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TG Therapeutics, Inc. (TGTX)
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We are increasing our PT on TGTX from $30/sh to $48/sh heading into what we believeto be a transformative 4Q for the company; we review our thesis on page 4 in theslide deck. We are expecting Ph3 ublituximab data before the year ends, and we remainconfident in clinical success for this program. In hematology, we are looking forward to thefull presentation of UNITY-CLL and UNITY-NHL at the American Society of Hematology inDec. In particular, we are focused on the safety profile in these studies as we think thatumbralisib (their PI3K delta) will continue to look differentiated from other players. Westill see upside to TGTX shares based on both of these events and we note that by end of2021 the company may have approvals for up to 4 different indications (MS, MZL, FL, andCLL). We also think that a late stage company like TGTX remains attractive to many largebiopharma players that are in need of near-term launch stories.We remain confident around upcoming ULTIMATE I & II Ph3 readouts in light of veryrobust Ph2 data for ublituximab. The original data was presented at ECTRIMS 2018 wherethe primary endpoint was response measured by over 95% B-cell depletion at week 4.There was a 100% response at week 4 in 48 patients and a median 99% depletion wasmaintained at week 24 and 48. Typical secondary endpoints were measured at week 48such as annualized response rate (ARR), Gd enhancing lesions, disease progression, andno evidence of clinical disease. The primary endpoint in Ph3 ULTIMATE I & II study isannualized relapse rate, and the Ph2 study showed an annualized relapse rate of .07 basedon 48 subjects at a mean follow-up of 47 weeks. In Ph2, general tolerability and infusionsite reactions looked manageable. In Ph3, patients get 1 hour infusions based on theirfindings in Ph2 which is differentiated from Ocrevus (~3.5 hour infusion).We have increased our speed to peak sales in MS and our peak sales estimate, and weincreased our probability of success estimate as we head into the Ph3 readout in 4Q.Previously, we assumed WW unadjusted peak ublituximab sales of $1.4B by 2035 vs. ournew estimate of $1.9B by 2028. Although we would expect TGTX will gradually build apresence in MS with its salesforce, we think our prior estimates were too conservative.We increased our prob of success from 65% to 75%. At 100% success, it adds $10/shareto our DCF. Although Kesimpta and Ocrevus are two other anti-CD20s on the market, wethink that the market is large enough for another player like ublituximab. We estimate thecurrent global market size at $20B, so even a small share should lead to a blockbuster. Wemodel a 20% price cut relative to Ocrevus and a 60% price cut to Kesimpta (priced at $85Kas a subQ monthly self-administered treatment). Although subQ is more convenient, wethink that a big part of the market likely will get 6-month infusions rather than choosingto administer themselves.With recent pullback, we think that risk/reward into MS looks fairly compelling (upside100-123%, downside 44%), assuming no changes to our CLL base case. ......
Our TGTX thesis:
We remain confident in upcoming MS readout and full data presentation for hematology in Dec
We are increasing our PT on TGTX from $30 to $48 as a result of increasing our ramp speed and peak sales for ublituximab for treating MS.
We previously assumed a ramp speed of 15 years and now assume 8 years to peak sales. Our WW unadjusted peak sales estimate is now $1.9B by 2028 vs. previous model of $1.4B by 2035.
We remain confident on Ph3 success for ublituximab in their ongoing MS study; we expect data in 4Q20. While we know the CLL and FL hit their clinical endpoints, we are focused on the full data presentation at ASH as we think that the safety profile is very important for their PI3K delta (umbralisib).
By the end of 2021, TGTX could have two approved clinical assets in hematology and MS.
We think no credit is given to their pipeline beyond these two assets, but we would expect the company continues to make progress on their pipeline over the next 12 months.October
Firstly, from an 8k on 10-15-2018 referencing a pr on 10-11-2018 we know that enrollment in the ultimate program was complete as of 10 -11- 2018. From page 9 of the 10k for 2018 we know that enrollment actually completed in the the month of October 2018. Combining both means enrollment actually completed sometime in the first 11 days of October 2018. Furthermore since this date is an extension past the original targeted enrollment completion it is reasonable to assume they schemed things so that both Ultimate 1 and ultimate 11 actually finished enrollment in this time frame. ( so as to allow both trials to finish up close together )
For simplicity we may then say both trial finished enrollment in the first week of October 2018
Secondly, enrollment IS NOT the same as initial treatment. Not the same thing. Enrollment simply means that a person has passed all criteria for the trial and signed on the dotted line. I would think that all of the latter enrolled patients would have received their initial treatments by the time a month has passed. So all patients should have received initial treatment by the end of the first week of November 2018
Trials are to measure results @ 96 weeks of treatment, however CEO noted in one of their presentations that while most patients were coming in for screening on time, a small percentage was straggling in 2 or 3 weeks late ( due to covid concerns ). So make it 99 weeks from the first week of November 2018 for the required screening to be done.
Then there is the time required for data analysis and the issue of whether they release the trial results separately or wait to release both at the same time.
Understand that the data from the two separate trials WILL NOT be analyzed at the same time. The assessment of the brain scans, etc, from one trial will first be done by a small number of true experts in the field while the data set from the other trial remains locked. This is done to prevent any possible mix up or contamination of patients and data between the two trials. Such an event could be catastrophic, could render the trial data useless. AFTER the experts have finished the first trial data and this data has been vigorously isolated, the data set from the other trial will be unlocked and given to the experts.
This is why MW mentioned in one of the recent presentations that they would have results soon if they released the trial results separately, but would have a bit more of a delay if they waited to released results of both trials together which he said they were leaning towards doing.
Anyway, should take about a month or so for data analysis of each trial. So something like 103 weeks from the first week of November 2018 to get one of the trial results separately, and about 107 weeks if they wait to release the results of both trials together.
For simplicity we may then say both trial finished enrollment in the first week of October 2018
FDA Grants Ublituximab/Umbralisib Combo Fast Track Status in CLL
October 21, 2020
Gina Mauro
The FDA has granted a fast track designation to the investigational CD20-directed monoclonal antibody ublituximab in combination with the PI3K-delta inhibitor umbralisib for the treatment of adult patients with chronic lymphocytic leukemia.
The FDA has granted a fast track designation to the investigational CD20-directed monoclonal antibody ublituximab in combination with the PI3K-delta inhibitor umbralisib (U2 regimen) for the treatment of adult patients with chronic lymphocytic leukemia (CLL).1
Positive topline results of the combination were unveiled in May 2020 from the phase 3 UNITY-CLL trial, in which the doublet improved progression-free survival (PFS) compared with obinutuzumab (Gazyva) plus chlorambucil in patients with previously untreated and relapsed/refractory disease.2 The study is being conducted under a Special Protocol Assessment agreement with the FDA.
An independent review panel determined that the chemotherapy-free U2 combination induced a statistically significant improvement in PFS (P < .0001), and the panel recommended that the trial be stopped early.
"We are extremely pleased to have received fast track designation for the ublituximab plus umbralisib regimen, or the U2 combination, to treat adult patients with CLL. The application for Fast Track was based on data from the UNITY-CLL phase 3 study that we announced earlier this year had met its primary endpoint of progression free survival,” said Michael S. Weiss, executive chairman and chief executive officer of TG Therapeutics, the developer of both agents.
In the phase 3 UNITY-CLL trial, patients with both treatment-naïve and relapsed/refractory CLL were initially randomized into 1 of 4 treatment arms: single-agent ublituximab; single-agent umbralisib; U2; or obinutuzumab plus chlorambucil. The trial design did allow for discontinuation of the 2 monotherapy arms following a positive assessment of the U2 combination. Randomization, at that point, continued with the U2 and obinutuzumab/chlorambucil arms only.
Overall, the trial enrolled 420 patients across these 2 arms, which comprised approximately 60% treatment-naïve patients and 40% of relapsed/refractory patients. The primary endpoint is PFS and, if positive, will be used to support the submission for full approval of the U2 combination in this patient population.
Previously, a number of doublet and triplet combinations including umbralisib and/or ublituximab have shown intriguing results in CLL. For example, the triplet regimen of pembrolizumab (Keytruda) plus umbralisib/ublituximab induced a 90% objective response rate (ORR) in patients with relapsed/refractory disease.3 Nine of 10 patients with CLL receiving the triplet achieved a response, including 1 complete response (CR) and 8 partial responses (PRs), according to data from a phase 1/2 study presented at the 2018 ASH Annual Meeting.
Furthermore, the triplet of umbralisib, ublituximab, and venetoclax (Venclexta) induced a CR rate of 44% as a treatment for patients with relapsed/refractory chronic CLL in a phase 1/2 dose-escalation study.4 At the end of 12 cycles of treatment with the regimen, the ORR was 100%, which included the CR rate of 44%. In an assessment of peripheral blood, all patients were negative for minimal residual disease (MRD). In the bone marrow, 78% were MRD-negative (< .01%) and 22% were MRD intermediate (.01% to 1.0%). At a median follow-up of 6.4 months (range, 0.7 to 19.0+), no patients had progressed.
In long-term data from the phase 3 GENUINE study, the combination of ublituximab and ibrutinib (Imbruvica) improved PFS, as determined by an independent review committee, versus single-agent ibrutinib in patients with relapsed/refractory high-risk CLL.5 Results showed that the ORR was 78%, which included a CR rate of 7%, compared with a 45% ORR in the single-agent ibrutinib arm where there were no CRs. Additionally, 19% of patients in the ublituximab arm were MRD negative versus 2% of patients on ibrutinib alone. Overall, 66% of patients had a >75% decrease in lymph node size with ublituximab plus ibrutinib compared with 52% for ibrutinib alone.
“This designation holds several important advantages to potentially expedite the development and regulatory review of U2 and underscores the significant unmet medical need that still exists for patients with CLL,” Weiss concluded. “We look forward to presenting data from the UNITY-CLL phase 3 trial later this year, which we plan to use as the basis of a U2 regulatory submission for CLL.”
References
TG Therapeutics announces fast track designation granted by the FDA to ublituximab in combination with umbralisib for the treatment of adult patients with chronic lymphocytic leukemia. News release. TG Therapeutics. October 21, 2020.
This stock will have Great phase 3 results I looked at phase 2 results last night again. It was so positive it would be extremely unlikely that we would diverge much from those results. which would make us the standard of care for MS. which will carry us over 50 possibly over 60. So try and not watch the stock so much because lately it can be painful.
I am holding tight through and beyond the data readouts. Be strong. Know what you have. Avoid margins.
Oct 21, 2020
PDF Version
NEW YORK, Oct. 21, 2020 (GLOBE NEWSWIRE) -- TG Therapeutics, Inc. (NASDAQ: TGTX), today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to the combination of ublituximab, the Company’s investigational glycoengineered anti-CD20 monoclonal antibody, and umbralisib, the Company’s investigational once-daily, oral, dual inhibitor of PI3K-delta and CK1-epsilon, for the treatment of adult patients with chronic lymphocytic leukemia (CLL).
Michael S. Weiss, Executive Chairman and Chief Executive Officer of TG Therapeutics stated, "We are extremely pleased to have received Fast Track designation for the ublituximab plus umbralisib regimen, or the U2 combination, to treat adult patients with CLL. The application for Fast Track was based on data from the UNITY-CLL Phase 3 study that we announced earlier this year had met its primary endpoint of progression free survival. This designation holds several important advantages to potentially expedite the development and regulatory review of U2 and underscores the significant unmet medical need that still exists for patients with CLL.” Mr. Weiss continued, “We look forward to presenting data from the UNITY-CLL Phase 3 trial later this year, which we plan to use as the basis of a U2 regulatory submission for CLL.”
ABOUT FAST TRACK
Fast Track is a program designed to expedite the development and review of drugs that treat serious conditions and that demonstrate the potential to address an unmet medical need. Filling an unmet medical need is defined as providing a therapy where none exists or providing a therapy that may be potentially better than available therapy.
A drug that receives Fast Track designation is eligible for more frequent interactions with the FDA, priority review if relevant criteria are met, and rolling submission of the Biologic License Application or New Drug Application.
ABOUT UNITY-CLL PHASE 3 TRIAL
UNITY-CLL is a global Phase 3 randomized controlled clinical trial comparing the combination of ublituximab plus umbralisib, or U2, to an active control arm of obinutuzumab plus chlorambucil in patients with both treatment-naïve and relapsed or refractory chronic lymphocytic leukemia (CLL). The trial randomized patients into four treatment arms: ublituximab single agent, umbralisib single agent, ublituximab plus umbralisib and an active control arm of obinutuzumab plus chlorambucil. A prespecified analysis was conducted to assess the contribution of ublituximab and umbralisib in the U2 combination arm and allowed for the termination of the single agent arms. Accordingly, the UNITY-CLL Phase 3 trial continued enrollment in a 1:1 ratio into the two combination arms: the investigational arm of U2 and the control arm of obinutuzumab plus chlorambucil. Full enrollment into the UNITY-CLL Phase 3 trial completed in October of 2017 with approximately 420 subjects enrolled to the two combinations arms. This trial enrolled approximately 60% treatment-naïve CLL patients and 40% relapsed or refractory CLL patients. The primary endpoint for this study was superior Progression Free Survival (PFS) for the U2 combination compared to the control arm to support the submission for full approval of the U2 combination in CLL. Positive topline results from this trial were announced in May 2020. The UNITY-CLL Phase 3 trial is being conducted under Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA).
ABOUT CHRONIC LYMPHOCYTIC LEUKEMIA
Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia, and in 2020 it is estimated there will be more than 20,000 new cases of CLL diagnosed in the United States1. Although signs of CLL may disappear for a period of time after initial treatment, the disease is considered incurable and many people will require additional treatment due to the return of malignant cells.
$TGTX Ublituximab the Ultimate Fast-Follower in the Fastest Growing Drug Class in Multiple Sclerosis; Reiterate Buy,
PT from $37 to $52
Stamina
Persistence
Knowledge
No margin
No stop gaps
Continuous due diligence will help you with the above.
If there are available therapies, a fast track drug must show some advantage over available therapy, such as:
Showing superior effectiveness, effect on serious outcomes or improved effect on serious outcomes
Avoiding serious side effects of an available therapy
Improving the diagnosis of a serious condition where early diagnosis results in an improved outcome
Decreasing a clinical significant toxicity of an available therapy that is common and causes discontinuation of treatment
Ability to address emerging or anticipated public health need
- ublituximab data for multiple Sclerosis is released
- ASH 20 Abstracts are released and the actual Dec ASH presentations
- TGTX holds the investor day
- margin call ins for the 14 million shares short (some losing all their belongings)
Today we have a dip of $1. So what in the greater scheme of events. As Jefferies said we could have a 50%+ spike on data read out ($15+).
Just to give you an idea of the market size potential here.