Biotech Values

[DewDiligence]

HCV: Most Likely to Succeed (IMHO)

[Reorganization of the ranking system: levels 4 and 5 merged; R7128 raised
from level 4 to level 2 due to INFORM-1 study; Albuferon raised from level 4
to level 3 due to success of first phase-3 trial; new entries for MK-7009,
BMS-790052, SCH900518, A-831; IDX375, IDX136/IDX316, and Presidio
Pharma; entry deleted for Sirna-034.]


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.)

1. The two leading protease inhibitors: Telaprevir (VRTX/JNJ; phase-3) and Boceprevir (SGP; phase-3). The Telaprevir program is further advanced, so let’s call Telaprevir and Boceprevir 1a and 1b, respectively.

These two drugs have shown comparable efficacy in 24-28 week regimens of phase-2 trials in the genotype-1, treatment-naïve setting: #msg-31190433, #msg-33793333, #msg-33282976. Background posts: VRTX PROVE-1/2 trials made simple: #msg-29019931; PROVE-1/2 detailed results: #msg-28746843; overview of Telaprevir phase-3 program: #msg-26228377; Boceprevir starts phase-3: #msg-29474929.

Telaprevir and Boceprevir are also being tested in the second-line setting, Telaprevir in 24- and 48-week regimens and Boceprevir in 36- and 48-week regimens. Background posts: Telaprevir phase-3 REALIZE study: #msg-32901932; Telaprevir phase-2b PROVE-3 study: #msg-29896176; Telaprevir ‘107’ open-label phase-2 extension for PROVE-1/2 failures: #msg-33282976; Boceprevir phase-3 RESPOND-2 study: #msg-29474929.

2. ITMN-191 and R7128, the two oral drugs that Roche is testing is the INFORM-1 study that does not include interferon or ribavirin: #msg-33967428, #msg-33446127, #msg-33497987. ITMN-191 a.k.a. R7227 (ITMN/Roche; phase 1b) is a protease inhibitor: #msg-28126092. R7128 (VRUS/Roche; phase-1b) is a nucleoside polymerase inhibitor: #msg-33300630 (kidney tox in monkeys), #msg-32238916, #msg-32651030.

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 or phase-3 that use an established MoA: Albuferon (HGSI/NVS; phase-3), an albumin-conjugated interferon : #msg-34043876, #msg-34071611, #msg-13781766, #msg-20275478; BI201335 (B-I; phase-2b), a protease inhibitor: #msg-33564560; and Locteron (Biolex; phase-2), a long-acting interferon made in transgenic plants that may qualify for the 505b2 approval pathway: #msg-28786162. (Biolex recently bought out its partner, OctoPlus, and raised $60M to fund the Locteron program: #msg-32662307, #msg-32662762.)

4. Agents in phase-1b or phase-2 that use an established MoA. These include TMC435 (Medivir/JNJ; phase-2), a protease inhibitor: #msg-33283588;; MK-7009 (MRK, phase-2a), a protease inhibitor: #msg-34337398, #msg-34335327; SCH 900518 (SGP, phase-2a), a protease inhibitor (SGP’s follow-up to Boceprevir): #msg-34338549; GS-9190 (GILD; phase-2 starting by year-end), a non-nucleoside polymerase inhibitor: #msg-32919311; ANA598 (ACHN, phase-1b), a non-nucleoside polymerase inhibitor: #msg-33172848, #msg-34334563; IFN-alpha-XL (FLML; phase-1b): #msg-28837983; and IFN-Lambda (ZGEN; phase-1b): #msg-33311734.

5. Very-early-stage compounds that use an established MoA. These include IDX184 (IDIX; phase-1), a nucleotide polymerase inhibitor: #msg-31043481, #msg-26915921; and ACH-1625 (ACHN; preclinical), a protease inhibitor: #msg-31459921; IDX375 (IDIX, preclinical), a non-nucleoside polymerase inhibitor: #msg-34334563, #msg-31043481; and IDX136/IDX316 (IDIX, preclinical), two related macrocyclic protease inhibitors of which IDIX will select one to advance into phase-1: #msg-31043481.

6. Early- and very-early-stage compounds that use a novel MoA. These include BMS-790052 (BMY, phase-1), an NS5A inhibitor: #msg-33270670; A-831 (AZN, status unknown), an NS5A inhibitor: #msg-16682361; ANA773 (ANDS, phase-1), an oral TLR7 modulator: #msg-33244419; IL-7 (Cytheris, phase-1/2) an injectable immunomodulator: #msg-33152073; GI-5005 (GlobeImmune, phase-2), an injectable immunomodulator: #msg-33322543; ACH-1095 (ACHN/GILD; preclinical), an NS4A inhibitor: #msg-31459921; an unnamed NS5A inhibitor from Presidio Pharma (status unknown): #msg-27791536; and clemizole (Stanford University; preclinical), an NS4B inhibitor: #msg-31857987.

JMHO, FWIW