Veru Inc.
Nasdaq:VERU
The Prostate Cancer Company
Novel Medicines
Veru Corporate Presentation
June 2020
Forward looking statements
This communication contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements are subject to known and unknown risks, uncertainties and assumptions, and if any such risks or uncertainties materialize or if any of the assumptions prove incorrect, our actual results could differ materially from those expressed or implied by such statements. Factors that may cause actual results to differ materially from those contemplated by such forward-looking statements include, but are not limited to, the following: risks related to the development of Veru Inc.'s (the "Company") product portfolio, including clinical trials, regulatory approvals and time and cost to bring to market; potential delays in the timing of and results from clinical trials and studies, including potential delays in the recruitment of patients and their ability to effectively participate in such trials and studies due to COVID-19, and the risk that such results will not support marketing approval and commercialization; potential delays in the timing of any submission to the FDA and regulatory approval of products under development and the risk that disruptions at the FDA caused by the COVID-19 pandemic may delay the review of submissions or approvals for new drugs; clinical results or early data from clinical trials may not be replicated or continue to occur in additional trials or may not otherwise support further development in the specified product candidate or at all; the Company's pursuit of a COVID-19 treatment candidate is at an early stage and it may be unable to develop a drug that successfully treats the virus in a timely manner, if at all; risks related to the Company's commitment of financial resources and personnel to the development of a COVID-19 treatment which may cause delays in or otherwise negatively impact its other development programs, despite uncertainties about the longevity and extent of COVID-19 as a global health concern; government entities may take actions that directly or indirectly have the effect of limiting opportunities for VERU-111 as a COVID-19 treatment, including favoring other treatment alternatives or imposing price controls on COVID-19 treatments; the risk that the Company's products may not be commercially successful; risks related to the impact of the COVID-19 pandemic on our business, the nature and extent of which is highly uncertain and unpredictable; risks relating to the ability of the Company to obtain sufficient financing on acceptable terms when needed to fund development and operations; product demand and market acceptance; competition in the Company's markets and therapeutic areas and the risk of new or existing competitors with greater resources and capabilities and new competitive product approvals and/or introductions; the risk that the Company's will be affected by regulatory developments, including a reclassification of products; price erosion, both from competing products and increased government pricing pressures; manufacturing and quality control problems; compliance and regulatory matters, including costs and delays resulting from extensive governmental regulation, and effects of healthcare insurance and regulation, including reductions in reimbursement and coverage or reclassification of products; some of the Company's products are in development and the Company may fail to successfully commercialize such products; risks related to intellectual property, including the uncertainty of obtaining patents, the effectiveness of the patents or other intellectual property protections and ability to enforce them against third parties, the uncertainty regarding patent coverages, the possibility of infringing a third party's patents or other intellectual property rights, and licensing risks; government contracting risks, including the appropriations process and funding priorities, potential bureaucratic delays in awarding contracts, process errors, politics or other pressures, and the risk that government tenders and contracts may be subject to cancellation, delay, restructuring or substantial delayed payments; the risk that delays in orders or shipments under government tenders or the Company's U.S. prescription business could cause significant quarter-to-quarter variations in the Company's operating results and adversely affect its net revenues and gross profit; a governmental tender award indicates acceptance of the bidder's price rather than an order or guarantee of the purchase of any minimum number of units, and as a result government ministries or other public sector customers may order and purchase fewer units than the full maximum tender amount or award; penalties and/or debarment for failure to satisfy tender awards; the Company's reliance on its international partners and on the level of spending by country governments, global donors and other public health organizations in the global public sector; risks related to concentration of accounts receivable with our largest customers and the collection of those receivables; the economic and business environment and the impact of government pressures; risks involved in doing business on an international level, including currency risks, regulatory requirements, political risks, export restrictions and other trade barriers; the Company's production capacity, efficiency and supply constraints and interruptions, including potential disruption of production at the Company's manufacturing facilities and/or of the Company's ability to timely supply product due to labor unrest or strikes, labor shortages, raw material shortages, physical damage to the Company's facilities, COVID-19 (including the impact of COVID-19 on suppliers of key raw materials), product testing, transportation delays or regulatory actions; risks related to the costs and other effects of litigation, including product liability claims; the Company's ability to identify, successfully negotiate and complete suitable acquisitions or other strategic initiatives; the Company's ability to successfully integrate acquired businesses, technologies or products; and other risks detailed in the Company's press releases, shareholder communications and Securities and Exchange Commission filings, including the Company's Form 10-K for the year ended September 30, 2019 and Form 10- Q for each of the quarters ended December 31, 2019 and March 31, 2020. All forward-looking statements are based on information available to us as of the date hereof, and Company does not assume any obligation and does not intend to update any forward-looking statements, except as required by law.
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Veru, the prostate cancer company, has revenues from Urology Specialty Pharmaceuticals and legacy product divisions
Veru
The Prostate Cancer
Company
Urology Specialty | The Female | |
Pharmaceuticals | Health Company | |
Division | Division | |
FC2 ®Female/internal | ||
TADFINTM- Targeting NDA | ||
submission late 2020 / early 2021 | condom | |
PREBOOST®/Roman Swipes | (legacy product) |
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Pipeline of proprietary product candidates
PRODUCT | TARGET | INDICATION | PRECLINICAL PHASE 1 PHASE 2 PHASE 3 | ||||
PROSTATE CANCER NOVEL MEDICINES | |||||||
Metastatic castration | Phase 1b | ||||||
and androgen | |||||||
blocking agent | Phase 2 | ||||||
Oral, targeted | resistant prostate | ||||||
cancer | Planned for Phase 3 | ||||||
α & β tubulin | |||||||
inhibitor | |||||||
VERU-111 | Nonmetastatic | ||||||
"Cytoskeleton | castration and | ||||||
disruptor" | androgen blocking | Planned for Phase 3 | |||||
agent resistant prostate | |||||||
cancer | |||||||
SARS-CoV-2 infection | Phase 2 | ||||||
Three-month depot | |||||||
VERU-100 | injection | Advanced prostate | Planned for Phase 2 | ||||
GnRH peptide | cancer | ||||||
antagonist | |||||||
Zuclomiphene citrate | Nonsteroidal | Hot flashes caused | Phase 2 | ||||
estrogen receptor | by prostate cancer | ||||||
agonist | hormone therapy | ||||||
Phase 1b portion completed and Phase 2 enrolling
Phase 3
FDA meeting Q3 2020
Phase 3
FDA meeting planned
2021
Completed positive
Phase 2
FDA meeting planned
2020
4
Experienced in clinical practice, drug development and commercialization
Mitchell Steiner, MD
CHAIRMAN, PRESIDENT & CHIEF EXECUTIVE OFFICER
CEO & President Aspen Park Pharmaceuticals, President of Urology at OPKO Health, Inc.; CEO GTx, Inc.; Hopkins trained urologist; Former Professor & Chairman of Urology University of Tennessee
Michele Greco, CPA | Gary Barnette, PhD |
CHIEF FINANCIAL & | CHIEF SCIENTIFIC OFFICER |
ADMINISTRATIVE OFFICER | Sr. VP Scientific and Reg Affairs |
CFO/EVP The Female Health | Camargo Pharm. Services, VP |
Clinical & Reg and Founder GTx, | |
Company, 28 years with Ernst & | |
Inc., Director Reg Affairs Solvay | |
Young, 15 years as an Audit | |
Pharma, Clinical Pharmacology/ | |
Partner | |
Biopharmaceutics Reviewer FDA, | |
PhD Basic Pharmaceutical | |
Sciences West Virginia University |
Harry Fisch, MD
CHIEF CORPORATE OFFICER &
VICE CHAIRMAN
Chairman Aspen Park Pharmaceuticals and Millennium Sciences, Inc.; urologist; Professor of Urology and Reproductive Medicine at New York Presbyterian/ Weill Cornell
Kevin Gilbert, JD, CPA
EVP CORPORATE
DEVELOPMENT
Corporate Development & Legal, Third Stream Bioscience, Attorney at McDermott, Will & Emery, Motorola, closed more than 100 transactions in 25 countries
Philip Greenberg, JD
EVP LEGAL
General Counsel Latin America Teva Pharmaceuticals with prior senior legal positions in international and North America divisions; Deputy General Counsel for IVAX Corporation
Phil Kuhn, MBA
EVP STRATEGY AND
COMMERCIALIZATION
Global Strategy and Commercial expertise in medical devices, diagnostics, and biologics; leadership roles at ISTO Biologics, Orthofix, Smith & Nephew, Boston Scientific, Johnson & Johnson, and
Abbott
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Prostate Cancer - Novel Medicines
6
Advanced prostate cancer is a chronic disease requiring active management of the disease and side effects from existing treatments
Our Strategy
New prostate cancer treatments directed to stopping cancer progression1
- Inadequate androgen deprivation therapy
- Testosterone surge during initial 2 weeks and repeated administration
- Micro increases in testosterone above 50ng/dL
- Testosterone not less than 20ng/dL
- Development of resistance to treatments
- Progression to metastases
- Skeletal related events with progression
New therapies to ameliorate side effects of prostate cancer treatments2
- Androgen Deprivation Therapy (ADT) - induced estrogen deficiency related side effects
- Hot flashes
- Bone loss and fractures
- Loss of libido
- Cognitive changes
- Adverse lipid changes
- Frailty- loss of muscle mass and strength because of testosterone deficiency
1So A et al Can Urol Assoc J 6:465-470 2012 ; 2Chen AC et al Current Urology Reports 6:210-216 2005
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Growing unmet need
Metastatic castration and androgen blocking agent resistant prostate cancer
Androgen blocking agent
- 15-25%of men have no response1
- 75-85%of men progress in 9-15 months1
ADT
Metastatic
hormone sensitive prostate cancer
Metastatic
castration resistant prostate cancer
ADT +
novel AB agent: enzalutamide or abiraterone
Metastatic castration and androgen blocking agent resistant prostate cancer
- Androgen Receptor (AR) targeted drug approaches have been exhausted
- Need for an oral drug with new mechanism of action
ADT = androgen deprivation therapy
AB agent= Androgen blocking agents: enzalutamide, abiraterone, and apalutamide
1ES Antonarakis. Clin Adv Hem Onc14:316-319 2016.
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Current therapeutic limitations to address this growing unmet medical need in metastatic castration resistant prostate cancer
- AR targeted drugs have been exhausted in the treatment of advanced prostate cancer1
- Men who progress on androgen blocking agents are being treated with IV chemotherapies which have challenges2
- Only available as intravenous administration
- Drug resistance is common- multidrug resistance proteins, tubulin mutations and overexpression
- Safety concerns - hypersensitivity reactions, neutropenia, and neurotoxicity (peripheral neuropathy & muscle weakness)
- We believe that an oral drug that has a different mechanism of action with a well tolerated side effect profile is needed so that the drug may be prescribed by both urologists and medical oncologists
1Ahmed, Alia et al. "Advances in androgen receptor targeted therapy for prostate cancer." Journal of cellular physiology vol. 229,3 (2014): 271-6. doi:10.1002/jcp.24456; | |
2Diamond E et al Curr Treat Options Oncol 16:9 2015; | 9 |
VERU-111 targets the cytoskeleton: "Railroad tracks disruptor"
Binds to α & β tubulin subunits of microtubules to disrupt intracellular receptor transport
Targets cytoskeleton and disrupts | Preclinical Product profile1-4,6 | |
microtubule assembly5 | ||
•Binds to "colchicine binding site" to crosslink α and β subunits to | ||
inhibit microtubule polymerization (low nM concentration) | ||
•High oral bioavailability | ||
•Not a substrate for multidrug resistance proteins (P-gp, MRPs, and | ||
BCRP) | ||
•Not a substrate for CYP3A4 | ||
•Decreases production of βI, βIII and βIV tubulin isoforms | ||
•Cleaves Poly (ADP-ribose) polymerase (PARP) protein | ||
•Favorable toxicity profile no neurotoxicity and no neutropenia or | ||
myelosuppression | ||
•Demonstrated activity against taxane, vinca alkaloid, | ||
VERU-111 | doxorubicin, enzalutamide, and abiraterone resistant prostate | |
cancers | ||
(Crosslinks α and β subunits to inhibit | •Has broad activity against other tumor types as well | |
microtubule polymerization) |
1Chen J et al. J Med Chem 55:7285-7289 2012 |2Li CM et al. Pharm Res 29:3053-3063 2012 |3Lu Y et al. J Med Chem 57:7355-7366 2014 |428 day rat and dog
toxicity studies on file at Veru, Inc.| 5Dumontet C et al. Nature Reviews Drug Discovery 9:790, 2010 | 6Markowski M et al J Clin Onc 37:167, 2019 | | 10 |
VERU-111 clinical development:
Positive results reported in May 2020 for Phase 1b clinical trial conducted in 7 US centers
- Trial design is an open label standard 3X3 to determine Maximum Tolerated Dose (MTD) in men who have metastatic castration resistant prostate cancer and who have also become resistant to an androgen blocking agent
- 7 day dose schedule- increasing doses per cohort of 3 after 1 cycle of 7 days oral daily VERU-111 followed by 14 days off drug for a 21 day cycle
- Expanded dose schedule- men who tolerated 7- day dosing cycle continued to 14 days on VERU- 111 followed by 7 days off and then to continuous dosing for full 21-day cycle. No drug holiday between cycles
- Patient characteristics
- Age - mean 75.6 years (range61-92 yo)
- 30 men were chemotherapy naive
- 9 men had previous IV taxane
- 30% had both abiraterone and enzalutamide
- Safety results
- Dose escalated from 4.5mg to 81mg
- MTD was determined to be 72mg; 3 of 11 men had reversible Grade 3 diarrhea
- Recommended Phase 2 dose is 63mg for continuous21-day cycle
- No Grade 3 diarrhea reported at doses ≤
63mg - No reports of neutropenia or neurotoxicity at doses ≤ 63mg
- No Grade 3 diarrhea reported at doses ≤
- Most common adverse events (mostly Grade 1 & 2)
- Nausea
- Vomiting
- Diarrhea
- Fatigue
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VERU-111 clinical development:
Positive results reported in May 2020 for Phase 1b clinical trial conducted in 7 US centers
Efficacy (antitumor activity)
- 8 men have reached at least four21-day cycles of continuous dosing
- PSA responses
- 6/8 had decrease in PSA
- 4/8 had ≥ 30% decline in PSA
- 2/8 had ≥ 50% decline in PSA
- Objective tumor responses
- 2 men had partial response (PR) (additional PR occurred in a subject who did not reach 4 cycles)
- 6 men had stable disease (SD)
- 7/8 men still on study with median duration of response 10 months (range6-14 months)
- Total of 10 men still on study1
- 7 men ≥ 4 continuous dosing for21-day cycles
- 3 men ≤ 4 continuous dosing for21-day cycles
Efficacy signals:
Eight men have reached ≥ 4 21-day cycles of continuous dosing
1As of May 05, 2020 | 12 |
VERU-111 Phase 1b clinical study case study
Subject with metastatic castration resistant node only disease dosed 3/19 after prostate cancer progression following treatment with leuprolide, bicalutamide, sipuleucel-T, enzalutamide, and abiraterone. VERU-111 for 11 months and -63% PSA from peak.
3/19 Screening CT scan: right anterior psoas muscle | 11/19 Screening CT scan: right anterior psoas muscle | |
cancerous lymph node 1.7cm X 1.4cm | cancerous lymph node 1.1cm X 1.0cm | 13 |
VERU-111 clinical development plan:
Open label Phase 2 clinical trial initiated 2/26/20 is enrolling
First in class, novel oral antitubulin agent that disrupts the cytoskeleton
Indication: metastatic castration resistant prostate cancer that has also become resistant to androgen blocking agent and prior to IV chemotherapy
Androgen blocking agent
•15-25% of men have no response1
•75-85% of men progress in 9-15 months1
ADT +
novel AB agent: | ||
Open label Phase 2 | ||
ADT | enzalutamide or | |
abiraterone | VERU-111 | |
(n=26) | ||
Metastatic | Metastatic | Metastatic castration and |
hormone sensitive | castration resistant | androgen blocking agent resistant |
prostate cancer | prostate cancer | prostate cancer with rising PSA |
and tumor progression |
Phase 2 trial design
- VERU-11163mg daily oral continuous dosing for 21- day cycles
- Efficacy endpoints
- Imaging-basedprogression free survival
- PSA responses (reductions)
- Monitor safety
1ES Antonarakis. Clin Adv Hem Onc14:316-319 2016. | 14 |
VERU-111 clinical development plan:
VERU will meet with FDA next quarter to reach agreement on pivotal Phase 3 clinical trial
- First indication: chemotherapy naïve men who have metastatic castration resistant prostate cancer and have failed one androgen blocking agent (abiraterone or enzalutamide)
- No FDA approved drug currently for this indication
- Phase 3: Efficacy and safety ofVERU-111 versus an alternative androgen blocking agent (abiraterone or enzalutamide) in men with metastatic castration resistant prostate cancer who have developed cancer progression while receiving an androgen blocking agent
Phase 3 trial design
- Open label
- VERU-11163mg daily oral continuous dosing for 21-day cycles versus an alternative androgen blocking agent
- Efficacy endpoints
- Primary endpoint
- Imaging-basedprogression free survival
ADT +
novel AB agent: enzalutamide or abiraterone
Metastatic | Metastatic castration and androgen |
blocking agent resistant | |
castration resistant | |
prostate cancer with rising PSA and | |
prostate cancer | |
tumor progression | |
VERU-111
63mg/day
Alternative androgen blocking agent
-
Secondary endpoints
Open label Phase 2
SequentialVERU-111•PSA responses (reductions) (n=26)•Assumptions
- Median iPFS- 9 months for VERU- 111 vs 3.4 months for Alternative
ABA - Sample size - 250 men
- 90% power, alpha=0.05, 6 months recruitment time, 12 month follow up
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VERU-111 market opportunity
- Estimated annual market for advanced prostate cancer drugs
- $6 billion market for novel androgen blocking agents for prostate cancer in 20181
- ZYTIGA®(abiraterone) $3.5 billion
- XTANDI®(enzalutamide) $2.59 billion
Prechemotherapy estimated annual | ||
market for oral agents for prostate cancer | ||
$4.9 billion global | ||
2018 - $6 billion | ||
annual sales in Japan, | ||
global annual sales; | ||
the Americas, EMEA, | ||
$3.1 billion in the US 1 | ||
15-25% of men have no response3 | Asia and Oceania 2,4 | |
Novel androgen | $1.5 billion | |
blocking agents for | 75-85% of men progress in 9-15 months3 | |
mCRPC | ||
$3.4 billion | ||
1MME LLC, Prostate Cancer Market Revenues (2018); 2Johnson & Johnson. 2019 Annual Report; 3ES Antonarakis. Clin Adv Hem Onc14:316-319 2016.;
4Astellas Pharma Inc. 2019 Annual Report | 16 |
VERU-111 has global intellectual patent protection
- Licensed from the Ohio State Innovation Foundation in 2015
- Composition of matter (molecule and polymorphs) issued or allowed patents
- 2 US latest expiry 2031 (with possible patent extension for NCE expiry 2036)
- 1 EU latest expiry 2029
- 2 Japanese latest expiry 2031
- 6 other countries (not counting EU jurisdictions)
- 4 patents pending
- Method of useVERU-111 for the treatment of prostate and breast cancer issued or allowed patents
- 3 US latest expiry 2031
- 1 EU latest expiry 2029
- 1 Japanese latest expiry 2029
- 6 other countries (not counting EU jurisdictions)
- 4 patents pending
- Other methods of useVERU-111
- 2 US latest expiry 2034
- 2ex-US latest expiry 2034
- 15 patents pending
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Veru's strategy is to focus on prostate cancer
VERU-111 clinical development plan summary
First in class, novel oral antitubulin agent that disrupts the cytoskeleton
Phase 1b | Phase 2 | Planned Phase 3s | ||||||||
Indication 1: Chemotherapy naïve metastatic | ||||||||||
castration and novel androgen blocking agent | ||||||||||
resistant prostate cancer | ||||||||||
Plan to meet with FDA | ||||||||||
Chemotherapy-naive | ||||||||||
Metastatic castration and | Q3 2020 | |||||||||
novel androgen blocking | Metastatic castration and | |||||||||
agent resistant prostate | novel androgen blocking | |||||||||
cancer ± 1 taxane | agent resistant prostate | |||||||||
(n=39) | cancer (n= 26) | |||||||||
Indication 2: Nonmetastatic castration and | ||||||||||
novel androgen blocking agent resistant | ||||||||||
12/18 FPI | 2/20 FPI | prostate cancer | ||||||||
Fully enrolled | Study enrolling | |||||||||
10 men still on study | 15 men on study | |||||||||
Plan to meet with FDA | ||||||||||
2021 |
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VERU-111 has shown antitumor activity in preclinical models of other tumor types:
- Triple negative breast cancer (taxane resistant)1
- Cervical cancer (taxane resistant)2
- Lung cancer (taxane resistant)3
- Ovarian cancer (taxane resistant)4
- Uterine cancer5
- Pancreatic cancer6
- Melanoma7
- Human promyelocytic leukemia (vincristine resistant)8
1Deng S et al Mol Cancer Ther 19:348-63, 2020 | 2Kashyap VK et al Cancer Lett 470:64-74, 2020 | 3Foyez M et al Data on file Veru, Inc. 2020 | 4,5Data on file Veru, Inc. 2020 |6Kashyap V et al J Experimental and Clinical Can Res 38:29, 2019 | 7Chen J et al J Med Chem 55:7285-7289, 2012; Hwang DJ et al ACS Med Chem Lett 6:993-997, 2015| 8Data on file Veru, Inc. 2014 |
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Quest for a better androgen deprivation therapy
Current commercial limitations
LHRH agonist | GnRH antagonist | ||
Long-acting products: LUPRON® | FIRMAGON® (degarelix) (SC) | ||
Depot (IM) and ELIGARD® (SC) are | |||
leuprolide products | |||
•Painful injection as | |||
•Concerns over initial surge | degarelix requires large | ||
in T levels- "T surge" | loading and | ||
maintenance dose | |||
• | Escapes from castration T | injected subQ | |
levels - periodic increases | |||
in T levels1 | • | Loading 6mL (2X | |
3mL) | |||
•Up to 17% of men do not | • | Maintenance 4 mL | |
achieve castration1 | every month | ||
• | Does not suppress FSH | •No long acting depot | |
available; must be given | |||
• | Generic | every month |
1Gomella LG et Rev Urol 2009 11:52-60.
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New potential product to addresses limitations of current ADT Long-acting 3 month depot GnRH antagonist may provide better alternative
VERU-100 target product profile2
- Novel proprietary GnRH antagonist decapeptide formulation1
- 3 month slow release subQ depot (1cc SQ injection) with no loading dose
- Immediate testosterone suppression no initial testosterone surge
- Suppression of testosterone to less than 20ng/dL
- Fewer testosterone escapes(micro-increases in testosterone)
- No black box warning for cardiovascular adverse effects
- Sustained suppression of FSH
1Developed in collaboration with Drug Delivery Experts, LLC (San Diego, California); 2Veru Inc. VERU-100 Target Prescribing Information | 21 |
VERU-100 for the treatment of advanced prostate cancer Clinical development program has been discussed with FDA
- Pre-INDmeeting with FDA on April 19, 2019 reached agreement on an expedited regulatory pathway:
- Clinical supply GMP manufacturing in progress
- Single Phase 2 - Open label, multicenter dose finding study of three doses ofVERU-100 in men with advanced prostate cancer (n=35)
- Single Phase 3 - Open label multicenter in men with advanced prostate cancer (n=100) - confirmed a single study with 100 men acceptable for pivotal study and NDA submission
- Veru plans to submit an Investigational New Drug application 3Q 2020 to support initiation of Phase 2 dose finding study
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ADT market for advanced prostate cancer is well established
Total global sales of ADT drugs in 2018 was $2.6 billion (IQVIA 2018)
VERU-100 could have peak sales of $750 million with 28% global market share
Year | Total | |
US | Ex-US | |
2018 | $1,150M1 | $1,484 M1 |
Intellectual property
Formulation patents expire in 2038
1MME LLC,VERU-100 Market as ADT for Advanced Prostate Cancer (2018)
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Androgen deprivation therapy for advanced prostate cancer
Estrogen deficiency related side effects
- Androgen deprivation therapy reduces testosterone and estrogen to castrate levels resulting in estrogen deficiency
Low estrogen side | Low testosterone side | ||
effects | effects | ||
• | Hot flashes | • | Muscle loss |
•Bone loss and fractures | |||
• | Frailty | ||
• | Loss of libido | ||
• | Muscle weakness | ||
• | Memory loss | ||
• | Increase fat body composition | ||
• | Unfavorable lipid changes | ||
Adapted from: Freedland S et al. Prostate Cancer and Prostatic Diseases 12:333-338 2009
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Hot flashes are one of the most common and debilitating side effects of androgen deprivation therapy1,2
Occur in up to 80% of men treated with ADT (leuprolide or degarelix) with 30- 40% having moderate to severe hot flashes1-3
Symptoms do not subside over time
- 48% of men at 5 years and 40% of men at 8 years still suffer from hot flashes2
Concern over hot flashes make patients less likely to begin ADT and can lead to early discontinuation3
1Gomella LG et al BJU IntS1:25-29 2007|2Karling P et al. J Urol152:1170-1173 1994|3Gonzalez BD et al J Urol 194:690-695 2015|
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Zuclomiphene, an oral estrogen receptor agonist, is planning to advance into pivotal Phase 3 following report of positive interim topline results from Phase 2 placebo controlled dose finding study
93 men who have moderate & severe hot flashes on ADT randomized in 24 US clinical sites
- Trial design- 12 week duration
- Primary efficacy endpoint- change in frequency of moderate & severe hot flashes from baseline
- Interim topline Day 42 results reported January 2020
- Hot flashes reduction from baseline
- 10mg group (p=0.15) - No effect
- 50mg group (p<0.001)
- Hot flashes at Day 42
- 50mg group(-41% reduction) vs No effect 10mg group (-21% reduction) (p= 0.03)
- Estrogenic biomarkers- estrogenic activity of 50 mg versus 10mg and placebo (p<0.0001)
- Safety data base- Zuclomiphene appears to be well tolerated with no reports of drug related SAEs and no reports of special interest side effects: gynecomastia, breast tenderness, or VTEs
Placebo | |
Randomize | |
10 mg | |
50 mg | |
Treatment duration 12 weeks
Next steps:
- Plan to have end of Phase 2 meeting with FDA in 2020
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Zuclomiphene:
Potential to be the first FDA approved drug for ADT-induced hot flashes
Market potential
- Indication: treatment ofADT-induced moderate to severe hot flashes in men with advanced prostate cancer
- Estimated 600,000 men on ADT in the U.S.1
- Number of men with hot flashes in 2020 expected to be 475,561 and 243,487 will have moderate to severe hot flashes2
- Independent market research sponsored by Veru estimates$600-800 million/year expected sales for Zuclomiphene in US 3
Intellectual property
- Patent (U.S. No. 9,913,815) issued March 2018 and Patent U.S. 10,463,635 issued January 2019 with expiry 2035- method of use
1Scher et al. PLoS ONE 2015 10:1-12 (DOI:10.1371/journal.pone0139440|2Delveinsight "Hot flashes associated with prostate cancer treatment: Market insights,
epidemiology, and market forecast. December 2019| 3Independent market research - Medical Marketing Economics, LLC 2018 | 27 |
SARS-CoV-2
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Global medical need for the treatment of coronavirus, also known as COVID-19 or SARS-CoV-2
SARS-CoV-2 Pandemic
- SARS-CoV-2is an enveloped, nonsegmented, positive RNA virus that has club-like spikes on surface
- Global pandemic with over 4,308,357 cases and 290,165 deaths worldwide and rising1
- Clinical presentation2
- Mild disease (81%) - URI symptoms with dry cough, sore throat, headaches, and muscle pain
- Severe disease (14%) - Dyspnea, blood oxygen saturation of <93% and lung infiltrates on imaging study with24-48 hours
- Critical disease (5%) - Respiratory failure, septic shock, and/or multiple organ failure as a result of a "cytokinestorm"---inflammatory over reaction that leads to shock and extensive tissue damage
- Treatment - supportive care and oxygen with mechanical ventilation and hemodynamic support for septic shock
- Mortality rates appear to be around 3.4%3
1Worldometers.info 5/12/2020 | 2Chinese CDA and Cascella et al 2020 | 3WHO March 09,2020
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Design drugs to target well-conserved coronavirus viral-host interactions: cytoskeleton (microtubules) and the SARS-CoV-2 replication cycle
Virus's most critical task is to hijack the host's internal transportation system, the microtubules in the cytoskeleton1
- Given the spatial distances between the point of virion entry at the plasma membrane to the different locations in the cell for viral replication and release of infectious virions out of the cell
- Viruses take control of their host's cellular machinery to carry out viral replication, assembly and to exit from the cell to spread infectious virions
- The cytoskeleton has three major types of protein filaments: microfilaments (actin), microtubules (tubulin), and intermediate filaments. The principal ones involved in viral replication and trafficking (transport) are microtubules and actin which are involved in cellular transport
- Microtubules are dynamic network systems
- Target microtubule networks to disrupt intracellular trafficking to impair virus and host interactions may be an effective way to treat coronavirus infections.
Microtubule trafficking highway network2
1Ward B Virology 411:244-250, 2011| 2Taken from Alsaadi et al Future Virology 14:275, 2019
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Coronavirus's spike (S) protein is the key structure that interacts with microtubules in the cytoskeleton during intracellular trafficking4
- The first stage of interaction with the microtubule cytoskeleton occurs when the spike (S) protein on the surface of coronavirus mediates attachment to the cell surface.1
- Interactions between tubulin and the cytosolic domain of the S protein of humancoronavirus-229E, human coronavirus-NL63, and TGEV are required for successful entry, assembly and release (egress) of viral particles.2
- Rudiger et al. (2016) demonstrated the interaction of tubulin is the last 39 amino acids of the S protein cytoplasmic tail ofalphacoronavirusesTGEV, human coronavirus NL63, and human coronavirus 229E and well as betacoronavirushuman SARS- CoV.2
Coronavirus | ||||||
Coronavirus | ||||||
egress3 | ||||||
entry3 | ||||||
SARS-CoV-2 structure4
1Ren et al Scientific Reports 5:11451,2015; 2Rudiger et al Virology 497:185-197, 2016|3Taken and adapted from Simpson et al. Viruses 12:117, 2020 | 4Taken from
Alsaadi et al Future Virology 14:275, 2019
31
Microtubule depolymerization agent, colchicine, has antiviral activity and has potent anti-inflammatory effects, but also has serious safety concerns
Colchicine- broad spectrum activity against multiple types of viruses in vitro
- Active against:
- Moloney Murine Leukemia virus4
- Porcine Reproductive and Respiratory Syndrome virus5
- Zika virus6
- Dengue6
- Respiratory Syncytial Virus7
Colchicine1is indicated for treatment of inflammation associated with:
- Gout
- Familial Mediterranean Fever (general polyserositis)
- Evidence that colchicine can reduce cytokine storm and septic shock2,3
- However, clinically colchicine has low therapeutic index,drug-drug interactions (substrate for P-gp), and potential for serious safety issues8
1Slobodnick A et al. Rhuematology 57:i4-i11, 2018 |2LaRiviere WB et al Amer J Res Crit Care Med 2020 Pubmed 31898912| 3Verweyen E et al. Amer J Res Crit Care Med 201:526,2020| | 5Cafruny WA et al. Virology
J 3:90, 2006| Taken from Alsaadi et al Future Virology 14:275, 2019|6Richter et al. Chemmedchem 14:469-483, 2019| 7Lu N et al. 3 Biotech 9:392, 2019| | 8Finkelstein Y et al. J Clin Tox 48:407-414, 2010. | 32 |
VERU-111 is a more potent inhibitor of microtubule polymerization than colchicine
in vitro1
Microtubule polymerization
Control
Colchicine (5 microM)
VERU-111 (5 microM)
VERU-111 (10 microM)
Tubulin (0.4 mg/assay) was exposed to 5, 10 μM of VERU-111 (6a) versus vehicle control, 5% DMSO
1Chen J et al. J Med Chem 55:7285-7289 2012 | 33 |
VERU-111, as a microtubule depolymerization agent, may have a two-pronged approach to the treatment ofSARS-CoV-2:antiviral andanti-inflammatoryagent
- Based onVERU-111's mechanistic similarities to other microtubule depolymerizing agents as well as its preclinical and clinical efficacy and safety experience:
- As an antiviral, it may have direct effects on Sprotein-microtubule trafficking with the potential to reduce the production of infectious virions particularly by affecting viral replication and assembly and virion egress.
- As ananti-inflammatory agent, it may reduce virally induced severe inflammation in the respiratory system and may reduce the incidence of cytokine storm and septic shock that can occur in patients that progress to severe acute respiratory pneumonia.
34
VERU-111as a potential treatment forSARS-CoV-2:Clinical development plan
Double-Blind,Placebo-Controlled, Phase 2 Study of VERU-111 for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Patients at High Risk for Acute Respiratory Distress Syndrome (ARDS)
- Approximately 40 subjects will be randomized 1:1 (20 18mgVERU-111 and 20 Placebo groups)
- Hospitalized subjects with documented evidence ofCOVID-19 infection with symptoms for less than 8 days and who are at high risk for ARDS will be enrolled.
- Subjects will receive study drug for up to 21 days.
- The primary efficacy endpoint of the study will be the proportion of patients that are alive and without respiratory failure at Day 29.
- Secondary endpoints include measured improvements on the WHO Disease Severity Scale (8 point ordinal scale)1
- The total study duration for a patient from screening to follow up visit is planned to be 62 days.
1WHO R&D Blueprint novel Coronavirus COVID-19 Therapeutic Trial Synopsis. World Health Organization 2/18/2020 Geneva, Switzerland p 5-6.
35
VERU-111, a novel microtubule polymerization agent, as a potential treatment for SARS-CoV-2: Regulatory pathway
Regulatory update
- FDA program: Coronavirus Treatment Acceleration Program (CTAP)
- FDA granted IND permission on May 12, 2020
- Phase 2 expected to commence in May 2020
36
Urology Specialty Pharmaceuticals
37
TADFINTMcapsule (tadalafil 5mg + finasteride 5mg combo) to improve compliance & safety
Co-administration of CIALIS (tadalafil 5 mg) and PROSCAR (finasteride 5 mg) is currently approved for the initial treatment of symptoms of BPH for up to 26 weeks1
- Drug-druginteraction and co- administration studies are completed for combination indication2
Each component is approved or, for PROSCAR, used off label for:
-
CIALIS (tadalafil 5 mg) daily- symptoms of
BPH and erectile dysfunction - PROSCAR (finasteride 5 mg)- symptoms and signs of prostate enlargement to decrease prostate size, reduces risk of acute urinary retention and need for surgery and prevents growth.
- PROPECIA (finasteride 1mg) daily- symptoms ofmale pattern hair loss
The solution: proprietary TADFINTMtablet formulation
- Increases convenience and compliance
1Cialis (tadalafil) FDA Package Insert | 2Casabé A et al. J Urol 191:727-733 2014
38
Pre-NDA meeting on Proprietary TADFINTMcapsule
- Single dose randomized two period, crossover study in 33 healthy males over the age 45 years
- Tadalafil Cmaxin TADFIN is 25% less than Tadalafil alone
- Process of getting 12 month stability data on commercial batches
- Pre-NDAmeeting held May 23, 2019
- NDA may be submitted after 12 months of stability data on manufactured/commercial drug batches
- NDA expected to be submitted in late 2020/early 2021
39
TADFINTMfor benign prostatic hyperplasia - market opportunity
Market potential
- BPH market is up to 25% of male population and estimated 1.1 billion males worldwide in 20181
- Company estimates US and global markets to be >$200 million through telemedicine and salesforce channels2
- Target men who have enlarged prostate >30cc as a cause for symptoms and signs of BPH
- Plan to launch via telemedicine channels and license US andex-US for upfront payments and royalties to urology specialty pharmaceutical companies
1Eikelany O et al. Therapeutics and Clinical Risk Management 11:507-513, 2015. ; 2IQVIA Data (2018) Assumption: $120 per prescription
40
Roman Swipes (PREBOOST®; 4% benzocaine wipes for premature ejaculation)
Veru entered into supply and distribution agreement with Get Roman (Roman Health Ventures Inc.) in February 2019
- Telemedicine company
- Multi-yearUS supply and distribution agreement
- Minimum sales requirement obligates purchase of millions/year
- US only
- Marketed as "Roman Swipes"
41
FC2®Female/internal Condom business revenues are growing
FC2 Female/Internal Condom is the only FDA approved female use product to prevent pregnancy and transmission of sexually transmitted infections
- Sold in U.S. and 149 other countries
- Manufacturing plant with annual capacity of 100 million units
- Public sector customers include UNFPA, USAID, Brazil, and South Africa
- FC2 business profitable from FY2006-present1
Rapidly growing US prescription business for high margin revenues
- Prescription business is rapidly growing via existing and new contracts with multiple telemedicine partners
1For fiscal year 2006 through fiscal year 2016, profitability is based on Veru's net income attributable to common stockholders. For fiscal year 2017, the first fiscal year which includes the financial results of Aspen Park Pharmaceuticals, Inc., profitability is based on operating income from our commercial segment.
42
Financial highlights: Veru Business Six Months Ended March 31, 2019 vs. 2020
Six Months Ended | Six Months Ended | |
March 31, 2019 | March 31, 2020 | |
43
Financial highlights: Veru Business Three Months Ended March 31, 2019 vs. 2020
Three Months Ended | Three Months Ended | |
March 31, 2019 | March 31, 2020 | |
44
Veru projected milestones
PRODUCT | INDICATION | 2019 |
PROSTATE CANCER NOVEL MEDICINES | ||
Metastatic castration | P1b | |
resistant & androgen | ||
blocking agent resistant | ||
prostate cancer | ||
VERU-111 | Nonmetastatic castration | |
Oral antitubulin | resistant & androgen | |
blocking agent resistant | ||
prostate cancer | ||
SARS-CoV-2 infection | ||
VERU-100 | Advanced hormone | |
GnRH antagonist | Pre-IND | |
sensitive prostate | ||
3 month subcutaneous | ||
cancer ADT | ||
depot | ||
Zuclomiphene | Hot flashes caused by | P2 |
Estrogen receptor | ||
ADT | ||
agonist |
Represent Management's current expectations and are not a guarantee of future results.
2020 | 2021 | 2022 |
P2
P3
P3
P2 | Intend to seek nondilutive | |
cash to fund Phase 3 | ||
IND | P2 | P3 |
P3 - 1
P3 - 2
2023
NDA
NDA
NDA
45
Veru projected milestones
PRODUCTINDICATION20192020202120222023
UROLOGY SPECIALTY PHARMACEUTICALS DIVISION* | ||||
TADFINTM | BPH | BE | NDA | US launch |
(tadalafil/finasteride) | ||||
Roman Swipes | Premature | ` | Marketed | |
ejaculation | ||||
THE FEMALE HEALTH COMPANY DIVISION | ||||
FC2 | Dual birth control | Marketed | ||
& STI prevention | ||||
Represent Management's current expectations and are not a guarantee of future results. | |
*Tamsulosin DRS granules and XR capsules and Solifenacin granules development programs are currently on hold | 46 |
Next Steps for 2020
Clinical stage assets
- VERU-111-
- Complete enrollment of in June 2020 for Phase 2 clinical study- Metastatic castration & androgen blocking agent resistant prostate cancer prior to IV chemo
- Meet with FDA and commence Planned pivotal Phase 3 clinical study - Metastatic castration & androgen blocking agent resistant prostate cancer prior to IV chemo
- InitiateSARS-CoV-2 Phase 2 clinical trial
- VERU-100- Aim to initiate Phase 2 clinical study in the 2nd half of 2020
- Zuclomiphene - Meet with FDA to reach agreement for planned Phase 3 clinical study
Sales of urology specialty products and legacy product - Believe that FC2 can continue to deliver strong sales revenue to support investment in the development of clinical prostate cancer drugs
- PREBOOST/Roman Swipes - Continue to grow sales via telemedicine
- FC2 female/internal condom - Increase sales in global public sector and US prescription business
- Target submission of TADFINTMfor BPH NDA by the end of 2020
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Veru Inc. published this content on 29 May 2020 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 29 May 2020 07:45:05 UTC