Helix BioPharma Corp. · TSX:HBP
Helix BioPharma — Investor Presentation (September 2023)
49 slides from Helix BioPharma's investor presentation, September 2023
Slide 1: New Directions in Cancer Therapy
New Directions in Cancer Therapy Partnering Presentation September 2023
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
Helix Corporate Presentation - Strictly Confidential • Helix BioPharma is developing a novel first and best-in-class anti-cancer therapy stemming from its proprietary technology platform • Our lead Tumor Defence Breaker™ L-DOS47 is a unique tumor microenvironment modifying drug. It breaks the tumor
Slide 4: Oncology Remains a Significant Unmet Medical Need
ONCOLOGY REMAINS A SIGNIFICANT UNMET MEDICAL NEED Lung Cancer in US Several tumor types impacting large populations have persistently high unmet need Colorectal Cancer in US Head and Neck Cancer in US From NCI SEER Program – Accessed 1/30/2023 4
Slide 5: 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 6: Effect of Acidosis on Tumor Progression
EFFECT OF ACIDOSIS ON 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 the glycolytic phenotype even in the presence of oxygen (Warburg effect) cau
Slide 7: Effect of Acidosis on Tumor Phenotype
EFFECT OF ACIDOSIS ON TUMOR PHENOTYPE 3. Increases 7. Promotes 1. Increases 2. Increases 5. Hinders Immuno-Oncology 4. Promotes 6. Higher Cancer Stem Cell Radiotherapy Chemotherapy Immune Cell Therapy Metastasis Mutation Rate Phenotype / Resistance Resistance Function Resistance Angiogenesis Acidic
Slide 8: L-DOS47: A Platform Technology Targeting Tumor Microenvironment
L-DOS47: A PLATFORM TECHNOLOGY TARGETING TUMOR MICROENVIRONMENT 1. Tumor acidity is an escape mechanism that cancer cells utilize to evade the anti-tumor immune response. 2. Tumor acidity has been shown to correlate with resistance to anti-cancer treatment and poor prognosis for cancer patients. 3.
Slide 9: L-DOS47: Anti-CEACAM6-Urease Bioconjugate
L-DOS47: ANTI-CEACAM6 -UREASE BIOCONJUGATE Conjugation of urease to a tumor-specific antibody allows targeted urease delivery by iv injection 9
Slide 10: Preclinical Studies
Preclinical Studies €? HELIXBIOPHARMA
Slide 11: CEACAM6 Is Overexpressed on Many Different Tumors
CEACAM6 IS OVEREXPRESSED ON MANY DIFFERENT TUMORS ES1, a pentameric version of AFAIKL2, detects CEACAM6 on a range of tumors Table 2. A comparison of the immunoreactivity of ES1 with non-squamous large cell lung carcinomas and non-lung carcinomas A C Immunohistostaining of moderately differentiated
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 urease) binds human CEACAM6, not other human CEACAMs (1, 3, and 5) or cynomolgus monkey CEACAM6 2.0 1.5 CEACAM6-A OD405 1.0 CEACAM1 CEACAM3 0.5 CEACAM5 CEACAM6 Monkey CEACAM6 0.0 0.1 1 10 100 L-DOS47 (ng/mL)
Slide 13: L-DOS47 Binds Well to NSCLC Adenocarcinoma Expressing 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. Additional analysis is ongoing. L-DOS47 300μm 300μm TMA from US BioLabs Lung Helix Corpor
Slide 14: L-DOS47 Binds Well to Pancreatic Adenocarcinoma
L-DOS47 BINDS WELL TO A HIGH PERCENTAGE OF PANCREATIC ADENOCARCINOMA EXPRESSING HIGH LEVELS OF CEACAM6 Representative example: 80% (8/10) cases were CEACAM6 positive TMA from TissueArray.com PDAC stained by Young Ou, scored by Martin Koebel, University of Calgary 14
Slide 15: L-DOS47 Binds Well to Colorectal Cancer Cases
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 *
Slide 16: Head and Neck Cancers Express Variable Levels of CEACAM6
HEAD AND NECK CANCERS EXPRESS VARIABLE LEVELS OF CEACAM6 Representative examples of high and low CEACAM6-expressing H&N Cancers. Additional analysis is ongoing. TMA from TissueArray.com stained by Young Ou, scored by Martin Koebel, University of Calgary 16
Slide 17: 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 fl
Slide 18: 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 19: L-DOS47 Enhances Cytotoxicity of Carboplatin
L-DOS47 ENHANCES CYTOTOXICITY OF CARBOPLATIN No L-DOS47 1mg/mL L-DOS47/4mM urea 100 **P < 0.01 and ***P<0.001 Survival 80 % Cell%Survival *** 60 *** 40 *** ** *** 20 *** *** *** *** ** *** 0 0 25 50 100 200 0 25 50 100 200 0 25 50 100 200 Carboplatin (mM) Carboplatin (mM) Carboplatin (mM) No Pemetre
Slide 20: 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 21: 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 22: 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 23: 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 24: Additional Ongoing Studies
Helix Corporate Presentation - Strictly Confidential • 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 • Advanced imaging to confirm biodistribution of L-DOS47 ADDITIONA
Slide 25: Clinical Studies
Clinical Studies €? HELIXBIOPHARMA
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 I & II 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 out of 26 patients showed stable disease with L-DOS47 monothe
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 - Strictly Confidential = Dose limiting toxicity 30
Slide 31: LDOS002 Systemic Exposure and ADA Titer
LDOS002 - SYSTEMIC EXPOSURE TYPICALLY DECREASES OVER TIME AS ADA TITER INCREASES, BUT EFFICACY IS STILL OBSERVED IN MONOTHERAPY LDOS002 Cohorts 2 - 16 LDOS002: ADA vs BORR (Doses 0.21 - 13.55 μg/kg) Highest ADA Titer Reached 1000000 1000000 2000 100000 100000 AUC0-t (hr*ng/mL) (Log Scale) 1500 10000
Slide 32: LDOS001: L-DOS47 with Pemetrexed/Carboplatin 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 and ADA Titer
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 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: Cohorts and Enrolment Timeline
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 L-DOS47 Platform Combination with Combination with Colorectal Cancer (CRC) Chemotherapy Chemotherapy* NSCLC – proof of concept with clinical data L-DOS47 Head and Neck Cancer (H&N) CRC CEACAM6 Expression H&N NSCLC Ongoing Combination with
Slide 40: Manufacturing
Manufacturing €? HELIXBIOPHARMA
Slide 41: Scaled-Up CMC Process for Clinical Trials and Launch
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 €? HELIXBIOPHARMA
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 CONJUGATES FOR UREASE CONJUGATES CANCER CELL GROWTH GROWTH USING UREASE AND THERAPEUTIC PURPOSES FOR DIAGNOSTIC A
Slide 44: Corporate
Corporate €? HELIXBIOPHARMA
Slide 45: 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: around 200 M Share price: CAD 0.205 (08/31/2023) Market Capitalization: CAD 44.42 M Backed by h
Slide 46: Management Team
MANAGEMENT TEAM Jacek Antas, CEO Gary Renshaw, MD, CMO Supervisory Board Chairman Former CMO Zhejiang DTRM Biopharma Over 25 years of experience in financial Former Oncology Director at Eisai services/Board member for various companies Hatem Kawar, CFO Experienced CFO with proven track rec
Slide 47: Board of Directors
BOARD OF DIRECTORS Jacek Antas Jerzy Leszczynski CEO, Chair Board of Directors Board Member Janusz Grabski Malgorzata Laube Board Member Board Member 47
Slide 48: 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 platforms that could help address these efficacy c
Slide 49: Thank You
Helix Corporate Presentation - Strictly Confidential Thank You! Contact: Christof Bohler cbohler@helixbiopharma.com
Helix BioPharma — Investor Presentation (September 2023) on 6ix