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Saatja: Peep Peterson <[email protected]> Saadetud: 04.08.2022 20:56 Adressaat: SM Info <[email protected]> Teema: Fwd: EMA’s Emergency Task Force (ETF) first review under Article 18 of the use of Sabizabulin for treating COVID-19 patients. Manused: EVIDoa2200145.pdf; Final NEJM Evidence PR__2.pdf; Final_EMA Review Sabizabulin for COVID.pdf; Final_MHRA Expedited Review Sabizabulin for COVID.pdf Outlook Androidi jaoks From: Sergi Trilla <[email protected]> Sent: Thursday, August 4, 2022 1:16:45 PM To: [email protected] <[email protected]> Subject: EMA’s Emergency Task Force (ETF) first review under Article 18 of the use of Sabizabulin for treating COVID-19 patients. To: Peep Peterson Minister of Health and Labor ****** Dear Mr. Peterson, I hope this email finds you all well. Thank you so much for allowing us to introduce you to our NCE, Sabizabulin. We are very proud to be the first product to be reviewed under the recent Article 18 of EMA Regulation 2022/123 for Emergency Use. Veru Inc. (NASDAQ: VERU) is a Miami-based biopharmaceutical company focused on developing novel medicines for COVID-19 and other viral and ARDS-related diseases and managing breast and prostate cancers. The Company announced on June 7, 2022, that it had submitted an Emergency Use Authorization request to the FDA for its novel, oral, once-daily sabizabulin treatment of moderate to severe hospitalized COVID-19 patients at high risk for ARDS. We are working towards having the drug available in Europe as soon as possible. The good news is that EMA is reviewing data on sabizabulin for COVID-19. As you will read on the following link dated July 27th, the review will assist the EU Member States, who may consider allowing the use of the medicine before a possible authorization. Moreover, the study is the first to be triggered under Article 18 of the new EU regulation (Reg 2022/123), which expanded the role of EMA during public health emergencies. The ETF will conduct this review and send recommendations to the Agency’s human medicines committee (CHMP), which will issue the Agency’s opinion. https://www.ema.europa.eu/en/news/ema-reviewing-data-sabizabulin-covid-19 I am attaching the NEJM publication that the EMA refers to and the last PRs we have launched. As we are already doing with other MoH in Europe and around the globe, we would like to open discussions with you to understand better this new procedure and the options to have the drug available for patients as soon as possible. I look forward to hearing from you soon and learning from your thoughts on potential next steps. Have a great day, Prof. Trilla The Patient Is Waiting! “The Patient is Waiting” is an old saying that seems appropriate at this time for Veru and is my reminder to quit wasting time and get back to work. Prof. Dr. Sergi X. Trilla, MBA Chief Business Officer 2916 North Miami Avenue, Suite 1000 Miami, FL 33127 Cell Europe: +34 679 430 460 Cell America: +1 (917) 310-3012 [email protected] NASDAQ: VERU Published July 6, 2022 DOI: 10.1056/EVIDoa2200145 ORIGINAL ARTICLE Oral Sabizabulin for High-Risk, Hospitalized Adults with Covid-19: Interim Analysis K. Gary Barnette, Ph.D.,1 Michael S. Gordon, M.D.,2 Domingo Rodriguez, M.D.,1 T. Gary Bird, Ph.D.,1 Alan Skolnick, M.D.,3 Michael Schnaus, M.D.,4 Paula K. Skarda, M.D.,5 Suzana Lobo, M.D.,6 Eduardo Sprinz, M.D.,7 Georgi Arabadzhiev, M.D.,8 Petar Kalaydzhiev, M.D.,9 and Mitchell Steiner, M.D.1 for the Phase 3 COVID-19 Investigators* Abstract BACKGROUND Sabizabulin is an oral, novel microtubule disruptor that has dual antiviral and anti-inﬂammatory activities in preclinical models. METHODS A randomized, multicenter placebo-controlled phase 3 clinical trial was con- ducted with hospitalized patients with moderate to severe Covid-19 who were at high risk for acute respiratory distress syndrome (ARDS) and death. Patients were randomly assigned (2:1) to 9 mg of oral sabizabulin or placebo daily (up to 21 days). The primary end point was all-cause mortality up to day 60. Key secondary end points were days in the intensive care unit (ICU), days on mechanical ventilation, and days in the hospital. RESULTS A total of 204 patients were randomly assigned to treatment: 134 to sabizabulin and 70 to placebo. Baseline characteristics were similar. Sabizabulin superiority was dem- onstrated by a planned interim analysis for the ﬁrst 150 randomized patients. Sabizabulin treatment resulted in a 24.9 percentage point absolute reduction and a 55.2% relative reduction in deaths compared with placebo (odds ratio, 3.23; 95% CI conﬁdence interval, 1.45 to 7.22; P50.0042). The mortality rate was 20.2% (19 of 94) for sabizabulin versus 45.1% (23 of 51) for placebo. For the key secondary end points, sabizabulin treatment resulted in a 43% relative reduction in ICU days (P50.0013), a 49% relative reduction in *A complete list of the Phase 3 days on mechanical ventilation (P50.0013), and a 26% relative reduction in days in the COVID-19 investigators is hospital (P50.0277) versus placebo. Adverse and serious adverse events were lower in provided in the Supplementary Appendix, available at the sabizabulin group compared with the placebo group. evidence.nejm.org. CONCLUSIONS Sabizabulin treatment resulted in a 24.9% absolute reduction in deaths The author afﬁliations are listed at the end of the article. compared with placebo in hospitalized patients with moderate to severe Covid-19 at high risk for ARDS and death, with a lower incidence of adverse and serious adverse Dr. Barnette can be contacted at [email protected] or at events compared with placebo. (Funded by Veru, Inc.; ClinicalTrials.gov number, Veru, Inc., 2916 N. Miami Blvd., NCT04842747.) Ste. 1000, Miami, FL 33127. NEJM Evidence is produced by NEJM Group, a division of the Massachusetts Medical Society. Downloaded from evidence.nejm.org on July 6, 2022. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. All rights reserved. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. intensive care unit (ICU), and days on mechanical ventila- tion. Sabizabulin had an acceptable side effect and safety Introduction proﬁle with no clinically meaningful differences in safety T he coronavirus disease 2019 (Covid-19) pan- observations compared with placebo, except for a higher demic is in its third year, with more than 509 incidence of respiratory failure and death in the placebo million conﬁrmed cases and 6.2 million deaths group.27 Accordingly, a randomized, double-blind, multi- worldwide thus far.1 There are now effective vaccines for center, global placebo-controlled phase 3 clinical trial was the general population2 and antiviral agents (molnuparivir conducted with hospitalized patients with moderate to and nirmatrelvir) for symptomatic patients in the nonho- severe Covid-19 infection who were at high risk for ARDS spitalized setting.3,4 However, despite the availability of and death. Here, the sabizabulin efﬁcacy and safety the antiviral remdesivir5 and anti-inﬂammatory/immuno- results from this study are reported. modulators including dexamethasone,6 anti-interleukin-6 receptor antibodies,7 and Janus kinase inhibitors8,9 for hospitalized patients at high-risk for acute respiratory dis- tress syndrome (ARDS), mortality and morbidity rates Methods remain signiﬁcantly high. OBJECTIVES, PATIENTS, AND OVERSIGHT The principal therapy for hospitalized patients with mod- Eligible patients were required to meet the following crite- erate to severe Covid-19 is supportive care and oxygen, ria: to be at least 18 years of age with laboratory-conﬁrmed with mechanical ventilation in cases of respiratory failure severe acute respiratory syndrome coronavirus 2 infection; and hemodynamic support for the management of septic to have a World Health Organization (WHO) 9-point ordi- shock.10-12 Complicating matters, Covid-19 case surges nal scale for clinical improvement28 score of 4 (oxygen by create an undue strain on hospital capacity that results in mask or nasal prongs) with a documented comorbidity excess deaths in all types of critical care patient popula- (asthma, chronic lung disease, diabetes, hypertension, tions beyond individuals with Covid-19.13 Effective and severe obesity with a body-mass index [BMI] of 40 or safe therapies are greatly needed to reduce the risk of greater, 65 years of age or older, primarily reside in a nurs- death in hospitalized patients with Covid-19 thereby ing home or long-term care facility, or immunocompro- reducing the impact of Covid-19 on critical care delivery. mised status), WHO 5 (noninvasive ventilation or high-ﬂow oxygen), or WHO 6 (intubation and mechanical ventilation); Sabizabulin is an orally available, novel microtubule disrup- and to have a baseline oxygen saturation (SpO2) level of tor that targets, binds, and crosslinks both the a- and 94% or lower on room air. This study was approved by an b-tubulin subunits to inhibit polymerization and to induce institutional review board or ethics committee for each site, depolymerization of microtubules in cells.14,15 Microtubules and written informed consent was required from the patient are intracellular transport structures critical for coronavirus or legally authorized representative. cellular entry, trafﬁcking, replication, and egress16-21 as well as for triggering the innate inﬂammatory response and cyto- The key exclusion criteria for the study were as follows: kine storm responsible for ARDS, septic shock, and fre- pregnant or currently breast feeding; WHO 7 score quently death.22-24 ARDS is one of the primary causes of (required ventilation plus additional organ support such as mortality in Covid-19 infection, as inﬁltration of immune long-term pressors, renal replacement therapy, or extra- cells in both lungs leads to alveolar-capillary membrane corporeal membrane oxygen), alanine aminotransferase injury and edema; increased lung permeability leads to exu- or aspartate aminotransferase greater than three times the dates ﬁlling the air sacs, with resultant hypoxemia.25 Pre- upper limit of normal, total bilirubin above the upper limit clinical studies demonstrate that sabizabulin has both of normal, creatinine clearance of less than 60 ml/min, signiﬁcant antiviral and anti-inﬂammatory activities by dis- and hepatic impairment. The Protocol (available with the rupting microtubule dynamics.26 full text of this trial at evidence.nejm.org) contains the full clinical trial protocol, which provides the complete inclu- In a phase 2, double-blind, placebo-controlled, clinical sion and exclusion criteria for the study and information trial of 39 patients with moderate to severe Covid-19 at on prohibited prior or concomitant therapies, trial blind- high risk for ARDS, sabizabulin treatment resulted in ing, ethical conduct, and responsibilities of the sponsor, as reductions in deaths, respiratory failure, days in the well as the statistical analysis plan. The study was NEJM EVIDENCE 2 NEJM Evidence is produced by NEJM Group, a division of the Massachusetts Medical Society. Downloaded from evidence.nejm.org on July 6, 2022. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. All rights reserved. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. designed by Veru, Inc. Clinical data were gathered and STATISTICAL ANALYSIS analyzed by Worldwide Clinical Trials (Raleigh, NC). The planned enrollment into the study was approximately Manuscript decision and ﬁrst draft authors were Drs. Bar- 210 patients. In the primary efﬁcacy analysis, the sample nette and Steiner (Veru, Inc.). All of the data were avail- size was calculated so there was 92.8% power to detect an able to all authors, who vouch for the accuracy and approximately 50% relative reduction in deaths in the completeness of the data as well as the adherence of the sabizabulin-treated group compared with placebo (expected trial to the protocol. mortality rate of 30% for the placebo group). Randomiza- tion was stratiﬁed by oxygen supplementation requirement PROCEDURES at baseline. A prespeciﬁed interim efﬁcacy analysis was Patients were randomly assigned to receive Sabizabulin or planned to occur when the ﬁrst 150 randomized patients placebo in a 2:1 ratio. Randomization was stratiﬁed by had been followed through day 60. This analysis was WHO COVID-19 ordinal clinical severity score (0 to 8).28 focused on the primary efﬁcacy end point of all-cause mor- Study drug was administered daily at approximately the tality according to prospectively set stopping boundaries same time each day for up to 21 days or until the patient that were reviewed by regulatory agencies. The primary was discharged from the hospital, whichever came ﬁrst. efﬁcacy analysis used logistic regression with covariates Dose selection of sabizabulin was derived from the no of treatment, site and region, standard of care at baseline, adverse effect level observed in nonclinical toxicity stud- sex, and WHO ordinal scale score at baseline. At the time ies. Sabizabulin (9-mg) capsules and matching placebo of the interim efﬁcacy analysis, a two-sided P value of less capsules were manufactured and tested by CoreRx (Clear- than 0.0160 was needed to demonstrate early efﬁcacy water, FL). The schedule of assessments is provided in the (superiority of sabizabulin over placebo) on the basis of the Supplementary Appendix available with the full text of prespeciﬁed alpha spending function. Missing data were this article at evidence.nejm.org. handled by multiple imputation. Statistical analyses were performed by Worldwide Clinical Trials. Efﬁcacy and safety results of this interim analysis were reviewed by the inde- EFFICACY pendent data monitoring committee (Advarra, Indianapolis, The primary efﬁcacy end point of the study was 60-day IN). all-cause mortality (proportion of patients who died during the study up to day 60) compared with placebo in the intent-to-treat (ITT) population. The key secondary end points were differences in days in the ICU, days on Results mechanical ventilation, and days in the hospital between the two treatment groups. The multivariate analysis of the PATIENTS primary end point included treatment, geographic region, Although a total enrollment of approximately 210 patients WHO ordinal scale score at baseline, standard-of-care was planned, 204 participants had been randomly therapy use, and sex. Prespeciﬁed subgroup analyses of assigned to treatment when the study was stopped for efﬁ- the primary end point was performed by region (country), cacy at the direction of the independent data monitoring by WHO ordinal scale score at baseline, and by standard- committee. The 150 randomized patients in the interim of-care use during the study (dexamethasone and remde- analysis were enrolled at 27 participating sites in ﬁve coun- sivir). The Holm29 step-down procedure was used to con- tries (66 patients in the United States [44.0%], 63 patients trol multiplicity for selected key secondary end points. in Brazil [42.0%], 18 in Bulgaria [12.0%], 2 in Argentina [1.3%], and 1 in Mexico [0.7%]) and underwent random SAFETY assignment (between May 18, 2021 and January 31, 2022), Safety assessment included treatment-emergent adverse with 98 randomly assigned to sabizabulin and 52 to pla- events, serious adverse events, and adverse events leading cebo (Fig. 1). Of the 150 patients in the interim analysis, to discontinuation from the study starting at randomiza- 145 patients completed the study with known vital status tion into the study through day 60. Medical Dictionary for at day 60. Baseline demographic and clinical characteris- Regulatory Activities version 24.0 was used for safety cod- tics were similar in the two groups in the interim efﬁcacy ing. The incidence of events was provided for each treat- analysis (Table 1). Enrolled patients had moderate to ment group and included all randomized patients. severe Covid-19 infection with a mean SpO2 on ambient NEJM EVIDENCE 3 NEJM Evidence is produced by NEJM Group, a division of the Massachusetts Medical Society. Downloaded from evidence.nejm.org on July 6, 2022. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. All rights reserved. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. 26 Patients did not pass screening 1 Withdrew consent 176 Patients consented 2 Had no qualifying positive Covid-19 test result 1 Had a WHO-4, but no qualifying comorbidity 3 Did not meet WHO score of 4, 5, or 6 1 Not willing to comply with protocol 1 Was pregnant or breastfeeding 5 Required ventilation + addt’l organ support 3 Had ALT/AST >3× ULN 1 Had total bilirubin >ULN 3 Had creatinine clearance <60 ml/min 1 Had any other comorbid disease that may 150 Patients randomly assigned to treatment interfere with drug absorption 4 Had other unspecified reason 98 Patients received sabizabulin 52 Patients received placebo 94 Patients had D60 mortality status data 51 Patients had D60 mortality status data 4 Withdrew consent / lost to follow-up 1 Withdrew consent / lost to follow-up 94 Included in ITT analysis 51 Included in ITT analysis 2 Died without receiving study drug 1 Died without receiving study drug 17 Died during the study 22 Died during the study 75 Were alive at day 60 28 Were alive at day 60 Figure 1. Patient Disposition (Interim Analysis Population). ALT denotes alanine aminotransferase; AST, aspartate aminotransferase; D60, day 60; ITT, intent to treat; ULN, upper limit of normal; and WHO, World Health Organization. air at baseline of 92.5% and required supplemental oxy- hospitalized patients with Covid-19 (Table S2), except the gen. The proportion of patients requiring oxygen by mask proportion of male patients in this study was slightly or nasal prongs, noninvasive ventilation or high-ﬂow oxy- higher than expected and the proportion of patients of gen, or intubation and mechanical ventilation was similar Black race was slightly lower than expected. between the treatment groups. The distribution of com- mon risk factors for ARDS and death was similar between treatment groups and included hypertension (59.2% for PRIMARY EFFICACY OUTCOMES: sabizabulin vs. 61.5% for placebo), 65 years of age or older ALL-CAUSE MORTALITY (45.9% for sabizabulin vs. 50.0% for placebo), diabetes Sabizabulin met the prespeciﬁed superiority criterion for efﬁ- (35.7% for sabizabulin vs. 40.4% for placebo), and obesity cacy at the time of the interim analysis. In the primary efﬁ- (deﬁned as a BMI of 35 or greater; 34.7% for sabizabulin cacy end point of mortality up to day 60, a statistically vs. 27.5% for placebo). Covid-19 nonvaccinated rates were signiﬁcant 24.9 percentage point absolute reduction and a also similar (54.1% for sabizabulin vs. 57.7% for placebo). 55.2% relative reduction in mortality was observed in the Receipt of standard of care was also similar between the sabizabulin-treated group compared with placebo (odds two groups, in which dexamethasone (83.7% for sabizabu- ratio, 3.23; 95% conﬁdence interval [CI], 1.45 to 7.22; lin vs. 80.7% for placebo) and remdesivir (34.7% for sabi- P=0.0042) (Fig. 2 and Table 2). The beneﬁcial effects of zabulin vs. 28.8% for placebo) were the most common sabizabulin were observed starting as early as day 3 after treatments. Overall, the demographics of the patients dosing; by day 15, statistically signiﬁcant reductions in mor- included in this study were similar to the ranges reported tality were observed. The beneﬁcial effects of sabizabulin by the Centers for Disease Control and Prevention for treatment on mortality were maintained through day 29, a NEJM EVIDENCE 4 NEJM Evidence is produced by NEJM Group, a division of the Massachusetts Medical Society. Downloaded from evidence.nejm.org on July 6, 2022. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. All rights reserved. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. Table 1. Demographic and Clinical Characteristics of Patients (Interim Efficacy Analysis Population). Sabizabulin Placebo Overall Parameter (n598)* (n552) (N5150) Age — yr Mean (SD) 59.4 (14.57) 60.3 (15.02) 59.7 (14.69) Median (minimum, maximum) 64.0 (25, 92) 64.0 (19, 86) 64.0 (19, 92) Age category — yr, No. (%) ,65 53 (54.1) 26 (50.0) 79 (52.7) $65 45 (45.9) 26 (50.0) 71 (47.3) Sex — No. (%) Male 69 (70.4) 33 (63.5) 102 (68.0) Female 29 (29.6) 19 (36.5) 48 (32.0) BMI† No. of patients 94 51 145 Mean (SD) 33.0 (7.43) 32.4 (7.96) 32.8 (7.57) Median (minimum, maximum) 31.9 (20.2, 61.7) 31.1 (22.9, 69.4) 31.7 (20.2, 69.4) BMI category — No. (%) ,35 61 (64.9) 37 (72.5) 98 (67.6) $35 33 (35.1) 14 (27.5) 47 (32.4) Ethnicity — No. (%) Hispanic or Latino 48 (49.0) 23 (44.2) 71 (47.3) Not Hispanic or Latino 50 (51.0) 29 (55.8) 79 (52.7) Race — No. (%) White 83 (84.7) 46 (88.5) 129 (86.0) Black or African American 6 (6.1) 2 (3.8) 8 (5.3) Asian 2 (2.0) 0 2 (1.3) American Indian or Alaska Native 1 (1.0) 2 (3.8) 3 (2.0) Other 6 (6.1) 2 (3.8) 9 (5.3) WHO 9-point ordinal scale for clinical improvement score (0–8) Descriptive Mean (SD) 4.7 (0.55) 4.8 (0.65) 4.7 (0.58) Median (minimum, maximum) 5.0 (4, 6) 5.0 (4, 6) 5.0 (4, 6) Frequencies — No. (%) WHO 4 (oxygen by mask or nasal prongs) 31 (31.6) 18 (34.6) 49 (32.7) WHO 5 (noninvasive ventilation or high-flow oxygen) 62 (63.3) 28 (53.8) 90 (60.0) WHO 6 (intubation and mechanical ventilation) 5 (5.1) 6 (11.5) 11 (7.3) Comorbidities — No. (%) Cancer 7 (7.1) 1 (1.9) 8 (5.3) Diabetes 35 (35.7) 21 (40.4) 56 (37.3) Hypertension 58 (59.2) 32 (61.5) 90 (60.0) History of heart failure 4 (4.1) 3 (5.8) 7 (4.7) Pneumonia 46 (46.9) 31 (59.6) 77 (51.3) Kidney issues 11 (11.2) 4 (7.7) 15 (10.0) Respiratory issues 65 (66.3) 29 (55.8) 94 (62.7) Oxygen saturation at baseline — % No. of patients 98 52 150 Mean (SD) 92.7 (3.43) 91.9 (7.53) 92.5 (5.21) Median (minimum, maximum) 93.0 (84, 100) 94.0 (48, 100) 93.0 (48, 100) (continued) NEJM EVIDENCE 5 NEJM Evidence is produced by NEJM Group, a division of the Massachusetts Medical Society. Downloaded from evidence.nejm.org on July 6, 2022. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. All rights reserved. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. Table 1. (cont.) Sabizabulin Placebo Overall Parameter (n598)* (n552) (N5150) Time from admission to randomization — d No. of patients 97 52 149 Mean (SD) 3.4 (2.22) 4.0 (2.79) 3.6 (2.45) Median (minimum, maximum) 3.0 (0, 13) 3.5 (0, 11) 3.0 (0, 13) Vaccination status — No. (%) Not vaccinated 53 (54.1) 30 (57.7) 83 (55.3) Vaccinated (1, 2, or 3 shots) 45 (45.9) 22 (42.3) 67 (44.7) Received standard of care — No. (%)‡ Dexamethasone 82 (83.7) 42 (80.7) 124 (82.7) Remdesivir 34 (34.7) 15 (28.8) 49 (32.7) Tocilizumab 10 (10.2) 5 (9.6) 15 (10.0) Baricitinib or tofacitinib 10 (10.2) 8 (15.4) 18 (12.0) * Patients received 9 mg of sabizabulin daily for up to 21 days. † The body-mass index (BMI) is the weight in kilograms divided by the square of the height in meters. ‡ The standard of care presented here is what was used at any time during the study (from days 1 until 60). standard time point that other studies have used as the efﬁ- (Fig. 3) were consistent with the overall study results favoring cacy end point, with mortality rate of 35.3% for placebo sabizabulin treatment regardless of standard-of-care treat- compared with 17% for sabizabulin—an absolute reduction ment received, baseline WHO ordinal clinical score, sex, age, of 18.3 percentage points and a relative reduction of 51.8 per- baseline comorbidities, BMI, or geographic location. centage points. From days 29 to 60, the death rate increased by 9.8 percentage points in the placebo group and by 3.2 per- In the United States, a 34.4 percentage point absolute centage points in the sabizabulin-treated group. Results of reduction in mortality at day 60 (55.5% relative reduction) subgroup analyses evaluating the relative risk of death was observed in the sabizabulin group compared with 50.0 Placebo 45.0 40.0 35.0 Percent Mortality 30.0 25.0 Sabizabulin 9 mg 20.0 15.0 10.0 5.0 0.0 0 10 20 30 40 50 60 70 Days on Study Figure 2. Cumulative Mortality Curve. NEJM EVIDENCE 6 NEJM Evidence is produced by NEJM Group, a division of the Massachusetts Medical Society. Downloaded from evidence.nejm.org on July 6, 2022. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. All rights reserved. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. Table 2. Primary Efficacy End Point of Mortality Up to Day 60. Primary End Point Sabizabulin* Placebo OR (95% CI) or Relative Difference (%) Vital status — No. (%) 98 52 Alive 75 (79.8) 28 (54.9) Dead 19 (20.2) 23 (45.1) Missing at day 60 4 1 Treatment comparison: sabizabulin vs. placebo 3.23 (1.45 to 7.22); P50.0042† Days in study — No. (%) 94 51 15 7 (7.4) 13 (25.5) 271.0 29 16 (17.0) 18 (35.3) 251.8 60 19 (20.2) 23 (45.1) 255.2 * Patients received 9 mg of sabizabulin daily for up to 21 days. † Primary study end point. The P value was generated using logistic regression with the multivariate analysis. CI denotes confidence interval; and OR, odds ratio. placebo. In the rest of the world (Brazil, Bulgaria, Mexico, sabizabulin versus 11.6% for placebo), pneumothorax (0.8% and Argentina), a 18.5 percentage point absolute reduction for sabizabulin vs. 10.1% for placebo), bacterial pneumonia in mortality at day 60 (55.6% relative reduction) was (0.8% for sabizabulin vs. 7.2% for placebo), and hypotension observed in the sabizabulin group compared with placebo. (2.3% for sabizabulin vs. 11.6% for placebo). The propor- At the time of this publication, all-cause mortality for the tion of patients with a serious adverse event observed dur- full ﬁnal data set (ITT population) of 204 randomized ing the study was also lower for the sabizabulin-treated patients was similar to that result observed in the interim group (29.2%) compared with placebo (46.4%) (Tables 4 efﬁcacy analysis population, with sabizabulin treatment and 5). The most frequently reported serious adverse resulting in a 51.6 percentage point relative reduction in events in either group were respiratory failure (9.2% for deaths compared with placebo. sabizabulin vs. 17.4% for placebo), acute kidney injury (3.8% for sabizabulin vs. 8.7% for placebo), pneumothorax SECONDARY EFFICACY OUTCOMES (0.8% for sabizabulin vs. 8.7% for placebo), septic shock Sabizabulin treatment resulted in a statistically signiﬁcant (1.5% for sabizabulin vs. 5.8% for placebo), and acute reduction in key secondary end points compared with pla- respiratory failure (4.6% for sabizabulin vs. 5.8% for pla- cebo (Table 3). There was a 43 percentage point relative cebo). Adverse events leading to discontinuation were reduction in days in the ICU (least-squares [LS] mean of 4.7% for sabizabulin versus 5.9% for placebo. -13.4 days; 95% CI, -21.5 to -5.3; P=0.0013), a 49 per- centage point relative reduction in days on mechanical ventilation (LS mean of -14.1 days; 95% CI, -22.4 to -5.6; P=0.0013), and a 26 percentage point relative reduction Discussion in days in the hospital (LS mean of -8.4 days; 95% CI, Vaccinations remains the mainstay for prevention of seri- -15.8 to -0.9; P=0.0277). In these analyses, the values of ous Covid-19 infection and death. Most patients will days were imputed to the maximum (60 days) for all recover from an acute Covid-19 illness.30 New antiviral patients who died during the study. agents molnupiravir and nirmatrelvir reduce the incidence of Covid-19–related hospitalization or death when taken in SAFETY a nonhospital setting within 3 to 5 days after Covid-19 The adverse events and serious adverse events observed in symptom onset.3,4 For patients who progress to moderate this study were consistent with patients with serious to severe Covid-19 illness requiring hospitalization, the risk Covid-19 illness. The proportion of patients who experienced of death remains high. In this setting, however, the antivi- any adverse event was lower in the sabizabulin-treated group ral molnupiravir did not demonstrate clinical beneﬁt.31 (61.5%) compared with the placebo group (78.3%) (Tables 4 and 5). The most frequently reported adverse events in Sabizabulin is a novel microtubule disruptor that has dual either group were respiratory failure (9.2% for sabizabulin antiviral and anti-inﬂammatory activities. Sabizabulin vs. 17.4% for placebo), acute kidney injury (8.5% for appears to be a member of a novel class of drugs that NEJM EVIDENCE 7 NEJM Evidence is produced by NEJM Group, a division of the Massachusetts Medical Society. Downloaded from evidence.nejm.org on July 6, 2022. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. All rights reserved. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. Relative Risk (95% CI) Overall Study 0.45 (0.27 to 0.74) Standard of Care Treatment Received on Study Remdesivir Tx 0.42 (0.22 to 0.82) No Remdesivir Tx 0.45 (0.22 to 0.90) Dexamethasone Tx 0.55 (0.33 to 0.94) *No Dexamethasone Tx 0 (0.00 to 0.41) Baseline Ordinate Scale WHO 4 0.094 (0.02 to 0.54) WHO 5 0.58 (0.34 to 1.02) WHO 6 0.40 (0.10 to 1.61) Sex Male 0.37 (0.20 to 0.68) Female 0.67 (0.29 to 1.57) Age < 65 years 0.36 (0.17 to 0.77) ≥ 65 years 0.55 (0.29 to 1.07) BMI <35 0.45 (0.23 to 0.87) ≥35 0.41 (0.20 to 0.89) Baseline Comorbidities Hypertension 0.54 (0.29 to 0.94) Diabetes 0.55 (0.28 to 1.06) Pneumonia 0.56 (0.30 to 1.07) Respiratory Issues 0.41 (0.23 to 0.76) Geographic Location U.S. 0.44 (0.24 to 0.81) Ex-U.S. 0.44 (0.20 to 0.99) 0.01 0.1 1 10 Relative Risk of Death Sabizabulin better Placebo better Figure 3. Subgroup Analyses of Primary Efﬁcacy End Point. Data are presented as point estimates for relative risk of death (95% conﬁdence intervals [CIs]). BMI denotes body-mass index; Ex-U.S., outside United States; Tx, treatment; and WHO, World Health Organization. * No deaths in the treated group. targets, binds, and crosslinks both the a- and b-tubulin sub- not a substrate for P-glycoprotein or CYP3A4, which may units of microtubules to inhibit polymerization and to result in higher and more consistent intracellular and blood induce depolymerization of microtubules, which alters concentrations of sabizabulin than colchicine.14 Thus, sabi- microtubule dynamics.14,15 Sabizabulin has a different zabulin has a different chemical structure and unique physi- chemical structure and unique physicochemical properties cochemical properties compared with colchicine. compared with the more familiar drug, colchicine. Although sabizabulin does bind to the b-tubulin subunit in the Oral daily dosing of 9 mg of sabizabulin up to 21 days dem- “colchicine binding” pocket, it inserts deeper and tighter in onstrated signiﬁcant efﬁcacy in this interim analysis of a ran- the pocket with more hydrogen bonding than colchicine.32 domized, double-blind, placebo-controlled global phase 3 Sabizabulin inhibits tubulin polymerization better than col- clinical trial in hospitalized adult patients with moderate to chicine in in vitro studies.14 Unlike colchicine, sabizabulin is severe Covid-19 who were at high risk for ARDS and death. NEJM EVIDENCE 8 NEJM Evidence is produced by NEJM Group, a division of the Massachusetts Medical Society. Downloaded from evidence.nejm.org on July 6, 2022. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. All rights reserved. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. Table 3. Secondary Efficacy End Points.* Treatment Comparison Secondary End Point† Mean (SD)‡ Median (Minimum, Maximum) LS Mean (SE) 95% CI P Value Days in ICU Sabizabulin 17.4 (23.93) 4.0 (0, 60) Placebo 30.8 (27.83) 17.0 (0, 60) Sabizabulin vs. placebo 213.4 (4.09) 221.5, 25.3 0.0013 Days on mechanical ventilation Sabizabulin 14.4 (24.01) 0.0 (0, 60) Placebo 28.5 (29.31) 11.0 (0, 60) Sabizabulin vs. placebo 214.1 (4.28) 222.5, 25.6 0.0013 Days in hospital Sabizabulin 25.6 (22.87) 14.0 (0, 60) Placebo 34.6 (24.63) 30.5 (0, 60) Sabizabulin vs. placebo 28.4 (3.76) 215.8, 20.9 0.0277 * CI denotes confidence interval, ICU intensive care unit, and LS least squares. † Results are reported for 98 patients in the sabizabulin group (who received 9 mg daily for up to 21 days) and 52 in the placebo group. ‡ Days in the ICU, on mechanical ventilation, or in the hospital was set at maximum value (60 days) in all patients that died during the study, as per the planned analysis for the study. Sabizabulin demonstrated a statistically signiﬁcant 24.9% Table 4. Treatment-Emergent Adverse Events for the Intent-to-Treat Population (5% of Patients in Either Treatment Group). absolute reduction and a 55.2% relative reduction in all-cause mortality by day 60, the primary efﬁcacy end point No. of Patients (%)/Events of the study. The cumulative mortality analysis showed that Sabizabulin Placebo the reduction in deaths with sabizabulin started within the Adverse Event (n5130) (n569) ﬁrst week of treatment and the relative reduction in deaths Any 80 (61.5)/341 54 (78.3)/285 reached 51.8% at day 29. This efﬁcacy was further supported Atrial fibrillation 6 (4.6)/6 4 (5.8)/4 by the consistency of the subgroup analyses of the primary Bradycardia 5 (3.8)/6 5 (7.2)/5 end point: a reduction in deaths with sabizabulin treatment Constipation 8 (6.2)/8 6 (8.7)/10 compared with placebo regardless of standard-of-care treat- Pneumonia 7 (5.4)/11 8 (11.6)/11 ment received, baseline WHO ordinal score, sex, age, base- Bacterial pneumonia 1 (0.8)/1 5 (7.2)/5 line comorbidities, BMI, or geographic location. Septic shock 2 (1.5)/2 4 (5.8)/4 Furthermore, the secondary efﬁcacy end points demon- Urinary tract infection 8 (6.2)/8 1 (1.4)/1 strated that sabizabulin treatment resulted in a signiﬁcant Hyperkalemia 5 (3.8)/5 6 (8.7)/7 reduction in days in the ICU, days on mechanical ventila- Hypernatremia 6 (4.6)/6 4 (5.8)/4 tion, and days in the hospital compared with placebo. With Hypokalemia 5 (3.8)/6 4 (5.8)/4 130 patients treated, sabizabulin had an acceptable side- Hypophosphatemia 2 (1.5)/3 4 (5.8)/5 effect and safety proﬁle. Signiﬁcantly fewer serious adverse Anxiety 3 (2.3)/4 4 (5.8)/4 events and adverse events were reported for sabizabulin Acute kidney injury 11 (8.5)/11 8 (11.6)/8 compared with placebo. There were also fewer treatment Acute respiratory failure 8 (6.2)/8 4 (5.8)/4 discontinuations due to adverse events in the sabizabulin Bronchitis chronic 2 (1.5)/2 4 (5.8)/4 group compared with placebo. The phase 3 reported safety Hypoxia 3 (2.3)/4 4 (5.8)/4 proﬁles suggest that sabizabulin treatment may have Pneumothorax 1 (0.8)/1 7 (10.1)/7 resulted in fewer Covid-19–related morbidities, especially Respiratory failure 12 (9.2)/13 12 (17.4)/12 respiratory failure, acute kidney injury, cardiac arrest, sep- Hypotension 3 (2.3)/3 8 (11.6)/8 tic shock, and hypotension. NEJM EVIDENCE 9 NEJM Evidence is produced by NEJM Group, a division of the Massachusetts Medical Society. Downloaded from evidence.nejm.org on July 6, 2022. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. All rights reserved. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. Author disclosures and other supplementary materials are available at Table 5. Treatment Emergent Serious Adverse Events for the ITT evidence.nejm.org. Population (>2% of Patients in Either Treatment Group). No. of Patients (%)/Events Author Affiliations 1 Veru, Inc., Miami Sabizabulin Placebo 2 Serious Adverse Event (n5130) (n569) Honor-Health Research Institute, Scottsdale, AZ 3 Memorial Hermann, Memorial City Medical Center, Houston Any 38 (29.2)/82 32 (46.4)/84 4 Methodist Hospital, St. Louis Park, MN Cardiac arrest 0 3 (4.3)/4 5 Regions Hospital, St. Paul, MN Covid-19 4 (3.1)/4 3 (4.3)/3 6 Fundaç~ ao Faculdade Regional de Medicina, S~ ao Jos e do Rio Preto, Pneumonia 3 (2.3)/5 4 (5.8)/5 Brazil Bacterial pneumonia 0 2 (2.9)/2 7 Infectologia, Hospital de Clınicas de Porto Alegre, Centro de Pesquisa Sepsis 3 (2.3)/4 2 (2.9)/2 Clınica, Porto Alegre, Brazil 8 Septic shock 2 (1.5)/2 4 (5.8)/5 University Multiproﬁle Hospital for Active Treatment, Zagora, Bulgaria 9 Acute kidney injury 5 (3.8)/5 6 (8.7)/6 University Multiproﬁle Hospital for Active Treatment, Soﬁa, Bulgaria Acute respiratory failure 6 (4.6)/6 4 (5.8)/5 Hypoxia 2 (1.5)/3 3 (4.3)/3 References Pneumothorax 1 (0.8)/1 6 (8.7)/6 1. Worldometer. Coronavirus cases. 2022 (https//www.worldometers. Pulmonary embolism 3 (2.3)/3 3 (4.3)/3 info/coronavirus). Respiratory failure 12 (9.2)/13 12 (17.4)/12 2. Gupta A, Gonzalez-Rojas Y, Juarez E, et al. Early treatment for Covid-19 with SARS-CoV-2 neutralizing antibody sotrovimab. N Engl J Med 2021;385:1941–1950. DOI: 10.1056/NEJMoa2107934. In this study, sabizabulin was evaluated in hospitalized 3. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. patients with moderate to severe Covid-19 illness. The Molnupiravir for oral treatment of Covid-19 in nonhospitalized inclusion criteria were selected by design to include patients patients. N Engl J Med 2022;386:509–520. DOI: 10.1056/ who were at the highest risk for ARDS and death due to NEJMoa2116044. Covid-19. Enrolled hospitalized patients had to demonstrate 4. Hammond J, Leister-Tebbe H, Gardner A, et al. Oral nirmatrelvir moderate to severe Covid-19 illness (at least oxygen supple- for high-risk, nonhospitalized adults with Covid-19. N Engl J Med mentation with SpO2 of 94% or less while breathing ambi- 2022;386:1397–1408. DOI: 10.1056/NEJMoa2118542. ent air). Patients with a WHO score of 4 (receiving 5. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treat- supplemental oxygen) had to have a comorbidity that placed ment of Covid-19 — ﬁnal report. N Engl J Med 2020;383:1813– them at high-risk for death; and no limitation was placed on 1826. DOI: 10.1056/NEJMoa2007764. the duration of Covid-19 symptoms before enrollment. 6. Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospital- Accordingly, the mortality rate in the placebo group for this ized patients with Covid-19. N Engl J Med 2021;384:693–704. DOI: study was 35.3% at day 29; by day 60, the mortality rate in 10.1056/NEJMoa2021436. this group further increased to 45.1%. It is apparent that the 7. Salama C, Han J, Yau L, et al. Tocilizumab in patients hospitalized mortality rate for hospitalized patients with moderate to with Covid-19 pneumonia. N Engl J Med 2021;384:20–30. DOI: 10. severe Covid-19 remains high even with available therapies, 1056/NEJMoa2030340. such as antiviral agent remdesivir, immunomodulators, or 8. Guimar~ aes PO, Quirk D, Furtado RH, et al. Tofacitinib in patients anti-inﬂammatory agents.5,6,8,9,12,33 By targeting microtu- hospitalized with Covid-19 pneumonia. N Engl J Med 2021;385: bule trafﬁcking, sabizabulin has both dual anti- 406–415. DOI: 10.1056/NEJMoa2101643. inﬂammatory and antiviral activity. These data demonstrate 9. Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus remdesivir that sabizabulin treatment signiﬁcantly reduced mortality for hospitalized adults with Covid-19. N Engl J Med 2021;384:795– with an acceptable side-effect and safety proﬁle in hospital- 807. DOI: 10.1056/NEJMoa2031994. ized patients with moderate to severe Covid-19 at high risk 10. National Institutes of Health. Coronavirus disease 2019 (COVID-19) for ARDS. treatment guidelines. 2022 (https://www.covid19treatmentguide lines. nih.gov). 11. Huang C, Wang Y, Li X, et al. Clinical features of patients infected Disclosures with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395: This study was funded by Veru, Inc. 497–506. DOI: 10.1016/S0140-6736(20)30183-5. NEJM EVIDENCE 10 NEJM Evidence is produced by NEJM Group, a division of the Massachusetts Medical Society. Downloaded from evidence.nejm.org on July 6, 2022. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. All rights reserved. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. 12. Berlin DA, Gulick RM, Martinez FJ. Severe Covid-19. N Engl J Med 23. Zahid A, Li B, Kombe AJK, Jin T, Tao J. 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Annu Rev Microbiol 2019;73:529–557. DOI: 10.1146/annurev-micro- 28. Dodd LE, Follmann D, Wang J, et al. Endpoints for randomized 020518-115759. controlled clinical trials for COVID-19 treatments. Clin Trials 2020;17:472–482. DOI: 10.1177/1740774520939938. 18. Naghavi MH, Walsh D. Microtubule regulation and function during virus infection. J Virol 2017;91:e00538-17. DOI: 10.1128/JVI. 29. Holm SA. A simple sequentially rejective multiple test procedure. 00538-17. Scand J Stat 1979;6:65–70. 19. D€ ohner K, Nagel CH, Sodeik B. Viral stop-and-go along microtu- 30. Tenforde MW, Kim SS, Lindsell CJ, et al. Symptom duration and risk bules: taking a ride with dynein and kinesins. Trends Microbiol factors for delayed return to usual health among outpatients with 2005;13:320–327. DOI: 10.1016/j.tim.2005.05.010. COVID-19 in a multistate healthcare systems network—United States, March July 2021. MMWR Morb Mortal Wkly Rep 2021;70:1294–1299. 20. Eichwald C, Arnoldi F, Laimbacher AS, et al. 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Investor and Media Contact: Samuel Fisch Executive Director, Investor Relations and Corporate Communications Email: [email protected] European Medicines Agency’s Emergency Task Force Has Initiated the Review of Veru’s Sabizabulin Treatment for Hospitalized COVID-19 Patients for Emergency Use in European Union Countries MIAMI – July 27, 2022 – Veru Inc. (NASDAQ: VERU), a biopharmaceutical company focused on developing novel medicines for COVID-19 and other viral and ARDS-related diseases and for the management of breast and prostate cancers, today announced that the European Medicines Agency’s (EMA) Emergency Task Force (ETF) has informed the Company that it has initiated the review of sabizabulin for the treatment of hospitalized COVID-19 patients at high risk for Acute Respiratory Distress Syndrome (ARDS). ETF stated: “The review will look at all available data, including data from a study involving hospitalized patients with moderate-to-severe COVID-19 who are at high risk of acute respiratory distress syndrome (ARDS) and death [NEJM Evidence publication DOI:10.1056/EVIDoa2200145]. The results of this study would indicate that sabizabulin treatment reduces the number of deaths in these patients compared with placebo (a dummy treatment). . . .The review will assist EU Member States who may consider allowing use of the medicine before a possible authorisation. The review is the first to be triggered under Article 18 of the new EU regulation (Reg 2022/123) that expanded the role of EMA during public health emergencies. The ETF will conduct this review and send recommendations to the Agency’s human medicines committee (CHMP), which will issue the Agency’s opinion. EMA will communicate on the outcome of the review when it concludes.” “COVID-19 infections are sharply rising in Europe. Unfortunately, the death rate in hospitalized patients with moderate to severe COVID-19 who are at risk for ARDS remains unacceptably high with current standard of care. By reducing deaths in hospitalized COVID-19 patients, sabizabulin has great potential to play a critical role in the battle against COVID-19 in the EU. We are excited with this development at the EMA by the Emergency Task Force. We were just notified yesterday that sabizabulin triggered Article 18,” said Mitchell Steiner, M.D., Chairman, President, and Chief Executive Officer of Veru. “This new emergency regulatory pathway may allow the availability of sabizabulin to EU member states prior to sabizabulin being approved by EMA. Separately, we were also informed by CHMP yesterday that the sabizabulin product is eligible for submission of an application for a centralized marketing authorization.” About Veru Inc. Veru is a biopharmaceutical company focused on developing novel medicines for COVID-19 and other viral and ARDS-related diseases and for the management of breast and prostate cancers. Infectious disease program: The Company has completed a positive Phase 3 COVID-19 study in hospitalized moderate to severe COVID-19 patients at high risk for ARDS. A double-blind, randomized, placebo-controlled Phase 3 COVID-19 clinical trial was conducted in approximately 210 hospitalized COVID-19 patients with moderate to severe COVID (≥ WHO 4- supplemental oxygen) at high risk for ARDS and death. The primary endpoint was the proportion of deaths by Day 60. Based on a planned interim analysis of the first 150 patients randomized, the Independent Data Monitoring Committee unanimously halted the study for overwhelming efficacy and safety. Treatment with sabizabulin 9mg once daily, an oral, first-in-class, new chemical entity, microtubule disruptor that has dual anti-inflammatory and antiviral properties, resulted in a clinically meaningful and statistically significant 55.2% relative reduction in deaths. On June 7, 2022, the Company submitted a request for emergency use authorization to FDA. On July 6, 2022, the Company announced the publication of the Phase 3 COVID-19 trial results evaluating the efficacy and safety of oral sabizabulin in The New England Journal of Medicine Evidence®. Oncology program: The Company’s late-stage breast cancer development portfolio comprises enobosarm, a selective androgen receptor targeting agonist, and sabizabulin. Current studies on the two drugs include: • Enrolling Phase 3 ARTEST study of enobosarm in androgen receptor positive, estrogen receptor positive, and human epidermal growth factor receptor two negative (AR+ ER+ HER2-) metastatic breast cancer with AR ≥ 40% expression (third-line metastatic setting), and which has been granted Fast Track designation by the FDA. • Enrolling Phase 3 ENABLAR-2 study of enobosarm + abemaciclib (a CDK 4/6 inhibitor) combination in AR+ ER+ HER2- metastatic breast cancer with AR ≥ 40% expression (second- line metastatic setting). The Company and Eli Lilly and Company have entered into a clinical study collaboration and supply agreement for the ENABLAR-2 study. Lilly will supply Verzenio® (abemaciclib). • Planned Phase 2b study of sabizabulin in AR+ ER+ HER2- metastatic breast cancer with AR < 40% expression (third-line metastatic setting). Veru’s late-stage prostate cancer portfolio comprises sabizabulin, VERU-100, a long-acting GnRH antagonist, and zuclomiphene citrate, an oral nonsteroidal estrogen receptor agonist. Current studies on these drugs include: • Enrolling Phase 3 VERACITY study in metastatic castration and androgen receptor targeting agent resistant prostate cancer prior to IV chemotherapy. • Enrolling Phase 2 dose-finding study of VERU-100 in advanced hormone sensitive prostate cancer. • Planned Phase 2b study of zuclomiphene citrate to treat hot flashes in men with advanced prostate cancer undergoing androgen deprivation therapy. Commercial sexual health program, Urev, has 2 FDA approved products: • ENTADFI™ (finasteride and tadalafil) capsules for oral use, a new treatment for benign prostatic hyperplasia, for which commercialization launch plans are underway. • FC2 Female Condom® (internal condom), for the dual protection against unplanned pregnancy and the transmission of sexually transmitted infections which is sold in the U.S. and globally. 2 Forward-Looking Statements The statements in this release that are not historical facts are “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995. Forward-looking statements in this release include statements regarding: whether and when the Company will receive an emergency use authorization or any approval from FDA or EMA or EU member countries or from any other regulatory authority outside the U.S. for sabizabulin for certain COVID-19 patients; whether and when sabizabulin will become an available treatment option for certain COVID-19 patients in the U.S., EU or anywhere else outside the U.S.; whether and when the Company will submit any marketing authorization application or emergency application for sabizabulin to EMA or to any EU member state; whether the Company will have sufficient supply of sabizabulin to meet demand, if an emergency use authorization or other approval is granted in the U.S. or in any other country; whether the Company will secure any advance purchase agreement with the U.S. government or any foreign government; whether the current and future clinical development and results will demonstrate sufficient efficacy and safety and potential benefits to secure FDA approval of the Company’s drug candidates and companion diagnostic; whether the drug candidates will be approved for the targeted line of therapy; the anticipated design and scope of clinical studies and FDA acceptance of such design and scope; whether any regulatory pathways, including the accelerated Fast Track designations, to seek FDA approval for sabizabulin, enobosarm or any of the Company’s drug candidates are or continue to be available; whether the expected commencement and timing of the Company’s clinical studies, including the Phase 3 ARTEST study, the Phase 3 ENABLAR-2 study, the sabizabulin monotherapy Phase 2b clinical study for 3rd line treatment of metastatic breast cancer, the Phase 2 registration clinical study for VERU-100, and the development of the companion diagnostic will be met; when clinical results from the ongoing clinical studies will be available, whether sabizabulin, enobosarm, VERU-100, zuclomiphene, and ENTADFI will serve any unmet need or, what dosage, if any, might be approved for use in the U.S. or elsewhere, and also statements about the potential, timing and efficacy of the rest of the Company’s development pipeline, and the timing of the Company’s submissions to FDA and MHRA and FDA’s and MHRA’s review of all such submissions; whether the companion diagnostic for enobosarm will be developed successfully or be approved by the FDA for use; and whether and when ENTADFI will be commercialized successfully. These forward-looking statements are based on the Company’s current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: the development of the Company’s product portfolio and the results of clinical studies possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical studies and the ability to enroll subjects in accordance with planned schedules; the ability to fund planned clinical development; the timing of any submission to the FDA, MHRA or any other regulatory authority and any determinations made by the FDA, MHRA or any other regulatory authority; the possibility that as vaccines and other antiviral medicines become widely distributed the need for new COVID-19 treatment candidates may be reduced or eliminated; government entities possibly taking actions that directly or indirectly have the effect of limiting opportunities for sabizabulin as a COVID-19 treatment, including favoring other treatment alternatives or imposing price controls on COVID-19 treatments; the Company’s existing products and any future products, if approved, possibly not being commercially successful; the effects of the COVID-19 pandemic and measures to address the pandemic on the Company’s clinical studies, supply chain and other third-party providers, commercial efforts, and business development operations; the ability of the Company to obtain sufficient financing on acceptable terms when needed to fund development and operations; demand for, market acceptance of, and competition against any of the Company’s products or product candidates; new or existing competitors with greater resources and capabilities and new competitive product approvals and/or introductions; changes in regulatory practices or policies or government-driven healthcare reform efforts, including pricing pressures and insurance coverage and reimbursement changes; risks relating to the Company's development of its own dedicated direct to patient telemedicine and telepharmacy services platform, including the Company's lack of experience in developing such a platform, potential regulatory complexity, and development costs; the Company’s 3 ability to protect and enforce its intellectual property; the potential that delays in orders or shipments under government tenders or the Company’s U.S. prescription business relating to the FC2 female condom could cause significant quarter-to-quarter variations in the Company’s operating results and adversely affect its net revenues and gross profit; 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 for its FC2 female condom; the concentration of accounts receivable with our largest customers and the collection of those receivables; the Company’s production capacity, efficiency and supply constraints and interruptions, including potential disruption of production at the Company’s and third party manufacturing facilities and/or of the Company’s ability to timely supply any of its product due to labor unrest or strikes, labor shortages, raw material shortages, physical damage to the Company’s and third party facilities, COVID-19 (including the impact of COVID- 19 on suppliers of key raw materials), product testing, transportation delays or regulatory actions; 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 from time to time in the Company’s press releases, shareholder communications and Securities and Exchange Commission filings, including the Company’s Form 10-K for the fiscal year ended September 30, 2021 and subsequent quarterly reports on Form 10-Q. These documents are available on the “SEC Filings” section of our website at www.verupharma.com/investors. The Company disclaims any intent or obligation to update these forward-looking statements. Verzenio® is a registered trademark of Eli Lilly and Company NEJM Evidence® is a registered trademark of the Massachusetts Medical Society 4 Investor and Media Contact: Samuel Fisch Executive Director, Investor Relations and Corporate Communications Email: [email protected] UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) Supports Expedited Review of Marketing Authorization Application for Sabizabulin Treatment in Hospitalized COVID-19 Patients MIAMI – July 25, 2022 – Veru Inc. (NASDAQ: VERU), a biopharmaceutical company focused on developing novel medicines for COVID-19 and other viral and ARDS-related diseases and for the management of breast and prostate cancers, today announced that the United Kingdom’s (UK’s) Medicines and Healthcare Products Regulatory Agency (MHRA) considers that the currently available safety and efficacy data will support an expedited review of the marketing authorization application for the Company’s sabizabulin treatment in hospitalized COVID-19 patients at high risk for Acute Respiratory Distress Syndrome (ARDS) when the application is submitted. “We are pleased that the MHRA has agreed to support the expedited review of our sabizabulin UK marketing authorization submission. With this decision, we plan to proceed toward the submission of our application as soon as possible,” said Mitchell Steiner, M.D., Chairman, President, and Chief Executive Officer of Veru. “COVID infections are sharply rising in the UK. Unfortunately, the death rate in hospitalized patients with moderate to severe COVID-19 who are at risk for ARDS remains unacceptably high with current standard of care. By reducing deaths in hospitalized COVID-19 patients, sabizabulin has great potential to play a critical role in the battle against COVID-19 in the UK and elsewhere.” About Veru Inc. Veru is a biopharmaceutical company focused on developing novel medicines for COVID-19 and other viral and ARDS-related diseases and for the management of breast and prostate cancers. Infectious disease program: The Company has completed a positive Phase 3 COVID-19 study in hospitalized moderate to severe COVID-19 patients at high risk for ARDS. A double-blind, randomized, placebo-controlled Phase 3 COVID-19 clinical trial was conducted in approximately 210 hospitalized COVID-19 patients with moderate to severe COVID (≥ WHO 4- supplemental oxygen) at high risk for ARDS and death. The primary endpoint was the proportion of deaths by Day 60. Based on a planned interim analysis of the first 150 patients randomized, the Independent Data Monitoring Committee unanimously halted the study for overwhelming efficacy and safety. Treatment with sabizabulin 9mg once daily, an oral, first-in-class, new chemical entity, microtubule disruptor that has dual anti-inflammatory and antiviral properties, resulted in a clinically meaningful and statistically significant 55.2% relative reduction in deaths. On June 7, 2022, the Company submitted a request for emergency use authorization to FDA. On July 6, 2022, the Company announced the publication of the Phase 3 COVID-19 trial results evaluating the efficacy and safety of oral sabizabulin in The New England Journal of Medicine Evidence®. Oncology program: The Company’s late-stage breast cancer development portfolio comprises enobosarm, a selective androgen receptor targeting agonist, and sabizabulin. Current studies on the two drugs include: • Enrolling Phase 3 ARTEST study of enobosarm in androgen receptor positive, estrogen receptor positive, and human epidermal growth factor receptor two negative (AR+ ER+ HER2-) metastatic breast cancer with AR ≥ 40% expression (third-line metastatic setting), and which has been granted Fast Track designation by the FDA. • Enrolling Phase 3 ENABLAR-2 study of enobosarm + abemaciclib (a CDK 4/6 inhibitor) combination in AR+ ER+ HER2- metastatic breast cancer with AR ≥ 40% expression (second- line metastatic setting). The Company and Eli Lilly and Company have entered into a clinical study collaboration and supply agreement for the ENABLAR-2 study. Lilly will supply Verzenio® (abemaciclib). • Planned Phase 2b study of sabizabulin in AR+ ER+ HER2- metastatic breast cancer with AR < 40% expression (third-line metastatic setting). Veru’s late-stage prostate cancer portfolio comprises sabizabulin, VERU-100, a long-acting GnRH antagonist, and zuclomiphene citrate, an oral nonsteroidal estrogen receptor agonist. Current studies on these drugs include: • Enrolling Phase 3 VERACITY study in metastatic castration and androgen receptor targeting agent resistant prostate cancer prior to IV chemotherapy. • Enrolling Phase 2 dose-finding study of VERU-100 in advanced hormone sensitive prostate cancer. • Planned Phase 2b study of zuclomiphene citrate to treat hot flashes in men with advanced prostate cancer undergoing androgen deprivation therapy. Commercial sexual health program, Urev, has 2 FDA approved products: • ENTADFI™ (finasteride and tadalafil) capsules for oral use, a new treatment for benign prostatic hyperplasia, for which commercialization launch plans are underway. • FC2 Female Condom® (internal condom), for the dual protection against unplanned pregnancy and the transmission of sexually transmitted infections which is sold in the U.S. and globally. Forward-Looking Statements The statements in this release that are not historical facts are “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995. Forward-looking statements in this release include statements regarding: whether and when the Company will receive an emergency use authorization or any approval from FDA or MHRA or from any other regulatory authority outside the U.S. for sabizabulin for certain COVID-19 patients; whether and when sabizabulin will become an available treatment option for certain COVID-19 patients in the U.S., UK or anywhere else outside the U.S.; whether and when the Company will submit a marketing authorization application for sabizabulin to MHRA’ whether the Company will have sufficient supply of sabizabulin to meet demand, if an emergency use authorization or other approval is granted in the U.S. or in any other country; whether the Company will secure any advance purchase agreement with the U.S. government or any foreign 2 government; whether the current and future clinical development and results will demonstrate sufficient efficacy and safety and potential benefits to secure FDA approval of the Company’s drug candidates and companion diagnostic; whether the drug candidates will be approved for the targeted line of therapy; the anticipated design and scope of clinical studies and FDA acceptance of such design and scope; whether any regulatory pathways, including the accelerated Fast Track designations, to seek FDA approval for sabizabulin, enobosarm or any of the Company’s drug candidates are or continue to be available; whether the expected commencement and timing of the Company’s clinical studies, including the Phase 3 ARTEST study, the Phase 3 ENABLAR-2 study, the sabizabulin monotherapy Phase 2b clinical study for 3rd line treatment of metastatic breast cancer, the Phase 2 registration clinical study for VERU-100, and the development of the companion diagnostic will be met; when clinical results from the ongoing clinical studies will be available, whether sabizabulin, enobosarm, VERU-100, zuclomiphene, and ENTADFI will serve any unmet need or, what dosage, if any, might be approved for use in the U.S. or elsewhere, and also statements about the potential, timing and efficacy of the rest of the Company’s development pipeline, and the timing of the Company’s submissions to FDA and MHRA and FDA’s and MHRA’s review of all such submissions; whether the companion diagnostic for enobosarm will be developed successfully or be approved by the FDA for use; and whether and when ENTADFI will be commercialized successfully. These forward-looking statements are based on the Company’s current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: the development of the Company’s product portfolio and the results of clinical studies possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical studies and the ability to enroll subjects in accordance with planned schedules; the ability to fund planned clinical development; the timing of any submission to the FDA, MHRA or any other regulatory authority and any determinations made by the FDA, MHRA or any other regulatory authority; the possibility that as vaccines and other antiviral medicines become widely distributed the need for new COVID-19 treatment candidates may be reduced or eliminated; government entities possibly taking actions that directly or indirectly have the effect of limiting opportunities for sabizabulin as a COVID-19 treatment, including favoring other treatment alternatives or imposing price controls on COVID-19 treatments; the Company’s existing products and any future products, if approved, possibly not being commercially successful; the effects of the COVID-19 pandemic and measures to address the pandemic on the Company’s clinical studies, supply chain and other third-party providers, commercial efforts, and business development operations; the ability of the Company to obtain sufficient financing on acceptable terms when needed to fund development and operations; demand for, market acceptance of, and competition against any of the Company’s products or product candidates; new or existing competitors with greater resources and capabilities and new competitive product approvals and/or introductions; changes in regulatory practices or policies or government-driven healthcare reform efforts, including pricing pressures and insurance coverage and reimbursement changes; risks relating to the Company's development of its own dedicated direct to patient telemedicine and telepharmacy services platform, including the Company's lack of experience in developing such a platform, potential regulatory complexity, and development costs; the Company’s ability to protect and enforce its intellectual property; the potential that delays in orders or shipments under government tenders or the Company’s U.S. prescription business relating to the FC2 female condom could cause significant quarter-to-quarter variations in the Company’s operating results and adversely affect its net revenues and gross profit; 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 for its FC2 female condom; the concentration of accounts receivable with our largest customers and the collection of those receivables; the Company’s production capacity, efficiency and supply constraints and interruptions, including potential disruption of production at the Company’s and third party manufacturing facilities and/or of the Company’s ability to timely supply any of its product due to labor unrest or strikes, labor shortages, raw material shortages, physical damage to the Company’s and third party facilities, COVID-19 (including the impact of COVID-19 on suppliers of key raw materials), product testing, transportation delays or regulatory actions; 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; 3 the Company’s ability to successfully integrate acquired businesses, technologies or products; and other risks detailed from time to time in the Company’s press releases, shareholder communications and Securities and Exchange Commission filings, including the Company’s Form 10-K for the fiscal year ended September 30, 2021 and subsequent quarterly reports on Form 10-Q. These documents are available on the “SEC Filings” section of our website at www.verupharma.com/investors. The Company disclaims any intent or obligation to update these forward-looking statements. Verzenio® is a registered trademark of Eli Lilly and Company NEJM Evidence® is a registered trademark of the Massachusetts Medical Society 4 Investor Contact: [email protected] Samuel Fisch - Executive Director, Investor Relations and Corporate Communications Media Contact: [email protected] Anthony Berry - Evoke Canale Medical Contact: [email protected] Tara Gonzales - Vice President, Medical Affairs Infectious Diseases Franchise Veru Announces New England Journal of Medicine Evidence Publication of Phase 3 Clinical Trial Results Demonstrating that Sabizabulin Treatment Significantly Reduced Deaths in High-Risk Hospitalized COVID-19 Patients -- Phase 3 Clinical Study Met Primary and Key Secondary Endpoints-- -- Primary Endpoint: Sabizabulin Treatment Showed Statistically Significant and Clinically Meaningful 55.2% Reduction in Deaths Compared to Placebo in Moderate-Severe Hospitalized COVID-19 Patients -- -- Key Secondary Endpoints: Sabizabulin Treatment had Significant and Clinically Meaningful Reduction in Days in ICU, Days on Mechanical Ventilation, and Days in the Hospital-- -- Sabizabulin was Well Tolerated with a More Favorable Safety Profile Compared to Placebo — --Company Submitted Request for Emergency Use Authorization to FDA on 6/7/22 -- MIAMI – July 6, 2022 – Veru Inc. (NASDAQ: VERU), a biopharmaceutical company focused on developing novel medicines for COVID-19 and other viral and ARDS-related diseases and for the management of breast and prostate cancers, today announced the publication of the results from a Phase 3 COVID-19 study evaluating the efficacy and safety of oral sabizabulin, a novel dual antiviral and anti-inflammatory agent, for the treatment of hospitalized moderate-severe COVID-19 patients at high risk for acute respiratory distress syndrome (ARDS) and death in The New England Journal of Medicine (NEJM) Evidence. The Phase 3 COVID-19 clinical trial is a double-blind, randomized, multicenter, and global placebo- controlled study evaluating oral, once-a-day dosing of sabizabulin 9 mg versus placebo in approximately 210 hospitalized moderate to severe COVID-19 patients ( WHO 4, supplemental oxygen) who were at high risk for ARDS and death. Patients were randomized in a 2:1 ratio to the sabizabulin treatment group versus placebo. Patients in both treatment groups were allowed to receive standard of care treatment including remdesivir, dexamethasone, anti-IL6 receptor antibodies, and JAK inhibitors. The trial was conducted in the United States, Brazil, Colombia, Argentina, Mexico, and Bulgaria. COVID-19 infections treated in the study included the Delta and Omicron variants. A planned interim analysis was conducted in the first 150 patients randomized into the study. The Independent Data Safety Monitoring Committee unanimously recommended that the Phase 3 study be halted early due to clear efficacy benefit. For the primary efficacy endpoint, which was death at or before day 60, sabizabulin treatment resulted in a clinically and statistically meaningful 55.2% relative reduction in deaths (p=0.0042) in the intent to treat population (ITT). At Day 60, the placebo group (n=52) had a 45.1% mortality rate compared to the sabizabulin-treated group (n=98) which had a 20.2% mortality rate. In the overall study of 204 randomized patients, the reduction in the all-cause mortality (ITT population) was similar to the results observed in the interim efficacy analysis patient population with sabizabulin treatment resulting in a 51.6% reduction in deaths compared to the placebo group. The key secondary endpoints included effects of sabizabulin treatment on mortality through Day 29, with a placebo mortality rate of 35.3% compared to sabizabulin treatment mortality rate of 17%, sabizabulin treatment resulted in an absolute reduction of 18.3 percentage points and a relative reduction in deaths of 51.8%. Sabizabulin treatment also resulted in a 43% relative reduction in days in ICU (p=0.0013), 49% relative reduction in days on mechanical ventilation (p=0.0013), and 26% relative reduction in days in hospital (p=0.0277) compared to placebo group. Adverse and serious adverse events were lower in the sabizabulin group compared to the placebo group. “We are proud and honored to have the Phase 3 COVID-19 study results published in The New England Journal of Medicine Evidence, a highly prestigious peer reviewed medical journal. The overall conclusion of this Phase 3 study is that sabizabulin treatment has a clear mortality benefit compared to placebo in hospitalized COVID-19 patients at high risk for ARDS receiving standard of care treatment with no significant safety signals,” said Gary Barnette, PhD, Chief Scientific Officer of Veru and co- author of the NEJM Evidence publication. “Unfortunately, COVID-19 is here to stay with new variants emerging and with rising rates of new cases, hospitalizations, and deaths. The current death rate from COVID-19 infection is unacceptable,” said Alan Skolnick, M.D., Principal Investigator with HD Research, who conducted this Phase 3 COVID- 19 study at Memorial Hermann Memorial City Medical Center in Houston TX, co-author of the NEJM Evidence publication. “We have battled this pandemic for two and a half years now, and we are still in desperate need for an effective treatment like sabizabulin to significantly reduce deaths in hospitalized COVID-19 patients. It’s in the hospital that we have the last real opportunity to prevent deaths from COVID-19 infection,” added Dr. Skolnick. “This landmark study published in The New England Journal of Medicine Evidence shows the high consistency of sabizabulin treatment to significantly reduce deaths across patient subgroups regardless of standard of care treatment received, baseline WHO scores, age, comorbidities, vaccination status, COVID-19 variant, or geography,” said Mitchell Steiner, M.D., Chairman, President, and Chief Executive Officer of Veru and co-author of the NEJM Evidence publication. “We have submitted a request for emergency use authorization with FDA and are in discussions with other regulatory authorities across the world.” Regulatory Discussion and Planning The Company submitted a request for an EUA application on June 7, 2022. The Company has scaled up manufacturing and expects to be able to produce sufficient commercial drug supply to address anticipated drug needs following potential FDA authorization in the U.S. and subsequent authorizations in other countries and regions. The Company is having discussions with government agencies to discuss purchases and reimbursement for sabizabulin in the U.S. and other countries around the world. 2 About Veru Inc. Veru is a biopharmaceutical company focused on developing novel medicines for COVID-19 and other viral and ARDS-related diseases and for the management of breast and prostate cancers. The Company’s late-stage breast cancer development portfolio comprises enobosarm, a selective androgen receptor targeting agonist, and sabizabulin. Current studies on the two drugs include: • Enrolling Phase 3 ARTEST study of enobosarm in androgen receptor positive, estrogen receptor positive, and human epidermal growth factor receptor two negative (AR+ ER+ HER2-) metastatic breast cancer with AR ≥ 40% expression (third-line metastatic setting), and which has been granted Fast Track designation by the FDA. • Enrolling Phase 3 ENABLAR-2 study of enobosarm + abemaciclib (a CDK 4/6 inhibitor) combination in AR+ ER+ HER2- metastatic breast cancer with AR ≥ 40% expression (second- line metastatic setting). The Company and Eli Lilly and Company have entered into a clinical study collaboration and supply agreement for the ENABLAR-2 study. Lilly will supply Verzenio® (abemaciclib). • Planned Phase 2b study of sabizabulin in AR+ ER+ HER2- metastatic breast cancer with AR < 40% expression (third-line metastatic setting). Veru’s late-stage prostate cancer portfolio comprises sabizabulin, VERU-100, a long-acting GnRH antagonist, and zuclomiphene citrate, an oral nonsteroidal estrogen receptor agonist. Current studies on these drugs include: • Enrolling Phase 3 VERACITY study in metastatic castration and androgen receptor targeting agent resistant prostate cancer prior to IV chemotherapy. • Enrolling Phase 2 dose-finding study of VERU-100 in advanced hormone sensitive prostate cancer. • Planned Phase 2b study of zuclomiphene citrate to treat hot flashes in men with advanced prostate cancer undergoing androgen deprivation therapy. Veru also has a commercial sexual health division – Urev, the proceeds of which help fund its drug development programs, comprised of 2 FDA approved products: • ENTADFI™ (finasteride and tadalafil) capsules for oral use, a new treatment for benign prostatic hyperplasia, for which commercialization launch plans are underway. • FC2 Female Condom® (internal condom), for the dual protection against unplanned pregnancy and the transmission of sexually transmitted infections which is sold in the U.S. and globally. Forward-Looking Statements The statements in this release that are not historical facts are “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995. Forward-looking statements in this release include statements regarding: whether and when the Company will receive an emergency use authorization or any approval from FDA or from any regulatory authority outside the U.S. for sabizabulin for certain COVID-19 patients; whether and when sabizabulin will become an available treatment option for certain COVID-19 patients in the U.S. or anywhere outside the U.S.; whether the Company will have sufficient supply of sabizabulin to meet demand, if an emergency use authorization or other approval is granted in the U.S. or in any other country; whether the Company will secure any advance purchase 3 agreement with the U.S. government or any foreign government; whether the current and future clinical development and results will demonstrate sufficient efficacy and safety and potential benefits to secure FDA approval of the Company’s drug candidates and companion diagnostic; whether the drug candidates will be approved for the targeted line of therapy; the anticipated design and scope of clinical studies and FDA acceptance of such design and scope; whether any regulatory pathways, including the accelerated Fast Track designations, to seek FDA approval for sabizabulin, enobosarm or any of the Company’s drug candidates are or continue to be available; whether the expected commencement and timing of the Company’s clinical studies, including the Phase 3 ENABLAR-2 study, the sabizabulin monotherapy Phase 2b clinical study for 3rd line treatment of metastatic breast cancer, the Phase 2 registration clinical study for VERU-100, and the development of the companion diagnostic will be met; when clinical results from the ongoing clinical studies will be available, whether sabizabulin, enobosarm, VERU-100, zuclomiphene, and ENTADFI will serve any unmet need or, what dosage, if any, might be approved for use in the U.S. or elsewhere, and also statements about the potential, timing and efficacy of the rest of the Company’s development pipeline, and the timing of the Company’s submissions to FDA and FDA’s review of all such submissions; whether any of the selective clinical properties previously observed in clinical studies of sabizabulin, enobosarm, VERU-100 or other drug candidates will be replicated in the current and planned clinical development program for such drug candidates and whether any such properties will be recognized by the FDA in any potential approvals and labeling; whether the companion diagnostic for enobosarm will be developed successfully or be approved by the FDA for use; and whether and when ENTADFI will be commercialized successfully. These forward-looking statements are based on the Company’s current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: the development of the Company’s product portfolio and the results of clinical studies possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical studies and the ability to enroll subjects in accordance with planned schedules; the ability to fund planned clinical development; the timing of any submission to the FDA and any determinations made by the FDA or any other regulatory authority; the possibility that as vaccines become widely distributed the need for new COVID-19 treatment candidates may be reduced or eliminated; government entities possibly taking actions that directly or indirectly have the effect of limiting opportunities for sabizabulin as a COVID-19 treatment, including favoring other treatment alternatives or imposing price controls on COVID-19 treatments; the Company’s existing products and any future products, if approved, possibly not being commercially successful; the effects of the COVID-19 pandemic and measures to address the pandemic on the Company’s clinical studies, supply chain and other third-party providers, commercial efforts, and business development operations; the ability of the Company to obtain sufficient financing on acceptable terms when needed to fund development and operations; demand for, market acceptance of, and competition against any of the Company’s products or product candidates; new or existing competitors with greater resources and capabilities and new competitive product approvals and/or introductions; changes in regulatory practices or policies or government-driven healthcare reform efforts, including pricing pressures and insurance coverage and reimbursement changes; the Company’s ability to successfully commercialize any of its products, if approved; risks relating to the Company's development of its own dedicated direct to patient telemedicine and telepharmacy services platform, including the Company's lack of experience in developing such a platform, potential regulatory complexity, and development costs; the Company’s ability to protect and enforce its intellectual property; the potential 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; 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; the concentration of accounts receivable with our largest customers and the collection of those receivables; the Company’s production capacity, efficiency and supply constraints and interruptions, including potential disruption of production at the Company’s and third party 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 and third party facilities, COVID-19 4 (including the impact of COVID-19 on suppliers of key raw materials), product testing, transportation delays or regulatory actions; 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 from time to time in the Company’s press releases, shareholder communications and Securities and Exchange Commission filings, including the Company’s Form 10-K for the fiscal year ended September 30, 2021 and subsequent quarterly reports on Form 10-Q. These documents are available on the “SEC Filings” section of our website at www.verupharma.com/investors. The Company disclaims any intent or obligation to update these forward-looking statements. Verzenio® is a registered trademark of Eli Lilly and Company 5

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