HCV Primer

Boehringer Ingelheim

HCV SCIENTIFIC LEXICON Identifying the right terms/phrases to describe a product is an important step in the branding process. The terms/phrases developed for this Lexicon were selected or created to best support the introductory positioning of Boehringer Ingelheim’s Faldaprevir and BI207127 for the treatment of HCV. You will notice the terms/phrases included in this Lexicon may not be ones currently used by physicians. If we were to use the same terms/phrases currently used in physician practices, it would not create a distinct and ownable space for Boehringer Ingelheim’s compounds. Therefore, it was necessary to ensure the terms/phrases in our Lexicon were unique, differentiating, and memorable.

Consistent use of our Lexicon will help build brand recognition, create an association between the terms/phrases and our brands, and strengthen the overall identity of the products. The Lexicon should be used in all communications, regardless of format or channel to help ensure continuity across audiences worldwide.

It’s important to know that while elements of the Lexicon have been tested with HCPs and KOLs, this is a working document that may change over time as the marketplace evolves.

These messages are fully and clearly substantiated by the currently available preclinical and clinical profiles of the Boehringer Ingelheim HCV compounds.

DISEASE STATE EFFECTS RATIONALE

In HCV, the liver is the key site where the virus lives and multiplies. A term that highlights this key site may build the need for a protease inhibitor (PI) that specifically targets the liver, which is the primary viral reservoir.

Additionally, the optimized liver-to-plasma ratio of Faldaprevir in the viral reservoir is a key advantage over other PIs.

VIRAL RESERVOIR USAGE

RATIONALE

Use Viral Reservoir to designate the specific target of Faldaprevir to eradicate HCV swiftly.

Use Viral Reservoir to describe the location in which HCV accumulates.

HCV doesn’t cause damage to the liver only, but may create a host of other potential complications that affect other areas of the body. This term encompasses the whole picture of the patient and the constellation of hepatic and extrahepatic symptoms, disease manifestations, comorbidities, or risk factors that may be improved by treatment with Faldaprevir.

• Hepatic: fibrosis, cirrhosis, liver cancer, etc

VIRAL C SYNDROME

• Extrahepatic: fatigue, flu-like symptoms, loss of appetite, nausea, cardiovascular and metabolic diseases, and higher risk of esophageal, prostate, and thyroid cancers USAGE

Use Viral C Syndrome to define the constellation of hepatic and extrahepatic symptoms, disease manifestations, comorbidities, or risk factors associated with HCV.

TREATMENT • Interferon (IFN)-based: at launch, Faldaprevir is a protease inhibitor used as part of an IFN-based regimen

INTERFERONBASED HIGHLY EFFECTIVE POLYMODAL THERAPY (iHEPT)

RATIONALE

• Polymodal: triple therapy with Faldaprevir + PegIFN/RBV USAGE

HIGHLY EFFECTIVE POLYMODAL THERAPY (HEPT)

RATIONALE

USAGE

iHEPT -> HEPT

• Highly effective: Faldaprevir + PegIFN/RBV has led to SVR in 41% of patients with GT-1 who were previously unresponsive to treatment

RATIONALE

Distributed December 12, 2012.

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Use interferon-based highly effective polymodal therapy (iHEPT) as a descriptor for the treatment regimen of Faldaprevir + PegIFN/RBV. • Interferon (IFN)-free: BI207127 is a nonnucleoside polymerase inhibitor used as part of an IFN-free regimen • Highly effective: after only 16 weeks of an all-oral therapy of Faldaprevir 120 mg QD + BI207127 600 mg TID, 59% of GT-1 treatment-naïve patients achieved SVR • Polymodal: Faldaprevir and BI207127 target 2 key viral proteins When BI207127 launches, remove the “i” and use highly effective polymodal therapy (HEPT) as a descriptor for the treatment regimen of Faldaprevir + BI207127 + RBV. Altogether, this will replace the term NSOC (New Standard of Care). Using iHEPT for Faldaprevir followed

by HEPT for BI207127 aligns with the Commercial Strategy to establish Faldaprevir as the springboard to interferon-free therapy. It is not mandatory to begin using the acronyms iHEPT and HEPT immediately.

It may be beneficial to familiarize your audience with the terms first, then introduce and begin using the acronyms when there is comfortability and recognition in the terms themselves.

DURATION OF THERAPY RATIONALE

RESPONSE CHECKPOINTS USAGE

RATIONALE

HIGH PERCENTAGE FIRST-ROUND CURE USAGE

This term will take response-guided therapy a step further and be used to differentiate Boehringer Ingelheim’s HCV treatments.

At 4 and 8 weeks, a patient’s viral load will be tested to help determine the patient’s duration of therapy and likelihood of achieving SVR (concordance).

Use Response Checkpoint to describe what RVR at 4 weeks with Faldaprevir allows you to achieve in terms of therapy duration and probability of SVR achievement.

In SILEN-C1, 87% of treatment-naïve patients treated with Faldaprevir + PegIFN/RBV achieved mRVR with similar SVR rates at 24 weeks to those treated to 48 weeks.

Use High Percentage First-Round Cure in discussions of treatment regimen and efficacy to highlight the high number of treatment-naïve patients who achieved SVR and build confidence in the high likelihood of success with Faldaprevir.

CONCORDANCE RATIONALE

EARLY SUCCESS INDICATOR USAGE

Patients who achieve RVR at the response checkpoint will go on to achieve SVR.

Use Early Success Indicator as a motivator for physicians and patients to continue treatment after patients have achieved RVR at the response checkpoint as they have been assured their body is responding well to therapy and are en route to SVR.

JAUNDICE

TRANSIENT BENIGN BILIRUBIN ELEVATION

RATIONALE

The inhibition of liver transporters and enzymes associated with the metabolism of bilirubin that occurs during Faldaprevir therapy may result in benign hyperbilirubinemia, which may cause a yellowing of the skin or eyes. In SILEN-C1, mild to moderate hyperbilirubinemia occurred in 6% of patients treated with Faldaprevir 120 mg + PegIFN/RBV. This is a treatment-limited reaction to Faldaprevir that resolves after therapy is complete and is not associated with liver failure.

USAGE

Use Transient Benign Bilirubin Elevation to discuss this adverse event with physicians and patients to reassure them that this is a benign reaction and is not permanent.

RATIONALE

These terms will further characterize “warehouse patients” by specifying the reason patients held off on treatment.

Required to Wait Patients who are contraindicated, unwilling, or ineligible to be treated with interferon and, therefore, have not yet been treated for HCV. Willing to Wait Patients who are willing to wait for an IFN-free regimen. The “wait and see” patients.

PATIENT TYPE

REQUIRED TO WAIT WILLING TO WAIT

USAGE

RATIONALE

Use Required to Wait and Willing to Wait to describe the appropriate patient type for Faldaprevir + BI207127 + RBV or the HEPT treatment regimen.

Patient population that has historically been least responsive to treatment.

difficult to cure USAGE

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Use Difficult to Cure to describe this patient population.

Boehringer Ingelheim

HCV GLOSSARY PRODUCT NAME

TERMINOLOGY

DEFINITION/ TERMS TO AVOID/ NOTES

FALDAPREVIR (FDV)

Next-wave protease inhibitor

BI207127

NS5B nonnucleoside polymerase inhibitor

FALDAPREVIR IS A POTENT, NEXTWAVE HCV NS3 PROTEASE INHIBITOR (PI) WITH A PK PROFILE THAT SUPPORTS ONCE-DAILY DOSING DESCRIBING THE MOLECULE IN THE FIRST INSTANCE

BI207127 IS A NONNUCLEOSIDE ANALOGUE INHIBITOR OF HCV NS5B RNA POLYMERASE THAT BINDS COVALENTLY TO THUMB-POCKET 1 OF NS5B

AVOID: PI when referring to inhibitors of the NS5B polymerase

PEGYLATED INTERFERON α AND RIBAVIRIN (PEGIFN/RBV OR PR IF SPACE IS LIMITED) DESCRIBING THE MOLECULE IN THE FIRST INSTANCE DESCRIBING OTHER DESCRIBING OTHER PRODUCTS PRODUCTS

FIRST-GENERATION PROTEASE INHIBITORS TRIPLE THERAPY

Telaprevir and boceprevir

PegIFN/RBV plus telaprevir or boceprevir

SIMEPREVIR, DANOPREVIR, AND GS 9256 ARE NS3 PROTEASE INHIBITORS SECOND WAVE DIRECT-ACTING ANTIVIRALS (DAAS)

Daclatasvir (BMS 790052) Sofosbuvir/GS 7977 (PSI 7977) Tegobuvir Mericitabine (RG 7128RO 5024048) on first use, then mercitabine Abbott 450 Abbott 333 AVOID: second-generation DAAs AVOID: referring to alisporovir as a DAA

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TERMINOLOGY

DEFINITION/ TERMS TO AVOID/ NOTES

DACLATASVIR IS AN NS5A INHIBITOR

DESCRIBING OTHER PRODUCTS (CONT’D)

GS 7977 IS A NUCLEOTIDE ANALOGUE INHIBITOR OF NS5B

Nucleotide inhibitor

MERICITABINE IS A NUCLEOSIDE ANALOGUE INHIBITOR OF NS5B

Nucleoside inhibitor

TEGOBUVIR IS A NONNUCLEOSIDE ANALOGUE INHIBITOR OF NS5B

DESCRIBING PATIENTS

TREATMENT-NAÏVE PATIENTS INFECTED WITH HCV GT-1

Patients who have not received prior treatment for HCV

TREATMENT-EXPERIENCED PATIENTS INFECTED WITH HCV

Patients who have received prior treatment for HCV but did not respond adequately to treatment

PATIENTS CO-INFECTED WITH HCV AND HIV

INTERFERON (IFN)-INTOLERANT PATIENTS

Patients who cannot receive IFN-based therapies due to intolerance or contraindications to IFN

PATIENTS WITH LIVER CIRRHOSIS

AVOID: cirrhotics Describe whether patients have compensated or decompensated cirrhosis

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TERMINOLOGY

DEFINITION/ TERMS TO AVOID/ NOTES

HCV RNA • BELOW THE LOWER LIMIT OF DETECTION (LLOD) OR UNDETECTABLE • BELOW THE LOWER LIMIT OF QUALIFICATION (LLOQ) SUSTAINED VIROLOGICAL RESPONSE (SVR12 OR SVR24)

HCV RNA <LLOD 12 or 24 weeks after the completion of treatment Avoid: “discontinuation of treatment” when discussing SVR

DESCRIBING VIROLOGICAL RESPONSE

DESCRIBING THERAPY

RAPID VIROLOGICAL RESPONSE (RVR)

HCV RNA <LLOQ at week 4

EXTENDED RAPID VIROLOGICAL RESPONSE (ERVR)

HCV RNA <LLOD at week 4 and week 12

EARLY TREATMENT SUCCESS (ETS)

HCV RNA <LLOQ at week 4 and <LLOD at weeks 5-18

END-OF-TREATMENT RESPONSE (ETR)

HCV RNA <LLOD at the end of treatment

VIRAL BREAKTHROUGH

HCV RNA rebound by >1 log from nadir or to ≥100 IU/mL if nadir was undetectable

RELAPSE

HCV RNA undetectable at end of treatment but detectable within 24 weeks of end of treatment

NULL RESPONSE

Absence of cEVR or pEVR at week 12 (i.e. <2 log10 decrease in HCV RNA at week 12)

PARTIAL RESPONSE

≥2 log10 decline in HCV RNA at week 12 but HCV RNA never undetectable (note the slight difference to pEVR)

LEAD-IN PHASE (LI)

Treatment phase with PegIFN/RBV before patient receives protease inhibitor

RESPONSE-GUIDED THERAPY (RGT)

RGT allows patients who have had an early response to treatment to receive PegIFN/RBV for a shorter duration

INTERFERON-BASED THERAPY (iBased)

Past and current HCV regimens that use interferon as the cornerstone of treatment

INTERFERON-FREE THERAPY (iFree)

Future HCV regimens that do not use interferon as part of treatment

Avoid: eRVR when referring to BI trials

Avoid: all-oral therapy or O2 Distributed December 12, 2012.

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Avoid: dual therapy or triple therapy

Boehringer Ingelheim

HCV Prelaunch Messages & Product PLATFORMS

These Prelaunch Messages were developed as a necessary next step toward the introduction of Boehringer Ingelheimâ&#x20AC;&#x2122;s Faldaprevir and BI207127 for the treatment of HCV. They should be used to begin preparing the market for the launch of these products.

The Prelaunch Messages should be used in all internal and external communications, regardless of format or channel to help ensure consistency across audiences worldwide. However, please be aware that they are subject to alterations based on project- and region-specific MLR requirements as well as language translations.

While the messages contained in this document should be used before and after the American Association for the Study of Liver Disease (AASLD) meeting, they will be updated periodically to ensure that the right messages are being highlighted at key milestones throughout the launch process.

These messages are fully and clearly substantiated by the currently available preclinical and clinical profiles of the Boehringer Ingelheim HCV compounds.

The Prelaunch

Messages Accomplish the Following

1. Differentiate Boehringer Ingelheim from competitors by emphasizing the unique benefits of the brands.

2. Include terms from the HCV Scientific Lexicon to ensure consistent language is used when discussing the brands.

3. Begin to build a cohesive and comprehensive story about Faldaprevir and BI207127.

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PRELAUNCH MESSAGES

PRODUCT PLATFORM

FALDAPREVIR

1. Faldaprevir is part of an iBased highly effective polymodal therapy designed to advance the treatment of HCV. 2. Faldaprevir is a potent, next-wave protease inhibitor, dosed 1 capsule once daily for 12 or 24 weeks.

3. In phase III clinical trials, Faldaprevir is being studied as part of an interferonbased highly effective polymodal therapy in a broad range of patients. This will allow for an accurate representation of real-world practice and greater assurance in treatment choice.

• Genotype 1 • Treatment naïve and experienced • Regardless of the extent of liver disease up to the threshold of decompensation • Co-infection with HIV 4. In phase II clinical trials, SVR rates with Faldaprevir + PegIFN/RBV reached as high as 83% in a broad range of treatment-naïve patients.

5. The high efficacy rates achieved with Faldaprevir + PegIFN/RBV in phase II clinical trials were accompanied by low rates of virological breakthrough and relapse.

6. In clinical trials, Faldaprevir + PegIFN/RBV continues to demonstrate advancements in safety and tolerability with placebo-like rates demonstrated for anemia and rash.

7. More than 700 patients have completed treatment with Faldaprevir + PegIFN/RBV in phase II clinical trials demonstrating its favorable safety and tolerability profile.

8. As evidenced by an optimized liver-to-plasma ratio, Faldaprevir, as part of an iBased highly effective polymodal therapy, was designed to specifically target the viral reservoir and eradicate HCV.

BI207127

1. BI207127 is a first-in-class nonnucleoside polymerase inhibitor being developed as part of a highly effective polymodal therapy.

2. BI207127, as part of a highly effective polymodal therapy, has shown the potential to eliminate interferon from HCV treatment when combined with Faldaprevir and RBV. 3. BI207127 is a dosed 2 times daily for 16 or 24 weeks.

4. The phase II trials of BI207127 as part of a highly effective polymodal therapy challenge current interferon-based therapies by including difficult-to-cure patients who mirror the reality of HCV demographics.

• Genotype 1 • Treatment naïve • Regardless of the extent of liver disease up to the threshold of decompensation 5. In the largest phase II interferon-free trial to date, up to 82% of genotype 1 patients achieved SVR after 28 weeks of combination treatment with BI207127 + Faldaprevir + RBV. 6. Preliminary results from the SOUND-C3 trial show that 100% of GT-1b treatmentnaive patients achieved SVR4 after treatment with BI207127 + Faldaprevir + RBV. 7. The high efficacy rates achieved with BI207127 + Faldaprevir + RBV in phase II clinical trials were accompanied by low rates of virological breakthrough and relapse.

8. Interferon-free therapy with BI207127 as part of a highly effective polymodal therapy will further improve tolerability for patients with HCV. 9. Nearly 400 patients have completed treatment with BI207127 + Faldaprevir + RBV in phase II clinical trials, demonstrating its favorable safety and tolerability profile.

10. The activity of BI207127 is not dependent on liver status up to the threshold of decompensation.

1. The average age of patients with HCV increases each year, and as age increases so does the risk of comorbidities.

2. A high percentage of people diagnosed with HCV suffer from additional comorbidities.

3. Current testing used to determine the extent of liver disease is difficult and often unreliable.

4. In HCV, the liver is the primary viral reservoir where the virus lives and multiplies.

DISEASE STATE MESSAGES

5. Over time, treatment-emergent resistance to DAAs will subside after completion of therapy and the HCV virus will once again be sensitive to therapy.

6. Patients with a lower viral load at baseline have a greater likelihood of achieving SVR with treatment.

7. HCV treatments have and continue to evolve, but current interferon-based therapies can only address certain challenges faced by patients with HCV. 8. Tolerability issues remain with current interferon-based therapies and as a result compliance suffers, ultimately leaving patients in need uncured.

9. HCV patients can often remain undiagnosed due to the asymptomatic nature of the disease. Consequently, a large number of patients first present to their physician with existing liver disease.

10. Patients with HCV GT-1a are the most difficult to cure of the GT-1 patient population.

1. Boehringer Ingelheim is making advancements in HCV where they are most needed.

BI CORPORATE MESSAGES

2. Boehringer Ingelheim is committed to HCV with a new approach to treatment for patients and physicians.

3. Boehringer Ingelheim is committed to finding solutions to the challenges faced by patients with HCV. 4. Boehringer Ingelheim is committed to an interferon-free future.

Distributed December 12, 2012.

FOR INTERNAL USE ONLY. DO NOT DISTRIBUTE.

Distributed December 12, 2012.

FOR INTERNAL USE ONLY. DO NOT DISTRIBUTE.

HCV CLAIMS MAP 2012

2013

2014

2015

POSITIONING STATEMENT

POSITIONING KEY THEMES

SHAPE THE MARKET

SHAPE THE MARKET

LAUNCH

INTERFERON-FREE THERAPY TRANSFORMED

• In Phase IIb studies, the safety profile of FDV 120 mg is comparable to that of placebo • Treatment with FDV is associated with transient benign hyperbilirubinemia, which is not indicative of liver injury.

This benign hyperbilirubinemia is due to the prominence of indirect or unconjugated bilirubin in the blood. Contrary to direct bilirubinemia, it is not indicative of liver injury • FDV at therapeutic doses is not associated with flu-like symptoms when compared to PegIFN/RBV • The pivotal Phase III STARTVerso 3 study has enrolled 625 treatment-experienced patients and will assess the efficacy and safety of FDV in this difficult-to-treat population • The 1220.48 trial consists of 200 patients from other Boehringer Ingelheim trials who were enrolled in PegIFN/ RBV-only groups and did not respond treatment • BI 207127 is a nonnucleoside polymerase inhibitor compound that binds to the thumb pocket-1 of HCV NS5B, creating a complementary partnership with FDV • NS5B thumb pocket-1 is highly conserved resulting in 1 study in which only 5/46 patients developed resistance (all GT-1b patients). In those patients who did develop resistance, the causative mutations resulted in poor viral reproductive fitness. The HCV wild type remained predominant • Should treatment with BI 207127 be unsuccessful, resistant variants remain susceptible to NS3 protease inhibitors • FDV and BI 207127 belong to different drug classes and have different targets, which results in a nonoverlapping resistance profile

• Current research being conducted suggests that FDV + PegIFN/RBV is an effective therapy for patients coinfected with HIV • FDV is expected to demonstrate a favorable profile in terms of drug interactions for patients coinfected with HIV. Many standard HIV treatments are highly dependent on CYP3A4 metabolism, which is inhibited by first generation DAAs • In Phase II studies, FDV increased the proportion of patients achieving SVR as compared to a PegIFN/RBVonly combination. The proportion of success was greater irrespective of GT-1 subtype, host IL28B sequence, baseline viral load, baseline ALT, or baseline GGT level • The linear structure of FDV allows for a noncovalent inhibition of the NS3 protease further resulting in low IC50 and EC50 values of 3nM • FDV contains a unique C-terminal carboxylic acid that binds covalently to the active site, and a bromoquinoline substitution that provides for increased potency • FDV specifically targets NS3/4A site with negligible activity on other proteases, thereby providing a favorable pharmacological profile • FDV has a half-life between 20 and 30 hours, which allows for once-daily dosing, and a steady state that is achieved after 1 week of therapy • The PK profile for FDV allows for once-daily dosing while maintaining optimal plasma concentrations, allowing for a simpler treatment regimen • FDV demonstrated consistently high SVR rates in difficult-tocure patient populations, such as those with cirrhosis • The addition of FDV to PegIFN/RBV in patients who were previously unresponsive to treatment has led to an SVR in 41% of patients with GT-1 • Viral resistance to FDV occurs infrequently in difficult-to-cure genotypes • SOUND-C2 was a Phase IIb open-label study where 362 treatment-experienced patients received FDV with varying dosages of BI 207127 BID or TID • SILEN-C2 tested the efficacy, safety, and tolerability of FDV in 288 partial and null responders • In clinical trials, Boehringer Ingelheim used a stringent inclusion criteria • In the SILEN-C2 study, null responders were defined as <1 log HCV RNA decline at any time during 12-week therapy with PegIFN/RBV and partial responders were defined as never having achieved an undetectable level of viral RNA and a maximal drop in load >1 log • In SILEN-C2, 76% of patients who did not respond to previous treatment with PegIFN/RBV achieved a first-round cure

• Unique polymorphisms in host DNA, specifically IL28B, can provide for a more robust response to FDV + BI 207127 + RBV • Current research being conducted is expected to show that FDV is a well-tolerated and effective therapy for patients coinfected with HIV • FDV, a next-wave protease inhibitor, is expected to demonstrate a favorable profile in terms of drug interactions for patients coinfected with HIV. Many standard HIV treatments are highly dependent on CYP3A4 metabolism, which is inhibited by first generation DAAs • FDV demonstrated consistently high SVR rates in difficult-tocure patient populations, such as patients with cirrhosis • BI 207127 has an effective concentration of 23nM against GT-1a, 11nM against GT-1b, and EC50 <100nM for all other genotypes

CLAIMS

• Preclinical studies demonstrate that levels of Faldaprevir (FDV) were significantly higher in the liver, with a liver-toplasma ratio of 42 • The linear structure of FDV allows for noncovalent binding at the NS3/4A active site with low IC50 and EC50 values of 3nM • FDV binds noncovalently with the active site of NS3/4A • FDV is highly potent (EC50 =3nM) in part as a result of a bromo-quinoline substitution on its proline residue • SILEN-C1 tested the efficacy, safety, and tolerability of FDV in 429 patients using varying dosages • SILEN-C1 results demonstrated SVR rates of 84% among GT-1 treatment-naïve patients in the FDV 240 mg QD group • In SILEN-C1, 91% of patients achieved a first-round cure • Viral breakthrough during treatment was observed in 3% to 6% of patients receiving FDV during the SILEN-C1 trial • 12.5% of the patients in the Phase IIb SILEN-C3 study had compensated cirrhosis • P ivotal Phase III trials STARTVerso 1 and STARTVerso 2 have enrolled 1281 patients internationally to test both the safety and efficacy of FDV in treatment-naïve patients with GT-1 • The STARTVerso 4 trial will demonstrate the safety and efficacy of FDV in 316 HIV coinfected patients • FDV will demonstrate a favorable profile in terms of drug interactions for patients coinfected with HIV as many medications in a standard HIV treatment regimen are highly dependent on CYP450 3A4 metabolism, which is inhibited by first generation DAAs • The combination of FDV and BI 207127 + RBV will provide a treatment option for patients who are intolerant to interferon • The high selectivity of BI 207127 for HCV RNA polymerase allows for minimal inhibition of host polymerases, which is responsible for normal DNA synthesis and repair • SOUND-C1 was an interferon-free Phase Ib trial that tested the efficacy of a highly effective polymodal therapy (HEPT) in 32 treatment-naïve patients • The Phase IIb SOUND-C2 trial included both GT-1 subtypes, as well as patients with cirrhosis and varying IL28B genotype • SVR12 rates of GT-1b patients with cirrhosis in the SOUND-C2 trial (9% of patients) were 80% • In the SOUND-C2 trial, the BI 207127 BID group experienced a relapse rate of 2% • The SVR rates between patients with compensated cirrhosis and patients without cirrhosis are comparable between groups in SOUND-C3 • Preliminary results from the SOUND-C3 trial show that 100% of GT-1b treatment-naive patients achieved SVR4 after treatment with BI207127 + FDV + RBV • The SOUND trials have shown that interferon-free combinations of FDV and BI 207127 + RBV have a good safety profile and are efficacious

Distributed December 12, 2012.

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HCV CLAIMS MAP 2012

2013

2014

2015

Q4

Q1

Q1

Q2

SILEN-C1. Hepatology. (3.3; 3.5; 3.4) SILEN-C2. Hepatology. (3.3; 3.6) SILEN-C3. J Hepatol. (3.4; 3.3; 3.5) SOUND-C1. Gastro. (4.3; 4.4) SOUND-C2. NEJM. (4.3; 4.4)

1220.02. J AIDS. (3.3; 3.5; 3.6) 1220.14. J Hepatol. (3.3; 3.5; 3.6) 1241.02. J Hepatol. (4.3; 4.4) SILENs. Resistance (3.7) 1220.02. Resistance (3.7) SOUND-C2. Cirrhotic subanalysis. (4.3) Mech of hyperbili w/1335. Antimicrob Chemo. (3.5; 3.6) Metab and dispos of 1335 in animals. (3.3; 3.5; 3.6) Bioanal of 1335 in various matrices. (3.3) Metabolites not circ in plasma. Drug Met Disp. (3.3; 3.5; 3.6)

1220.30 & 1220.47. Predictors Resp. (3.1; 3.3; 3.4; 3.5; 3.9) 1220.30 & 1220.47. Safety. (3.1; 3.3; 3.4; 3.5; 3.9) 1220.30 & 2120.47 Anemia & Hema. (3.1; 3.3; 3.4; 3.5; 3.9)

1220.08. Gastro. (3.1; 3.3; 3.4; 3.5; 3.9)

Q3 1220.19. 24 wk SVR12. AIDS. (3.5; 3.6) 2120.54. Liver Int. (3.1; 3.3; 3.4; 3.5; 3.9)

Q2 PUBLICATIONS (schedule based on publications provided by BI)

1220.30 & 2120.47. Anemia & Hema. (3.1; 3.3; 3.4; 3.5; 3.9) 1220.30 & 2120.47. HOMA State. (3.1; 3.3; 3.4; 3.5; 3.9) SILENs. Viral kinetics. (3.3; 3.5; 3.6) SILEN-C1 & 2. Effect of 3-day lead in. (3.3) SILENs. Predictors of response. (3.3) SILENs. Metabolism and safety. (3.3; 3.5; 3.6) SILENs. Billirubin, mechanisms, and safety. (3.5; 3.6) 1220.02. Potency modeling. J Hepatol. (3.3) SOUND-C2. Secondary endpoints. (4.3; 4.4) SOUND-C1 & 2. Viral kinetics. (4.3, 4.4) SOUND-C1 & 2. Resistance. (4.1; 4.2; 4.3; 4.4) Q4 1220.30 & 1220.47. NEJM. (3.1; 3.3; 3.4; 3.5; 3.6; 3.9) 1220.07. NEJM. (3.1; 3.6) 1220.30 & 2120.47. Resistance. (3.1; 3.3; 3.4; 3.5; 3.9)

STARTVerso 1/BI 1220.47/NCT01297270 STARTVerso 2/BI 1220.30/NCT01343888 BI PHASE III CLINICAL TRIALS

STARTVerso 3/BI 1220.07/NCT01358864 STARTVerso 4/BI 1220.19/NCT01399619 HCVerso 1/BI 1241.20 HCVerso 2/BI 1241.36 HCVerso 3/BI 1241.30

BI LAUNCHES Distributed December 12, 2012.

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FDV

FDV + BI207127