Cogent Biosciences, Inc. (COGT) 2019 Q1 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Unum Therapeutics First Quarter 2019 Results Conference Call. (Operator Instructions) As a reminder, this conference call is being recorded.

I would now like to turn the conference over to Stephanie Ascher. Ma'am, you may begin.

Good morning 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 first quarter ended March 31, 2019. With me on our call today are Chuck Wilson, Chief Executive Officer; Michael Vasconcelles, Chief Medical Officer; Seth Ettenberg, Chief Scientific Officer; and John Green, Vice President of Finance. Following our prepared remarks, we'll open the line for questions.

Before we begin, I need to remind you that estimates and other forward-looking statements included in this call represent the company's view as of today, May 13, 2019. 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. Chuck?

Good morning. I'm glad you're able to join us for our first quarter earnings call. Today, we'll provide a quick snapshot of where we stand as we continue to advance our pipeline of programs. Mike will give an update on our 4 ongoing clinical trials, and Seth will talk about our current research efforts to expand our technology platform with a particular focus on targeting solid tumors. We'll then conclude with a summary of our financial performance by John.

We remain on track to deliver on key milestones across our pipeline of hematologic and solid tumor programs. In our program targeting hematological cancers, we're continuing dose escalation with the objective of establishing potential best-in-class product profiles that may compete effectively with other approved and investigational products. In our solid tumor programs, our 2 technology platforms, ACTR and BOXR, are well positioned to address many of the efficacy and safety challenges faced by T cell therapies.

As a reminder, we've evaluated 2 different ACTR product candidates, ACTR707 and ACTR087, in combination with rituximab to treat patients with relapsed/refractory non-Hodgkin lymphoma. These trials have been very important for us in providing clinical proof of concept for the ACTR technology. At the end of last year, we selected ACTR707 as our lead to move forward and announced our decision to wind up the ACTR087 program. We've made progress since then on both fronts, as Mike will describe in more detail. Importantly, we've now escalated through 4 dose levels with ACTR707. And as of last week, we've seen no dose-limiting toxicities.

As part of our collaboration with Seattle Genetics to develop a BCMA-targeted therapy for multiple myeloma, we've made good progress through the early stages of dose escalation in our ongoing ATTCK-17-01 Phase I trial with a first-in-human targeted antibody. With 3 required low-dose cohorts cleared in 2018, as dose escalation continues into 2019, we're moving into dose levels that may be expected to have pharmacological activity based on preclinical studies.

Our focus on developing therapies to address solid tumors continues to grow. We've now activated multiple clinical sites in the ATTCK-34-01 study, our first ACTR T cell study targeting HER2+ advanced cancers. We expect additional sites to come online through the year as we continue to enroll and treat patients with dose escalation phase of the study.

We're also continuing preclinical studies with BOXR1030, our first product candidate to emerge from our BOXR or Bolt-On Chimeric Receptor platform. The BOXR platform was developed to broadly enable engineered T cell therapies in solid tumors by overcoming immunosuppression in the tumor microenvironment. We look forward to progressing this program towards potential future clinical testing.

I'll now turn it to Mike to discuss updates from our ongoing clinical pipeline.

Thanks, Chuck. We continue to be very excited about our product candidates' potential as well as the productivity of the ACTR platform that's led to our pipeline depth in both hematologic and solid tumors. Starting with our hematologic programs. We've continued to make progress with our lead product candidate, ACTR707, in combination with rituximab to treat relapsed/refractory non-Hodgkin lymphoma. We presented preliminary results from our ATTCK-20-03 Phase I study at the 2018 ASH Annual Meeting in December, sharing data for patients treated at the first 2 dose levels. We showed that 4 patients out of 9 treated achieved a complete response without dose-limiting toxicities. We've continued to advance the dose escalation phase of the trial, completing enrollment at Dose Level 3 earlier this year. All patients in this cohort were treated with 55 million ACTR707 dose, and no dose-limiting toxicities were observed, allowing us to advance to Dose Level 4.

We're continuing to enroll and treat patients in this cohort at 18 million ACTR+ T cells. As of last week, no DLTs and no severe adverse events of cytokine release syndrome or neurologic events have been reported in this trial. We plan to complete dose escalation in the second half of 2019 and based on these data, define a preliminary recommended Phase II dose of ACTR707.

Several different patient populations with non-Hodgkin lymphoma may benefit from the ACTR707, rituximab combination. We look to include such patients in safety expansion cohorts at the preliminary recommended Phase II dose and plan to refinalize to allow us to treat those patients in the study. We anticipate initiating enrollment in the safety expansion phase as early as the second half of this year and continuing into 2020, and we expect to report data from the dose escalation phase of the trial at the end of the year.

In parallel, we're wrapping up the ATTCK-20-2 Phase I trial, our second lymphoma study in which we are evaluating, ACTR087 combined with rituximab. We've completed enrollment in an expansion cohort at the preliminary recommended Phase II dose of 35 million ACTR+ T cells. We're continuing ACTR087 treatment, safety and response assessments. And as of last week, no severe adverse events of cytokine release syndrome or neurologic events had been observed in the expansion cohort. We plan to report data on all enrolled patients in this study at the end of 2019.

Our multiple myeloma program includes our ATTCK-17-01 study, which is evaluating the combination of ACTR087 with SEA-BCMA, an investigational glycoengineered antibody targeting BCMA developed by our collaborator, Seattle Genetics. As we reported at ASH in 2018, we completed assessment of the initial 3 cohorts of patients in the dose escalation phase of the study. Treatment has been generally well tolerated and no dose-limiting toxicities or severe adverse events of CRS or neurologic events have been reported as of last week.

In these initial cohorts, we consistently administered 30 million ACTR+ T cells, while progressively increasing the dose of the SEA-BCMA antibody. This year, we've continued to progress through dose escalation; enrollment and dosing of patients at Dose Level 4, where we're administering 30 million ACTR+ T cells and 2 milligrams per kilogram of SEA-BCMA has been completed. Enrollment and dosing of patients at Dose Level 5 with 50 million ACTR+ T cells and 2 milligrams per kilogram of SEA-BCMA is ongoing.

As a reminder, the clinical protocol requires us to make changes in dose for one investigational agent at a time. However, our adaptive trial design provides flexibility in how we may do so. We plan to continue to enroll and dose patients through the dose escalation phase of the trial this year to report updated data in the second half of 2019.

I'd now like to focus on our solid tumor pipeline. We continue to make progress with our ACTR program directed toward patients with HER2 over-expressing advanced cancers in our ATTCK-34-01 Phase I dose-finding study.

In this trial, we're testing ACTR707 in combination with trastuzumab. For patients with gastric cancer or breast cancer, study enrollment requires that they have received and progressed through all available HER2-targeted therapies. We initiated the first clinical site in this study in December 2018. And as Chuck mentioned, we continue to activate additional clinical sites. Enrollment, dosing and assessment of patients in the first dose cohort is ongoing. And in this cohort, we're treating patients with 25 million ACTR+ T cells and a dose of trastuzumab that's approximately 50% of the approved dose. As of last week, no DLTs and no severe adverse events of CRS or neurologic events have been reported in this trial. We plan to report initial clinical data from at ATTCK-34-01 at the end of 2019.

Now let me turn the call over to Seth Ettenberg, our Chief Scientific Officer, who will discuss our BOXR platform.

Thanks, Mike. For of those of you who aren't yet familiar with BOXR, these are T cells engineered to co-express 2 different genes. The first gene is a chimeric receptor, like an ACTR or a CAR, which targets the T cells to attack tumor cells. The second gene, which we call the bolt-on, is designed to alter biological pathways in the T cell allowing it to overcome some of the immunosuppressive properties of solid tumors. We call these genes bolt-ons with the expectation that they can be easily inserted into a variety of different engineered cell therapies to improve their functionality. They can work independent of the targeting receptor. We see the BOXR platform as an important complement to the ACTR technology, allowing us to broadly capture the potential of T cells in solid tumors.

BOXR1030 is the first product candidate from the BOXR platform. It's engineered to specifically target tumor cells expressing an oncofetal antigen called glypican-3, also known as GPC3. This antigen is expressed in several solid tumor indications, including hepatocellular carcinoma and squamous cell lung cancer. A characteristic of these particular solid tumors is their enhanced metabolic activity leading to a depletion of free nutrients, like glucose from their local environment. Nutrient competition within the tumor microenvironment is a form of immunosuppression and can limit the ability of T cells to kill, proliferate and exert antitumor activity.

BOXR1030 was designed to express a specific metabolic enzyme that enable T cells to continue to function even under nutrient-restricted conditions. We've been able to show that the benefit of this bolt-on using stringent xenograft models in immunocompromised mice. In these models, a traditional CAR-T is incapable of controlling tumor growth. We see no difference between untreated control animals and those receiving CAR-T treatment. By co-expressing the BOXR1030 bolt-on gene in the same parental CAR-T cell, however, we enable potent antitumor activity and consistently drive complete tumor regressions.

This is a very exciting finding, and we're taking steps to bring BOXR1030 into clinical testing. These include testing to further validate the specificity of BOXR1030 T cell activity and comprehensive assessments of preclinical safety for the product candidate. Process development is also initiated to optimize the method of manufacturing BOXR1030 cells, building on our existing ACTR T cell manufacturing experience. In addition, we've continued to expand our understanding of how BOXR1030 works, defining the mechanism of action for bolt-on -- for the bolt-on gene in T cells. We look forward to sharing more details on the program later this year at a major scientific conference.

With that, let me turn the call over to John Green, Vice President of Finance, who'll discuss our financial.

Thank you, Seth. I'll now turn to our financial results for the first quarter. In the first quarter of 2019, we realized collaboration revenue of $3.1 million compared to $2.2 million in the same quarter of 2018. This increase reflects the recognition of a portion of the $25 million upfront payment received from Seattle Genetics under Unum's collaboration agreement as well as reimbursement of research and development costs attributed to the collaboration agreement.

R&D expenses were $12.4 million for the first quarter of 2019 compared to $8.1 million for the same period last year. This increase reflects higher clinical trial costs for active Phase I clinical trials as well as increased personnel-related costs, materials and facility-related costs relating to scaling manufacturing processes, and increased consulting costs to support these activities. General and administrative expenses for the first quarter of 2019 were $2.5 million compared to $1.1 million for the same period last year, with this increase primarily due to higher personnel-related costs due to increased headcount and increased expenses around operating as a public company.

Net loss for the first quarter was $11.7 million compared to $6.8 million in the same period last year. As of March 31, 2019, Unum had cash, cash equivalents and marketable securities of $67.1 million, which we anticipate will be sufficient to fund operating expenses and capital expenditure requirements into early 2021 without considering available borrowings under our loan and securities agreement.

With that, I'll turn it back to Chuck to wrap up.

Thanks, John. We look forward to reporting on our progress throughout the year across our pipeline. To summarize some of the key future milestones we've outlined today: With our lymphoma program testing ACTR707 with rituximab, we expect to complete the dose escalation phase of the ATTCK-20-03 study in the second half of 2019 and to report results from dose escalation phase in late 2019. In addition, we expect to initiate cohort expansion in the second half of 2019 to confirm the preliminary recommended Phase II dose. We also expect to report data in late 2019 from the fully enrolled ATTCK-20-2 trial testing ACTR087 plus rituximab in relapsed/refractory non-Hodgkin lymphoma.

With our myeloma program testing ACTR087 plus SEA-BCMA, we expect to progress dose escalation of both T cell and antibody in the ATTCK-17-01 study and to report clinical data from multiple dose cohorts in the second half of 2019. With our advanced HER2+ cancer program testing ACTR707 plus trastuzumab, we expect to report initial clinical data from ongoing dose escalation in the ATTCK-34-01 trial in late 2019. And finally, with our BOXR platform, we expect to report additional preclinical characterization of BOXR1030, including mechanism of action in the second half of 2019.

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

(Operator Instructions) And our first question comes from Peter Lawson with SunTrust.

Thanks for the clinical safety updates. Just around -- when should we think about timing around updates around clinical benefits? And if there's anything you can mention about that, it would be great. And should we kind of view today's update kind of to mean that you haven't seen any clinical responses yet? Or you have and you're kind of holding that back for a conference.

Just to clarify. So I think, our intention in these calls is to provide really sort of operational updates and to give a very high-level view in terms of the safety observations in each study. As we've indicated previously, our practice in terms of sharing data from the studies is really through medical conferences, and we provide the guidance, I think, for each of those programs in terms of when -- approximately when we intend to be presenting those results.

So there's nothing to read in terms of observations with respect to efficacy. We're essentially -- we're looking to present those again at scientific conferences.

Got you. And then the safety updates, say for 17-01, how many are at that kind of higher dose level?

Yes, again, we haven't -- we don't like to get into the specifics in terms of individual patients. Again, the high-level summary really reflects the safety observations we've seen across the entire program.

(Operator Instructions) Our next question comes from Yaron Werber with Cowen.

I just have one question regarding the ATTCK-34-01 program. I'm just wondering if you guys can share some details on the enrollment status. Like how many cohorts or patients you'll be sharing at the end of this year?

Sure. So again, just to clarify, we don't provide sort of specifics in terms of individual patients on specific trials. We're currently enrolling and treating patients in the first dose cohort. And ultimately, depending upon the pace of enrollment, we'll be continuing to progress through additional cohorts and again, reporting data late in 2019 from the study.

And I'm currently showing no further questions at this time. I'd like to turn the call back over to Chuck Wilson for closing remarks.

Great. Thank you very much for joining us today. We look forward to continue to provide you with updates on all of our programs through the rest of this year.

Ladies and gentlemen, this concludes today's conference. Thanks for your participation. Have a wonderful day.