Benitec Biopharma Ltd (BNTC)

[Blane]

Benitec Due Diligence - As of April 8,2015

Stock Tickers
US:BNIKF (OTC) & BTEBY (ADR)
Australian: ASX:BLT

If you are new Benitec, this post has the majority of due diligence nuggets dug out for you by various board members. Welcome to Benitec Biopharma Ltd!

Benitec Biopharma is an Australian Biotech Company that is currently developing a platform method of treating diseases. Unlike traditional drugs, Benitec has developed a system of treatment utilizing viral vectors and a patented process known as ddRNAi, or DNA-directed RNA interference. What this means is that when their treatment is delivered, the modified virus takes the treatment into the target cell, and modifies that cell's DNA so that it effectively produces the therapy/cure itself. Benitec is currently utilizing this technology, in its first clinical trial, to target Hepatitic C. Other disease targets in development in-house are Hepatitis B, Non Small Cell Lung Cancer, Cancer Associated Pain, Age Related Macular Degeneration & Oculophayngeal Muscular Dystrophy.

Out-licenced Programs include HIV through Calimmune, Cancer Vaccine through Regen Biopharma, Retinitis Pigmentosa through Genable, Huntington's through uniQure, and Intractable Pain through Circuit Therapeutics.

To see Benitec’s in-house and out-licenced programs, click here:http://www.benitec.com/pipeline/in-house-programs

Presentations:
Benitec’s most recent presentation given by the Chief Business Officer Carl Stubbings on March 4th, 2015 in New York. https://content.knowledgevision.com/player/mobile/version/4/0/index.html?config=https://view.knowledgevision.com/config/account/03807/presentation/2fd5789be50d44b7a94e60b8da14c858/config/config.xml&kv_id=KnowledgeVisionEmbeddedContent85420f78c8ff49558bcf79a451250ecf&kv_presentationId=MTk0NTM4&kv_presentationVersion=1.0&kv_duration=1174&kv_slideCount=19&kv_trackUrl=https%3A//track.knowledgevision.com/itrack/&kv_licenseId=3807&kv_subAccountId=-1

Benitec’s most recent presentation given by Chief Medical Officer Dr. David Suhy can be viewed here: http://www.wsw.com/webcast/roth29/bteby/


ddRNAi:

Benitec announced the appointment of a Vice President of Manufacturing. That announcement can be seen here:http://blt.live.hqi.com.au/IRM/Company/ShowPage.aspx/PDFs/1483-10000000/MANUFACTURINGEXPERTAPPOINTED

Numerous articles detailing why Benitec has so much potential for revolutionizing how we treat diseases, and as a company itself, can be seen here:
http://seekingalpha.com/instablog/24166073-24166073/2773743-why-benitec-biopharma-bnikf-has-a-very-bright-future-ahead

It also details insights from the author on what very KEY points were made during theinvestor Briefing that took place this March as well.
UPDATE: November 9, 2014 – Another article by Pannobhaso on Seeking Alpha seeks to prognosticate the future of Benitec and ddRNAi here:http://seekingalpha.com/instablog/19837781-pannobhaso/3444735-ddrnai-center-of-excellence

Another article detailing more about Benitec’s patented ddRNAi tech can be read here:
http://seekingalpha.com/instablog/19837781-pannobhaso/2771933-ddrnai-is-in-the-eye-of-the-beholder?source=kizur_seekingalpha

Benitec as a company that has the potential to dramatically change the cost of healthcare can be read here:
http://seekingalpha.com/article/2083973-benitec-the-health-payers-dream-biotech

How Benitec’s method of ddRNAi is distinct from the typical RNAi treatment can be read here:
http://seekingalpha.com/article/2054223-benitec-an-undiscovered-biotechnology-with-a-twist

Short Hairpin RNA (short hairpin RNA “shRNA”) scientific videos can be seen here. These are more scientific in nature, and walkthrough the pathophysiology of how this functions:
Part 1
https://m.youtube.com/watch?v=tKDN4TSDw-Y

Part 2
https://m.youtube.com/watch?v=3qmHJlCn4FA

Part 3
https://m.youtube.com/watch?v=pjqwalEodTk

Part 4
https://m.youtube.com/watch?v=__tfPZv-qvg

Hepatitis C:

March 11, 2015 Update! - The fourth patient has been dosed today in Benitec’s Phase I/IIa clinical trial of TT-034 for hepatitis C.

The dosing regimen is as follows:

Sub-therapeutic Level Dosing:
Cohort 1: (2 Patients) Dosed Sequentially (One after the other).
Patient 1: Dosed May 28, 2014
Patient 2: Dosed November 13, 2014

Cohort 2: (3 Patients) Dosed Sequentially (1) then Parallel (2). In other words, the first patient will be dosed, and then if deemed same, the next two patients will be dosed at the same time.
6 Week Observation period per subject and between cohorts before dose escalation
Patient 1: Dosed January 7, 2015.
Patient 2: Dosed March 11, 2015

Patient 3: Waiting to be dosed

Therapeutic Level Dosing:
Cohort 3:

Cohort 4:

Cohort 5:

The most recent release regarding this trial can be seen here: http://blt.live.irmau.com/IRM/ShowDownloadDoc.aspx?SiteId=421&AnnounceGuid=5f998aac-8871-497d-b59b-c490d09e2900
It details how short hairpin RNAs were detected in the first 3 patient's, and that no adverse effects have been experienced by any of the patients so far.


For more information on dosing timlines, please see:http://www.irasia.com/listco/au/benitec/press/p140711.htm
November 9, 2014 Update: A November 3rd Interview regarding the TT-034 Clinical trial for Hepatitis C can be heard here: http://www.brrmedia.com/event/129281. In it, it details why certain people were excluded from the trial. This accounts for the delay in dosing the second patient in the first cohort next, and also talks about Benitec’s recent licensee Circuit Therapeutics. Dr. David Suhy, Benitec’s Senior Vice President of Research and Development, released an article this month detailing a comparison between Gilead Sciences recently approved Hepatitis C treatment, Harvoni, and TT-O34. That article can be read here:http://www.benitec.com/documents/1411_Harvoni_Why_Hep_C_Focus_is_a_Plus.pdf

Clinical Trials on ClinicalTrials.gov can be seen here:http://www.clinicaltrial.gov/ct2/show/NCT01899092?term=tt-034&rank=1

For a more scientific review regarding TT-034 as a recombinant adeno-associated virus serotype 8 (AAV8) agent used in the treatment of diseases (More specifically HCV in this case), can be seen here:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951910/

As of July 19, Benitec released a presentation for the Bioshare Summit in Australia. It details TT-034 and ddRNAi in comparison to Isys and Alnylam. This presentation can be seen here:

http://present.knowledgevision.com/player/mobile/version/2/0/index.html?config=http://present.knowledgevision.com/account/brr/player/BLT20140718/config/config.xml&kv_id=KnowledgeVisionEmbeddedContentdc93b1db7dfa4120a77642bb03edafa8&kv_presentationId=ODA2OTY%253D&kv_presentationVersion=1.0&kv_duration=907.778&kv_slideCount=29&kv_trackUrl=http%3A//track.presentation-cloud.net/&kv_licenseId=138&kv_subAccountId=-1
Or here:

http://www.brrmedia.com/event/124682/

Also, an Instablog on Seeking Alpha by Pannobhaso regarding TT-034’s intial positive results can be seen here: http://seekingalpha.com/author/pannobhaso/instablog


The VIDEO portion of their latest Spotlight Presentation can be watched here:http://www.finnewsnetwork.com.au/archives/finance_news_network76292.html

Hepatitis B:

The Hepatitis B therapy will leverage the approach generated by the Hepatitis C program. Clinical Constructs have been generated, testing of cellular models are ongoing, and In-vivo testing will commence soon.

There is no current cure for Hepatitis B, and the Hepatitis B market is huge (350 Million Worldwide) compared to Hepatitis C.

The most recent information on this particular program can be viewed in the Roth Presentation given by Dr. David Suhy. That can be seen here: http://www.wsw.com/webcast/roth29/bteby/


Tribetarna: (Lung Cancer):

Benitec’s treatment for lung cancer is another avenue that is currently being worked on, and is detailed in a Youtube video from UNSW Australia… and can be watched here:
https://www.youtube.com/watch?v=UESv1hzrRek

Mouse models have shown re-sensitivity to chemotherapy after treatment with ddrnai.

A Recent Announcement on January 8, 2015 detailed two peer-reviewed articles supporting Tribetarna’s expanded indications to pancreatic and renal cancer. That announcement can be seen here:http://blt.live.hqi.com.au/IRM/Company/ShowPage.aspx/PDFs/1499-10000000/RESEARCHSUPPORTSADDITIONALCANCERINDICATIONS

AMD:
(1.75 Million people). This therapy uses ddrnai to suppress the expression VEGFA protein.
The most recent information on this particular program can be viewed in the Roth Presentation given by Dr. David Suhy. That can be seen here: http://www.wsw.com/webcast/roth29/bteby/

Collaboration with 4D Therapeutics on developing a vector that transduces cells of the whole eye are underway.


HIV and Callimune:

Here is a YouTube link regarding Tye Olson, one of the indivuals who is doing the Calimmune HIV trial using altered T-Cells with Benitec’s Tech. His trial is mentioned starting at around 6:20. This video was posted 04/14/2014.https://www.youtube.com/watch?v=ymRJLICsMbQ&feature=youtu.be&app=desktop

A gene therapy presentation in regards to a cure for HIV can be seen here: www.isheid.com/presentations/mercredi/16-00/hutter/hutter.pdf
On June 25, 2014, a PR was released announcing that Calimmune has been given the green light to treat its second group in the HIV gene therapy trial. That announcement can be seen here:http://www.businesswire.com/news/home/20140625005962/en/Calimmune-Approved-Treat-Group-HIV-Stem-Cell#.U8HG3PldXzc

A recent post on Seeking Alpha with author Pannobhaso has listed Benitec’s ddRNAi technology in the fight against HIV in various ways. This article can be viewed here:http://seekingalpha.com/article/2418705-benitecs-ddrnai-targeting-fight-against-hiv

The 2015 Palm Springs Symposium on HIV Schedule of Events can be viewed here:http://cri.bio.uci.edu/events/2013-palm-springs-symposium-on-hivaids-hiv-infection-towards-a-cure/

As of 08/14/2014, An interesting patent application on HIV resistant stem cells and ddRNAi can be seen here: http://www.freepatentsonline.com/y2014/0227236.html

Huntington's Disease:

uniQure has licensed out Benitec's technology for Huntington's Disease.

Other Disease Areas to Note:

Alzheimer’s Public Forum – October 31, 2014
http://ausbiotech.org/updates/details.asp?cat=4&id=1164&returnToUrl=%2Fdefault%2Easp

Financials:

If you’re interested in viewing an Australian stock blog like Investorhub, you can view this one:http://www.topstocks.com.au/new_asx_stock_forum.php
as well as this one: http://hotcopper.com.au/search_do.asp?fid=1&symbol=382

As of 5-29-2014, Benitec has also announced it has chosen New York Bank of Mellon as its authorized U.S. representative and Depository Bank to establish an ADR (American Depositary Receipt) Facility. The announcement can be seen here:http://www.benitec.com/documents/140530USADRTOBEESTABLISHED.pdf

Other ddRNAi programs are potentially in the works for possibly ALS and can be read in a blog here: http://seekingalpha.com/author/pannobhaso/instablog

I will try to continually update this post when new information comes out. Again, Welcome!

For more information regarding the Australian releases on the ASX, please refer to this link: http://www.benitec.com/investor-centre/asx-announcements

Blane