Replies to post #140014 on Biotech Values

[mcbio]

Medivir’s 2011 annual report

Thanks DD. Have you had a chance to read it yet? If so, any comments? (I still need to.)

Do you think the early positive results for the GS-7977+daclatasvir combo bode well for 7977+TMC435? Also, I wonder how long it will be before we see an interferon and ribavirin-free HCV trial combining 7977+daclatasvir+TMC435.

[mcbio]

Re: Medivir 2011 annual report (select parts)

What I thought were some pertinent passages from a quick glance at the annual report:

1. Pg. 20 - "TMC435’s profile opens new possibilities

Based on results from phase II trials, TMC435’s safety profile looks very positive, for treatment-naive and treatment-experienced
patients. Until the present, TMC435 has achieved exceptionally positive results on treatment-experienced patients with advanced liver disease. TMC435 does not cause any additional adverse events, which distinguishes it from first-generation protease
inhibitors and many of the other pharmaceuticals
in different drug classes that are behind TMC435 in development."

2. Pg. 21 (referencing combo trials of TMC435+7977 and TMC435+daclatasvir) - "The results from these phase II trials are
scheduled to be available from late-2012 onwards. Assuming the data is positive and that the parties share a common interest, TMC435 combinations may continue directly into phase III registration trials."

3. Pg. 22 - "What’s most important in the search for a new treatment?

Better treatment outcomes and fewer adverse events. For individual patients, the most important thing is the pharmaceutical producing fewer adverse events, a shorter treatment time and simpler dosing, with fewer doses per day. All these are contributors to better treatment outcomes. As long as hepatitis C therapy includes interferon and ribavirin, we won’t be able to avoid their adverse events, with interferon being particularly problematic. It would be best if the new pharmaceutical brought into treatment causes as few adverse events as possible. Unfortunately, boceprevir and telaprevir have additional specific adverse events, and require patients to take a lot of tablets. However, the treatment times of most previously untreated patients can be reduced, which hopefully means more patients still complete their treatment and can be cured.”

[mcbio]

Medivir/BMY - expand testing of TMC435

http://www.medivir.se/v4/en/ir_media/pressrelease.cfm?year=2012&releaseid=659101

Medivir announces TMC435 in an expanded clinical collaboration

18-Apr-12
· Expanded clinical study program evaluating a combination of TMC435 and daclatasvir (BMS-790052)
· TMC435 and BMS-986094 (formerly INX-189), two direct-acting antivirals in combination, will be evaluated in clinical trial

Stockholm, Sweden - Medivir AB (OMX:MVIR), the research-based speciality pharmaceutical company focused on the development of high-value treatments for infectious diseases, announces that its development partner, Janssen R&D Ireland has broadened its clinical collaboration agreement with Bristol-Myers Squibb Company (NYSE:BMY).

· This announcement concerns an expansion of the clinical collaboration agreement between Tibotec Pharmaceuticals (now Janssen R&D Ireland) and Bristol-Myers Squibb (NYSE:BMY) announced by Bristol-Myers Squibb on 2nd December 2011
· Bristol-Myers Squibb and Janssen have agreed, pending the outcome of the upcoming phase II study, to further study daclatasvir (BMS-790052) and TMC435 in a phase III trial.
· Bristol-Myers Squibb and Janssen have agreed to conduct a drug-drug interaction study with TMC435 and BMS-986094. Results from the DDI study will guide the further evaluation of the use of TMC435 and BMS-986094 in HCV patients.

TMC435 and daclatasvir (BMS-790052)
In the agreement announced on 2ndDecember 2011, TMC435, a once daily potent NS3/4A protease inhibitor (PI) in phase III development for the treatment of genotype-1 chronic hepatitis C virus (HCV) infection will be investigated in a combination in a phase II trial with Bristol-Myers Squibb´s investigational NS5A replication complex inhibitor, daclatasvir (BMS-790052), also in phase III development.

In the upcoming phase II study the companies will evaluate the potential to achieve sustained viral response 12 and 24 weeks post treatment in null responder and interferon intolerant patients with HCV genotype 1. This study is planned to start later in 2012.

TMC435 and BMS-986094 (INX-189)
The expanded clinical agreement also includes clinical evaluation of a combination of TMC435 and the nucleotide polymerase NS5B inhibitor BMS-986094, formerly known as INX-189. A drug-drug interaction (DDI) study with TMC435 and BMS-986094 will be conducted. Results from the DDI study will guide the further evaluation of the use of TMC435 and BMS-986094 in HCV patients.

Charlotte Edenius, Executive VP Research & Development, of Medivir commented: “We are very excited to see this expanded collaboration between Janssen and Bristol-Myers Squibb and to be investigating TMC435 with the nucleotide BMS-986094 and to expand the clinical collaboration evaluating TMC435 with daclatasvir. This represents one of several strategies to explore TMC435 in interferon free regimens; a development we believe will be an important advancement in the HCV field for patients.”

About TMC435
TMC435 is a highly potent once-daily (q.d.) investigational drug that is being jointly developed by Janssen R&D Ireland and Medivir to treat chronic hepatitis C virus infections in genotype 1 patients.

TMC435 - On-going global phase III program in brief:

· TMC435-C208 or QUEST-1 in 375 treatment-naïve genotype-1 patients
· TMC435-C216 or QUEST-2 in 375 treatment-naïve genotype-1 patients
· TMC435-C3007 or PROMISE in 375 genotype-1 patients who have relapsed after prior interferon-based treatment
· Phase III program in Japan, includes 417 genotype-1 treatment naïve and treatment experienced patients
· TMC435-C3001 is a phase III efficacy, safety and tolerability study comparing TMC435 versus telaprevir, each in combination with Pegylated Interferon a-2a (PegINF) and ribavirin (RBV), in hepatitis C genotype-1 infected patients who were null or partial responders to prior PegINF/RBV therapy
· TMC435-C3011 is an open label, single arm phase III trial to explore the efficacy, safety and tolerability of TMC435 150 mg once daily, in combination with PegIFN/RBV in 100 treatment naïve or treatment experienced, hepatitis C genotype-4 infected patients

For additional information from these studies, please see www.medivir.com and www.clinicaltrials.gov

About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The World Health Organization estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.

For more information about Medivir, please contact:

Medivir Mobile: [phone]
Rein Piir, EVP Corporate Affairs & IR
M:Communications [e-mail]
Europe: Mary-Jane Elliott, Amber Bielecka, Hollie Vile [phone]

About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is TMC435, a novel protease inhibitor in phase III clinical development for hepatitis C that is being developed in collaboration with Janssen Pharmaceuticals.

In June 2011, Medivir acquired the specialty pharmaceutical company BioPhausia to ensure timely commercialisation of TMC435 in the Nordic markets, once approved.

Medivir’s first product, the unique cold sore product Xerese®/Xerclear®, was launched on the US market in 2011. Xerese®/Xerclear®, which has been approved in both the US and Europe, is being launched in collaboration with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia. Rights in North America, Canada and Mexico were sold to Meda AB in June 2011. Medivir has retained the Rx rights for Xerclear® in Sweden and Finland.

For more information about Medivir, please visit the Company’s website: www.medivir.com

[mcbio]

Medivir @ EASL (4/21/12 slide presentation)

(Link to slides at: http://www.medivir.se/v4/en/ )

1. Slide 2 - 15 marketed products in Nordics generating annual sales of Euro60M (EBITDA ~Euro12M). Aiming for profitability in a few years.

2. Slide 6 - Aiming for candidate selection of unpartnered HCV nuke(s) in 4Q12. Medivir has both purines and pyrimidine nukes that have properties similar to most advanced nukes (assuming GS-7977 here). Unpartnered NS5A inihibitor at pre-clinical optimization phase. Partnered nuke w/JNJ/Tibotec selected and IND prep activities ongoing (supposed to enter Phase 1 this year; not sure how this one compares to unpartnered nukes).

3. Slide 7 - TMC435 has activity against GTs 1,2,4,5,6.

4. Slide 14 - ASPIRE adverse events for TMC435:
A. AEs leading to discontinuation - 9% for TMC435 vs. 5% for placebo arm.
B. Grade 3/4 AEs - 36% for TMC435 vs. 26% for placebo arm.
C. Photosensitivity AEs - 6% for TMC435 vs. 2% for placebo arm.

[Not sure if you have any concerns here; obviously in the future the placebo arm components will presumably be dropped from combo treatment, thus decreasing overall AEs. All told, any concerns with TMC435 AEs here, though?]

5. Slide 21 - Cirrhotic patient data largely missing (from trials to date). These are most difficult patients to treat and make up substantial portion of available patient pool. SVR36 may be needed to capture real life relapse rate in IFN-free (and ribavirin?) setting. Ribavirin will not be part of future HCV combos due to severe side effects and safety issues.

6. Slide 22 - goal for next gen treatment is 2 DAAs in combo (I actually don't like this assertion as I think it puts more pressure on Medivir and TMC435. I think TMC435 could most assuredly find a home in a 3-drug cocktail but if only 2 then that obviously narrows the window and opportunity. I doubt GILD will use TMC435 in an HCV DAA combo so that perhaps puts a lot of pressure on Medivir to hope that BMY will need to use TMC435 with either daclatasvir or BMS-094. If not, Medivir will have to find someone else or hope to pair TMC435 with their nuke partnered w/JNJ or one of their unpartnered ones, though all of those are far behind.}

7. Slide 23 - 37% of patients in the ASPIRE trial were in the two most difficult to treat cirrhotic patient groups (F3/F4).