Corporate Presentation June 2017

Transcription

1 Corporate Presentation June 2017

2 Safe Harbor Certain of the statements and the projections set forth in this presentation constitute forward-looking statements. Forward-looking statements include, without limitation, any statement that may predict, forecast, indicate, or imply future results, performance or achievements, and may contain the words estimate, project, intend, forecast, anticipate, plan, planning, expect, believe, will, will likely, should, could, would, may or words or expressions of similar meaning. All such forwardlooking statements involve risks and uncertainties, including but not limited to the factors set forth in the Risk Factors section of this presentation and to the particular risks inherent in any development stage company that has developed new products for which it has not yet demonstrated market acceptance or generated any historical sales. Prospective investors are cautioned that there also can be no assurance that the forwardlooking statements included in this presentation will prove to be accurate. In light of the significant uncertainties inherent in the forward-looking statements included herein, the inclusion of such information should not be regarded as a representation or warranty by us or any other person that our objectives and plans will be achieved in any specified timeframe, if at all. Except to the extent required by applicable laws or rules, we do not undertake any obligation to update any forward-looking statements or to announce revisions to any of the forward-looking statements. Oncolix

3 Breakthrough technology for gynecological cancers Corporate Presentation June 2017 Michael T. Redman - CEO Oncolix

4 Investment Highlights Leadership Compelling Science Novel Target Clinical Stage Robust IP News Flow Experienced management & board public and private companies Prolanta is a first-in class therapeutic protein with blockbuster potential in gynecological cancers MD Anderson discovered the autophagy mechanism of action Phase I ovarian cancer trial underway, will be completed in Q Prolanta covered by 8 US patents, foreign patents, orphan designation, Healthcare Act Upcoming milestones include interim Phase I data, trial completion, initiation of Phase 2 Oncolix

5 First-in-Class Prolactin Receptor Antagonist Human Prolactin: is associated with gynecological and other cancers. is involved in cell proliferation signaling. (JAK2/STAT5 and others) and angiogenesis. dimerizes with prolactin receptors for signaling. is implicated in chemotherapy resistance. has a receptor that is over-expressed on gynecological cancers. Prolanta (G129R): is a recombinant protein that is an analog of a human prolactin. has a single amino acid mutation at position 129 of prolactin, which prevents the binding and activation of the prolactin receptor. works by novel mechanisms of action autophagy but also has the potential to prevent chemoresistance in patients. is covered by eight issued US patents and more foreign patents. Prolanta has the potential to be a major breakthrough for the treatment of ovarian cancer Oncolix

6 Prolactin s Role in Cancer Receptor is over-expressed in many cancers Breast: 90% Ovarian: 80% Endometrial: 80% Elevated prolactin levels are found in gynecological and other cancers Involved in cell proliferation signaling (JAK/STAT5, Ras/Raf/MAPK and other pathways) and angiogenesis Implicated in chemotherapy resistance (GST downregulation) Autocrine/paracrine effect evident in many cancers Oncolix

7 Prolanta (G129R) Recombinant analogue of prolactin produced in E. coli. Expression system developed by Monsanto. Single amino acid substitution (arginine replaces glycine at sequence 129) to create antagonist to prolactin: PROLANTA ARG Antagonist binds to only Site 1 receptor, not Site 2. Dimerization of two receptors blocked, which result in disruption of relevant signaling pathways. PRLR 1 PRLR 2 Packaged as lyophilized protein for subcutaneous injection. Oncolix

8 Autophagy Autophagy is broadly accepted as an avenue to pursue to treat a wide range of cancers as evidenced by recent articles in Nature, JCO, and Cancer Cell Types of programmed cell death: Apoptosis (Type I) Autophagy (Type II) Autophagy process: 1. Cell signal inducing autophagy 2. Formation of double-membrane vesicle (autophagosome) 3. Fuse with lysosome (autophagolysosome) 4. Cell death In conclusion, we now have good reasons to think that manipulation of autophagy may provide a useful way to prevent cancer development, limit tumor progression, and increase the efficacy of cancer treatments. Hippert et al, Cancer Research, 2006 The key findings from our studies are that promoting autophagic cell death through antagonism of tumor-associated prolactin can inhibit the growth and progression of human ovarian cancer. Sood et al, MD Anderson Cancer Center, submitted to Cancer Cell 2012 Oncolix

9 2016 Nobel Prize in Chemistry Dr. Yoshinori Ohsumi Father of Autophagy Recipient of the 2016 Nobel Prize for Chemistry for his work in autophagy Oncolix

10 Lead Indication: Ovarian Cancer While Prolanta may be effective in breast, prostate and gynecological cancers; ovarian cancer selected as lead indication based on the following: Clear regulatory pathway in platinum resistant ovarian cancer Unmet medical need opens up FDA accelerated approval opportunity Shorter and less expensive clinical trials Less competition for patients in this indication Potential for 1st line therapy Enhanced partnering opportunity due to higher incidence of ovarian cancer in EU Prolanta s potential as a potent drug for ovarian cancer supported by in vivo preclinical research from MD Anderson Prolanta was effective in reducing number and size of tumors. Prolanta was synergistic in combination with first line chemotherapeutics: Demonstrated synergy with chemotherapy Prolactin associated with chemo-resistance, so antagonism with Prolanta increases efficacy Dual mechanism of action in ovarian cancer: Prolanta induces autophagy in ovarian cancer cells that express a long-form of prolactin receptor (the form necessary for most intracellular signaling) Prolanta may also prevent chemoresistance by preventing GST upregulation Oncolix

11 Ovarian Cancer Statistics Incidence 2017e (US): 22,440 Deaths (US): 14,080 Diagnosed late stage: 77% 5-year survival in late stage: 28% Prevalence (US): 188,117 Prevalence (EU): 318,000 Standard of Care: Chemotherapy Oncolix

12 $1 Billion Annual Opportunity U.S. Ovarian Cancer Market Assumption: $40,000 per patient Sensitive to Chemo>6 mos. 25% 5,505 Patients - $220 Million US Incidence 22,240/Year* Resistant to Chemo <6 mos. 25% Refractory or cannot tolerate Chemo 27% 5,506 Patients - $220 Million 5,929 Patients - $237 Million Diagnosed early or unstaged 23% 5,060 Patients - $0 US Prevalence 188,000* Recurrent From prior years 10,000 Patients - $400 Million *Source: National Cancer Institute, 2017 Oncolix

13 Prolanta Opportunity as First-Line Therapy (combination with chemo) Standard of care in ovarian cancer is platinum and taxane therapy, but almost all patients develop resistance. 2 nd line chemo (Doxil, Hycamtin, Gemzar, vinorelbine, cyclophosphosphamide) response rate is 10 to 15%. Prolactin has been implicated in the process by which cancer cells become resistant to platinum and taxane therapies, as well as 2 nd line therapies. Blocking the prolactin receptor with Prolanta should enhance first-line therapy (e.g., used in combination with platinum and taxane). Chemotherapy side effects include: Renal toxicity nausea neuromotor toxicity cardiovascular events neutropenia thromobocytopenia, and anemia Prolanta may be effective as a first line therapy in combination with chemotherapy Oncolix

14 MD Anderson Ovarian Cancer Research In vivo orthotopic models of ovarian cancer: Prolanta was effective in reducing number and size of tumors. Prolanta was synergistic in combination with taxanes in reducing number and size of tumors: Literature also indicates synergy with platinum drugs. Prolactin associated with chemo-resistance, so antagonism with Prolanta increases efficacy. Mechanism of action studies in ovarian cancer: Prolanta induces autophagy in ovarian cancer cells that overexpress prolactin receptors Prolanta may prevent chemo-resistance by prolactin receptors Oncolix

15 MD Anderson Ovarian Cancer Research Prolanta as a monotherapy reduces the size and number of tumors in orthotopic ovarian cancer models (SKOV3 shown). SKOV3 Using lowest (100ug/day) dose IG10 Prolanta was synergistic with taxanes in multiple orthotopic ovarian cancer models. [Dose 100ug/day] Oncolix

16 Prolanta shows evidence of synergistic effect in breast cancer models Cummulative Tumor Volume (mm 3 ) control Herceptin G129R G129R + Herceptin ** ** ** ** * * ** ** ** * * ** ** * * * * ** Prolanta (G129R) was effective as a monotherapy in a breast cancer model, and was synergistic with Herceptin. Prolanta Alone Prolanta+Herceptin Days post inoculation Each value is a mean ± SD of 6-8 mice/group ** P < 0.01 and * P < 0.05 versus control P < 0.05 versus Herceptin alone Oncolix

17 Prolanta monotherapy or combination therapies Accumulating evidence suggests that PRL (Prolactin) opposes cytotoxicity by a wide variety of anticancer drugs. LaPensee et al, Endocrine-Related Cancer, 2010 Standard of care for ovarian cancer: 1st Line: Platinum and taxane therapy, almost all patients develop resistance 2nd line: Doxil, Hycamtin, Gemzar, vinorelbine, cyclophosphosphamide; Response rate is 10 to 15% Blocking prolactin receptors with Prolanta should enhance first-line therapy (e.g., used in combination with platinum and taxane): Blocking the effects of prolactin should enhance the apoptotic effect of platinum therapy Prolactin has been implicated in the process by which cancer cells become resistant to platinum therapy, as well as 2nd line therapies Prolanta is also synergistic with taxane therapies Oncolix

18 IND FDA has cleared Oncolix s IND for a Phase I human trial of Prolanta in recurrent and persistent ovarian cancer Manufacturing is a scalable, cgmp process with reproducibility across multiple lots Toxicity / Toxicokinetic Data Cynomolgus monkey and rabbit studies performed by Charles River Laboratories No significant adverse effects noted Oncolix

19 Global Market Potential and Risk Analysis (Ovarian Cancer Only) Assumptions: Ovarian cancer indication only Annual price of $40,000 (US, Japan, Canada) and $30,000 (Europe) Market Potential: $3 billion market $1,078 million (US) $1,710 million (W. Europe) $ 313 million (Japan) $ 95 million (Canada) Risk Analysis: Orphan status & unmet medical need: refractory & platinum resistant ovarian cancer Potential to receive regulatory approval on a well controlled Phase IIb clinical trial or smaller Phase III trials than indications such as breast cancer No direct competition - Prolanta is additive or synergistic to current therapies and no other prolactin receptor antagonists in human clinical trials in the US Lower trial costs: ovarian trials significantly less than breast cancer trials Pricing: Comparative Cost $6,000 to $10,000 per month - Avastin approved for OC in Europe Manufacturing: Prolanta IND cleared by US FDA includes the Chemistry, Manufacturing and Controls (CMC) package Drug is manufactured by an FDA-inspected facility in large commercial equipment and is one scaleup level from full commercial production Intellectual property: Eight US issued patents and additional foreign patents Multiple indications: Prolanta has the potential to treat other gynecological cancers Oncolix

20 Clinical Development Plan for Ovarian Cancer Phase I Safety/Efficacy (First 3 Patients Completed) Monotherapy in 12 to 18 Platinum Resistant Subjects 99-day trial File for Accelerated Approval (Fast Track) (Breakthrough) Phase I Safety/Efficacy Combination with Platinum/Taxane in 20 Recurrent Patients 28-day trial Phase IIa Efficacy Trial Combination with Platinum/Taxane vs Chemo alone in Recurrent Patients 40 Patients (Combo) 40 Patients (Chemo Alone) 9-month trial Phase IIb Pivotal Trial (USA) Combination with Platinum/Taxane vs Chemo alone in Recurrent Patients 160 Patients (Combo) 80 Patients (Chemo Alone) 9 to 12 month trial Oncolix

21 Ovarian Cancer Clinical Trials Monotherapy & chemo combination strategy Phase I (monotherapy) [in progress] ipot (Initial Prolanta Ovarian Trial) Subjects, recurrent or persistent disease Safety, biomarker evaluation and efficacy trends Three escalating doses 99-day trial Phase I (combination with chemo) Prolanta+chemotherapy Safety, biomarkers and efficacy (PFS and OS) 20 Patients in dose escalation phase (28 days) Commences after Phase I monotherapy trial Phase IIa (combination with chemo) Prolanta+chemotherapy vs chemotherapy alone Safety, biomarkers and efficacy (PFS and OS) 40 Patients in each arm (9 months) Phase IIb Pivotal (combination with chemo) Prolanta+chemotherapy vs chemo alone Biomarkers and efficacy (PFS and OS) 240 Patients (160 Patients Combo and 80 Patients Chemo) 9 to 12 month trial Oncolix

22 Company Evolution : Company structures and advances Prolanta manufacturing Redman hired as CEO of a new company formed by GHS to focus on autologous melanoma vaccine Company named Oncolix, GHS invests $3.0 million and receives shares in exchange for IP Redman evaluates other in-house opportunities, identifying G129R (Prolanta), which had been dropped due to manufacturing costs Oncolix licenses a high-yielding E. coli expression system for G129R from Monsanto, which is expected to result in a substantial reduction in the cost of goods Oncolix terminates the autologous melanoma vaccine GHS leads $3.5 million round with manufacturer contributing $1.5 million in-kind investment : Oncolix advances $2.4 million of funding from the Texas Emerging Technology Fund Clinical protocol for Phase 1 trial in ovarian cancer submitted to FDA supported by preclinical toxicology studies and drug characterization : Recent progress: US IND granted to Oncolix to commence Phase I trial MD Anderson announces Prolanta s novel mechanism of action at the AACR meeting in Chicago Granted orphan status in the U.S. for ovarian cancer Completed $4.2 million Series A financing round in January 2015 ($15 million raised to date) Commenced Phase I dose-escalation trial for ovarian cancer Capital raise in progress up to $5+ million Oncolix

23 Leadership Michael Redman, CEO, BOD Formerly CEO of Bone Medical, CEO and founder of Opexa Pharmaceuticals; VP, Corporate Development, Aronex Pharmaceuticals; VP, Business Development, Repros Therapeutics Extensive Licensing and acquisition experience; Phase I through III clinical trial management Author of successful grant /award applications Donald Payne, Senior Vice President Formerly CFO of Sensus Drug and LifeCell Corporation; founding CEO of Nanospectra Biosciences Extensive finance, technical writing, clinical trial and audit experience Author of successful grant/award applications; co-inventor of two patents William Gannon, MD, Chief Regulatory Officer Numerous managerial experience with multinational CROs, biotech and pharmaceutical companies, primarily cancer Substantial regulatory submissions and execution of Phase I through Phase IV both US and international Anil Sood, MD, Advisor Professor & Director, Blanton-Davis Ovarian Cancer Research Program, MD Anderson Cancer Center Discovered Prolanta s mechanism of action (Autophagy) Preclinical efficacy and biomarker evaluation of Prolanta Jerry Youkey, MD, Chairman of BOD Dean, U of SC Medical School VP, Greenville Hospital System Dale Zajicek, BOD Former president, BioVectra Expert in manufacturing Oncolix

24 Wen Chen Inventor of Somavert and Prolanta Chen also invented G120R (Somavert ), developed by Austin, TXbased Sensus Drug Development Corp. Features same amino acid substitution but with growth hormone First clinical validation of receptor antagonism Now approved by FDA and sold by Pfizer 2016 sales: $232 million for acromegaly (chronic gigantism, an orphan indication) Wen Chen, PhD Professor Clemson University Oncolix

25 Milestones and Capital Raised $3 MM GHS Jan 07 $3.5 MM GHS Jan 09 $1.5 MM BioVectra (PIK) Aug 09 $2.4 MM ETF Oct 2010 $2.4 MM $1.1MM ETF Bridge Oct Loan 2010 Mar 2012 $4.2+ MM Jan 2015 License or Sell Company Product Indication Research Mfg Optimization Pre-clinical Phase I Phase IIa Phase IIb Prolanta Ovarian Cancer N/A N/A Prolanta Ovarian/ Combo Therapy Prolanta Uterine Cancer Prolanta Breast Cancer To be pursued with a pharmaceutical partner or post-approval of ovarian indication Oncolix

26 Capital Requirements Expanded Clinical and Regulatory Involvement VP Clinical Operations (2018) Director of Clinical Operations, CRA (2017) Director of Project Management (2017) HIRED Expanded sponsored research at MD Anderson to uterine cancer Sponsored research at UC-SF for breast cancer Capital Requirements Through Phase 2b $29.8 million capital raise to fund ovarian cancer monotherapy through Phase IIb trial results (monotherapy)and combination with chemotherapy trials through Phase 2b $ 5.1 M $8.9M 15.8M Oncolix

27 Financing History Greenville Hospital System (GHS) $7.7 million BioVectra (PIK) $1.5 million Emerging Technology Fund $3.9 million Clinical Accelerator (10% PIK) $0.05 million PoC Capital/Integrium (PIK) $1.5 million Series B in progress $5.0 million (estimate) Institutional Investors Family Offices Accredited Investors Oncolix

28 Capitalization Percentage of Fully Diluted GHC Research and Development 47.0 CEO 4.9 Founding Scientists and Others 6.1 Contract Manufacturer and CRO 11.9 Texas Emerging Technology Fund % Oncolix

29 Prolanta Investment Highlights Unmet medical need provides opportunity for accelerated approval through well-defined regulatory pathway Novel Mechanisms of Action Autophagy (programmed cell death) that selectively targets gynecological cancer cells Inhibition of cell proliferation signaling (JAK/STAT5/RAS/Raf) Reduction of Glutathione-S-Transferase clearance of chemotherapy agents, enhancing platinum and taxane therapy Strong preclinical evidence of efficacy Synergistic or additive to current therapies Reliable manufacturing under an FDA-reviewed process with proven scalability Proprietary patent position Positioned to be used primarily as a combination with chemotherapy or as a monotherapy in those patients who have failed chemotherapy Oncolix

30 Supplemental Information

31 G129R Efficacy (Growth Inhibition) 3-D Cultured HeyA8 Spheroids Real-time video microscopy for visualizing growth inhibition by Prolanta (G129R) (A) Time-lapse photomicroscopy was used to study HeyA8 ovarian cancer cells cultured in the Matrigel embedded condition (spheroids). Cells were either treated with (1) control (2) prolactin (PRL), (3) Prolanta (G129R) or (4) combination of PRL+G129R. Representative photomicrographs taken during filming are shown in phase contrast; approximate time elapsed (minutes): (a) 240; (b) 600 and (c) 2800 minutes. (B) Quantitative measurement of spheroid structure formulated at 48 hours of treatments with (1) control (2) PRL, (3) G129R or (4) combination of PRL+G129R. * p<0.05; ** p<0.01. Oncolix

32 Prolactin Confers Resistance to Chemotherapy The efficacy of therapeutic doses of chemotherapy drugs (red box) was reduced by pretreatment with prolactin in MDA-MD-468 breast cancer cells. The mechanism of action was not determined. Chemotherapy Drug Dose (ng/ml) Pretreatment with prolactin (PRL, 25 ng/ml) for 24 hours followed by chemotherapy drug exposure for 4 days. Chemotherapy drug exposure for 4 days * Significant difference versus control (chemotherapy drug alone) LaPensee, et al. Carcinogenesis vol.30 no.8 Oncolix