Helix Biopharma Corp. · TSX:HBP
Helix Biopharma — Investor Presentation (September 2024)
50 slides from Helix Biopharma's investor presentation, September 2024
Slide 1: L-DOS47: An Unconventional ADC Approach For Cancer Therapy
L-DOS47: An Unconventional ADC Approach For Cancer Therapy Partnering Presentation September 2024
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 but
Slide 3: Executive Summary
Executive Summary • We are developing a novel first and best-in-class anti-cancer therapy stemming from our proprietary technology platform • Our lead Tumor Defence Breaker L-DOS47 is a unique tumor microenvironment modifying drug. L-DOS47 neutralizes tumor acidity potentially allowing for better ef
Slide 4: The Hallmarks of Cancer
THE HALLMARKS OF CANCER • The characteristics of cancer can be organized into multiple hallmarks or traits • These hallmarks provide a framework to study cancer and to develop drugs • Targeted drugs are developed against specific traits, but cancers often acquire resistance and escape • Missing are
Slide 5: Acidosis Promotes Tumor Progression
ACIDOSIS PROMOTES TUMOR PROGRESSION • Hypoxia, poor vasculature and increased flux of carbons through fermentative glycolysis leads to extracellular acidosis in solid tumors (Pasteur effect). • Cancer cells can maintain a glycolytic phenotype even in the presence of oxygen (Warburg effect) causing f
Slide 6: L-DOS47: Anti-CEACAM6-Urease Bioconjugate Targeting Acidosis
L-DOS47: ANTI-CEACAM6 -UREASE BIOCONJUGATE TARGETING ACIDOSIS Conjugation of urease to a tumor-specific antibody allows targeted urease delivery by iv injection Tian B et al. Bioconjugate Chemistry, 2015 Helix Corporate Presentation
Slide 7: L-DOS47: A Novel Platform Technology Targeting Tumor Acidity
L-DOS47: A NOVEL PLATFORM TECHNOLOGY TARGETING TUMOR ACIDITY ALKALINE Anti-CEACAM6 nanobody Urease L-DOS47* (680 kDa) ACIDIC CEACAM6-expressing tumor Slide courtesy of Dr. Dimitri Stowbur, University of Tübingen Helix Corporate Presentation *Product (L-DOS47) from Helix BioPharma, Toronto, Canada
Slide 8: L-DOS47: A Novel Platform Technology Targeting Tumor Acidity
L-DOS47: A NOVEL PLATFORM TECHNOLOGY TARGETING TUMOR ACIDITY ALKALINE anti-CEACAM6 Anti-CEACAM6 nanobodies bind nanobody tumor cells expressing CEACAM6 Urease Conversion: Urea into NH3 and CO2 L-DOS47* (680 kDa) ACIDIC CEACAM6-expressing tumor Slide courtesy of Dr. Dimitri Stowbur, University of Tüb
Slide 9: L-DOS47: A Novel Platform Technology Targeting Tumor Acidity
L-DOS47: A NOVEL PLATFORM TECHNOLOGY TARGETING TUMOR ACIDITY ALKALINE anti-CEACAM6 Anti-CEACAM6 nanobodies bind nanobody tumor cells expressing CEACAM6 Urease Conversion: Urea into NH3 and CO2 L-DOS47* (680 kDa) ACIDIC Tumor cell regression through neutralization of the pH in the TME Slide courtesy
Slide 10: L-DOS47: A Novel Platform Technology Targeting Tumor Acidity
L-DOS47: A NOVEL PLATFORM TECHNOLOGY TARGETING TUMOR ACIDITY 1. Tumor acidity is an escape mechanism cancer cells use to evade anti-tumor immune responses 2. Acidosis correlates with treatment resistance and poor prognosis for cancer patients 3. L-DOS47 is designed to reduce tumor acidity with a nov
Slide 11: Preclinical Studies
Preclinical Studies odee ss HELIX * biopharma
Slide 12: L-DOS47 Binds to Human CEACAM6 with High Specificity
L-DOS47 BINDS TO HUMAN CEACAM6 WITH HIGH SPECIFICITY L-DOS47 (multiple AFAIKL2 conjugated to L-DOS47 binds the human pancreatic urease) binds human CEACAM6, adenocarcinoma cell line BxPC3 that not other human CEACAMs (1, 3, and expresses high levels of CEACAM6. 5) or cynomolgus monkey CEACAM6 2.0 16
Slide 13: L-DOS47 Binds Well to Pancreatic Adenocarcinoma Expressing High CEACAM6
L-DOS47 BINDS WELL TO PANCREATIC ADENOCARCINOMA EXPRESSING HIGH LEVELS OF CEACAM6 A CEACAM6 B L-DOS47 Examples of PDAC cases with high (orange boxes) and 80 80 low (blue boxes) A. CEACAM6 expression and 20 20 B. L-DOS47 binding 0 – low medium high on a TMA comprising duplicate cores from ten cancer
Slide 14: L-DOS47 Binds Well to Colorectal Cancer Cases Expressing High CEACAM6
L-DOS47 BINDS WELL TO A HIGH PERCENTAGE OF COLORECTAL CANCER CASES EXPRESSING HIGH LEVELS OF CEACAM6 Representative examples of high and low CEACAM6- expressing CRC tumors. 75% of cases (15/20) expressed high levels, 15% were low expressors and 10% did not express CEACAM6* TMA from TissueArray.com s
Slide 15: L-DOS47 Binds Well to NSCLC Adenocarcinoma Expressing High CEACAM6
L-DOS47 BINDS WELL TO A HIGH PERCENTAGE OF NON-SMALL-CELL LUNG ADENOCARCINOMA EXPRESSING HIGH LEVELS OF CEACAM6 anti-CEACAM6 Representative examples of high 300μm 300μm and low CEACAM6- expressing NSCLC tumors. L-DOS47 300μm 300μm TMA from US Biolab stained by Young Ou, scored by Martin Koebel, Univ
Slide 16: L-DOS47 Localizes to CEACAM6-Expressing Tumors
L-DOS47 LOCALIZES TO CEACAM6-EXPRESSING TUMORS 8% of iv – injected L-DOS47 accumulated by 48 hours post-injection Fluorescence image of subcutaneous A549 lung tumor in nude mouse 72 hours after injection with Cy5.5-labelled L-DOS47 Fluorescence of extracted tumor (magnified) Mean normalized peak flu
Slide 17: L-DOS47 Rapidly Clears Liver and Kidneys
L-DOS47 RAPIDLY CLEARS LIVER AND KIDNEYS Kidney accumulation of injected L-DOS47 Cy5.5 peaked at 18% at 2-6 hours and decreased thereafter % Conjugate accumulated Ex vivo images of isolated liver (left) and kidneys (right) 72 hours post-injection The percentage of total possible fluorescence was cal
Slide 18: L-DOS47 Enhances Cytotoxicity of Carboplatin
L-DOS47 ENHANCES CYTOTOXICITY OF CARBOPLATIN 100 80 %Survival *** % Cell Survival 60 40 *** 20 *** *** 0 0 25 50 100 200 Carboplatin (M) • A549 lung adenocarcinoma cells treated for 72 hours • Carboplatin only (blue bars); with L-DOS47 + urea (red bars) • L-DOS47 + urea alone cytotoxic (first red b
Slide 19: L-DOS47 Does Not Activate Primary Human or Monkey PBMCs In Vitro
L-DOS47 DOES NOT ACTIVATE PRIMARY HUMAN OR MONKEY PBMCs IN VITRO In the absence of its substrate, urea, L-DOS47 does not impact viability or induce proliferation in unstimulated PBMCs Human and monkey PBMCs were treated in vitro with a range of L-DOS47 concentrations (1 – 50 μg/mL, corresponding to
Slide 20: L-DOS47 Reduces Acidity Increasing Immune Cell Responses In Vitro
L-DOS47 REDUCES ACIDITY THEREBY INCREASING IMMUNE CELL RESPONSES IN VITRO A 0.4 unit increase in pH significantly enhances IL-2 secretion by CD8+ T cells untreated -CD3/-CD28 2000 IL-2 concentration (pg/mL) + L-DOS47 **** **** + L-DOS47 + 2 mM urea 8.2 1500 8.1 + L-DOS47 + 4 mM urea 8.0 1000 *** 7
Slide 21: L-DOS47 Increases Tumor pH In Vivo
L-DOS47 INCREASES TUMOR pH IN VIVO CEST MRI reveals pH increases between 4-72 hours post-L-DOS47 administration. baseline 72h post-LDOS47 • Murine KPC961 pancreatic cancer cells expressing human CEACAM6 were orthotopically established in B6.129 mice • CEST MRI images were taken prior to and at vario
Slide 22: L-DOS47 Inhibits Tumor Growth in Combination with Anti-PD1
L-DOS47 INHIBITS TUMOR GROWTH IN COMBINATION WITH ANTI-PD1 Tumor growth in an orthotopic pancreatic tumor model Tumor growth • Anti-PD1 + L-DOS47 significantly 1500 reduced KPC961-1B6 tumor growth compared to anti-PD1 alone Tumor volume (mm3) 1000 Control n=26 Anti-PD1 n=35 • Tumor volumes were meas
Slide 23: L-DOS47 Inhibits Tumor Growth in Combination with Anti-PD1
L-DOS47 INHIBITS TUMOR GROWTH IN COMBINATION WITH ANTI-PD1 • d: Comparison of tumor growth and regression between anti-PD1 (purple), L-DOS47 (red) and anti-PD1 in combination with L-DOS47 (green) → significant reduction in tumor growth • e: Reduction in tumor volume in pancreatic cancer in mm³ from
Slide 24: Additional Ongoing Studies
Helix Corporate Presentation • In vitro and in vivo assessment of impacts of L-DOS47, pH changes and ammonium on primary human immune cells as well as on CEACAM6 and checkpoint marker expression on tumor cells ADDITIONAL • Advanced imaging to confirm biodistribution of L-DOS47 ONGOING • Assessment o
Slide 25: Clinical Studies
Clinical Studies odee ss HELIX * biopharma
Slide 26: Tumor Defence Breaker Technology Platform
TUMOR DEFENCE BREAKER TECHNOLOGY PLATFORM CLINICAL TRIALS L-DOS47 monotherapy NSCLC (clinical trial # NCT02340208) PRECLINICAL PHASE 1 PHASE 2 L-DOS47 combo PEM/CARBO NSCLC (clinical trial # NCT02309892) PRECLINICAL PHASE 1 PHASE 2 L-DOS47 combo DOXO Pancreas (clinical trial # NCT04203641) PRECLINIC
Slide 27: LDOS002 Study Design: Monotherapy Phase 1 & 2 in NSCLC
LDOS002 STUDY DESIGN: MONOTHERAPY PHASE 1 & 2 IN NSCLC Phase I: • Dose escalation with modified Fibonacci, 3 + 3 design • L-DOS47 was administered once weekly over 14 days (Days 1 and 8) followed by 7 days rest cycle q 21 days Phase 2: • Cohort 16 dose (13.55 µg/kg) selected for Phase II • Dosing sc
Slide 28: LDOS002 Results: Monotherapy Tumor Reduction and Stable Disease
LDOS002 RESULTS: L-DOS47 MONOTHERAPY SHOWED NOTEWORTHY TUMOR REDUCTION AND STABLE DISEASE IN SECOND PLUS LINE OF THERAPY L-DOS47 MONOTHERAPY IN NSCLC 1. L-DOS47 as a monotherapy is safe and well tolerated up to a dose of 13.55 µg/kg 2. 22/26 patients showed stable disease with L-DOS47 monotherapy 3.
Slide 29: LDOS002: Dose Dependent Benefit in Probability of Survival
LDOS002: DOSE DEPENDANT BENEFIT IN PROBABILITY OF SURVIVAL WAS OBSERVED WITH L-DOS47 MONOTHERAPY DESPITE HEAVILY PRE-TREATED PATIENT POPULATION % Prior lines of Therapy Treatment Median PFS (months) (0/1/≥2) Probability of Survival 100 Quartile 1 (0.12 - 0.46 ug/kg) L-DOS47 33.3/8.3/58.3 2.4 (0.12 -
Slide 30: LDOS002 Phase I: TEAEs with ≥5% Incidence
LDOS002 Phase I: TEAES WITH ≥ 5% INCIDENCE Helix Corporate Presentation = Dose limiting toxicity
Slide 31: LDOS002 - Systemic Exposure Decreases as ADA Titer Increases
LDOS002 - SYSTEMIC EXPOSURE TYPICALLY DECREASES OVER TIME AS ADA TITER INCREASES, BUT EFFICACY IS STILL OBSERVED IN MONOTHERAPY LDOS002 Cohorts 2 - 16 (Doses 0.21 - 13.55 μg/kg) 1000000 2000 100000 AUC0-t (hr*ng/mL) 1500 10000 ADA Titer 1000 1000 100 500 10 1 0 0 20 40 60 80 100 Days AUC0-t (hr*ng/m
Slide 32: LDOS001: L-DOS47 with Pemetrexed/Carboplatin Dose Escalation in NSCLC
LDOS001: L-DOS47 COMBINED WITH PEMETREXED/CARBOPLATIN DOSE ESCALATION IN NSCLC LDOS001 Phase I Trial Design • Dose escalation with 7 dosing cohorts • Standard “3+3” design, accelerated design; 3 cohorts (1.5, 3.0 and 6.0 µg/kg) • Protocol defined up to four treatment cycles of combination treatment
Slide 33: LDOS001: Extended Duration of Response and Clinical Benefit
LDOS001: PATIENTS CONTINUING ON ONCE WEEKLY L-DOS47 MAINTENANCE DOSING SHOWED EXTENDED DURATION OF RESPONSE AND CLINICAL BENEFIT Duration of Response: Efficacy Evaluable (N=5) Duration of Clinical Benefit: Efficacy Evaluable (N=9) Duration of Response is calculated from date of first response (first
Slide 34: LDOS001 - Systemic Exposure Decreases as ADA Titer Increases
LDOS001 - SYSTEMIC EXPOSURE TYPICALLY DECREASES OVER TIME AS ADA TITER INCREASES, BUT EFFICACY IS STILL OBSERVED AUC_ADA (All Doses: 0.59 - 9.0 ug/kg) LDOS001: ADA vs BORR Highest ADA Titer Reached 10 7 500 100000 10 6 400 AUC (hr*ng/mL) (Log Scale) 10000 10 5 ADA Titer 300 10 4 1000 200 10 3 100 10
Slide 35: TEAEs Summary: LDOS001, LDOS002 and LDOS003 (in NSCLC)
TREATMENT EMERGENT ADVERSE EVENTS (TEAES) SUMMARY: LDOS001, LDOS002 AND LDOS003 (IN NSCLC) L-DOS47 Related Any Relationship L-DOS47 Related All TEAEs System Organ Class Any Grade Grade ≥3 Grade ≥3 (N=99) (N=119) (N=119) (N=119) Blood and lymphatic system disorders 22 (22.2%) 6 (5.0%) 11 (9.2%) 2 (1.
Slide 36: TEAEs Related to L-DOS47 by Study
TEAES RELATED TO L-DOS47 BY STUDY ALL TEAEs L-DOS47 ALL TEAEs L-DOS47 ALL TEAEs L-DOS47 All TEAEs System Organ Class LDOS002 Related LDOS001 Related LDOS003 Related (N=99) (N=76) LDOS002 (N=14) LDOS001 (N=9) LDOS003 Blood and lymphatic system disorders 22 (22.2%) 6 (7.9%) 1 (1.3%) 7 (50.0%) 2 (14.3%
Slide 37: LDOS006: Phase Ib/II L-DOS47 Doxorubicin in Advanced Pancreatic Cancer
LDOS006: PHASE IB/II L-DOS47 DOXORUBICIN COMBINATION IN ADVANCED PANCREATIC CANCER Phase Ib: • Initial dose escalation phase applying a standard 3 + 3 algorithm, combining doxorubicin with L-DOS47 in a 4-week cycle • Patients in each cohort receive weekly L-DOS47 (Days 1, 8, 15, 22) in combination d
Slide 38: LDOS006: Phase Ib/II Doxorubicin Combination Cohorts
LDOS006: PHASE IB/II L-DOS47 DOXORUBICIN COMBINATION IN ADVANCED PANCREATIC CANCER Cohort 1 Cohort 1 Cohort 2 Cohort 3 (Amended)* Cohort 4 L-DOS47 3 μg/kg + L-DOS47 6 μg/kg + L-DOS47 9 μg/kg + Phase II L-DOS47 3 μg/kg + L-DOS47 13.55 μg/kg + Doxorubicin 20 Doxorubicin 15 Doxorubicin 15 Dose TBD Doxo
Slide 39: L-DOS47 Platform: Portfolio-in-a-Product Strategy
L-DOS47 PLATFORM: PORTFOLIO-IN-A-PRODUCT STRATEGY NSCLC Combination with Colorectal Cancer (CRC) Chemotherapy* Mucinous Ovarian Cancer L-DOS47 ✓ CEACAM6 Expression (MOC) • Ongoing preclinical NSCLC testing • Preparation clinical trial(s) Combination with Immuno- CRC Oncology (IO)* Other modalities,
Slide 40: Manufacturing
Manufacturing odee ss HELIX * biopharma
Slide 41: Well-Established Scaled-Up CMC Process
A WELL-ESTABLISHED SCALED-UP CMC PROCESS WILL ALLOW RAPID SUPPLY FOR CLINICAL TRIALS AND LAUNCH L-DOS47 CMC Program Current Status • Three lots of L-DOS47 and 5 lots of Poly 80, 1% diluent have been used in clinical trials, all with excellent stability • Up to 8 years shelf life for L-DOS47 • Up to
Slide 42: Intellectual Property
Intellectual Property odee ss HELIX * biopharma
Slide 43: Strong Barrier to Entry with IP
STRONG BARRIER TO ENTRY WITH IP RESTORING FUNCTION METHOD AND COMPOSITION FOR ANTIBODY-UREASE USE OF ANTIBODY- USE OF UREASE FOR INHIBITING TUMOR ACIDIFIED T CELLS INHIBITING CANCER CELL GROWTH CONJUGATES FOR UREASE CONJUGATES CANCER CELL GROWTH USING UREASE AND WEAKLY BASIC THERAPEUTIC PURPOSES FOR
Slide 44: Corporate
Corporate odee ss HELIX * biopharma
Slide 45: Partnering Objectives
PARTNERING OBJECTIVES 1. Collaboration on controlled randomized trial – L-DOS47 plus or minus Mucinous ovarian (MOC) 1a. L-DOS47 + SOC chemotherapy/immuno-oncology drug To be defined with partners a)Mucinous ovarian cancer (MOC) is of interest TRIAL CEACAM6 + acidic pH b) CRC, (PDAC) as possible bas
Slide 46: Corporate Brief
CORPORATE BRIEF ▪ Est. 1996, clinical-stage biopharmaceutical company ▪ Listed/trades on the Toronto Stock Exchange (TSX): Helix BioPharma Corp. (“Helix”) / Ticker symbol – HBP ▪ Shares outstanding: 49 M ▪ Share price: CAD 1,32 (09/11/2024) ▪ Market Capitalization: CAD 65 M ▪ Backed by high-net-wort
Slide 47: Management Team
MANAGEMENT TEAM Jacek Antas, CEO Thomas Mehrling, PhD, MD, CMO ▪ Supervisory Board Chairman ▪ Over 20 years of experience in building ▪ Over 25 years of experience in financial oncology business from scratch services/Board member for various ▪ Success story in developing and companies building oncol
Slide 48: Board of Directors
BOARD OF DIRECTORS Jacek Antas Jerzy Leszczynski CEO, Chair Board of Directors Board Member Janusz Grabski Malgorzata Laube Board Member, Chair Audit Board Member
Slide 49: Summary
Helix Corporate Presentation - Strictly Confidential • Current standards of care, including checkpoint inhibitors, have limited efficacy in addressing cancers • Helix is developing novel anti-cancer therapies stemming from its proprietary technology platform that could help address these efficacy ch
Slide 50: Thank You! Contact
Helix Corporate Presentation - Strictly Confidential Thank You! Contact: Jacek Antas, CEO corporate@helixbiopharma.com
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