Cogent Biosciences, Inc. (COGT) 2018 Q3 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Unum Therapeutics Third Quarter 2018 Earnings Conference Call. (Operator Instructions) As a reminder, this conference call may be recorded for replay purposes. It is now my pleasure to hand the conference over to Ms. Stephanie Ascher. Ma'am, you may begin.

Good afternoon, and welcome to the Unum Therapeutics Quarterly Investor Conference Call. Today, we'll be sharing updates on our company's progress and our financial results for the third quarter of 2018 ended September 30, 2018. With me on our call today are Chuck Wilson, CEO; Michael Vasconcelles, CMO; Seth Ettenberg, CSO; and Christiana Stamoulis, President and CFO. Following our prepared remarks, we'll open the line for questions.

Before we begin our prepared remarks, I need to remind you that estimates and other forward-looking statements included in this call represent the company's view as of today, November 12, 2018. Unum Therapeutics disclaims any obligation to update these statements to reflect future events or circumstances. Please refer to today's press release as well as Unum's filings with the SEC for information concerning risk factors that could cause actual results to differ materially from those expressed or implied by such statements. Please also note that this call is being simultaneously webcast online. With that, let me introduce Chuck Wilson, CEO. Chuck?

Thank you, Stephanie. We've made a lot of progress since our August update and today, we'll be covering a number of topics, including updates across our clinical stage programs and preclinical activities. Mike Vasconcelles, our CMO, will provide you with an update on our ACTR programs in lymphoma, myeloma and solid tumors; Seth Ettenberg, our CSO, will tell you about our recent research efforts to expand our technology platform in cellular therapy, with a particular focus on targeting solid tumors. As he will discuss, we believe we've made important discoveries and ways to substantially improve T-cell functionality. These discoveries can be applied to a number of different types of T-cell therapies, which Seth will describe in more detail. And Christiana Stamoulis, our President and CFO, will then conclude with a summary of our financial performance and other important business updates.

First, we are excited to announce today that we have selected ACTR707 in combination with rituximab as our lead candidate for further development in lymphoma. This decision was based on the encouraging data to date from the combination, the continuing progress in the ATTCK-20-03 study and our desire to efficiently manage resources. Though the data are preliminary, we're encouraged by what we've seen thus far in ATTCK-20-03 and believe that the combination of ACTR707 with rituximab has a potentially best-in-class profile relative to the CD19 directed CAR-T therapy. As a reminder, we initiated the ATTCK-20-03 study at the end of 2017 with the aim of assessing the safety and [anti-tumor] activity of ACTR707 as a CD28 containing ACTR construct in combination with rituximab.

In September of this year, we reported initial data from the study, focused on the first dose cohort. In the first dose cohort of ATTCK-20-03, 3 of 6 treated patients achieved a complete response. At the same time, we observed no non-hematologic serious adverse events, including no cytokine release syndrome and no neurologic events. Enrollment in ACTR707 dosing are completed in the second dose cohort of the study and are ongoing in the third dose cohort. As we announced earlier this month, we will be reporting updated data from the ATTCK-20-03 study at the American Society of Hematology, or ASH, meeting in December. We look forward to showing data for this trial as it continues mature. Operationally, this decision to focus our lymphoma efforts on ATTCK-20-03 and ACTR707 will allow us to streamline our efforts in anticipation of the potential initiation of pivotal studies while conserving overall spend on the program. I'll now turn over to Mike to discuss more updates from our ongoing clinical pipeline.

Thanks, Chuck. We're really very excited about the potential of our product candidates as well as the productivity of the ACTR platform that's led to our pipeline depth. With this progress, we look forward to developing additional product candidates that combine ACTR T-cells with antibodies targeting different tumor types as we expand our portfolio in the future. As Chuck has already discussed, we intend to focus our efforts in non-Hodgkin lymphoma on ACTR707 in combination with rituximab. We are currently completing enrollment of dose Level 3 in the ATTCK-20-03 study and expect to initiate cohort expansion in the first half of 2019 at the recommended Phase II dose for ACTR707. In parallel, we intend to conclude enrollment in the ATTCK-20-2 study. Though the initial rate of enrollment into the cohort expansion phase of the ATTCK-20-2 study was lower than anticipated, it's been accelerating of late such that we expect to conclude the study with clinical data that furthers our understanding of the factors that define appropriate ACTR dosing. We look forward to continuing to work with all of our outstanding clinical investigators who have supported our lymphoma program as we complete ATTCK-20-2 as described above, expand ATTCK-20-03 and plan for potential pivotal clinical trials in patients with non-Hodgkin lymphoma.

For our multiple myeloma program, we are continuing the dose escalation phase of our ATTCK-17-01 clinical trial, where we are testing ACTR087 in combination with SEA-BCMA, a proprietary antibody developed with our collaboration partner, Seattle Genetics. As announced earlier this month, we will be presenting data from initial patient cohorts at the 2018 ASH meeting in December in San Diego. Under ASH embargo rules, we can't discuss the data that will be presented at the conference beyond what's been communicated in the abstract. However, let me briefly remind you of the study design to help you better understand the preliminary data we expect to present there. The ATTCK-17-01 clinical trial is an open-label multicenter Phase I dose escalation study using adaptive design principles to assess the safety, tolerability and anti-myeloma activity of ACTR087 in combination with SEA-BCMA in patients with relapse or refractory multiple myeloma. This is the first in-human experience with SEA-BCMA. Therefore, defining safety of the antibody requires starting dose escalation with very low dose levels of the antibody. We have completed enrollment and treated all patients in the first 3 dose cohorts, and we expect to report preliminary data from these early dose cohorts at the ASH meeting, focusing primarily on safety and early biomarker data from the combination.

We're excited about this combination in patients with multiple myeloma based upon a number of differentiating characteristics. First, combining ACTR087 with a novel antibody brings together anti-myeloma mechanisms of action that is unique with this combination. Second, by initiating dosing of the antibody right after leukapheresis, we have the potential to exert anti-myeloma effect early in the treatment regimen. Finally, through dose adjustments of both the antibody and ACTR087, we can establish dosing of both agents that we hope will optimize the therapeutic index of the combination. So as you can see, real potential exists to develop a meaningful combination for patients with relapsed or refractory myeloma.

Moving on to our newest clinical program, we are on track to initiate the multicenter ATTCK-34-01 Phase I trial utilizing ACTR707 in combination with trastuzumab to target HER2+ advanced cancers by year-end. This is our first ACTR T-cell and antibody combination directed toward solid tumors, a clinical study that has historically been challenging for T-cell therapies. As we've outlined in the past, our preclinical studies highlight a number of ways in which we think ACTR T-cells are likely to be superior to CAR T-cells in solid tumors, and we're excited to be on the cusp of clinically testing these ideas.

With respect to HER2+ overexpressing cancer specifically, one particular challenge is the requirement to discriminate between tumor cells expressing high amounts of HER2 protein on their cell surface from normal noncancerous cells that express much lower amounts. As we presented at the 2017 AACR-NCI-EORTC triple meeting, preclinical data demonstrates that, unlike certain CAR T-cells that target HER2, ACTR T-cells are highly selective for cancer cells over noncancerous cells, efficiently killing HER2 overexpressing tumor cells while sparing a broad panel of noncancerous cells. Earlier this year, the FDA cleared our IND submission containing these and other preclinical data with this combination, and we are now in the process of initiating the clinical trial for patients with advanced cancer overexpressing HER2. We expect to open the first clinical site in this trial by the end of this year, with initial data to follow in 2019. We will be presenting preclinical data describing the ACTR combination as well as more details of the trial design at the San Antonio Breast Cancer Symposium in December in San Antonio.

In addition, we will be hosting an investor event in New York next week, on November 19, where we will be further discussing these data and other research activity targeted toward optimizing T-cell therapies in solid tumors. We're pleased to have 1 of our academic investigators, Dr. Charles Fuchs, Director of the Yale Cancer Center, join us for that breakfast to share his perspective on the need for novel cell therapies for his patients with gastrointestinal cancers. So with that, now let me turn the call over to Seth, who will describe some recent preclinical advances coming from our research team.

Thanks, Mike. Beyond our ACTR platform-related activities, we've been exploring ways that we can broadly improve the fitness and functionality of engineered T-cell therapies, enabling them to be more effective in solid tumors. A key hallmark of solid tumors is that they create an environment that actively blocks T-cell attack through the presence of certain cell types, protein factors and molecules that have an immunosuppressive activity. In addition, solid tumors often consume the nutrients required for T-cell metabolism and may lack some of the cellular signals that enable T-cells to activate properly when they encounter a tumor cell. At the Society of Immunotherapy of Cancer annual meeting, SITC, this past weekend, our research team presented our approach to address these challenges. We call this approach Bolt-On Chimeric Receptor, or BOXR for short. BOXR T-cells express a chimeric receptor, like an ACTR or a CAR, that targets a T-cell to tumor cells. At same time, an additional transgene, including a separate protein product, is effectively bolted on to the same T-cell in order to improve its fitness or functionality. We selected and synthesized dozens of bolt-on transgenes based on their potential to overcome the challenges in solid tumors I summarized earlier. As presented at SITC, we have used a battery of functional assays to simulate the adverse conditions present in the solid tumor microenvironment, allowing us to evaluate the impact of bolt-on transgenes on T-cell functions and to select the best ones for potential further development. Through these studies, we've identified specific bolt-ons that work with either ACTR T-cells or CAR T-cells or both, to significantly improve their functionality. As an example, we have shown that bolt-on transgenes that alter pathways involved in cellular metabolism can convert a standard second-generation CAR T-cell directed towards liver and lung tumor cells into a highly potent and effective agent, eliminating tumors in our most stringent nonclinical animal models. In separate experiments, using a different transgene that provides co-stimulatory signals to counter chronic T-cell stimulation, we're able to significantly enhance ACTR attack of ovarian cancer cells. We see the BOXR technology as an important complement to the ACTR technology, extending upon and approving the foundation for Unum's T-cell platform. We are actively seeking patent protection for BOXR and have completed filings for several patent applications covering different aspects of the technology. We envision a growing pipeline in the future composed of both ACTR and BOXR T-cell programs. We plan to disclose more details on this new platform, along with our broader efforts in solid tumors at our investor event next Monday. With that, let me hand the call over to Christiana, who will discuss our financials.

Thank you, Seth. I will turn now to our financial results for the third quarter. In the third quarter of 2018, we recorded collaboration revenue of $2 million compared to $2.3 million in the same quarter last year. This decrease was due to the adoption on January 1, 2018 of the new revenue recognition standard which changed the manner in which we recognize revenue from our collaboration agreement with Seattle Genetics.

R&D expenses were $10.3 million in the third quarter of 2018 compared to $8.2 million in the same quarter last year, primarily reflecting the expanded clinical development activity this year. G&A expenses were $2.4 million in the third quarter of 2018 compared to $1.3 million in the same quarter last year, with the increase primarily due to expenses around operating as a public company as well as higher personnel-related costs.

Net loss for the third quarter of 2018 was $10.2 million compared to $7 million for the same quarter last year, with the increase largely reflecting the increased operating costs in the 2018 period. Finally, we ended the third quarter of 2018 with approximately 30 million shares outstanding.

As of September 30, 2018, we had cash, cash equivalents and marketable securities of $87.1 million. As a result of our decision to conclude enrollment in the ATTCK-20-2 study in the first half of 2019, we anticipate that this capital is sufficient to fund our operations and capital expenditure requirements through at least the end of June 2020 without considering available borrowings under our loan and security agreement.

Looking forward, we expect a very active remainder of 2018. At the ASH meeting in December, we plan to provide updated data from the ATTCK-20-03 trial and also report preliminary data from early cohorts of the ATTCK-17-01 trial. At the upcoming investor event on November 19, we plan to disclose more details on our BOXR technology as well as our broader efforts in solid tumors. This event will be available also via live webcast. We are also on track to initiate by end of the year the Phase I study ATTCK-34-01 testing ACTR707 in combination with trastuzumab in HER2+ factors. We expect to share updated preclinical data of these product candidates as well as more details of the trial design at the San Antonio Breast Cancer Symposium.

With that, we'll open the call for questions.

(Operator Instructions) And our first question will come from the line of Marc Frahm with Cowen and Company.

Maybe just for -- to start with [again,] Mike. When making the decision of moving with ACTR707 in lymphoma, can you just talk about kind of what drove that decision? Was it the safety? Was it the efficacy? Is it just the amount of expansion you're seeing? What really drove that?

Hi, Mark. Yes, I think it was really several factors. It's not just the data that we've seen in the first dose level of the 20-03 study, but it's really building on the momentum we've seen in that study and then really, an interest to continue to just judiciously manage our resources as we move forward in lymphoma and bring other programs online. And so I think it's really the totality of the issues that led us to decide at this point in time, to really focus on the ACTR707 with rituximab in non-Hodgkin lymphoma.

Okay. And then maybe I missed it when you ran through the ASH presentations. Might we see anything from dose Level 3 at ASH? Or is it just going to be the dose Level 2 patients that will get added to what we've seen already?

[No], so I think it will primarily be follow-up from dose Level 1. We'll have some early data from dose Level 2 and then we'll be able to expect to give a status on dose Level 3, but more operationally for the third dose level.

Okay, great. And then last one. Just as you're thinking about starting up with the HER2, when kind of think -- obviously, it can be upregulating a variety of different tumor types. Are there particular tumor types that you think are more or less amenable to T-cell therapy, kind of -- what do you think, maybe colorectal versus breast cancer and things like that?

Yes, I think with our approach, we don't want to be necessarily too presumptuous for any specific histology. I think just given where we know trastuzumab has demonstrated some benefit, we're expecting that the predominant number of patients will be those with either breast cancer or gastric cancer. But we purposely have designed the study to really allow or bring in any other patients that overexpressed HER2. And as you know, there's a pretty large number of cancers that -- a small overall percentage that do overexpress HER2, so we look forward to potentially having some of those patients enroll as well.

(Operator Instructions) And our next question will come from the line of Peter Lawson with SunTrust.

Just to clarify. On the selection of 707 over 087, is that across the entire pipeline? Or is that just focused around NHL?

Yes, no, just to be clear -- this is Mike. Just to be clear, this is a lymphoma-specific decision. We continue with all of our other programs as we've defined specifically, our program in collaboration with Seattle Genetics, utilizing SEA-BCMA as bringing forward the ACTR087 drug product.

Got you. And then would we see the comparison of that data at some point, 707 versus 087?

Yes. Well, we're obviously committed to bringing forward the data from both studies as they -- as those data mature. We will see some updated data with the 20-03 study with 707 next month, as we talked about. And then into '19, as we wrap up the 20-2 study, those data will be presented, and then as we build on the momentum we've seen in 20-03 through completion of dose escalation and then the expansion. So the data will all be available as we march into 2019, but not in a direct comparative sense. Those studies really aren't designed for that. But certainly, the data will be made available.

Okay. And then you mentioned at ASH, we'd see the follow-up on dose Level 1, maybe dose level 2. When do we see, you think, dose level 3?

When, did you say?

Yes.

Yes, so we expect dose data in 2019 and I think probably early next year, we'll be sort of laying out when we see data forthcoming across the whole portfolio in terms of [specificity] and timing, yes.

And I'm showing no further questions in the queue at this time. So now, it is my pleasure to hand the conference back over to Mr. Chuck Wilson, President and Chief Executive Officer, for some closing comments or remarks.

Great. Thank you very much, and thanks, everyone, for joining us this afternoon for our quarterly investor call. As you can see, we believe Unum has a differentiated approach with best-in-class potential to address a wide range of cancers. We look forward to continuing to provide updates over the coming weeks. As we've mentioned, next Monday, the 19th, we'll be hosting an investor event focused on Unum's efforts in solid tumors in New York, featuring guest speaker, Charles Fuchs, Director of the Yale Cancer Center. We'll be discussing the challenges and opportunities with HER2 malignancies, including gastric cancer, as well as discussing the market opportunity, clinical validation of ACTR707 and trial design of the Phase I study. In addition, we plan to provide more details on the new BOXR platform to support our growing efforts in solid tumors. We hope many of you can join us.

Thank you again.

Ladies and gentlemen, thank you for your participation on today's conference. This does conclude our program, and we may all disconnect.

Everybody, have a wonderful day.