can you do with serially biopsied GBMs?
What can you do with serially biopsied GBMs?
Slide 20: Administer an intratumoral agent like an OV
For the first longitudinal biopsy clinical trial in USA, there is a need to justify the serial procedures Instead of a systemic agent/drug, administer an Intratumoral agent (like an OV)!
Slide 21: Questions
Questions • Can we accrue/ consent patients to undergo multiple serial procedures? • Can patients tolerate multiple serial procedures without serious adverse events/ dose-limiting toxicities and/or “serial procedure” limiting toxicity? • Can we obtain biopsies from multiple sites in tumor? • How man
Slide 22: DF/HCC Trial #16-557 Arm C Status
DF/HCC Trial #16-557 Arm C Status Day 0 Day 15 Day 30 Day 60 Day 90 Day 120 Patient 1 6 biopsies 6 biopsies 8 biopsies 6 biopsies Completed 1 Location 1 Location 1 Location 1 Location Day 0 Day 15 Day 30 Day 60 Day 90 Day 120 Patient 2 9 biopsies 6 biopsies 5 biopsies 13 biopsies 12 biopsies 12 biop
Slide 23: No Serious Adverse Events or DLTs from serial biopsies or injections
No Serious Adverse Events or DLTs from serial biopsies or serial CAN-3110 injections
Slide 24: Multiple injections of CAN-3110 associated with survival exceeding 12 months
Treatment with multiple injections of CAN-3110 is associated with survival that exceeds 12 months in 3/6 rGBM subjects Francesca Barone, Six out of 12 patients have been treated in arm C with 1x10^8 pfu MD PhD (Candel Therapeutics) MTMG OS in Patient Sex Age #injections Status status months 1 54 M u
Slide 25: How do we make it work? It takes a village
How do we make it work? “It takes a village”! IND/ Clinical trial protocols/clinical data acquisition Agent storage and maintenance/ FDA/ rgeries and patient care/ Sample collection: tumor, csf, pbmcs) (Brigham) Nafisa Masud; Dan Triggs; Jen Gantchev, PhD; Mike Regan; Mike Prabhu; Brigham research p
Slide 26: BTC GBM biospecimen allocation flow chart
BTC GBM biospecimen allocation flow chart Permanent QC H&E and FFPE DNA/RNA Extraction for eventual bulk RNA/DNA seq from FFPE sections Core 1 Digital Pathology analysis (Dr. Huse MDACC) CODEX Spatial Protein Imaging IF (TBD) Core 2 Single Cell RNA Sorting and Sequencing (Sharma lab MDACC) T/BCR Seq
Slide 27: MRI enhancement versus histology inflammation at each timepoint
Although MRI scans show increased enhancement with each timepoint (tumor progression?), traditional histology shows increased inflammatory reaction at each timepoint
Slide 28: Localizing each biopsy site with the MRI
How do we spatially and longitudinally localize each biopsy site with the MRI? Alex L. Ling PhD (BWH Neurosurgery)
Slide 29: Integrated multimodal spatial and longitudinal analyses of serial biopsies
Integrated multimodal spatial and longitudinal analyses of collected serial biopsies Alex L. Ling PhD (BWH Neurosurgery)
Slide 30: Questions
Questions • Can we accrue/ consent patients to undergo multiple serial procedures? YES • Can patients tolerate multiple serial procedures without serious adverse events/ dose-limiting toxicities and/or “serial procedure” limiting toxicity? YES • Can we obtain biopsies from multiple sites in tumor? Y
Slide 31: Summary
Summary • Longitudinal injections of CAN-3110 with serial biopsies are well tolerated. Preliminarily mOS is 12.3 months with 3/6 patients alive • Concomitant serial MRIs show increased enhancement (Progression?), but traditional histology shows increased inflammation • Serial biopsies currently bein
Slide 32: Current GBM TeamLab Members
Zaki Abou Mrad Kelsey Hopland Vinay Puduvalli Nathalie Agar Amin Hossain David Reardon Current GBM Ryuhjin Ahn Kadir Akdemir Jian Hu Harry Huo Michael Regan Jordina Rincon Torroella Tejus Bale Jason Huse Nikki Schultz TeamLab Members Anna Ball Gerard Baquer Wen Jiang Sonali Jindal Sohrab Shah Padman