Good day ladies and gentlemen and welcome to Oncternal's Therapeutics Inc. First Quarter 2021 Financial Results Call. At this time it is my pleasure to turn the floor over to your host Richard Vincent. Sir the floor is yours..

Thank you, Malinda. Good afternoon, everyone, and thank you for joining us today. Joining me on the call this afternoon are our President and CEO, Dr. James Breitmeyer; and our Acting CMO, Dr. Edwina Baskin-Bey. We welcome all of you.

Today's call includes a business update and discussion of our 2021 first quarter financial results which will be followed by Q&A. Today’s press release and replay of today’s earnings call will be available on the Investor Relations section of Oncternal's website for at least the next 30 days.

We also filed our 10-Q for the first quarter 2021 earlier today. Please note that certain information discussed on the call today is covered under the Safe Harbor provisions of the Private Securities Litigation Reform Act..

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 biological pathways implicated in cancer genesis and/or progression.

We are particularly pleased with progress made during the first quarter of 2021 to advance the development of some cirmtuzumab our investigational potentially first in class humanized monoclonal antibody that binds with high affinity to a biologically important epitopes on ROR1 also known as Receptor-tyrosine kinase-like Orphan Receptor 1.

Encouraging updated interim clinical trial results with cirmtuzumab plus paclitaxel in patients with advanced HER2 negative breast cancer were presented at the American Association for Cancer Research or AACR annual meeting.

Cirmtuzumab also demonstrated single agent activity and enhanced the anti-proliferative effect of commonly used chemo therapies in preclinical studies of ovarian cancer, including platinum resistant cells in another presentation at AACR.

Our clinical trial of cirmtuzumab plus ibrutinib in patients with mantle cell lymphoma or MCL or chronic lymphocytic leukemia, or CLL continues to progress and was selected for presentation at the American Society for Clinical Oncology or ASCO 2021 annual meeting. And we will provide additional details on each of these..

Thank you, Jim. In October 2017, CERN awarded an $18.3 million grant to the researchers at the UC San Diego School of Medicine to advance ROR phase ½ clinical trial evaluating cirmtuzumab in combination with ibrutinib for the treatment of patients with B-cell lymphoid malignancies, including MCL and CLL..

Thank you Rich. I would now like to highlight data presented at the AACR 2021 annual meeting and the upcoming milestones that we expect to reach over the next several months.

So as Jim mentioned we continue to support a phase 1B clinical trial in combination with Paclitaxel for the treatment of women with HER2 negative metastatic or locally advanced unresectable breast cancer. Under AACR the UC San Diego investigators presented results showing an objective response rate of 57% with an encouraging toxicity profile.

These results were consistent with the previously reported interim results of the study and compared quite favorably to historical results for single agent Paclitaxel, in particular for patients, such as those who had received a median of six prior therapies for metastatic disease.

The trial is expected to be completed soon with one additional evaluable patients to be enrolled for a total of 15 evaluable patients.

Also at AACR this year we present the data from a preclinical study investigating cirmtuzumab in combination with chemotherapeutic agents, cisplatin and Paclitaxel used to treat high grade serous ovarian cancer and endometrial cell lines in vitro.

Cirmtuzumab demonstrated single agent activity and enhanced the anti-proliferative effect of chemotherapeutic agents in both ovarian and endometrial cancer cell models including those that were platinum resistant in ovarian cancer.

We expect further preclinical data in additional ROR1 expressing tumors to be available in the second half of this year, 2021. A clinical data update from our ongoing phase ½ trial of cirmtuzumab plus ibrutinib for patients with mantle cell lymphoma was selected to be presented at the ASCO meeting on June 7 of this year, 2021..

Dr. Jim Breitmeyer you may have your mute button..

Thank you, Melinda. Thank you and thank you Edwina. In closing, we have a strong balance sheet with multiple potential catalysts in the next year, and a clear priority of deploying our financial and operating resources to develop promising candidates in rare and common cancers. We look forward to updating you during the remainder of 2021.

Thank you for joining us today. With that I'll turn things back to Melinda for the Q&A portion of this afternoon's call..

Thank you. The floor is now open for questions. And we'll go to Hartaj Singh with Oppenheimer for our first question. Please go ahead..

Good afternoon, Jackie and for Hartaj Singh. Thanks for taking our questions.

First, just on your ongoing hire for the marine officer, was the pipeline there and what kind of quality or experience are you looking for also certain personnel in NCL? I know you will have to ask, but just based on your current discussions with your KOL what are some additional data sets you need to get before going to the FDA and discussing the kind of mess up there and this type follow up.

Thanks..

Thanks. Thank you for the questions. Jackie. We're very happy with the recruiting process for a full time CMO. Although I have to say that we could not have been luckier than to have Edwina Baskin-Bey join us as an acting CMO she kindly did, while this search was underway. She has been a spectacular addition to the team.

We do, we are getting great candidates. And we expect to be in a position to announce a full time CMO recruit with extensive oncology experience sometime in the near future. But as you know, of course, that sort of recruiting is only finished with the signing of the very last document.

So with the Jackie, your question on mantle cell lymphoma is basically when do we think we'll be ready to continue our dialogue with the FDA about a potential registration path and the answer to that question is now. We are continuing our dialogue with the FDA, about potential accelerated approval and full approval alternatives.

And if those discussions are timely, then we would hope to be able to have something to discuss with you in the second half of this year..

Got it. greatly feel very helpful. And I also said Dr. Baskin-Bey for updating the current status of that, actually sponsored trial and very good data at AACR indeed. Just want to ask what are yourself bringing that trial forward yourself? And like the type of patient you want to include in a future trial.

It seems like in the current investigator sponsored portion that's how included both chemotherapy treated and also chemotherapy naive patient, just any color on that aspect?.

Sure Edwina , I think I'll take this so. So your question is going forward in breast cancer and this particular study, in HER2 negative patients did include patients with a median of six prior treatments. And so they were extensively, heavily pretreated.

Some of them had been through multiple hormonal interventions, while others had, as you said, been treated with chemotherapy. But in any case, extensively pretreated.

And so we will be, breast cancer is one of several indications that we are taking a hard look at right now and establishing priorities based on a full assessment of market conditions, regulatory pathways, competitive landscape, science and clinical considerations.

And our plan here is to have an Analyst Day later this year where we lay out our thoughts about breast cancer and other indications in terms of priority setting and particulars around potential clinical trials..

Wonderful. We definitely look forward to that. And then last question is TK216. Can you maybe give us some comps or examples that could inform your potential fast to market strategy and then for TK216 in additional indications.

I guess from like an stage or medical need perspective which is the indication do you think mimic your Again, thanks for taking the questions..

Sure Jackie. So we think that there was an interesting analogy for a very rapid approval by the FDA in a sarcoma indication and that is TAZVERIK brought forward by Epizyme and a single arm study in epithelioid sarcoma of 62 patients was sufficient to achieve accelerated approval.

So we do view that as a potential best case analogy in a rare sarcoma with a substantial unmet medical need..

Yes. Got it..

Thank you..

Next we go to the line of Carl Byrnes with Northland Capital Markets. please go ahead..

Thank you. Congratulations on your progress. A couple of my questions have been answered. But I was just curious if you had any comments with respect to the progression of enrollment with mantle cell lymphoma patients in this study concerning that was expanded for MCL.

And then also with respect 216 enrollment was progressing very well there despite COVID and I'm wondering if there's any updates that remains the cases I imagine it would be, and with respect to study, to that study what might be done in terms of limiting extensively heavily pretreated population and Ewing sarcoma. Thanks..

Edwina those you can respond to Carl..

Hi Carl, thanks for the question. I'll start with the last one first. It's first on my mind, TK216 in terms of enrollment, we have been enrolling really quite well, thanks for realizing that to COVID. And we continued to do so as a part of our phase 2 expansion cohort. And we will have an updated number for you on that expansion in ASCO.

And as it relates to the type of patient population I believe, as you're familiar from a previous data, we have been treating heavily pretreated patients with a median lines of therapy from previous presentations of two or three medium lines and metastatic disease.

And as we're starting to notice where we may be more advantageous we may be able to delineate that to further and investigate more. But I would say just stay tuned for our ASCO presentation. Now the first question I believe it has to do with MCL Carl I think you're going to have to repeat it for me..

Yes. No worries. Thank you. That was very helpful. Just with respect to enrollment with MCL patients, if I recall correctly, from the initial structure this sort of trial, it was expanded to include more MCL patients given the ROR1 CR response. Thanks..

That is correct and we continue to do so. As you're aware, CLL is close to enrollment and we're following up those patients long term and will continue to show that data at each update. And MTC again, phase 2 expansion is enrolling really quite well. And you'll see an update in the numbers at ASCO..

Great, thanks. And again, congratulations on the progress..

Thank you, Carl. .

Thank you. .

Thank you. .

Next we go to the line of Robert Burns with H.C. Wainwright. Please go ahead..

Hi, guys, thanks for taking my questions and congrats on the quarter. Three from me, if I may. So the first one being around the potential in solid tumors pursuant to that plus a chemo agent.

So Jim, you said earlier, we're supposed to or that we will get a sort of, we'll get some color around your sort of strategy in that arena later this year at the Analyst Day. I was just curious if you could provide any color around when you think you might initiate a phase ½ trial in solid tumors whether that could be late 2021 or early 2022.

And I'll stop there. And I'll ask my questions after the response..

Yes. That's fine Rob. Happy to have you go one question at a time. And thank you for the questions.

So we are potentially interested in initiating additional clinical trials in solid tumors and at this point, with everything else that's going on and as we've been really accelerating our CART program I think that it could be late this year or early next year that we initiate additional studies.

We haven't started actively opening studies at this point. And as you know, it can easily take more than six months to get something opened..

No, absolutely. Thanks for the color. My second question. So I know we're supposed to see some incremental data at ASCO for both cirmtuzumab plus ibrutinib as well as the TK216.

Can you provide any sort of granularity into what we can expect from the increase in patient numbers there?.

So that's embargoed, of course. But I think in for both MCL and Ewing sarcoma there are I think you'll find substantial numbers of new patients that will be reported at ASCO compared to previous disclosures..

Okay, not a problem. My last question is regarding your discussions with the FDA.

I'm just sort of curious you believe that you can potentially modify the phase 2 to make a registrational or whether you'll have to run a separate phase 2 trial? And what sort of proposals have you put forth to the FDA with regard to trial design?.

Sure, Rob.

So I think that it's unlikely at this time that we would continue the existing study and a new study with registration potential is more likely for a number of reasons that I think you would agree with when we get to that point And so we have discussed single arm and randomized studies with the FDA and various control groups and so it's really, it's been really good dialogue with FDA.

We've got really helpful feedback from them. And so we're continuing to discuss study design right now. And I'd say that it's most likely that you would see a new randomized study as the most likely design..

Awesome. Thanks, guys. And congrats on the quarter again..

All right..

And we take our last question from Kumar Raja with Brookline Capital Market. Please go ahead..

Congratulations and thanks for taking my questions.

With regard to the solid cancer data, preclinical data, can you provide insight with regard to like, what indications this will be and what combinations this will be and also in terms of the synergistic effects that are seen in ovarian cancer, how do you think that will be replicated in human trials? Do you think they need to be sequenced or they can be dosed at the same time.

Just trying to get your thoughts on how that will be implemented?.

Thank you for the questions Kumar. So we are in process for this ranking exercise in solid tumors. What I can tell you, I'll tell you some examples that we're considering and these are, they're not a finalist yet but they're in the running. So ovarian cancer combined with potentially Taxol or Platinum is a possibility.

Lung cancer, combined with OC ibrutinib is a possibility. Breast cancer combined with paclitaxel remain something that we're quite interested in and so I think those are examples where ROR1 expression is high in the tumor. ROR1 activity has been demonstrated and cirmtuzumab activity is has been demonstrated in preclinical models.

And so there that makes them all interesting to us..

And with regard to ROR1 party program, how are things going on in China, like how they opened up, what’s the COVID-19 status there and you know, given that you are planning first off ‘22 what needs to be done before that can start?.

Thank you Kumar. So we really made substantial progress inside and outside China. And so our friends and colleagues at Shanghai pharma have been doing some significant preclinical work. They have a dedicated biologicals group that is responsible for the CART program.

You may have noticed an endpoint news article that came out earlier this year, Shanghai pharma announced a $2 billion U.S.

commitment to build out a 3 million square foot biotech park in Shanghai province and interestingly in this endpoint article the programs that the spokesperson from Shanghai mentioned would be going into this biotech park where the ROR1 CART and cirmtuzumab. And so there's substantial work and investment going on with Shanghai.

We're happy with their progress. We're also happy with our own internal progress including the Karolinska and Lentigine collaborations and were happy with progress made at UC San Diego and their work with construct design and thinking about they would love to be the first clinical trial site in the United States.

So really all of the different aspects of the CART program are progressing nicely..

Got. And maybe finally, in terms of antibody supply, can you provide an update, like where we are, how much supply you have and will that be sufficient for all ongoing trials and client trials? Thank you..

Thank you for all of your questions, Kumar. And so antibody supply is good.

We have recently produced another batch successfully with the highest titer and yield and the best purity that we've ever had and so with that batch, we have a very ample supply of antibody for at least two years and potentially more than that and I'll say that we're very happy with our collaboration with Wuxi Biologics, who is our antibody manufacturer.

They have been a very good strategic partner. And with that operator, I think that may be the last question..

That was the last question. So we'll turn to Dr. Breitmeyer for closing remarks..

So thank you everybody for your time and attention. Thank you for all the questioners, for interesting and insightful questions on our program. We look forward to updating you again with our second quarter results in the future and appreciate your attention to Oncternal in our mission to help patients with some of the worst cancers.

And with that, goodbye for today..

Thank you. This does conclude today's teleconference. We thank you for your participation. You may disconnect your lines at this time. Have a great day..