Biotech Values

[iwfal]

XNCR - Summary of the recent analyst day presentation:

a) Further clarity on items currently in trials:

1) Summary of 5871 (anti-B-cell) protocols of on-going Ph2s in SLE and in IGG4 disease. IGG4 is single arm, single site trial copying protocol of Rituximab trial and based on Responder Index (very similar to vasculitis index). Could have data at end of 2016, but guidance is 2017. SLE trial is 90 pts in RCT. Protocol is to give steroids, to allow taper off immunosuppresant, and randomize those who respond to this lead in. Trial is to provide either treatment or placebo until they lose benefit seen with initial steroids. (Separately note that they are also planning a SC trial later this year to check PK vs IV).

2) 7195 (anti IgE). Nothing new (historical note that they have not yet been able to shake their adverse events of frequent transient thrombocytopenia (in the recently completed trials the low loading dose did not prevent the later, larger dose from creating thrombo), but they have a trial planned to start Q3 trying SC) Note: in response to Q it was said that they have not yet found the mechanism of the thrombo.

b) Oncology pipeline updates - won't try to recapitulate all the details. But some of the things I found most interesting:

1) Unlike their event last year they did not mention anything about targeting regulatory T-Cells.

2) Their focus was on bispecifics that target two different checkpoints.

3) They mentioned the future possibility of a bispecific that antagonizes a checkpoint and agonizes an immune costim.

4) My comment: most of the preclinical IL-2 data didn't look spectacular. Yes, a bispecific that targets PD-1 and xxx produces somewhat more IL-2, but not clear it is above the noise threshold of the test (i.e. for every test they used a straight PD-1 inhibitor as a comparator - and the IL-2 effects of that comparator bounce around a fair amount)

c) Raw science - I found the first presentation on this by far the most interesting. Michael Curran spoke on the topic "Hypoxia Drives Tumor Immune Suppression and Immunotherapy Resistance" (starts about 1 hour mark) and there was, for me, substantive new information:

1) Background/assertion: some of the cancer types that are known to be unresponsive to IO (e.g. prostate and pancreatic) are believed to be unresponsive because they are hypoxic and the hypoxia inhibits T-cell immune response.

2) He presented material on a mouse model that spontaneously develops prostate cancer and the effects of treating the mouse with TH-302 (a drug that reverses tumor hypoxia) with various combos of IO. Pretty dramatic effects.

3) In passing he mentioned things that were interesting: A) showed data that PD-1 plus PD-L1 is synergistic, B) summarized the added tox of PD-1 agent plus CTLA-4 isn't worse tox, but is instead more frequent tox, C) mentioned that oxaliplatin is significantly more immune priming than the other platins.

4) Also, in passing, gave details about TH-302: A) failed all its ph3s but showed efficacy in Japanese cohort (well known that Japanese patients respond differently in NSCLC, but now I am curious about other cancer types), B) they are planning a combo trial of Ipi and TH-302 to start later this year.