PRO 140. First self-administered antibody therapy for HIV in late-stage clinical development

Transcription

1 PRO 140 First self-administered antibody therapy for HIV in late-stage clinical development In early-stage development for cancer indications and other immunological disorders CytoDyn Investor Presentation August 2018 OTCQB: CYDY

2 Forward-Looking Statements This presentation contains certain forward-looking statements that involve risks, uncertainties and assumptions that are difficult to predict, including statements regarding the proposed transaction with ProstaGene, the likelihood of closing the proposed transaction with ProstaGene, the Company s clinical focus, and the Company s current and proposed trials. Words and expressions reflecting optimism, satisfaction or disappointment with current prospects, as well as words such as believes, hopes, intends, estimates, expects, projects, plans, anticipates and variations thereof, or the use of future tense, identify forward-looking statements, but their absence does not mean that a statement is not forward-looking. The Company s forward-looking statements are not guarantees of performance and actual results could differ materially from those contained in or expressed by such statements. In evaluating all such statements, the Company urges investors to specifically consider the various risk factors identified in the Company s Form 10-K for the fiscal year ended May 31, 2018 in the section titled Risk Factors in Part I, Item 1A, any of which could cause actual results to differ materially from those indicated by the Company s forward-looking statements. The Company s forward-looking statements reflect its current views with respect to future events and are based on currently available financial, economic, scientific, and competitive data and information on current business plans. Investors should not place undue reliance on the Company s forward-looking statements, which are subject to risks and uncertainties relating to, among other things: (i) the sufficiency of the Company s cash position and the Company s ongoing ability to raise additional capital to fund its operations, (ii) the Company s ability to complete its Phase 2b/3 pivotal combination therapy trial for PRO 140 (CD02) and to meet the FDA s requirements with respect to safety and efficacy to support the filing of a Biologics License Application, (iii) the Company s ability to meet its debt obligations, if any, (iv) the Company s ability to identify patients to enroll in its clinical trials in a timely fashion, (v) the Company s ability to achieve approval of a marketable product, (vi) design, implementation and conduct of clinical trials, (vii) the results of the Company s clinical trials, including the possibility of unfavorable clinical trial results, (viii) the market for, and marketability of, any product that is approved, (ix) the existence or development of vaccines, drugs, or other treatments for infection with HIV that are viewed by medical professionals or patients as superior to the Company s products, (x) regulatory initiatives, compliance with governmental regulations and the regulatory approval process, (xi) general economic and business conditions, (xii) changes in foreign, political, and social conditions, and (xiii) various other matters, many of which are beyond the Company s control. Should one or more of these risks or uncertainties develop, or should underlying assumptions prove to be incorrect, actual results may vary materially and adversely from those anticipated, believed, estimated, or otherwise indicated by the Company s forward-looking statements. The Company intends that all forward-looking statements made in this presentation will be subject to the safe harbor protection of the federal securities laws pursuant to Section 27A of the Securities Act of 1933, as amended, to the extent applicable. Except as required by law, the Company does not undertake any responsibility to update these forward-looking statements to take into account events or circumstances that occur after the date of this presentation. Additionally, the Company does not undertake any responsibility to update investors upon the occurrence of any unanticipated events which may cause actual results to differ from those expressed or implied by these forward-looking statements. 2

3 Leronlimab Monoclonal Antibody PRO 140, Leronlimab, is a Humanized Monoclonal Antibody First monoclonal antibodies developed by Kohler & Milstein in 1975, awarded Nobel prize in 1984 Monoclonal antibodies have selective specificity, outstanding safety record PRO 140 targets CCR5, HIV entry doorway and validated cancer target MERCK and Pfizer are testing 2 CCR5 antagonists. One already approved for HIV >50 monoclonal antibodies are marketed in the U.S. *Monoclonal antibodies global market size - $138.6 billion by 2024 * 3

4 Recent Developments CD02 Phase 3, pivotal trial with PRO 140 in combination therapy for HIV Achieved primary endpoint (p=0.0032) 81% of patients achieved suppressed viral load with plasma HIV-1 RNA <50 copies/ml No SAEs related to PRO 140 Rolling BLA submission expected to be complete in 1H2019 CD03 Phase 3 HIV investigative monotherapy trial with PRO patients enrolled, enrollment continuing About 40% response rate at 350 mg About 70% response rate at 525 mg Increasing dose to 700 mg Phase 2 graph-versus-host disease (GvHD) Modified protocol to improve enrollment and reflect positive preclinical findings Interim data review following treatment of first 10 patients in the new protocol New, broader focus with PRO 140 to include cancer and other immunological disorders Promising preclinical (in vitro) results in breast cancer Encouraging preclinical (animal) results in colon cancer and MS 4

5 PRO 140 for HIV: Clinical Trial Overview Trial Stage Study # patients Design / Findings Status P-Cl. Ph1 Ph2 Ph3 2 Phase 1 studies 54 Healthy patients, no safety concerns Complete 1302 IV Phase 1 study IV Phase 2 study SC Phase 2 study 44 CD01 Phase 2b 43 CD02 Phase 2b/3 Pivotal-Fastest path to approval CD03 Phase 2b/3 Investigative Trial Largest market size 52 Intravenous, single-dose VL reduction for 3 weeks Intravenous, single-dose VL reduction for 3 weeks Subcutaneous, long-acting, selfadministered, proof-of-concept shown 12-week drug-substitution monotherapy Long-term monotherapy extension: 14 patients with VL suppression at 12 weeks Combination therapy in HAART failures, 1 week efficacy + 24 weeks durability 303 Long-term monotherapy Complete Complete Complete Complete Jan Ongoing Complete 300 patients original trial Enrollment completed 5

6 PRO 140 A Humanized Monoclonal Antibody Blocking HIV entry receptor (CCR5) Blocking CCR5/CCL5 interaction with PRO 140 for use in CANCER Humanized monoclonal antibody Binds to CCR5 co-receptor on white blood cells HIV CD4 PRO 140 HAART Blocks HIV entry into white blood cells T-Cell CCR5 6

7 HIV is No Longer a Life-Threatening Disease But Serious Problems Remain The goal today is: 1) Zero transmission Viral load = undetectable transmission rate = ZERO Why do only 35% of HIV patients in U.S. have undetectable viral load? 2) Higher quality of life Current standard of care: side Effects + toxicity 3) Better compliance Current standard-of-care: 1 to multiple pills/day 7

8 PRO 140 Advantages over HAART PRO 140 HAART No serious side effects and no serious adverse events (SAEs) in >400 patients in 8 clinical trials Side Effects Ranges from mild to severe (Diarrhea, nausea, lethargy, depression) Negligible toxicity Toxicity Problems with short- and long-term toxicity No drug resistance in patients on monotherapy for over 3 years Weekly, easy, subcutaneous self administration Resistance Compliance 76% of HIV patients have at least one resistance Daily lifetime dosing with only 35% of patients with complete viral load suppression 8

9 CD02 Pivotal Combination Therapy Protocol 9

10 CD02 Pivotal Combination Trial with PRO patients prescreened for R5 strain and failing current HAART regimen (3 class resistance or 2 class resistance with limited treatment options) Primary efficacy endpoint: reduction in viral load after 1 week following single PRO 140 dose All patients continue current HAART; 50% receive PRO 140 / 50% receive placebo PRO 140 patients achieved statistically significant reduction - p = week open-label with all patients on weekly PRO 140 with optimized HAART 81% of patients completing trial achieved HIV viral load suppression of <50 cp/ml While 92% had viral load suppression of <400 cp/ml. Recent approved drugs for this population range from 43% after 24 weeks to 45% after 48 weeks with vial load suppression of < 50 cp/ml No reported SAEs related to PRO patients requested to continue PRO 140 in extension study Regulatory path expected first FDA approval for PRO 140 in combination therapy Submission of rolling BLA with full BLA submission expected in 1H2019 Safety data from 150 eligible patients from all CytoDyn HIV trials 10

11 Viral Suppression Rate of other Approved Drugs Entry Inhibitors - Heavily Treatment-Experienced (HTE) Patients Dosing Schedule Suppressed viral load Maraviroc*, oral, 2X daily Ibalizumab**, IV, biweekly PRO 140 (leronlimab), subcutaneous selfinjection, weekly 45% at 48 weeks 43% at 24 weeks ~ 81% at 24 weeks *Maraviroc: **Ibalizumab: 11

12 Potential Approval for PRO 140 in HIV in 2019 Timeline for submitting rolling BLA Non-Clinical - 4Q18 Clinical - 4Q18 CMC (Manufacturing) - 1Q19 Final Complete package: 1Q19 BTD: Impact on BLA review timeline? 12

13 PRO 140 HIV Indication Phase 3 Monotherapy 13

14 CD03 PRO 140 Investigative Monotherapy Trial All patients prescreened for R5 strain with viral load suppression maintained with HAART Ongoing open-label, 48-week trial with all patients receiving PRO 140 weekly injections Investigative trial with focus on increasing responder rate and no harm to non-responders Increasing response rate First dose level of 350 mg produced responder rate of ~ 40% Second dose level of 525 mg increased responder rate to ~ 70% so far (1 to 9 months) Third dose level for planned increase to 700 mg to evaluate improved response rate Options for non-responders 100% of non-responders re-suppressed viral load with prior HAART regimen No reported SAEs related to PRO 140 in any trial to date Regulatory path Conduct pivotal Phase 3 monotherapy trial Submit PRO 140 for approval for label expansion as monotherapy, subject to approval as combination therapy 14

15 Viral Suppression Rate of Approved HIV Drugs HAART-Viral Life Cycle Inhibitors First-line Treatment Patients Daily Single Pill Suppressed viral load (48-week trial) Combivir 70% Atripla 80% Complera 86% Stribild 87% Triumeq 88% Genvoy 96W 88% Truvada+EFV 80% GlobalData - PharmaPoint Human Immunodeficiency Virus (HIV) Global Drug Forecast and Market Analysis to

16 Number of patients 16 Number of patients HIV - CD03 Low Dose Vs. Higher Dose LOWER DOSE (350 mg) = 45% HIGHER DOSE (525 mg) = 73% Adding the high dose rescue arm = 81% Passing Failed 60 Passing Failed Week number into Trial Week number into Trial 16

17 U.S. Market Size for HIV Indication for PRO 140 Year HIV patients Patients using HAART 1 resistance 2 resistance 3 resistance ,373, , , ,248 28, ,400, , , ,291 27, ,421, , , ,842 27, ,432, , , ,677 26, ,450, , , ,750 24, ,468, , , ,950 23, ,487, , , ,164 21, ,506, , , ,545 20, ,514, , , ,548 17,727 Source: GlobalData &

18 18 U.S. Market Potential for PRO 140 in HIV Alone Initial approval Combination Therapy HAART failures: ~ 70,000* patients with 2 or more drug class resistances 70,000 patients x 70% (R5-HIV strain) = 49,000 HIV patient R5 eligible 49,000 patients x $24,000 (current market pricing) = ~ $1.2 billion Label Expansion Switch to Monotherapy Maintenance Target population (suppressed viral load) = 17.5% of 1.3 million HIV+ = 227,500** 227,500 patients x 70% (R5-HIV) = 159,250 patients 159,250 patients x $24,000 (current market pricing) = ~ $3.8 billion * Market size BioVid Market Research: 2 class resistance ~ 5% to 20% ~ 70,000 to 280,000 patients ** Market size BioVid Market Research: Monotherapy ~ 60% to 100% suppressed viral load among ~ 480,000 to 770,000

19 Level of Unmet Need HIV-PRO 140 U.S. Market - Research From BIOVID Executive Summary MDs unmet needs in HIV treatment align well with PRO 140 strengths Unmet need differs based on suppression status. While the vast majority (80%) of virologically suppressed are highly satisfied with existing HIV treatment, patients with multiple failures are much less satisfied. Physicians top stated unmet needs align nicely with PRO 140 strengths. % MDs Highly satisfied ~80% Virologically suppressed MD Top Reported Unmet Needs Less frequent dosing Novel mechanism of action % MDs with Extremely High Unmet Need Among Suppressed Patients Among Multi-class Failures 23% 40% 10% 40% ~27% 2-class failures More non-oral formulations Improved drug interaction profile 23% 37% 13% 27% ~7% 3-class failures High genetic barrier to resistance Regimens with fewer active agents 10% 27% 7% 27% Base size: Total Physicians (n=30) 19

20 HIV-U.S. Market Size - Research Report From BIOVID Executive Summary Most MDs will trial PRO 140 monotherapy within 3 months of launch, while 2 of 3 will adopt its use within the 1 st year Estimated Time to Trial and Adoption of PRO % 83% 69% 90% 93% 93% 93% 97% 97% 90% 67% 23% 43% 23% 37% 40% 65% 3% Within the first month 2-3 months 4-6 months 7-12 months months19-24 months Longer than Trial Adoption 2 years Base size: Total Physicians (n=30) *Benchmark data based on BioVid s proprietary Demand database (full database) 20

21 U.S. Market Size - Research Report From BIOVID Executive Summary Even prior to seeing PRO 140, physicians show clear, strong interest in option with attributes similar to PRO 140 Percent of Physicians Highly Interested for Various Patient Groups (% highly interested Top-2 Box) How interested would you be in a novel, FDA-approved, self-injectable, singledrug, HIV maintenance regimen that is dosed weekly with no evidence of resistance or adverse events? Virologically suppressed 2-class failures 3-class failures 43% 50% 70% Base size: Total Physicians (n=30) 21

22 U.S. Market Size - Research Report From BIOVID Executive Summary However, patients show a strong PRO 140 call to action Patient Reactions to PRO 140 (pre-video review) Monotherapy Patients Combo Therapy Patients PRO 140 is a significant improvement vs. current options 55% 55% Highly likely to start a conversation with my doctor 70% 60% Highly likely to try to find more information about PRO % 60% Would schedule an appointment within 3 months to discuss PRO % 65% Effort needed to make PRO 140 part of daily routine Level of concern about taking PRO 140 as instructed Very little/moderate effort 85% 95% A lot of effort 10% 5% Way too much effort to take on 5% 0% 5% 15% 5% 10% 25% 40% 40% 60% Level of concern about taking PRO 140 long-term 45% 5% 5% 15% 35% 35% 35% 25% Monotherapy patients are slightly more likely to act upon their interest in PRO 140 by talking to their MD and/or searching for more product details on their own Both patient types see PRO 140 as requiring minimal effort to implement in their daily routine, and the majority do not have significant concerns with self-injecting PRO 140 once/weekly long-term Very concerned Somewhat concerned A little bit concerned Not concerned 22 Base Size: Total Patients; Monotherapy Candidates (n=20); Combination Therapy Candidates (n=20) (OTCQB: CYDY)

23 PRO 140 Additional Likely Scenario for Market Number of Patients Treated, ART (N) 788, ,875 Single-Tablet Regimens (STRs) 514, ,586 NNRTI-based STRs 152, ,121 Atripla (efavirenz/emtricitabine/tdf) 51,244 18,765 generic efavirenz/emtricitabine/tdf - 23,660 Complera (rilpivirine/emtricitabine/tdf) 14,979 13,054 Odefsey (rilpivirine/emtricitabine/taf) 71,742 76,692 doravirine/lamivudine/tdf 14,979 17,949 INI-based STRs 251, ,423 Stribild (elvitegravir/cobicistat/emtricitabine/tdf) 18,133 17,133 Genvoya (elvitegravir/cobicistat/emtricitabine/taf) 78,837 81,588 Triumeq (dolutegravir/abacavir/lamivudine) 35,477 34,267 dolutegravir/lamivudine 59,128 64,454 bictegravir/emtricitabine/taf 59,916 70,981 PI-based STRs 36,265 38,346 Prezista STR (darunavir/cobicistat/emtricitabine/taf) 36,265 38,346 NRTI-free STRs (Short- and Long- Acting) 73, ,696 dolutegravir/rilpivirine 45,726 61,191 cabotegravir/rilpivirine 27,593 46,505 Add PRO 140 to any STR 17 SCENARIO A Most likely benefits: 1) ~100% suppression rate 2) Very few switches 3) Adherence increase dramatically 4) Resistance almost zero 5) Side effect + toxicity added by PRO 140 is almost zero Adding PRO 140 to a generic version of Atripla or any STR that becomes generic will make a new HAART with most likely better suppression rate than any latest STR GlobalData Human Immunodeficiency Virus (HIV) Global Forecast

24 PRO 140 Additional Likely Scenario for Market Multiple-Pill Regimen Components 274, ,290 Fixed-Dose NRTI Backbones and NRTIs 275, ,607 Truvada (emtricitabine/tdf) 81,991 30,187 generic emtricitabine/tdf - 51,400 Descovy (emtricitabine/taf) 96,970 98,721 Epzicom (abacavir/lamivudine) 3,153 1,632 generic abacavir/lamivudine 22,863 17,133 Viread (TDF) 6,307 4,079 generic TDF 25,228 24,476 Other Fixed-Dose NRTI Backbones 3,153 3,264 Other NRTIs 35,477 36,714 NNRTIs 25,228 22,029 Sustiva (efavirenz) generic efavirenz 2,365 2,448 Intelence (etravirine) 1, Edurant (rilpivirine) 1, MK-1439 (doravirine) 18,133 16,318 generic nevirapine PIs 137, ,500 Prezista (darunavir) 3,942 2,448 generic darunavir 42,572 44,057 Prezcobix (darunavir/cobicistat) 18,133 16,318 Reyataz (atazanavir) 7,095 2,448 generic atazanavir 15,767 13,870 Evotaz (atazanavir/cobicistat) 13,402 12,238 Kaletra (lopinavir/ritonavir) 1, generic lopinavir/ritonavir 10,249 10,198 generic fosamprenavir 1,577 1,632 Other PIs 23,651 24,476 INIs 111, ,353 Tivicay (dolutegravir) 67,012 62,822 Isentress (raltegravir) 44,149 37,530 Number of Patients Treated, Add-on & Salvage Therapies (N) 85,933 49,768 Attachment, Entry, and Fusion Inhibitors 18,921 17,949 Fuzeon (enfurvitide) Selzentry Fostemsavir- Ibalizumab - - Pharmacokinetic Enhancers (Boosters) 67,012 31,819 GlobalData Human Immunodeficiency Virus (HIV) Global Forecast Add PRO 140 to any 2 pillcombination or to any 1 pill 24 SCENARIO B New HAART with 2 pill combination acting as STR like the above Example: Truvada + PRO 140 or 2 combination that acts as HAART. Example: Dolutegravir+PRO 140 POSSIBILY: ~100% SUPPRESSION RATE SCENARIO C PRO 140 use as add-on to any combination

25 PRO 140 Most Likely Market Scenario # of Patients Treated, ART (N) 788, ,875 Single-Tablet Regimens (STRs) 514, ,586 NNRTI-based STRs 152, ,121 INI-based STRs 251, ,423 PI-based STRs 36,265 38,346 NRTI-free STRs 73, ,696 SCENARIO A Multiple-Pill Regimen Components 274, ,290 NNRTIs 25,228 22,029 PIs 137, ,500 INIs 111, ,353 SCENARIO B # of Patients Treated, Add-on & Salvage Therapies (N) 85,933 49,768 Attachment, Entry, and Fusion Inhibitors Fuzeon (enfurvitide) Selzentry Fostemsavir-Ibalizum. 18,921 17,949 SCENARIO C Pharmacokinetic Enhancers (Boosters) 67,012 31,819 GlobalData Human Immunodeficiency Virus (HIV) Global Forecast

26 PRO 140 Important Milestones for HIV 2018/2019 Milestones Phase Pivotal HIV Combination Trial Primary Endpoint Medical Conference Presentations (CROI and ASM Microbe) Publication Studies HIV Combination Trial Primary Endpoint Study Publication of Monotherapy (Phase 2b) Pivotal Phase 3 Endpoint Achieved (ASM Microbe late breaker) Target Dates p= Completed 2H2018 Completed Presented BLA Submission (2 section out of 3 Clinical and non-clinical) 2018 BLA submission (last section CMC) Phase 3 pivotal trial for label expansion approval 1Q2019 1Q2019 HIV Breakthrough Therapy Designation (BTD) 2018 Exploring partnership with small and large Pharma

27 PRO 140 Immunologic Indications Additional potential PRO 140 applications GvHD Autoimmune disorders Cancer including tumor metastasis (Dr. Richard Pestell) 27

28 Weight gm mean ± SE Survival % Effect of PRO 140 on Xeno-GvHD Human BM Transplanted Into Immuno-Deficient Mice Control PRO 140 P < P <.01 Control PRO Day Day

29 Expansion into Cancer Indications Named world-renowned oncologist Dr. Richard Pestell to be Chief Medical Officer Lead PRO 140 non-hiv development programs Led 2 National Cancer Institute-designated cancer centers Lombardi Comprehensive Cancer Center at Georgetown University Sidney Kimmel Cancer Center at Thomas Jefferson University Founded ProstaGene to develop CCR5 technology in cancer Important focus on metastasis of many types of cancer Research showed nearly 50% of 2,200 patients with breast cancer had overexpressed CCR5 Published preclinical studies provide support CCR5 inhibitors effectively blocked breast and colon cancer spread; blocked prostate cancer metastasis to bones and brain 29

30 CCL5 Control PRO140 Vicriviroc Distance of Invasion ( m) CCR5 is Expressed in >50% of Breast Cancer Metastatic cancer. 50% of breast cancers CCR5+ PRO -140 reduces breast cancer invasion P< P<0.001 Control PRO140 (1/500) Vicriviroc Professor Richard Pestell, PhD, MD 30

31 Relative FI of Fluo-4 Relative FI of Fluo-4 PRO140 (1/100) Control Breast PRO 140 Cancer Blocks Breast Cancer Ca +2 signaling A 20 sec before adding CCL5 60 sec after adding CCL5 240 sec after adding CCL5 60 sec after adding FBS B 3 2 CCL5 FBS C 3 2 CCL5 FBS Control PRO Time (Sec) Time (Sec) Professor Richard Pestell, PhD, MD 31

32 Maraviroc Control CCR5 Antagonists Block Breast Cancer Metastasis Time (weeks) Professor Richard Pestell, PhD, MD 32

33 Maraviroc Control Professor Richard G. Pestell CCR5 Antagonists Block Prostate Cancer Metastasis Professor Richard Pestell, PhD, MD

34 PRO 140 Blocks Colon Cancer Growth in Mice SW480 Human Colon Carcinoma Xenografts in NCr Nude Mice PRO 140, 2 mg i.p. twice/week, started day 1, n=16 tumors/group Tumor Volume in mm3 (mean ± SE) mg dosing Control PRO 140 p= Day mg dosing Control PRO 140 p= Day Daniel Lindner, M.D., Ph.D. Cleveland Clinic 34

35 Chemotherapy Increases CCR5 Expression in Cancer Cells CCR5 governs DNA damage repair and breast cancer stem cell expansion. Cancer Res. Pestell et al :7, 1657 Daniel Lindner, M.D., Ph.D. Cleveland Clinic 35

36 Objective Tumor Response, Phase 1 Trial advanced-stage metastatic colorectal cancer who are refractory to standard chemotherapy, including regorafenib Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients Cancer Cell

37 Objective Tumor Response, Phase 1 Trial advanced-stage metastatic colorectal cancer who are refractory to standard chemotherapy, including regorafenib Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients Cancer Cell

38 38 CCR5 Inhibitor Breast Cancer Study *Current pilot study funded by a FALK grant March 2018-July 2019 Phase 1b/II August 2019-July 2021 (Phase II)

39 Patents Issued 1. US Patent issued September 27, 2016 as U.S. Patent No. 9,453,836. Use of modulators of CCR5 in the treatment of cancer and cancer metastasis US Provisional Patent Application Nos. 61/646,593 and 61/646,586 (Reference Nos PR & PR1) 2. Australian issued Patent No , Title: Prostate Cancer Cell Lines, Gene Signatures And Uses Thereof. Ref AU. issued August 25, 2016 Prostate Cancer Cell Lines, Gene Signatures And Uses Thereof: 61/450,767 Patent Methods and Compositions For The Diagnosis, Prognosis And Treatment Of Cancer Related Applications. 03/09/2011 and 09/03/2012, PCT/US2012/028546, agents file ref WO issued patent. Pending 1. CCR5 and cancer stem cells, 4/13/15, WO 2016/ Circulating tumor cells and therapy, 2/12/15, US 15/738,020 39

40 Publications CCR5 Governs DNA Damage Repair and Breast Cancer Stem Cell Expansion. Jiao X, Velasco-Velázquez MA, Wang M, Li Z, Rui H, Peck AR, Korkola JE, Chen X, Xu S, DuHadaway JB, Guerrero-Rodriguez S, Addya S, Sicoli D, Mu Z, Zhang G, Stucky A, Zhang X, Cristofanilli M, Fatatis A, Gray JW, Zhong JF, Prendergast GC, Pestell RG. Cancer Res Apr 1;78(7): doi: / CAN Epub 2018Jan 22.PMID: CCR5 receptor antagonists block metastasis to bone of v-src oncogene-transformed metastatic prostate cancer cell lines.sicoli D, Jiao X, Ju X, Velasco-Velazquez M, Ertel A, Addya S, Li Z, Andò S, Fatatis A, Paudyal B, Cristofanilli M, Thakur ML, Lisanti MP, Pestell RG. Cancer Res Dec 1;74(23): doi: / CAN PMID: Select item CCR5 antagonist blocks metastasis of basal breast cancer cells. Velasco-Velázquez M, Jiao X, De La Fuente M, Pestell TG, Ertel A, Lisanti MP, Pestell RG. Cancer Res Aug 1;72(15): doi: / CAN Epub 2012 May 25.PMID:

41 Expanded Role for PRO 140 in Cancer Preclinical studies show PRO 140 s ability to selectively target CCR5 receptor Dr. Pestell s preclinical research shows CCR5 receptor is vital in cancer cell invasion and metastasis Preclinical findings show PRO 140 as effective in blocking breast cancer invasion as small molecule CCR5 inhibitors (see CytoDyn press release dated 6/26/18) PRO 140 could have advantage of less frequent dosing and improved safety profile compared with other small molecule CCR5 antagonists Announced LOI to acquire ProstaGene Planned IND filing to initiate Phase 2 trial in colon cancer 41

42 PRO 140 Milestones - Cancer and Other Indications Milestones Complete acquisition of ProstaGene Colon cancer animal study Published studies GvHD (Preclinical study) Orphan Drug Designation for GvHD Target Dates 3Q18 4Q18 Completed FDA Granted IND submission for colon cancer (Phase 2) 2018 IND submission for MS (Phase 2) 2018 File IND for breast cancer inhibition of metastasis 1H