Greetings, ladies and gentlemen, and welcome to the Oncternal Therapeutics Fourth Quarter Financial Results Conference Call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation.

[Operator Instructions] As a reminder, this conference is being recorded.It is now my pleasure to introduce your host Richard Vincent, Chief Financial Officer. Thank you, sir. You may begin..

Thank you, operator. Good afternoon, everyone, and thanks for joining us. I'd like to welcome you to our business update and 2019 fourth quarter and full-year financial results conference call. Joining me on the call this afternoon are our President and CEO, Dr. Jim Breitmeyer; and our Chief Medical Officer, Dr.

Frank Hsu.Today's call includes the business update and discussion of our 2019 fourth quarter and full-year 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. We plan to file our 10-K for the full-year 2019 today.

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-K for the year ended December 31, 2019.This conference call contains time-sensitive information about information that is accurate only as of the date of this live broadcast, March 16, 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 cancer treatments for patients with cancer that have critical unmet medical need. We're 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.

Throughout 2019 and into early 2020, we have made steady progress on all four of the cancer indications we are studying with our clinical product candidates, cirmtuzumab and TK216, mantle cell lymphoma or MCL, Ewing sarcoma, breast cancer and chronic lymphocytic leukemia or CLL.We are particularly enthusiastic about the 50% complete response rate we recently reported for MCL patients treated with the combination of cirmtuzumab and ibrutinib and with the complete remission achieved with TK216 treatment of a young man with Ewing sarcoma.

Preclinical work is also identifying additional clinical targets for our existing product candidates and for our ROR1-targeted CAR-T program.So, let me turn this over to our Chief Medical Officer, Dr. Frank Hsu, who will provide more detail on these clinical results and our other programs..

Thanks, Jim.I'll spend the next few minutes updating progress on our clinical programs and taking you through a more in-depth look at our diverse product candidates.

Our most advanced clinical program evolves cirmtuzumab, which is a monoclonal antibody designed to inhibit R-O-R1 or also known as ROR1, which is also known as the receptor tyrosine kinase-like Orphan Receptor 1.

This agent is currently under investigation in the Phase 1/2 clinical trial in combination with ibrutinib for patients with CLL or MCL.As Jim mentioned, we have some new data in mantle cell lymphoma that we'd like to highlight. As you're probably aware, ibrutinib nerve has become the standard-of-care for patients with these diseases.

Although effective published data indicate that the ability of single agent of ibrutinib to induce complete remissions and relapsed/refractory MCL is limited, and patients previously treated with 2 or more prior regimens have had complete response rates of only about 23%.Thus, there is substantial room for improvement for patients.

We believe that an agent that complements ibrutinib to increase the number of patients achieving a CR with little or no added toxicity, may be -- may provide meaningful clinical benefit.Since we presented interim results at the ASH meeting, annual meeting in December 2019, this complete response rate for cirmtuzumab-ibrutinib combination for patients with MCL has increased from 25% to 50% and now includes six of 12 evaluable patients with relapsed refractory MCL enrolled in the dose escalation portion of the study.All six CRs are ongoing as of the data cutoff of March 6, 2020, including one patient who has remained in CR for over 21 months on study.

For the six patients achieved CRs within four months while on steady, these responses are based on standard Cheson criteria for evaluating responses in lymphoma and one of the six was a complete metabolic response by PET scan with a bone marrow biopsy pending.As of the same data cutoff, the overall objective response rate for patients with MCL in the study has increased from 63% to 83% with 10 to 12 patients achieving a CR or partial response with a median follow-up of 6.4 months.

It's particularly interesting to note that many of these patients have been heavily pretreated.Overall, enrolled patients had a median of two prior therapies before participating, including chemotherapy; autologous stem cell transplant; autologous stem cell transplant followed by a CAR-T therapy; and autologous stem cell transplant, which was later followed by allogeneic Stem cell transplant, and patients who had received a ibrutinib with rituximab followed by hyper‐CVAD consolidation chemotherapy.The overall clinical benefit that is the complete response rate, the PR rate and/or stable disease rate, stands at 100% as of the data of cutoff.

And this includes six CRs, four patients with PRs and two patients who had stable disease. We believe that these are very encouraging early results that may indicate activity of cirmtuzumab in MCL.

We're now enrolling additional patients with MCL into an expansion cohort where we are further examining the safety and efficacy of the recommended dose regimen of cirmtuzumab plus ibrutinib.At the ASH meeting in December 2019, we also presented interim clinical data for our patients with CLL from this Phase 1/2 clinical trial.

Most encouraging was that no patient had experienced disease progression while on study at a median follow-up of 9.9 months as of the data cutoff, which was early November 2019.

29 of the 34 patients achieved a complete or partial response, and the partial response included those patients with lymphocytosis, for an objective response rate of 85% for this group. One patient achieved a complete response and remained in remission for at least six months after completion of the trial and discontinuation of all anti-CLL therapy.

Every patient experienced a reduction in measurable disease, and the total clinical benefit rate was 100%.

Patients with CLL are now enrolling in a randomized portion of the study, comparing ibrutinib plus cirmtuzumab to ibrutinib alone.In both, MCL and CLL, the combination of cirmtuzumab and ibrutinib has continued to be well tolerated in the study with adverse events consistent with those reported for ibrutinib alone.

There have been no dose-limiting toxicities, no discontinuations and no serious adverse events attributed to cirmtuzumab alone.

Interestingly, neutropenia, which is a clinically relevant side effect of ibrutinib was only reported on 13% of patients with CLL or MCL receiving ibrutinib plus cirmtuzumab study in the study, when it's been reported at higher rates for ibrutinib alone in studies described in the ibrutinib describing information.As Jim mentioned earlier, cirmtuzumab has also been examined in the Phase 1 investigator-sponsored trial in combination with paclitaxel for the treatment of patients with HER2-negative, metastatic or locally advanced unresectable breast cancer.

Early data from the study was present at the San Antonio Breast Cancer Symposium in December of 2019. Of the seven evaluable patients, four achieved a partial response for an objective response rate of 57%, including one partial response that continued on cirmtuzumab alone for at least 30-weeks after discontinuing paclitaxel.

This is the higher rate of response and would be expected for this regimen of weekly paclitaxel, based on the published literature. The combination of cirmtuzumab and paclitaxel has been well tolerated in this trial, with no study discontinuation for toxicities, and no dose limiting toxicities observed. Enrollment into the study is ongoing.

We look forward to building on this momentum in 2020 and hope to present additional clinical data for cirmtuzumab at scientific venues late this year.Next, I'd like to discuss our clinical program with the novel small molecule TK216.

This agent was designed to inhibit the biologic activity of ETS or E26 transformation-specific family transcription factor oncoproteins, in a variety of tumor types.

Our lead indication for this compound is relapsed/refractory Ewing sarcoma, which is a rare pediatric bone cancer with a critical unmet medical need, and no standard second line systemic therapy.Ewing sarcoma qualifies as an orphan indication. And orphan designation and fast track status from the FDA has been received for this program.

At the Connective Tissue Oncology Society or CTOS meeting in November of 2019, one of our investigators presented interim Phase 1 data on the TK216 for the treatment of patients with relapsed/refractory Ewing sarcoma.In this Phase 1 study, TK216 was examined extensively at dose levels and for different lengths of time for safety and for pharmacokinetic parameters.

Based on these data, a recommended dose regimen was chosen. And in December of 2019, we announced the opening of a patient expansion arm using this dose and schedule.

We have seen clinical responses, a deep and sustained clinical response was reported for patient who received TK216 dose regimen that was subsequently selected as the recommended Phase 2 dose.

Following two cycles of TK216 therapy given as a single agent, this heavily pre-treated young patient achieved the confirmed objective response, which included resolution of several pulmonary lesions. The response has continued at more than 10 months of treatment with the patient receiving TK216 plus vincristine in subsequent treatment courses.

The final remaining tumor nodule, which was less than a centimeter in diameter, was later surgically removed, leading to a surgical complete remission. Treatment with TK216 has been well-tolerated by this patient.The expansion arm is anticipated to enroll approximately 18 patients with the relapsed/refractory Ewing sarcoma.

We look forward to exploring the broad potential of this novel targeted therapy and hope to provide additional updates in the second half of 2020.Our third program is a ROR1-targeted CAR-T therapy, which is in preclinical development in collaboration with the University of California, San Diego.

ROR1 is present on many different neoplasms, including both, hematologic and solid malignancies, and provides an opportunity to target new cancer indications.

The ROR1 targeting component of the CAR-T uses the fragment of our cirmtuzumab antibody, that's designed to bind to cancer cells with high affinity but not to recognize normal human tissues.In February 2020, we presented ROR1 CAR-T preclinical data at the ASCO-SITC Clinical Immunology (sic) [Immuno-Oncology] Symposium.

ROR1 CAR-T therapy -- cell therapy demonstrated expansion, persistence and antitumor activity in an animal model of human leukemia.

In these preclinical studies, anti-ROR1 CAR-T were able to prolong survival and clear leukemia cells from major tissue reservoirs including bone marrow, kidneys and spleen.This research is being conducted by our UC, San Diego collaborators under a grant from the California Institute of Regenerative Medicine or CIRM.

We are pleased with the preclinical results of this ROR1 CAR-T program and look forward to advancing it into the clinic.I'd like to turn it now back over to our CEO, Jim Breitmeyer for further discussion..

Thank you, Frank, for that summary of our clinical and preclinical programs.

I'd now like to highlight the upcoming milestones that we expect to reach over the next several months.We expect to present additional clinical data for patients with MCL treated with cirmtuzumab plus ibrutinib, including 15 patients in the dose finding and expansion cohorts of the Phase 1/2 study in mid-2020.

We also expect to present additional clinical data for patients with CLL treated with cirmtuzumab plus ibrutinib, including at least 12 months of follow-up four 34 patients in the dose finding and expansion cohorts of the Phase 1/2 study, also in mid-2020.We expect additional clinical data to be available from the Phase 1b investigator-sponsored study of cirmtuzumab plus paclitaxel in patients with HER2 negative breast cancer in the second half of 2020.

We expect to present clinical data for patients with Ewing Sarcoma, including 7 to 12 patients treated with TK216 plus vincristine in the expansion cohort of the study in the second half of 2020. We expect to treat the first patient with our ROR1-targeted TK216 by the end of 2020 in the collaboration with Shanghai Pharma Ltd.

We expect to generate IND-enabling preclinical data for additional ETS-driven cancers and in ROR1-driven cancers, such as lung cancer.I'll now turn it over to Rich Vincent, our Chief Financial Officer, to review our financial results..

Thank you, Jim.In October 2017, CIRM awarded an $18.3 million grant to the researchers at the University of California San Diego School of Medicine to advance our Phase 1/2 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 approximately $14 million in development milestones under research sub-awards throughout the award period.

In conjunction with this award, our 2019 grant revenue was $0.7 million for the fourth quarter and $2.4 million for the full year.Total 2019 operating expenses were $4.9 million for the fourth quarter and $35.5 million for the full year.

The full-year total includes a one-time non-cash charge required in process of research and development expenses of $18.1 million that was recorded in connection with the closing of our merger in June 2019.Research and development costs for the fourth quarter totaled $2.6 million, and for the full year totaled $10.2 million.

General and administrative expenses for the fourth quarter totaled $2.3 million, and for the full year totaled $7.3 million. Net loss for the fourth quarter was $4.2 million or a loss of $0.27 per share basic and diluted.

Net loss for the full year 2019 was $34.2 million or a loss of $3.31 per share basic and diluted.As of December 31, 2019, we had $20.1 million in cash and cash equivalents.

We believe these funds will be sufficient to progress our product candidates and fund our operations into the third quarter of 2020.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 indications.

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] Our first question comes from the line of Hartaj Singh with Oppenheimer. Please proceed with your question..

Great. Thank you, everyone.

Can you hear me fine?.

Yes, perfectly, Hartaj..

Great. Thank you. So just a couple of questions. Great data on MCL, and CLL seems to continue to progress. One question I wanted to ask you was, it seems that at time goes by, you're seeing an increase in response rate, the complete response rate, the overall response rates from when we met at ASH and presented the data there to now four months later.

Is there something specific to the mechanism of action of cirmtuzumab with ibrutini and you're seeing that? Because I don't think ibrutinib has a similar effect, right? And you get a good effect from ibrutinib upfront, but doesn't seem to increase over time. Just correct me if I'm wrong there..

Hartaj, this is Jim. Thank you for the question. There is -- in CLL, for example, there's some continued accumulation of complete responses in CLL patients after a year of therapy. But the mantle cell patients usually either get a response fairly early or they don't.

So, we are also very encouraged by the fact that the clinical results strengthen over time, every time we do an interim analysis. Let me let Frank Hsu speculate about the mechanism that might be in play here..

I think one aspect which does need to be clarified is that at ASH, we presented the valuable data from eight of our patients; four of them haven't reached their initial evaluation time point. So, some -- and at least two of the complete revisions that we reported, now the two additional ones, those are fairly recent patients.

So, that data just came in. The other two have been PRs, which converted. And with those patients, they just continued to shrink and shrink and shrink. It took little longer to get there. And when they did, we reported them of course immediately.

And so, it's one of the things, which in some cases, for whatever reason, they had a disease which just took a little bit longer to resolve. But the first -- the other two were part of the four patients which we did not initially report on at ASH..

And Hartaj, you'll recall that serum from patients with mantle cell and CLL do demonstrate elevated levels of Wnt5a for ROR1. So, there is a -- we expect that the ability of cirmtuzumab to block Wnt5a signaling will continue over time..

Got it. No, that’s great. Another question I just had was I know that previously when we had spoken, the combination seems to actually sort of down regulate some of the more, obtrusive side effects of ibrutinib. I know the patient numbers are still small, but you are getting a combination for longer and longer periods of time.

Are you still seeing that or is that trying to ameliorate a little bit, meaning the some of the hypertension -- some of the other issues ibrutinib, I think seem to be downplayed a little bit with the combination?.

Sure. So, we've -- we're trying to be careful about discussing this aspect of the program because reporting of side effects can be rather qualitative and may differ from one study to another.

And so, for that reason, we decided that the neutropenia that is a well-described and important side effect with ibrutinib, given alone, was something that is perhaps less subject to reporting bias, since the patients get a complete blood count every month while they're on the study.

And so, when we saw a 13% overall rate of neutropenia on the study, which Frank and his team have verified with a deep dive into the adverse event data just recently. So, this is a fresh number. That does compare favorably to substantial higher rates of neutropenia reported for ibrutnib, for example in Imbruvica package insert.

So, some of these other side effects can be subjective. And so, we're going to be taking a hard look at adverse events, between the two arms in the randomized portion of the study, which is now enrolling patients. And we'll have in our own study patients with ibrutinib alone and patients with ibrutinib plus cirmtuzumab..

Great. Thank you, Jim. So, another question I just wanted to ask was on the CLL. I know, you're going to have the 12-month follow-up on 34 patients, mid-2020.

Are we going to see a kind of, also look at sort of various I guess breakdowns of CLL by mutation status or anything like that by these 34 patients? Are you going to be doing a deeper dive into the types of patients? And the only reason I ask is, is there a probability that there's some patients in CLL you could see faster track to approval for example in certain subsets versus others?.

Frank, would you like to address that question?.

Sure. We are looking at that. We have already discussed a report that we have looked at various risk factors associated with CLLs that include the IG, verbal heavy chain reaching mutated and unmutated status, and then some other gene rearrangements such the p53 and del 13.

And when you look at all those factors, a significant portion of our CLL patients do fit into a higher-risk category. So, this is something which we hope to share in more detail at our future meetings where we hope to have -- be able to present all our data at once..

Great. Thank you, Frank. And then, last question -- and thank you for letting me have all these questions.

Just last one is, Jim and everyone, I mean, if you were to handicap sort of mantle cell lymphoma versus CLL, even TK216, the data that you're accruing and then I assume you’re going to be having the regulatory interaction, which you are already having them going forward.

Is there any one of these that you think is more amenable to an accelerated approval or breakthrough therapy designation than the other? I know that those are very difficult. I think, statistics are like 1 in 12 or something -- or 12% actually get them.

Just any thoughts there of MCL versus CLL versus TK216 in terms of any potential for accelerated approval of BTD?.

Sure. Hartaj, I'll respond. We believe that Ewing sarcoma is an indication that is a particularly likely to enjoy expedited registration treatment from the FDA. And there's a great example for that in the recent approval of a drug from Epizyme.

Tazemetostat, their experimental agent was approved for the treatment of epithelioid sarcoma on the basis of a single study with a single arm open label treatment with 62 patients and objective response rate of 15% and 1 complete response out of 62.

And so, the desperate condition in Ewing sarcoma after failure or frontline therapy is similar to epithelioid sarcoma’s high unmet medical need.

And this devastating pediatric cancer is particularly likely we believe to be treated in an expedited fashion by FDA.Between mantle cell lymphoma and CLL, we believe that MCL is more likely to be approvable with an expedited approval based on recent regulatory history.

And several agents have been approved for the treatment of mantle cell by accelerated approval. And so, we do believe that that is a potential pathway that appears -- to our to our view, appears a little bit more likely than a small single arm study for accelerated approval would be for patients with CLL..

Our next question comes from the line of Matt Kaplan with Ladenburg. Please proceed with your question..

I apologize. I was disconnected for a minute, so if my question was asked already.

So, I just want to dig in a little bit more to the MCL data and thinking about the randomized cohort now that you have open? And what we should be looking for there, given the strong results that you've seen so far in terms of the ICR rate? What should be -- what are you looking from the combination versus improvement alone?.

Frank, go ahead..

Just to clarify, your question -- you're talking about MCL, correct? Not CLL?.

Yes..

Okay. So, the randomized portion of study is only for CLL. And so, currently, the MCL patients are in an expansion cohort where we're just adding more patients at the recommended dose regimen.

And so, that's expanding our experience and getting more data at that dose regimen level?.

Okay.

So, no intention to do a randomized cohort there yet?.

Not at this moment..

And just help us understand the regulatory path forward in MCL.

What you're thinking at this point?.

We’re looking at all options right now. And I think that our plan is to have discussions with FDA, which will help direct our ability to make a registration strategy. But, at this point, I don't think I can comment exactly what our successful plan might be..

Thank you. Our next question comes from the line of Carl Byrnes with Northland Securities. Please proceed with your question..

Great. Thanks for the question. Congratulations on the compelling MCL interim data.

Of the six complete responses that you mentioned, obviously, they were heavily pre-treated, do you believe that the 50% CR that you’re seeing in this heavily pre-treated population would potentially support frontline therapy, considering the existing frontline therapy is 24% or so? Thanks..

That's a question which we don't have the data in the treatment naïve group or moving it up forward as of yet. So, it is speculative to. But, data from other drugs would suggest that of course, as you move it up, you're much more sensitive to the treatment effects and your rate of response does go up.

So, speculating, it would be our hope that one could do that.

But I think that we are doing quite successfully right now in a difficult-to-treat and unmet need population where patients who have received two or more prior therapies have a much lower response rate and yet we are fortunately seeing initially in early responses a good response, and we are hopeful that that will continue when we do additional expansion on our patients..

Thank you. It appears we have no additional questions at this time. So, I'd like to turn the floor back over to management for any additional concluding comments..

So, operator, thank you very much. And callers, thank you very much for listening in on Oncternal’s fourth quarter 2019 earnings call. We appreciate your interest. We appreciate the caller's questions and look forward to updating you a quarter from now. Thank you and goodbye..

Ladies and gentlemen, this does conclude today's teleconference. We thank you for your participation and you may disconnect your lines at this time..