Replies to post #178000 on Biotech Values

[ariadndndough]

Jaybe
Nice to hear from you and as you know respect
Your opinion

I like tgtx here. Market cap only 150 million for 2
Drugs with early and improving results

It's the toxicity that I hope makes this drug different
Very low so far

The main drivers going forward are the combo
Results coming soon. It's the low tox that may allow
Combo were the others could not

Appreciate you looking into tgtx
Your friend
Dough

[bellweather1]

I know its early and 6 CLL patients is too few to judge

Hi jaybe,


I don't want to speak for Doug, but it's my understanding that it's often takes several cycles(unlike some anti CD-20s) to show efficacy with PI3K inhibitors, so 67% for a Jan readout seems fine for the moment, because I think we can assume that the efficacy will only improve with time.

In addition, since PI3Ks are all likely to have their major value in combos, when the ceo recently confirmed that efficacy continues to improve with time, but more importantly, that TGR-1202, (as of the recent Qtr call), continues to show no signs of liver or any other unmanageable toxicity, I think that's a lot more important. This is after all a dose escalation study, so max efficacy doesn't usually materialize at the outset.

In other words, if TG-1202 does what it was presumably designed to do(to avoid liver toxicity by eliminating certain aspects of previous PI3K chemical structures associated with toxicity), then it's efficacy should increase nicely with the 3-4 fold formulation and administration advantages recently identified, and the lack of toxicity issue will be a critical advantage.

Although I agree that this is yet to be demonstrated, I think the absence of any liver tox to date is very encouraging in this class of drugs.

But I agree with Doug-I appreciate you looking into tgtx and please advise us of any reservations you may have.

Best,

bw

[GD]

Ibrutinib's 100% only with ofatumumab:

1: Abstract # 6508: A phase Ib/II study evaluating activity and tolerability of BTK inhibitor PCI-32765 and ofatumumab in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and related diseases.
Dr. Samantha Mary Jaglowski et al. The Ohio State University, Columbus, Ohio.

Most adverse events were Grade 1 and 2, and commonly reported Grade 3 infectious events were as expected in this patient population
Overall response rate is 100% in CLL/SLL/PLL patients. Progression free survival with a median follow-up of 9.8 months is 100%.

single-agent:

2: Abstract # 6507: The Bruton's tyrosine kinase inhibitor PCI-32765 in treatment-naïve chronic lymphocytic leukemia patients: Interim results of a phase Ib/II study.
Dr. John C. Byrd et al., The Ohio State University, Columbus, Ohio.

Non-hematologic toxicities of ibrutinib single agent remain manageable and tolerable with no new signals; hematologic toxicities were uncommon.
Overall response rate in the 420 mg cohort is 81% using ibrutinib as a single agent. 12% of patients achieved a complete response with no morphologic evidence of CLL. Progression free survival with a median follow-up of 14.4 months is 96% in the 420 mg cohort.

final results: ORR 71%
Ibrutinib Frontline Chronic Lymphocytic Leukemia Study Results Published in The Lancet Oncology

After a median follow-up of 22.1 months (range, 18.4-23.2), the overall response rate (ORR) for patients was 71 percent (95% CI, 52-86), which included 55 percent partial response, 3 percent nodular partial response and 13 percent complete response. An additional 13 percent of patients achived a partial response with lymphocytosis. The median time to initial response was 1.9 months (range, 1.5-7.4); the median time to best response and complete response were 5.9 months (range, 1.8-22.1) and 12.0 months (range, 7.1-15.6), respectively.

3: Ibrutinib Study Results in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia Published in The New England Journal of Medicine

study participants were enrolled selected to receive either ibrutinib 420 mg (n=51) or 840 mg (n=34) as a once-daily, oral monotherapy. Both doses were associated with overall response rates of 71 percent.