0001429560 false 0001429560 2020-08-07 2020-08-07 iso4217:USD xbrli:shares iso4217:USD xbrli:shares

 

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

FORM 8-K

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of The Securities Exchange Act of 1934

 

Date of Report (Date of earliest event reported): August 7, 2020

 

TREVENA, INC.

(Exact name of registrant as specified in its charter)

 

Delaware 001-36193   26-1469215
(State or other jurisdiction of
incorporation) 		(Commission File No.)     (IRS Employer
Identification No.)

 

955 Chesterbrook Boulevard, Suite 110

Chesterbrook, PA 19087

(Address of principal executive offices and zip code)

 

(610) 354-8840

(Registrant’s telephone number, including area code) 

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class   Trading Symbol(s)   Name of each exchange on which registered
Common Stock, $0.001 par value   TRVN   The Nasdaq Stock Market LLC

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter). Emerging growth company ¨

 

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨

 

 

 

 

 

 

  Item 2.02. Results of Operations and Financial Condition.

 

On August 10, 2020, Trevena, Inc. (the "Company") issued a press release announcing that the U.S. Food and Drug Administration has approved its lead drug candidate, OLINVYK (oliceridine) injection, that is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternate treatments are inadequate. The press release also announced certain financial information for the quarter ended June 30, 2020. A copy of the press release is furnished hereto as Exhibit 99.1.

 

The information under this caption and contained in the press release attached hereto as Exhibit 99.1 is furnished by the Company in accordance with Securities Exchange Commission Release No. 33-8216. This information shall not be deemed "filed" for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the "Exchange Act"), or incorporated by reference in any filing under the Securities Act of 1933, as amended (the "Securities Act"), or the Exchange Act whether made before or after the date of this Current Report on Form 8-K, except as shall be expressly set forth by specific reference in such a filing.

 

Item 7.01 Regulation FD Disclosure

 

On August 10, 2020, the Company updated its website to include an updated corporate presentation deck. A copy of the updated corporate deck is attached hereto as Exhibit 99.2.

 

Additionally, on August 10, 2020, the Company filed its Quarterly Report on Form 10-Q for the quarter ended June 30, 2020 with the Securities and Exchange Commission.

 

The information set forth on this Item 7.01 and furnished hereto as Exhibit 99.2 shall not be deemed “filed” for purposes of Section 18 of the Exchange Act, and is not incorporated by reference into any of the Company’s filings under the Securities Act or the Exchange Act, whether made before or after the date hereof, except as shall be expressly set forth by specific reference in any such filing.

 

Item 8.01 Other Events

 

The information contained in Item 2.02 is incorporated in its entirety into this Item 8.01.

 

  Item 9.01 Financial Statements and Exhibits.

 

(d) Exhibits.

 

Exhibit
No. 		  Description
99.1   Press Release dated August 10, 2020
99.2   Updated Corporate Presentation Deck dated August 10, 2020
104   The cover page from this Current Report on Form 8-K, formatted in Inline XBRL.

 

 

 

SIGNATURES

 

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

 

TREVENA, INC.

 

   
Date: August 10, 2020 By: /s/ Barry Shin
    Barry Shin
    Senior Vice President & Chief Financial Officer

 

 

 

 

Exhibit 99.1

 

Trevena Announces FDA Approval of OLINVYK™ (oliceridine) injection   

--

OLINVYK is a new chemical entity approved in adults for the management of acute pain severe enough to require an IV opioid analgesic

 

OLINVYK product availability expected in fourth quarter of 2020

 

Company funded through year-end 2021, including OLINVYK commercialization  

-- 

Company to host conference call at 8:30 a.m., today, August 10, 2020 

-- 

CHESTERBROOK, Pa., August 10, 2020 (GLOBE NEWSWIRE) -- Trevena, Inc. (Nasdaq: TRVN), a biopharmaceutical company focused on the development and commercialization of novel medicines for patients with central nervous system (CNS) disorders, today announced that the U.S. Food and Drug Administration (FDA) has approved OLINVYK in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. OLINVYK will be commercially available when the U.S. Drug Enforcement Administration (DEA) issues its controlled substance schedule in approximately 90 days.

 

“The approval of OLINVYK marks an exciting step forward in Trevena’s mission of translating cutting-edge scientific discovery into therapeutic benefit for patients in need. I would like to thank all of the patients, investigators, and our employees who helped us achieve this important milestone,” said Carrie L. Bourdow, President and Chief Executive Officer. “We will work quickly to bring this novel IV analgesic to patients and healthcare providers in need of alternative treatment options.”

 

Each year, approximately 45 million hospital patients in the United States receive an IV opioid to treat their acute pain. Many of these patients are complex and difficult to treat, such as the elderly, obese, or renally-impaired. Current hospital trends suggest that the number of these complex patients is growing, representing an increasing burden on the healthcare system.

 

OLINVYK is an opioid agonist that is the first new chemical entity in this IV drug class in decades and offers a differentiated profile that addresses a significant unmet need in the acute pain management landscape. OLINVYK delivers IV opioid efficacy with a rapid 2-5 minute onset of action. In addition, OLINVYK requires no dosage adjustments in patients with renal impairment, a large patient population with significant medical complications.

 

 

 

 

The FDA approval of OLINVYK was based on results from the Phase 3 development program, which evaluated OLINVYK in over 1,500 patients with moderate to severe acute pain. In two pivotal efficacy studies in hard- and soft-tissue surgical models, OLINVYK demonstrated rapid analgesic efficacy statistically significant vs. placebo. In a large, open-label, “real world” safety study, OLINVYK was safe and well-tolerated in a medically complex patient population, including the elderly, obese, and patients with comorbid conditions such as diabetes and sleep apnea.

 

“Complex patients present unique challenges in the management of their postoperative acute pain, due to the presence of medical comorbidities that can complicate dosing,” said Gregory Hammer, M.D., Professor of Anesthesiology, Perioperative and Pain Medicine, and of Pediatrics at Stanford University. “OLINVYK represents a new alternative for clinicians, due to its rapid onset of action, effective pain relief, and unique profile.”

 

The Company expects to make OLINVYK available in the fourth quarter of 2020 following scheduling by the DEA, which may take up to 90 days. The Company is committed to an ethical and responsible marketing campaign for OLINVYK and will have safeguards in place to monitor for and mitigate the risk of non-medical uses of OLINVYK.

 

The Company also today announced $54.8 million in cash and cash equivalents as of June 30, 2020, which the Company expects will be sufficient to fund operating expenses, including the commercialization of OLINVYK, through year-end 2021.

 

Conference Call and Webcast Information

 

The Company will host a conference call and webcast with the investment community on August 10, 2020, at 8:30 a.m. Eastern Time featuring remarks by Carrie Bourdow, President and Chief Executive Officer, Mark Demitrack, M.D., Chief Medical Officer, Robert Yoder, Chief Business Officer, and Barry Shin, Chief Financial Officer.

 

Title:   Conference Call to Provide Update Following Recent FDA Approval of OLINVYK
     
Date:   Monday, August 10, 2020
     
Time:   8:30 a.m. ET
     
Conference Call Details:   Toll-Free: 855-465-0180
International: 484-756-4313
Conference ID: 4976734
     
Webcast:   https://www.trevena.com/investors/events-presentations/ir-calendar

 

OLINVYK Efficacy and Safety Data

 

The efficacy of OLINVYK was established in two randomized, double-blind, placebo- and morphine-controlled studies which enrolled 790 patients with moderate to severe acute pain (pain intensity of ≥4 on a 0-10 numeric rating scale) after orthopedic surgery-bunionectomy or plastic surgery-abdominoplasty.

 

 

 

 

In each study, patients were randomized to one of three OLINVYK treatment regimens, a placebo-control regimen, or a morphine-control regimen. The loading dose for all OLINVYK treatment regimens was 1.5 mg; demand doses were 0.1, 0.35, or 0.5 mg, according to the assigned treatment group; supplemental doses were 0.75 mg. A lockout interval of 6 minutes was used for all PCA regimens. Etodolac 200 mg was available as rescue medication. Patients using the approved OLINVYK doses of 0.35 and 0.5 mg had a statistically significantly greater SPID-48/24 than patients using placebo.

 

The most common adverse reactions (≥10%) in these controlled trials were nausea, vomiting, dizziness, headache, constipation, pruritus, and hypoxia. When stratified by the 27 mg daily dosing limit, discontinuation of OLINVYK due to adverse reactions occurred in 4% of patients who received a daily dose ≤ 27 mg, and less than 1% of patients who received a daily dose >27 mg.

 

In an open-label safety study of patients with moderate to severe acute pain following a surgical procedure or due to a medical condition, a total of 768 patients received at least one dose of OLINVYK. OLINVYK was administered via clinician-administered bolus dosing, PCA, or a combination of the two. Bolus dosing was initiated at 1 to 2 mg, with supplemental doses of 1 to 3 mg every 1 to 3 hours, as needed, based on individual patient need and previous response to OLINVYK. If OLINVYK was administered via PCA, the loading dose was 1.5 mg, the demand dose was 0.5 mg, and the lockout interval was 6 minutes. Supplemental doses of 1 mg were given as needed, taking into account the patient's utilization of PCA demand doses, individual patient need, and previous response to OLINVYK.

 

The most frequent condition treated in the open-label safety study was postsurgical acute pain, and included (in order of decreasing frequency): orthopedic, gynecologic, colorectal, general, plastic, urologic, neurologic (including spinal), bariatric, and cardiothoracic surgical procedures. Of the 768 patients treated with OLINVYK, 32% were age 65 years or older and 78% had a Body Mass Index ≥ 25 kg/m2. OLINVYK was administered as needed; 55% of patients received OLINVYK via clinician bolus administration only, and 45% of patients received OLINVYK via PCA self-administration or a combination of clinician bolus- and PCA self-administration. Discontinuation of OLINVYK in this study due to adverse drug reactions occurred in 3% of patients who received a daily dose ≤ 27 mg and 1% of patients who received a daily dose >27 mg.

 

Full Prescribing Information, including the Boxed Warning, is available at www.OLINVYK.com.

 

IMPORTANT SAFETY INFORMATION

 

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CENTRAL NERVOUS SYSTEM (CNS) DEPRESSANTS

Addiction, Abuse, and Misuse

 

OLINVYK exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing OLINVYK, and monitor all patients regularly for the development of behaviors or conditions.

 

Life-Threatening Respiratory Depression

 

Serious, life-threatening, or fatal respiratory depression may occur with use of OLINVYK. Monitor for respiratory depression, especially during initiation of OLINVYK or following a dose increase.

 

 

 

 

Neonatal Opioid Withdrawal Syndrome

 

Prolonged use of OLINVYK during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. 

 

Risk From Concomitant Use With Benzodiazepines or Other CNS Depressants

 

Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.

 

INDICATIONS AND USAGE

 

OLINVYK is a new chemical entity indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate.

 

Limitations of Use

 

Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve OLINVYK for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]:

 

· Have not been tolerated, or are not expected to be tolerated
· Have not provided adequate analgesia, or are not expected to provide adequate analgesia.

 

The cumulative total daily dose should not exceed 27 mg, as total daily doses greater than 27 mg may increase the risk for QTc interval prolongation.

 

CONTRAINDICATIONS

 

OLINVYK is contraindicated in patients with:

 

· Significant respiratory depression
· Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
· Known or suspected gastrointestinal obstruction, including paralytic ileus
· Known hypersensitivity to oliceridine (e.g., anaphylaxis)

 

WARNINGS AND PRECAUTIONS

 

· OLINVYK contains oliceridine, a Schedule [controlled substance schedule pending], that exposes users to the risks of addiction, abuse, and misuse. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed OLINVYK. Assess risk, counsel, and monitor all patients receiving opioids.

 

 

 

 

· Serious, life-threatening respiratory depression has been reported with the use of opioids, even when used as recommended, especially in patients with chronic pulmonary disease, or in elderly, cachectic and debilitated patients. The risk is greatest during initiation of OLINVYK therapy, following a dose increase, or when used with other drugs that depress respiration. Proper dosing of OLINVYK is essential, especially when converting patients from another opioid product to avoid overdose. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status.
· Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia with risk increasing in a dose-dependent fashion. In patients who present with CSA, consider decreasing the dose of opioid using best practices for opioid taper.
· Prolonged use of opioids during pregnancy can result in withdrawal in the neonate that can be life-threatening. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using OLINVYK for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
· Profound sedation, respiratory depression, coma, and death may result from the concomitant use of OLINVYK with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, or alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate, prescribe the lowest effective dose, and minimize the duration.
· OLINVYK was shown to have mild QTc interval prolongation in thorough QT studies where patients were dosed up to 27 mg. Total cumulative daily doses exceeding 27 mg per day were not studied and may increase the risk for QTc interval prolongation. Therefore, the cumulative total daily dose of OLINVYK should not exceed 27 mg.
· Increased plasma concentrations of OLINVYK may occur in patients with decreased Cytochrome P450 (CYP) 2D6 function or normal metabolizers taking moderate or strong CYP2D6 inhibitors; also in patients taking a moderate or strong CYP3A4 inhibitor, in patients with decreased CYP2D6 function who are also receiving a moderate or strong CYP3A4 inhibitor, or with discontinuation of a CYP3A4 inducer. These patients may require less frequent dosing and should be closely monitored for respiratory depression and sedation at frequent intervals. Concomitant use of OLINVYK with CYP3A4 inducers or discontinuation of a moderate or strong CYP3A4 inhibitor can lower the expected concentration, which may decrease efficacy, and may require supplemental doses.
· Cases of adrenal insufficiency have been reported with opioid use (usually greater than one month). Presentation and symptoms may be nonspecific and include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If confirmed, treat with physiologic replacement doses of corticosteroids and wean patient from the opioid.
· OLINVYK may cause severe hypotension, including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics). Monitor these patients for signs of hypotension. In patients with circulatory shock, avoid the use of OLINVYK as it may cause vasodilation that can further reduce cardiac output and blood pressure.
· Avoid the use of OLINVYK in patients with impaired consciousness or coma. OLINVYK should be used with caution in patients who may be susceptible to the intracranial effects of CO2 retention, such as those with evidence of increased intracranial pressure or brain tumors, as a reduction in respiratory drive and the resultant CO2 retention can further increase intracranial pressure.

 

 

 

 

Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy. 

· As with all opioids, OLINVYK may cause spasm of the sphincter of Oddi, and may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.
· OLINVYK may increase the frequency of seizures in patients with seizure disorders and may increase the risk of seizures in vulnerable patients. Monitor patients with a history of seizure disorders for worsened seizure control.
· Do not abruptly discontinue OLINVYK in a patient physically dependent on opioids. Gradually taper the dosage to avoid a withdrawal syndrome and return of pain. Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving OLINVYK, as they may reduce the analgesic effect and/or precipitate withdrawal symptoms.
· OLINVYK may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.
· Although self-administration of opioids by patient-controlled analgesia (PCA) may allow each patient to individually titrate to an acceptable level of analgesia, PCA administration has resulted in adverse outcomes and episodes of respiratory depression. Health care providers and family members monitoring patients receiving PCA analgesia should be instructed in the need for appropriate monitoring for excessive sedation, respiratory depression, or other adverse effects of opioid medications.

 

ADVERSE REACTIONS

 

Adverse reactions are described in greater detail in the Prescribing Information.

The most common (incidence ≥10%) adverse reactions in Phase 3 controlled clinical trials were nausea, vomiting, dizziness, headache, constipation, pruritus, and hypoxia.

 

About OLINVYK™ (oliceridine) injection

 

OLINVYK is a new chemical entity approved by the FDA in August 2020. It is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. OLINVYK will not be available for distribution until the United States Drug Enforcement Administration assigns it to its schedule of controlled substances. For more information, please visit www.OLINVYK.com.

 

About Trevena

 

Trevena, Inc. is a biopharmaceutical company focused on the development and commercialization of novel medicines for patients with CNS disorders. The Company has one approved product in the U.S., OLINVYK™ (oliceridine) injection, indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. The Company also has four novel and differentiated investigational drug candidates: TRV250 for the acute treatment of migraine, TRV734 for maintenance treatment of opioid use disorder, and TRV027 for acute lung injury / abnormal blood clotting in COVID-19 patients. The Company has also identified TRV045, a novel S1P receptor modulator that may offer a new, non-opioid approach to treating a variety of CNS disorders.

 

 

 

 

Forward-Looking Statements

 

Any statements in this press release about future expectations, plans and prospects for the Company, including statements about the Company’s strategy, future operations, clinical development and trials of its therapeutic candidates, plans for potential future product candidates, commercialization of approved drug products and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “objective,” “predict,” “project,” “suggest,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” “ongoing,” or the negative of these terms or similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the commercialization of any approved drug product, the status, timing, costs, results and interpretation of the Company’s clinical trials or any future trials of any of the Company’s investigational drug candidates; the uncertainties inherent in conducting clinical trials; expectations for regulatory interactions, submissions and approvals, including the Company’s assessment of the discussions with the FDA or other regulatory agencies about any and all of its programs; uncertainties related to the commercialization of OLINVYK; available funding; uncertainties related to the Company’s intellectual property; uncertainties related to the ongoing COVID-19 pandemic, other matters that could affect the availability or commercial potential of the Company’s therapeutic candidates; and other factors discussed in the Risk Factors set forth in the Company’s Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in other filings the Company makes with the SEC from time to time. In addition, the forward-looking statements included in this press release represent the Company’s views only as of the date hereof. The Company anticipates that subsequent events and developments may cause the Company’s views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, except as may be required by law.

 

For more information, please contact:

 

Investor Contact:

Dan Ferry

Managing Director

LifeSci Advisors, LLC

daniel@lifesciadvisors.com

(617) 430-7576

 

Company Contact:

Bob Yoder

SVP and Chief Business Officer

Trevena, Inc.

(610) 354-8840

 

 

 

 

Exhibit 99.2

 

INNOVATING FOR PATIENTS Nasdaq TRVN August 2020

 

 

5432-1-BA_CORPORATE_PAGE_02.JPG F35:%5(-L33/-2+ S7%7)1)276 '; @41 1D@1:@ @4-@ ?@-@191:@? /;:@-5:10 5: @45? <>1?1:@-@5;: ->1 :;@ 01?/>5<@5;:? ;2 45?@;>5/-8 2-/@? >13->05:3 '>1B1:-, I:/. (@41 HC;9<-:EI ;> HC1I), @41E ->1 2;>C->0-8;;75:3 ?@-@191:@? >1281/@5:3 9-:-3191:@J? /A>>1:@ .18512? -:0 1D<1/@-@5;:?. F;>C->0-8;;75:3 ?@-@191:@? ->1 ?A.61/@ @; 7:;C: -:0 A:7:;C: >5?7?, A:/1>@-5:@51?, -:0 ;@41> 2-/@;>? @4-@ 9-E /-A?1 ;A> ;> ;A> 5:0A?@>EJ? -/@A-8 >1?A8@?, 81B18? ;2 -/@5B5@E, <1>2;>9-:/1, ;> -/451B191:@? @; .1 9-@1>5-88E 05221>1:@ 2>;9 @4;?1 -:@5/5<-@10 .E ?A/4 ?@-@191:@?. ,;A /-: 501:@52E 2;>C->0-8;;75:3 ?@-@191:@? .E @1>95:;8;3E ?A/4 -? H-:@5/5<-@1,I H.1851B1,I H1?@59-@1,I H1D<1/@,I H5:@1:0,I H9-E,I H9534@,I H<8-:,I H;.61/@5B1,I H<>105/@,I H<>;61/@,I H?A331?@,I H@->31@,I H<;@1:@5-8,I HC588,I HC;A80,I H/;A80,I H?4;A80,I H/;:@5:A1,I H;:3;5:3,I ;> @41 :13-@5B1 ;2 @41?1 @1>9? ;> ?5958-> 1D<>1??5;:?. F;>C->0-8;;75:3 ?@-@191:@? /;:@-5:10 5: @45? <>1?1:@-@5;: 5:/8A01, .A@ ->1 :;@ 8595@10 @;, (5) ?@-@191:@? >13->05:3 @41 @595:3 ;2 -:@5/5<-@10 /85:5/-8 @>5-8? 2;> ;A> <>;0A/@ /-:050-@1?; (55) @41 @595:3 ;2 >1/15<@ ;2 /85:5/-8 0-@-2;> ;A> <>;0A/@ /-:050-@1?; (555) ;A> 1D<1/@-@5;:? >13->05:3 @41 <;@1:@5-8 ?-21@E, 1225/-/E, ;> /85:5/-8 A@585@E ;2 ;A> <>;0A/@ /-:050-@1?; (5B) @41 ?5F1 ;2 <-@51:@ <;<A8-@5;:? @->31@10 .E ;A> <>;0A/@ /-:050-@1? -:0 9->71@ -0;<@5;: ;2 ;A> <;@1:@5-8 0>A3? .E <4E?5/5-:? -:0 <-@51:@?; (B) @41 @595:3 ;> 8571854;;0 ;2 >13A8-@;>E 2585:3? -:0 -<<>;B-8?; -:0 (B5) ;A> /-?4 :110?. A/@A-8 >1?A8@? 9-E 05221> 9-@1>5-88E 2>;9 @4;?1 5:05/-@10 .E ?A/4 2;>C->0-8;;75:3 ?@-@191:@? -? - >1?A8@ ;2 B->5;A? 59<;>@-:@ 2-/@;>?, 5:/8A05:3: @41 /;991>/5-85F-@5;: ;2 -:E -<<>;B10 0>A3 <>;0A/@, @41 ?@-@A?, @595:3, /;?@?, >1?A8@? -:0 5:@1><>1@-@5;: ;2 ;A> /85:5/-8 @>5-8? ;> -:E 2A@A>1 @>5-8? ;2 -:E ;2 ;A> 5:B1?@53-@5;:-8 0>A3 /-:050-@1?; @41 A:/1>@-5:@51? 5:41>1:@ 5: /;:0A/@5:3 /85:5/-8 @>5-8?; 1D<1/@-@5;:? 2;> >13A8-@;>E 5:@1>-/@5;:?, ?A.95??5;:? -:0 -<<>;B-8?, 5:/8A05:3 ;A> -??1??91:@ ;2 @41 05?/A??5;:? C5@4 @41 FDA ;> ;@41> >13A8-@;>E -31:/51? -.;A@ -:E -:0 -88 ;2 ;A> <>;3>-9?; A:/1>@-5:@51? >18-@10 @; @41 /;991>/5-85F-@5;: ;2 "LI!),K; -B-58-.81 2A:05:3; A:/1>@-5:@51? >18-@10 @; ;A> 5:@1881/@A-8 <>;<1>@E; A:/1>@-5:@51? >18-@10 @; @41 ;:3;5:3 C")ID-19 <-:0195/, ;@41> 9-@@1>? @4-@ /;A80 -221/@ @41 -B-58-.585@E ;> /;991>/5-8 <;@1:@5-8 ;2 ;A> @41>-<1A@5/ /-:050-@1?; -:0 ;@41> 2-/@;>? 05?/A??10 5: @41 %5?7 F-/@;>? ?1@ 2;>@4 5: ;A> A::A-8 %1<;>@ ;: F;>9 10-K -:0 $A->@1>8E %1<;>@? ;: F;>9 10-$ 25810 C5@4 @41 &1/A>5@51? -:0 ED/4-:31 C;995??5;: (&EC) -:0 5: ;@41> 2585:3? C1 9-71 C5@4 @41 &EC 2>;9 @591 @; @591. I: -005@5;:, @41 2;>C->0-8;;75:3 ?@-@191:@? 5:/8A010 5: @45? <>1?1:@-@5;: >1<>1?1:@ ;A> B51C? ;:8E -? ;2 @41 0-@1 41>1;2. *1 -:@5/5<-@1 @4-@ ?A.?1=A1:@ 1B1:@? -:0 01B18;<91:@? 9-E /-A?1 ;A> B51C? @; /4-:31. H;C1B1>, C4581 C1 9-E 181/@ @; A<0-@1 @41?1 2;>C->0-8;;75:3 ?@-@191:@? -@ ?;91 <;5:@ 5: @41 2A@A>1, C1 ?<1/525/-88E 05?/8-59 -:E ;.853-@5;: @; 0; ?;, 1D/1<@ -? 9-E .1 >1=A5>10 .E 8-C. 2

 

 

5432-1-BA_CORPORATE_PAGE_03.JPG 5)9)2%?6 E;4)5-)2')( L)%()56,-4 )%1 C-<<51 . B:?<0:A $9.:2-.6; & C12./ E?.,<;2=. #//2,.9 '/:>> A;;71.-?8 ')$, C12./ .0*4 & &.0<4*;79@ #//2,.9 !-<6 A. D185><-/6, !.D. ')$, C12./ !.-2,*4 #//2,.9 B-<<C '459 ')$, C12./ F26*6,2*4 #//2,.9 &:.1<> (. ,:01< ')$, C12./ B<:26.:: #//2,.9 1:9 #. !:?701<, J<. Cha &"a# C-<<51 . B:?<0:A J?751 H. !/H?34 '/:>> B<-?9=>159, !.D. J-61 &. "?99 !5/4-17 &. D:?341<>C A991 !. $45775;=, !.D. !-B591 G:A19, $4.D. B-<.-<-,-995 3 B#A&D #F DI&EC(#&' 'E"I#& !A"AGE!E"(

 

 

5432-1-BA_CORPORATE_PAGE_04.JPG 5)9)2%: I2239%7-9) CNS C314%2< OLINVYK !) !$d!ca*ed !$ ad+"*) f%( * e #a$age#e$* %f ac+*e &a!$ )e,e(e e$%+g *% (e'+!(e a$ !$*(a,e$%+) %&!%!d a$a"ge)!c a$d f%( - %# a"*e($a*!,e *(ea*#e$*) a(e !$ade'+a*e. P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c%#. 4 )C )8J C;8@<64? AG<GLy (*A (86;4A<F@ B9 A6G<BAy +BC +EBB9-B9-CBA68CG OLIN$%K? &5564:*) '= FDA 'CE 2AAC@G65 7@C E96 >2?286>6?E @7 24FE6 A2:? :? 25F=ED DEA D4965F=:?8 A6?5:?8; AC@5F4E 2G2:=23:=:EJ :? *4 2020 L&6,* 2&60*8, 8&6,*8*) 1&93(-45&+ ., 9@DA:E2= A2E:6?ED; 9& AC@465FC6D :D :?:E:2= 4@C6 7@4FD $1.58+ >2C<6E @AA@CEF?:EJ 7@C 4@C6 7@4FD N4:*1 CN! 5.5*1.3* '6H >6492?:D>D 7@C 24FE6 >:8C2:?6, @A:@:5 FD6 5:D@C56C, 6A:=6ADJ, A2:? 'CED E2C86E:?8 D:8?:7:42?E F?>6E ?665D " $027 +46 CO$ID-19 '@G6= &(A E@ EC62E C(/#D-19 24FE6 =F?8 :?;FCJ / 23?@C>2= 4=@EE:?8 )@C DEF5J :? 4@==23@C2E:@? H:E9 #>A6C:2= C@==686 %@?5@?; E@A=:?6 52E2 6IA64E65 :? L6 >@?E9D !41.) +.3&3(.&1 547.8.43 $54.8& :? 42D9 2D @7 6/30/2020 F?5D @A6C2E:@?D E9C@F89 J62C-6?5 2021

 

 

5432-1-BA_CORPORATE_PAGE_05.JPG M807-40) E;4)'7)( C%7%0<676 (&)027 "7=.4 A(1 9.,.8;79 :.4.,;2=. *0762:; A?3 2020: ';<-@ 262;2*;276 %1 2021: (78426. -*;* (IC A&D' / -.9:<8-7 /7:>>593 (C#)ID-19) C-**!"-/!1)-, 3)1( I+.%/)!* C-**%'% L-,$-, I# ) (&)734 G-897;.26 :.4.,;2=. *0762:; (5<-78272-9.,.8;79) C-**!"-/!1)-, 3)1( N!1)-,!* I,01)121% -, D/2' A"20% $7C :;<-@ -*;* ("IDA) #;5:50 ?=1 05=:<01< 24%/ C"' "7=.4 '1$ 9.,.8;79 57-<4*;79 24%/ N!1)-,!* I,01)121%0 -& 1H 21: I"D /24260 P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c%#. /-1250, /-1734, /-1027, 4A7 /-1045 4E8 <AI8FG<:4G<BA4? CEB7H6GF 4A7 4E8 ABG 4CCEBI87 5L G;8 !DA BE 4AL BG;8E E8:H?4GBEL 4:8A6L. A-D. A6HG8 -8FC<E4GBEL D<FGE8FF .LA7EB@8y $)D $AI8FG<:4G<BA4? )8J DEH:y +BC +EBB9-B9-CBA68CG 5 (&)045C-**!"-/!1)-, 3)1( 05=:<01<= H%!*1( (&)250 G-897;.26 :.4.,;2=. *0762:;A/?>1 853<-591 24%//57&'76%1)2752H 21: C4262,*4 :;<-@ 262;2*;276 (-.4;* 9.,.8;79) # I"),KD ".> ,1.52,*4 .6;2;@A/?>1 ;-59 I# A$$&#)ED 8/07/2020%4 2020: $97-<,; *=*24*+4. (5<-78272-9.,.8;79) $&E-C I"ICA$HA'E 1$HA'E 2$HA'E 3"DA E+$EC(ED CA(A ,'('

 

 

5432-1-BA_CORPORATE_PAGE_06.JPG OLIN"$K> (30-')5-(-2)) -2.)'7-32: N3: A44539)( 6 P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c%#.

 

 

5432-1-BA_CORPORATE_PAGE_07.JPG OLIN"$K: D-**)5)27-%7)( P53*-0) *35 A'87) P%-2 (%#'/1$ :D :?5:42E65 :? 25F=ED 7@C E96 >2?286>6?E @7 24FE6 A2:? D6G6C6 6?@F89 E@ C6BF:C6 2? :?EC2G6?@FD @A:@:5 2?2=86D:4 2?5 7@C H9@> 2=E6C?2E:G6 EC62E>6?ED 2C6 :?256BF2E6 E);-7. =;-16 +4161+)4 8:)+<1+-8@=FD / )CA; ?@ 24E:G6 >6E23@=:E6D -? +0-51+)4 -6<1<A D:DE:?4E 7C@> #/ >@CA9:?6 D)<) 16 +7584-@ 8)<1-6<; E=56C=J, @36D6, C6?2= :>A2:C65 & 78171, -..1+)+A "2C5-2?5 D@7E-E:DDF6 DFC86C:6D '-44-+0):)+<-:1B-, ;).-<A I <74-:)*141<A #/ >@CA9:?6 52E2 :?4=F565 :? =236= #)81, )6)4/-;1) 2-5 >:? @?D6E @7 A2:? C6=:67 P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c%#. OLINVYK !) $%* c%##e(c!a"". a,a!"ab"e a$d !*) c%$*(%""ed )+b)*a$ce )c ed+"e !) &e$d!$g U.S. DEA ac*!%$. ?

 

 

5432-1-BA_CORPORATE_PAGE_08.JPG OLIN"$K: B53%( I2(-'%7-32 *35 A'87) P%-2 L(9., (*<;, 4(92,; 67769;<50;@ US ).*&$3"#,& ".",'&2)$ (/20)3", -"1+&3 4.)3 5/,4-&1 45M patients receive IV opioids annually to treat acute pain1 I) 78272-: C $590=(33,+ (5(3.,:0* ,--0*(*@ 38% 45% I) #;5:50= 7,*4 *6.:;1.;2,: C #67 :<9.,90,:: #6;(3 25,, (9;/9673(:;@, *63,*;64@, /,950( 9,7(09, :705, -<:065, C-:,*;0652 I) "'AID' I *,.;*526781.6 17% OLINVYK !) !$d!ca*ed !$ ad+"*) f%( * e #a$age#e$* %f ac+*e &a!$ *% (e'+!(e a$ !$*(a,e$%+) %&!%!d a$a"ge)!c a$d f%( - %# a"*e($a*!,e *(ea*#e$*) a(e !$ade'+a*e. )e,e(e e$%+g P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c%#. 8 ).A$DF ABAFG8EB<74? 4AG<-<A9?4@@4GBEL 7EH:F. $(. ($DA. F4?8F 4H7<G 20 7y $1 ).A$DF 4A7 *9<E@8IN. 2 D89<A<G<I8 74G454F8, 4A7 )4G<BA4? 1<G4? .G4G<FG<6F E8CBEG, CDC 20 .

 

 

5432-1-BA_CORPORATE_PAGE_09.JPG OLIN"$K: D-67-2'7 F531 I" M354,-2) I H<(531354,32) S+, #! #& >1,900 #& #-# ,a$* IV %')("#&! #&c$, ! a* ac+#-! c'%(a)a+') NCE .#+" 2032+ COM (a+!&+1 !:<;4591 HC0<:8:<;4:91 P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c%#. 2032 6B@CBF<G<BA B9 @4GG8E C4G8AG 8KC<E4G<BA 7B8F ABG <A6?H78 CBG8AG<4? C4G8AG 8KG8AF<BAF. OLIN !K

 

 

5432-1-BA_CORPORATE_PAGE_10.JPG OLIN"$K: I" O4-3-( E**-'%'< %2( R%4-( O26)7 , Efficac+ achie)ed i" ha%d 'i&&(e & &#f' 'i&&(e !#de & $7.< %1;;=-($" D-24) H):, %1;;=-($" D-48) , Ra$id #"&e': $e%ce$'ib e $ai" %e ief *i'hi" 2-5 !i"('e& ,FA6C:@C A2:? C6=:67 GD. A=2463@ (A<0.01) ,FA6C:@C A2:? C6=:67 GD. A=2463(A<0.02) , OLINVYK efficac+ da'a i" $ee%-%e)ie*ed j#(%"a & The Journal of Pain Research1 (5+ Pain Practice2 &5.) 437*8 (2-5 >:?) & L3 9@FC 5FC2E:@? P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c%#. 10 1<F6HF< - 8G 4?. % +4<A -8F. 20 y 2 27P 43. +H5?<F;87 20 (4E. 2 .<A:?4 )& 8G 4?. +4<A +E46G. 20 y 7 5-73 . +H5?<F;87 20 %HA 04.

 

 

5432-1-BA_CORPORATE_PAGE_11.JPG OLIN"$K: #)00-C,%5%'7)5-=)( S%*)7< I 30)5%&-0-7< Ad. *+ d*-" * ac,$('+ * )(*, d $' 05% (! OLINVYK-,* a, d )a,$ ',+ +,*a,$!$ d b/ da$%/ d(+ (P#a+ 3 )$.(,a% ,*$a%+ )((% d)1 P"2)&-21 4)2( "-6 TEAE (%) !-A?1-);95@5:3 H1-0-/41 D5FF5:1?? C;:?@5<-@5;: HE<;D5-#>A>5@A? &10-@5;: &;9:;81:/1 B-/7 <-5: H;@ 28A?4 #>A>5@A? 31:. P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c%#. *'$)12& +E8F6E<5<A: $A9BE@4G<BA. )BG 4A 478DH4G8 54F<F 9BE 6B@C4E<FBA B9 E4G8F 58GJ88A G;8 *'$)12& GE84G@8AG :EBHC 4A7 G;8 @BEC;<A8 GE84G@8AG :EBHC. 11 Ke/ c'*+-d)#-e)* a**'c#a+ed .#+" IV '(#'#d*: C/-)3).' -C2? C6DF=E :? D:8?:7:42?E 962=E9 C:D<D 2?5 4@>AC@>:D6 C64@G6CJ C S/-./,&.$& -,:8?:7:42?E A2E:6?E D276EJ 4@?46C?, 42? =625 E@ C6DA:C2E@CJ 56AC6DD:@? C O2 2"341"3)/. < 90% -#?56A6?56?E AC65:4E@C @7 62C=J A@DE-@A C6DA:C2E@CJ 4@>A=:42E:@?D P+"$&#. (N = 162) OLIN !K 7 27 ,' (N = 316) M.0/()-& (N = 158) 73 86 96 35 52 70 10 26 52 30 26 30 11 18 25 9 14 14 3 12 17 6 9 19 5 7 13 4 6 10 4 6 6 4 4 8 1 2 10

 

 

5432-1-BA_CORPORATE_PAGE_12.JPG Da$a in (Real W "ld U#e): C m!le' S%"ge"ie# & Pa$ien$# B96(+ 9(5., 6-:<9.,90,: I 4,+0*(3 796*,+<9,: C4251*< 5&8.*387 ;*6* .3(19)*) A A 32% B 65 @.*9: 46% B!I B 30 C7-579+2-2;2.:: -2*+.;.:, 7+:;9<,;2=. :4..8 *86.*, C#$D, ,19762, I ,*6,.9 8*26 C76,752;*6; 5.-2,*;276:: *6;2.5.;2,:, *6;2+27;2,: A M918.51* .35&8.*38 &3) 4985&8.*38 7*88.3,7 A H7:82;*4 9.,7=.9@ A C92;2,*4 ,*9. A E5.90.6,@ -.8*9;5.6; A A5+<4*;79@ :<902,*4 ,.6;.9: L4; ).7(438.39&8.43 +46 AE7 / 1&(0 4+ *++.(&(= A 2% /79 *-=.9:. .=.6;: A 4% /79 4*,3 7/ .//2,*,@ P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c%#. B8E:8F8 .D 8G 4?. % +4<A -8F84E6;, 20 . /E<4? @B78?87 E84?-JBE?7 HF8 HFH4? C4G<8AG 64E8 J<G; *'$)12& <AFG847 B9 FG4A74E7 $1 BC<B<7. .88 !DA 7E49G :H<74A68 9BE $A7HFGEL D<FGE<5HG<A: .6<8AG<9<6 4A7 (87<64? +H5?<64G<BAF BA 0A4CCEBI87 )8J 0F8F. 12 105/-8 C->05;@4;>-/5/ B->5-@>5/ ?A>31>E E91>31:/E !1A>;8;35/ (>;8;35/ #8-?@5/ ?A>31>E G1:1>-8 ?A>31>E C;8;>1/@-8 ?A>31>E GE:1/;8;35/ ">@4;<105/ 050100150200250 !A9.1> ;2 <-@51:@? 11 18 18 33 39 44 60 84 115 115 231 N = 768

 

 

5432-1-BA_CORPORATE_PAGE_13.JPG OLIN"$K: E%6) 3* D36-2+ %2( A(1-2-675%7-32 3 =0(3: ;6 (336> -69 -3,?0)3, +6:, (+1<:;4,5; ;(0369,+ ;6 7(;0,5; 5,,+: B74=; D7;16/: 1 5/ )6, 2 5/ =1)4: M#?:E:2= 1.5 >8 5@D6 M,:?8=6 5@D6D @G6C 3 >8 92G6 ?@E 366? 6G2=F2E65 "CA D7;16/: 30 5/ =1)4 M M M #?:E:2= 1.5 >8 5@D6 0.35 >8 / 0.5 >8 56>2?5 5@D6D H:E9 6->:?FE6 =@4<-@FE 0.75 >8 DFAA=6>6?E2= 5@D6D 2E 1 9@FC 2?5 9@FC=J 2D ?66565 For PCA use only )5-8? ->1 588A?@>-@5B1 ;:8E C !LI &(K 1 5/ D 5798016-5 5/ C 27 5/ +<5<4);1=-,)14@ ,7:-4151; P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c%#. OLINVYK !) $%* c%##e(c!a"". a,a!"ab"e a$d !*) c%$*(%""ed )+b)*a$ce )c ed+"e !) &e$d!$g U.S. DEA ac*!%$. 13 +CA +4G<8AG-CBAGEB??87 AA4?:8F<4 3 56*7*38&8.437: 1 50I5:2604.--7:. =2*4 2 50I25 (150I54):2604.--7:. =2*4 30 50I305 (150I54):2604.-8;-<:. =2*4 F79 I) *-5262:;9*;276 764@ "7 9./920.9*;276 I 9.,76:;2;<;276

 

 

5432-1-BA_CORPORATE_PAGE_14.JPG Customer Engagement Strategy 14

 

 

5432-1-BA_CORPORATE_PAGE_15.JPG C3145),)26-9) D%7% A9%-0%&0) %7 L%82', &033 :<7769; -<;<9, *644,9*0(30A(;065 (5+ /6:70;(3 -694<3(9@ <7;(2, Hea$+" Ca)e P)ac+#+#'&e)* (HCP*) M M M '6H 496>:42= 6?E:EJ 2DE, 67764E:G6 #/ @A:@:5 A2:? C6=:67 C=:?:42= 52E2 :? 4@>A=6I A2E:6?ED / E2C86E65 DFC86C:6D H'*(#+a$ F')%,$a)/ C'%%#++ee* M )F3=:D965 9625-E@-9625 EC:2=D GD. #/ >@CA9:?6 M )F3=:D965 962=E9 64@?@>:4 / 4@DE @77D6E 52E2* P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c%#. OLINVYK !) $%* c%##e(c!a"". a,a!"ab"e a$d !*) c%$*(%""ed )+b)*a$ce )c ed+"e !) &e$d!$g U.S. DEA ac*!%$. 15 KC86G87 GB 58 CH5?<F;87 4G G<@8 B9 ?4HA6;

 

 

5432-1-BA_CORPORATE_PAGE_16.JPG R3&867 S)7 3* P))5-R)9-):)( P8&0-'%7-326 C6479,/,5:0=, 6=,9=0,> 6-OLIN%'K +,=,3674,5; 796.9(4 "0);-1 I "0);-2 ,)<) 15 59'1.(&8.437 ;-+76,):A )6)4A;-; 7 59'1.(&8.437 P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c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

 

 

5432-1-BA_CORPORATE_PAGE_17.JPG S7%/),30()561 P36-7-9) F))(&%'/ *531 F35180%5< M)27:1<A 7. ;<)3-074,-:; >1-? & 57:8016-); 413-4A <7 *-:-84)+-, *A !L &(K: L)*&+6 2. R&/+"$& )-P0"$2)$& (-=100; ,3+2)/+& 0&1/.-1&1 /&0,)22&%) 74% 7. .7:5=4):A ;<)3-074,-:; .16, !L &(KE; 8=*41;0-, ,)<) +4161+)44A 5-)616/.=4:2 I# 0243,-1) 66 I# ,:(420243,21) I# *)16%1:/ 0*-40)8 E93%4)/ 06,)4 0 20 40 60 80 N70&)4 2* M)16-215 #81-?1 ?11 I9<;>@-:@ &-21@E I:2;>9-@5;: 5:/8A05:3 B"+ED *A%!I!G -@ @41 1:0 ;2 <>1?1:@-@5;:. FA88 #>1?/>5.5:3 I:2;>9-@5;: -@ CCC."LI!),K./;9. 1) Q)a! (a( *e P& c #g &e'ea&ch, Cha&!e' R *e& A''$c a(e', A%& ! 2020. 2) ,A&e (he "%&$*e"e#(' # &e'% &a($&+ 'afe(+ e*e#(' a#d Gl ($!e&ab ! (+ c! # ca!!+ "ea# #gf)!?-Ba'ed $# OLlNVYK Ph3 c! # ca! (& a! da(a. 1? K1C E90;:59> (@=. I) 8:<;4591) $4-<8-/5=> (9=50) $4C=5/5-9 (9=50) &.:829*;79@ '*/.;@ E=.6;: *6-GI (74.9*+242;@ 72% 76% 41 23 14 13 2

 

 

5432-1-BA_CORPORATE_PAGE_18.JPG H364-7%0 P,%51%'< C326-()5%7-326 ".% 1&%4$& $/232 ../ ../ ../ D1..-9-6;1);-, )+<;-8)16 897.14-$8,826 05 /6:70;(3 *6:;: 7,9 7(;0,5; -69 5(<:,( I =640;05.1 $).-;@ 16 +7584-? 8);1-6;: H-),-;7-0-), 8--9-9-=1->-, +4161+)4 -=1,-6+-3 $28,000 7,9 *90;0*(3 9,:709(;69@ ,=,5; I :,8<,3(,2 ../ ../ C758-4416/ 0-)4;0 -+76751+ 57,-4 I5*9,(:,+ /6:70;(3 3,5.;/ 6-:;(@: 87 "%%)3)/.", +(@:2 F795<4)9@ :;)3-074,-9 .--,*)+3 :<8879;: B$100I,)@4 *78E74, "(, % +4<A +4??<4G<I8 C4E8 +;4E@, 20 y 74G4 54F87 BA 5 FHE:<64? CEB687HE8 64G8:BE<8F <A6?H7<A: C4E7<BG;BE46<6 I I4F6H?4E, "8A8E4? I CB?BE86G4?, *5 I "LA, *EG;BC87<6, 4A7 0EB?B:<6. 2 *I8E7L> !%, +'B. *A8, 20 . 3 /;8F8 CH5?<64G<BAF J<?? 58 HF87 <A 4 @4AA8E 6BAF<FG8AG J<G; !DA(A F86G<BAF4 4A7 G;8 !DA "H<74A68 G;8E8HA78E. 4 B4F87 BA 74<?L 7BF<A: <A A/# )A QE84? JBE?7R BC8A ?458? F498GL FGH7L 4A7 2020 C-A CE<6<A: FGH7L. /;8 CE<68 9BE *'$)12& ;4F ABG 588A 8FG45?<F;87. 18 I-01/5& $,).)$", /43$/-&2 OLIN !K

 

 

5432-1-BA_CORPORATE_PAGE_19.JPG %5+)7)( A''3827 L%82', I50;0(3 -6*<:: *6473,? 7(;0,5;: 05 3 2,@ :<9.0*(3 (9,(: >12 75*(.&18.*7 &(6477 7*88.3,7 >5,800 -475.8&17 .3 8-* #! 8550 (/20)3",2 8500 ASC2 C@>>F?:EJ %2C86 C68:@?2= DJDE6>D "@DA:E2= @FEA2E:6?E A>3F=2E@CJ DFC8:42= 46?E6CD 84 20&$)",3)&2 A?6DE96D:@=@8J (CE9@A65:4 C@=@C64E2= !J?64@=@8:4 1 A.CF 4@5H?4GBEL FHE:<64? 68AG8EF 30-40 +<:;75-9-.)+16/ 974-: M &65:42= ,4:6?46 %:2:D@?D M "@DA:E2= A44@F?E &2?286CD I6+4<,-: =19;<)4 HC" -6/)/-5-6; M-,1+)4 E,<+);176 897/9)5: Physician specialties Inpatient & hospital outpatient

 

 

5432-1-BA_CORPORATE_PAGE_20.JPG L%82', -1)0-2) P3(5505. <5+,9>(@ -69 (5 ,--0*0,5; (5+ ,--,*;0=, *644,9*0(3 3(<5*/ 1Q 2021 4Q 2020 La,&c" D,736@4,5; 6-*<:;64,9--(*05. ;,(4: A4' 7 C DEA Sc"ed,$#&! C "97,<+; )=)14)*4-16 ;9),-+0)66-4 A(()'-a$ C M(5<-(*;<905. 3 =0(3 79,:,5;(;065: P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c%#. OLINVYK !) $%* c%##e(c!a"". a,a!"ab"e a$d !*) c%$*(%""ed )+b)*a$ce )c ed+"e !) &e$d!$g U.S. DEA ac*!%$. 20

 

 

5432-1-BA_CORPORATE_PAGE_21.JPG OLIN"$K A44539%0 S75%7)+< A003:6 *35 G53:7, 61<1)4 +7:-.7+=; (9!) M M M 8C@25 :?5:42E:@? & 5@D:?8 / 25>:? #/ @A:@:5 677:424J & 72DE @?D6E C@>A=6I A2E:6?ED: 6=56C=J, @36D6, C6?2= DFC8:42= AC@465FC6D ")<1-6< & ":7+-,=:-#1;3 P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c%#. 21 .BHE68 D89<A<G<I8 #84?G;64E8y A@8E<64A #BFC<G4? AFFB6<4G<BA. AFFH@8F M 00 I 74L CE<68 9BE B?<68E<7<A8 $8-+1)4<A %):/-<; E@8)6,-, ):-); 7. .7+=; (28!) M %6G6C286 C6DA:C2E@CJ 2?5 !# D276EJ GD. #/ >@CA9:?6 E@ 6IA2?5 M C@8?:E:G6 7F?4E:@? & 255:E:@?2= "EC(' L15! 52JD @7 E96C2AJ (:?:E:2= 4@C6 7@4FD) $1.58+ 2&60*8 45546893.8=* C45! 8)<1-6<; EB;-9010 -<1-= :2 2:/?= (28!) I9In5>5i-ti7a/l: l<a1u2n:/ch?= f(o9c!u)s

 

 

5432-1-BA_CORPORATE_PAGE_22.JPG TRV027 NCE 'a%ge'i"g 'he AT1 %ece$'#% i" COVID-19 22

 

 

5432-1-BA_CORPORATE_PAGE_23.JPG M807--O5+%2 D%1%+) F531 C3532%9-586 E30405(;065 6-ACE2 796;,05 3,(+: ;6 *90;0*(3 /69465(3 04)(3(5*,: C7976)=19<: *16,: ;7 )6, -41516);-: ACE21 C L-),: ;7 )++<5<4);176 7. )6/17;-6:16 II: - A+<;-4<6/ 162<9@ )6, )*6795)4 *477, +47;: - C)6 4-), ;7 A#D$ I 8<4576)9@ -5*741:5 I :;973-SARS-C. -2 C 66% - 94% 579;)41;@ 9);-.79 C!&ID-19 9-4);-, A#D$2* ACE2 C B1I3 7. 07:81;)41A-, C!&ID-19 8);1-6;: ,-=-478 +47;;16/ +75841+);176:3 23 A-D. A6HG8 -8FC<E4GBEL D<FGE8FF .LA7EB@8. &H54 & 8G 4?., )4G (87, 2005. 2 "<5FBA +" 8G 4?, (87 % AHFG, 2020. $A C4G<8AGF E8DH<E<A: I8AG<?4G<BA. 3 &?B> !A 8G 4?, /;EB@5 -8F, 2020.

 

 

5432-1-BA_CORPORATE_PAGE_24.JPG R"027: N): MOA *35 CO"ID-19 M,*/(50:4 ;(9.,;,+ ;6 04796=, 3<5. -<5*;065 (5+ 79,=,5; ()5694(3 *36;;05. %#&027 A6027;.6:26 II A(1 9.,.8;79 C.44 :<9/*,. C.44 26;.9279 G 8:7<-16 F-)::-;<16 %#&027 1; <0-764A ;-4-+<1>-A%1 :-+-8<7: )/761;< $).-<A I <74-:)*141<A -;<)*41;0-, 16 C700 8)<1-6<; 24 L93, 6*5&.6 A38.-.3+1&22&846= L93, )&2&,* A'3462&1 '144) (1487

 

 

5432-1-BA_CORPORATE_PAGE_25.JPG R"027 CO"ID-19 S78(< - I14)5-%0 C300)+) L32(32 I5=,:;0.(;, ,--,*; 6-#!%027 65 )366+ *36;;05., 3<5. -<5*;065, (5+ 6;/,9 *3050*(3 6<;*64,: C #)6,751A-,, ,7<*4--*416,, 84)+-*7-+76;9744-, 8977.-7.-+76+-8; :;<,@ C = B60 (30 8-9 )95) C!&ID-19 8);1-6;: -"@DA:E2=:K65, ?@?-G6?E:=2E65 -N18 J62CD @=5 C I& 16.<:176 7. 84)+-*7 79 %#&027 .79 7 ,)@: (12 5/I09) P1)-"17 &.%0/).3: #-,<+;176 7. )*6795)4 +47;;16/ )::7+1);-, >1;0 C!&ID-19* I6-2,*;79 7/ (&)027D: .//.,; 76 1.*4;1 7<;,75.: *::7,2*;.->2;1 26,9.*:.-579;*42;@ 26 C#)ID-19 25 +E<@4EL 8A7CB<AG D-7<@8E ?8I8?F. ;GGCF II6?<A<64?GE<4?F.:BII6G2IF;BJIE86BE7I)C/044 0.

 

 

5432-1-BA_CORPORATE_PAGE_26.JPG M807-40) E;4)'7)( C%7%0<676 -78272-9.,.8;79) A?3 2020: ';<-@ 262;2*;276 A&D' / -.9:<8-7 /7:>>593 C-**!"-/!1)-, 3)1( :.4.,;2=. *0762:; (&)734 G-897;.26 :.4.,;2=. *0762:; (5<-78272-9.,.8;79) C-**!"-/!1)-, 3)1( N!1)-,!* I,01)121% -, D/2' A"20% $7C :;<-@ -*;* ("IDA) #;5:50 ?=1 05=:<01< 24%/ C"' C-**!"-/!1)-, 3)1( "7=.4 '1$ 9.,.8;79 57-<4*;79 24%/ 1H 21: I"D /24260 H%!*1( P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c%#. /-1250, /-1734, /-1027, 4A7 /-1045 4E8 <AI8FG<:4G<BA4? CEB7H6GF 4A7 4E8 ABG 4CCEBI87 5L G;8 !DA BE 4AL BG;8E E8:H?4GBEL 4:8A6L. A-D. A6HG8 -8FC<E4GBEL D<FGE8FF .LA7EB@8y $)D $AI8FG<:4G<BA4? )8J DEH:y +BC +EBB9-B9-CBA68CG 26 (&)045 05=:<01<= N!1)-,!* I,01)121%0 -& A/?>1 ;-59I# A$$&#)ED 8/07/2020 %4 2020: $97-<,; *=*24*+4. (&)027 "7=.4 A(1 9.,.8;79(C#)ID 19)# I+.%/)!* C-**%'% L-,$-,%1 2021: (78426. -*;* (IC ) (&)250 G-897;.26 :.4.,;2=. *0762:;A/?>1 853<-591 24%//57&'76%1)2752H 21: C4262,*4 :;<-@ 262;2*;276 (-.4;* 9.,.8;79) (5< ".> ,1.52,*4 .6;2;@ # I"),KD $&E-C I"ICA$HA'E 1$HA'E 2$HA'E 3"DA E+$EC(ED CA(A ,'('

 

 

5432-1-BA_CORPORATE_PAGE_27.JPG R"250: N): MOA *35 A'87) 5)%71)27 3* M-+5%-2) D,3;( 9,*,7;69: $5;(77,+ 76;,5;0(3 05 CN" :7(*, M0.9(05, 9,79,:,5;: ( 3(9., 4(92,; 67769;<50;@; ;6;(3 40.9(05, +9<. 4(92,; = B$3.5B D-4<) :-+-8<7:; 0)>-=619=-,1;<:1*=<176 <0:7=/07=< <0-*:)16 Every year in the US1: C 20-30% 7. 51/9)16-:<..-9-9: ,7 67; 9-:876, ;7 I +)667; ;74-9);-;0-5)93-;-4-),16/ ;918;)6 ,9</ +4):: 650M 51/:)16-; <:-)<-, -)+0 A-): 1.2M E# >1;1<; ,=-<7 51/:)16-; C A8897?. 50% 7. 51/9)16-<9: )4:7 :<..-9 .975 )6?1-;@2 D4G4 9EB@ D86<F<BA -8FBHE68F, +;4E@46BE @<:E4<A8 @4E>8G ?4A7F64C8 4A7 9BE864FG 20 . 2 (BI8A 8G 4?., % )8HEB? )8HEBFHE: +FL6;<4GEL, 20 . $6BAF @478 5L !E88C<> 9EB@ JJJ.9?4G<6BA.6B@ 2? P3(@ 04769;(5; 963, 05 9,.<3(;065 6-7(05, 466+, (5+ (5?0,;@

 

 

5432-1-BA_CORPORATE_PAGE_28.JPG R"250: #)00-30)5%7)( -2 P,1 H)%07,< "30827))5 PK S78(< "<)*<;(5,6<: +6:,: <7 ;6 30 4. :;<+0,+; 56 "AE: 6):,9=,+ $16/4-,7;-80):5)+7316-<1+; 7. %#&250 /1>-6 *A $C 162-+<176 C &,33 ;63,9(;,+, >0;/ 56 "AE: (*96:: )96(+ 9(5., 6-+6:,: C P9,+0*;()3, PK: +6:,-796769;065(3 ),;>,,5 0.1 4. ;6 30 4. "C C H(3--30-, *65:0:;,5; (*96:: (33 +6:,: C N6 EEG -05+05.: 6):,9=,+ 05 (5@ :<)1,*; .C FH56HG4A8BHF. !BFF?8E (% 8G 4?., C). DEH:F, AH: 2020y34( 53-5.

 

 

5432-1-BA_CORPORATE_PAGE_29.JPG R"734: M%-27)2%2') ,)5%4< *35 O4-3-( !6) D-635()5 ",3,*;0=, (.650:4 (; D 9,*,7;69: P6;,5;0(3 -69 04796=,+ ;63,9()030;@ O.'/).' $/,,"#/1"3)/. 6)3( N"3)/.", I.23)343& /. D14' A#42& (NIDA) M '@?4=:?:42= 6G:56?46 @7 :>AC@G65 E@=6C23:=:EJ H:E9 -+/734 >2.5M 7,673, 05 $.". :<--,9 -964 67060+ <:, +0:69+,91 M '#DA DEF5J 56>@?DEC2E65 C65F465 5CF8-D66<:?8 3692G:@C :? 2?:>2= >@56= @7 C6=2AD62 M CFCC6?E E96C2A:6D ?@E H6== E@=6C2E65, 42? 9:?56C A2E:6?E 2596C6?46 NIDA-,&ded ()'' -' -c'&ce(+ (a+#e&+ *+,d/ #&#+#a+ed 2 C8AG8E 9BE B8;4I<BE4? #84?G; .G4G<FG<6F 4A7 ,H4?<GL. 2 )$DA 74G4 BA 9<?8.

 

 

5432-1-BA_CORPORATE_PAGE_30.JPG TRV045: Ne'$-Gene"a$ion 51P Mod%la$o" fo" CN5 Di#o"de"# N,> MOA (; "1P, >0;/6<; (::6*0(;,+ 3@47/67,50( *:*67*7 P&.3 *75437* 100 ** * 80 M ,1) C646AE@CD :? E96 C', A=2J F?:BF6 C@=6 :? >@5F=2E:?8 ?6FC@EC2?D>:DD:@? / >6>3C2?6 6I4:E23:=:EJ 60 40 d yperalgesia 20 M #? 2?:>2=D, -+/045 C6G6CD65 A24=:E2I6=-:?5F465 9JA6C2=86D:2 H:E9@FE :>>F?6-DFAAC6DD:?8 24E:G:EJ 0 F)-'.+), .% 0.03 m g/kg po TR 045 1.0 m g/kg sc - - :?8@=:>@5 C65F465 =J>A9@4JE6D 3J 78% -+/045 925 ?@ 67764E @? =J>A9@4JE6D A:4.)7 L=25-45*3.& 6 5 4 3 2 1 0 ** Vehicle M '@?-@A:@:5 &(A H:E9 3C@25 A@E6?E:2= 7@C C', :?5:42E:@?D - - C9C@?:4 A2:?, C#)', 5:236E:4 ?6FC@A2E9J EA:=6ADJ, 24FE6 / 49C@?:4 A2:? 6G2=F2E:@?D F?56CH2J F)-'.+), .% 0.03 m g/kg po TR 045 3.7 m g/kg sc C$+) @BHF8 @B78? +46?<G4K8? @:I>:, <.C. BA D4LF , 3, 5, 7. #LC8E4?:8F<4 @84FHE87 4F % ABA-E8FCBAF8 GB 0.4 : 1BA !E8L 9<?4@8AG IF. 54F8?<A8, G8FG87 30S 49G8E 7BF<A: BA D4L 3. 'L@C;B6LG8F @84FHE87 49G8E 3 74LF B9 7BF<A:. D4G4 4E8 @84A O F.8.@. A 5-7 @<68I:EBHC. C<0.05 BE C<0.0 IF. 6BAGEB? 30 P *$)# *a% L/&)#(c/, + (103 c %%+ I μL) % W$,# N('-R +)('+ ,( Pa$' S,$&-%-+ alone N. 0&%3$2).-%&1/)2& 3.75 %.1)-' (B?. -.;B1) taxel-induce Pacli h

 

 

5432-1-BA_CORPORATE_PAGE_31.JPG 5)9)2%: I2239%7-9) CNS C314%2< OLINVYK !) !$d!ca*ed !$ ad+"*) f%( * e #a$age#e$* %f ac+*e &a!$ )e,e(e e$%+g *% (e'+!(e a$ !$*(a,e$%+) %&!%!d a$a"ge)!c a$d f%( - %# a"*e($a*!,e *(ea*#e$*) a(e !$ade'+a*e. P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c%#. 31 )C )8J C;8@<64? AG<GLy (*A (86;4A<F@ B9 A6G<BAy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

 

 

5432-1-BA_CORPORATE_PAGE_32.JPG APPENDIX 32

 

 

5432-1-BA_CORPORATE_PAGE_33.JPG R3&867 C0-2-'%0 D)9)0341)27 P53+5%1 OLINVYK *+, #! #& > 1,900 #& #-# ,a$* Phase 1 Phase 2 Phase 3 M N4 )47&,* &)/9782*387 7@C 6=56C=J / C6?2==J :>A2:C65 '@ <?@H? 24E:G6 >6E23@=:E6D 4 -*&)-84--*&) 86.&17 :7. I$ 2465-.3*: M M M M #/ @A:@:5 677:424J +2A:5 @?D6E @7 24E:@? 06==-492C24E6C:K65 C6DA:C2E@CJ D276EJ / !# E@=6C23:=:EJ %@H C2E6D @7 G@>:E:?8 2?5 C6D4F6 2?E:6>6E:4 FD6 M L&6,* 7&+*8= 789)=: M +62=-H@C=5 FD6 :? 4@>A=6I A2E:6?ED 2?5 E2C86E DFC86C:6D P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c%#. 33 FH5=86GF 8KCBF87 GB *'$)12& <A +; 3 y C4G<8AGF GE84G87 J<G; *'$)12& <A +;2 4A7 +;3 ,535

 

 

5432-1-BA_CORPORATE_PAGE_34.JPG P5-1%5< E**-'%'< E2(43-27 A',-)9)( -2 :3 P-937%0 S78(-)6 OLIN%'K (*/0,=,+ I% 67060+ ,--0*(*@ # < 0.0001 p == 0.0004 80% p < 0.0001 70% 80% 70% p == 0.029 60% 60% 50% 50% 40% 40% 30% 30% 20% 10% 20% 10% 0% 0% #8-/1.; 0. 1 93 0. 35 93 0. 5 93 #8-/1.; 0. 1 93 0. 35 93 0. 5 93 -*)#%/)$),% -*)#%/)$),% P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c%#. 34 *'$)12& E8:<@8AF .5 @: ?B47<A: 5B?HF, J<G; 0. , 0.35, BE 0.5 @: 4I4<?45?8 BA 78@4A7 8I8EL @<AHG8F. D<FC?4L87 C-I4?H8F 4E8 9BE *'$)12& IF. C?4685B J<G; #B6;58E: @H?G<C?<6<GL 47=HFG@8AG. 1<F6HF< - 8G 4?. % +4<A -8F. 20 y 2 27P 43. +H5?<F;87 20(4E. .<A:?4 )& 8G 4?. +4<A +E46G. 20 y7 5-73 . +H5?<F;87 20%HA 04. A-"+'&1)$ 0&1/.-%&0 0"2& A-"+'&1)$ 0&1/.-%&0 0"2& H):, <1;;=-$7.< <1;;=-

 

 

5432-1-BA_CORPORATE_PAGE_35.JPG OLIN"$K: I" O4-3-( E**-'%'< -2 2 P,%6) 3 RC 6 $<=,A 1 (!:<078-,1+ D H):, %1;;=-) 3 $CA 9.025.6: :;<-2.-(0.1, 0.35, 0.5 50) =:. 84*,.+7 *44 -7:.: $<0.01 =:. 84*,.+7 10 9 8 7 6 5 4 3 2 1 0 P/%')&2 (1=? ) 0LIN#$K 0 10+ (1=?6) 0LIN#$K 0 350+ (1=? ) 0LIN#$K 0 50+ (1=? ) 0 4 8 12 16 20 24 28 32 36 40 44 48 10 9 8 7 6 5 4 3 2 1 0 $<=,A 2 ("4);<1+ $=:/-:A D $7.< %1;;=-) 3 $CA 9.025.6: :;<-2.-(0.1, 0.35, 0.5 50) =:. 84*,.+7 0.35 I 0.5 50 -7:.: $<0.02 =:. 84*,.+7 P/%')&2 (1=81) 0LIN#$K 0 10+ (1=??) 0LIN#$K 0 350+ (1=80) 0LIN#$K 0 50+ (1=80) 0 4 8 12 16 20 24 T)-& ((/412) 35 P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c%#. A5&1"'& NRS P"). S$/1& OLINVYK O-,c(& 0.1 &" 0.35 &" 0.5 &" P%ac b( % C203/)6)( 86% 0% 8?% ?4% % 0/C L0E 11% 3% 5% 22% % !)5'7) M)(5 31% 21% 18% 4 % OLINVYK O-,c(& 0.1 &" 0.35 &" 0.5 &" P%ac b( % C203/)6)( 83% 8?% 84% 60% % 0/C L0E % 4% 5% 34% % !)5'7) M)(5 41% 20% 1?% ??%

 

 

5432-1-BA_CORPORATE_PAGE_36.JPG N3 A''8180%7-32 D)64-7) R)4)%7)( D36-2+ M<3;0-D6:, ; # ";<+@ K*= 6*79187 x 2 %( 3#g e,e(. 2 () 40093 (<;?5@5B1 A ": -//?8?7->5:9 >4<:?34 24 4<= !.*6 %(,I <105: *; 22 7/ 24 8726;: A ": /->13:<5/-7 %(/ :?>751<= C >60 5: >500 5: *+:74<;. A *177 >:71<->10, 9: 'AE=* 92% 9.*,1.-5*? -*24@ -7:. *",) )**)'6 21" 342/21+%6-21 %6 626%/ '707/%6-8) (%-/: (25)5 >2? 0+ ,%5 126 &))1 567(-)( -1 % 6,2427+," 567(: "26%/ '707/%6-8) (%-/: (25)5 )9'))(-1+ 2? 0+ 3)4 (%: 0%: -1'4)%5) 6,) 4-5. *24"' -16)48%/ 342/21+%6-21 ",)4)*24), 6,) '707/%6-8) 626%/ (%-/: (25) 2* 0LIN#$K 5,27/( 126 )9'))( 2? 0+ P"ea)e )ee I#&%(*a$* Safe*. I$f%(#a*!%$ !$c"+d!$g BOXED WARNING a* * e e$d %f &(e)e$*a*!%$. F+"" P(e)c(!b!$g I$f%(#a*!%$ a* ---.OLINVYK.c%#. 3 FH5=86GF ABG 7BF87 7H8 GB ?46> B9 I8ABHF 4668FF7<F6BAG<AH4G<BA 7H8 GB 4 ABA-F8E<BHF 47I8EF8 8I8AG (4FL@CGB@4G<6 ABA-FHFG4<A87 I8AGE<6H?4E G46;L64E7<4 J<G; 6BA9BHA7<A: ;LCB>4?8@<4 4A7 AB @84A<A:9H? ,/ CEB?BA:4G<BA 7HE<A: 7BF<A:, FH5=86G 6B@C?8G87 7BF<A: 5HG ABG 8I4?H45?8 7H8 GB 8DH<C@8AG @4?9HA6G<BA 36 O*)#%/)$),%M-4)&*-4!#), 20 15 10 M%!, 66QT#I 5 (+0%#) [90% CI 0 -5 ?9>11<= -10 -15 0246810 12 14 16 18 20 22 24 T)+% ((-2/0) (2793 9-D)/;:@>;8) " = 68 41-7>4C @:7

 

 

5432-1-BA_CORPORATE_PAGE_37.JPG ln$e"ac$i n Be$&een $he AT1 Rece!$ " and ACE2 in COVlD-19 D6>59,.<3(;065 6-ACE2 )@ *6965(=09<: 05+09,*;3@ 79646;,: (*;0=(;065 6-;/, A#1 9,*,7;69 C C6965(=09<: )05+: ;6 (5+ +6>59,.<3(;,: (5.06;,5:05 *65=,9;05. ,5A@4, 2 (ACE2)1 C D,*9,(:, 05 ACE2 ,3,=(;,: (5.06;,5:05 II 3,=,3: - A6/17;-6:16 II )+;1=);-: A%1 9-+-8;79 - 7 *9-)3,7>6 7. )6/17;-6:16 II 16;7 A6/(1-7) o '@C>2==J, A?8(1-7) 24ED 2D 2 O-2CC6DE:?-3:2D65 =:82?5 2E E96 A-1 C646AE@C2 o )C@E64E:G6 E96C2A6FE:4 36?67:ED :? E96 =F?8D3 3? &H54 & 8G 4?., )4G (87, 2005. 2 /8<K8<E4 'B 8G 4?., .6< -8C, 20 7. 3 .4AGBF -A. 8G 4?., +;LF<B? -8I, 20 . SARS-C-V-2 ACE2 V)/!* %,1/5 !,$ ACE2 $-3,/%'2*!1)-,

 

 

5432-1-BA_CORPORATE_PAGE_38.JPG Del$a Rece $o" Agoni#$# Ha&e Uni!%e Benefi$# P6;,5;0(3 <;030;@ -69 ( =(90,;@ 6-CN" 05+0*(;065: T)#(+a&* I D#+a&* C #(9.,;: :,96;6505 9,*,7;69: 4,+0(;, =(:*<3(9 ,?*0;()030;@ ((::6*0(;,+ C% 90:2)1 C M0.9(05,-:7,*0-0* ;9,(;4,5; CGRP* C #(9.,;: CG!P 9,*,7;69: 9,.<3(;, 5,<965(3 :;9<*;<9,: 05=63=,+ 05 7(05 :0.5(305.2 C M0.9(05,-:7,*0-0* ;9,(;4,5; De$+a )ece(+') a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

 

 

5432-1-BA_CORPORATE_PAGE_39.JPG IMPORTANT SAFETY INFORMATION 3

 

 

5432-1-BA_CORPORATE_PAGE_40.JPG L/2/9'9/438 4, "8+ B+)':8+ 4, 9.+ 7/808 4, '**/)9/43, '(:8+, '3* 2/8:8+ </9. 45/4/*8, +;+3 '9 7+)422+3*+* *48+8, 7+8+7;+ OLIN#$K ,47 :8+ /3 5'9/+398 ,47 <.42 '19+73'9/;+ 97+'92+39 459/438 %+.-., 343-45/4/* '3'1-+8/)8 47 45/4/* )42(/3'9/43 574*:)98&: G H';+ 349 (++3 941+7'9+*, 47 '7+ 349 +=5+)9+* 94 (+ 941+7'9+* G H';+ 349 574;/*+* '*+6:'9+ '3'1-+8/', 47 '7+ 349 +=5+)9+* 94 574;/*+ '*+6:'9+ '3'1-+8/'. !.+ ):2:1'9/;+ 949'1 *'/1> *48+ 8.4:1* 349 +=)++* 27 2-, '8 949'1 *'/1> *48+8 -7+'9+7 9.'3 27 2-2'> /3)7+'8+ 9.+ 7/80 ,47 Q!) /39+7;'1 574143-'9/43. CONTRAINDICATIONS OLIN#$K /8 )4397'/3*/)'9+* /3 5'9/+398 </9.: • /-3/,/)'39 7+85/7'947> *+57+88/43 • A):9+ 47 8+;+7+ (743)./'1 '89.2' /3 '3 :3243/947+* 8+99/3-47 /3 9.+ '(8+3)+ 4, 7+8:8)/9'9/;+ +6:/52+39 • K34<3 47 8:85+)9+* -'8974/39+89/3'1 4(897:)9/43, /3)1:*/3-5'7'1>9/) /1+:8 • K34<3 .>5+78+38/9/;/9> 94 41/)+7/*/3+ (+.-., '3'5.>1'=/8) WARNINGS AND PRECAUTIONS • OLIN#$K )439'/38 41/)+7/*/3+, ' ).+*:1+ [controlled substance schedule pending] )4397411+* 8:(89'3)+, 9.'9 +=548+8 :8+78 94 9.+ 7/808 4, '**/)9/43, '(:8+, '3* 2/8:8+. A19.4:-. 9.+ 7/80 4, '**/)9/43 /3 '3> /3*/;/*:'1 /8 :3034<3, /9 )'3 4)):7 /3 5'9/+398 '557457/'9+1> 57+8)7/(+* OLIN#$K. A88+88 7/80, )4:38+1, '3* 243/947 '11 5'9/+398 7+)+/;/3-45/4/*8. • +7/4:8, 1/,+-9.7+'9+3/3-7+85/7'947> *+57+88/43 .'8 (++3 7+5479+* </9. 9.+ :8+ 4, 45/4/*8, +;+3 <.+3 :8+* '8 7+)422+3*+*, +85+)/'11> /3 5'9/+398 </9. ).743/) 5:1243'7> */8+'8+, 47 /3 +1*+71>, )').+)9/) '3* *+(/1/9'9+* 5'9/+398. !.+ 7/80 /8 -7+'9+89 *:7/3-/3/9/'9/43 4, OLIN#$K 9.+7'5>, ,4114</3-' *48+ /3)7+'8+, 47 <.+3 :8+* </9. 49.+7 *7:-8 9.'9 *+57+88 7+85/7'9/43. P745+7 *48/3-4, OLIN#$K /8 +88+39/'1, +85+)/'11> <.+3 )43;+79/3-5'9/+398 ,742 '349.+7 45/4/* 574*:)9 94 ';4/* 4;+7*48+. M'3'-+2+39 4, 7+85/7'947> *+57+88/43 2'> /3)1:*+ )148+ 4(8+7;'9/43, 8:55479/;+ 2+'8:7+8, '3* :8+ 4, 45/4/* '39'-43/898, *+5+3*/3-43 9.+ 5'9/+39A8 )1/3/)'1 89'9:8. • O5/4/*8 )'3 )':8+ 81++5-7+1'9+* (7+'9./3-*/847*+78 /3)1:*/3-)+397'1 81++5 '53+' (C A) '3* 81++5-7+1'9+* .>54=+2/' </9. 7/80 /3)7+'8/3-/3 ' *48+-*+5+3*+39 ,'8./43. I3 5'9/+398 <.4 57+8+39 </9. C A, )438/*+7 *+)7+'8/3-9.+ *48+ 4, 45/4/* :8/3-(+89 57')9/)+8 ,47 45/4/* 9'5+7. INDICATIONS AND USAGE OLIN#$K /8 ' 3+< ).+2/)'1 +39/9> /3*/)'9+* /3 '*:198 ,47 9.+ 2'3'-+2+39 4, '):9+ 5'/3 8+;+7+ +34:-. 94 7+6:/7+ '3 /397';+34:8 45/4/* '3'1-+8/) '3* ,47 <.42 '19+73'9/;+ 97+'92+398 '7+ /3'*+6:'9+. 40 WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; NEONATAL OPIOID WITHDRAWAL SYNDROME; ,# RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CENTRAL NERVOUS SYSTEM (CNS) DEPRESSANTS A##("2(-,, A!31$, ,# M(131$ OLINVYK $6.-1$1 . 2($,21 ,# -2'$0 31$01 2-2'$ 0(1)1 -% -.(-(# ##("2(-,, !31$, ,# +(131$, 5'("' " , *$ # 2--4$0#-1$ ,# #$ 2'. A11$11 $ "' . 2($,291 0(1) !$%-0$ .0$1"0(!(,& OLINVYK, ,# +-,(2-0 ** . 2($,21 0$&3* 0*7 %-0 2'$ #$4$*-.+$,2 -% !$' 4(-01 -0 "-,#(2(-,1. L(%$-T'0$ 2$,(,& R$1.(0 2-07 D$.0$11(-, S$0(-31, *(%$-2'0$ 2$,(,&, -0 % 2 * 0$1.(0 2-07 #$.0$11(-, + 7 -""30 5(2' 31$ -% OLINVYK. M-,(2-0 %-0 0$1.(0 2-07 #$.0$11(-,, $1.$"( **7 #30(,& (,(2( 2(-, -% OLINVYK -0 %-**-5(,& #-1$ (,"0$ 1$. N$-, 2 * O.(-(# W(2'#0 5 * S7,#0-+$ P0-*-,&$# 31$ -% OLINVYK #30(,& .0$&, ,"7 " , 0$13*2 (, ,$-, 2 * -.(-(# 5(2'#0 5 * 17,#0-+$, 5'("' + 7 !$ *(%$-2'0$ 2$,(,& (% ,-2 0$"-&,(8$# ,# 20$ 2$#, ,# 0$/3(0$1 + , &$+$,2 ""-0#(,& 2-.0-2-"-*1 #$4$*-.$# !7 ,$-, 2-*-&7 $6.$021. I% -.(-(# 31$ (1 0$/3(0$# %-0 .0-*-,&$# .$0(-# (, .0$&, ,2 5-+ ,, #4(1$ 2'$ . 2($,2 -% 2'$ 0(1) -% ,$-, 2 * -.(-(# 5(2'#0 5 * 17,#0-+$ ,# $,130$ 2' 2 ..0-.0( 2$ 20$ 2+$,2 5(** !$ 4 (* !*$. R(1) F0-+ C-,"-+(2 ,2 U1$ W(2' B$,8-#( 8$.(,$1 -0 O2'$0 CNS D$.0$11 ,21 C-,"-+(2 ,2 31$ -% -.(-(#1 5(2' !$,8-#( 8$.(,$1 -0 -2'$0 CNS #$.0$11 ,21, (,"*3#(,& *"-'-*, + 7 0$13*2 (, .0-%-3,# 1$# 2(-,, 0$1.(0 2-07 #$.0$11(-,, "-+ , ,# #$ 2'. R$1$04$ "-,"-+(2 ,2 .0$1"0(!(,& %-0 31$ (, . 2($,21 %-0 5'-+ *2$0, 2(4$ 20$ 2+$,2 -.2(-,1 0$ (, #$/3 2$; *(+(2 #-1 &$1 ,# #30 2(-,1 2-2'$ +(,(+3+ 0$/3(0$#; ,# %-**-5 . 2($,21 %-0 1(&,1 ,# 17+.2-+1 -% 0$1.(0 2-07 #$.0$11(-, ,# 1$# 2(-,.

 

 

5432-1-BA_CORPORATE_PAGE_41.JPG WARNINGS AND PRECAUTIONS • P74143-+* :8+ 4, 45/4/*8 *:7/3-57+-3'3)> )'3 7+8:19 /3 </9.*7'<'1 /3 9.+ 3+43'9+ 9.'9 2'> (+ 1/,+-9.7+'9+3/3-. O(8+7;+ 3+<(4738 ,47 8/-38 4, 3+43'9'1 45/4/* </9.*7'<'1 8>3*742+ '3* 2'3'-+ '))47*/3-1>. A*;/8+ 57+-3'39 <42+3 :8/3-OLIN#$K ,47 ' 574143-+* 5+7/4* 4, 9.+ 7/80 4, 3+43'9'1 45/4/* </9.*7'<'1 8>3*742+ '3* +38:7+ 9.'9 '557457/'9+ 97+'92+39 </11 (+ ';'/1'(1+. • P74,4:3* 8+*'9/43, 7+85/7'947> *+57+88/43, )42', '3* *+'9. 2'> 7+8:19 ,742 9.+ )43)42/9'39 :8+ 4, OLIN#$K </9. (+3?4*/'?+5/3+8 47 49.+7 CN *+57+88'398 (+.-., 343-(+3?4*/'?+5/3+ 8+*'9/;+8/.>5349/)8, '3=/41>9/)8, 97'36:/1/?+78, 2:8)1+ 7+1'='398, -+3+7'1 '3+89.+9/)8, '39/58>).49/)8, 49.+7 45/4/*8, 47 '1)4.41). B+)':8+ 4, 9.+8+ 7/808, 7+8+7;+ )43)42/9'39 57+8)7/(/3-4, 9.+8+ *7:-8 ,47 :8+ /3 5'9/+398 ,47 <.42 '19+73'9/;+ 97+'92+39 459/438 '7+ /3'*+6:'9+, 57+8)7/(+ 9.+ 14<+89 +,,+)9/;+ *48+, '3* 2/3/2/?+ 9.+ *:7'9/43. • OLIN#$K <'8 8.4<3 94 .';+ 2/1* Q!) /39+7;'1 574143-'9/43 /3 9.474:-. Q! 89:*/+8 <.+7+ 5'9/+398 <+7+ *48+* :5 94 27 2-. !49'1 ):2:1'9/;+ *'/1> *48+8 +=)++*/3-27 2-5+7 *'> <+7+ 349 89:*/+* '3* 2'> /3)7+'8+ 9.+ 7/80 ,47 Q!) /39+7;'1 574143-'9/43. !.+7+,47+, 9.+ ):2:1'9/;+ 949'1 *'/1> *48+ 4, OLIN#$K 8.4:1* 349 +=)++* 27 2-. • I3)7+'8+* 51'82' )43)+397'9/438 4, OLIN#$K 2'> 4)):7 /3 5'9/+398 </9. *+)7+'8+* C>94).742+ P450 (C$P) 2D6 ,:3)9/43 47 3472'1 2+9'(41/?+78 9'0/3-24*+7'9+ 47 89743-C$P2D6 /3./(/9478; '184 /3 5'9/+398 9'0/3-' 24*+7'9+ 47 89743-C$P3A4 /3./(/947, /3 5'9/+398 </9. *+)7+'8+* C$P2D6 ,:3)9/43 <.4 '7+ '184 7+)+/;/3-' 24*+7'9+ 47 89743-C$P3A4 /3./(/947, 47 </9. */8)439/3:'9/43 4, ' C$P3A4 /3*:)+7. !.+8+ 5'9/+398 2'> 7+6:/7+ 1+88 ,7+6:+39 *48/3-'3* 8.4:1* (+ )148+1> 243/947+* ,47 7+85/7'947> *+57+88/43 '3* 8+*'9/43 '9 ,7+6:+39 /39+7;'18. C43)42/9'39 :8+ 4, OLIN#$K </9. C$P3A4 /3*:)+78 47 */8)439/3:'9/43 4, ' 24*+7'9+ 47 89743-C$P3A4 /3./(/947 )'3 14<+7 9.+ +=5+)9+* )43)+397'9/43, <./). 2'> *+)7+'8+ +,,/)')>, '3* 2'> 7+6:/7+ 8:551+2+39'1 *48+8. • C'8+8 4, '*7+3'1 /38:,,/)/+3)> .';+ (++3 7+5479+* </9. 45/4/* :8+ (:8:'11> -7+'9+7 9.'3 43+ 2439.). P7+8+39'9/43 '3* 8>259428 2'> (+ 34385+)/,/) '3* /3)1:*+ 3':8+', ;42/9/3-, '347+=/', ,'9/-:+, <+'03+88, */??/3+88, '3* 14< (144* 57+88:7+. I, )43,/72+*, 97+'9 </9. 5.>8/414-/) 7+51')+2+39 *48+8 4, )479/)489+74/*8 '3* <+'3 5'9/+39 ,742 9.+ 45/4/*. • OLIN#$K 2'> )':8+ 8+;+7+ .>549+38/43, /3)1:*/3-479.489'9/) .>549+38/43 '3* 8>3)45+ /3 '2(:1'947> 5'9/+398. • !.+7+ /8 /3)7+'8+* 7/80 /3 5'9/+398 <.48+ '(/1/9> 94 2'/39'/3 (144* 57+88:7+ .'8 '17+'*> (++3 )425742/8+* (> ' 7+*:)+* (144* ;41:2+ 47 )43):77+39 '*2/3/897'9/43 4, )+79'/3 CN *+57+88'39 *7:-8 (+.-., 5.+349./'?/3+8 47 -+3+7'1 '3+89.+9/)8). M43/947 9.+8+ 5'9/+398 ,47 8/-38 4, .>549+38/43. I3 5'9/+398 </9. • A8 </9. '11 45/4/*8, OLIN#$K 2'> )':8+ 85'82 4, 9.+ 85./3)9+7 4, O**/, '3* 2'> )':8+ /3)7+'8+8 /3 8+7:2 '2>1'8+. M43/947 5'9/+398 </9. (/1/'7> 97')9 */8+'8+, /3)1:*/3-'):9+ 5'3)7+'9/9/8, ,47 <478+3/3-8>259428. • !.+7+ /8 /3)7+'8+* 7/80 /3 5'9/+398 <.48+ '(/1/9> 94 2'/39'/3 (144* 57+88:7+ .'8 '17+'*> (++3 )425742/8+* (> ' 7+*:)+* (144* ;41:2+ 47 )43):77+39 '*2/3/897'9/43 4, )+79'/3 CN *+57+88'39 *7:-8 (+.-., 5.+349./'?/3+8 47 -+3+7'1 '3+89.+9/)8). M43/947 9.+8+ 5'9/+398 ,47 8/-38 4, .>549+38/43. I3 5'9/+398 </9. )/7):1'947> 8.4)0, ';4/* 9.+ :8+ 4, OLIN#$K '8 /9 2'> )':8+ ;'84*/1'9/43 9.'9 )'3 ,:79.+7 7+*:)+ )'7*/') 4:95:9 '3* (144* 57+88:7+. • A;4/* 9.+ :8+ 4, OLIN#$K /3 5'9/+398 </9. /25'/7+* )438)/4:83+88 47 )42'. OLIN#$K 8.4:1* (+ :8+* </9. )':9/43 /3 5'9/+398 <.4 2'> (+ 8:8)+59/(1+ 94 9.+ /397')7'3/'1 +,,+)98 4, CO2 7+9+39/43, 8:). '8 9.48+ </9. +;/*+3)+ 4, /3)7+'8+* /397')7'3/'1 57+88:7+ 47 (7'/3 9:2478, '8 ' 7+*:)9/43 /3 7+85/7'947> *7/;+ '3* 9.+ 7+8:19'39 CO2 7+9+39/43 )'3 ,:79.+7 /3)7+'8+ /397')7'3/'1 57+88:7+. M43/947 8:). 5'9/+398 ,47 8/-38 4, 8+*'9/43 '3* 7+85/7'947> *+57+88/43, 5'79/):1'71> <.+3 /3/9/'9/3-9.+7'5>. • A8 </9. '11 45/4/*8, OLIN#$K 2'> )':8+ 85'82 4, 9.+ 85./3)9+7 4, O**/, '3* 2'> )':8+ /3)7+'8+8 /3 8+7:2 '2>1'8+. M43/947 5'9/+398 </9. (/1/'7> 97')9 */8+'8+, /3)1:*/3-'):9+ 5'3)7+'9/9/8, ,47 <478+3/3-8>259428. • OLIN#$K 2'> /3)7+'8+ 9.+ ,7+6:+3)> 4, 8+/?:7+8 /3 5'9/+398 </9. 8+/?:7+ */847*+78 '3* 2'> /3)7+'8+ 9.+ 7/80 4, 8+/?:7+8 /3 ;:13+7'(1+ 5'9/+398. M43/947 5'9/+398 </9. ' ./8947> 4, 8+/?:7+ */847*+78 ,47 <478+3+* 8+/?:7+ )439741. • D4 349 '(7:591> */8)439/3:+ OLIN#$K /3 ' 5'9/+39 5.>8/)'11> *+5+3*+39 43 45/4/*8. G7'*:'11> 9'5+7 9.+ *48'-+ 94 ';4/* ' </9.*7'<'1 8>3*742+ '3* 7+9:73 4, 5'/3. A;4/* 9.+ :8+ 4, 2/=+* '-43/89/'39'-43/89 (+.-., 5+39'?4)/3+, 3'1(:5./3+, '3* (:9475.'341) 47 5'79/'1 '-43/89 (+.-., (:57+3475./3+) '3'1-+8/)8 /3 5'9/+398 <.4 '7+ 7+)+/;/3-OLIN#$K, '8 9.+> 2'> 7+*:)+ 9.+ '3'1-+8/) +,,+)9 '3*/47 57+)/5/9'9+ </9.*7'<'1 8>259428. • OLIN#$K 2'> /25'/7 9.+ 2+39'1 47 5.>8/)'1 '(/1/9/+8 3++*+* 94 5+7,472 549+39/'11> .'?'7*4:8 ')9/;/9/+8 8:). '8 *7/;/3-' )'7 47 45+7'9/3-2')./3+7>. • A19.4:-. 8+1,-'*2/3/897'9/43 4, 45/4/*8 (> 5'9/+39-)4397411+* '3'1-+8/' (PCA) 2'> '114< +'). 5'9/+39 94 /3*/;/*:'11> 9/97'9+ 94 '3 '))+59'(1+ 1+;+1 4, '3'1-+8/', PCA '*2/3/897'9/43 .'8 7+8:19+* /3 '*;+78+ 4:9)42+8 '3* +5/84*+8 4, 7+85/7'947> *+57+88/43. H+'19. )'7+ 574;/*+78 '3* ,'2/1> 2+2(+78 243/947/3-5'9/+398 7+)+/;/3-PCA '3'1-+8/' 8.4:1* (+ /3897:)9+* /3 9.+ 3++* ,47 '557457/'9+ 243/947/3-,47 +=)+88/;+ 8+*'9/43, 7+85/7'947> *+57+88/43, 47 49.+7 '*;+78+ +,,+)98 4, 45/4/* 2+*/)'9/438. )/7):1'947> 8.4)0, ';4/* 9.+ :8+ 4, OLIN#$K '8 /9 2'> )':8+ ;'84*/1'9/43 9.'9 )'3 ,:79.+7 7+*:)+ )'7*/') 4:95:9 '3* (144* 57+88:7+. ADVERSE REACTIONS A*;+78+ 7+')9/438 '7+ *+8)7/(+* /3 -7+'9+7 *+9'/1 /3 9.+ P7+8)7/(/3-I3,472'9/43. !.+ 2489 )42243 (/3)/*+3)+ @10%) '*;+78+ 7+')9/438 /3 P.'8+ 3 )4397411+* )1/3/)'1 97/'18 <+7+ 3':8+', ;42/9/3-, */??/3+88, .+'*').+, )4389/5'9/43, 57:7/9:8, '3* .>54=/'. • A;4/* 9.+ :8+ 4, OLIN#$K /3 5'9/+398 </9. /25'/7+* )438)/4:83+88 47 )42'. OLIN#$K 8.4:1* (+ :8+* </9. )':9/43 /3 5'9/+398 <.4 2'> (+ 8:8)+59/(1+ 94 9.+ /397')7'3/'1 +,,+)98 4, CO2 7+9+39/43, 8:). '8 9.48+ </9. +;/*+3)+ 4, /3)7+'8+* /397')7'3/'1 57+88:7+ 47 (7'/3 9:2478, '8 ' 7+*:)9/43 /3 7+85/7'947> *7/;+ '3* 9.+ 7+8:19'39 CO2 7+9+39/43 )'3 ,:79.+7 /3)7+'8+ /397')7'3/'1 57+88:7+. M43/947 8:). 5'9/+398 ,47 8/-38 4, 8+*'9/43 '3* 7+85/7'947> *+57+88/43, 5'79/):1'71> <.+3 /3/9/'9/3-9.+7'5>. 41