Oncternal Therapeutics Inc (ONCT) 2021 Q1 法說會逐字稿

Good day, ladies and gentlemen, and welcome to your Oncternal Therapeutics, Inc. First Quarter 2021 Financial Results Call. (Operator Instructions)

At this time, it is my pleasure to turn the floor over to your host, Richard Vincent. Sir, the floor is yours.

Thank you, Melinda. 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 a 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. 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, 2021. This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, May 6, 2021. 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 hand the call over to our CEO, Dr. 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 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 cirmtuzumab, our investigational, potentially first-in-class humanized monoclonal antibody that binds with high affinity to a biologically important epitope 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 antiproliferative effect of commonly used chemotherapies in preclinical studies of ovarian cancer, including platinum-resistant cells in another presentation at AACR. Our clinical trial of cirmtuzumab plus ibrutinib with patient -- 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 (sic) [of] Clinical Oncology or ASCO 2021 Annual Meeting. Edwina will provide additional details on each of these.

ROR1 has become an increasingly visible target in the oncology space recently, and we believe we have one of the most advanced and diverse pipelines targeting ROR1. One reason for this attention was 2 major acquisitions in late 2020: the Boehringer Ingelheim acquisition of NBE-Therapeutics and its NBE-002 ROR1 targeting antibody drug conjugate, or ADC; and the Merck & Company acquisition of Bios Inc. (sic) [VelosBio Inc.] and VLS-101, its ROR1 targeting ADC. VLS-101 utilizes cirmtuzumab to target ROR1 and was invented and had its initial development at Oncternal until we spun out VelosBio.

Separately, we are continuing to support 2 investigator-sponsored clinical studies at UC San Diego: first, a Phase Ib clinical trial of cirmtuzumab in combination with paclitaxel for the treatment of women with HER2-negative metastatic or locally advanced unresectable breast cancer; and second, a Phase II clinical trial of cirmtuzumab in combination with venetoclax, a Bcl-2 inhibitor, in patients with relapsed/refractory CLL. We also continue to make solid progress on Oncternal's investigational ROR1 targeting CAR-T cell therapy program.

In January, we announced a research and development collaboration with the Karolinska Institute in Stockholm, Sweden to advance novel ROR1 targeting CAR-T and CAR-NK cell therapies from the laboratory into the clinic. In addition, we announced an agreement with Lentigen Technology to manufacture clinical-grade lentiviral vectors to support and accelerate Oncternal's investigational ROR1 targeting CAR-T cell therapy program. These agreements are in addition to our existing collaboration with UC San Diego under a grant from the California Institute of (sic) [for] Regenerative Medicine and a partnership with Shanghai Pharma.

We are tremendously excited by the potential of cell therapies targeting ROR1, which may allow the selective targeting of tumor cells that express ROR1, while relatively sparing healthy tissues. We also advanced the development of TK216, our investigational targeted small molecule inhibitor of the E26 transformation-specific or ETS family of oncoproteins. We were pleased to learn that our updated clinical data from the study was accepted for an oral presentation at the ASCO 2021 meeting.

With that, I will now turn the call over to Rich Vincent, our CFO, to review our financial results.

Thank you, Jim. 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 the 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 grant revenue was $0.7 million for the first quarter ended March 31, 2021.

Our total operating expenses for the quarter ended March 31, 2021, were $6.7 million. Research and development expenses for the quarter totaled $3.9 million, and general and administrative expenses totaled $2.8 million. Net loss for the first quarter was $5.9 million for a loss of $0.12 per share, basic and diluted. As of March 31, 2021, we had $111.2 million in cash and cash equivalents. We believe these funds will be sufficient to support our operations into 2023. As of March 31, we had 49.4 million shares of common stock outstanding.

Now I will turn the call over to Dr. Edwina Baskin-Bey.

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 Ib clinical trial in combination with paclitaxel for the treatment of women with HER2-negative metastatic or locally advanced unresectable breast cancer. And at 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 6 prior therapies for metastatic disease. The trial is expected to be completed soon with one additional evaluable patient to be enrolled for a total of 15 evaluable patients.

Also at AACR this year, we presented data from a preclinical study investigating cirmtuzumab in combination with chemotherapeutic agents, cisplatin and paclitaxel, used to treat high-grade serious ovarian cancer and endometrial cell lines in vitro. Cirmtuzumab demonstrated single-agent activity and enhanced the antiproliferative effects of chemotherapeutic agents in both ovarian or 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 I/II 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. Also a clinical data from our ongoing Phase I/II trial of TK216 for patients with relapsed or refractory Ewing sarcoma was selected for an oral presentation at the ASCO Meeting, and this will be presented on June 4, 2021, at 11:30 in the morning Eastern Standard Time. We also expect further preclinical data in additional ETS driven tumors to be available in the second half of this year, 2021. We are currently targeting to treat the first patient with our ROR1 CAR-T cell therapy in the first half of 2022 next year.

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

Dr. Breitmeyer, you may have your mute button.

Thank you, Melinda, 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.

(Operator Instructions) And we'll go to Hartaj Singh with Oppenheimer for our first question.

This is Jackie Yan for Hartaj today. First, just on your ongoing hire for new Chief Medical Officer. Wondering what's the time line there and what kind of quality or experience are you looking for? Also cirmtuzumab in MCL, I know you will update at ASCO. But just based on your current discussions with your KOLs, what are some additional data or steps you need to get before going to the FDA and discussing the next step there? Then I just have some follow up.

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 as she kindly did while this search was underway. She has been a spectacular addition to the team. We do -- we're 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. Got it. That's great. Super helpful. And also thanks, Dr. Baskin-Bey, for updating the current status of that investigator-sponsored trial and very good data at AACR indeed. Just want to ask what are yourselves bringing that trial forward -- yourself? Like the type of patient you want to include in a future trial. It seems like in the current investigator-sponsored portion, that trial included both chemotherapy treated and also chemotherapy naive patient. Just any color on that aspect.

Sure. Edwina, I think I'll take this. So your question is going forward in breast cancer. And this particular study in HER2-negative patients did include patients with a median of 6 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.

I look forward to that. And then the last question is just on TK216. Can you maybe give us some good comps or examples that could inform your potential fast-to-market strategies? And then for TK216 in additional indications, I guess, from mechanistic or medical need perspectives, which sarcoma indication do you think mimic Ewing sarcoma in lung?

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.

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

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 the CIRLL study, considering that, that was expanded for MCL? And then also with respect to 216, enrollment was progressing very well there despite COVID. And I'm wondering if there's any updates that remains the case, as I imagine it would be. And with respect to a follow-up study to that, say, what might be done in terms of limiting extensively, heavily pretreated population in new Ewing sarcoma?

Edwina, those -- you can respond to Carl?

Carl, thanks for the question. I'll start with the last one first because 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've continued to do so as a part of our Phase II 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 our previous data, we have been treating heavily pretreated patients with median lines of therapy from previous presentations of 2 or 3 median lines and metastatic disease. And as we're starting to notice where we may be more advantageous, we may be able to delineate that as we move further and investigate more. But I would say to stay tuned for our ASCO presentation. Now the first question, I believe it had to do with MCL. But Carl, I think you're going to have to repeat it for me.

Oh yes, no worries. That was very helpful. Just with respect to enrollment with MCL patients. And if I recall correctly, from the initial structure of the CIRLL trial, it was expanded to include more MCL patients given the ORR, CR response?

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

Great. And again, congratulations on the progress.

Thank you, Carl.

Next, we go to the line of Rob Burns with H.C. Wainwright.

3 from me, if I may. So the first one being around the potential in solid tumors for cirmtuzumab 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 do you think you might initiate a Phase I/II trial in solid tumors, whether that could be late 2021 or early 2022? And then I'll stop there and I'll ask my questions after the response.

Yes, that's fine, Rob. And happy to have you go one question at a time. And thank you for the question. 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 you know, we've been really accelerating our CAR-T 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 6 months to get something open.

No. Absolutely. 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 it's -- 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 II to make it registrational or whether you'll have to run a separate Phase II 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 a 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.

Congrats on the quarter again.

All right.

And we take our last question from Kumar Raja with Brookline Capital Markets.

Congratulations. 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 synergies, the CapEx that was 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 finalists yet, but they're in the running. So ovarian cancer, combined with potentially Taxol or platinum is a possibility. Lung cancer, combined with osimertinib is a possibility. Breast cancer combined with paclitaxel remains 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 has been demonstrated in preclinical models. And so they are -- that makes them all interesting to us.

And with regards to ROR1 CAR-T program, how are things going on in China? Like have they opened up? What's the COVID-19 status there? And given that you are planning first of '22, what needs to be done before that can start?

Thank you, Kumar. So we're -- we've 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 CAR-T program. You may have noticed an Endpoints News article that came out earlier this year, Shanghai Pharma announced a USD 2 billion commitment to build out a 3 million square foot biotech park in Shanghai province.

And interestingly, in this Endpoints article, the programs that the spokesperson from Shanghai mentioned would be going into this biotech park were the ROR1 CAR-T 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 Lentigen collaborations, and we're 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 CAR-T program are progressing nicely.

And maybe finally, in terms of the antibody supply, can you provide an update like where we are? How much supply you have? And would that be sufficient for all the ongoing trials and planned trials?

Thank you for all of your questions, Kumar. And so antibody supply is good. We have recently produced another batch successfully with the highest, tighter 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 2 years and potentially more than that. And we're -- 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 of 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.