New Advances in Cancer Treatments. March 2015

Transcription

1 New Advances in Cancer Treatments March 2015

2 Safe Harbour Statement 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 instead include financial projections and estimates; statements regarding plans, goals, objectives, intentions and expectations with respect to Helix s future business, operations, research and development, including the focus of Helix on its DOS drug candidate generally and L-DOS47 in particular, the anticipated timelines for the commencement or completion of certain activities, including enrolment of patients in Helix s Phase I/II clinical trial for L-DOS47 in Poland, the expansion of the DOS47 platform into other compounds and indications and other information in future periods. Forward-looking statements, which may be identified by words including, without limitation, expects, plans, will, intends, may, pending, objective, exploring, potential, projected, possible and other similar expressions, are intended to provide information about management s current plans and expectations regarding future operations. Although Helix believes that the expectations reflected in such forward-looking statements are reasonable, such statements involve risks and uncertainties that may cause actual results or events to differ materially from those anticipated and no assurance can be given that these expectations will be realized, and undue reliance should not be placed on such statements. Risk factors that could cause actual results or events to differ materially from the forward-looking statements include, without limitation: (i) the inherent uncertainty involved in scientific research and drug development, including with respect to costs and difficulties in predicting accurate timelines for the commencement or completion of certain activities; (ii) the risks associated with delay or inability to complete clinical trials successfully and the long lead-times and high costs associated with obtaining regulatory approval to market any product which may result from successful completion of such trials; (iii) need to secure additional financing on terms satisfactory to Helix or at all, including that the additional funding required in order to complete the proposed U.S. Phase I clinical trial will be obtained on terms satisfactory to Helix or at all; (iv) clinical trials that yield negative results, or results that do not justify future clinical development, including that Helix s ongoing Polish Phase I/II clinical trial for L-DOS47 and/or that Helix s proposed U.S. Phase I clinical trial will yield negative results; (v) Helix s clinical development plan for the proposed US Phase I clinical trial does not proceed in the manner or on the timelines anticipated by Helix or at all; and (vi) those risks and uncertainties affecting Helix as more fully described in Helix s most recent Annual Information Form, including under the headings Forward-Looking Statements and Risk Factors, filed under Helix s profile on SEDAR at (together, the Helix Risk Factors ). Certain material factors and assumptions are applied in making the forward-looking statements, including, without limitation, that the Helix Risk Factors will not cause Helix s actual results or events to differ materially from the forward-looking statements. Helix. Forward-looking statements and information are based on the beliefs, assumptions and expectations of Helix s management on the date of this presentation, and are presented solely to acquire a better understanding of Helix and may not be appropriate for other purposes nor should this presentation be redistributed to other parties. Helix does not assume any obligation to update any forward-looking statement or information should those beliefs, assumptions or expectations, or other circumstances change, except as required by law.

3 Corporate Goal Helix is a leader in the development of novel therapeutics in the field of oncology Our proprietary technology represents a novel approach to the treatment of cancer, which we believe can be applied to multiple cancer types The company intends to advance this technology and the drug candidates to mid-stage clinical trials ultimately for sale or license to the pharmaceutical industry 3

4 The DOS Technology Tumours have a much different local environment (much lower ph) than normal tissue This is caused by the high metabolism of tumours leading to the creation of acid surrounding the tissue This highly acidic environment is linked to several issues in the treatment of cancer, including tumour growth, metastasis, and drug resistance Helix s technology allows us to potentially change the tumour microenvironment to both: a) Direct cytotoxic effect on tumours, and b) boost the efficacy of other therapeutics 4

5 The DOS Technology Urease is an enzyme that can convert urea (found in all tissue) to ammonia and can be used to increase ph in tissue Helix creates antibody conjugates (DOS47 compounds) by coupling urease to a targeting antibody DOS47 candidates specifically bind to cancer cell surfaces and enzymatically generates ammonia in the tumour microenvironment SD antibody (L) Cross-linker Urease L-DOS47 5

6 The DOS Technology DOS47 compounds act against solid tumours by: 1. Specific attachment to the cell surface of solid tumours 1. Direct cytotoxic effect against tumours with the generation of ammonia 2. Adjust the ph to work synergistically with other cancer therapeutics 7

7 DOS47 - Novel Treatment of Solid Tumours

8 DOS47 Platform Advantages No need to internalize the drug Action is at the tumour surface to manipulate microenvironment Delivers cytotoxic ammonia directly to tumour while changing ph Can use antibodies that have no activity, only need specificity No need to target biologically relevant pathways, only differentially expressed tumour antigens Can confer activity to previously inactive antibodies Mechanism is independent of cell growth cycle or signalling pathway MOA is universal, not pathway dependent With new targeting antibodies, can use same MOA to target different tumour types Potential to have combination effect Basic environment may facilitate uptake of other chemotherapeutics 11

9 BiPhasix DOS Platform Development L-DOS47 Pipeline Research Preclinical Phase I Phase II Phase III Non-small Cell Lung Cancer - Monotherapy Non-small Cell Lung Cancer Combination Ductal Breast Cancer Colon Cancer v-dos p-dos Solid Tumour Pancreatic Cancer TIFN HPV-mediated Cervical Lesions 12

10 L-DOS47 Lead Candidate Lead candidate is L-DOS47 for the treatment of non-squamous nonsmall cell lung cancer (NSCLC) Uses a camelid antibody specific to CEACAM-6, which is highly expressed in lung, colon, breast and pancreatic cancers Pre-clinical testing in cell and animal models showed potential in both monotherapy and combination therapy of NSCLC with good safety profiles Preclinical and safety studies have been reviewed by regulators in EU and North America and we have been given approvals to begin human testing for both monotherapy treatment and combination treatments 13

11 Specific to tumours L-DOS47 distributes to tumour preferentially Tumour specific localization Full Body Scan A549 tumour (8 x 7 mm) L-DOS47-Cy5.5 Filtered Scan L-DOS47-Cy5.5 Cy5.5 emission

12 Normalized Fluorescence Intensity %Change in Tumor Volume Direct effect on Tumours L-DOS47 stays on tumour persistently and retards growth hrs 24hrs 48hrs 72 hrs Vehicle Cisplatin L-DOS47 (35U/kg) L-DOS47 (20U/kg) L-DOS47 (10U/kg) Time post injection (hours) Days Imaging in xenograft tumour model shows specificity for tumour and remain at high concentrations for at least 72 hours L-DOS47 retards tumor growth in lung cancer xenograft model 9

13 Enhances Other Chemotherapeutics L-DOS47 enhances chemo drugs The cytotoxic effect of weakly basic drugs is directly related to the solution ph (left panel). At an acidic tumour ph (<6.8), the effectiveness of these drugs is significantly reduced. L-DOS47 can dramatically raise the effectiveness of these drugs (e.g. navelbine, right panel). This synergistic effect is directly related to its enzymatic properties of generating ammonia from urea and raising solution ph. Depending on the dosages and available urea, a 2 10 fold drug effect enhancement can be observed 10

14 L-DOS47 Phase I / II Trial Conducted in 5 Centers in Poland to assess safety (phase I) and then preliminary efficacy (phase II) It is a 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 Dosed once a week for 2 weeks, 1 week rest (3-week cycles) Have tested 30 patients to date in Phase I No indications of safety issues with L-DOS47 14

15 L-DOS47 Phase I / II Trial Second Interim Data Review completed Sept 30 th, 2014 Reviewed PK, safety, toxicology, and radiological assessments of first 24 patients from cohorts

16 L-DOS47 Phase I / II Interim Review No safety issues beyond those observed in pre-clinical toxicology studies or expected in the population of patients being studied No Dose Limiting Toxicities Pharmacokinetic data supports continued dose escalation Immunogenicity consistent with what was observed preclinically 16

17 L-DOS47 Phase I / II Interim Review For the first 24 patients treated: Twelve (12) or 50% of patients treated with LDOS-47 had an radiological assessment of stable disease as compared to their baseline radiology before treatment following at least two cycles Two (2) patients completed six (6) dosing cycles (18 weeks) before discontinuing therapy. 17

18 L-DOS47 Summary Given the safety profile and the information from the interim analysis, Helix has been approved for combination studies by the US FDA We are exploring the application of L-DOS47 in other indications (breast, colon, pancreatic) as a second market for the product Helix expects to have a second drug candidate ready for pre-ind discussions of initial human studies in

19 L-DOS47 Clinical Development Plan Phase I with expansion cohort to assess preliminary efficacy Combination (Pem/Carbo) First-line therapy in non-squamous NSCLC Pathway to approval in First-line with most popular combination; Most direct reg. approval and market acceptance Phase I Monotherapy (ongoing) Phase II Monotherapy Second-line therapy in non-squamous NSCLC Pathway to approval as maintenance therapy; back-up pathway and label broadening strategy Phase I with expansion cohort to assess preliminary efficacy Combination (Vinorelbine) Second-line non-squamous NSCLC Third-line Breast Cancer Pathway to game-changing first line, potential to 2 nd / 3 rd line label broadening; Provides guidance in breast cancer development path 19

20 Topical Interferon (TIFN) Study IFN002/HPV % 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% 0.0% Pap Smear Resolution (Pap IIID Cohort) Treated Control CIN Resolution Treated Control Two Phase II studies completed: Study IFN002/HPV001 Safety/efficacy study 41 patients (Tx vs. observational control) 18-doses TIFNα2b + 6 week follow-up Study IFN005 Pharmacokinetic + safety/efficacy study 14 patients (no control) 35-doses TIFNα2b + 2 week follow-up TIFNα2b well tolerated in both studies 28.6% CIN 1 or % No CIN No significant systemic penetration (as assessed in Study IFN005) Pronounced CIN resolution findings Study IFN005 CIN Status (on biopsy) Following TIFNα2b Treatment 24

21 Strategic Plan We intend to maximize corporate value by developing L-DOS47 and other candidates to Phase II clinical status Value is achieved in 2016 through the partnering of candidates at Phase II to large pharma companies (either product-by-product or acquisition of company) AND through IPO in US market to build liquid share trading at potentially higher value Helix builds value by: Developing lead candidates to Phase II Entering into strategic alliances to build pipeline and support scientific concept Identifying potential transactions to expand scope of corporate activities (licenses, acquisitions, etc.) 25

22 Strategic Plan Continued development of lead candidates - Helix expects that opportunities for partnering, licensing, or acquisition will come near or very soon after Phase II results in 2016 Enter into strategic R&D collaborations in 2015 for new pipeline candidates from DOS platform Explore Growth Opportunities to expand portfolio and increase value Begin discussions regarding partnering of Helix product candidate by 2016 to support liquidity for shareholders 26

23 Strategic Plan Summary Build Internal Pipeline LDOS-47 clinical studies New pre-clinical programs New Product Opportunities Licensing / Acquisition Increase value Diversify company Build liquidity and valuation into shares US listing eg NASDAQ Access to institutional players Greater liquidity for shareholder Better reflection of market value Licensing or Acquisition of Helix candidates Realization of value Transformative event Build External Relationships New candidates Exposure to market External validation

24 Strategic Plan Execution Developing L-DOS47 to Phase II Phase I Poland (LDOS002 Trial) Phase I Topline Results Q Phase II Topline results early 2016 Final report H

25 Strategic Plan Execution Developing L-DOS47 to Phase II US Combination Study w/ Pem/Carbo (LDOS001 Trial) Dose Escalation Complete enrollment in Q Interim Analysis before end of 2015 Expansion Group Complete Enrollment by Q Topline results Q

26 Strategic Plan Execution Developing L-DOS47 to Phase II Phase I/IIa Canada/EU (LDOS003 Trial) Developing new protocols based on feedback / data from Polish Study Dose Escalation Interim Analysis late 2015-early 2016 Expansion Group Complete Enrollment by Q Topline results Q

27 Strategic Plan Execution Enter Strategic Research Collaborations in 2015 Current discussions with multiple companies for initial research collaborations Focussed on new DOS candidates and other related research Benefits Helix through the creation of new clinical candidates, external validation Expand pipeline to build additional value / market cap in Helix Used to build external validation of Helix science and products Build relationships that can lead to licensing / acquisition opportunities 30

28 Strategic Plan Execution Explore Acquisition / Licensing Opportunities Build pipeline non-organically Identify and acquire companies / products that broaden pipeline and diversify product risk at different stages of development Concentrating on acquiring Phase II or other novel opportunities Leverage new acquisitions to access institutional financing Develop a financing opportunities to run concurrently with close of acquisitions Use transactions to seek additional liquidity for Helix 32

29 Strategic Plan Summary Build Internal Pipeline LDOS-47 clinical studies New pre-clinical programs New Product Opportunities Licensing / Acquisition Increase value Diversify company Build liquidity and valuation into shares US listing eg NASDAQ Access to institutional players Greater liquidity for shareholder Better reflection of market value Licensing or Acquisition of Helix candidates Realization of value Transformative event Build External Relationships New candidates Exposure to market External validation