Agenus - Earnings Call - Q1 2020

Transcript

Speaker 0

Good morning, ladies and gentlemen. Thank you for standing by, and welcome to the Agenus First Quarter twenty twenty Conference Call. At this time, all participants are in a listen only mode. After today's presentation, there will be an opportunity to ask questions. Please note this event is being recorded.

I would now like to turn the conference over to Doctor. Jennifer Buell, President and Chief Operating Officer of Agenus. Doctor. Buell, please go ahead.

Speaker 1

Thank you. Thank you, Stan. 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 projection. 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 Doctor. Garo Arman, Chairman and Chief Executive Officer doctor Dan Chand, head of drug discovery doctor Birju Yit, lead scientist for allogeneic iNKT cells and Christine Klaskin, our vice president of finance. I will now turn the call over to Garo.

Speaker 2

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 nineteen pandemic. I hope you and your families are safe and well. Our team at Agenus 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 priorities. We operate with approximately one third of the workforce on-site 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 60,000,000 in cash milestone payments for 2020.

As we have announced, we've already received 15,000,000 based on the sales of Shingrix, which has our QS-twenty one adjuvant in it. However, given the environment, the remaining 45,000,000 is uncertain because of the disruptions caused by COVID. And hence, we've taken measures to result in annualized cost savings of approximately $50,000,000. These savings are driven by reductions of both external and internal expenditures. And importantly, they will result in slowing down of 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. 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-four molecule eleven eighty one, about which you will hear much more from Doctor. Buell. Our advancing of iNKT cell therapy to the clinic for the treatment of cancer and COVID-nineteen patients that you will hear from Doctor. Burjew, 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.

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 Doctor. Jen Buell, our president and chief operating officer, to provide you with an update on our highest priority programs starting with AGEN1181, our multipurpose next gen CTLA four. Jen?

Speaker 1

Thank you very much, Garo, and hello, everyone. As Garo mentioned, I'll start by providing an update on AGEN eleven eighty one. 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 Gareth said, it's our multifunctional T cell antibody, which also binds to CTLA four.

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 fours, superior combinations with PD one, as you see on slide four, as well as important potential safety benefits, such as a reduction in endocrinopathies for patients treated. 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 four due to a genetic polymorphism that impacts about forty percent 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 AGEN eleven eighty one. We have also seen no endocrinopathies. None of the safety related side effects that we see with Yervoy related to hypothesitis or otherwise. Very important features. Fc engineering is something that we know to be really quite important.

We've published on this technology and our technique on our eleven eighty one, agent eleven eighty one molecule in cancer cell last year. We've also, as Dan will speak to you today, we've also engineered our TIGIT molecule in order to bring similar enhancements. We've shown you data that supports the benefit of this engineering, and we're also now seeing data from late stage clinical trials with a Fc engineered HER two antibody called margetuximab. You may be aware of some of that data. So on slide five, I'd like to summarize.

AGEN1181 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. 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-nineteen, and this could impact, of course, some clinical trials, as well as, you know, patient access, patients with cancer getting access to their therapies. However, in spite of this reality,

Speaker 3

we continue to accrue to our

Speaker 1

trial without interruption. Our principal investigators have informed us that based on the data available to date, AGEN eleven eighty one has life saving attributes that supports the continued enrollment of this trial. And today, we have a queue of patients waiting to be enrolled. Now you may remember, as I mentioned earlier, that AGEN1181 was deliberately designed to improve the efficacy and safety of first generation CTLA fours. In addition, this antibody is expected to expand the patient population who will benefit.

And now I'm gonna highlight some data that supports the design of this molecule and the activity that we're seeing. In our dose escalation trial, AGEN1181 alone and in combination with fostamatinib demonstrated a clinical benefit rate of seventy percent. This includes complete responses, partial responses, as well as disease stabilization of patients with late stage cancer. 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 has a genetic polymorphism in her CD 16 allele that rendered her unlikely to respond to a first generation CTLA-four. In spite of these negative odds, we are thrilled to see that this patient is a confirmed complete responder on AGEN1181 monotherapy at one mg per kg. 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 in 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 AGEN1181 in combination with balstilimab, our PD one antibody. If I can turn your attention now to slide seven. Last week, we convened with our advisory board.

Now this advisory board is comprised of top immuno oncology experts, some of whom are specialists in the CTLA four mechanism, some of whom were the first to dose patients with the first generation CTLA-four over twenty years ago. After an extensive review session, our advisors endorsed our accelerated development path for AGEN1181, 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 option available to these patients. These tumors are highly prevalent, or said differently, large cancer market, large commercial market opportunity.

These opportunities include PD-one refractory non small cell lung cancer, PD-one refractory melanoma, and microsatellite stable tumors like colorectal cancer, as well as endometrial, which are the two cases that I've 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 program, our PD-one program, valsilimab, which we call Vally, and our CTLA-four program, zalifrelimab, 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.

The data that we've presented now from our programs, balsilimab and valsilimab, are based on a large cohort of 55 patients who had a median of twelve months of follow-up. Importantly, 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 Agenus 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 twenty six percent. As a reference, Merck was granted accelerated approval for their PD-one antibody based on 11 responses in 77 patients, with a response rate of fourteen percent. As you can see here, our combination has the potential to become the most effective treatment available to patients with metastatic cervical cancer. And a few comments regarding cervical cancer patients and our plan. Cervical cancer is a horrifying disease, particularly for young women who come from economically disadvantaged backgrounds and have limited access to health care.

Patients are diagnosed and then treated with toxic chemotherapy, which has many difficult side effects and little clinical benefit. 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 bali xali, our PD-one and CTLA-four 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 balstilimab alone and in combination with zalifrelimab in relapsedrefractory or metastatic cervical cancer. We plan to submit our BLA filings this year, and we'll continue to keep you informed on our progress. Now I'm gonna 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 IO. I agree.

Speaker 3

Today, I'm

Speaker 1

joined by two of our lead scientists responsible for our next innovation expected to enter the clinic very soon. Doctor Dan Chan and Doctor Bourjou Yit are leading our TIGIT and our INKT programs respectively,

Speaker 2

who

Speaker 1

are joining us here to talk about these programs today. As you know, TIGIT is shaping up as a powerful combination partner with PD-one antibodies, especially in tumors expressing TIGIT. We've designed two different approaches to optimally target TIGIT. First, our SD engineered anti TIGIT antibody has outperformed all tested competitor antibodies and showed superior T cell activation when combined with PD-one or LAG-three antagonists. And our TIGIT bispecific molecule, AGEN1777, which has demonstrated potent tumor killing as a monotherapy and difficult to treat cancers where PD-one 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 nineteen. 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. Raju 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.

Raju?

Speaker 3

Thank you, Gao and Jen. So invariant natural killer T cells, short 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 nineteen. 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. 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 kill cancer without requiring genetic manipulation. So employing iNKTs in an unmodified form, patients can receive the treatment quickly and at a significantly lower cost. And third, iNKTs are expected to target SARS CoV two and cells infected with the virus.

INKT should be agnostic to mutations of the current strain and other coronaviruses. While severe complications of SARS code two infection are characterized by a life threatening respiratory disorder and other organ failure, our allogeneic INKT therapy, agent seven ninety seven, 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. 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 nineteen.

Agent seven ninety seven could also promote long term immunity against COVID nineteen, 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 I and K T cells from a single donor are manufacturable and scalable. 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 eight thousand seven hundred ninety seven in cancer and infectious disease, we are ready to quickly design optimal combinations with our cell therapy and checkpoint antibody.

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, John Chan, to discuss our TIGIT program.

Speaker 4

Thank you, Virgil, and hello, everyone. Today, I'm excited to discuss two of our TIGIT antibody, 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 p d one antibodies, especially in tumors expressing TIGIT. Our portfolio of TIGIT targeting antibodies includes an Fc enhanced TIGIT monospecific, AGEN thirteen twenty seven, and our TIGIT bispecific, AGEN seventeen seventy seven. 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. TIGIT 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. TIGIT is overexpressed in multiple tumors and is known to be a key player in driving resistance to anti p d one.

And as a result, tumors grow. Blocking TIGIT with antibodies, like our monospecific TIGIT antibody, agent thirteen twenty seven, or or a TIGIT bispecific, agent seventeen seventy seven unleashes important immune cells such as T cells and NK cells to kill many types of cancer. Agenus was the first to discover and report in cancer cell and at AACR in 2019 that TIGIT antibodies require Fc gamma receptor coengagement to promote optimal T cell activity against tumors. Overtigit, AGEN thirteen twenty seven, is engineered with this Fc enhancement and has outperformed all tested competitor antibodies and showed superior T cell activation when combined with p d one or LAG three antagonist or OX 40 or CD one thirty seven agonist. We presented this data at AACR two thousand nineteen.

Our TIGIT is an ideal combination partner for addressing nonresistance mechanisms to current checkpoint therapy and with the potential to provide deeper responses. In addition to superior function demonstrated against tested competitors, our molecule is designed to, one, maximize antitumor activity, like the robust activity observed with our Fc engineered AGEN eleven eighty one that has already shown remarkable activity in early clinical trials. Our preclinical data with our TIGIT also showed superior tumor killing compared to competitor molecules as seen on slide 11. Two, be an optimal combination partner for anti p d one antibodies for more tumor potent tumor killing, particularly for TIGIT expressing tumors, including non small cell lung cancer. 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 described this vulnerable population earlier and showed patients with a polymorphism experienced benefit from our Fc engineered AGEN1181, including a complete response in patients with this polymorphism. We are actively advancing IND enabling activities to bring AGEN thirteen twenty seven to the clinic early next year. Importantly, TIGIT has also been implicated as an important target for overcoming resistance to anti p d one therapy. Our bispecific TIGIT antibody, AGEN seventeen seventy seven, is designed to be used as monotherapy for tumors which are unresponsive to p d one antibody. AGEN seventeen seventy seven is a first in class TIGIT bispecific that leverages our internal multispecific platform to co target another inhibitor receptor not yet disclosed, but also expressed on T cells and NK cells.

We discovered that co targeting TIGIT with this undisclosed target using our bispecific 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 one monotherapy is ineffective. Therefore, AGEN seventeen seventy seven can be important therapy in p d one relapsedrefractory tumors. While PD one, PD L one antibodies have been a spectacular commercial success, only a small proportion of patients have had sustainable long term benefit. Therefore, there's a substantial need for therapies in patients who relapse or do not respond to PD one monotherapy.

We expect to file an IND on AGEN seventeen seventy seven or TIGIT bispecific by the 2020. There is growing conviction that targeting TIGIT 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 2021. Now I will turn the call over to Christine Klaskin to provide a financial update.

Speaker 3

Thank you, Dom.

Speaker 5

We ended the 2020 with a cash balance of $92,000,000 as compared to $62,000,000 at December 3139. For the first quarter ending on 03/31/2020, we reported a cash burn from our operations of $32,000,000 Net loss for the quarter was $45,000,000 or $0.31 per share, which included non cash expenses of $16,000,000 We generated net income for the same period in 2019 of $17,000,000 or $0.14 per share. In the 2019, we recognized revenue of $80,000,000 which included revenue related to the upfront license fee from our transaction with Gilead in addition to non cash royalties earned. For this same period in 2020, we recorded revenue of $15,000,000 primarily related to non cash royalties earned. I'll now turn the call back to Garo to close.

Speaker 2

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 two sixty persons, But it's not the number that matters. We have capabilities to innovate, to develop, to manufacture our discoveries, and that 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. 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 IO.

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 antibodies. 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. We've developed operations team and delivered the full target accrual of our clinical trials in the last two years.

And these may sound like trivial to some, but we have delivered 11 GMP manufactured batches for our own trials and partnered programs at our manufacturing site at Agenus West. And the team there have done an absolutely terrific job. And as we've said before, we're continuing operations with no interruptions. We have a queue of additional batches to manufacture this year. And as Burjoo said, we have launched a cell therapy company, AgenTus, which designed a very unique allogeneic cell therapy approach with the kind of advantages that we're talking about.

For example, for COVID-nineteen, 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 costs down. And most importantly, it drives the speed of patient availability up. Now, with all of this, we've also talked about in the past that to date, we have generated over $540,000,000 in cash from partnerships, collaborations, transactions with multiple pharmaceutical companies like Gilead, 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 given the fact that my colleagues have done a terrific job of keeping you abreast of everything that is going on, I will stop here and entertain any questions that you may have.

Speaker 0

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, Your first question comes from Matt Sipps from William Blair.

Speaker 6

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 part of the TIGIT bispecific. I know you didn't mention specifically what the other part was, but maybe sort of the mechanism that you're targeting there.

And then just a follow-up, I think previously you had mentioned that with the lowest dose of eleven eighty one, you had a pending response. And I was just wondering if that was still pending or a confirmed non response. Thank you.

Speaker 2

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 eleven eighty one question. But as some of you may know, we have a very sophisticated competitive intelligence capability at Agenus. 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. 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, Matt.

Speaker 4

Thank you for the question. 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 monospecific 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.

Speaker 1

Thanks, Dan, and thanks Hunter. Regarding eleven eighty one, we presented data on two different patients, both of the responses have been confirmed by independent radiology review.

Speaker 2

And also, might add, they have been continuing. Think it's 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, eleven eighty one, are indicative of lasting responses that may convert into a curative outcome. Next question, please. Your

Speaker 0

next question comes from Mayank Min. Sammy? Just one moment while I open your line. Your line is now live. Please go ahead.

Speaker 7

Thanks for taking my question. Congrats team on the progress, and appreciate the efforts you're putting in on COVID nineteen. Just quickly on Zali Valley. On the BLA filings, could you just remind us it seems like the clinical section is is full. Like, are you just working on the nonclinical side?

Like, 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?

Speaker 1

Sure. Thanks very much, Mayan, for the question. Nice to hear you. Regarding process, so 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 the agency has remarked on the quality of our 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. 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 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 our strategy and our trial design. And now it's a matter of continuing to engage them to provide updates on each of our molecules, our pharmacology and nonclinical, our manufacturing and clinical. Those, some of which have been completed, and, of course, a couple of which are continuing to to proceed until our filing date. And as Garo mentioned, we'll be filing in the second half of this year.

Speaker 7

Great. And then on one one eight one about the recent advisory board meeting you had. Could could you just talk maybe qualitatively to the stable disease that you're seeing? Are these in lung and colon cancers that that is informing sort of your next choice to go into these these bigger indications? Any color there would be great.

Speaker 1

So, Mayans, 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 slides I presented today, including lung and melanoma enrolled in the trial. And 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, 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 RECIST 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, you know, I'll leave it at that so that we don't restrict ourselves to what we can present at some upcoming conferences.

Speaker 7

And I understand and appreciate the qualitative color. And and maybe just one final one on the COVID nineteen efforts you have. I mean, the it seems like you're nearing IND acceptance. So any color on how you're thinking to develop, and what institutions that you may, decide to partner with? Obviously, there are certain hot hotspots that are that could benefit from having a trial like this.

So any color there?

Speaker 2

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 of 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 the, this exploratory clinical trial.

Speaker 7

Oh, so to clarify that these are going to be non severe COVID nineteen initially patients?

Speaker 1

So Mayank, first, on the hotspots, yes, be the cells will be in the New York population. We have collaborators and important, New York hospitals who have been at the frontline 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 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.

Speaker 7

Okay. Great. And 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, Daryl?

Speaker 2

So as I mentioned, we have received the first tranche of the GSK Shingrix royalty milestone. So that's behind us, that's $15,000,000 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 Shingrix revenues going forward, it's unlikely that we will meet the revenue milestone, which would have driven the second payment for us. So that's one. Now, additionally, there are two sets of milestone payments that we were contemplating from two separate companies.

And what we've done is have a more conservative posture and say we have no control over the timing of the clinical trials associated with, either one of these situations. So we're planning for no milestones. Now that doesn't mean we're not gonna get them. 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, $50,000,000 worth of 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.

Speaker 7

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

Speaker 2

Thank you very much. Any other questions? Okay. Well, that concludes our, call. And I may, want to turn this over to Stan who will do a stellar job of concluding remarks.

Dan, would you end the conference?

Speaker 0

Thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.