Helix Biopharma Corp. · TSX:HBP
Helix Biopharma — Investor Presentation (April 2023)
43 slides from Helix Biopharma's investor presentation, April 2023
Slide 1: New Directions in Cancer Therapy
New Directions in Cancer Therapy Investor Presentation April 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-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 defence a
Slide 4: 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 0.21 (04/09/2023) § Market Capitalization: CAD 42 M § Backed by high
Slide 5: 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 6: Board of Directors
BOARD OF DIRECTORS Jacek Antas Jerzy Leszczynski CEO, Chair Board of Directors Board Member Christopher Maciejewski Malgorzata Laube Board Member Board Member Helix Corporate Presentation - Strictly Confidential 6
Slide 7: 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 7 From NCI SEER Program – Accessed 1/30/2023
Slide 8: Estimated IO Market by 2030
ESTIMATED IO MARKET BY 2030 Growing aging populations, increasing obesity and changes in lifestyle including smoking and drinking has led to a significant increase in patients suffering from various kinds of cancers. Increasing clinical and economic burden is putting a significant stress on our heal
Slide 9: 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 10: 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 11: 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 12: 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 12
Slide 13: Preclinical Studies
Preclinical Studies €2 HELIXBIOPHARMA
Slide 14: 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 15: L-DOS47 Binds to Human CEACAM6 with High Specificity
L-DOS47 BINDS TO HUMAN CEACAM6 WITH HIGH SPECIFICITY L-DOS47 is specific to human CEACAM6, not binding other human CEACAMs (1, 3, and 5) or cynomolgus monkey CEACAM6 2.0 1.5 OD405 CEACAM6-A 1.0 CEACAM1 CEACAM3 0.5 CEACAM5 CEACAM6 Monkey CEACAM6 0.0 0.1 1 10 100 L-DOS47 (ng/mL) • ELISA binding assay
Slide 16: 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 a-CD3/a-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 17: 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 18: 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 19: 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 20: L-DOS47 Increases Tumor pH In Vivo
L-DOS47 INCREASES TUMOR pH IN VIVO CEST MRI reveals pH increase between pre-dose and 30min post-L-DOS47 administration Proof of concept, single experiment CEST MRI of Isovue 370 for pH imaging [1] of a Panc02 clone 38 SC tumor. (a) T2 weighted image, (b) CEST MRI before L-DOS47 injection, (c) ~30 mi
Slide 21: L-DOS47 Enhances Cytotoxicity of Carboplatin and Pemetrexed
L-DOS47 ENHANCES CYTOTOXICITY OF CARBOPLATIN AND PEMETREXED No L-DOS47 1µg/mL L-DOS47/4mM urea 100 **P < 0.01 and ***P<0.001 80 %Survival *** 60 *** 40 *** *** ** 20 *** *** *** *** ** *** 0 0 25 50 100 200 0 25 50 100 200 0 25 50 100 200 Carboplatin (µM) Carboplatin (µM) Carboplatin (µM) No Pemetre
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 a subcutaneous pancreatic tumor model • Anti-PD1 + L-DOS47 reduced Panc02 tumor growth compared to anti- PD1 alone • Tumor volumes were measured by ultrasound • Preliminary experiment, significant orthotopic tumor data availa
Slide 23: 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 24: Clinical Studies
Clinical Studies Investor Presentation March 2023
Slide 25: Tumor Defence Breaker Technology Platform
TUMOR DEFENCE BREAKER TECHNOLOGY PLATFORM CLINICAL TRIALS L-DOS47 monotherapy NSCLC (clinical trial # NCT02340208) PRECLINICAL PHASE 1 PHASE 2, stage 1 L-DOS47 combo PEM/CARBO NSCLC (clinical trial # NCT02309892) PRECLINICAL PHASE 1 PHASE 2 L-DOS47 combo DOXO Pancreas (clinical trial # NCT04203641)
Slide 26: A Robust Clinical Strategy to Establish Safety and Efficacy of L-DOS47
A ROBUST CLINICAL STRATEGY TO ESTABLISH SAFETY AND EFFICACY OF L-DOS47 IN CANCER PATIENTS Objective Studies Status Outcomes L-DOS47 is safe and tolerated LDOS002 Phase I/II Phase I and stage 1 of phase II Safety and tolerability as a at all doses studied Monotherapy in advanced non- complete monothe
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 • 16 dosing cohorts ranging from 0.12 to 13.55 μg/kg • A dose-limiting toxicity (DLT) was defined as any NCI CTCAE v4.0, ≥ Grade 3 non-hematologic and any ≥ Grade 4 hematologic AE
Slide 28: LDOS002 Results: Dose Response Trend in PFS at 16 Weeks
LDOS002 RESULTS: A DOSE RESPONSE TREND WAS OBSERVED IN PFS AT 16 WEEKS WITH L-DOS47 MONOTHERAPY IN NSCLC Phase I • L-DOS47 as a monotherapy is safe and well tolerated up to a dose of 13.55 µg/kg • A dose response trend was observed when comparing the percentage of patients who were progression free
Slide 29: LDOS001 L-DOS47 Pemetrexed/Carboplatin Dose Escalation in NSCLC
LDOS001 L-DOS47 PEMETREXED/CARBOPLATIN DOSE ESCALATION IN NSCLC LDOS001 Phase I Trial Design • Dose escalation study: 7 dosing cohorts • Standard “3+3” design, with accelerated of “1+2” dose design for middle three cohorts (1.5, 3.0 and 6.0 µg/kg) • Patients received up to four treatment cycles of c
Slide 30: LDOS006: Phase Ib/II L-DOS47 Doxorubicin Combination 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 • Patients in each cohort receive weekly L-DOS47 (Days 1, 8, 15, 22) in combination with a fixed dose o
Slide 31: LDOS006: Phase Ib/II Doxorubicin Combination Cohorts
LDOS006: PHASE IB/II L-DOS47 DOXORUBICIN COMBINATION IN ADVANCED PANCREATIC CANCER Cohort 1 Cohort 1 Cohort 4 Cohort 2 Cohort 3 (Amended)* L-DOS47 3 μg/kg + L-DOS47 6 μg/kg + L-DOS47 9 μg/kg + (Planned Amendment) Phase II L-DOS47 3 μg/kg + Doxorubicin 20 Doxorubicin 15 Doxorubicin 15 L-DOS47 13.55 μ
Slide 32: L-DOS47 Platform: Portfolio-in-a-Product Strategy
L-DOS47 PLATFORM: PORTFOLIO-IN-A-PRODUCT STRATEGY NSCLC L-DOS47 Platform Example companies Combination with Chemotherapy Combination with Colorectal Cancer (CRC) Chemotherapy üNSCLC – proof of concept with clinical data Head and Neck Cancer ØCRC L-DOS47 (H&N) ü CEACAM6 Expression ØH&N NSCLC Combinat
Slide 33: Manufacturing
Manufacturing €2 HELIXBIOPHARMA
Slide 34: Scaled-Up CMC Process for Rapid Supply
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 35: Intellectual Property
Intellectual Property €2 HELIXBIOPHARMA
Slide 36: 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 37: Business Development
Business Development Investor Presentation March 2023
Slide 38: R&D Partnerships in Oncology
R&D PARTNERSHIPS IN ONCOLOGY R&D partnerships in oncology. Source: DealForma database. Financials based on disclosed figures as of 2 Aug 2022. Helix Corporate Presentation - Strictly Confidential 38
Slide 39: Example Target Companies That Could Have Interest in L-DOS47
EXAMPLE OF TARGETS COMPANIES THAT COULD HAVE INTEREST IN L-DOS47 • Ongoing outreach to these and several other companies • Interest to use LDOS47 in combination with their assets • Could be of interest beyond current IO therapies to their growing portfolio • In combination with newer modalities like
Slide 40: Example Comps for Helix BioPharma
EXAMPLE COMPS FOR HELIX BIOPHARMA Licensor and licensee Total deal value Description ($ million), date Cullinan Oncology and $588 Cullinan Oncology Licenses U.S. Rights to the First Clinical-Stage B7H4 x 4- Harbour BioMed ($25M upfront; $148M development 1BB Bispecific Immune Activator from Harbour
Slide 41: Use of the Proceeds: $10M Till Dec 2024
USE OF THE PROCEEDS: $10M TILL DEC 2024 Pre-clinical Studies with Moffitt and Tubingen University - $3M Ø New collaboration with University Hospital Tubingen to assess therapeutic responses of L-DOS47 in several cancer models expressing CEACAM6, with advanced preclinical metabolic imaging Ø Ongoing
Slide 42: Summary
SUMMARY 1. Current standards of care, including checkpoint inhibitors, are limited by the efficacy in addressing cancers 2. Helix is developing novel anti-cancer therapies stemming from its proprietary technology platforms that could help address these efficacy challenges turning it into a significa
Slide 43: Thank You!
43 Thank You! Helix Corporate Presentation - Strictly Confidential