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spk27: Good day, and thank you for standing by. Welcome to the Alana's Therapeutics third quarter 2022 financial results conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you'll need to press star 1 1 on your telephone. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Alex Lobo, with Stern Investor Relations. Please go ahead.
spk24: Thank you. Good morning, and welcome to the Alanos Therapeutics third quarter 2022 financial results conference call and audio webcast. Please note that today's webcast contains slides, which are available through the audio webcasting platform. A copy of the presentation will be available on our website after today's call. Earlier this morning, Alanos issued a press release announcing financial results for the three months ended September 30th, 2022. We encourage everyone to read today's press release, as well as the Alanos quarterly report on Form 10-Q for the quarter ended September 30th, 2022, which was filed this morning with the SEC. The company's press release and quarterly report will also be available on the Alanos website at alanos.com. In addition, this conference call is being webcast through the investor relations section of the company's website and will be archived there for future reference. Please note that certain information discussed on today's call covered under the safe harbor provisions of the private securities litigation reform act of 1995. Participants are cautioned that this conference call contains time sensitive information that is accurate only as of the date of this live broadcast, November 14th, 2022. Actual results could differ materially from those stated or implied by forward-looking statements made on today's call due to risks and uncertainties associated with the company's business. Information on potential risks and uncertainties are set forth in our most recent public filings with the SEC at sec.gov. The company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this live webcast. except it may be required by applicable securities law. With me today are Kevin Boyle Sr., Chief Executive Officer, Abhi Srivastava, Vice President of Technical Operations, Drew Denneker, Vice President of Research and Development, and Mike Wong, Vice President of Finance. With that said, I would like to turn the call over to Kevin Boyle. Kevin, you may begin.
spk32: Thank you, Alex. And as we finish this Veterans Day weekend, I just want to thank you to all those folks that have served our country. Good morning to everybody today. We appreciate you joining us for an update on the remarkable progress we have made over the past year. As you can see on slide four, our team has worked diligently to transform our promising technology and research and development efforts into meaningful clinical progress. We are very pleased to report that we achieved the first in human confirmed partial response in our clinical trial for a patient treated with sleep and beauty TCRT cells. It is even more impressive that this response happened at the first dose level. We've been gaining momentum in our TCRT library phase 1-2 trial as we are working closely with our investigators to identify patients at MD Anderson who have a match to one of our TCRs in our library. I am pleased to say that we anticipate treating our next patient before the end of this year. In our manufacturing suite, we have updated our standard operating procedures and hired additional personnel so we can manufacture multiple products at the same time, increasing potential throughput in our state-of-the-art C-GMP suite. We have consistently produced high-quality TCR T-cells at clinical scale and have successfully manufactured our product at the second dose level. We continue to advance our Hunter program, identifying new TCRs to add to our library, thereby increasing the addressable market for our TCRT cell therapy. We remain committed to being strategic and prudent with our cash spent. I believe we have demonstrated our good stewardship of shareholder capital as our highly engaged team of employees continues to advance our programs while spending less than half compared to last year. On slide five, we remind you of our pipeline. The company's success is not based on a single product. Alanos is a promising solid tumor platform. We are differentiated from other TCR-T companies in that we target hotspot mutations with T-cells that have been transposed with TCRs using our proprietary non-viral sleeping beauty technology. Our lead program is the TCR-T Library Phase 1-2 trials. It is a basket trial targeting hotspot mutations across six solid tumor indications, lung, colorectal, endometrium, pancreas, ovary, and bile duct cancers. We are actively enrolling patients at MD Anderson Cancer Center with one of these six cancers based on matching mutation and HLA pairings that are available in our TCR library, which currently consists of 10 TCRs, four KRAS, five TP53, and one AGFR. Three of these 10 TCRs have been associated with confirmed partial responses in a clinical setting, giving us great confidence in the power of TCRs to treat solid tumors. We'll speak in a moment about the confirmed partial response we saw in our trial at the first dose level in a patient treated with a KRAS TCR, as well as provide an update on this patient at the six-month mark. A second TCR we have in our library was the subject of a case study in the New England Journal of Medicine involving a pancreatic cancer patient with a partial response to one of our KRAS TCRs. The third TCR yielding a clinical response was reported by the NCI and was a breast cancer patient treated with the same TP53 TCR as our second patient. We will now provide an update on our clinical program. Recently, we had the honor of being invited to showcase early data from our Phase 1-2 trial in a proper talk at the CRI ENCI AACR 6th International Cancer Immunotherapy Conference, or SCICON 22 for short. As we turn to slide 7, we will share our great enthusiasm and excitement over the early clinical data from this trial. The findings presented at SCICON 2022, to our knowledge, represent the very first time that an objective clinical response was observed using a non-viral TCRT cell therapy in a solid tumor. The team is very excited to be among the leaders in the field, and the team's working hard to achieve even greater accomplishments. We are pleased to disclose data from our first two patients who were treated at dose levels one and two, respectively. Moving from dose level 1 to dose level 2 in the first two patients highlights the strength of our adaptive clinical trial design and robustness of our manufacturing platform. We observed a manageable safety profile in both patients with no dose-limiting toxicities. We were also able to detect TCR T-cell persistence out to six months. Most excitingly, our product is efficacious. achieving a confirmed partial response in the first patient at the lowest dose level. This early clinical validation has reinforced our belief that we are taking the right approach targeting tumor-specific hotspot mutations using our commercially scalable, non-viral Sleeping Beauty technology. We've produced evidence that our technology is safe, the cells persist, and our product is efficacious. Now I used to live in horse country in Louisville, Kentucky, and we would call this a winning trifecta. We are very excited about the promising results and the buzz created by this early data, generating increased interest from patients and clinicians alike. We are actively working with our investigators at MD Anderson to screen and enroll additional patients into the trial, and we anticipate the next patient being treated in the fourth quarter. I'd like to provide an in-depth review of the results that we presented at SCICON, in addition to highlighting six-month follow-up data from patient number one. On slide nine, you can see that the first patient dose was diagnosed with non-small cell lung cancer, had previously progressed on multiple prior lines of treatment, and was refractory to checkpoint inhibitors. The patient had HLA-A11 and a KRAS G12D mutation, matching one of the 10 TCRs within our library. This patient received standard CyFlu lymphodepletion prior to an infusion at the first dose level of 9 billion TCR T-cells, which were produced by our employees using Sleeping Beauty at our in-house CGMP manufacturing facility. The potential power of our TCR T-cells is supported by these scans, with the patient experiencing complete resolution, of a non-small cell lung cancer target lesion in their right lower lobe, shown in red circles through week 24. There was also significant and durable reduction of non-measurable disease in the right lung, as noted in the orange circles. Moving to slide 10, you can see that the patient also experienced a sustained reduction in their right upper lobe lesion
spk33: reflected in the red circles through week 24.
spk32: What a visual these images provide of the potential benefit of our TCRT cell therapy to the patient, as demonstrated by significant clearance of this target tumor. On slide 11, we have the third set of images for patient 1. The right pilar lymph node target lesion in the red circle was reduced relative to baseline at all time points including six months post-infusion. The patient also had large non-measurable disease in the right lung at baseline, shown in the orange circle. This area of disease was also reduced out to week 24 relative to the baseline. However, there was some perceived growth of this non-measurable disease at week 24 relative to the 12-week scan. That prompted the investigator to biopsy this area. The pathology report confirmed that tumor cells were present in this non-measurable disease, and the patient is now off study as a result. The overall progression-free survival for this patient 1 was 6 months, which is encouraging result for the first patient at the lowest dose level. Overall, as you can see on slide 12, the results in this first patient are extremely promising. We believe that the results give us an early look into the potential of our TCRT cell therapies to effectively kill large established solid tumors even at the lowest dose levels. The patient achieved an objective partial response with a regression of 46.3% in target lesions at six weeks. which subsequently deepened to 51.2% at week 12. And the reduction in measured lesions was sustained at 46.3% at 24 weeks. Persistence of TCR T-cells was observed in the blood of approximately 30% of all T-cells at 24 weeks. We also observed infiltration of both helper and killer TCR T-cells in the progressing tumors. suggesting that our TCRT cells can home to the tumor microenvironment. The KRAS G12D mutation and HLA-A11 were detected in the progressing tumor, indicating that the target remained intact and was not lost. Collectively, these results support our belief that the patient received significant clinical benefit from the administration of our TCRT cell therapy. A six-month progression-free survival, which is what patient one achieved, is competitive with the only approved KRAS targeted therapy, a KRAS G12C specific small molecule, that has a six and a half month progression-free survival. And there are no approved targeted therapies for KRAS G12D or KRAS G12V, both of which are in our library, and both with the potential to benefit a large patient population. Next, we will take a look at the second patient treated under our study, a colorectal cancer patient. On slide 14, we summarize patient two. This patient was diagnosed with colorectal cancer and had previously progressed on standard of care treatment. The patient had H11A02 and a TP53R175H mutation. and received standard CyFlu lymphodepletion prior to an infusion at the second dose level of 64 billion TCR T-cells. The patient achieved a best overall response of stable disease at six weeks, but was determined to have progressed progressive disease at the 12-week scan and went off study. TCR T cell persistence was observed in the blood of approximately 20% of all T cells at 12 weeks, which continues to demonstrate the potential of our TCR T cells to continue to work long after being administered. Following an independent radiology report, it was determined that disease progression was due to new lesions in the liver and the lung. We were able to detect the TP53 mutation in the progressing lesion suggesting that the target was retained. Of note, this particular TCR has previously been used by the NCI in a patient with metastatic breast cancer, achieving a partial response with cell persistence out to six months. So we remain confident in targeting TP53 mutations and look forward to enrolling more patients with this TCR and other TCRs in our library. Now, before turning over to Avi for a manufacturing update and details on the product characteristics of the TCR T-cells for the first two patients, I will summarize why we are so encouraged by the early clinical data. Here on slide 16, you can see some of the key takeaways from this initial clinical data. In both patients, the TCR T-cell therapy was well tolerated and presented a manageable safety profile. with no dose-limiting toxicities. TCR T cell persistence was observed at relatively high levels in both patients until their last follow-up. The ability of our TCR T cells to be a living drug and survive in great concentration is quite encouraging for the prospects of a durable response. And most importantly, evidence of efficacy was observed in both patients. with tumor infiltration suggesting that our Sleeping Beauty manufactured T-cells can survive in the hostile tumor microenvironment. Additionally, these data also provide proof of concept that we can successfully manufacture TCR T-cells for both KRAS and TP53 mutations at sufficient doses at our in-house CGMP manufacturing facility. Overall, we are really excited about these early findings, which highlight the potential of Sleeping Beauty TCR T-cell therapy to achieve measurable regression in solid tumors, even at the lowest dose levels. Based on the early responses seen in the clinic, there is excitement building among clinicians, and patients are being referred to MD Anderson specifically for consideration of enrollment in this trial. We are working closely with our investigators to continue to screen and enroll patients at the second dose level. We anticipate dosing our next patient into the study in the fourth quarter. We look forward to presenting an update on the trial in 2023. Now, as I turn the call over to Avi to review the robust and repeatable manufacturing process, I want to say what a great addition Avi has been to Alano's. His NCI training and familiarity with the TCR T-cell program has enabled him to be an immediate contributor.
spk29: Avi?
spk21: Thank you, Kevin, and good morning, everyone. Having joined the ALANUS team three months ago, I want to begin by saying how thrilled I am to be part of this fantastic team and to be contributing to the incredible science and technology that we use to treat patients with the solid tumors. I have a highly motivated and enthusiastic team who are continuing to improve with patient manufacturing and expanding our production capabilities. I have enjoyed our very productive conversations with MD Anderson PIs who are fully engaged and motivated to place additional patients on our trial. And internally, I'm thrilled to be working closely with the R&D team led by Drew whom I know from my old NIH days, as we work together to expand our product pipeline. As mentioned earlier, and highlighted in more detail on slide 18, we have treated two patients in our TCRT-11 trial. We have proven that we can manufacture patient cells for both KRAS and PP53 mutation in our own in-house CGMC manufacturing facility. We easily met the acceptance criteria for both dose levels one and two with high rates of viability, purity, and percentage of PCR positivity. We are highly encouraged by our ability so far to consistently and reproducibly manufacture quality clinical products. Now turning to slide 19, as we noted earlier this year, our CGMP suite production capacity was approximately one product per month. This was sufficient to support our TCRT library trial through the early stages. And manufacturing has not been a limiting factor to enrollment. Now, as momentum builds, and we continue to screen and enroll additional patients in the trial, we are executing on a multi-pronged strategy to expand our manufacturing capacity. We have already implemented new SOPs that allow for simultaneous production of multiple products in our own CGMP suite. successfully completing process qualification runs with cryopreserved TCR T cells, which will add flexibility for patient scheduling and treatment. We expect to file an IND amendment to move from fresh to cryopreserved product by the end of 2022, and begin implementing this change in the first half of 2023. In addition, this process is expected to enable us to reduce the manufacturing process time from 30 days to 26 days, representing a 13% decrease. While we are very encouraged by our plan to bring manufacturing to 26 days, we will continue to prioritize our work on reducing the manufacturing time further. And finally, we have also expanded our team by hiring additional manufacturing staff to enable multiple shifts in our in-house suite. As a result of all these initiatives, I'm happy to report that we have doubled our existing manufacturing capacity to produce two products simultaneously. This is a major step forward for our program. and for patients who need our therapy. I'm so proud of our fully committed team who has not turned down a single patient yet due to manufacturing limitations. Let me now hand the call over to Drew, who is going to highlight our ongoing R&D effort as well as presentation on our Hunter platform at the CIPSE annual meeting starting on slide 20.
spk05: Thank you, Avi. It's great to have you on board and to work with you again. Good morning, everyone on the call. As you've heard from both Avi and Kevin, we've been busy breaking new ground here at Awanos. I'm extremely encouraged by what we've observed in our first in human experience with Sleeping Beauty TCRT and our developments with Hunter, which now sets us up to have an end-to-end program from TCR discovery to clinical translation. As we continue to receive additional information from the translational assessments, we anticipate these data will give us more insight into clinical experience at a deeper level. We are pleased by the observed safety, persistence, and potential efficacy of our sleeping beauty TCR T cells. We're just getting started, but it's been validating and powering time for the team to know that we have the right platform and the right cells to make a major difference in the lives of cancer patients. As we continue to enroll and treat additional patients in the clinical study, we have been diligently working on our R&D efforts, particularly in advancing our human neoantigen T-cell receptor discovery platform, or Hunter. Now turning to slide 21. We believe Hunter is a differentiated platform that has multiple advantages relative to others in the TCR discovery space. Let's start with the starting material. Traditional TCR discovery is typically done with healthy donor T cells with a limited number of HLAs and mutations. Because the healthy donor is not known to have the mutation, there is a question to whether the T cell really saw and reacted to the target in its natural context. Often this healthy donor approach can require further enhancement of the T cell receptor to make it recognize the tumor, which increases the risk profile. In contrast, we do not manipulate the TCRs we find. They seem to both recognize the tumor and bind the target stronger because they are found in tumor infiltrating T cells, also known as TILs. This is likely because the TILs that we use for TCR discovery were presumably inside the cancer trying to fight it and likely visualize the mutation in its natural context. We use these naturally occurring TCRs taken from the TILs in one patient and use them for treatment as TCR T cells in another patient with the same target. Another distinction of our program is the throughput. We can quickly screen many TCRs using our transposon system without having to grow the T cells in the lab. We also use a fast universal reporter cell line that further increases our speed. Other competing systems typically rely on viral transduction of the TCR into donor T cells, which can be labor intensive and time consuming. Additionally, we do not limit ourselves to testing for specific HLAs or mutations, based on common peptide prediction algorithms. The platforms that use this method may be limited in their searching capabilities. In contrast, we let the biology drive the discovery of the target and use an unbiased population of mutation and HLA combinations, meaning we can potentially search for and identify any possible T cell response to a mutation. We believe our Hunter platform maximizes the output of TCR discovery. Moving on to slide 22. Last Thursday, we presented new data at the CITSE conference that demonstrated the ability of Hunter to quickly identify and validate neoantigen reactive TCRs. The poster is available on our website, and we encourage you to have a look to see why we are so excited about this platform. Our goal in the presented study was to establish that our Hunter platform is robust and accurate before we move towards a hotspot mutation focused screening approach. To that end, we evaluated hundreds of thousands of HLA mutation and TCR combinations in a high throughput setting with state-of-the-art proprietary technology to build our TCR discovery infrastructure. Nine patients with either Colorectal, endometrial, or breast cancers were evaluated. All patients screened had at least one detectable neoantigen-reactive TCR, including one shared KRAS Q61H mutation and 21 unique personalized mutations. Both CD4 and CD8 T cells were reactive, indicating that both helper and killer T cell populations could be sources for TCR discovery. Roughly one in eight TCRs was reactive to a mutation, and an average of three unique specificities were identified per patient. These data are being used to further define the important genes and characteristics of mutation reactive T cells, which will continue to reduce the time and associated cost of TCR discovery. As we look ahead, we plan to expand the application of Hunter to grow the library in a two-pronged approach. First, we plan to add more mutations to the existing KRAS, TP53, and EGFR mutations in the library. Second, we aim to add more HLA restrictions to the existing mutations. We believe this will expand the patient population who could benefit from TCR T cell therapy. We've already begun our KRAS-focused approach against G12D and G12V. Indeed, two of the five initial patients we screened had TCRs reactive to KRAS G12 and V. These findings provide evidence of the ability of Hunter to discover exclusively owned hotspot mutation reactive TCRs that could be added to the current clinical library. Our enthusiasm to screen specifically for hotspot mutations is further strengthened by these results. And we are actively moving forward with numerous samples with KRAS, TP53, and EGFR mutations. Moving on to slide 23. During the past quarter, we pre-screened over 250 solid tumor samples for presence of one of the hotspot mutations we are interested in studying. We also looked at HLAs, cell viability, relative proportions of tumor and infiltrating T cells, and other factors as part of the pre-screening process. From the initial set of samples, we are continuing with roughly a quarter of them for full TCR discovery workup. This was an efficient and cost-effective way to find the best possible tumors in a short time period. The pool of samples currently under investigation comes from a diverse group of solid tumor indications, that are representative of our treatment populations. We are looking at two EGFR mutations, LA58R and exon 19 deletion, which are the dominant mutations in EGFR and are highly prevalent in lung cancers. We chose four KRAS mutations, G12C, G12D, G12V, and G13D, based on their prevalence in solid tumors, especially gastrointestinal and lung cancers. Given our early efficacy signals in the clinic targeting KRAS G12D, we are encouraged to add more TCRs reactive to G12D and other KRAS mutations into our clinical program. TP53 is well known to be among the most commonly mutated genes in all of cancer and has been shown to be highly immunogenic in previous studies, including ones that I helped lead at the NCI. Even though TP53 is mutated in multiple locations, there are eight hotspots that we were focused on setting. We believe we will be successful in discovering TCRs reactive to mutated TP53 and that they will be applicable to a large number of patients in a broad range of cancer types. As we saw in our initial data set where all patients had a response to one of the mutations expressed by their cancer, Hunter may also be suitable for personalized TCR T-cell therapies for most solid tumors. The NCI, under the leadership of Dr. Rosenberg, is pursuing a similar approach for rapid TCR identification to decrease the time from discovery to treatment, and their system could be applied in conjunction with our Cooperative Research and Development Agreement, or CRADA. We believe that the use of sleeping beauty transposition will further decrease the cost and time to treatment and could be critical for the commercial application of fully autologous personalized TCR T-cell therapy. I would now like to turn the call over to Mike Wong to review the financial results for the third quarter starting on slide 24. Mike.
spk26: Thank you, Drew. Let me review our financials for the three months ended September 30th, 2022, which are highlighted on slide 25. For the third quarter of 2022, we reported a net loss of approximately $8.9 million, or 4 cents net loss per share, compared to a net loss of approximately $22.7 million, or 11 cents net loss per share for the third quarter of 2021. Collaboration revenue was approximately $2.9 million for the third quarter of 2022, compared to approximately $0.4 million for the third quarter of 2021. The increase was primarily due to the achievement of sales-based milestones of Darin O'Parson in Japan by Selesia Pharma KK. Research and development expenses were approximately $7.9 million for the third quarter of 2022, compared to approximately $14.5 million for the third quarter of 2021, a decrease of 46%. The decrease was primarily due to lower program-related costs of $3.6 million, mainly related to the winding down of our IL-12 and CAR-T programs, a $4.9 million decrease in employee-related expenses due to our reduced headcount, and a $0.6 million decrease in consulting and facilities expenses. These decreases were partially offset by a one-time $2.5 million expense to MD Anderson following the achievement of sales-based milestones in Japan by Salacia. General and administrative expenses were approximately $3.3 million for the third quarter of 2022, compared to approximately $8.2 million for the same period in 2021, a decrease of 60%. The decrease was primarily due to lower employee-related expenses of $3.2 million due to our reduced headcount and a $1.7 million decrease in consulting and professional services expenses. As of September 30th, 2022, Alanos had approximately $37.8 million in cash and cash equivalents and $13.9 million of restricted cash. Our operating cash burn for the third quarter of 2022 was approximately $6.1 million compared to approximately $9.6 million in the third quarter of 2021. A decrease of approximately $3.4 million or 36%. That concludes our financial update. I would now like to turn the call to Kevin for closing remarks.
spk32: Thank you, Mike. As we turn to slide 27, let's talk about the upcoming milestones that we expect will be value drivers for the company in the near term. Our team has made significant progress across our business this year, focusing on our novel Sleeping Beauty TCR T-cell platform, targeting solid tumors. And the team is poised for continued clinical progress, treating more patients and generating additional valuable translational data. Our top priority is continued enrollment of patients into our library TCRT clinical trial. And towards this end, we expect to dose the next patient in the fourth quarter. As we mentioned earlier, we have seen tremendous excitement building among clinicians. We have dozens of patients in pre-screening that are being followed specifically for consideration of enrollment in this trial. We look forward to providing additional updates on the trial in 2023 at a major medical conference. We expect to file an IND amendment in the fourth quarter that we believe will be a big value driver for the company. First, the IND will add two new TCRs to our clinical trial, targeting frequent mutations and HLAs. This will greatly increase the addressable market for our therapy, and we'll be able to increase the number of patients in the queue at MD Anderson. Secondly, the IND makes an important improvement in our manufacturing process as we move from fresh to cryopreserved TCRT cell product. As Abhi mentioned, this will add flexibility for patient scheduling and treatment and reduce manufacturing time from 30 to 26 days. We expect this new process to go into effect in the first half of 2023. I'd also like to briefly touch on the development of our membrane-bound IL-15 program. Earlier this year, we presented data at ASGCT that highlighted the ability of membrane-bound IL-15 TCRT cells to specifically target and kill tumors while also establishing long-lived tumor-specific TCRT cells. We are continuing to advance this program towards an IND filing in the second half of 2023 and believe it has the potential to increase the survival of TCR T cells in the harsh tumor microenvironment and deepen clinical responses. Lastly, we continue to work with the NCI to develop proof of concept with a fully autologous, personalized TCR T cell therapy using Sleeping Beauty. Dr. Rosenberg and team are some of the world's experts in this field and bring significant experience to the CRADA and TCR discovery and clinical trials with T-cell therapy. We believe that this personalized approach may be a broadly applicable strategy for cancer therapy in the future. Our team has been focused on delivering results this year and made significant progress across our business, while simultaneously reducing our operating cash burn year over year. Before we open the call to questions, I want to express my gratitude to our team, partners, patients, and shareholders for their support. We remain excited about the progress we have made to date and look forward to building upon our successes in 2023. We are working to transform the way solid tumors are being treated and confidently expect our early success will lead to even greater accomplishments in the year ahead. We thank you for being a part of this journey as we continue our mission to improve the lives of patients suffering from solid tumor cancers. We will now open the call to questions. Liz?
spk27: As a reminder, if you'd like to ask a question at this time, please press star 1 1 on your telephone. Our first question comes from the line of Prakkar Agarwal with Cantor Fitzgerald. Your line is now open.
spk18: Hi. Good morning, everyone. Thanks for taking my questions. Congratulations on all the progress and finishing up the 3Q. So my first question is, the second patient was dosed in June based on my estimate. So it's almost taking six months for the next set of patients to be dosed. Maybe talk about why it's taking so long, the key bottlenecks that you're working through. And if you could also comment on what dose will the third patient be given. And I had a couple of follow-ups.
spk32: Hi, Prakhar. Thanks for the questions. So as you see in the early SICON data with the first confirmed partial response at the lowest dose, there's really a lot of excitement and interest that's building in this study. So the SICON proffered talk at the end of September was a really great accelerant to this trial and for enrollment. In fact, just recently, this data, once it was presented at SCICON, was shared with all of the doctors on the stem cell transplant team over at MD Anderson. And the interest is really strong and the pipeline is building. And by adding these two new TCRs in the IND filing, that'll even further expand the patient funnel and allowing even more patients to be tracked and to benefit from this therapy. The cryopreservation also is going to increase the flexibility for scheduling and will further eliminate any hurdles whatsoever to enrolling patients on this trial. So I think there's a reason that we've been investing in increasing our manufacturing capacity as we expect enrollment to build and to treat many more patients in 2023.
spk18: Okay, thank you, Kevin. And a couple of follow-ups. So maybe a question for Drew. For patient one, I think the target was not lost, and there are still persistent T cells at six months. So any color on the level of memory stem cells, or if you could provide more details from your translation work on possible reasons for progression at six months, and how could BFS be improved with higher doses?
spk05: Yeah, thanks, Prakara, and good morning. Thanks for the questions. We're very excited to see persistence in this patient up to six months and the circulation of over 30% of their cells, which is quite high. And we were also encouraged to not only see it in the circulation, but also in the tumor from this biopsy that was taken from the right lung. So, we know that the TCR T cells are getting into this harsh tumor microenvironment. So, it's very encouraging. We're also encouraged that the KRSG12D and the HLA-A11 were both present in the tumor so that they're all positives going forward. We are still looking at some of the characteristics of those cells per your question. Now we don't have the data at this point, but we're very interested in knowing what's going on in the cells. We're very encouraged by the results, the clinical results that the patient had, and really looking forward to treating other patients.
spk18: Got it. And lastly, Kevin, This is a key question for investors. If you can talk about the cash runway, I might have missed this, and the possible financing avenues you think might make sense for the company given the next clinical catalyst sometime in 2023. Thank you.
spk32: Certainly, Prakash. So our cash runway is still into the second quarter of 2023. And as a biotech, we're always exploring financing options. There is great interest based on this encouraging early data. which is giving us a lot of flexibility and options available to us. We appreciate our supportive and loyal shareholder base and have also been experiencing a lot of interest from new prospective investors who see the potential and power of our TCR T-cell therapy. Reminder, we do have the ATM in place, so that's yet another option in addition to we worked very hard earlier this year to have the shelf in place as well. So we have many different options and have teed ourselves up to be able to fundraise in any number of fashions. So we're very confident in our ability to expand our cash runway and look forward to providing updates in the future.
spk09: Thank you.
spk27: Our next question comes from the line of James Shin with Wells Fargo. Your line is now open.
spk13: Hey, good morning, guys. Thanks for taking my question. I just want to go back to patient number one real quick. It sounds like you're still doing work on things, and it sounds like HLA and G12D were still present in the tumor, which is great. So will you be looking at any exhaustion signals to suggest that maybe that's why the response is going to persist? And then related, When you guys moved to the cryopreserve product, can you say what sort of changes you saw from the freeze process relative to the current warm cells?
spk07: Yeah, thanks, James. Drew here.
spk05: Good morning. I'll take the first one and then kick over to Avi for the manufacturing questions. So in regards to patient one, we're very encouraged with the targets still there. very encouraged that the T cells are infiltrating into the tumor. We're looking at exhaustion markers because we actually have some of the cells that are alive from that tumor. We look at their ability to be responsive to not only the mutation, but kind of an in vitro tumor system. So we're looking at all that. We are quite encouraged and want to use the clinical data that we get to drive the kind of hypotheses around what's going on in the clinical setting. So I'm going to kick over to Avi for the cryopreserve question.
spk21: Yeah. Thanks, Drew. I want to start by saying that our manufacturing platform is very robust and reproducible. We have been able to produce high purity, high viability, and high PCR positivity cell product. When it comes to moving from fresh to cryopreserved product, there's not any change in our overall manufacturing process, except we have just added a formulation, a cryopreservant in the formulation. And we have done a process qualification run, and based on that, we can say that our overall manufacturing process is very similar to what we have as a fresh product.
spk09: Thanks, guys. Appreciate it. Thanks, James.
spk27: Our next question comes from a line of Chris Howerton with Jefferies. Your line is now open.
spk09: Chris, you may be on mute. We can move to the next caller, Liz.
spk27: Our next question comes from the line of Yale Jen with Laidlaw. Your line is now open.
spk15: Hello.
spk06: Morning, Yale. Hey, how are you?
spk14: Sorry, I didn't hear my name. My first question is that the next patient, you mentioned that will be the second dose level. We understood that last patient was reduced to 64 billion cells. How should we think about the next one? Would that be in the same ballpark or...
spk32: Right. Thanks, Gail. Yes, indeed, the patient number three will be at the second dose level. That's where we intend to treat the patient. As you're aware, there is a range for the dose levels. And so the dose level two is anywhere from approximately 10 billion TCR T cells to a 70 TCRT, 70 billion TCRT cells. And so, though we're not communicating on the exact number in that range, we would anticipate, and that's really at the guidance of the treating physician where the dose level is.
spk15: Okay, great.
spk14: That's very helpful. One more question here is that in terms of the two added new TCRT I didn't get it quite clearly. Could you just repeat what specifically those are, the configuration of those two?
spk05: Yeah, thanks, Gail. This is Drew here. We're very excited to add these new TCRs to the library as part of the IND amendment that we're filing. We haven't gotten clearance from the FDA for those TCRs just yet, so we haven't announced the specific identities of them, but we will once they've been cleared, and we anticipate that they will be cleared because we've already expanded the library from six to ten late last year. So that's our expectation, but we don't want to be presumptuous with the FDA. So taking a bit of caution here, we can say that we do think it's going to make a significant increase in the number of patients that can be enrolled in the trial and that we can bring TCR T cell therapy to as we move forward.
spk14: Okay, great. That's very helpful. Maybe the last of this housekeeping question here, in terms of this quarter, you have a 2.9 million revenues from the last pharma. Do we anticipate this to be a one-time event or it could occur periodically going forward? And thanks.
spk26: Mike, you want to take that? Sure. Thanks, Yael. We're definitely very pleased with the regulation on the regulatory approval and the achievement for commercial sale of their They're a person in Japan, and this source of non-delusional funding for the company. We anticipate the upfront payment that we received from Silasia in the third quarter of 2022 will be the most meaningful payment that we'll receive over the next few years.
spk15: Okay, great. That's very helpful, and congrats on all the progress.
spk08: Thank you. Thank you.
spk27: Our next question comes from the line of Thomas Flatton with Lake Street Capital Markets. Your line is now open.
spk02: Great. Thanks for taking the questions. Drew, just back to those TCRs. I'm assuming it's safe to assume that they're within the three genes that you guys are already focused on, right?
spk05: Yeah, that is correct, Thomas. It will be within KRAS TP53. or EGFR. And again, to reiterate that we're looking to add more mutations within the existing genes and to add more HLAs within the existing mutations. So, it's consistent with that thesis. It'll be, you know, along those same lines.
spk02: Got it. And going back to the first question about enrollment pacing, you know, if you look at the time that's elapsed since patient number two enrolled, has it been availability of patients? Was there manufacturing that kind of stood in the way of another patient enrolling sooner? I'm just trying to get some more insight into that timeframe that has elapsed.
spk32: I can assure you that manufacturing has never been a rate-limiting step whatsoever. We have a very strong manufacturing platform and are simply building up the throughput capacity for anticipation of the enrollment to come. We all long anticipated that until we had an early data release that enrollment might be at a slower pace than we would like. But we're now very excited with the proffered talk at SICON. The confirmed partial response at the lowest dose level is really building momentum. There had been a few patients that unfortunately, you know, these are patients that have just very tragic diseases with heavy disease burden. And as a result, there were patients that did match the HLA and the TCRs, but unfortunately had other exclusion criterias because of their health declining at a fast pace. So it's unfortunate that when other therapies failed them, they did not meet the inclusion criteria from a health perspective, even though they matched one of our TCRs. And so what we're excited about with the two new TCRs coming in, with the move from fresh to cryopreserved product, we believe that we'll be able to produce cells even earlier in a patient's journey, which will allow us to, we believe, treat more patients. And I can tell you that the excitement, we have a lot of inbound inquiries, people coming from different geographies, people responding to the Not only our presentation of that, but the two case studies mentioned by Providence and NCI. So, again, a reminder, three different TCRs on our clinical trial have now been clinically validated by having confirmed partial responses. So, we're very excited about the prospect of enrolling and treating many more patients in 2023 and anticipate the treatment pattern to increase quite dramatically.
spk02: I appreciate all that color. And just to confirm for me, and perhaps I missed it, how many patients do you anticipate treating at dose level two, assuming no DLTs or ICAMs?
spk32: You know, we're going to let the science speak for itself there. So we're going to follow very closely, working with the PIs to determine that. So we'll certainly update as we go along.
spk11: Excellent. I appreciate you guys taking the questions. Thank you. Thank you.
spk27: As a reminder, if you'd like to ask a question at this time, please press star 1 1 on your touch tone telephone. Our next question comes to a line of Chris Howerton with Jefferies. Chris, your line is now open.
spk12: Hi, this is Anthea for Chris Howerton. Sorry about the audio issue earlier. Thank you for taking our questions and congratulations on a great quarter. We have two questions. First, if there are any differences in the purity and viability of the TCRT cells using the cryopreserved process. And second, what tumor types are you expecting to dose in your next patient and what the next data cut will be? Thank you.
spk21: Thank you for the question. Let me start by saying that, you know, first two patients, you know, when we looked at the characteristics of these two different cells, they had a really high viability, purity, and TCR positivity. But we compared with fresh versus cryopreserved products based on our early EQ qualification run. We do not see any differences in terms of the characteristics.
spk19: We still maintain the same amount of viability, purity, and TCR positivity.
spk31: And we have not disclosed what the indication will be for the patients ahead.
spk32: We do anticipate presenting additional data in 2023 at a major medical conference. And at that time, we'll share much more translational data on the patients that we have and share additional information about the indications. So, again, we do reiterate that we have six different solid tumor indications that we're treating with our Phase I-II basket trial.
spk23: Got it. Thank you for taking our questions.
spk17: Thank you.
spk27: I'm showing no further questions in queue at this time. This concludes today's conference call. Thank you for participating.
spk00: You may now... And during Q&A, you can dial... The conference will begin shortly. To raise your hand during Q&A, you can dial star 1 1. Thank you. Thank you.
spk17: Thank you.
spk27: Good day, and thank you for standing by. Welcome to the Alano's Therapeutics third quarter 2022 financial results conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you'll need to press star 1 1 on your telephone. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Alex Lobo, with Stern Investor Relations. Please go ahead.
spk24: Thank you. Good morning, and welcome to the Alanos Therapeutics third quarter 2022 financial results conference call and audio webcast. Please note that today's webcast contains slides, which are available through the audio webcasting platform. A copy of the presentation will be available on our website after today's call. Earlier this morning, Alanos issued a press release announcing financial results for the three months ended September 30th, 2022. We encourage everyone to read today's press release, as well as the Alanos quarterly report on Form 10-Q for the quarter ended September 30th, 2022, which was filed this morning with the SEC. The company's press release and quarterly report will also be available on the Alanos website at alanos.com. In addition, this conference call is being webcast through the investor relations section of the company's website, and will be archived there for future reference. Please note that certain information discussed on today's call covered under the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. Participants are cautioned that this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, November 14, 2022. Actual results could differ materially from those stated or implied by forward-looking statements made on today's call due to risks and uncertainties associated with the company's business. Information on potential risks and uncertainties are set forth in our most recent public filings with the SEC at sec.gov. The company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this live webcast, except it may be required by applicable securities law. With me today are Kevin Boyle Sr., Chief Executive Officer, Abhi Srivastava, Vice President of Technical Operations, Drew Dennegar, Vice President of Research and Development, and Mike Wong, Vice President of Finance. With that said, I would like to turn the call over to Kevin Boyle. Kevin, you may begin.
spk32: Thank you, Alex. And as we finish this Veterans Day weekend, I just want to thank you to all those folks that have served our country. Good morning to everybody today. We appreciate you joining us for an update on the remarkable progress we have made over the past year. As you can see on slide four, our team has worked diligently to transform our promising technology and research and development efforts into meaningful clinical progress. We are very pleased to report that we achieved the first in human confirmed partial response in our clinical trial for a patient treated with Sleeping Beauty TCR T-cells. It is even more impressive that this response happened at the first dose level. We've been gaining momentum in our TCRT Library Phase 1-2 trial as we are working closely with our investigators to identify patients at MD Anderson who have a match to one of our TCRs in our library. I am pleased to say that we anticipate treating our next patient before the end of this year. In our manufacturing suite, we have updated our standard operating procedures and hired additional personnel so we can manufacture multiple products at the same time, increasing potential throughput in our state-of-the-art cGMP suite. We have consistently produced high-quality TCR T-cells at clinical scale and have successfully manufactured our product at the second dose level. We continue to advance our Hunter program, identifying new TCRs to add to our library, thereby increasing the addressable market for our TCR T-cell therapy. We remain committed to being strategic and prudent with our cash spent. I believe we have demonstrated our good stewardship of shareholder capital as our highly engaged team of employee continues to advance our programs while spending less than half compared to last year. On slide five, we remind you of our pipeline. The company's success is not based on a single product. Alanos is a promising solid tumor platform We are differentiated from other TCRT companies in that we target hotspot mutations with T-cells that have been transposed with TCRs using our proprietary non-viral sleeping beauty technology. Our lead program is the TCRT Library Phase 1-2 trial. It is a basket trial targeting hotspot mutations across six solid tumor indications, lung, colorectal, endometrium, pancreas, ovary, and bile duct cancers. We are actively enrolling patients at MD Anderson Cancer Center with one of these six cancers based on matching mutation and HLA pairings that are available in our TCR library, which currently consists of 10 TCRs, four KRAS, five TP53, and one AGFR. Three of these 10 TCRs have been associated with confirmed partial responses in a clinical setting. giving us great confidence in the power of TCRs to treat solid tumors. We'll speak in a moment about the confirmed partial response we saw in our trial at the first dose level in a patient treated with a KRAS TCR, as well as provide an update on this patient at the six-month mark. A second TCR we have in our library was the subject of a case study in the New England Journal of Medicine involving a pancreatic cancer patient with a partial response to one of our KRAS TCRs. The third TCR yielding a clinical response was reported by the NCI and was a breast cancer patient treated with the same TP53 TCR as our second patient. We will now provide an update on our clinical program. Recently, we had the honor of being invited to showcase early data from our Phase 1-2 trial in a proper talk at the CRI ENCI AACR 6th International Cancer Immunotherapy Conference, or SCICON 22 for short. As we turn to slide 7, we will share our great enthusiasm and excitement over the early clinical data from this trial. The findings presented at SCICON 2022, to our knowledge, represent the very first time that an objective clinical response was observed using a non-viral TCRT cell therapy in a solid tumor. The team is very excited to be among the leaders in the field, and the team's working hard to achieve even greater accomplishments. We are pleased to disclose data from our first two patients who were treated at dose levels one and two, respectively. Moving from dose level one to dose level two, in the first two patients, highlights the strength of our adaptive clinical trial design and robustness of our manufacturing platform. We observed a manageable safety profile in both patients with no dose-limiting toxicities. We were also able to detect TCR T-cell persistence out to six months. Most excitingly, our product is efficacious, achieving a confirmed partial response in the first patient at the lowest dose level. This early clinical validation has reinforced our belief that we are taking the right approach targeting tumor-specific hotspot mutations using our commercially scalable, non-viral Sleeping Beauty technology. We've produced evidence that our technology is safe, the cells persist, and our product is efficacious. Now, I used to live in horse country in Louisville, Kentucky, and we would call this a winning trifecta. We are very excited about the promising results and the buzz created by this early data, generating increased interest from patients and clinicians alike. We are actively working with our investigators at MD Anderson to screen and enroll additional patients into the trial, and we anticipate the next patient being treated in the fourth quarter. I'd like to provide an in-depth review of the results that we presented at SCICON, in addition to highlighting six-month follow-up data from patient number one. On slide nine, you can see that the first patient dose was diagnosed with non-small cell lung cancer, had previously progressed on multiple prior lines of treatment, and was refractory to checkpoint inhibitors. The patient had HLA-A11 and a KRAS G12D mutation, matching one of the 10 TCRs within our library. This patient received standard CyFlu lymphodepletion prior to an infusion at the first dose level of 9 billion TCR T-cells, which were produced by our employees using Sleeping Beauty at our in-house CGMP manufacturing facility. The potential power of our TCR T-cells is supported by these scans, with the patient experiencing complete resolution, of a non-small cell lung cancer target lesion in their right lower lobe, shown in red circles through week 24. There was also significant and durable reduction of non-measurable disease in the right lung, as noted in the orange circles. Moving to slide 10, you can see that the patient also experienced a sustained reduction in their right upper lobe lesion
spk33: reflected in the red circles through week 24.
spk32: What a visual these images provide of the potential benefit of our TCRT cell therapy to the patient, as demonstrated by significant clearance of this target tumor. On slide 11, we have the third set of images for patient 1. The right pilar lymph node target lesion in the red circle was reduced relative to baseline at all time points including six months post-infusion. The patient also had large non-measurable disease in the right lung at baseline, shown in the orange circle. This area of disease was also reduced out to week 24 relative to the baseline. However, there was some perceived growth of this non-measurable disease at week 24 relative to the 12-week scan. That prompted the investigator to biopsy this area. The pathology report confirmed that tumor cells were present in this non-measurable disease, and the patient is now off study as a result. The overall progression-free survival for this patient one was six months, which is encouraging result for the first patient at the lowest dose level. Overall, as you can see on slide 12, the results in this first patient are extremely promising. We believe that the results give us an early look into the potential of our TCRT cell therapies to effectively kill large established solid tumors even at the lowest dose levels. The patient achieved an objective partial response with a regression of 46.3% in target lesions at six weeks. which subsequently deepened to 51.2% at week 12. And the reduction in measured lesions was sustained at 46.3% at 24 weeks. Persistence of TCR T cells was observed in the blood of approximately 30% of all T cells at 24 weeks. We also observed infiltration of both helper and killer TCR T cells in the progressing tumor. suggesting that our TCRT cells can home to the tumor microenvironment. The KRAS G12D mutation and HLA-A11 were detected in the progressing tumor, indicating that the target remained intact and was not lost. Collectively, these results support our belief that the patient received significant clinical benefit from the administration of our TCRT cell therapy. A six-month progression-free survival, which is what patient one achieved, is competitive with the only approved KRAS targeted therapy, a KRAS G12C-specific small molecule that has a six-and-a-half-month progression-free survival. And there are no approved targeted therapies for KRAS G12D or KRAS G12V, both of which are in our library, and both with the potential to benefit a large patient population. Next, we will take a look at the second patient treated under our study, a colorectal cancer patient. On slide 14, we summarize patient two. This patient was diagnosed with colorectal cancer and had previously progressed on standard of care treatment. The patient had H11A02 and a TP53R175H mutation. and received standard CyFlu lymphodepletion prior to an infusion at the second dose level of 64 billion TCR T-cells. The patient achieved a best overall response of stable disease at six weeks, but was determined to have progressed progressive disease at the 12-week scan and went off study. TCR T cell persistence was observed in the blood of approximately 20% of all T cells at 12 weeks, which continues to demonstrate the potential of our TCR T cells to continue to work long after being administered. Following an independent radiology report, it was determined that disease progression was due to new lesions in the liver and the lung. We were able to detect the TP53 mutation in the progressing lesion suggesting that the target was retained. Of note, this particular TCR has previously been used by the NCI in a patient with metastatic breast cancer, achieving a partial response with cell persistence out to six months. So we remain confident in targeting TP53 mutations and look forward to enrolling more patients with this TCR and other TCRs in our libraries. Now, before turning over to Abhi for a manufacturing update and details on the product characteristics of the TCR T-cells for the first two patients, I will summarize why we are so encouraged by the early clinical data. Here on slide 16, you can see some of the key takeaways from this initial clinical data. In both patients, the TCR T-cell therapy was well tolerated and presented a manageable safety profile. with no dose-limiting toxicities. TCR T cell persistence was observed at relatively high levels in both patients until their last follow-up. The ability of our TCR T cells to be a living drug and survive in great concentration is quite encouraging for the prospects of a durable response. And most importantly, evidence of efficacy was observed in both patients. with tumor infiltration suggesting that our Sleeping Beauty manufactured T-cells can survive in the hostile tumor microenvironment. Additionally, these data also provide proof of concept that we can successfully manufacture TCR T-cells for both KRAS and TP53 mutations at sufficient doses at our in-house CGMP manufacturing facility. Overall, we are really excited about these early findings, which highlight the potential of Sleeping Beauty TCR T-cell therapy to achieve measurable regression in solid tumors, even at the lowest dose levels. Based on the early responses seen in the clinic, there is excitement building among clinicians, and patients are being referred to MD Anderson specifically for consideration of enrollment in this trial. We are working closely with our investigators to continue to screen and enroll patients at the second dose level. We anticipate dosing our next patient into the study in the fourth quarter. We look forward to presenting an update on the trial in 2023. Now, as I turn the call over to Avi to review the robust and repeatable manufacturing process, I want to say what a great addition Avi has been to Alano's. His NCI training and familiarity with the TCR T-cell program has enabled him to be an immediate contributor.
spk29: Abhi?
spk21: Thank you, Kevin, and good morning, everyone. Having joined the LONUS team three months ago, I want to begin by saying how thrilled I am to be part of this fantastic team and to be contributing to the incredible science and technology that we use to treat patients with the solid tumors. I have a highly motivated and enthusiastic team who are continuing to improve with patient manufacturing and expanding our production capabilities. I have enjoyed our very productive conversations with MD Anderson PIs who are fully engaged and motivated to place additional patients on our trial. And internally, I'm thrilled to be working closely with the R&D team led by Drew whom I know from my old NIH days as we work together to expand our product pipeline. As mentioned earlier and highlighted in more detail on slide 18, we have treated two patients in our TCRT laboratory trial. We have proven that we can manufacture patient cells for both KRAS and TP53 mutation in our own in-house CGMT manufacturing facility. We easily met the acceptance criteria for both dose levels one and two with high rates of viability, purity, and percentage of TCR positivity. We are highly encouraged by our ability so far to consistently and reproducibly manufacture quality clinical products. Now turning to slide 19, as we noted earlier this year, our CGMP suite production capacity was approximately one product per month. This was sufficient to support our TCRT library trial through the early stages. And manufacturing has not been a limiting factor to enrollment. Now, as momentum builds, and we continue to screen and enroll additional patients in the trial, we are executing on a multi-pronged strategy to expand our manufacturing capacity. We have already implemented new SOPs that allow for simultaneous production of multiple products in our own CGMP suite. successfully completing process qualification runs with cryopreserved TCR T cells, which will add flexibility for patient scheduling and treatment. We expect to file an IND amendment to move from fresh to cryopreserved product by the end of 2022, and begin implementing this change in the first half of 2023. In addition, this process is expected to enable us to reduce the manufacturing process time from 30 days to 26 days, representing a 13% decrease. While we are very encouraged by our plan to bring manufacturing to 26 days, we will continue to prioritize our work on reducing the manufacturing time further. And finally, we have also expanded our team by hiring additional manufacturing staff to enable multiple shifts in our in-house suite. As a result of all these initiatives, I'm happy to report that we have doubled our existing manufacturing capacity to produce two products simultaneously. This is a major step forward for our program. and for patients who need our therapy. I'm so proud of our fully committed team who has not turned down a single patient yet due to manufacturing limitations. Let me now hand the call over to Drew, who is going to highlight our ongoing R&D effort as well as presentation on our Hunter platform at the CIPSE annual meeting starting on slide 20.
spk05: Thank you, Avi. It's great to have you on board and to work with you again. Good morning, everyone on the call. As you've heard from both Avi and Kevin, we've been busy breaking new ground here at Awanos. I'm extremely encouraged by what we've observed in our first in human experience with Sleeping Beauty TCRT and our developments with Hunter, which now sets us up to have an end-to-end program from TCR discovery to clinical translation. As we continue to receive additional information from the translational assessments, we anticipate these data will give us more insight into clinical experience at a deeper level. We are pleased by the observed safety, persistence, and potential efficacy of our sleeping beauty TCR T cells. We're just getting started, but it's been validating and powering time for the team to know that we have the right platform and the right cells to make a major difference in the lives of cancer patients. As we continue to enroll and treat additional patients in the clinical study, we have been diligently working on our R&D efforts, particularly in advancing our human neoantigen T-cell receptor discovery platform, or Hunter. Now turning to slide 21. We believe Hunter is a differentiated platform that has multiple advantages relative to others in the TCR discovery space. Let's start with the starting material. Traditional TCR discovery is typically done with healthy donor T cells with a limited number of HLAs and mutations. Because the healthy donor is not known to have the mutation, there is a question to whether the T cell really saw and reacted to the target in its natural context. Often this healthy donor approach can require further enhancement of the T cell receptor to make it recognize the tumor, which increases the risk profile. In contrast, we do not manipulate the TCRs we find. They seem to both recognize the tumor and bind the target stronger because they are found in tumor infiltrating T cells, also known as TILs. This is likely because the TILs that we use for TCR discovery were presumably inside the cancer trying to fight it and likely visualize the mutation in its natural context. We use these naturally occurring TCRs taken from the TILs in one patient and use them for treatment as TCR T cells in another patient with the same target. Another distinction of our program is the throughput. We can quickly screen many TCRs using our transposon system without having to grow the T cells in the lab. We also use a fast universal reporter cell line that further increases our speed. Other competing systems typically rely on viral transduction of the TCR into donor T cells, which can be labor intensive and time consuming. Additionally, we do not limit ourselves to testing for specific HLAs or mutations based on common peptide prediction algorithms. The platforms that use this method may be limited in their searching capabilities. In contrast, we let the biology drive the discovery of the target and use an unbiased population of mutation and HLA combinations, meaning we can potentially search for and identify any possible T cell response to a mutation. We believe our Hunter platform maximizes the output of TCR discovery. Moving on to slide 22. Last Thursday, we presented new data at the CITSE conference that demonstrated the ability of Hunter to quickly identify and validate neoantigen reactive TCRs. The poster is available on our website, and we encourage you to have a look to see why we are so excited about this platform. Our goal in the presented study was to establish that our Hunter platform is robust and accurate before we move towards a hotspot mutation focused screening approach. To that end, we evaluated hundreds of thousands of HLA mutation and TCR combinations in a high throughput setting with state-of-the-art proprietary technology to build our TCR discovery infrastructure. Nine patients with either Colorectal, endometrial, or breast cancers were evaluated. All patients screened had at least one detectable neoantigen-reactive TCR, including one shared KRAS Q61H mutation and 21 unique personalized mutations. Both CD4 and CD8 T cells were reactive, indicating that both helper and killer T cell populations could be sources for TCR discovery. Roughly one in eight TCRs was reactive to a mutation, and an average of three unique specificities were identified per patient. These data are being used to further define the important genes and characteristics of mutation reactive T cells, which will continue to reduce the time and associated cost of TCR discovery. As we look ahead, we plan to expand the application of Hunter to grow the library in a two-pronged approach. First, we plan to add more mutations to the existing KRAS, TP53, and EGFR mutations in the library. Second, we aim to add more HLA restrictions to the existing mutations. We believe this will expand the patient population who could benefit from TCR T cell therapy. We've already begun our KRAS-focused approach against G12D and G12V. Indeed, two of the five initial patients we screened had TCRs reactive to KRAS G12Z. These findings provide evidence of the ability of Hunter to discover exclusively owned hotspot mutation reactive TCRs that could be added to the current clinical library. Our enthusiasm to screen specifically for hotspot mutations is further strengthened by these results. And we are actively moving forward with numerous samples with KRAS, TP53, and EGFR mutations. Moving on to slide 23. During the past quarter, we pre-screened over 250 solid tumor samples for presence of one of the hotspot mutations we are interested in studying. We also looked at HLAs, cell viability, relative proportions of tumor and infiltrating T cells, and other factors as part of the pre-screening process. From the initial set of samples, we are continuing with roughly a quarter of them for full TCR discovery workup. This was an efficient and cost-effective way to find the best possible tumors in a short time period. The pool of samples currently under investigation comes from a diverse group of solid tumor indications, that are representative of our treatment populations. We are looking at two EGFR mutations, LA58R and exon 19 deletion, which are the dominant mutations in EGFR and are highly prevalent in lung cancers. We chose four KRAS mutations, G12C, G12D, G12V, and G13D, based on their prevalence in solid tumors, especially gastrointestinal and lung cancers. Given our early efficacy signals in the clinic targeting KRAS G12D, we are encouraged to add more TCRs reactive to G12D and other KRAS mutations into our clinical program. TP53 is well known to be among the most commonly mutated genes in all of cancer and has been shown to be highly immunogenic in previous studies, including ones that I helped lead at the NCI. Even though TP53 is mutated in multiple locations, there are eight hotspots that we were focused on setting. We believe we will be successful in discovering TCRS reactive to mutated TP53 and that they will be applicable to a large number of patients in a broad range of cancer types. As we saw in our initial data set where all patients had a response to one of the mutations expressed by their cancer, Hunter may also be suitable for personalized TCR T-cell therapies for most solid tumors. The NCI, under the leadership of Dr. Rosenberg, is pursuing a similar approach for rapid TCR identification to decrease the time from discovery to treatment, and their system could be applied in conjunction with our Cooperative Research and Development Agreement, or CRADA. We believe that the use of sleeping beauty transposition will further decrease the cost and time to treatment and could be critical for the commercial application of fully autologous personalized TCR T-cell therapy. I would now like to turn the call over to Mike Wong to review the financial results for the third quarter starting on slide 24. Mike.
spk26: Thank you, Drew. Let me review our financials for the three months ended September 30, 2022, which are highlighted on slide 25. For the third quarter of 2022, we reported a net loss of approximately $8.9 million, or 4 cents net loss per share, compared to a net loss of approximately $22.7 million, or 11 cents net loss per share, for the third quarter of 2021. Collaboration revenue was approximately $2.9 million for the third quarter of 2022, compared to approximately $0.4 million for the third quarter of 2021. The increase was primarily due to the achievement of sales-based milestones of Darin O'Parson in Japan by Selesia Pharma KK. Research and development expenses were approximately $7.9 million for the third quarter of 2022, compared to approximately $14.5 million for the third quarter of 2021, a decrease of 46%. The decrease was primarily due to lower program-related costs of $3.6 million, mainly related to the winding down of our IELTS 12 and CAR T programs, a $4.9 million decrease in employee-related expenses due to our reduced headcount, and a $0.6 million decrease in consulting and facilities expenses. These decreases were partially offset by a one-time $2.5 million expense to MD Anderson following the achievement of sales-based milestones in Japan by Salacia. General and administrative expenses were approximately $3.3 million for the third quarter of 2022, compared to approximately $8.2 million for the same period in 2021, a decrease of 60%. The decrease was primarily due to lower employee-related expenses of $3.2 million due to our reduced headcount and a $1.7 million decrease in consulting and professional services expenses. As of September 30th, 2022, Alanos had approximately $37.8 million in cash and cash equivalents and $13.9 million of restricted cash. Our operating cash burn for the third quarter of 2022 was approximately $6.1 million compared to approximately $9.6 million in the third quarter of 2021. A decrease of approximately $3.4 million or 36%. That concludes our financial update. I would now like to turn the call to Kevin for closing remarks.
spk32: Thank you, Mike. As we turn to slide 27, let's talk about the upcoming milestones that we expect will be value drivers for the company in the near term. Our team has made significant progress across our business this year, focusing on our novel Sleeping Beauty TCR T-cell platform targeting solid tumors. And the team is poised for continued clinical progress, treating more patients and generating additional valuable translational data. Our top priority is continued enrollment of patients into our library TCRT clinical trial. And towards this end, we expect to dose the next patient in the fourth quarter. As we mentioned earlier, we have seen tremendous excitement building among clinicians. We have dozens of patients in pre-screening that are being followed specifically for consideration of enrollment in this trial. We look forward to providing additional updates on the trial in 2023 at a major medical conference. We expect to file an IND amendment in the fourth quarter that we believe will be a big value driver for the company. First, the IND will add two new TCRs to our clinical trial, targeting frequent mutations and HLAs. This will greatly increase the addressable market for our therapy, and we'll be able to increase the number of patients in the queue at MD Anderson. Secondly, the IND makes an important improvement in our manufacturing process as we move from fresh to cryopreserved TCRT cell product. As Avi mentioned, this will add flexibility for patient scheduling and treatment and reduce manufacturing time from 30 to 26 days. We expect this new process to go into effect in the first half of 2023. I'd also like to briefly touch on the development of our membrane-bound IL-15 program. Earlier this year, we presented data at ASGCT that highlighted the ability of membrane-bound IL-15 TCRT cells to specifically target and kill tumors while also establishing long-lived tumor-specific TCRT cells. We are continuing to advance this program towards an IND filing in the second half of 2023 and believe it has the potential to increase the survival of TCR T cells in the harsh tumor microenvironment and deepen clinical responses. Lastly, we continue to work with the NCI to develop proof of concept with a fully autologous, personalized TCR T cell therapy using Sleeping Beauty. Dr. Rosenberg and team are some of the world's experts in this field and bring significant experience to the CRADA and TCR discovery and clinical trials with T-cell therapy. We believe that this personalized approach may be a broadly applicable strategy for cancer therapy in the future. Our team has been focused on delivering results this year and made significant progress across our business, while simultaneously reducing our operating cash burn year over year. Before we open the call to questions, I want to express my gratitude to our team, partners, and shareholders for their support. We remain excited about the progress we have made to date and look forward to building upon our successes in 2023. We are working to transform the way solid tumors are being treated and confidently expect our early success will lead to even greater accomplishments in the year ahead. We thank you for being a part of this journey as we continue our mission to improve the lives of patients suffering from solid tumor cancers. We will now open the call to questions. Liz?
spk27: As a reminder, if you'd like to ask a question at this time, please press star 1-1 on your telephone. Our first question comes from the line of Prakkar Agarwal with Cantor Fitzgerald. Your line is now open.
spk18: Hi, good morning, everyone, and thanks for taking my questions. Congratulations on all the progress and the finishing of the 3Q. So my first question is, the second patient was dosed in June, based on my estimate. So it's almost taking six months for the next set of patients to be dosed. Maybe talk about why it's taking so long, the key bottlenecks that you're working through. And if you could also comment on what dose will the third patient be given. And I had a couple of follow-ups.
spk32: Hi, Prakhar. Thanks for the questions. So as you see in the early CyCon data with the first confirmed partial response at the lowest dose, there's really a lot of excitement and interest that's building in this study. So the CyCon proffered talk at the end of September was a really great accelerant to this trial and for enrollment. In fact, just recently, this data, once it was presented at CyCon, was shared with all of the doctors on the stem cell transplant team over at MD Anderson. and the interest is really strong and the pipeline is building. And by adding these two new TCRs in the IND filing, that'll even further expand the patient funnel and allowing even more patients to be tracked and to benefit from this therapy. The cryopreservation also is going to increase the flexibility for scheduling, and will further eliminate any hurdles whatsoever to enrolling patients on this trial. So I think there's a reason that we've been investing in increasing our manufacturing capacity as we expect enrollment to build and to treat many more patients in 2023. Okay.
spk18: Thank you, Kevin. And a couple of follow-ups. So Maybe a question for Drew. For patient one, I think the target was not lost, and there are still persistent T cells at six months. So any color on the level of memory stem cells, or if you could provide more details from your translation work on possible reasons for progression at six months, and how could PFS be improved with higher doses?
spk05: Yeah, thanks, Prakara, and good morning. Thanks for the questions. We're very excited to see persistence in this patient up to six months and the circulation of over 30% of their cells, which is quite high. And we were also encouraged to not only see it in the circulation, but also in the tumor from this biopsy that was taken from the right lung. So, we know that the TCR T cells are getting into this harsh tumor microenvironment. So, it's very encouraging. We're also encouraged that the KRSG12D and the HLA-A11 were both present in the tumor so that they're all positives going forward. We are still looking at some of the characteristics of those cells per your question now. We don't have the data at this point, but we're very interested in knowing what's going on in the cells. We're very encouraged by the results, the clinical results that the patient had, and really looking forward to treating other patients.
spk18: Got it. And lastly, Kevin, This is a key question for investors. If you can talk about the cash runway, I might have missed this, and the possible financing avenues you think might make sense for the company given the next clinical catalyst sometime in 2023. Thank you.
spk32: Certainly, Prakash. So our cash runway is still into the second quarter of 2023. And as a biotech, we're always exploring financing options. There is great interest based on this encouraging early data. which is giving us a lot of flexibility and options available to us. We appreciate our supportive and loyal shareholder base and have also been experiencing a lot of interest from new prospective investors who see the potential and power of our TCR T-cell therapy. Reminder, we do have the ATM in place, so that's yet another option in addition to we worked very hard earlier this year to have the shelf in place as well. So we have many different options and have teed ourselves up to be able to fundraise in any number of fashions. So we're very confident in our ability to expand our cash runway and look forward to providing updates in the future.
spk09: Thank you.
spk27: Our next question comes from the line of James Shin with Wells Fargo. Your line is now open.
spk13: Hey, good morning, guys. Thanks for taking my question. I just want to go back to patient number one real quick. It sounds like you're still doing work on things, and it sounds like HLA and G12D were still present in the tumor, which is great. So will you be looking at any exhaustion signals to suggest that maybe that's why the response is going to persist? And then related, When you guys moved to the cryopreserve product, can you say what sort of changes you saw from the freeze process relative to the current warm cells?
spk07: Yeah, thanks, James. Drew here.
spk05: Good morning. I'll take the first one and then kick over to Avi for the manufacturing questions. So in regards to patient one, we're very encouraged with the target still there. very encouraged that the T cells are infiltrating into the tumor. We're looking at exhaustion markers because we actually have some of the cells that are alive from that tumor. We look at their ability to be responsive to not only the mutation, but kind of an in vitro tumor system. So we're looking at all that. We are quite encouraged and want to use the clinical data that we get to drive kind of hypotheses around what's going on in the clinical setting. So I'm going to kick over to Avi for the cryopreserve question.
spk21: Yeah, thanks Drew. I want to start by saying that our manufacturing platform is very robust and reproducible. We have been able to produce high purity, high viability, and high PCR positivity cell product. When it comes to moving from fresh to cryopreserved product, there's not any change in our overall manufacturing process, except we have just added a formulation cryopreservant in the formulation. And we have done a process qualification run, and based on that, we can say that our overall manufacturing process is very similar to what we have as a fresh product.
spk09: Thanks, guys. Appreciate it. Thanks, James.
spk27: Our next question comes from a line of Chris Howerton with Jefferies. Your line is now open. Chris, you may be on mute. We can move to the next caller, Liz. Our next question comes from the line of Yale Jen with Laidlaw. Your line is now open.
spk06: Hello. Morning, Yale. Hey, how are you? Sorry, I didn't hear my name.
spk14: My first question is that The next patient, you mentioned that will be the second dose level. We understood that last patient was reduced to 64 billion cells. How should we think about the next one? Would that be in the same ballpark? Or is there another follow-up question?
spk32: Right. Thanks, Gail. Yes, indeed, the patient number three will be at the second dose level. That's where we intend to treat the patient. As you're aware, there is a range for the dose levels. And so the dose level two is anywhere from approximately 10 billion TCR T-cells to a 70 TCRT, 70 billion TCRT cells. And so, though we're not communicating on the exact number in that range, we would anticipate, and that's really at the guidance of the treating physician where the dose level is. Okay, great.
spk14: That's very helpful. One more question here is that in terms of the two added new TCRT I didn't get it quite clearly. Could you just repeat what specifically those are, the configuration of those two?
spk05: Yeah, thanks, Gail. This is Drew here. We're very excited to add these new TCRs to the library as part of the IND amendment that we're filing. We haven't gotten clearance from the FDA for those TCRs just yet, so we haven't announced the specific identities of them, but we will once they've been cleared, and we anticipate that they will be cleared because we've already expanded the library from 6 to 10 late last year. So that's our expectation, but we don't want to be presumptuous with the FDA. So taking a bit of caution here, we can say that we do think it's going to make a significant increase in the number of patients that can be enrolled in the trial and that we can bring TCR T cell therapy to as we move forward.
spk14: Okay, great. That's very helpful. Maybe the last of this housekeeping question here, in terms of this quarter, you have a 2.9 million revenues from the last pharma. Do we anticipate this to be a one-time event or it could occur periodically going forward? And thanks. Mike, you want to take that?
spk26: Sure. Thanks, Yael. We're definitely very pleased with the regulatory approval and the achievement for commercial sale of their products. Sarah Parson in Japan, and this source of non-diluted funding for the company. We anticipate the upfront payment that we received from Solasia in the third quarter of 2022 will be the most meaningful payment that we'll receive over the next few years.
spk15: Okay, great. That's very helpful, and congrats on all the progress.
spk08: Thank you. Thank you.
spk27: Our next question comes from the line of Thomas Flatton with Lake Street Capital Markets. Your line is now open.
spk02: Great. Thanks for taking the questions. Drew, just back to those TCRs. I'm assuming it's safe to assume that they're within the three genes that you guys are already focused on, right?
spk05: Yeah, that is correct, Thomas. It will be within KRAS TP53. or EGFR. And again, to reiterate that we're looking to add more mutations within the existing genes and to add more HLAs within the existing mutations. So, it's consistent with that thesis. It'll be, you know, along those same lines.
spk02: Got it. And going back to the first question about enrollment pacing, you know, if you look at the time that's elapsed since patient number two enrolled, has it been availability of patients? Was there manufacturing that kind of stood in the way of another patient enrolling sooner? I'm just trying to get some more insight into that timeframe that has elapsed.
spk32: I can assure you that manufacturing has never been a rate-limiting step whatsoever. We have a very strong manufacturing platform and are simply building up the throughput capacity for anticipation of the enrollment to come. We all long anticipated that until we had an early data release that enrollment might be at a slower pace than we would like. But we're now very excited with the proffered talk at SICON. The confirmed partial response at the lowest dose level is really building momentum. There had been a few patients that unfortunately, you know, these are patients that have just very tragic diseases with heavy disease burden. And as a result, there were patients that did match the HLA and the TCRs, but unfortunately had other exclusion criterias because of their health declining at a fast pace. So it's unfortunate that when other therapies failed them, they did not meet the inclusion criteria from a health perspective, even though they matched one of our TCRs. And so what we're excited about with the two new TCRs coming in, with the move from fresh to cryopreserved product, we believe that we'll be able to produce cells even earlier in a patient's journey, which will allow us to, we believe, treat more patients. And I can tell you that the excitement, we have a lot of inbound inquiries, people coming from different geographies, people responding to the Not only our presentation of data, but the two case studies mentioned by Providence and NCI. So, again, a reminder, three different TCRs on our clinical trial have now been clinically validated by having confirmed partial responses. So, we're very excited about the prospect of enrolling and treating many more patients in 2023 and anticipate the treatment pattern to increase quite dramatically.
spk02: I appreciate all that color. And just to confirm for me, and perhaps I missed it, how many patients do you anticipate treating at dose level two, assuming no DLTs or ICAMs?
spk32: You know, we're going to let the science speak for itself there. So we're going to follow very closely, working with the PIs to determine that. So we'll certainly update as we go along.
spk11: Excellent. I appreciate you guys taking the questions. Thank you. Thank you.
spk27: As a reminder, if you'd like to ask a question at this time, please press star 1 1 on your touch tone telephone. Our next question comes to a line of Chris Howerton with Jefferies. Chris, your line is now open.
spk12: Hi, this is Anthea for Chris Howerton. Sorry about the audio issue earlier. Thank you for taking our questions and congratulations on a great quarter. We have two questions. First, if there are any differences in the purity and viability of the TCRT cells using the cryopreserved process. And second, what tumor types are you expecting to dose in your next patient and what the next data cut will be? Thank you.
spk21: Thank you for the question. Let me start by saying that, you know, first two patients, you know, when we looked at the characteristics of these two different cells, they had a really high viability, purity, and TCR positivity. But we compared with fresh versus cryopreserved products based on our early PQ qualification run.
spk19: We do not see any differences in terms of the characteristics. We still maintain the same amount of viability, purity, and TCR positivity.
spk31: And we have not disclosed what the indication will be for the patients ahead.
spk32: We do anticipate presenting additional data in 2023 at a major medical conference. And at that time, we'll share much more translational data on the patients that we have and share additional information about the indications. So, again, we do reiterate that we have six different solid tumor indications that we're treating with our Phase I-II basket trial.
spk23: Got it. Thank you for taking our questions.
spk17: Thank you.
spk27: I'm showing no further questions in queue at this time. This concludes today's conference call. Thank you for participating.
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