Cogent Biosciences, Inc. (COGT) 2018 Q4 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Unum Therapeutics Fourth Quarter 2018 Results Conference Call. (Operator Instructions)

I would now like to hand the call over to Ms. Stephanie Ascher. 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 fourth quarter ended December 31, 2018, and full year of 2018. With me on our call today are Chuck Wilson, CEO; Michael Vasconcelles, Chief Medical Officer; Seth Ettenberg, Chief Scientific Officer; and John Green, Vice President, Finance. 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, March 28, 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, CEO. Chuck?

Good morning. I'm pleased to be able to provide a number of updates today reporting progress across several fronts, including advances in our clinical stage programs in lymphoma and myeloma and the rapid expansion of our solid tumor pipeline. Mike will provide you with an update on our ongoing clinical trials and Seth will talk about our 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 and key milestones for 2019.

We made important progress across our entire pipeline in 2018 and look forward to building upon that in 2019. In our programs targeting hematologic cancers, we see a clear path to establishing potential best-in-class product profiles that may compete effectively with other approved and investigational products. In our solid tumor program, we see a unique opportunity for our technology platforms to address the historical challenges that T cell therapies have faced in this setting using truly novel approaches.

Among the key highlights we'll be talking about today, we continue to be pleased with the safety and activity that we've seen to date with ACTR in non-Hodgkin lymphoma and our decision to move forward with ACTR707 in this indication. Mike will summarize the data that we shared with ASH in December and provide some updates in terms of where we stand today. We've also made good progress in wrapping up the ATTCK-20-2 study, which has positively impacted our runway, as John, our VP Finance, will describe later.

In our collaboration with Seattle Genetics to develop a BCMA-targeted therapy for multiple myeloma, we've made good progress in the early stages of dose escalation with a first-in-human targeted antibody. With these initial cohorts cleared, the stage is now set as we move into dose levels that may be expected to have pharmacological activity based on preclinical studies as dose escalation continues in 2019.

We've also made significant progress on the solid tumor front. In the second half of 2018, we announced that our IND for the ACTR plus trastuzumab combination has cleared FDA review. In December of 2018, we activated the first clinical site in the ATTCK-34-01 study, allowing us to begin to screen and enroll patients.

Today, we're also announcing that we've initiated preclinical development of BOXR1030, the first product candidate to emerge from our new BOXR or Bolt-On Chimeric Receptor, platform. As we described at the SITC conference in November, the BOXR platform was developed to broadly enable engineered T cell therapies in solid tumors by overcoming immunosuppression in the tumor microenvironment. As Seth will describe, we expect to develop BOXR1030 to treat a variety of liver and lung cancers that are characterized by an altered metabolic state. The initiation of preclinical development puts this program on track towards future clinical testing.

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

Thanks, Chuck. We continue to be very excited about the potential of our product candidates in both hematologic and solid tumors. Having demonstrated proof of concept of the ACTR platform broadly in hematologic cancers with 3 programs, we're well positioned to advance and expand our solid tumor pipelines as well.

I'll start with our hematologic programs, specifically our ACTR707 product candidate combined with rituximab to treat relapsed/refractory non-Hodgkin lymphoma. As you recall, this is our lead program in non-Hodgkin lymphoma. At the 2018 ASH Annual Meeting in December, we presented preliminary results from patients in the first 2 dose levels of the ATTCK-20-03 study. Of the 6 patients treated at Dose Level 1, 3 achieved a complete response. 1 of 3 patients treated at Dose Level 2 also achieved a complete response. Since the ASH presentation, we've continued dose escalation, completed enrollment and safety assessment at Dose Level 3 and initiated enrollment at Dose Level 4. Through the first 3 dose cohorts, we've observed no dose-limiting toxicity and no severe adverse events, cytokine release syndrome or neurologic events. Once we've completed the dose-escalation phase of the trial, we expect to begin cohort expansion at the preliminary recommended Phase II dose currently anticipated for the second half of 2019.

Moving on to our second lymphoma program with ACTR087, we've also made good progress in completing enrollment of our dose confirmation expansion cohort in the ATTCK-20-2 study ahead of our anticipated time line. This accelerated enrollment reflects not only the enthusiasm of our investigators, but of course, the commitment of patients. As such, we anticipate reporting data for all enrolled patients in this study by year-end.

Turning now to multiple myeloma and our ATTCK-17-01 study. As you recall, we are studying the combination of ACTR087 with SEA-BCMA, an investigational glycoengineered antibody targeting BCMA and developed by our collaborator, Seattle Genetics. As we reported at the ASH Annual Meeting in December, we've completed assessment of the initial cohorts of patients in the dose-escalation phase of study. Therapy was well tolerated with no dose-limiting toxicity or severe adverse events, cytokine release syndrome or neurologic events observed within the first 3 dose levels.

Having evaluated the safety of SEA-BCMA in combination with ACTR087 at these low antibody doses, we've continued dose escalation into an antibody dose range that is expected to have pharmacologic activity based upon our nonclinical study. Specifically, enrollment at Dose Level 4 is ongoing with SEA-BCMA at 2 milligrams per kilogram. All dose levels to date have administered SEA-BCMA with 30 million ACTR+ T cells. We expect subsequent cohorts to study higher doses of both ACTR087 and SEA-BCMA. As a reminder, the 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 expect to continue to enroll and dose patients through the dose-escalation phase of the trial throughout the year and report data from these dose cohorts in the second half of 2019.

Switching gears and now focusing on our solid tumor pipeline. As we've shared, we continued to make good progress with our ACTR program directed toward patients with HER2-overexpressing cancers. The ATTCK-34-01 study was initiated at the end of 2018. In the Phase 1 dose-binding study, we're testing ACTR707 with trastuzumab, enrolling patients with advanced HER2 cancers regardless of the site of origin, although patients with primary cancer of the CNS are excluded. For women with breast cancer or those patients with gastric cancer, study enrollment requires they've received and progressed through all available HER2-targeted therapy.

At the first clinical study in solid tumors with ACTR, the primary study objective is to assess the safety and tolerability of the combination and to define the doses of each agent for subsequent development. In our first dose cohort, we are administering 25 million ACTR+ T cells, the same dose used in the first cohort of our lymphoma study. And we're dosing trastuzumab at approximately 50% below the standard dose. Additional study objectives include assessment of antitumor activity, ACTR T cell persistence, trastuzumab pharmacokinetics and several biomarkers such as cytokine inflammatory marker levels in treated patients. We anticipate that initial clinical data from the ongoing dose escalation will be available to present at year's end.

Now let me turn the call over to Seth Ettenberg, our Chief Scientific Officer, who will describe our new platform, BOXR, in more detail.

Thanks, Mike. As we described in our last earnings call, we have been exploring ways that we can expand our technology platform and broadly improve the functionality of engineered T cell therapy, enabling them to be more effective in solid tumors. This is a novel approach we call Bolt-On Chimeric Receptor, or BOXR for short. BOXR T cells express a chimeric receptor like an ACTR or a CAR that targets the T cell to attack tumor cell. The BOXR T cells also express a second additional transgene that is effectively bolted on to the cell in order to change its biological pathways and improve function in a stressed tumor microenvironment. We shared some of the details of our approach and some specific examples from the early phase of these efforts at last year's SITC meeting. These included examples of both ACTR-targeted and CAR-targeted T cell as well strategies for overcoming a variety of different mechanisms that solid tumors use to suppress immune cells. I would encourage anyone who is interested in learning more to review our SITC presentation, which is available on our website.

Since November, we have selected our first product candidate to emerge from these efforts, BOXR1030. This product consists of a T cell co-expressing a glypican-3-directed CAR in an undisclosed metabolism-enhancing bolt-on transgene. Glypican-3 is a well-known oncofetal antigen, which is selectively expressed in a variety of tumor types including certain liver and lung cancers. These tumors are known to deplete their local environment of required nutrients such as glucose, compromising T cell functionality and correlating with poor patient outcomes. In our preclinical studies, we have shown that expression of our metabolic bolt-on transgene enables complete tumor regression across a range of stringent xenograft models. Without the bolt-on transgene, we see little to no antitumor activity in these same stringent models.

Having selected BOXR1030 as our first BOXR product candidate, we recently initiated preclinical development activities, which put the program on the path to clinical testing. These activities include safety screening and process development to support GMP manufacturing. We look forward to sharing more details on the program in the future. Along these lines, we are planning to present more information on the identity of the BOXR1030 bolt-on transgene as well as preclinical characterization of its mechanism of action in medical meetings in the second half of 2019.

Finishing up, I'd like to emphasize that we see the BOXR platform as an important complement to the ACTR technology, which allows us to broadly capture the potential of T cell therapies in solid tumors. To date, we've demonstrated that BOXR bolt-on transgenes can improve the functionality of both ACTR and CAR-targeted T cells. In addition to counteracting metabolic mechanisms of immunosuppression, we've also identified a number of additional BOXR transgenes that address completely independent mechanisms as well. We look to use this bolt-on toolbox in combination with a variety of targeting receptors to create novel engineered T cells tailored for many different applications and ultimately bring these therapies to patients.

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

Thank you, Seth. I will now turn to our financial results for the fourth quarter. In the fourth quarter of 2018, we realized collaboration revenues of $3.8 million compared to $2.1 million in the same quarter of 2017. The 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 reimbursements of research and development costs associated with the ATTCK-17-01 study.

R&D expenses were $10.8 million for the fourth quarter of 2018 compared to $7.6 million for the same period in 2017. This increase is driven by 3 key components, which include clinical trial costs for the active Phase I clinical trials, increased personnel and consulting costs and expenses relating to scaling manufacturing capacity. G&A expenses for the fourth quarter were $2 million compared to $1.4 million for the same period in 2017 with the increase primarily due to expenses around operating as a public company and higher personnel-related costs.

Net loss for the fourth quarter was $8.6 million compared to $6.7 million for the same period in 2017 with the increase largely reflecting the increased operating costs. We ended the fourth quarter of 2018 with approximately 30 million shares outstanding.

As of December 31, 2018, Unum had cash, cash equivalents and marketable securities of $78.6 million. We anticipate that this capital is sufficient to fund operating expenses and capital expenditure requirements into early 2021 without considering available borrowings under our loan and securities agreement. The extension of our runway is driven by several factors including the accelerated completion of the ATTCK-20-2 study. Our total cash burn for the year ended 2018 was $36.3 million.

With that, I'll now turn the call back to Chuck.

Thanks, John. Looking forward, we expect a very active 2019 making progress across our entire pipeline. To summarize some of the key future milestones we've outlined today. With our lymphoma program testing ACTR707 plus 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 the dose-escalation phase in late 2019. In addition, we expect to initiate cohort expansion to confirm the preliminary recommended Phase II dose in the second half of 2019. With enrollment now completed in the ATTCK-20-2 study testing ACTR087 plus rituximab in relapsed/refractory non-Hodgkin lymphoma, we expect to report data for all enrolled patients in late 2019.

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 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 lastly, with our BOXR program, we expect to report additional preclinical characterization of BOXR1030 including mechanism of action in the second of 2019.

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

(Operator Instructions) Our first question comes from the line of Peter Lawson with SunTrust.

Just on ATTCK-20-30 (sic) [ATTCK-20-03], just on the, what was it, 4 [DLs], have you -- are they still ongoing? And have you seen further responses? And when could we see further data for 20-03?

Let me turn you over to Mike Vasconcelles who can give you the update.

So yes, the data that we summarized are the data that we presented at ASH. And we -- as we stated, as we continue with dose escalation, we look forward to sharing updated data towards the end of this year as we expect to complete dose escalation in the study.

And then just on the BOXR1030, what should we expect to see in the second half as regards to update on that program, and congratulations there.

Yes, let me turn it over to Seth who can take you through that.

Sure. So for BOXR1030, we expect and we are currently performing key experiments to help bring 1030 to the clinic. And once these experiments are completed, we'll have more definitive timing. But your expectations for reporting later this year would be at an academic conference. We're likely to disclose the transgene that's used in BOXR1030 that enhances metabolic fitness of the T cell as well as the mechanism of action of that transgene.

Got you, okay. And then just as regards to data readouts and venues, should we really be thinking kind of ASH as the main venue for you or SITC fall into that as well?

Yes, so just to clarify our overall sort of strategy in terms of communication, we do prefer to present at leading medical and scientific conferences with, again, meaningful data sets, so for example, complete patient cohorts, et cetera. We generally don't disclose, which means we're presenting that until abstracts or titles are publically released, but hopefully the timing guidance we provided is helpful.

(Operator Instructions) Our next question is from the line of Yaron Werber of Cowen.

This is [Leo] on for Yaron. Hello?

Yes, hello.

Yes, I have 2 questions. First of all, I recall that you guys decided to move forward with the ACTR707 in lymphoma based on the totality of the safety and efficacy. So I'm just curious, what drove the decision to test ACTR087 in multiple myeloma? How -- what makes that decision?

This is Mike. So just a couple of points to keep in mind, there's a temporal component to keep in mind. We -- our first ACTR drug product is ACTR087. We moved forward in lymphoma and then really immediately thereafter, with our colleagues in Seattle Genetics, initiated the program in myeloma and we continue to be very bullish, frankly, on that construct. ACTR707, just to remind you, really came out of our labs as a high-throughput screening effort to support our solid tumor program, but we did see nice nonclinical signaling in hematologic cancer cell line so we wanted to get initial experience there. Lymphoma, and just as you nicely summarized, I think kind of the totality of the evidence when we chose to really start to narrow the lymphoma program sort of lean toward 707. But again, we look forward, since we fully enrolled the ATTCK-20-2 study with ACTR087, to be able to share those data and we're confident they're going to be informative to the myeloma program and ACTR platform overall.

If I could emphasize, I think -- again, the decision to select 707 over 087 in combination with rituximab really is a lymphoma-specific decision. Again, and reiterating what Mike said, we're really encouraged of what we've seen to date with the myeloma program with 087 and expect that to continue.

I see, that's helpful. A follow-up question regarding the 34-01 study, did you see any early signals for -- in terms of efficacy or toxicity?

Right. So just as a reminder, we activated the study at the end of last year and we're exactly in the phase of continuing to open up sites, screen, enroll and treat patients. So we really look forward to start to answer those questions and share those data toward the end of this year.

Our next question is from the line of David Nierengarten of Wedbush.

With regards to 34-01, have you actually enrolled a patient yet? I was curious about that. And then if you could remind us of your dosing at the recommended level of Herceptin or if you are dosing a bit lower to start with.

Sure. Again, just to sort of remind you sort of general strategy, we don't like to essentially provide through a single patient or -- with less than a full update. We are -- we will continue to inform you as where we stand in terms of dose escalation as we escalate doses, et cetera. But again, we'll stay away from commenting on individual patients. In terms of the dose of trastuzumab, we're starting at essentially 50% of the standard recommended of the approved dose for trastuzumab, have the ability as we do -- go through dose escalation to both escalate antibody and ACTR T cell dose.

And if you could remind me again, what is the step-up on the dose for Herceptin? Is it 50% of recommended and then the next step would be 75% or 100%? Or is that not defined yet or disclosed?

Yes. So I think we have a plan. I think initially, we're starting at 1 mg per kg with a plan to escalate to 2 mg per kg. It is an Adaptive Bayesian design which gives us flexibility in both dosing levels, the number of dosing levels, cohort size, et cetera.

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

Great. Thank you very much. It's been a pleasure talking to you today. We look forward to continuing to provide you updates on all of our programs through this year. And we look forward to speaking again in [10 more weeks]. Thank you.

Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Everyone, have a great day.