Replies to post #79102 on Biotech Values

[mcbio]

MBRX - Roche advances HCV nuke based on MBRX technology into pre-clinic

MBRX up about 90% after hours, but note the caveat at the end of the release regarding their finances.

http://finance.yahoo.com/news/Metabasis-Therapeutics-bw-15454204.html?.v=1

"Metabasis Therapeutics, Inc. (Nasdaq: MBRX - News) announced today that it received a $2 million payment from Roche in recognition of advances made on their research collaboration, which is focused on applying Metabasis’ HepDirect® liver-targeting technology to Roche’s proprietary lead nucleosides in order to develop new treatments for hepatitis C viral (HCV) infection. In addition, Metabasis announced that Roche has formally accepted MB11362 as a clinical candidate for development.

Metabasis and Roche entered into a collaboration and license agreement in August 2008 which included a $10 million upfront payment and provided for additional payments upon achievement of predetermined preclinical and clinical development events, as well as regulatory and commercialization events for each product, and royalties on net sales of products from the collaboration. As part of the collaboration, a HepDirect prodrug of a Roche proprietary nucleoside monophosphate was identified and evaluated in various pre-clinical studies conducted by scientists at Metabasis and Roche. The results of these studies led to a decision by Roche to advance MB11362 into pre-clinical development.

Metabasis reported last week that it had restructured the Company due to difficulties in raising capital from a financing or other sources. Metabasis continues to seek additional capital in the near-term, and if it is unsuccessful in raising additional capital, the Company may be forced to cease its operations entirely...."

[mcbio]

MBRX/IDIX connection?

http://www.mbasis.com/pipeline/index.html

MBRX notes on its pipeline page that it is entitled to royalties on an undisclosed HCV target being focused on by MRK and IDIX apparently in the discovery stage based upon the use of MBRX's liver targeting technology. Do you have any idea what they're referring to? Is IDIX actively pursuing additional HCV compounds in the discovery stage employing MBRX technology? I assume that IDX184, IDX375, and IDX136/316 are based entirely on IDIX's own proprietary liver targeting technology.

[mcbio]

PGNX - Focusing on 2nd Gen Viral Entry Inhibitor for Hep C

I haven't seen any comments on the viral entry inhibitor approach to treat Hepatitis C. The discussion has generally been about HIV for these drugs I believe but I guess it makes sense that they will be tested in other viral diseases. Comments?

http://finance.yahoo.com/news/Progenics-Provides-Update-on-bw-15462627.html?.v=1

Progenics Pharmaceuticals, Inc. (Nasdaq: PGNX - News) today announced the discontinuation of development for PRO 206, a pre-clinical compound for the treatment of hepatitis C virus (HCV) infection. The decision was made as part of a portfolio review, and is in line with the Company’s ongoing initiative to allocate resources to the most important programs in order to increase its operating efficiencies. The Company will instead focus on its second-generation HCV-entry inhibitor portfolio and anticipates selection of a new development candidate in 2010.

“Our research and development team has built a robust platform for HCV drug discovery,” said Paul J. Maddon, M.D., Ph.D., Founder, Chief Executive Officer and Chief Science Officer, Progenics Pharmaceuticals, Inc. “While our review indicated that PRO 206 did not satisfy the criteria for further development, our ongoing research and development efforts have yielded new compounds demonstrating comparable potency to PRO 206. These second-generation compounds also indicate a broader spectrum of activity in laboratory studies against the hepatitis C virus.”

[DewDiligence]

The global* HCV market will rise to $7.7B in 2013, according to the marketing firm, Decision Resources:

http://finance.yahoo.com/news/Hepatitis-C-Virus-Market-Will-prnews-2382775659.html

I think this forecast is much to low, but I’m not inclined to pay big bucks for the Decision Resources report to see the analysis.

*Includes the US, Japan, and the big-5 countries of Western Europe (Germany France, UK, Spain, Italy).

[DewDiligence]

HCV: Most Likely to Succeed (IMHO)

[New or updated entries for PSI-7851 (VRUS); PSI-938 (VRUS);
MB11362 (Roche/MBRX); unnamed entry inhibitor (PGNX);
CF102 (Can-Fite).]


The following paragraphs are in descending order of likelihood of success. There is no claim of completeness here; i.e. paragraphs 3-6 do not necessarily mention all of the applicable drug candidates within the grouping. Please see #msg-36688204 for the semantics of the terms nucleoside and nucleotide.

1. The two leading protease inhibitors: Telaprevir (VRTX/JNJ; phase-3) and Boceprevir (MRK; phase-3). The Telaprevir program is further advanced, so let’s call Telaprevir and Boceprevir 1a and 1b, respectively. Both drugs have shown very impressive efficacy in phase-2 trials, although neither has a completely clean safety profile (see references below).

Telaprevir in the treatment-naïve setting: phase-3 program: #msg-27623529 (ADVANCE study), #msg-26228377 (both studies); phase-2b program: #msg-29019931 (PROVE-1/2 trials made simple), #msg-28746843 (PROVE-1/2 detailed results); C208 study of BID vs TID dosing: #msg-33270634.

Telaprevir in the second-line setting: phase-3 program (REALIZE study): #msg-32901932; phase-2 program: #msg-37316151 (PROVE-3 study), #msg-28749322 (‘107’ open-label extension for PROVE-1/2 failures).

Boceprevir in the treatment-naïve setting: phase-3 program (SPRINT-2 and RESPOND-2): #msg-29474929; phase-2b program: #msg-37298987, #msg-37298085 (SPRINT-1 results from EASL 2009); #msg-31190433 (musings on interim results).

Boceprevir in the second-line setting: phase-3 (RESPOND-2) study: #msg-29474929.


2. ITMN-191 and R7128, the two oral drugs that Roche is testing in the INFORM-1 study that does not include interferon or ribavirin: #msg-37309589 (data reported at EASL 2009); #msg-37312942 (VL chart with annotations by ghmm); #msg-37208214 (PR on expanded trial design), #msg-37209844 (clinicaltrials.gov listing), #msg-36388140 (EASL 2009 abstract), #msg-36455893 (musings by tony111 and ghmm).

ITMN-191 a/k/a/ R7227 (ITMN/Roche; entering phase-2b) is a protease inhibitor: #msg-37306972 (phase-2b design), #msg-34747018 (phase-1b data in tabular form). R7128 (VRUS/Roche; phase-2b) is a nucleoside polymerase inhibitor: #msg-34746768.

Although ITMN-191 and R7128 are not necessarily the best drugs in their respective classes, the fact that Roche is testing them in INFORM-1 gives them a leg up on competing drugs at the same stage of development, IMO.

3. Agents in phase-2b, phase-3 or later that use an established MoA: Albuferon (HGSI/NVS; BLA submission pending): #msg-36140577 (phase-3 data), #msg-36254180 (lack of SPA!), #msg-34770426 (new trial with monthly dosing); BI201335 (B-I; phase-2b), a protease inhibitor: #msg-33564560, #msg-34774813; and Locteron (Biolex; phase-2b), a long-acting interferon made in transgenic plants that may qualify for the 505b2 approval pathway: #msg-37298340 (phase-2a data from EASL 2009), #msg-37178496 (phase-2b design).

4. Agents in phase-1b or phase-2a that use an established MoA. These include TMC435 (Medivir/JNJ; phase-2), a protease inhibitor: #msg-37298740; SCH 900518 (MRK, phase-2a), a protease inhibitor (follow-up to Boceprevir): #msg-34338549, #msg-34774813; GS-9190 (GILD; phase-2), a non-nucleoside polymerase inhibitor: #msg-32919311; IDX184 (IDIX; phase-1b), a nucleotide polymerase-inhibitor: #msg-36392616 (EASL 2009 abstract), #msg-34763865 (PR for trial commencement), #msg-26915921 (how IDX184 is better than NM283); PSI-7851 (VRUS, phase-1b), a nucleotide polymerase inhibitor: #msg-38526044; IFN-alpha-XL (FLML; phase-1b): #msg-28837983; ABT-450 (ABT/Enanta, phase-1), a protease inhibitor: #msg-35708745; VCH-222 (VRTX, phase-1b), a non-nucleoside “thumb” polymerase inhibitors that VRTX acquired from ViroChem (VCH-759 is a backup): #msg-37089807; IFN-Lambda (BMY/ZGEN; phase-1b): #msg-34768182 (BMY partnership), #msg-37277825 (interim phase-1b data); MK-7009 (MRK, phase-2a), a protease inhibitor that might bite the dust due to MRK’s acquisition of SGP: #msg-34337398, #msg-34335327.

5. Very-early-stage compounds that use an established MoA. These include ACH-1625 (ACHN;phase-1), a protease inhibitor: #msg-39146155; IDX375 (IDIX, preclinical), a non-nucleoside “palm” polymerase inhibitor: #msg-34334563, #msg-31043481; MK-3281 (MRK, phase-1), a non-nucleoside “thumb” polymerase inhibitor: #msg-36508769; PSI-938 (VRUS, preclinical), a purine-analog nucleoside polymerase inhibitor: #msg-39322313; ‘hyperglycosylated’ interferon (Alios BioPharma, preclinical): #msg-35612425; IDX136/IDX316 (IDIX, preclinical), two closely related macrocyclic protease inhibitors of which IDIX will select one to advance into phase-1: #msg-37246670 (EASL 2009 PR), #msg-37315636 (EASL 2009 poster); and VX-813/VX-985 (VRTX, phase-1/preclinical), protease inhibitors from VRTX being developed as follow-on compounds to Telaprevir: #msg-36022752.

6. Early- and very-early-stage compounds that use a novel MoA. These include CF-102 (Can-Fite, phase-1/2), a polymerase inhibitor that purportedly induces apoptosis: #msg-39588570; BMS-790052 (BMY, phase-1), an NS5A inhibitor: #msg-33270670; MB11362 (Roche/MBRX, preclinical), MoA undisclosed: #msg-38456136; A-831 (AZN, status unknown), an NS5A inhibitor: #msg-16682361; a preclinical NS5A program that GSK acquired from GNLB: #msg-33209281, #msg-33211420; IL-7 (Cytheris, phase-1/2) an injectable immunomodulator: #msg-33152073; Debio 025 (Debiopharm, phase-2a), a cyclophilin inhibitor: #msg-37359213; NIM811 (NVS, status unknown), a cyclophilin inhibitor: #msg-36507550; GI-5005 (GlobeImmune, phase-2), an injectable immunomodulator: #msg-37298510; ACH-1095 (ACHN; preclinical), an NS4A inhibitor that GILD dropped and may be dead: #msg-37842823; an unnamed NS5A inhibitor that VRTX acquired from ViroChem (preclinical): #msg-36022752; an unnamed NS5A inhibitor from Presidio Pharma (status unknown): #msg-27791536; clemizole (Stanford University; preclinical), an NS4B inhibitor: #msg-31857987; nitazoxanide (Romark/Chugai, phase-2): #msg-35738696; ITX5061 (iTherX, phase-2a), MoA unknown: #msg-35319690; and an unnamed entry inhibitor from PGNX (preclinical): #msg-38519885.

7. Miscellaneous long shot programs. These include ANA598 (ANDS, possibly entering phase2), a non-nucleoside “palm” polymerase inhibitor that caused severe rash in phase-1 monotherapy (#msg-38420301); ANA773 (ANDS, phase-1), an oral TLR7 modulator that ANDS discontinued in Jun 2009 and is nominally available for partnering: #msg-38418158; taribavirin (VRX, phase-2b), a “legacy” prodrug of ribavirin that has been floating around for a long time: #msg-38280961 (musings on final phase-2b data), #msg-37299101 (detailed 60-week data). (VRX, under a different name, is the inventor of ribavirin.)

JMHO, FWIW