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Replies to #82027 on Biotech Values
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dewophile

08/09/09 1:37 PM

#82038 RE: DewDiligence #82027

HCV drugs in development

based on clinicaltrials.gov BMS-790052 is now in phase II (the single dose ascending trial - listed as a phase 2 but is really a 1b - is completed, and the phase II in combination with SOC is now enrolling). one would think the 1b data would be presented soon unless BMY is holding back for competitive reasons (BMY seems to be cagey with their HCV development program - they have 2 other drugs in 1b the targets of which i still think are not disclosed - BMS-791325 and BMS-650032)

also i vaguely recall ABT had a drug moving under the radar into phase 2 for an undisclosed target, but now I can't find the trial listed

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DewDiligence

08/09/09 6:06 PM

#82052 RE: DewDiligence #82027

HCV: Most Likely to Succeed (IMHO)

[Updated entries for BMS-790052 (thanks,
dewophile) and ITMN-191 (ritonavir boosting).]



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-40319474 (boosting with ritonavir), #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-40115833; 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: #msg-34337398, #msg-34335327; and ANA598 (ANDS, entering phase-2), a non-nucleoside “palm” polymerase inhibitor that caused severe rash in phase-1 monotherapy (#msg-40064675).

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. Agents in phase-2 or earlier 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-2), an NS5A inhibitor: #msg-40350075, #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-39883747; 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 programs that are nominally alive but not receiving any financial support. These include ANA773 (ANDS, phase-1), an oral TLR7 modulator that ANDS discontinued in Jun 2009 and is nominally available for partnering: #msg-38418158; and 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