After reading the Bioshare Artical Here's My Thoughts and...

After reading the Bioshare Artical Here's My Thoughts and RESPONSE" Enjoy..


Last week Biotron attended the AASLD Liver Meeting in Washington DC. iam certain they would have heard the latest data from unpublished trials, and would have attend summary and overview sessions of the meeting presented by key international opinion leaders. I guess the key take home message is that there is expected to be several different treatment approaches for HCV depending on genotype, disease status, patient polymorphisms, etc. And secondly, that the expected approval of sofosbuvir and simeprevir is not the end.

Biotron is familiar with the results of all published studies, and they would have read the FDA background packages for sofosbuvir and simeprevir. The conclusions as set out in Bio Shares Artical do not fit with Biotrons own or others reading of the state of play in the HCV drug development field.

I recommend that All review the presentationthat Michelle Gave at last Friday's AGM. It give a fair and honest account of the field, and of where treatment gaps lay. The aim was not to cover all drugs in development as Biotron didn't want to bore shareholders into a stupor. However, it is an overview that shows clearly where Biotron having had opportunities to analyse results of trials and also receive advise from advisory groups made up of the key international opinion leaders, BIT225's future lies.

Specifically addressing points raised by Bio Shares:

• BIT's rationale for developing BIT225 is that it can address drug resistance issues that could emerge with other classes of HCV drugs

NOTE - This is not Biotrons sole rationale. It is an important one, as any virologist that has ever been involved with HIV drug development will attest. At this point in time, the DAAs have only been tested under limited trial conditions. Once widely available, and in real world conditions, patient compliance is expected to be an issue - and this may lead to resistant mutations developing. It's better to be ready than in denial of it happening. In the case of SOF plus RBV there is only ONE direct-acting antiviral drug - and viruses are good at working out how to get around drugs. Ditto for SIM. RBV (ribavirin) is not believed to be a DAA - in fact, it has an unknown mechanism of action.

Other rationales for development of BIT225 for treatment of HCV include:

- Current treatment regimens that include SOF or SIM still contain RBV. There is a need for additional classes to add in, or to replace RBV.
- Current treatment periods with SOF and RBV are out to 12 weeks for gen 1, 2 and out to 24 weeks for gen 3. This is going to be expensive, and costs are going to be a key part of what drugs actually get used and reimbursed by insurers. Adding in other classes of DAAs may reduce treatment periods, ideally down to 4 - 6 weeks.
- Coinfected patients are a key group with significant unmet need. Protease inhibitors have drug-drug interactions. This means modification of the antiretroviral therapy that the patient may have been on for a long time, or excluding HCV PIs from use. BIT225 has shown good efficacy in the interim data from the coinfected study. Biotron presented the data as a late-breaker at AASLD last week. There is a very high level of competition for late-breaking abstracts. Biotron would have had significant interest in results from industry. The dual anti-HIV and anti-HCV activity of BIT225 is considered a bonus.

• Recently Gilead Sciences' sofusbuvir with ribavirin was recommended for approval by the FDA, for treating HCV genotypes 2 and 3

NOTE - Yes it was. Despite less than ideal results in gen 3, on the basis of superiority or non-inferiority to current standard of care (which is less than ideal). Specifically, treatment with 12 weeks gave ~30% SVR, 16 weeks gave ~60% SVR and 24 weeks gave ~80% SVR. Nice for them. BUT 24 weeks is a long time, and will cost a lot. See point above on this. And 80% is not 100% (and remember this is not real world setting). The very strong message is that there is some way to go with gen 3s.

• Sofusbuvir with pegylated interferon was also recommended for approval for treating HCV genotypes 1 and 4

NOTE - Yes it was. Once again, on the basis of superiority or non-inferiority to current standard of care. BUT it still contains IFN which everyone is trying to get away from. This is not an all oral DAA combination. It is less than ideal.

• Sofusbuvir cuts duration of treatment from 24 to 12 weeks, and delivers up to a 90% cure rate

NOTE - only for Gen 1, 2. Not the case for gen 3. See point above. And once again, 90% is not 100%, and this is still not real world.

• Gilead has a pan-genotype and interferon and ribavarin free regime of sofusbuvir and GS-5816 moving into Phase II

NOTE - Nice for them. Some way to go though, and not same class as BIT225.

• Johnson & Johnson's simeprevir with peg-interferon and ribavarin for genotype 1, was also recommended for approval

NOTE - SUbjects with a particular polymorphism in HCV gen 1a (Q80K polymorphism) have a reduced response to SIM + PEG/RBV (similar response as PEG/RBV alone). The rate is quite high in the USA, so it is expected that FDA approval will require gen 1a patients to be prescreened for this before SOF can be used. Their market is expected to be reduced. BIT225 has shown excellent activity against both gen 1a and 1b.

• BIT intends to commence a 12 week trial of BIT225 in genotypes 1 and 3 subjects later in 2013

NOTE - That is the aim. The reason for this trial is to show safety with 3 months dosing so that BIT225 can be combined in future trials with other DAAs. And to get additional gen 1 and 3 efficacy data. This trial design was on the recommendation of Biotron's US-based, highly experienced and relevant advisory group.

Comment: The number of new and improved HCV drugs nearing FDA approval diminish the prospects for BIT225

NOTE -Biotron disagree. Treatment decisions are being make on the basis of relatively small amounts of data, in a rush to be first. As Biotron has seen with Boceprevir and Telaprevir (PIs approved over last 12/18 months), being first doesn't always count for much. Biotron is confident in our reading of the field, and in how we are positioning BIT225.