Agenus (NASDAQ:AGEN) Q1 2020 Earnings Call

0:00 Good morning, ladies and gentlemen. Thank you for standing by and welcome to the Agenus First Quarter 2020 Conference Call. At this time, all participants are in a listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your touchtone phone. To withdraw your question, please press star then 2. Please note this event is being recorded. I would now like to turn the conference over to Dr. Jennifer Buell, President and Chief Operating Officer of Agilent. Dr. Buell, please go ahead.

0:45 Thank you. Thank you, Sian. Today's call is being webcast and will be available on our website with our accompanying slide material for replay. Before we start, we'd like to remind you that this call will include forward-looking statements, including statements regarding our clinical development and regulatory plans and timelines, as well as timelines for data release and cash projections. These statements are subject to risks and uncertainties, and we refer you to our SEC filings for more details on these risks. As a reminder, this call is being recorded for audio broadcast. I'm Jennifer Buell, President and Chief Operating Officer of Agenus, and joining me today are Dr. Garo Armen, Chairman and Chief Executive Officer, Dr.

1:35 Dan Chan, Head of Drug Discovery, Dr. Birju Yit, Lead Scientist for Allogeneic INK T-cells, and Christine Klaskin, our Vice President of Finance. I will now turn the call over to Garo.

1:55 Thank you very much, Jen. And a special thank you to all of you for joining us during this time when the world has turned upside down because of the COVID-19 pandemic. I hope you and your families are safe and well. Our team at Agenis has found a productive way to operate in this new norm. At the earliest signal of the pandemic, Our team reacted swiftly and took proactive measures to protect our employees, their families, and our business. As a result, our operations in Burpee, Lexington, and Cambridge have remained open with a rotating work schedule for safety and with limited interruption to our key priority.

2:50 We operate with approximately one-third of the workforce onsite and the remainder working from home. And that has not disrupted any part of our operations so far. And importantly, to the best of our knowledge, none of our employees have been infected with the virus so far and would like to keep it that way. Earlier this year, we projected Receipt of approximately 60 million in cash milestone payments for 2020. As we have announced, we've already received 15 million based on the sales of Shingrix, which has our QS21 adjuvant in it. However, given the environment, the remaining 45 million is uncertain.

3:48 because of the disruptions caused by COVID. And hence, we've taken measures to result in annualized cost savings of approximately $50 million. These savings are driven by reductions of both external and internal expenditures. And importantly, they will result in slowing down all several programs, but we do not expect these steps to affect our near-term or medium-term commercial launch prospects. We also expect that our high priority clinical development and research programs will proceed as planned.

4:40 Our proactive measures are designed to deliver our key milestones this year. including plans for our BLA filings, our acceleration of clinical development of our next-gen multipurpose CTLA-4 molecule 1181 about which you will hear much more from Dr. Buell, our advancing of INKT cell therapy to the clinic for the treatment of cancer and COVID-19 patients, that you will hear from Dr. Bourdieu, who will also tell you about the advantages of our INKT cells, including, for example, substantially reduced costs associated with cell therapy when we practice INKTs.

5:29 And also, you will hear that we're advancing important programs like our TIGIT molecules into the clinic. And as you know, we have started this program a number of years ago, and now we're ready to take that into the clinic. I will now turn the presentation to Dr. Jen Buell, our president and chief operating officer, to provide you with an update on our highest priority programs, starting with AGEN 1181, our multipurpose NextGen CTLA-4. Jen?

6:10 Thank you very much, Garo. And hello, everyone. As Garo mentioned, I'll start by providing an update on Agen 1181. And there's a summary of this program on slide four that we'll review today. This molecule is familiar to many of you. As Garo said, it's our multifunctional T-cell antibody, which also binds to CTLA-4. Now, importantly, This molecule is engineered. The FC region of this molecule is engineered. We did this because we knew of some key features that this engineering could provide. Those features included increased immunogenicity, increased T-cell activation, beyond which we see with first-generation CTLA-4s, superior combinations with PD-1, as you see on slide four, as well as important potential safety benefits such as a reduction in endocrinophobies for patients treated.

7:17 And we expect to increase or broaden the patient population of responders, patients who will respond who are unlikely to respond to a first generation CTLA-4 due to a genetic polymorphism that impacts about 40% of the population. And what we're going to talk to you about today are data from this trial which will show that as the molecule has been designed to benefit patients who harbor this genetic polymorphism, patients are benefiting from HN1181. We have also seen no endocrinopathy, none of the safety-related side effects that we see with Yervoy related to hypophysitis or otherwise.

8:04 Very important features. Upstate Engineering is something that we know to be really quite important. We've published on this technology and our techniques on our Agent 1181 molecule in Kansas Hill last year. We've also, as Dan will speak to you today, we've also engineered our T-shirt molecule in order to bring similar enhancements. We've shown you data. that supports the benefits of this engineering. And we're also now seeing data from late-stage clinical trials with the SC-engineered HER2 antibody called margoteximab. You may be aware of some of that data. So on slide five, I'd like to summarize. ACEN 1181 is advancing in a phase one dose escalation trial. This next-generation antibody has shown profound activity in the form of objective responses, which are unusual to see this early in clinical development.

9:05 We're hopeful that based on the current trends and as patients continue on therapy, that we'll continue to see more patients with more durable responses. Now, you may have heard that a number of hospitals have been converted to treat patients with COVID-19, and this could impact, of course, some clinical trials, as well as patient access. Patients with cancer getting access to their therapies. However, in spite of this reality, we continue to accrue to our trial without interruption. Our principal investigators have informed us that based on the data available to date, HN1181 has life-saving attributes that support the continued enrollment of this trial.

9:50 And today, we have a queue of patients waiting to be enrolled. Now you may remember, as I mentioned earlier, that HN1181 was deliberately designed to improve the efficacy and safety of first-generation CTLA-4s. In addition, this antibody is expected to expand the patient population who will benefit. And now I'm going to highlight some data that supports the design of this molecule and the activity that we're seeing. In our dose escalation trial, HN1181 alone and in combination with Valsilumab demonstrated a clinical benefit rate of 70%. This includes complete responses, partial responses, as well as disease stabilization of patients with late stage cancer.

10:40 Now during our last call, we described a patient with refractory endometrial cancer. This patient had late stage disease, she had failed all prior therapies, and importantly, She had a very poor prognostic based on available biomarkers that help us determine a patient's likelihood to respond to therapy. These markers include the patient was negative for PD-L1, the patient had microsatellite stable disease, which is unlikely to respond to immune therapies, and this patient had the genetic polymorphism in her CD16 allele that rendered her unlikely to respond to a first-generation CTLA-4. In spite of these negative odds, we are thrilled to see that this patient is a confirmed complete responder on AGEN 1181 monotherapy at 1 mg per K.

11:35 Now on slide six, I want to highlight another very exciting case. This patient is a patient with refractory endometrial cancer with a similarly poor prognostic profile with metastatic disease and multiple locations as you can see here. This patient is now also a confirmed partial response in her target lesions and a complete response in her non-target lesion. This patient responded to a very low dose of HN1181 in combination with valpilumab, our PD-1 antibody. If I can turn your attention now to slide seven, Last week, we convened with our advisory board.

12:27 Now, this advisory board is comprised of top immune oncology experts, some of whom are specialists in the CTLA-4 mechanism, some of whom were the first to dose patients with the first-generation CTLA-4 over 20 years ago. After an extensive review session, Our advisors endorsed our accelerated development path for Agent 1181, which we are now in the process of launching as we speak. For this phase of development, we will pursue a fast-to-market strategy. This means going after cancers where there is limited or no effective treatment options available to these patients.

13:12 These tumors are highly prevalent, or said differently, large cancer market, large commercial market opportunities. These opportunities include PD-1 refractory non-small cell lung cancer, PD-1 refractory melanoma, and microsatellite stable tumors like colorectal cancer, as well as endometrial, which are the two cases that I shared with you just a few moments ago. We'll continue to keep you updated as these programs progress and mature. I'll now turn to our lead programs, our PD-1 program, Balfilamab, which we call Bally, and our CTLA-4 program, Zalafilamab, which we call Zally. The results that you see on slide eight show the evolution of cancer therapies for women with cervical cancer, starting with chemotherapies on the left and VEGF inhibitors, which are still widely used despite their limited benefit.

14:12 The data that we've presented now from our programs, valacilumab and valacilumab, are based on a large cohort of 55 patients who had a median of 12 months of follow-up. Importantly, all responses were confirmed by an independent radiology review, which is a gold standard in assessing outcomes in cancer. We've summarized our findings in a recent Agenis newsletter, which is available on our website. Notably, we have observed 14 objective responses. These include four complete responses and 10 partial responses in these 55 patients evaluated so far. This is a response rate of 26%.

15:02 As a reference, Merck was granted accelerated approval for their PD-1 antibody based on 11 responses in 77 patients. with a response rate of 14%. As you can see here, our combination has the potential to become the most effective treatment available for patients with metastatic cervical cancer. And a few comments regarding cervical cancer patients and our plans. Cervical cancer is a horrifying disease, particularly for young women who come from economically disadvantaged backgrounds and have limited access to healthcare. Patients are diagnosed and then treated with toxic chemotherapy, which has many difficult side effects and little clinical benefit.

15:51 Their cancer ultimately progresses with little to no effective treatment options available to them, as you can see here. We're committed to changing this reality. Data from our cervical cancer clinical trials with the Genesis Bally-Zaly or PD-1 and CTLA-4 antibodies has shown a near doubling of responses As compared to currently available treatments. And importantly, most importantly for us, is that these responses are durable. These patients are not converting or progressing once they're responding, which is incredibly important to patients. And also importantly, we're seeing patients with long-term disease stabilization who later convert to response. During our recent year-end call, we mentioned that we received fast-track designation from the FDA for the investigation of falcilumab alone and in combination with zalofilumab in relapsed refractory or metastatic cervical cancer.

16:51 We plan to submit our BLA filings this year and will continue to keep you informed on our progress. Now I'm going to wrap up with two very exciting programs. During a recent meeting with clinical experts, they noted that we have the most productive research engine in I.O. I agree. Today I'm joined by two of our lead scientists responsible for our next innovation, expected to enter the clinic very soon. Dr. Dan Chan and Dr. Bourjoo Eat are leading our TIGIT and our INKT programs, respectively. They're joining us here to talk about these programs today. As you know, TIGIT is shaping up as a powerful combination partner with PD-1 antibodies, especially in tumors expressing TIGIT.

17:43 We've designed two different approaches to optimally target TIGIT.

17:48 First, our FD-engineered anti-TIGIT antibody has outperformed all tested competitor antibodies and showed superior T-cell activation when combined with PD-1 or Live3 antagonists. and our TIGIT bispecific molecule, HN1777, which has demonstrated potent tumor killing as a monotherapy and difficult to treat cancers where PD-1 antibodies alone are ineffective. In addition to these two TIGIT antibodies, we're rapidly advancing our allogeneic cell therapy to the clinic to treat patients with cancer and to treat patients with COVID-19.

18:34 We expect both INDs to be cleared shortly, and as a matter of fact, one may clear as early as this week. I note that like us, the FDA has been working through weekends to process applications, which is very heartening during this health crisis. Brigitte will tell you more about these cells. She's trained in molecular biology and immunology, and she joined us from the Harvard Beth Israel Deaconess Medical Center. Thank you, Garo and Jen.

19:08 So, in very natural to the T cells, for I and K T cells, have several advantages over other allogeneic approaches in development, including, but not limited to, their significant expansion capacity, their use in an allogeneic setting without requiring genetic manipulation, and their ability to suppress graft-versus-host disease. I am excited to report that our team filed two INDs to advance our INKT cells to combat cancer and separately COVID-19. INKT cells are a rare population of lymphocytes, and importantly, in late stage cancer, the frequency and the function of INKT cells is highly correlated with overall survival.

19:59 Unmodified INKTs are a natural component of the innate immune system and their reduced numbers or function is associated with poor immune response to cancers and poor prognosis of patients with late stage disease. You can see on slide nine some of the notable advantages of INKT cells. So first of all, INKT cells can penetrate into the tissue, which gives them a critical advantage to target solid tumors that are not served by approved cell therapy. Secondly, INKT cells can cure cancer without requiring genetic manipulation. So, employed INKTs in an unmodified form, patients can receive the treatment quickly and at a significantly lower cost.

20:51 And third, INKTs are expected to target SARS-CoV-2 and cells infected with the virus. INKT should be agnostic mutations of the current strain and other coronaviruses. While severe complications of SARS-CoV-2 infection are characterized by a life-threatening respiratory disorder and other organ failure, our allogeneic INKT therapy, agent 797, is expected to help clear the virus while controlling harmful inflammation caused by the virus. Preclinical data demonstrates that INKT activation induces a rapid antiviral response and enhances immunity to respiratory and other infections.

21:38 Also, INKTs have been shown to prevent lung injury in preclinical models by reducing the number of inflammatory cells, dampening exacerbated inflammation, and thus preventing or controlling tissue damage. This may be especially important in COVID-19. Agent 797 could also promote long-term immunity against COVID-19, which would be an important outcome to protect both recovered patients from reinfection and to protect healthy individuals from the disease. So finally, an important benefit of our allogeneic approach is its scalability. We have demonstrated that INKT cells from a single donor are manufacturable and scalable.

22:26 Just based on our early process development work, we have developed a scalable process designed to manufacture about a thousand doses from a single donor. While our near-term clinical trials will help define the key features of AGES 797 in cancer and infectious disease, we are ready to quickly design optimal combinations with our cell therapy and checkpoint antibodies. My colleagues will be presenting data at AACR on our optimal combinations with key insights into the criticality of these approaches and the significant differentiation that agenus has in delivering these combinations. Thank you very much, and now I will turn it over to my colleague, Don Chan, to discuss our TIGIT program.

23:11 Thank you, Birju, and hello, everyone. Today, I'm excited to discuss two of our TIGIT antibodies, why they are important, and how we believe they will change the treatment paradigm. As Jen mentioned, TIGIT is shaping up as a powerful combination partner with PD-1 antibodies, especially in tumors expressing TIGIT. Our portfolio of TIGIT-targeting antibodies includes an SC-enhanced TIGIT monospecific, agent 1327, and our TIGIT bispecific, agent 1777.

23:56 We believe both molecules have unique advantages over other TIGIT antibodies that are in clinical development. Since TIGIT may be new to many of you, I will describe what TIGIT is as seen on slide 10. is a receptor primarily expressed on T cells and NK cells. TIGIT attenuates innate and adaptive immune responses by inhibiting the actions of T cells and NK cells. In addition, it increases the immune suppressive activity of regulatory T cells.

24:42 TIGIT is overexpressed in multiple tumors and is known to be a key player in driving resistance to anti-PD1. And as a result, tumors grow. Blocking TIGIT with antibodies, like for a monospecific TIGIT antibody, agent 1327, or for a TIGIT bispecific, agent 1777, unleashes important immune cells, such as T cells, and NK cells to kill many types of cancer. HNS was the first to discover and report in cancer cell and at AACR in 2019 that TIGIT antibodies require SC gamma receptor co-engagement to promote optimal T cell activity against tumors.

25:43 Over TIGIT, AGEN 1327, is engineered with this FE enhancement and has outperformed all tested competitor antibodies and showed superior T-cell activation when combined with PD-1 or LAG3 antagonists or OX40 or CD137 agonists. We presented this data at AACR 2019. Our digit is an ideal combination partner for addressing non-resistance mechanisms to current checkpoint therapy and with the potential to provide deeper responses.

26:29 In addition to superior function demonstrated against tested competitors, our molecule is designed to one, maximize anti-tumor activity like the robust activity observed with our FC-engineered AGEN1181 that has already shown remarkable activity in early clinical trials. Our preclinical data with our digits also shows superior tumor killing compared to competitor molecules as seen on slide 11. Two, be an optimal combination partner for anti-PD1 antibodies for more potent tumor killing, particularly for TIGIT-expressing tumors, including non-small cell lung cancer.

27:25 And three, expand the population of cancer patients who will benefit from TIGIT by targeting all genetic polymorphic variants of this particular FC receptor. We describe this vulnerable population earlier and showed patients with the polymorphism experienced benefits from our SC engineers, agent 1181, including a complete response in patients with this polymorphism. We are actively advancing IND enabling activities to bring agent 1327 to the clinic early next year.

28:12 Importantly, TIGIT has also been implicated as an important target for overcoming resistance to anti-PD-1 therapy. Our bispecific TIGIT antibody, agent 1777, is designed to be used as monotherapy for tumors which are unresponsive to PD-1 antibodies. Agent 1777 is a first-in-class Tidget Bi-specific that leverages our internal multi-specific platform to co-target another inhibitor receptor not yet disclosed but also expressed on T cells and NK cells.

28:58 We discovered that co-targeting Tidget with this undisclosed target using our bi-specific approach provides superior immune activation as compared to the combination of mono-specific antibodies to the same target. This TIGIT bispecific approach, when used alone, has potent tumor-killing activity in a colon cancer model where PD-1 monotherapy is ineffective. Therefore, agent 1777 can be important therapy in PD-1 relapsed refractory tumors. While PD-1, PD-L1 antibodies have been a spectacular commercial success, only a small proportion of patients have had sustainable long-term benefit.

29:55 Therefore, there is a substantial need for therapies in patients who relapse or do not respond to PD-1 monotherapy. We expect to file an IND on Agents 1777 or Tidget I-specific by the end of 2020. There is growing conviction that Targeting Tidget will provide a breakthrough in IO, and we are uniquely positioned with two distinct molecules on track to be launched into clinical development as early as the first half of 2021. Now, I will turn the call over to Christine Klaskin to provide a financial update.

30:44 Thank you, Dawn. We ended the first quarter of 2020 with a cash balance of $92 million as compared to $62 million at December 31st, 2019. For the first quarter ending on March 31st, 2020, we reported a cash burn from our operations of $32 million. Net loss for the quarter was $45 million, or 31 cents per share, which included non-cash expenses of $16 million. We generated net income for the same period in 2019 of $17 million or 14 cents per share. In the first quarter of 2019, we recognized revenue of $80 million which included revenue related to the upfront license fee from our transaction with Gilead in addition to non-cash royalties earned.

31:40 For this same period in 2020, We recorded revenue of $15 million, primarily related to non-cash royalties earned. I'll now turn the call back to Garo to close.

31:54 Thank you, Christine, and thank you very much to the team who explained our current state of affairs and our prospects very well. Today, we are a company of 260 persons. but it's not the number that matters. We have capabilities to innovate, to develop, to manufacture our discoveries and we're currently building our commercial capabilities to become a fully integrated company. We have stressed all along speed and innovation are key in our business. Particularly a business that has Very, very exciting prospects going forward.

32:45 And Jen Buell talked about the fact that our external advisors have made comments about the fact that we may be the most innovative, productive company in the field of I.O. Now, we can all, of course, do these things because we have end-to-end capabilities from novel target discovery to full GMP manufacturing for anybody. This has been critical to our productivity. We have brought 14 new discoveries to the clinic and launched six clinical trials and we are gearing up to file our first BLA in the third quarter of this year.

33:33 We've developed our clinical operations team and delivered The full target accrual of our clinical trials in the last three years. And these may sound like trivial to some, but we have delivered 11 GMP manufactured batches for our own trials. The team there have done an absolutely terrific job. And as we've said before, we're continuing our operations with no interruptions. We have a queue of additional batches to manufacture this year. And as Burju said, we have launched a cell therapy company, Agentis, which designed a very unique allogeneic cell therapy approach. With the kind of advantages that we're talking about, for example, for COVID-19, it offers potentially the capability of being an antiviral therapy for anti-inflammation therapy all in one. And do this with a single cell source, which means it's an off-the-shelf cell therapy that drives cost Now, with all this, we've also talked about in the past that to date

35:12 we have generated over $540 million in cash from partnerships, collaborations, transactions with multiple pharmaceutical companies like Iliad, Merck, GSK, and Insight, as well as Urogen. and all in the last four years plus. And also importantly, we expect additional partnership transactions this year. We are in term sheet discussions with companies already. Now, I think even the fact that my colleagues have done a terrific job I will stop here and entertain any questions that you may have.

36:14 We will now begin the question and answer session. To ask a question, you may press star then one on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. At this time, we will pause momentarily to assemble our roster. Your first question comes from Matt Fitz from William Blair. Please go ahead. Hi, this is Hunter on for Matt. Just a couple of quick questions. I was wondering if you could provide some color on the unmentioned I think previously you had mentioned that with the lowest dose of 1181, you had a pending response, and I was just wondering if that was still pending or a confirmed non-response.

37:07 Thank you.

37:24 Okay, so let me just make a general comment and then I'll turn it over to Dan and then to Jen to address the 1181 question. But as some of you may know, we have a very sophisticated competitive intelligence capability at Agenis. And this has been a critical component of our decision making Our strategy that drives from research strategy onwards. So I had mentioned that we've been working on TIGIT for quite some time. But all along, we have evaluated what is happening with competitors out there in the TIGIT field and what is it that we can add incrementally or leapfrog the other programs so that we come up with an advantage, with a product that offers advantages to our company of course, but also importantly advantages to the patients.

38:28 And our TIGIT programs are specifically designed to address what is needed, what are the advantages we can provide. So Dan will answer your question more specifically now. Thank you for the question.

38:43 The second target, in our bispecific, which we have not yet disclosed, is a first-in-class target that is expressed on T cells and NK cells. What we have discovered is that the best way to target this first-in-class unidentified, which we have not yet disclosed target, is to do so in the form of a bispecific that includes TIGIT. Overall, what we have discovered is that when we co-target TIGIT and this yet to be identified receptor, we see superior activity as compared to that of model specific approaches to each of these targets. I would like to emphasize that the second target, which we have not yet disclosed, is a first in class target.

39:35 Thanks, Dan, and thanks, Hunter. Regarding 1181, we presented data on two different patients. Both of the responses have been confirmed by independent radiology review.

39:51 And also, I might add, they have been continuing. I think one of the hallmarks of immunotherapy for everybody is the benefit of having responses Last for a long time or convert to a curative outcome. And I think everything that we're seeing from our first generation products, Bally and Zally, to our second generation products so far, 1181, are indicative of lasting responses that may convert into a curative outcome. Next question, please. Your next question comes from . Just one moment while I open your line.

40:48 Your line is now live. Please go ahead. Thanks for taking my question. Congrats, team, on the progress. And I appreciate the efforts you're putting in on COVID-19. Just quickly on Valley Valley. On the BLA filings, could you just remind us, it seems like the clinical section is full. Are you just working on the non-clinical side? What are some of the other things you have to do if there's an FDA meeting before you're able to submit the BLA? Could you just remind us on the process?

41:20 Sure. Thanks very much, Mayan, for the question. Nice to hear you. Regarding the process, we're pursuing rolling submissions. which include meeting with the FDA to discuss different components of the filings. And what I'll share with you is that for elements like our manufacturing component, the quality, the agency has remarked on the quality of our manufacturing and the completeness of our prior interactions with them for INDs and otherwise. We have already engaged and discussed and are very confident in the completeness of a number of the modules, including manufacturing.

42:05 On the clinical side, we're continuing to collect data. We've completed accrual, and as you know, patients with refractory cervical cancer, if they are to progress, they do so in relatively short amount of time. So we'll have a good sense of our complete cohort. Very actively, and we're in the process of analyzing the data and readiness for the submission. So the interactions, we've had a series of interactions with the agency because we accelerated this program from a first-in-man study rapidly to a phase two expansion in refractory cervical cancer, at which point we met with the agency and we discussed our strategy and our trial designs. and now it's a matter of continuing to engage them to provide updates on each of our molecules, our pharmacology and non-clinicals, our manufacturing and clinicals.

43:02 And some of which have been completed and of course a couple of which are continuing to proceed until our filing date. And as Garo mentioned, we'll be filing in the second half of this year. Great. and then on 1181 about the recent advisory board meeting you had, could you just talk maybe qualitatively to the Sable disease that you're seeing? Are these in lung and colon cancers that is informing sort of your next choice to go into these bigger indications? Any color there would be great.

43:39 So my answer, I'll be thoughtful about my response here because we are anticipating some upcoming data presentations at major medical conferences. So what I will share with you are some, this is a solid tumor study and we have represented cancers that we've discussed with the advisory board and you see on the slide I presented today including lung and melanoma enrolled in the trial. We've seen activity beyond those indications as well, including other gynecologic cancers like ovarian, for example. An important case that will be described in much more detail soon is a gynecologic case with very long and durable disease stabilization.

44:28 You know, nearly a year, which is incredibly unusual for this highly refractory case. So this is disease stabilization that has not yet met the Rhesus criteria for a response, but looks really quite active. We're seeing some similar trends in other tumor types, disease stabilization in the majority of patients treated. And so you could... I'll leave it at that so that we don't restrict ourselves to what we can present at some upcoming conferences. And I understand and appreciate the qualitative color. And maybe just one final one on the COVID-19 efforts you have. I mean, it seems like you're nearing IMD acceptance.

45:14 So any color on how you're thinking to develop and what institutions, if you may, decided to partner with. Obviously, there are certain hotspots that could benefit from having a trial like this. So, any colors there?

45:32 Well, I think, Mayank, we need to first get signals from the clinic. And the objective of our first trial now is to see, to look at a whole bunch of blood markers for these patients and see how they respond to therapy in a dose escalation study. And so bear with us. I think it's premature for us to really determine what the next steps are going to be beyond this exploratory clinical trial. Oh, so to clarify that these are going to be non-severe COVID-19 initially patients? Right.

46:18 So Mayank, first on the hot spots, yes, the cells will be in the New York population. We have collaborators in important New York hospitals who have been at the front line of this. The cells, we will be exploring, because the cells can mitigate the virus and also dampen harmful inflammation, which in some cases patients experience after viral clearance. So there are two very important features. We will first explore the cells in a more severe setting. We will evaluate the persistence of the cells, of course, the activity of the cells in viral clearance, as well as in dampening harmful cytotoxic release syndrome, CRS.

47:09 Okay, great. And just one last thing on financials. I believe there were two different tranches of milestones you were anticipating, one Shingrix related and one progression of, I think, some pipeline molecules with Gilead. So in your revised guidance, any color on what you are seeing that might be addressed for the remainder of the year? Garo, maybe?

47:37 Okay, so as I mentioned, we have received the first tranche of the GSK-Shingrick's royalty milestone. So that's behind us. That's $15 million. There was a second tranche potentially due in the second half of this year, but given the guidance provided by GSK, which suggested a significant downtick in Shingrick's revenues going forward, it's unlikely that we will meet the revenue milestone, which would have driven the second tranche Thank you very much. Planning for no milestones. That doesn't mean we're not going to get them.

48:48 It just means that we want to be conservative and plan for no additional milestones for the balance of the year so that we can prudently manage our finances. And as I had mentioned, we have initiated $50 million or so annualized savings. which are already in place I might add and that will of course give us a little bit more comfort and then in terms of new potential collaborations we are in term sheet discussions with two separate parties and I expect that that will result in upfront cash payments that will help us manage our cash for the balance of the year and into next year.

49:46 Appreciate the color and looks like it will be a wash. Thank you.

49:51 Thank you very much. Any other questions? Okay. Well, that concludes our poll and I may want to turn this over to Sian who will do a stellar job of concluding remarks. Dan, would you end the conference? Thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.