Helix Biopharma Corp. · TSX:HBP
Helix Biopharma — Biotech Showcase January 2018
32 slides from Helix Biopharma's conference presentation, January 2018
Slide 1: Helix BioPharma Corp
Helix BioPharma Corp Jan 2018 Biotech Showcase
Slide 2: Forward-looking Statements
Forward-looking Statements This presentation document contains certain forward-looking statements and information (collectively, “forward- looking statements”) within the meaning of applicable securities laws. Forward-looking statements are statements and information that are not historical facts bu
Slide 3: Company Brief
Company Brief ▪ Helix BioPharma Corp. (“Helix”) / Ticker symbol: HBP ▪ Est. 1996, clinical-stage, Immuno-oncology company ▪ Listed/trades on the Toronto Stock Exchange (TSX) and Frankfurt Stock Exchange (FSE) ▪ Shares outstanding = 100.06M ▪ Market cap = CAD 84.5 million ▪ Share price = CAD 0.84 ▪ 5
Slide 4: Product Development Pipeline
Product Development Pipeline Preclinical Phase I Phase II Phase III TIFN HPV Associated Cervical Intraepithelial Neoplasia (CIN)1 L-DOS47 L-DOS47 monotherapy NSCLC 2 L-DOS47 VIN/CIS NSCLC 3 L-DOS47 PEM/Carbo NSCLC V-DOS47 V-DOS47 CAR-T Solid Tumours Hematologic CAR-T Malignancies 1 Partnered 2 Phase
Slide 5: Acidosis and Tumor Progression
Acidosis and Tumor Progression Nature Communications 6:8752 2015 5
Slide 6: Dysregulated pH is Emerging as a Hallmark of Cancer
Dysregulated pH is Emerging as a Hallmark of Cancer 6 Nature Reviews Cancer 11, 671-677 (September 2011)
Slide 7: Suppression of Cytokine Production at Low pH
Suppression of Cytokine Production at Low pH B 120 110 100 90 % IL -2 r e le a s e 80 70 60 * 50 40 30 20 10 ** 0 ** 0 3 6 12 18 L a c tic a c id (m M ) • A. Lactic acid (10, 15mM LA) or low pH but not sodium lactate (15mM NaL) suppress the production of IL-2 and IFN-γ in activated mouse T and NK ce
Slide 8: Acidity Affects Adoptive T cell Therapy
Acidity Affects Adoptive T cell Therapy Effect of bicarbonate on adoptive T-cell transfer. A, Tumor growth after adoptive transfer of T cells or controls in combination with or without buffer therapy. Group mean differences between T cells vs. T cells vs bicarbonate were not significant. However, the
Slide 9: Tumor pH and Check-Point Inhibitors
Tumor pH and Check-Point Inhibitors Buffer therapy enhances efficacy of anti-immunotherapy in B16 melanoma. C57BL/6 9 Cancer Res; 76(6) March 15, 2016
Slide 10: Therapeutic Strategy Against Acidosis
Therapeutic Strategy Against Acidosis • Inhibitors (small molecules or antibodies) to target: – Carbonic anhydrase isoforms – V-ATPase inhibitors and proton pump inhibitors – Na+/HCO3− co-transporters, anion exchangers and Na+/H+ exchanger 1 – Monocarboxylate transporter inhibitors • Targeting a spe
Slide 11: DOS47
Targeting the Tumor Acidic Barrier DOS47
Slide 12: DOS47
DOS47 • DOS47 is a technology that changes the Tumor microenvironment from acidic to alkaline using the enzyme ‘urease’ • Alkalinizing the Tumor has the potential to – To exert direct cytotoxic effect on Tumors – to increase the action of certain chemo-therapies – to correct an impaired immune micro
Slide 13: L-DOS47
Helix First Clinical Drug Candidate L-DOS47 13
Slide 14: L-DOS47
L-DOS47 • L-DOS47 is a conjugate of urease with a proprietary camelid single domain antibody specific for CEACAM6 • CEACAM6 is a cell surface Tumor antigen highly expressed on lung, colon, pancreatic and other cancer cells • L-DOS47 is in clinical studies for the treatment of non- squamous, non-smal
Slide 15: L-DOS47 Binds to CEACAM6 Positive Cancer Patient Tissues
L-DOS47 Binds to CEACAM6 Positive Cancer Patient Tissues Age-matched Tumor Tissue Samples Normal Tissue Positive Negative Negative Kidney carcinoma 12/12 12/12 Parathyroid adenoma 1/1 n/a Plaenta, umbilical cord, allantois n/a 1/1 Myofibroblastic Tumor 1/1 n/a Prostate carcinoma 4/4 4/4 Thyroid carc
Slide 16: L-DOS47 Inhibits Tumor Growth in Lung and Pancreatic Models
L-DOS47 Inhibits Tumor Growth in Lung and Pancreatic Models 350 300 %Change in Tumor 250 Volume 200 150 100 50 0 0 5 10 15 20 Days A549 (lung) BxPC3 (Pancreatic) L-DOS47 (10,20,35U/kg) L-DOS47 (7,35,175ug/kg) Cisplatin control Paclitaxel control Tian et. al. Bioconjug Chem. 2015 Jun 17;26(6):1144-55
Slide 17: L-DOS47 Restores Acid Induced Cytokine Suppression
L-DOS47 Restores Acid Induced Cytokine Suppression A 25 B 7.7 PD-1 expression (S/N) 7.6 20 7.5 7.4 untreated 15 7.3 7.2 a-CD3/a-CD28 7.1 + 12 mM lactic acid (LA) pH 10 7.0 6.9 + LA + L-DOS47 5 6.8 + LA + L-DOS47 + 2 mM urea 6.7 + LA + L-DOS47 + 4 mM urea 6.6 0 6.5 α-CD3/α-CD28 - 1 1 1 1 1 6.4 (A) Tr
Slide 18: L-DOS47 Clinical Update
L-DOS47 Clinical Update • L-DOS47 Phase I / II Trial (LDOS002) – Monotherapy in advanced NSCLC patients – Phase I and stage 1 of Phase II completed • L-DOS47 Phase I with Expansion Trial (LDOS001) – Combination with pemetrexed and carboplatin in NSCLC patients (1st line) – Currently enrolling • L-DO
Slide 19: L-DOS47 Monotherapy Phase I / II Trial (LDOS002)
L-DOS47 Monotherapy Phase I / II Trial (LDOS002) • Monotherapy treatment protocol in NSCLC patients that have not responded to other treatments; • Stage IIIb / IV, metastatic, and progression after several lines of chemo, rad, surgery or chemo-naïve patients that have refused other lines of therapy;
Slide 20: L-DOS47 Monotherapy Swimmer Plot
L-DOS47 Monotherapy (Cohorts 13 to 16) LDOS002 Swimmer Plot Response Evaluable Population Weeks 0.0 4.0 8.0 12.0 16.0 20.0 24.0 28.0 32.0 36.0 40.0 44.0 Patients (Dose Levels 5.76 to 13.55 µg/kg) 20
Slide 21: Waterfall Plot: Target Lesion Response
Waterfall Plot: Target Lesion Response (Cohorts 9 - 16) 40% 34% Radiological Progression Change in Target Lesion 30% Stable Disease Stable Disease (> 16 weeks) 20% 15% 12% 12% 10% 10% 4% 4% 1% 1% 0% 0% 0% -1% -1% -2% -2% -3% -5% -6% -10% -8% -8% -9% -13% -20% 21
Slide 22: LDOS002 Monotherapy Phase I Summary
LDOS002 Monotherapy Phase I Summary • Currently has completed 16 cohorts • MTD at 13.55 µg/kg • One Dose Limiting Toxicity (DLT); • No safety issues beyond those observed in pre-clinical toxicology studies or expected in the population of patients being studied; • Immunogenicity consistent with what
Slide 23: LDOS002 Monotherapy Phase II (Stage 1) Summary
LDOS002 Monotherapy Phase II (Stage 1) Summary • Non-randomised study using Simon’s optimal two-stage design • Patients were dosed twice a week for 2 weeks follow by 1 week rest (3-week cycle) at 13.55 µg/kg • 21 patients were successfully dosed with 19 considered evaluable at stage 1 • L-DOS47 was
Slide 24: L-DOS47 PEM/CARBO Phase I (LDOS001)
L-DOS47 PEM/CARBO Phase I (LDOS001) • Combination therapy in first-line treatment of NSCLC: – Stage IIIb / IV, metastatic, and chemo-naïve; • Patients receive 4 cycles of combination treatment with L-DOS47 + pemetrexed/carboplatin • Patients who have not progressed following 4 cycles of combination
Slide 25: LDOS001 PEM/CARBO Phase I Cohort 1 and 2 Summary
LDOS001 PEM/CARBO Phase I Cohort 1 and 2 Summary • Three patients dosed at 0.59 µg/kg (cohort 1); six patients dosed at 0.78 µg/kg (cohort 2) • One patient in cohort 1 with PR (36%) and 5.9 months PFS with L-DOS47 alone in the maintenance phase • One patient in cohort 2 with stable disease and 13.3
Slide 26: LDOS003 VIN/CIS Randomized Phase II Study
LDOS003 VIN/CIS Randomized Phase II Study • Phase IIb, open-label, randomized study in patients with metastatic lung adenocarcinoma. • In Part 1 of the study (dose escalation), patients will receive eight (8) doses of L-DOS47 over four (4) cycles. • On Day 1 and Day 8 of each cycle, L-DOS47 will be
Slide 27: CAR-T
SINGLE DOMAIN ANTIBODY CAR-T 27
Slide 28: VHH Based CAR-T
VHH Based CAR-T • VHH domains – High specificity and affinity – Amendable to humanization – Target ‘hidden epitope’ – Easily adapted to CAR construct • Helix is applying know-how in tumour microenvironment therapeutic development and in VHH antibody design to generate a variety of novel CAR-Ts – Sol
Slide 29: Anti-CEACAM6 CAR-T in vivo study In Pancreatic Cancer
Anti-CEACAM6 CAR-T in vivo study In Pancreatic Cancer 1000 in j in j 800 in j in j in j ) 3 ) 3 T u m o r v o lu m e (m m 800 m ock T T u m o r v o lu m e (m m m ock T 600 PBS P B S 600 C A R -T C A R -T 400 400 200 200 * * * * * * * 0 0 * * 0 5 10 15 20 25 30 35 0 5 10 15 20 25 30 S tu d y D a y S
Slide 30: Helix CAR-T Initiatives
Helix CAR-T Initiatives • Design novel cell based therapeutics based on unique know-how of tumor microenvironment and VHH single domain antibodies • New Collaboration with ProMab Biotechnologies, Inc to accelerate CAR-T development with next- generation technologies • Plans are being reviewed for a
Slide 31: Executive Summary
Executive Summary • Helix develops novel anti-cancer therapies stemming from its proprietary technology platforms • L-DOS47 is an unique tumour microenvironment immuo-conjugate drug • L-DOS47 is well tolerated as a single agent in late stage NSCLC patients • L-DOS47 is being tested in combination wi
Slide 32: Acknowledgement
Acknowledgement • The Maria Sklodowska-Curie Institute of Oncology Poland • Military Institute of Health Institute Poland • Mazovian Centre of Pulmonary Diseases and Tuberculosis in Otwock Poland • Poznan University of Medical Sciences Poland • National Tuberculosis and Lung Diseases Research Instit