Oncternal Therapeutics Inc (ONCT) 2020 Q1 法說會逐字稿

Greetings, and welcome to the Oncternal Therapeutics Inc. First Quarter Financial Results Conference Call. (Operator Instructions) As a reminder, this conference is being recorded.

It is now my pleasure to introduce your host, Mr. Rich Vincent, Chief Financial Officer. Please go ahead, Mr. Vincent.

Thank you, operator. Good afternoon, everyone, and thank you for joining us. I'd like to welcome you to our Business Update and 2020 first quarter financial results conference call. Joining me on the call this afternoon are our President and CEO, Dr. James Breitmeyer; and our Chief Medical Officer, Dr. Frank Hsu.

Today's call includes a business update and discussion of our 2020 first quarter results, which will be followed by Q&A. Please note that today's press release is available on the Investor Relations section of Oncternal's website. Earlier today, we filed our 10-Q for the first quarter 2020. A replay of today's earnings call will be available on the Investors section of our website for at least the next 30 days.

Please note that certain information discussed on the call today is covered under the safe harbor provisions of the Private Securities Litigation Reform Act. We will be making forward-looking statements during this call about future events such as our business and product development strategies and future financial and operating performance. Our actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with our business. These forward-looking statements should be considered in conjunction with and are qualified by the cautionary statements contained in today's press release and our SEC filings, including our Form 10-Q for the quarter ended March 31, 2020.

This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, May 7, 2020. We undertake no obligation to revise or update any forward-looking statements to reflect events or circumstances occurring after the date of this conference call.

With that, it's my pleasure to introduce our CEO, Jim Breitmeyer.

Thank you, Rich, and good afternoon, everyone. At Oncternal, we are committed to developing novel treatments for patients with cancer who have critical unmet medical needs. We are advancing a robust product pipeline with clinical and preclinical product candidates that target several such cancer indications. Our development efforts focus on untapped biological pathways implicated in cancer genesis and/or progression. In the first quarter of 2020, we have made steady progress on all 4 of the cancer indications we are studying with our clinical product candidates, and this includes the clinical trial studying TK216 for Ewing sarcoma and the clinical trial studying cirmtuzumab for mantle cell lymphoma, or MCL, as well as breast cancer and chronic lymphocytic leukemia, or CLL. We are particularly enthusiastic about the 50% complete response rate we recently reported for patients with MCL, treated with the combination of cirmtuzumab and ibrutinib; and the 28.5% response rate we recently reported for patients with relapsed/refractory Ewing sarcoma treated with TK216.

Everybody is thinking about COVID-19 and its effect on the biotechnology industry. And at this point, I can report that Oncternal's programs continue to move forward, and our employees are doing a wonderful job of managing the challenges related to the pandemic. Oncternal's first priority during this unprecedented public health emergency has been protecting the safety of the patients on our clinical trials, along with the safety of the staff at clinical sites and that of our own employees while ensuring regulatory compliance and data integrity. Enrollment of new patients into our studies has slowed, as reported by most other drug developers, but we have continued to enroll additional relapsed/refractory patients into the Ewing sarcoma study in the last few weeks despite COVID-19-related constraints, highlighting the excitement that our recent deep clinical responses to TK216 have engendered among investigators and the patient community. We believe we have adequate supplies of TK216 and cirmtuzumab clinical trial material through at least the end of 2020. WuXi, our antibody manufacturer in China, is back to full operations. Preclinical studies of TK216 and cirmtuzumab are continuing, but many of the laboratories of our academic collaborators are in partial lockdown, so we do expect some delays in preclinical results concerning potential new indications.

Overall, I'm happy to report that Oncternal remains on track to meet our previously disclosed clinical data milestones for 2020, and I will review them for you shortly. I will now call -- turn the call over to our Chief Medical Officer, Dr. Frank Hsu, who will provide more detail on the clinical programs.

Thank you, Jim. I'll spend the next few minutes updating you on the progress of our clinical programs and taking you through more in depth look at our diverse product candidates. In April 2020, we announced an interim clinical data update for TK216, which is a novel investigational small molecule inhibitor that targets the E26 transformation-specific, or ETS, family of oncoproteins. In our ongoing multicenter Phase I clinical trial, we've been investigating the effect of this agent in patients with relapsed/refractory Ewing sarcoma, which is a relatively rare and really difficult-to-treat malignancy. As of the data cutoff date of March 26, 2020, 7 patients have been treated at the recommended Phase II dose for the RP2D of TK216, which is 200 milligrams per meter square per day for 14 days with or without vincristine. Patients were evaluable for clinical responses. 2 of the 7 patients, 28.5%, had achieved a partial response. 2 had stable disease and 3 had progressive disease. 2 additional patients had rapidly progressing disease early in the first treatment cycle and exited the trial before being evaluated for toxicity or efficacy and per protocol were replaced with 2 new patients.

Both responding PR patients remain on treatment and are doing well. One of these patients receiving single-agent TK216 had a complete regression of all metastatic lung lesions, except one. After maintaining a sustained PR on TK216 and then TK216 plus vincristine, the last residual lung lesion was surgically removed. And so the patient achieved a surgical-complete remission. The second responding patient achieved a 90% reduction of target lesions and resolution of nontarget lesions following 2 cycles of TK216 in combination with vincristine. Overall, safety events associated with TK216 have been manageable. For instance, related events such as neutropenia have responded quickly to G-CSF.

Now I'm going to switch the discussion over to our cirmtuzumab program. In March 2020, we announced an interim clinical data update for cirmtuzumab, which is a ROR1 targeted monoclonal antibody in combination with ibrutinib in patients with relapsed/refractory mantle cell lymphoma, enrolled in our ongoing Phase I/II clinical trial. The new data indicates that 6 of 12 evaluable patients or 50% achieved a complete response by Cheson criteria. One of the 6 had a complete metabolic response as determined by PET scan. Overall, a best objective response CR or PR response rate of 83% was observed. We believe these results compare well to reported outcomes from ibrutinib or other BTK inhibitors in similar MCL populations.

Now at the same time, the CLL portion of our ongoing clinical study continues to enroll and treat patients. 34 patients were enrolled into the dose escalation and expansion portions of the study. And as expected, that all active patients in this group will reach actually 1 year of therapy by the second half of 2020. We are planning to update both the MCL and CLO data from this trial at an upcoming medical meeting. Now regarding breast cancer, which is an ISD study, we expect additional clinical data to be available from the Phase I investigator sponsor study of Cirm plus Taxol in patients with HER2-negative breast cancer in the second half of 2020.

Now our final program is the development of a ROR1 CAR-T cell therapy. In February 2020, we presented ROR1 CAR-T preclinical data at the ASCO-SITC Clinical Immunology Symposium. ROR1 CAR-T cell therapy demonstrated expansion, persistence and antitumor activity in an animal model of human leukemia. This research is being conducted by our collaborators at the University of California, San Diego or UC San Diego, under a grant from the California Institute Regenerative Medicine, otherwise known as CIRM.

Now this work continues through a partnership with Shanghai Pharma. The timing of the program has been delayed due to COVID-19 pandemic events in China. And our goal is now to initiate a first-in-human study in 2021.

Finally, performing clinical trials has been a challenge during the COVID-19 pandemic. Oncternal has been fortunate to remain active and be able to run our clinical studies. We have continued to enroll new patients, although at a slower pace, and have worked with our investigators and their sites to maximize continued visits and treatment of our existing patients when possible.

In addition, we have worked to provide self-administered medications directly to our patients to help reduce travel. And we have been working to develop a broader network of sub-investigator sites, help administer IV drugs closer to home. These efforts and combined with the dedicated patients and tremendous investigators, for whom we are very thankful, have allowed us to continue to treat our patients in our studies and trials.

Now I'd like to turn it over -- back over to Rich Vincent, our Chief Financial Officer, to review our financial results.

Thank you, Frank. In October 2017, CIRM awarded an $18.3 million grant to the researchers at the UC San Diego School of Medicine to advance our Phase I/II clinical trial evaluating cirmtuzumab in combination with ibrutinib for the treatment of patients with B-cell lymphoid malignancies, including MCL and CLL. We are conducting this study in collaboration with UC San Diego and expect to receive $14 million in development milestones under research sub-awards throughout the award period. In conjunction with this award, our grant revenue was $0.6 million for the first quarter ended March 31, 2020.

Our total operating expenses for the quarter ended March 31, 2020, were $5.3 million. Research and development expenses totaled $2.7 million and general and administrative expenses totaled $2.6 million. Net loss for the fourth quarter was $4.7 million for a loss of $0.31 per share basic and diluted. As of March 31, 2020, we had $16 million in cash and cash equivalents. We believe these funds will be sufficient to fund our operations into the fourth quarter of 2020. As of March 31, 2020, we had approximately 15.4 million shares of common stock outstanding.

Now I will turn the call back to our CEO, Jim Breitmeyer.

Thank you, Rich, for that summary of our financial results and Frank, for the clinical summary.

I would now like to highlight the upcoming milestones that we expect to reach over the next several months. Despite the disruptions related to the COVID-19 pandemic, we remain on track to achieve the same key clinical data readouts for cirmtuzumab and TK216 that we had planned for this year. Specifically, we expect to present clinical data from 7 to 12 patients with relapsed/refractory Ewing sarcoma who have been treated with TK216 plus vincristine in the expansion cohort of the study in the second half of 2020. We expect to present a clinical data update for patients with MCL treated with cirmtuzumab plus ibrutinib, including data from 15 patients in the dose-finding and expansion cohorts of the Phase I/II study in mid-2020. We expect to present a clinical data update for patients with CLL treated with cirmtuzumab plus ibrutinib, including up to 12 months of follow-up, 34 patients in the dose-finding and expansion cohorts of the Phase I/II study in mid-2020. We expect a clinical data update to be available from the Phase Ib investigator-sponsored study of cirmtuzumab plus paclitaxel in patients with HER2-negative breast cancer in the second half of 2020. We expect to treat the first patient with our ROR1-targeted CAR-T in the first half of 2021, in a collaboration with Shanghai Pharma Limited.

In closing, we have a well-defined work plan ahead of us with multiple potential catalysts in 2020 and a clear priority of deploying our financial and operating resources to advance our product candidates in multiple clinical indications to benefit patients with cancer. We look forward to updating you during the remainder of 2020.

With that, I'll turn things back to the operator for the Q&A portion of this afternoon's call.

(Operator Instructions) First question is from Hartaj Singh, Oppenheimer.

Great. That's great that you're continuing on with the work in this pretty heinous pandemic. Just a couple of questions. And thanks for the upcoming milestones, I think those are very clear. There's a lot of data flow in the next 6 to 9 months. My question would be specifically on regulatory interactions. So if you could just maybe just walk through cirmtuzumab and MCL and CLL and then TK216. Once you present this data, what are the key regulatory interactions you expect off of that? And then the second question, as a follow-up to that would be, which of these 3 would you expect to sort of go into that next range of clinical trials and would any one of the 3 be in a trial that would be a sort of accelerated approval sort of trial and ideally in 2021? And then I got a quick follow-up.

Thank you, Hartaj. That's quite a compound question. So I'll start out -- and this is Jim. I'll start out and then turn over to Frank. So from a regulatory perspective, we have always believed that -- let's start with TK216. We've always believed that a -- that evidence of objective responses in a relatively small number of patients would be sufficient to go and discuss the TK216 program for Ewing sarcoma with the FDA because the treatment landscape for Ewing sarcoma is so dismal with only a single combination regimen as frontline standard of care and no standard second line. So as you can imagine, we're encouraged by having had 2 substantial clinical responses out of the first 7 patients with the Phase II regimen, and we believe that with a little bit more data that we would be ready to go to the FDA and talk about a pathway to an accelerated approval that would be based on objective response rate for TK216 in Ewing sarcoma. In mantle cell lymphoma, we believe that a 50% complete response rate with the combination of ibrutinib plus cirmtuzumab and is notable compared to ibrutinib alone, particularly considering an interesting safety profile that appears to be -- to have fewer adverse events than other ibrutinib combinations that have been presented recently. So we think that we are quite close to having enough information in mantle cell lymphoma to have a discussion with the FDA about a potential accelerated approval.

For CLL, with the data that you've seen so far and that we discussed today, we think that we need a little bit more time for the data to mature to see if we would go to talk to the FDA about a complete response endpoint or a progression-free survival endpoint. And so we'll know more about that after our next data update. With that, let me turn it over to Frank Hsu and let him discuss with you what potential registration studies might look like for Ewing sarcoma and MCL as a next step.

Thank you, Jim. This is obviously something which is very much in discussion matter within our group about how best to proceed. As Jim has pointed out, we have some exciting data both in TK216 and Cirm, particularly with the mantle cell program that we've been highlighting. Right now, as Jim mentioned, we have some exciting data with TK216, which shows that we have activity. We would like to expand on that and then discuss with FDA potential registration pathways that might, as has been alluded to, be something which we hope could be negotiated to an accelerated program. But that's all within FDA negotiations, of course. The other main program is the mantle cell program. As Jim mentioned, we believe our results, which, although in a small group of patients, if hold -- if they hold up, indicate that we have a very active combination right now when compared to historical data. And that is something which in negotiations with FDA, there are several paths in which one could imagine an accelerated trial being set up for it, but that is very, very much something which we have to have an ongoing discussion with the FDA. So there's nothing right to comment on about that until we get further guidance on that.

Great. And that's actually very, very helpful. The other question I have is that you've indicated that you've got enough drug supply, drug material, it looks like, to get through the rest of the year. You've got cash in hand through the end of the year. How are you thinking, I mean, if, let's say, your regulatory discussions, especially after you present this data in the middle part of the year, sort of heat up for either Ewing sarcoma or TK216 or MCL with cirmtuzumab to go into an accelerated approval kind of trial. I know those probabilities historically tend to be low, but it all depends on the data. But just how are you thinking about manufacturing and sort of from a cash and financial perspective and how to get ready for 2021?.

Hartaj, this is Jim. Thank you for that question really around manufacturing strategy with a potential fast track clinical program. So we have we've reviewed alternatives in depth. And we have -- we do have plans in place to continue to improve our manufacturing processes. We're already happy with the way that we're manufacturing, both TK216 and cirmtuzumab and with some modest additional work, we believe that we can produce potentially commercial-grade material that -- and we do have a plan that we think the CMC side of things can keep up with the clinical side of things, even under a best case, fast track regulatory pathway. Of course, it's quite a juggling act with finances. And so we are very carefully gating spending on the CMC side to be related to clinical results so that we're not getting out over our skis on CMC spending.

The next question is from Carl Byrnes, Northland Securities.

First, congratulations on your progress on the impressive results to date. I was just wondering if there were any abstracts or presentation publications that you anticipate from the studies near term.

Carl, this is Jim. And yes, that's easy. We -- you will see an abstract from us at ASCO when the abstracts are disclosed in about a week.

Great. So that will be -- that's what -- they're disclosed on May 13 for the 29th to 31st ASCO virtual?

Yes.

We have a question from Robert Burns, H.C. Wainwright.

Congrats on the quarter, guys. Two questions from me, if I may. So I wanted -- the first one, I wanted to get your thoughts around the positive top line results we saw from the Phase III UNITY-CLL trial, and the fact that it was stopped early due to superior efficacy. I was wondering how you're viewing that from a competitive landscape development and whether it changes your calculus within development of cirmtuzumab for CLL? And then my second question, so I was looking at the investigator-sponsored trial in breast cancer for cirmtuzumab, and I noted that they're including both HR positive, HER2-negative as well as triple-negative breast cancer, but they exclude -- specifically exclude patients who had prior exposure to a taxane. Now given the IMpassion130 regimen that's in frontline TNBC and the use of other taxanes as single agent within the front line, I was curious how you're thinking about that if -- how you're thinking about the development of cirmtuzumab in that indication. If the data is positive, would you specifically exclude TNBC moving forward, just considering how much of it is actually administered in the frontline setting?

Thank you, Rob. So let me -- I'll handle the breast cancer-related question first. And so when this investigator-sponsored study was initiated, the triple-negative results, including taxanes, had not been presented. And we didn't have any preclinical data. And on prior taxane exposure and response to subsequent taxanes and cirmtuzumab. And so we're -- the ISD is designed to get a clean result with patients that are seeing taxanes for the first time. So we will consider very carefully the evolving landscape and we're also doing -- we're developing some preclinical models to see if prior taxane exposure is an important factor for the subsequent response to taxanes plus cirmtuzumab. So basically, I'm saying it's an open question. So then let me turn over to Frank Hsu to discuss our results in the context of the CLL landscape.

Well, as you pointed out, the CLL landscape has been changing quickly and dramatically. The UNITY study, which you talked about, was stopped on the basis of PFS. So that data hasn't been released as far as I could find or know about, except that it supposedly is superior at this point. So we'll need to gauge or make an assessment of that once that data has been fully vetted but -- and released to public. But at the moment, we're still relatively early. We do not know our overall effects on PFS. The PFS can take a bit of time with CLL, as you're aware, to mature. And so I think that we are still showing some very interesting results that we've reported in the past that we have an active agent. The question will remain is whether or not we will impact PFS in the long term. And we don't have enough long-term follow-up with enough patients yet to know the answer to that.

I think Frank's comments were clear.

For the update that's going to be coming in mid-2020, would there be any PFS data associated with that update? Because I know -- yes, for the Phase I/II mid-2020 update, is there going to be any PFS data associated with it?

Frank, go ahead.

Yes. We haven't released any of the data yet. I'm not sure how much we're embargoed. But as much data as we can, will be presented at the meeting.

And Rob, you'll recall that we -- when we last disclosed CLL data in March, I think, that the -- that we had not seen a single event of CLL disease progression. So PFS was sitting at 100%. And so we're certainly crossing our fingers that it is -- that, that kind of continuing data, something near that, might show up again. But of course, we don't know at this point.

There are no further questions at this time. I would like to turn the call back over to Mr. Rich Vincent for closing remarks. Please go ahead, sir.

Thank you, operator. And on behalf of Oncternal, thank you all again for joining us today. Everyone stay safe and healthy, and we look forward to future updates.

This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.