Recurrent Ovarian Cancer Phase 1b/2 Results

Transcription

1 Recurrent Ovarian Cancer Phase 1b/2 Results June 3 rd, IMV Inc. All rights reserved.

2 Forward-looking Statements Except for historical information, this presentation contains forward-looking statements, which reflect IMV s current expectations regarding future events. These forward-looking statements involve known and unknown risks and uncertainties that could cause IMV s actual results to differ materially from those statements. Those risks and uncertainties include, but are not limited to, our ability to access capital, the successful and timely completion of clinical trials, the receipt of all regulatory approvals and other risks detailed from time to time in our ongoing quarterly filings and annual information form. The forward-looking statements in this presentation are also based on a number of assumptions which may prove to be incorrect. Forward-looking statements contained in this presentation represent views only as of the date of this presentation and are presented for the purpose of assisting potential investors in understanding IMV s business, and may not be appropriate for other purposes. IMV does not undertake to update forward-looking statements, whether written or oral, that may be made from time to time by or on its behalf, except as required under applicable securities legislation. Investors are cautioned not to rely on these forward-looking statements and are encouraged to read IMV s continuous disclosure documents, including its current annual information form, as well as its audited annual consolidated financial statements which are available on SEDAR at and on EDGAR at IMV Inc. All rights reserved.

3 Agenda 1. Management assessment Fred Ors, CEO 2. ASCO presentation highlights - Update on clinical results Dr. Gabriela Rosu, Chief Medical Officer - Mechanism of action Dr. Marianne Stanford, Vice President Research IMV Inc. All rights reserved.

4 Update on phase 1/2b clinical trial with Incyte December: reported Top-line data from 100 mg epacadostat dosing cohort in 10 evaluable patients January: safety lead-in in 300 mg in 6 patients completed with no DLT (Dose Limiting Toxicity) February: all sites re open for enrollment of up to 40 patients in 300 mg dose cohort - 25 patients enrolled from February to May April: phase 2 expansion with up to 32 additional subjects - DPX-Survivac and low dose cyclophosphamide with, or without, epacadostat - Goal is to evaluate contribution of each investigational drug in the combination regimen June 3 rd : Update on clinical results: ASCO presentation - Update on clinical results with additional patients from 300 mg dose cohort at first CT scan (day 56) - Completed tumor biopsy analyzes from first cohort to demonstrate DPX-Survivac mechanism of action and correlation with tumor regression IMV Inc. All rights reserved.

5 Summary of the results Enrollment going well with 39 patients enrolled so far including 25 in the 300 mg dose Seeing promising level of activity in the 300 mg cohort at day 56-2 tumor regression so far including 1 PR with tumor regression ongoing for 9 months - 4 SDs ongoing - Most PRs appear after second CT scan (day 140) - Data in 300 mg dose should reach maturity before the end of the year First time and ground-breaking clinical demonstration of Mechanism of Action (MOA) - All clinical responses correlate with DPX-Survivac MOA - All PRs analyzed have evidence of increased T cell infiltration in the tumors post treatment - All PDs show little or no increase of T cell infiltration except one with evidence of MHC pathway and immune suppressive resistance 5

6 100 mg epacadostat versus 300 mg at day 56 Response at Day mg 300mg Best Response 100mg 300mg PR 1 * PR 3 SD 5 6 SD 4 Ongoing PD 4 2 PD 3 Total Evaluable Patients 10 8 Total Evaluable Patients 10 Goal of 16 minimal and up to 40 PR+SD 60% 75% PR+SD 70% TDB * The only patient with data evaluable at day 140 was reported PR (-43%) All rights reserved.

7 Next Steps Potential to further investigate the profile of the responders to better define the population who could benefit most from this treatment 300 mg dose update on clinical activity before the end of the year (day 140 CT scans and more) Phase 2 expansion initiated - Evaluation of DPX-Survivac activity with and without epacadostat First patient expected in Q3 Combinations with Merck Keytruda (pembrolizumab) in Ovarian cancer and DLBCL ongoing - First indication of level of activity in the summer Basket trial in 5 solid tumor indications in preparation - Announcement of the partner in the summer - First patient expected in the fall IMV Inc. All rights reserved.

8 Clinical data from the DeCidE 1 trial: Assessing the first combination of DPX-Survivac, low dose cyclophosphamide (CPA), and epacadostat (INCB024360) in subjects with stage IIc-IV recurrent epithelial ovarian cancer Oliver Dorigo 1, Janos L. Tanyi 2, James Strauss 3, Amit Oza 4, Tanya Pejovic 5, Prafull Ghatage 6, Jeannine Villella 7, Sharad Ghamande 8, Stephan Fiset 9, Lisa MacDonald 9, Lance Leopold 10, Gabriela Rosu 9 1 Stanford University, California, USA, 2 University of Pennsylvania, Pennsylvania, USA, 3 Mary Crowley Research Center, Texas USA, 4 Princess Margaret Cancer Centre, Ontario, Canada, 5 Oregon Health & Sciences University, Oregon, USA, 6 Tom Baker Cancer Centre, Alberta, Canada, 7 Lenox Hill Hospital, New York, USA, 8 Georgia Cancer Center, Georgia, USA, 9 IMV Inc., Nova Scotia, Canada, 10 Incyte Corporation, Delaware, USA 8

9 Triple Combination Immunotherapy DPX-Survivac: novel T cell activating therapy containing a mix of HLA class I peptides designed to evoke a T cell response against survivin Cyclophosphamide: low dose metronomic used as an immune modulator Epacadostat: potent and selective oral inhibitor of the enzyme indoleamine 2,3 dioxygenase 1 (IDO1) Cyclophosphamide DPX-Survivac Epacadostat Chen and Mellman, 2013 Immunity 39(1):1 9

10 DPX-Survivac (A T-cell Activation Therapy) Unique oil-based formulation (DPX) forcing continuous uptake of peptide antigen by the APC Designed to target survivin, a member of the inhibitor of apoptosis protein (IAP) family. Five peptides have different HLA restrictions (HLA-A1, A2, A3, A24, B7) Combination covers approximately 85% of the North American population Presumed MOA is to elicit a cytotoxic T lymphocyte response against tumor cells presenting the survivin peptides on HLA class I molecules 10

11 DeCidE 1 : Phase 1b Non-randomized, Open Label, Uncontrolled Safety and Effectiveness Study Study Day EOS DPX-Survivac (0.25 ml) DPX-Survivac (0.1 ml) mcpa (BID for 1 week) Epacadostat (up to 300 mg BID) PBMC/Plasma collection Routine Radiology Tumor Biopsy Primary objectives: safety, levels of cell mediated immunity, changes in immune cell infiltration Secondary objectives: clinical responses (RECIST v1.1) and CA-125 responses Data cut-off 16Mar

12 Subject Profile Parameter Group 1 (N=14) Group 2 (N=12*) Age: Mean (Range) 65 (35-79) 57 (36-72) ECOG: 0 11 (79%) 6 (50%) 1 3 (21%) 6 (50%) HLA Match 14 (100%) 12 (100%) Cancer Type: EOC 8 (57%) 9 (75%) FT 3 (21%) 1 (8%) P 3 (21%) 2 (17%) Stage at Diagnosis: 3c 10 (71%) 8 (67%) 4 4 (29%) 2 (17%) 1 st Line Platinum Sensitivity: S 11 (79%) 10 (83%) R 3 (21%) 2 (17%) Last Line Platinum Sensitivity: S 6 (43%) 1 (8%) R 8 (57%) 11 (92%) Prior Lines: Mean (Range) 3.1 (1-7) 4.5 (1-7) Group 1: DPX-Survivac, mcpa, < 100 mg BID epacadostat All tested subjects expressed survivin Group 2: DPX-Survivac, mcpa, 300 mg BID epacadostat *Enrollment to Group 2 is ongoing EOC (epithelial ovarian), FT (fallopian tube), P (peritoneal) Platinum Resistant (R) = 3-6m after first line, 0-6m after last line One subject diagnosed as 1c and one as 3a 12

13 Evaluable Subjects All subjects receiving a single dose of treatment are evaluable for safety 14 subjects in Group 1 12 subjects to date in Group 2 Subjects who complete both the day 56 scan and biopsy are evaluable for all other endpoints 10 subjects in Group 1 6 subjects to date in Group 2 (one result pending) 2 subject withdrew due to DLT (one SD, one no scan) 4 subjects withdrew due to unrelated SAE prior to day 56 (one PD, three no scan) 3 subjects withdrew consent following early PD 13

14 Safety (CTACE v 4.03) Systemic Events Toxicity G 1 G 2 G 3 G 4 Total (%) Nausea 10 (38) 4 (15) (54) Fatigue 9 (35) 2 (8) 2 (8) - 13 (50) Diarrhea 2 (8) 3 (12) (19) Rash/Rash Maculo-papular - 2 (8) 2 (8) - 4 (15) Vomiting 3 (12) 1 (4) (15) Lipase Increased (8) 1 (4) 3 (12) Abdominal Distension 2 (8) 1 (4) (12) WBC Count Decreased 2 (8) 1 (4) (12) Pyrexia 3 (12) (12) Decreased 3 (12) (12) Injection site reactions Toxicity G 1 G 2 G 3 G 4 Total (%) Induration 13 (50) 1 (4) (54) Erythema 13 (50) (50) Pruritus 5 (19) (19) Warmth 5 (19) (19) Atrophy 3 (12) 1 (4) (15) Pain 3 (12) (12) Bruising 2 (8) (8) Exfoliation 2 (8) (8) Rash 2 (8) (8) Group 1 N = 14 Group 2 N = 12, enrollment ongoing Appetite Dehydration - 2 (8) (8) Dizziness 2 (8) (8) Pruritus 2 (8) (8) Events possibly, probably, or definitely related to study treatment and occurring >1 subject 14

15 Percent Change From Baseline in Target Lesions (modified RECIST v 1.1) Best Reported Response Best Response Target Lesion Response PR = 4 SD = 8 PD = 4 Response over time Subjects considered evaluable if they complete the D56 biopsy and scan After ending treatment subjects enter an extended follow-up for PFS and OS 15

16 T Cell Infiltration to the Tumor Correlates with Objective Clinical Response Screen Subject (71y, FT cancer, plat-sens, 1 previous line of therapy, tumor burden 37 mm, ECOG = 0, HLA-A02 -A24) Screen D56 D140 D196 D252 D308 D mm 37 mm SD, 0% 27 mm SD, -27% 23 mm PR, -37% 23 mm PR, -37% 24 mm PR, -35% 24 mm PR, -35% D56 D0 D140 D196 16

17 On-treatment Activation of T cell Receptor Signaling Pathway (by RNAseq) PR PR SD SD PD PD PD PD Image source: KEGG Pathway Database 17

18 F o ld c h a n g e ( m R N A le v e l) F o ld c h a n g e ( m R N A le v e l) N o r n a liz e d m R N A c o u n t s N o r n a liz e d m R N A c o u n t s Low Pre-treatment Levels of HLA and b2m Correlates with Poor Clinical Outcome Subject (67y, P cancer, plat-sens, 1 previous line of therapy, tumor burden 80 mm, ECOG = 0, HLA-A02) Best Response: confirmed progression Pre-treatment levels of HLA and b2m in tumor tissue of individual subjects (RNAseq) b2m HLA-A HLA-B HLA-C 0 0 On-treatment upregulation of immunosuppressive transcripts in tumor tissue relative to baseline tumor levels PD-L1 PD IDO1 TGFb FoxP3 18

19 S F U ( p e r P B M C ) Cellular Immunity and Infiltration of Immune Cells Endpoint Investigation Samples Collected 1 o Induction of systemic antigen specific T cells by ex vivo IFN-g ELISPOT Explor. Induction of systemic antigen specific T cells by ex vivo Granzyme B ELISPOT and in vitro tetramer analysis 1 o Induction of T cell infiltration into tumors measured by multiplex IHC Explor. Explor. Induction of T cell infiltration into tumors post treatment using RNA sequencing and RNA scope analysis Migration of antigen specific T cells to tumor using TCRb sequencing of systemic and tumor T cells 2 o Demonstration of tumor barriers to treatment using mihc and RNA scope PBMC PBMC Pre- and ontreatment biopsy Pre- and ontreatment biopsy D56 PBMC and ontreatment biopsy Pre- and ontreatment biopsy Individual subject responses to survivin peptide pool IFNg ELISPOT S t u d y D a y All evaluable subjects in Group 1 have demonstrated an increase in systemic survivin-specific T cells 19

20 Survivin-specific T cell clones within the tumor Have utilized TCR-β sequencing technology to correlate the presence of survivin-specific T cell clones in the peripheral blood to the presence of the same clones within tumor tissue - Expand survivin specific T cells from the PBMC of treated subjects - Purify the antigen specific T cells from the blood of subjects post treatment using FACS sorting using survivin antigen specific tetramers - Sequence the T cell clones from the 95+% pure population - Look for the specific T cell clones in the pre-treatment and post-treatment biopsy samples - Challenge has been to have all the necessary samples from the subjects to complete the analysis Have completed preliminary analysis on two subjects from Cohort 1 - One subject ( ; SD) had evidence of the presence of survivin-specific T cell clones within the tumor post treatment - One subject ( ; PD) had no evidence of survivin-specific T cell clones within the tumor, consistent with additional data on resistance to treatment IMV Inc. All rights reserved.

21 Conclusions 26 recurrent EOC/FT/P subjects with measurable disease enrolled Group 1 (DPX-Survivac, mcpa, < 100 mg BID epacadostat) enrollment complete Group 2 (DPX-Survivac, mcpa, 300 mg BID epacadostat) enrollment ongoing Study treatments are being well tolerated Low grade injection site reactions and mild to moderate GI events Active immune response detected in all assayed subjects Demonstrated increase in antigen specific systemic T cells On-treatment increases in tumor CD8 + T cells Measurable decrease in tumor burden reported in several subjects 16 evaluable subjects of 26 subjects enrolled: 4 with best response of PR at target lesions, 8 with SD MOA showing correlation between tumor regression and T cell infiltration We plan to further investigate the profile of the responders to better define the population who could benefit most from this treatment 21

22 Acknowledgments A sincere thank you to our patients and their families Thank you to the co-investigators, study coordinators, and their teams at the following centers: Stanford University University of Pennsylvania Mary Crowley Cancer Center Princess Margaret Cancer Centre Oregon Health & Sciences University Tom Baker Cancer Centre Lenox Hill Hospital Georgia Cancer Centre This study is sponsored by IMV Inc. and funded by both IMV Inc. and Incyte Corporation Related online abstract e17550 NCT

23 Next Steps Potential to further investigate the profile of the responders to better define the population who could benefit most from this treatment 300 mg dose update on clinical activity before the end of the year (day 140 CT scans and more) Phase 2 expansion initiated - Evaluation of DPX-Survivac activity with and without epacadostat First patient expected in Q3 Combinations with Merck Keytruda (pembrolizumab) in Ovarian cancer and DLBCL ongoing - First indication of level of activity in the summer Basket trial in 5 solid tumor indications in preparation - Announcement of the partner in the summer - First patient expected in the fall IMV Inc. All rights reserved.

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