Q4 2023 Nektar Therapeutics Earnings Call
Participants
Vivian Wu; Director, IR; Nektar Therapeutics
Howard Robin; President & CEO; Nektar Therapeutics
Jonathan Zalevsky; Chief Research and Development Officer; Nektar Therapeutics
Sandra Gardiner; CFO; Nektar Therapeutics
Mary Tagliaferri; Chief Medical Officer; Nektar Therapeutics
Jessica Fye; Analyst; JPMorgan Chase & Co.
Julian Harrison; Analyst; BTIG Research
Andy Hsieh; Analyst; William Blair & Company
Presentation
Operator
Good day, and thank you for standing by, and welcome to the Nektar Therapeutics Fourth Quarter 2023 financial results conference call. (Operator Instructions) Once again, please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Vivian Wu. Please go ahead.
Vivian Wu
Thank you, Crystal, and good afternoon, everyone. Thank you for joining us today. With us on the call are Howard Robin, our President and CEO; Dr. Jonathan Zalevsky, our Chief of Research and Development; Dr. Mary Tagliaferri, our Chief Medical Officer; Sandra Gardiner, our Chief Financial Officer; and Jennifer Ruddock, our Chief Business Officer.
On today's call, we expect to make forward-looking statements regarding our business, including statements regarding the therapeutic potential of future development candidates and programs. The timing of the initiation of clinical studies and the availability of clinical data for drug candidates, the timing and plans for future clinical data presentations, the formation and future development plans or success of our agreement expectations following our corporate restructuring and reorganization, financial guidance and certain other statements regarding the future of our business.
Because forward-looking statements relate to the future, they're subject to uncertainties and risks that are difficult to predict, many of which are outside of our control. Our actual results may differ materially from these statements. Important risks and uncertainties are set forth in our Form 10-Q that was filed on November 8, 2023, which is available at sec.gov. We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments or otherwise. A webcast of this call will be available on the IR page of Nektar's website at arqule.
With that said, I would like to hand the call over to our President and CEO, Howard Robin. Howard?
Howard Robin
Thank you, Vivian, and thank you for all joining us today. 2023 was a pivotal year for Nektar, we refocused the company's development pipeline on immunology and inflammation with our primary near term goal to advance rest bags to meaningful data catalysts in the first half of 2025.
REZPEG is poised to be highly disruptive in the biologic treatment landscape for atopic dermatitis by offering a novel agonistic mechanism as peg is designed to both dampen the inflammatory response and simultaneously restore immune balance by directly expanding functional T-reg cells and engaging multiple immuno regulatory pathways in patients with atopic dermatitis and other autoimmune disorders through a unique mechanism.
REZPEG also has the potential to provide patients with superior efficacy as well as more favorable infrequent dosing. There are over 30 million people in the US alone battling this chronic skin condition and it can greatly impact quality of life and mental health for these patients.
We made significant advancements advancements in 2023 with respect to our recipe program, most notably we regain the full rights to respect from Eli Lilly and now own the program 100% with no encumbrances. We move to quickly design the Phase IIb study in atopic dermatitis based on the promising results from the Phase Ib placebo-controlled randomized study of red bag, which showed an 83% drop in eczema skin scores after just 12 weeks of treatment.
Our Phase IIb global study in this indication was launched in October of '23, and enrollment is on track for data readout in the first half of '25. In late 2023, we also began work designing a Phase IIb study in alopecia areata, another area of high unmet need for studies. Starting this month, there are approximately 7 million patients in the United States and 160 million people worldwide who have alopecia areata.
JAK inhibitors are the primary treatment option for patients with alopecia, but have a significant rebound effect with treatment cessation and several black-box warning based on the data we generated to date on red bag in the skin related autoimmune condition of atopic dermatitis, psoriasis and in patients with cutaneous manifestations of lupus. We believe red peg has strong scientific rationale in the setting of alopecia. It could have the potential to be a highly differentiated treatment option with a similar remit of effect for this underserved patient population.
As I stated earlier, we look forward to the Phase IIb data for our atopic dermatitis study and for our alopecia study in the first half of 2025. These will be highly meaningful data catalysts for Nektar.
In addition to respect, we have another important immunology program that we're moving towards the clinic. This is a first-in-class differentiated mechanism and immunology, a TNFR2 agonist antibody, NKTR-165. TNFR2 has been shown to potentiate the suppressive effects and overall functional properties of T regs in the program is built on what we've learned through our deep experience with Red Peg and the direct field and represents a promising mechanism for treatment of autoimmune diseases, including multiple sclerosis and ulcerative colitis.
We're currently conducting IND-enabling studies with the goal of targeting an IND submission in the first half of next year in line with our objectives to advance our immunology pipeline. Today, we announced a $30 million financing that further bolsters Vector's financial position as we head into transformative data cutoff. Importantly, we're pleased to bring on a new, high-quality, long-term investor TCG crossover, who clearly shares our belief in the potential of REZPEG. At a price of $1.20 per share, the transaction represents a premium of over 80% connectors 30 days. This puts us in a strong financial position and extends our cash runway from our previous guidance, which was the middle of 2026 to now well into the third quarter of 2026.
And with that, I'll hand the call over to JZ for an R&D discussion.
Jonathan Zalevsky
Thank you, Howard. Let's begin today with REZPEG, which is the most advanced IL-2 based T-regs mechanism in the field across the rest peg studies that have been conducted to date, we have observed a consistent and highly predictable clinical pharmacology profile with respect to target engagement as well as the peak and duration of T-reg mobilization. It has demonstrated a well-tolerated safety profile and clear clinical efficacy in atopic dermatitis and also psoriasis and in patients with cutaneous manifestations of lupus. Our deep experience with respect to date across the totality of the clinical program gives us conviction in our ongoing Phase IIb studies in atopic dermatitis and alopecia areata. Specifically in atopic dermatitis, there are three important issues that patients with this disease continue to face.
First, there is a need for great efficacy, specifically a deeper magnitude of response and rapid onset of treatment. Second, patients like durable responses and therapy free remission. Once current therapies or discontinued patients rebound rapidly. And third, treatments with favorable safety profiles are lacking. This is especially important given the chronic nature of the disease and the need for continuous dose. We believe there are major opportunities in this disease state that the differentiated profile of REZPEG could potentially address diving into our Phase Ib data in atopic dermatitis.
Through the 12-week induction period, REZPEG demonstrated dose-dependent efficacy across both physician assessed, and patient reported efficacy measurements, reaching statistical significance across many of these measures. At the highest dose level, REZPEG demonstrated a very rapid onset of response with over 40% of patients achieving easy 75 by week three after only two doses of REZPEG. This rapid onset of action rivals that of JAK inhibitors, which have outperformed to pull them out of this parameter.
At the end of the induction period of 12 weeks, we observed a profound magnitude of efficacy and 83% reduction in percent change from baseline, easy score with the highest dose. This is the largest magnitude of change that we've seen for a biologic and outside of one JAK inhibitor Importantly, we are encouraged by the extended durability seen for REZPEG. Long after the completion of the 12-week induction period, many patients maintained durable disease control for an additional 36 weeks after the end of dosing.
And this type of extended disease control after the end of dosing is not observed for daclizumab or for JAK inhibitor. Durability of the EZ 75 response was observed with approximately 70% of the EZ75 responders, maintaining that response for 36 weeks after the end of the 12-week induction period. This is a very exciting result and suggested REZPEG has the potential to be the first re-bid of therapy for atopic dermatitis.
For both patient reported outcomes and physician assessed endpoints, we observed the same trend rapid onset of effect dose-dependent and long durability of control. Additionally, REZPEG was well tolerated and treat them with respect did not induce antidrug antibodies in patients which has been reported that some examples of the IL-2 mutant class. These promising data have us and KOLs very enthusiastic about the potential for long lasting responses and in frequent maintenance dosing.
With respect in the setting of atopic dermatitis. In October 2023, we initiated the Phase IIb study of REZPEG biologic naive atopic dermatitis patients and enrollment is well underway. Our goal is to enroll roughly 400 patients with three different regimens of REZPEG versus placebo evaluated over a 16-week induction period. After the induction period, patients that meet the threshold to advance from induction to maintenance will be re-randomized into one or two maintenance regimen at different dosages at either once a month or once-every-three-month dosing. And that schedule will continue for another 28 weeks. Our enrollment for this study is on track, and we expect data in the first half of 2025.
Moving to alopecia areata, we believe REZPEG has strong scientific rationale in this indication. Alopecia areata is also a disease of the skin where your immune system starts to attack the hair follicle, thereby weakening the ability of stem cells to grow hair with prolonged immune attack. This eventually causes that hair follicle to release the hair altogether leading to Apache hair loss. And as the disease progresses to Boulder, biologically speaking, red bag through its central pathway of T-reg rescue, which is uniquely poised to address the diversity of immunohematology, providing broad potential for targeting multiple dermal diseases, including alopecia, for example, in alopecia.
There are almost no immune cells in normal hair follicles, meaning the hair follicle is in immune privileged tissue. T-regs are very important in maintaining that immune privilege and people with alopecia areata, develop a breakdown for that immune privilege space. We think the T-regs mechanism of rice pay can restore immune privilege and could provide durable disease control, which we believe would be game-changing in this indication. Jacque inhibitors are the only agents approved in alopecia and they do not provide disease durability after a patient discontinued treatment with JAK inhibitors.
It can take a patient anywhere from 9 to 18 months to grow hair. And once a patient starts taking a JAK inhibitor, which may happen for a variety of reasons, including toxicity, their hair falls out again rapidly. There is a high unmet need in this patient population for tolerable treatment options that provide durable response. And we believe that restoration of immune privilege is key to obtain durability. For these reasons, we believe there's an opportunity for Westpac to become a novel biologic therapy and alopecia areata.
We are initiating a Phase 2b study of REZPEG in alopecia. This the Phase IIb study plans to recruit roughly 80 patients with severe to very severe alopecia who will be randomized to REZPEG or placebo. Patients will be treated for a period of 36 weeks and observed up to 60 weeks in total. Our primary endpoint for this study is the mean percent improvement in SALT for the Severity of Alopecia Tool at week 36, which is the validated outcome measure used for regulatory approval. We will also be looking at a number of other secondary endpoints, including proportion of patients who saw a reduction.
Now turning to NLTR0165, our TNFR2 agonist antibody. TNFR2 is highly expressed on T-regs myeloid suppressor cells, regulatory B cells, neuronal cells and others. And TNFR2 agonism has been shown to potentiate the suppressive effect and overall functional properties of T-regs. And these other suppressive cell populations. If TNFR2 is absent it is associated with autoimmunity and other genetic conditions that resemble FoxP three loss of function.
In contrast, its presence has been associated with immuno regulatory function and protective effects for multiple cell populations and tissues in the body. This TNFR2agonist program in our pipeline is built upon many years of direct experience gained from REZPEG. For example, we know that essential T-regs such as timing T regs require substantial checks that signal that is physiologically provided by the IL-2 receptor pathway. And this is essential theme and the mechanism of action of REZPEG.
In contrast, T-regs that leave the central compartment and infiltrate the distal organs and tissues, they are less dependent on the jacks that pathway and instead shift their reliance onto NF-kappa B pathway engagement for their maintenance of suppressive function.
TNFR2 is the most abundant TNF superfamily member expressed on T-regs and the key driver of NF-kappa B signaling and those dots and consequently, a bona fide TNFR2 agonist would be an incredibly exciting addition to our pipeline. Examples of indications that could be addressed by TNFR2 agonism include multiple sclerosis, mucosal immunology conditions such as alternative colitis of the GI or other oral mucosal diseases and even dermal autoimmune diseases like vitiligo, we have identified several the TNFR2 two antibody programs from an artificial intelligence-based antibody discovery campaign with our partner biologic design.
The lead antibody is called NKTR0165, and it has highly desirable properties, including exquisite TNFR2, selectivity, TNFR2 agonism and primary human cells activity in multiple preclinical efficacy models and a very well tolerated profile and early non-GLP toxicology. We have developed a manufacturing cell line for Lilly and are conducting upstream and downstream process development with the aim to enter the clinic for this program in the first half of 2025.
Later this year, we plan to present the first preclinical data of NKTR0165 at an upcoming medical conference. As we move forward with our IND-enabling studies, there is growing interest for a novel selective TNFR2 agonist like NKTR0165. And thus, we remain open to the opportunity of working with companies that have interest in these areas to strategize on the best path forward.
Now let's switch gears to our IL-15 based oncology program, NKTR255. NKTR255 is IL-15 based mechanism of action holds great promise as a combination agent with cell therapies and other mechanisms such as checkpoint inhibitors. And we are exploring the best partnering paths for continued development for this drug candidate.
Our Nectar sponsored trial combining NKTR255 with the approved CD19 CAR-T use Breyanzi and use Karta for treatment of patients with large B-cell lymphoma has enrolled 15 patients in the dose escalation portion of the study combination of NKTR255 in Breyanzi is also being studied in a separate investigator-sponsored trial at Fred Hutch. We are targeting the potential submission of data from these studies at medical meetings in the second half of this year.
A clinical trial in non-small cell lung cancer sponsored and funded by April data, which evaluates the combination enables that as tumor infiltrating lymphocytes cell therapy plus NKTR255 and checkpoint inhibitor is also ongoing and enrolling patients. And with our partner, Merck KGA, we have also been evaluating NKTR255 in combination with Philadelphia versus single agent Bavencio in the Phase two JAVELIN bladder memory study. And that study is on track to potentially report interim PFS data later this year. And with that, I will turn the call over to Sandy for a review of our financial guidance. Sandy?
Sandra Gardiner
Thank you, JZ, and good afternoon, everyone. We ended the year in a very strong financial position with $329.4 million in cash and investments and with no debt on our balance sheet. As Howard stated earlier, today's announcement of a $30 million financing further strengthens our cash position. Our revenue was $23.9 million for the fourth quarter of 2023 and $90.1 million for the full year of 2023.
Our operating costs and expenses for the fourth quarter of 2023 were $57.4 million and $353.8 million for the full year 2023. Our nonoperating expenses for the fourth quarter of 2023 were $8.6 million and $12.6 million for the full year 2023.
Q4 2023 included a non-cash charge of $6.1 million or $0.03 per share for the reclassification of the foreign currency translation adjustment to income related to the wind-down of our India legal entity. As a reminder, our India facility was sold in December 2022 for approximately $12 million with the wind-down of the entity occurring in 2023.
Our net loss for the fourth quarter of 2023 was $42.1 million or $0.22 per share. For the full year of 2023, our net loss was $276.1 million or $1.45 per share, excluding $111.8 million in noncash goodwill and other impairment charges. Net loss on a non-GAAP basis for the full year 2023 was $164.3 million or $0.86 basic and diluted loss per share.
Looking forward to 2024 and beyond, our financial position remains strong in part, reflecting the cost savings initiatives we undertook last year. We plan to end 2024 with $200 million to $225 million in cash and investments. In addition to the $30 million pipe we announced this morning, our 2024, our cash guidance also includes [$15 million], resulting from an amendment executed today on a former 2020 agreement with certain entities of health care royalty.
Our cash runway now still extends well into the third quarter of 2026, which will take us through key value-generating milestones, including Phase two risk take data in a topic, dermatitis and alopecia areata. Our revenue for the full year of 2024 is expected to be between $75 million and $85 million, which includes $55 million to $65 million in noncash royalties and $20 million to $25 million in product sales.
We anticipate full year R&D expense will range between $120 million and $130 million dollars. This includes approximately $5 million to $10 million of noncash depreciation and stock-based compensation. The increase in R&D spend for 2024 over 2023 represents an increased investment into red bag Phase IIb studies in atopic dermatitis and alopecia areata as well as IND enabling studies for our antibody program, NKTR0165. This increase is partially offset by decreased spending on NKTR0255 clinical studies and cell therapy, which are completing in 2024.
The remaining ongoing clinical studies for NKTR255 are primarily funded by our external partners. We expect G&A expense for the full year of 2024 to be between $70 million and $75 million, which includes $5 million to $10 million of noncash depreciation and stock-based compensation expense.
Our full year non-cash interest expense is expected to be between $20 million and $25 million. As I stated earlier, we expect to end this year with $200 million to $225 million in cash and investments. And with that, we will now open the call for questions. Crystal?
Question and Answer Session
Operator
(Operator Instructions) Jay Olson, OpCo.
Oh, hey, this is John on the line for Jay. Thank you for taking the question and congrats on the progress. And maybe just a REZPEG 80 study. I'm wondering if you can talk about the initial feedback from doctors and patients participating in the study are especially in a context that there are many other competing trials out there? And also if you also could comment on the recruitment progress thus far versus your internal expectation, that will be great. And I have a quick follow-up question after that.
Howard Robin
Mary, you want to take that question?
Mary Tagliaferri
Yes, sure, Howard. Thank you. Hi, Joe. This is Mary Tagliaferri here. When we look at the aggregate data from site activation screening activities and enrollment, we are on track to have our top line induction data from the IDE study in the first half of 2025. And in terms of the feedback, we're really pleased with the type of screening we're seeing and we believe this is driven by the data that was presented by Jonathan Silverberg as the APB. 2023 to the doctors really do see that one ReadyTech has a very rapid onset of action.
Number two, the depth of response that was seen with the mean percent change in easy after only 12 weeks of treatment. When most studies looking at the induction period of 16 weeks for doctors have been very impressed with. And then certainly for the benefit of their patients, they really love the durability that we saw when patients were off treatment for nine consecutive months and they were able to maintain that very deep response and easy. This is all very, very attractive for recruiting for the study. So we're doing very well. I have heard on that other side there. It's with enrollment and we're not experiencing that.
Got it. Thank you. And just a quick follow-up. I'm just wondering to what extent you can leverage the clinical sites for the AD study for the upcoming alopecia areata initiation. So can you just use the same sites or are there some other a layer of working to do?
Mary Tagliaferri
So we are going to use 12 sites that are participating in the AD study in our alopecia study. And those physicians are very excited to have an opportunity for a second skin disease to evaluate risk pick in alopecia areata. And again, they're really eager to see and durability of response because, of course, when they treat their patients with Check inhibitors, and the growth back phone immediately. They start to lose their hair once they discontinue treatment with the JAK inhibitor. So the promise have an age of durability and restore immune privilege is definitely really encouraging and exciting to that since I've been speaking to that.
Operator
Roger Song, Jefferies.
Hi team. This is Kambiz on for Roger, on maybe just following up on the alopecia areata study on how many total clinical sites will be enrolling and what's kind of the geographic distribution of those sites and then what are some key baseline characteristics for the patients in those studies will be on most of them be a JAK inhibitor refractory on any detail there would be appreciated. (multiple speakers)
Mary Tagliaferri
Yeah, thanks, Howard. We have slightly over [30 sites]. We're going to be in Canada in the United States and in Poland from you as you may imagine when you're in Poland, they definitely have an access issue. And also it takes a very long time for those patients to get into see a dermatologist. So it's actually a very favorable environment to enroll patients. These patients on are going to be JAK inhibitor naive patients. And then our key inclusion criteria is severe to very severe alopecia and so these patients all have to have a salt greater than or equal to 50. And of course, this is the same patient population where baricitinib endoleaks jacket and into Pfizer's JAK inhibitor and eligibility criteria for their pivotal trial.
Operator
Jessica Fye, JPMorgan.
Jessica Fye
For the Phase IIb atopic derm trial, what's the threshold efficiencies need to be considered a responder and be randomized at week 16? And then also curious, what's your latest thinking on whether the agency or the alopecia trial will readout first and why?
Mary Tagliaferri
Yes, Hi, Jessica. It's Mary. So to be re-randomized, the patient has to have EC 50s, four of when they are rebranded to the maintenance. And once a month or once every three months, they will be on the same dose that they were randomized to in the induction period and you have a second question?
Jessica Fye
Just the timing of alopecia versus AD data?
Mary Tagliaferri
Yes. So we expect the AD trial read out first.
Operator
Julian Harrison, BTIG.
Julian Harrison
Hi. Congrats on the progress and thank you for taking my questions on. I'm curious if you could remind us how you're thinking about efficacy beyond 12 weeks of dosing with breast peg in the atopic derm. How do you expect to plateau at some point? Or do you expect response rates to maybe be progressive through 44 weeks of dosing.
And then with regards to the Lilly litigation, sorry if I miss it, I'm wondering if you could comment on its current status and timing of next steps?
Howard Robin
Mary why don't you take the first part and I'll take the second part?
Mary Tagliaferri
Yes, you know, I definitely think that as we have extend our induction period from 12 to 16 weeks, we're going to see a greater number of patients experienced a deeper response. And so I very much look forward to seeing what the mean percent changes. As you know, the mean percent change from baseline to 12 weeks was 83%. And as such, greater than any other biologic agents, if you look at UP or odd per year, lebri or Maemo are Roca. We definitely saw the deepest response, but I do believe that we'll probably see more patients who experience the EC75 and even [EC9], as we go out four weeks in the induction period.
Howard Robin
With regard to Lilly Lilly, after after we filed our complaint in federal courts, Lilly tried to convince the federal court judge dismissed the case. As you know, and last week, the federal judge refused Lilly's request and the judge agreed to allow Nicolas claims primary claims to move forward, and we expect the judge to set a trial date in 2025. The court also ordered the parties to engage in mediation within the next three months to tried to resolve the issue. And so we're very, very happy the cases moving forward. The judge did not dismiss the case, and we look forward to indicating ourselves through the litigation process Excellent.
Operator
Andy Hsieh, William Blair.
Andy Hsieh
I have two quick ones for us. One is can you talk about this ebbs and flow dynamic of associate with hair loss and alopecia, would you be enrolling kind of severe and really severe patients kind of mitigate that variability? And the second question has to do with the TNF receptor 165 program and we know that the receptor family is a trimer. So I guess to maximally agonize this receptor, you might have to have like a like a trimer design. I'm just curious if that's kind of a part of the design that goes into clone 165 and downstream from there, there's also kind of clustering. So is that also a part of the design of the molecule?
Sandra Gardiner
Mary, do you want to take the hair loss and then JZ can take the TNF one?
Mary Tagliaferri
So, hi, Andy, it's Mary. So you're exactly right. Once patients go into the severe and very severe, generally speaking, there is not a regrowth of hair and that you're exactly right, but that's why the eligibility criteria and even for the threshold for approval by the FDA is this patient and it does patients to start out with some experience, the catchy hair loss. But as the disease progresses, certainly the hair becomes more extreme and even towards baldness. But once a patient loses their hair, it's very soon or they tend to have regrowth of their hair without some sort of medical intervention and an old pass over the second question to Jay.
Jonathan Zalevsky
Thanks, Mary, and thanks, Andy, for your question. So you are right to TNF proteins or drivers. But as we've learned more and more about the biophysics of the receptors and the way the plot domains, right, which are the cystine which domains I hold together the receptor subunits, they actually work to create dimers receptors. And then a trimer comes along and clusters, six receptors or three pairs of dimers.
So and then you can get additional clustering and some of this ultra structure has been published and some structural studies have been done well, we've come to understand a through learning about the cell biology of these receptors. The way these divers, the TIL multiple arise. And the way the apoptosis for binding to the receptor to work is that the epitope is actually fundamentally important.
One of the things we discovered with NKTR0165 is that it's an episode that has its own unique properties and it can signal in a completely cluster independent fashion. For example, it doesn't need FC. It doesn't even these balances. That's one of the things that's really unique and highly differentiated about the antibodies that we've created and keeping in mind all of these ultra structural forms of the receptor and then the different states that the receptor can occupies is obviously one of the key things that's important for developing a success.
Operator
And I am showing no further questions from the phone lines. And I'd like to turn the conference back over to Howard Robin for any closing remark.
Howard Robin
I will say thank you, everyone, for joining us today. And as we stated on our call, we really remain focused on executing the development of REZPEG in our immunology focus research programs. I'd like to thank all of our employees for their very hard work and thank all of our shareholders, new and existing for their continued support. And we look forward to providing you with updates on our progress. So stay tuned, and thanks for joining us again.
Operator
Thank you. This concludes today's conference call. Thank you for your participation. You may now disconnect, and everyone have a wonderful day.
