Last Updated on June 6, 2019 by Kevin Douglass
Recently, TG Therapeutics (TGTX) reported positive results from its Phase 2b registrational directed trial UNITY-NHL study. Updated results from this study were presented at AACR earlier this year, and most recently at ASCO. For my previous coverage of TGTX, I recommend reading my complete company overview here, and then my most recent update here. In today’s continued coverage, I will outline next notable catalyst and the important dates to be aware of.
International Conference on Malignant Lymphoma
The International Conference on Malignant Lymphoma (ICML) runs June 18th to 22nd. AS previously announced to shareholders, TGTX will have four presentations at this conference: three oral presentations and one poser presentation. The one poster presentation is over a preclinical data, which I am less interested in at this point. What I am interested in is the three oral presentations. They are:
- Umbralisib Monotherapy Demonstrates Efficacy and Safety in Patients with Relapsed/Refractory Marginal Zone Lymphoma: A Multicenter, Open-Label, Registration Directed Phase 2 Study – June 22
- A Phase 2 Study to Assess the Safety and Efficacy of Umbralisib in Patients with Chronic Lymphocytic Leukemia (CLL) Who Are Intolerant to Prior BTK or PI3K Delta Inhibitor Therapy – June 20
- Phase I/II Study of Umbralisib (TGR-1202) in Combination with Ublituximab (TG-1101) and Pembrolizumab in Patients with Rel/Ref CLL and Richter’s Transformation – June 20
Most notably, only the abstract titles are available at this time. The abstracts will be released on June 12th to the ICML website www.lymphcon.ch on June 12, 2019. Now it is uncertain how much data will be in these abstracts. That typically varies conference to conference. Some conferences permit more descriptive abstracts alluding to granular data being presented at the conference, while other conferences require that more granular data be in the abstract. Either way, even if there is limited data in the abstracts, interested parties will only have a short period of time they need to wait for the conference to see the entire data set.
Taking a brief look at the highlighted oral presentations and their allure, we will start from the top. The UNITY-NHL Marginal Zone Lymphoma (MZL) was a main focus of my ASCO article covering TGTX, so I will not rehash this discussion, and would recommend reviewing the discussion of that article here. Essentially, I previously speculated we may see final data or the entire dataset for all patients instead of just the interim data, however that did not come to fruition. So now, we may see that data at ICML instead, which likely fits the timeline previously discussed better, and would be a fitting venue. This would also coincide with management’s guidance to meet with the FDA in the second half of 2019 and file for approval. As this is TGTX’s most advanced program from a regulatory stance, the entire dataset will be quite important.
The next abstract that peaks my interest is “Phase I/II Study of Umbralisib (TGR-1202) in Combination with Ublituximab (TG-1101) and Pembrolizumab in Patients with Rel/Ref CLL and Richter’s Transformation.” We previously saw data from this study at ASH in 2018. Why am I so interested in this? Well Richter’s Transformation is a genetic transformation of CLL that results in a significantly more aggressive form of blood cancer with a much poorer prognosis. This occurs in roughly 5% to 10% of CLL patients. The highly toxic regimen of R-CHOP has yielded favorable results, albeit in a small phase 2 trial. TGTX seeks to utilize a combination of its medications to provide a much more tolerable regimen for the treatment of these patients. Also in this study are relapsed/refractory CLL patients. These patients also often face highly toxic regimens. One of the agents TGTX seeks to leverage is an immuno-oncology agent. Initially, the trial is being done with Merck’s pembrolizumab, however now they seek to replace pembrolizumab with TGTX’s own immuno-oncology agent TG-1501. This would allow TGTX to reap more revenue down the road. While the initial data at ASH was for 14 patients, I am hoping data is provided on more patients to further validate the promising results previously seen. I am also hoping to hear more on the progress they have made regarding the trial amendment to utilize TG-1501 instead of pembrolizumab.
Finally, the third presentation will be “A Phase 2 Study to Assess the Safety and Efficacy of Umbralisib in Patients with Chronic Lymphocytic Leukemia (CLL) Who Are Intolerant to Prior BTK or PI3K Delta Inhibitor Therapy.” It is well known that PI3K inhibitors can have difficult to manage safety profiles. These agents include idelalisib and Verastem’s duvelisib. While umbralisib is a PI3K inhibitor, its slightly different selectivity profile is proposed to make it more tolerable that the aforementioned agents, and this far, the limited data seems to support this idea. Essentially, this trial seeks to test the use of umbralisib in patients who could not tolerate ibrutinib or idelalisib. Initial data was presented at EHA in 2018. This data appeared largely positive, with umbralisib showing signs of efficacy and tolerability in these patients. Now that we are a year later and the trial was fully accrued in June of 2018, this data set should be quite robust. Furthermore, the early results seen last year showed that 47% of patients were able to tolerate umbralisib longer than their previous therapy, which I find encouraging. But most notable, the majority of patients appear to have still been on therapy at that time (figure below). With the additional patients and time, I am excited to see how this data has matured, both in efficacy and tolerabilty.
In my eyes, these presentations will be large updates for TGTX. TGTX has amassed and continues to amass a very robust set of data for umbralisib, seeking to differentiate it from other PI3K compounds on the market. With several potential indications for umbralisib, tolerability will be essential. The MZL is an important update, as the presentation may be the data submitted to the FDA for potential approval in the second half of this year. Second, the combination with immuno-oncology agent pembrolizumab, and eventually TG-1501, could fit into a good niche for patients with Richter’s Transformation and be marketed as a chemotherapy free regimen. Finally, positive data from the CLL trial could definitely help differentiate umbralisib from other PI3K agents, especially given it would be used after these agents, creating a nice market for TGTX. With several shots on goal at ICML, I am excited for these updates on important programs in TGTX’s pipeline.
This is in no form a recommendation to buy/sell securities.
I/we long TGTX