Replies to post #100777 on Biotech Values

[mcbio]

IDIX @ BMO (8/5/10)

1. At the 26:30 mark, the CFO/CBO, briefly touched on partnering for 184 and indicated that the objective at the beginning of the year was to partner 184. That objective has not changed and IDIX is quite pleased where they are in discussions and they continue to move forward.

2. At about the 28 mark or so, there's some discussions about IDIX's planned pivotal HCV trials. J.P., if I understood him correctly, anticipates that IDIX's first pivotal trial will include 184 + 320 + peg/riba against telaprevir + peg/riba. Before moving to its own triple combo of DAAs, IDIX must first satisfy itself that a two drug combo is not enough (IDIX doesn't believe that will be enough).

3. In conjunction with the first pivotal, IDIX plans to run a Phase 2b of I believe a triple combo to see initially if pegIFN can be eliminated and ultimately to test a triple combo to see if riba can be eliminated in addition to peg.

4. NS5As are becoming increasingly popular because they are the most potent HCV drugs in development.

[DewDiligence]

HCV: Most Likely to Succeed (IMHO)

[New Boceprevir entry re cherry-picking of
patients in the RESPOND-2 study (#msg-53025126).]


The following paragraphs are in descending order of likelihood of success. There is no claim of completeness in this compilation, i.e. paragraphs 2-6 do not necessarily mention all of the applicable drug candidates within a given grouping.

Please see #msg-49115388 for the distinction between a nucleoside and a nucleotide; also see #msg-43114117 for historical perspective from the HIV arena.


1. The two leading protease inhibitors: Telaprevir (VRTX/JNJ; phase-3 almost completed/NDA submission in progress) and Boceprevir (MRK; phase-3 completed/NDA submission late 2010). Between these two, I consider Telaprevir the favorite for the reasons mentioned in the prologue of #msg-52949888; however, this assessment could conceivably change when MRK presents the complete phase-3 dataset for Boceprevir at the AASLD conference in Oct-Nov 2010. The table in #msg-52978824 compares the Telaprevir and Boceprevir data in the first- and second-line settings with the caveat that the trial designs and patient pools for the two sets of trials have some differences; see #msg-53025126 about the exclusion of null responder patients from the Boceprevir RESPOND-2 study.

Telaprevir in the first-line setting: #msg-50595952 (results of phase-3 ADVANCE study—PR); #msg-50595752 (results of ADVANCE study—data table); #msg-50633310 (tepid investor reaction/Stevens-Johnson Syndrome); #msg-26228377 (ILLUMINATE—the smaller of the two phase-3 trials); #msg-52754317 (phase-3b study of TID vs BID dosing); #msg-43114192 (‘C208’ phase-2 study of BID vs TID dosing); #msg-29019931 (summary of results from phase-2b); #msg-28746843 (detailed results from phase-2b).

Telaprevir in the second-line setting:: #msg-32901932 (phase-3 REALIZE study); #msg-48759554 (phase-2b PROVE-3 study).

Boceprevir in the first- and second-line settings: #msg-52949888 (PR with results of SPRINT-2 and RESPOND-2 studies); #msg-53025126 (exclusion of null responder patients from RESPOND-2 study); #msg-50187183 (NDA submission will exclude phase-3 anemia study); #msg-52963584, #msg-37298085 (questions about anemia and EPO use); #msg-31190433 (musings on SPRINT-1 phase-2b data).


2. Other programs in phase-2b or later: BI 201335 (Boehringer Ingelheim; phase-2b), a protease inhibitor: #msg-50285996 (safety profile), #msg-47877812 (abstract from 2010 EASL), #msg-42086185 (abstract from 2009 AASLD), #msg-33564560 (phase-2b design), #msg-51243571 (all-oral trial with BI 207127); Debio 025 (NVS/Debiopharm; phase-2b), a cyclophilin inhibitor: #msg-46432280; GI-5005 (GlobeImmune; phase-2b), an injectable immunomodulator: #msg-49095438 (phase-2b data); #msg-49171909 (IL-28 B genotype data); IFN-Lambda (BMY/ZGEN; phase-2b): #msg-50805665, #msg-43360640 (phase-2a/2b trial description), #msg-34768182 (BMY partnership), #msg-43123220 (final phase-1b data); ITMN-191 (Roche/ITMN; phase-2b; a/k/a Danoprevir/RG7227), a protease inhibitor: #msg-49099924 (phase-2b data without ritonavir), #msg-52702788 (INFORM-3 delay), #msg-46797334 (Dew’s bearish take), #msg-43632598 (first report of liver tox), #msg-45340745 (phase-2b design change and delay), #msg-49046274 (phase-1b data with ritonavir [PR]), #msg-47860488 (phase-1b data with ritonavir [abstract]), #msg-49056848 (ghmm’s musings on ritonavir data), #msg-44330890 (slides from 2009 HepDart), #msg-43185247 (INFORM-1 data from 2009 AASLD); Locteron (Biolex; phase-2b), a long-acting interferon made in transgenic plants that may qualify for the 505b2 approval pathway: #msg-49286341 (interim phase-2b data from 2010 EASL), #msg-37298340 (final phase-2a data), #msg-40953698 (manufacturing agreement); nitazoxanide (Romark/Chugai; phase-2a completed): #msg-49791818; PSI-7977 (VRUS; phase-2a completed), a nucleotide polymerase inhibitor that’s a single-isomer formulation of PSI-7851: #msg-49886718 (phase-2a data), #msg-49115305 (comparison to IDX184 data), #msg-40115833 (phase-1b data for PSI-7851); RG7128 (Roche/VRUS; phase-2b), a nucleoside polymerase inhibitor: #msg-46762882 (phase-2b overview), #msg-51072553 (12-week interim safety analysis from PROPEL trial in gentotype-1/4), #msg-43185247 (INFORM-1 data from AASLD 2009); TMC435 (Medivir/JNJ; phase-2b), a protease inhibitor: #msg-52204240 (24-week data from phase-2b), #msg-50276630 (safety signals), #msg-49286281 (presentations at 2010 EASL), #msg-43361309 (overview of phase-2 program at 2009 AASLD), #msg-37298740 (phase-2a data at 2009 EASL).


3. Programs in phase-1b/2a with an established MoA: ABT-072 (ABT; phase-2), a non-nucleoside polymerase inhibitor: #msg-47086871; #msg-47060142; ABT-333 (ABT; phase-2a), a nucleoside polymerase inhibitor: #msg-47060142, #msg-42098204; ABT-450 (ABT/Enanta; phase-2a), a protease inhibitor: #msg-47060142, #msg-35708745; ACH-1625 (ACHN; phase-1b), a protease inhibitor: #msg-50099890 (phase-1b data table), #msg-50044936, #msg-51176124 (general musings on program); ANA598 (ANDS; phase-2a), a non-nucleoside “palm” polymerase inhibitor: #msg-52795076 (interim SVR12 data from phase-2a), #msg-50475044 (12-week phase-2a data), #msg-50504158 (phase-2a EVR table and questions about non-ITT reporting), #msg-50475368 (bearish assessment), #msg-40064675 (musings on phase-1b data); BI 207127 (Boehringer Ingelheim; phase-2a), a non-nucleoside polymerase inhibitor: #msg-51499515; BMS-650032 (BMY; phase-2a), a protease/NS3 inhibitor that’s being tested in an all-oral trial with BMS-790052: #msg-44700187, #msg-40361108; BMS-790052 (BMY; phase-2a), an NS5A inhibitor that’s being tested in an all-oral trial with BMS-650032: #msg-44700187 (phase-2 combination trial), #msg-49176213 (phase-2a monotherapy data from 2010 EASL); GS9256 (GILD, phase-2a), a protease inhibitor that has been tested with GS9190: #msg-52702788, #msg-46036072; IDX184 (IDIX; phase-2a), a nucleotide polymerase inhibitor: #msg-49096739, #msg-49003061 (interim phase-2a data [table]), #msg-49096739 (interim phase-2a data [PR]), #msg-49115305 (comparison to PSI-7977 data), #msg-52028450, #msg-49731578 (combination with IDX320), #msg-39719159, (phase-1b monotherapy data), #msg-49115388, #msg-26915921 (nucleotide/liver-targeted MoA), #msg-49055353, #msg-47954632 (in vitro data in combination with other IDIX drugs); IDX320 (IDIX; phase-1b), a macrocyclic protease inhibitor: #msg-51127676 (phase-1b monotherapy trial), #msg-52028450, #msg-49731578 (combination with IDX184), #msg-51165077 (half-life and dosing frequency), #msg-49055353, #msg-47954632 (PK, DDI, in vitro data in combination with other IDIX drugs); IFN-alpha-XL (FLML; phase-2a): #msg-44688995; MK-7009 (MRK; phase-2a), a protease inhibitor: #msg-34337398, #msg-34335327; PPI-461 (Presidio Pharma; phase-1b), an NS5A inhibitor: #msg-52296077; VX-222 (VRTX; phase-2; f/k/a VCH-222), a non-nucleoside “thumb” polymerase inhibitor (acquired from ViroChem) being tested with Telaprevir+SoC as well as with Telaprevir alone: #msg-47189924 (combo trial with Telaprevir), #msg-47242513 (musings on combo trial), #msg-49096553 (phase-1b monotherapy data [PR]), #msg-47879091 (phase-1b monotherapy data [abstract]).


4. Very-early-stage programs with an established MoA: ACH-2684 (ACHN; preclinical), a protease inhibitor: #msg-46160360; ACH-2928 (ACHN; preclinical), an NS5A inhibitor: #msg-52524948; AVL-181 and AVL-192 (Avila Therapeutics; preclinical): a pair of related protease inhibitors: #msg-49093995; EDP-239 (Enanta; preclinical): an NS5A inhibitor: #msg-47301187; ‘hyperglycosylated’ interferon (Alios BioPharma; preclinical): #msg-35612425; IDX375 (IDIX; phase-1), a non-nucleoside “palm” polymerase inhibitor: #msg-45350536 (phase-1 PK data), #msg-49055353, #msg-47954632 (in vitro data in combination with other IDIX drugs); INX-189 (INHX, phase-1), a nucleotide polymerase inhibitor: #msg-50110448; PSI-938 (VRUS; phase-1b), a purine-analog nucleotide prodrug: #msg-52714527; PSI-661 (VRUS; preclinical; f/k/a PSI-839), a purine-analog nucleotide prodrug billed as the successor to PSI-938: #msg-42245955; three unnamed compounds with undisclosed MoA’s (GILD; phase-1): #msg-49224935; an unnamed NS5A inhibitor (IDIX; preclinical): #msg-47110147; an unnamed NS5A inhibitor (GSK via Genelabs; status unknown): #msg-33209281, #msg-33211420; an unnamed second-generation protease inhibitor (Roche/ITMN; preclinical): #msg-49783993; an unnamed NS5A inhibitor (VRTX via ViroChem; preclinical): #msg-36022752.


5. Programs in phase-2a or earlier with a novel MoA: ACH-1095 (ACHN; preclinical), an NS4A inhibitor that GILD dropped while retaining the right to opt back in: #msg-41217537; AVL-181 (Avila Therapeutics; preclinical), a small-molecule drug that purportedly binds to an infected hepatocyte: #msg-47113598; CF102 (Can-Fite; phase-1/2), a polymerase inhibitor that purportedly induces apoptosis: #msg-39588570; Clemizole (Eiger Biopharmaceuticals; phase-1), an old antihistamine repositioned as an NS4B inhibitor: #msg-51892107; CTI-1027 (Conatus; phase-2): #msg-46034554; IL-7 (Cytheris; phase-1/2) an injectable immunomodulator: #msg-33152073; IMO-2125 (IDRA; phase-1), a TLR9 agonist: #msg-49094332; ITX5061 (iTherX; phase-2a), MoA unknown: #msg-35319690; MB11362 (Roche/MBRX; preclinical), MoA undisclosed: #msg-38456136; NOV-205 (NVLT, phase-2), supposedly an immunomodulator: #msg-48269914; SCY-635 (Scynexis; phase-1b), a cyclophilin inhibitor: #msg-46669845; SD-101 (DVAX; phase-1b), a TLR9 agonist: #msg-45932364; SPC3649 (Santaris; preclinical), MoA based on microRNA: #msg-44177354; an unnamed entry inhibitor (PGNX; preclinical): #msg-38519885; an unnamed miR-122 inhibitor (GSK/Regulus; preclinical): #msg-47081015.


6. Programs on the back burner: A-831 (AZN; status unknown), an NS5A inhibitor: #msg-49610323; Albuferon/Zalbin (HGSI/NVS; post-BLA): #msg-51249417 (no-go with FDA), #msg-49185693 (EU MAA withdrawn), #msg-36140577 (phase-3 data), #msg-48180658, #msg-48213975 (phase-2 data with monthly dosing); ANA773 (ANDS; phase-1), an oral TLR7 modulator that ANDS discontinued in Jun 2009 and is nominally available for partnering: #msg-38418158; GS9190 (GILD; phase-2a), a non-nucleoside polymerase inhibitor with manifold safety and efficacy issues that had been tested with GS9256: #msg-52702788, #msg-46036072; MK-3281 (MRK; phase-1), a non-nucleoside “thumb” polymerase inhibitor: #msg-50798497; SCH 900518/narlaprevir (MRK; phase-2a), a protease inhibitor originally owned by Schering-Plough that MRK discontinued following a pipeline pruning: #msg-47224801 (3/1/10 announcement of discontinuation), #msg-43169835 (interim phase-2a data), #msg-34338549 (final phase-1b data); 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); VX-813/VX-985 (VRTX; phase-1/preclinical), protease inhibitors that were previously touted as the backups to Telaprevir: #msg-45333927.


JMHO, FWIW