Q3 2022 Alaunos Therapeutics Inc Earnings Call

Good day, and thank you for standing by and welcome to the a lot of 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 the session you will need to press star one one 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.

Thank you.

Morning, and welcome to the Alon and Therapeutics third quarter 2020 financial results conference call and audio webcast.

Yes.

Please note that today's webcast contain slides, which are available to the audio webcast.

A copy of the presentation will be available on our website after today's call.

Earlier this morning, <unk> issued a press release announcing financial results for the third.

The months ended September 32022.

We encourage everyone to read today's press release as well as the allowance quarterly report on Form 10-Q for the quarter ended September 32022.

Which was filed this morning with the SEC.

The company's press release and quarterly report will also be available on <unk> website at <unk> Dot 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 provision 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 Companys 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 LIBOR webcast.

Except as may be required by applicable securities law.

With me today are Kevin Boyle, Senior Chief Executive Officer, Avi Srivastava, Vice President of technical operations <unk>.

<unk>, Vice President of research and development and Mike Huang Vice President of Finance.

With that said I would like to turn the call over to Kevin.

Kevin you may begin.

Thank you Alex and as we finish this veterans day.

Weekend I just wanted to thank you to all of 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 frequent getting TCR T cells. It is even more impressive that this response happened at the first dose level.

We have been gaining momentum in our TCR T Library phase one two trial as we are working closely with our investigators to identify patients at MD Anderson, who have a match to one of our <unk> and our library.

I am pleased to say that we anticipate treating our next patient before the end of this year.

And 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 and our state of the art C GMP suites.

We have consistently produced high quality TCR T cells at clinical scale.

We've successfully manufactured our product at the second dose level.

We continue to advance our Hunter program identifying new tcr's 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 spend.

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 Companys success is not based on a single product.

<unk> is a promising solid tumor platform.

We are differentiated from other TCR T companies and that we target hotspot mutations with T cells that have been transposed with TCR.

Our proprietary non viral sleeping beauty technology.

Our lead program is the TCR T Library phase one two 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 HOA pairings that are available in our TCR library.

Which currently consist of 10 tcr's.

<unk> <unk> 53, and one egfr.

Three of these 10 Tcr's had been associated with confirmed partial responses in a clinical setting.

US great confidence in the power of Tcr's to treat solid tumors.

We will speak in a moment about the confirmed partial response, we saw in our trial at the first dose level and a patient treated with a K Ras TCR as well as provide an update on this patient at the six month Mark.

Our 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 <unk> TCR.

The third TCR, yielding a clinical response was reported by the NCI and what's a breast cancer patient treated with the same <unk> 53, 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 one two trial and the proper talk at the Cri NCI.

ACR six international cancer Immunotherapy conference.

<unk> 22 for short.

As we turn to slide seven we will share our great enthusiasm and excitement over the early clinical data from this trial.

The findings presented its icon 2022 to our knowledge represents a very first time that an objective clinical response was observed using a non viral TCR T 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 and 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 are also able to detect TCR T cell persistence out to six months.

Most excitingly our product is efficacious, achieving a confirmed partial response and 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 have produced evidence that our technology is safe the cells persist and our product is efficacious.

No 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 patients being treated in the fourth quarter.

Okay.

I'd like to provide an in depth review of the results that we presented at <unk> Com. 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 <unk> 11, and <unk> mutation matching one of the 10 tcr's within our library.

This patient received standard Psi flu lymphoid depletion 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 and they're right lower lobe shown in red circles through week 24.

There is also significant and durable reduction of non measurable disease and the right long 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 reflected in the red circles through week 24.

What a visual these images provide the potential benefit of our TCR T cell therapy to the patient as demonstrated by significant clearance of this target tumor.

On slide 11, we have the third set of images per patient one.

The REIT pilot 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 long 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 confirms 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 TCR T cell therapies to effectively kill large established solid tumors, even at the lowest dose levels.

The patients 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 with 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 TCR T cells can home to the tumor microenvironment.

The <unk> <unk> mutation and HLA 11 were detected in the progressing tumor, indicating that the target remains intact and was not lost.

Collectively these results support our belief that the patient received significant clinical benefit from the administration of our TCR T cell therapy.

Our six month progression free survival, which is what patient one achieved is competitive with the only approved <unk> targeted therapy are.

K Ras <unk> specific small molecule.

That has a six five month progression free survival.

And there are no approved targeted therapies for <unk> 12, D or <unk>, 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 too.

This patient was diagnosed with colorectal cancer and had previously progressed on standard of care treatment.

The patient had <unk> 11.

And a T P 53, or $1 75, H mutation and receive standard Psi flu litho depletion 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 TP 53 mutations in the progressing lesion, suggesting that the target was retained.

Of note. This particular TCR is previously been used by the NCI and a patient with metastatic breast cancer, achieving a partial response with cell persistence out to six months.

So we remain confident in targeting T. P 53, mutations and look forward to enrolling more patients with this TCR and other tcr's 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 manufacturer T cells can survive in the hostel tumor micro environment.

Additionally, these data also provide proof of concept that we can successfully manufacture TCR T cells for both <unk> and <unk> hundred 53 mutations as 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 our lives.

As NCI training and familiarity with the TCR T cell program has enabled him to be an immediate contributor.

Amit.

Thank you, Kevin and good morning, everyone.

Having joined the <unk> team three months ago, I want to begin by saying how thrilled I am to be part of this fantastic team and.

It could be contributing to the incredible science and technology that can be used to treat patients with 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 a very productive conversations with MD Anderson.

Who are fully engaged and motivated to place additional patients on our trial.

And internally.

Still to be working closely with the R&D team led by Joe.

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 TCR T lab at a time.

We have proven that we can manufacture patients out for both data and <unk> mutation in our own in house Cgmp manufacturing facility.

We easily met our acceptance criteria for both dose levels, one and two with.

With high rates of viability purity and percentage of PCR positivity.

Okay.

We are highly encouraged by our ability so far too.

Was it simply and to produce fully manufactured 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 TCR T liability trial.

The early stages.

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.

Expand our manufacturing capacity.

We have already implemented <unk> debt.

That allows for simultaneous reduction of multiple products in our own cgmp suites.

This includes successfully completing process qualifications on with cryo preserved TCR T cells.

Which will add flexibility, but based on the scheduling and treatment.

We expect to file an IND amendment to move from fresh to cryo preserve product by the end of 2022.

And began implementing this team 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 2006 days.

We'll continue to prioritize our work on reducing the manufacturing time further.

And finally, we have also expanded our team.

By Heidi additional manufacturing staff.

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.

For patients who need our therapy.

I am so proud of our fully committed team who have not turned down a single patient use.

Due to manufacturing limitations.

Let me now hand, the call over to June who is going to highlight our ongoing R&D effort as well as presentation on our Hunter platform at the <unk> annual meeting starting on slide 20.

Nope.

Thank you Avi, it's great to have you onboard and to work with you again good morning, everyone on the call.

As you've heard from both RV and Kevin we've been busy breaking new ground here at autos I am.

I'm extremely encouraged by what we've observed in our first in human experience with the sleeping beauty TCR T 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 were.

We're just getting started but it's been validating empowering time for the team to know that we have the right platform 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 Neo antigen T cell receptor discovery platform or Hunter.

Now turning to slide 21, we.

We believe Hunter is a differentiated platform that has multiple advantages relative to others in the TCR discovery space.

Let's start with starting to mature.

Traditional TCR discovery is typically done with healthy donor T cells with a limited number of Hla's and mutations.

The healthy donor is not known to have a mutation. There is a question to whether the T cells really solved and reacted to the target and its natural context.

Often this healthy donor approach can require further enhancement of the T cell receptor to make it recognized the tumor which increases the risk profile.

In contrast, we do not manipulate the tcr's we find they.

They seem to both recognize the tumor and bind the target stronger because they are found in tumor infiltrating T cells also known as pills.

This is likely because of the tools that we use for TCR discovery, where presumably inside the cancer trying to fight it and likely visualize the mutation and its natural context.

We use these naturally occurring TCR is taken from the hills in one patient and use them for treatment as TCR T cells and another patient with the same targets.

Okay.

Another distinction of our program is the throughput.

We can quickly screen, many tcr's using our transposon system without having to grow the T cells in the lab.

We also use a fast universal reporter Salon that further increases our speed.

They're 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 HLA for mutations based on common peptide prediction algorithms.

The platforms that use this method may be limited and they're searching capabilities.

In contrast, we let the biology driving 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 <unk> conference that demonstrated the ability of hunter to quickly identify and validate new antigen reactive TCR.

The poster is available on our website and we encourage you to have a look to see why we're 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 competitions, and the high throughput settings with state of the art proprietary technology to build our TCR discovery infrastructure.

Nine patients with either.

Colorectal and dmitry or breast cancers were evaluated.

All patients screened had at least one detectable neo antigen reactive TCR, including one shared K Ras <unk> 61, H mutation and 21 unique personalized mutations.

Both CD four and CDA T cells were reactive indicating that both helper and killer T cell populations could be sources for TCR discovery.

Roughly $1 <unk> was reactive to a mutation in 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 and a two pronged approach.

First we plan to add more mutations to the existing K Ras <unk>, three and Egfr mutations in the library.

Second we aim to add more easily 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 K Ras focused approach against <unk> D and G <unk>.

Indeed, two of the five initial patients we screened had tcr's reactive to <unk> 12.

These findings provide evidence of the ability of hunter to discover exclusively owned hotspot mutation reactive TCR that can be added to the current clinical library.

Our enthusiasm.

<unk> specifically for hotspot mutations is further strengthened by these results and we are actively moving forward with numerous samples with K Ras <unk>, three 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 Hla's cell viability relative proportions of tumor infiltrating T cells and other factors as part of this training prescreening process.

From the initial set of samples we are continuing with roughly a quarter of them for full TCR discovery work up.

This was an efficient and cost effective way to find the best possible tumor 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 to Egfr mutations la five to eight are in exon 19, deletion, which are the dominant mutations in egfr and are highly prevalent and lung cancers.

We chose four K Ras mutations <unk> and <unk> <unk> based on their prevalence in solid tumors, especially gastrointestinal and lung cancers.

Given our early efficacy signals in the clinic targeting <unk> D. We are encouraged to add more TCR is reactive to <unk> and other K Ras mutations into our clinical program.

T 15 T. P 53 is well known to be among the most commonly mutated genes in all of cancer as it's been shown to be highly immunogenic and previous studies, including ones that I hopefully at the NCI.

Even though <unk> 53 is mutated multiple locations. There are eight hotspots that we were focused on setting.

We believe we will be successful in discovering tcr's reactive to mutated <unk> 53, and that they will be applicable to a large number of patients and 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 creative.

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.

<unk> fully it's August personalized TCR T cell therapy.

I would now like to turn the call over to Mike <unk> to review the financial results for the third quarter, starting on slide 24.

Thank you drew let me review our financials for the three months ended September 32022.

Are highlighted on slide 25.

For the third quarter of 2022, we reported a net loss of approximately $8 $9 million or <unk> <unk> net loss per share.

Impaired to a net loss of approximately $22 7 million or 11 net loss per share.

For the third quarter of 2021.

Collaboration revenue was approximately $2 9 million for the <unk>.

Third quarter of 2022.

Compared to approximately zero point $4 million.

For the third quarter of 2021.

The increase was primarily due to the achievement of sales based milestones of Darren a person in Japan isolation pharma K K.

Research and development expenses were approximately $7 9 million for.

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.

$3 $6 million, mainly related to the winding down of our IL 12 and car T programs.

<unk> 9 million decrease in employee related expenses due to our reduced head count.

And the zero point $6 million decrease in consulting and facilities expenses.

Okay.

These decreases were partially offset by a one time $2 5 million dollar expense to MD Anderson following the achievement of sales based milestones in Japan.

Asia.

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 at.

A decrease of 60%.

The decrease is primarily due to lower employee related expenses.

Of three $2 million did try reduced head count and a $1 $7 million decrease in consulting and professional services expenses.

As of September 32022.

<unk> 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 six 1 million <unk>.

Compared to approximately $9 $6 million in the third quarter of 2021.

A decrease of approximately $3 million to $4 million or.

Of our 36%.

That concludes our financial update.

I would now like to turn the call to Kevin for closing remarks.

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 TCR T 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 amongst clinicians and we have dozens of patients and 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 R&D will add two new tcr's to our clinical trial targeting frequent mutations and HLA.

This will greatly increase the addressable market for our therapy, and we will be able to increase the number of patients in the queue at MD Anderson.

Secondly, the IMD makes an important improvement in our manufacturing process as we move from fresh to cryo preserve TCR T cell product.

As Avi mentioned this wide flexibility for patients scheduling and treatment and reduced 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 <unk> that highlighted the ability of membrane bound IL 15, TCR T cells to specifically target and kill tumors. While also establishing long lived tumor specific TCR T 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, and 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 brings significant experience to the crater in TCR discovery and clinical trials with T cell therapy.

We believe that this personalized approach may be 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.

As a reminder, if you'd like to ask a question at this time. Please press star one one on your telephone.

Our first question comes from the line of <unk> Agarwal with Cantor Fitzgerald. Your line is now open.

Hi, good morning, everyone.

Thanks for taking my questions. Congratulations on all the progress on the commissioning of the <unk>. So.

My first question is this.

Patient was dosed in June based on my estimates with almost taking six months for the next set of patients to be dosed, but maybe talk about why that why as things go along the key bottlenecks that you are working through.

And if you could also comment on what dose will be given and I had a couple of follow ups.

Hydropower, thanks for the questions.

So as you see in the early Sycon 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 this icon.

<unk> talk at the end of September was a really great accelerant to this trial and for enrollment.

In fact, just recently this Dan.

Once it was presented at <unk> with shared with all of the doctors on the stem cell transplant team over at MD Anderson.

The interest is really strong and the pipeline is building and by adding these two new <unk> in the IND filing.

That will even further expand the patient funnel and allowing even more patients to be tracked and to benefit from this therapy.

The cryo preservation also is going to increase the flexibility for scheduling.

We will.

Further eliminate any hurdles whatsoever to enrolling patients on this trial.

So I think there is 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. Thank you Kevin.

Couple of follow ups. So maybe a question for drew for patient Ron I think the target was not lost and there are some persistent diesels at six months. So any color on the level of memory stem cells and or if you could provide more details from your transformation of work on possible reasons for progression at six months and how could we improve.

The higher doses.

Yeah. Thanks <unk>. Good morning, Thanks for the questions were very excited to see.

Persistence in this patient up to six months in the circulation.

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 launch window. The TCR T cells are getting into this harsh tumor microenvironment, so thats very encouraging.

We're also encouraged that the <unk> D and the HLA <unk> or both.

<unk>.

And the tumor so those are 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 were very encouraged by.

The results of the clinical results of the patient had.

And really looking forward to training other patients.

Got it and lastly, Kevin.

This is a key question plan versus if you can talk about the cash run rate I might have missed this on the possible financing avenues, you think might make sense for the company given the next clinical catalyst at some time in 2023. Thank.

Thank you.

Certainly per car 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 are supportive and loyal shareholder base and have also been.

Experiencing a lot of interest from new perspective, investors, who see the potential and power of our TCR T cell therapy.

A 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.

In place as well so we have many different options and have teed ourselves up to be able to fund raise.

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.

Thank you.

Thank you.

Okay.

Our next question comes from the line of James Sheehan with Wells Fargo. Your line is now open.

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 <unk> still present in tumors, which is great.

Will you be looking at any exhaustion signals suggest that maybe thats why the response is going to persist.

And then related when you guys move to the cryo preserve product can you say what sort of changes you saw from these process relative to the current warm cells.

Okay. Thanks, James through here and good morning, I'll take the first one and then kick over to Avi for May.

Maybe factoring question so in regards to patient one.

We're very encouraged with the target's still theyre very encouraged of the T cells are infiltrating into the tumor.

Booking ads exhaustion markers there because we actually have some of the cells that are alive from that tumor we can look at there.

Our ability.

So to be responsive to not only that mutation.

But kind of in vitro tumor system. So we're looking at all of that we are quite encouraged and wanting to use the clinical data that we get to drive return.

Hypotheses around.

What's going on in the <unk>.

Clinical setting so.

Kick over to Avi for the Cryo preserve question yes.

Yes.

Sue.

I want to start by saying that our manufacturing platform is very robust and reproducible.

<unk> been able to produce high purity of high reliability and high PCR positivity self product when it comes to.

More than <unk> <unk> to <unk>.

<unk> preserve product theres, not theres not any change in our overall manufacturing process that we have just added our formulation a cryopreserved went in the population and we have done a process qualification done and based on that we can say that our overall manufacturing processes very similar to what we have is the best product.

Yes.

Thanks, guys I appreciate it.

Thanks James.

Our next question comes from the line of Chris Howerton with Jefferies. Your line is now open.

Christian maybe on mute.

Hey, guys. The next caller list.

Our next question comes from the line of Yale Jen with Laidlaw. Your line is now open.

Hello.

Good morning Al.

Sorry, I didn't hear my name.

Thanks for taking my questions My first question.

The next page.

That will be the second dose level.

Okay.

So at $2 84 billion.

How should we think about.

Our next one will be in the same ballpark.

Sure.

Hello.

And then I have a follow up question.

Okay.

Alright, Thanks, Yale, Yes, indeed, the patient number three will be at the second dose level, that's where we intend to treat the patient as you are 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.

70, <unk> 70 billion TCR T cells, and so no we're not communicating on the exact number in that range, we would anticipate and that's really the guidance of the treating physician where the dose levels.

Okay, Great. That's very helpful. One more question here.

In terms of the two added new TCR T.

I didn't get it quite clearly could you just repeat what specifically those are.

The complication of that those two.

Yes, Thanks, Yale District here.

We're excited to add these new TCR library as part of the IMD Amendment that we're filing yet.

We haven't gotten clearance from the FDA for that those ccr's just yet so we haven't announced the specific identities.

Once they've been cleared and we anticipate it will be clear because we've already expanded the library from six to 10 late last year. So that's our expectation, but we don't want to be presumptuous with the FDA. So taken 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 that we can.

Bring TCR T cell therapy to.

As we move forward.

Okay, Great. That's very helpful and maybe the last just housekeeping question here in terms of this quarter you have.

So two night.

Mainland revenues from Soliris.

<unk>.

Pharma do.

We anticipate this to be a one time event or it could occur periodically going forward. Thanks.

Mike you want to take that.

Alright, thanks, Yeah.

We're definitely very pleased.

Okay.

Thats all I have got it wrong.

The achievement for a congressional said.

They're our partner in Japan.

This non dilutive funding.

Company.

We anticipate the upfront payment that we received from Asia in the third quarter of 2022 will be the most meaningful payment that will receive over the next few years.

Okay, Great that's very helpful and congrats on the progress.

Thank you thanks, Joe.

Our next question comes from the line of Thomas Flaten with Lake Street Capital markets. Your line is now open.

Great. Thanks for taking the questions drew just back to the CCR is I'm, assuming it's safe to assume that they are within the three genes that you guys are already focused on Ryan.

Yes that is correct Thomas will be within Kers, GBP, three <unk> Egfr and <unk>.

Again to reiterate that we are looking to add more mutations within the existing genes and to add more HLA is within the existing mutation. So it's consistent with that thesis it'll be along those same lines.

Got it and going back to the first question about enrollment pacing. If you look at the at the time that has elapsed since patient number two enrolled has it been availability of patients was there was there manufacturing that kind of stood in the wave.

Another patient enrolling sooner I'm, just trying to get some more.

Insight into that timeframe that that has elapsed.

I can assure you that manufacturing has never been a rate limiting step whatsoever, we have a very strong manufacturing platform and.

Or simply <unk>.

Building up the throughput capacity for anticipation of the enrollment to come.

We we all along 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 proper talk at Si com. The confirmed partial response at the lowest dose level is really building momentum there had been a few patients that unfortunately. These are 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 TCR mutation the tcr's.

But unfortunately had other exclusion criterias because of their worsening.

Their health declining at a fast pace so its unfortunate that when other therapies failed them.

They did not meet the inclusion criteria.

Health perspective, even though they matched one of our TCR.

So what we're excited about with the two new Tcr's coming in.

With the move from fresh to cryo preserve product, we believe that we'll be able to produce cells even earlier.

In Ah patients 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.

Bonding to the novelty of our presentation on that.

Case studies.

<unk> and NCI.

So again, a reminder, three different TCR on our clinical trial.

Now been clinically validated by having confirmed partial responses.

So there we're very excited about the prospect of enrolling and treating many more patients in 2023 and anticipate the treatment path.

Turn to increase quite dramatically.

Alright, I appreciate all that color and then just to confirm for me and perhaps I missed it how many patients do you anticipate treating at dose level, two assuming no no dlp's or I camps.

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 will certainly update as we go along.

Excellent I appreciate you guys, taking my questions. Thank you.

Thank you.

As a reminder, if you'd like to ask a question at this time. Please press star one one on your Touchtone telephone.

Our next.

<unk> comes from the line of Chris Howerton with Jefferies. Chris Your line is now open.

Hi, This is anthea, Chris Howerton, sorry about the audio issue earlier.

Thank you for taking our questions and congratulations on a great quarter.

Two questions first is there any differences in the purity and viability of the TCR T cells, using the cryo preserved process and second and.

What tumor types are you expecting to dose and your next patient and what the next data cut will be thank you.

Yes.

Thank you.

Question.

Let me start by saying that in the first two patients when they looked at the list without being.

To the principal.

Holly liability.

<unk> 50 compared.

Compared with distressed versus kind of preserve products based on our early PQ qualification runs.

Do not be any differences in terms of the credit facility.

Same amount of liabilities.

And in ECR that possibility.

Great.

We have not disclosed.

Okay.

Patients ahead.

I would anticipate presenting additional data in 2023 at a major medical conference and at that time share much more translational background of patients that we have and share information about the indications, though again, we do reiterate that we have six different solid tumor indications that we're treating with our phase one to pass.

The trial.

Got it thank you for taking our questions.

Thank you.

I'm showing no further questions in queue at this time.

This concludes today's conference call. Thank you for participating you may now.

During Q&A you can dial stuff.

The conference will begin shortly to raise your hand during Q&A you can dial star one one.

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[music].

Good day, and thank you for standing by and welcome to the <unk> 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 will need to press star one one 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 Lupo with Stern Investor Relations. Please go ahead.

Thank you.

Good morning, and welcome to the <unk> Therapeutics third quarter 2022 financial results conference call and audio webcast.

Please note that today's webcast contain 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, <unk> issued a press release announcing financial results for the three months ended September 32022.

We encourage everyone to read today's press release as well as the <unk> quarterly report on Form 10-Q for the quarter ended September 32022.

Which was filed this morning with the SEC.

The company's press release and quarterly report will also be available on the <unk> website at <unk> Dot 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 covenant of the Safe Harbor provision provisions of the private Securities Litigation Reform Act of 1095.

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 Companys business.

Information on potential risks and uncertainties are set forth in our most recent public filings with the SEC at SEC Dot Gov.

The company undertakes no obligation to revise or update any forward looking statements to reflect events or circumstances. After the date of this LIBOR webcast.

Except as may be required by applicable securities law.

With me today are Kevin Boyle, Senior Chief Executive Officer, Avi Srivastava, Vice President of technical operations.

<unk>, Vice President of research and development and Mike Huang Vice President of Finance.

With that said I would like to turn the call over to Kevin Bryant.

Kevin you may begin.

Thank you Alex and as we finish this veterans day week.

Weekend I just wanted 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 our 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 have been gaining momentum in our TCR T Library phase one two trial as we are working closely with our investigators to identify patients at MD Anderson, who have a match to one of our <unk> and our library.

I am pleased to say that we anticipate treating our next patient before the end of this year.

And 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 and our state of the art C GMP suite.

We have consistently produced high quality TCR T cells at clinical scale.

If successfully manufactured our product at the second dose level.

We continue to advance our Hunter program identifying new tcr's 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 spend.

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 Companys success is not based on a single product.

<unk> is a promising solid tumor platform.

We are differentiated from other <unk> companies and that we target hotspot mutations with T cells that have been transposed with TCR is using our proprietary non viral sleeping beauty technology.

Our lead program is the TCR T Library phase one two 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 tcr's.

For K, Ras <unk> 53, and one egfr.

Three of these 10 Tcr's had been associated with confirmed partial responses in a clinical study, giving us great confidence in the power of Tcr's to treat solid tumors.

We will speak in a moment about the confirmed partial response, we saw in our trial at the first dose level and a patient treated with a K Ras TCR as well as provide an update on this patient at the six month Mark.

Our 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 <unk> TCR.

The third TCR, yielding a clinical response was reported by the NCI and was a breast cancer patient treated with the same <unk> 53, 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 one two trial and the proper talk at the Cri NCI ACR six international cancer Immunotherapy conference or <unk> 22 for shortly.

As we turn to slide seven we will share our great enthusiasm and excitement over the early clinical data from this trial.

The findings presented its icon 2022 to our knowledge represents a very first time that an objective clinical response was observed using a non viral TCR T cell therapy in a solid tumor.

The team is very excited to be among the leaders in the field.

And the team is 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 are also able to detect TCR T cell persistence out to six months.

Most excitingly our product is efficacious, achieving a confirmed partial response and 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 have 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 patients being treated in the fourth quarter.

Okay.

I'd like to provide an in depth review of the results that we presented at <unk> Com. In addition to highlighting six month follow up data from patients 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 <unk> 11, and <unk> mutation matching one of the 10 tcr's within our library.

This patient received standard Psi flu litho depletion 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 and they're right lower lobe shown in red circles through week 24.

There is also significant and durable reduction of non measurable disease and the right long 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 reflected in the red circles through week 24.

What a visual these images provide the potential benefit of our TCR T cell therapy to the patient as demonstrated by significant clearance of this target tumor.

On slide 11, we have the third set of images per patient one.

The right highlight 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 long 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 confirms 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 TCR T cell therapies to effectively kill large established solid tumors, even at the lowest dose levels.

The patients 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 with 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 TCR T cells can home to the tumor microenvironment.

The <unk> <unk> mutation and HLA 11 were detected in the progressing tumor, indicating that the target remains intact and was not lost.

Collectively these results support our belief that the patient received significant clinical benefit from the administration of our TCR T cell therapy.

Our six month progression free survival, which is what patient one achieved is competitive with the only approved <unk> targeted therapy.

K Ras <unk> specific small molecule.

That has a six five month progression free survival.

And there are no approved targeted therapies for Kers, GE 12, D or <unk>, 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 too.

This patient was diagnosed with colorectal cancer and had previously progressed on standard of care treatment.

The patient had <unk> 11.

And a T P 53, or $1 75, H mutation and receive standard Psi flu litho depletion 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 <unk> three mutation in the progressing lesion, suggesting that the target was retained.

Of note. This particular TCR is previously been used by the NCI and a patient with metastatic breast cancer, achieving a partial response with cell persistence out to six months.

So we remain confident in targeting T. P 53, mutations and look forward to enrolling more patients with this TCR and other tcr's 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.

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 manufacturer T cells can survive in the hostel tumor microenvironment.

Additionally, these data also provide proof of concept that we can successfully manufacturer TCR T cells for both <unk> and <unk> hundred 53 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 our lives.

As NCI training and familiarity with the TCR T cell program has enabled him to be an immediate contributor.

Avi.

Thank you, Kevin and good morning, everyone.

Having joined the alliance 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 can be used to treat patients with 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.

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 Joe, 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 <unk> trial.

We have proven that we can manufacture patient cell for both data and deep efficacy mutation in our <unk>.

One in house Cgmp manufacturing facility.

We easily met our acceptance criteria for both dose levels, one and two.

With high rates of liability.

Alrighty and percentage of PCR positivity.

Okay.

We are highly encouraged by our ability so far too.

Anthony and reproducible manufacturer 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 ECR liability trial.

The early stages.

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.

Expand our manufacturing capacity.

We have already implemented <unk>.

That allows for simultaneous reduction of multiple products in our own cgmp suite.

This includes successfully completing process qualifications on with cryo preserved ECR T cells.

Which will add flexibility, but based on the scheduling and treatment.

We expect to file an IND amendment to move from fresh to cryo preserve product by the end of 'twenty to 'twenty two.

And began implementing this team in the first half of 2023.

In addition, this.

<unk> 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 2006 days we.

We will continue to prioritize our work on reducing the manufacturing time further.

And finally, we have also expanded our team.

Hi, Heidi additional manufacturing staff.

Enable multiple shifts in our in house suite.

As a result of all these initiatives.

I am happy to report that we have doubled our existing manufacturing capacity.

Abuse to product simultaneously.

This is a major step forward for our program.

For patients who need our therapy.

I am 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 June who is going to highlight our ongoing R&D effort as well as presentation on our Hunter platform at the <unk> annual meeting starting on slide 20.

Thank you Avi, it's great to have you onboard and to work with you again good morning, everyone on the call.

As you've heard from both albeit Kevin we've been busy breaking new ground here of autos I'm extremely encouraged by what we've observed in our first in human experience with the sleeping beauty TCR T 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 empowering time for the team to know that we have the right platform 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 Neo antigen T cell receptor discovery platform or Hunter.

Now turning to slide 21, we.

We believe Hunter is a differentiated platform that has multiple advantages relative to others in the TCR discovery space.

Let's start with starting with Europe .

Traditional TCR discovery is typically done with healthy donor T cells with a limited number of Hla's and mutations.

The healthy donor is not known to have a mutation. There is a question to whether the T cell really saw and reacted to the target and its natural context.

Often this healthy donor approach can require further enhancement of the T cell receptor to make it recognized the tumor which increases the risk profile.

In contrast, we do not manipulate the tcr's refi they've.

They seem to both recognize the tumor and bind the target is stronger.

<unk>.

Are found in tumor infiltrating T cells also known as pills.

This is likely because the tools that we use for TCR discovery, where presumably inside the cancer trying to fight it and likely visualize the mutation and its natural context.

We use these naturally occurring TCR is taken from the tills in one patient and use them for treatment as TCR T cells and another patient with the same target.

Another distinction of our program is the throughput.

We can quickly screen, many tcr's 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 HLA for mutations based on common peptide prediction algorithms.

The platforms that use this method may be limited and they're searching capabilities.

In contrast, we let the biology driving 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.

Lastly, today, we presented new data at the <unk> conference that demonstrated the ability of hunter to quickly identify and validate new antigen reactive TCR.

The poster is available on our website and we encourage you to have a look to see why we're so excited about this platform.

Our goal in the presented the 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 and the high throughput settings 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 neo antigen reactive TCR, including one shared K Ras Q 61, H mutation and 21 unique personalized mutations.

Both CD four and CDA T cells were reactive indicating that both helper and killer T cell populations could be sources for TCR discovery.

Roughly $1 <unk> was reactive to a mutation in 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 and a two pronged approach.

First we plan to add more mutations to the existing K Ras <unk>, three and Egfr mutations in the library.

Second we aim to add more easily 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 K Ras focused approach against <unk> and <unk> 12.

Indeed, two of the five initial patients we screened.

Tcr's reactive to <unk> 12 fee.

These findings provide evidence of the ability of hunter to discover exclusively owned hotspot mutation reactive TCR that can be added to the current clinical library.

Our enthusiasm.

Scream, specifically for hotspot mutations is further strengthened by these results and we are actively moving forward with numerous samples with K Ras <unk>, three 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 Hla's cell viability relative proportions of tumor infiltrating T cells and other factors as part of the screening prescreening process.

From the initial set of samples we are continuing with roughly a quarter of them for full TCR discovery work up.

This was an efficient and cost effective way to find the best possible tumor 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 to Egfr mutations la five to eight are in exon 19, deletion, which are the dominant mutations in egfr and are highly prevalent and lung cancers.

We chose four K Ras mutations <unk> 12, and <unk> 13 based on their prevalence in solid tumors, especially gastrointestinal and lung cancers.

Given our early efficacy signals in the clinic targeting <unk> D. We are encouraged to add more TCR is reactive to <unk> and to other K Ras mutations into our clinical program.

<unk> <unk> 53 is well known to be among the most commonly mutated genes in all of cancer and its been shown to be highly immunogenic and previous studies, including ones that I hopefully at the NCI.

Even though <unk> 53 is mutated in multiple locations. There are eight hotspots that we were focused on study.

We believe we will be successful in discovering tcr's reactive to mutate at <unk> 53, and that they will be applicable to a large number of patients and 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 creator.

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.

<unk> fully it's August personalized TCR T cell therapy.

I would now like to turn the call over to Mike <unk> to review the financial results for the third quarter, starting on slide 24.

Thank you drew let me review our financials for the three months ended September 32022, which are highlighted on slide 25.

For the third quarter of 2022, we reported a net loss of approximately $8 9 million or <unk> <unk> net loss per share.

Compared to a net loss of approximately $22 7 million or 11 net loss per share.

For the third quarter of 2021.

Collaboration revenue was approximately $2 9 million for.

For the third quarter of 2022.

Compared to approximately zero point $4 million.

For the third quarter of 2021.

The increase was primarily due to the achievement of sales based milestones of Darren a person in Japan isolation pharma K K.

Research and development expenses were approximately $7 $9 million.

For the third quarter of 2022 <unk>.

Compared to approximately $14 5 million for the third quarter of 2021, a decrease of 46%.

The decrease was primarily due to lower programming related costs.

$3 $6 million.

Mainly related to the winding down of our IL 12 and car T programs.

$4 $9 million decrease in employee related expenses due to our reduced head count.

And a zero point $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 isolation.

General and administrative expenses were approximately $3 $3 million.

The third quarter of 2022.

Compared to approximately $8 $2 million.

Same period in 2021 at.

A decrease of 60%.

The decrease was primarily due to lower employee related expenses.

A three $2 million due to our reduced head count and a $1 7 million decrease in consulting and professional services expenses.

As of September 32022.

<unk> 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 six $1 million compared to approximately $9 6 million in the third quarter of 2021.

A decrease of approximately $3 million to $4 million.

Our 36%.

That concludes our financial update.

I would now like to turn the call to Kevin for closing remarks.

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 TCR T clinical trial and towards this end, we expect to dose the next patient in the fourth quarter.

As we mentioned earlier, we are seeing tremendous excitement building amongst clinicians and we have dozens of patients increased 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 R&D will add two new tcr's to our clinical trial targeting frequent mutations and HLA.

This will greatly increase the addressable market for our therapy, and we will be able to increase the number of patients in the queue at MD Anderson.

Secondly, the IMD makes an important improvement in our manufacturing process as we move from fresh to cryo preserve TCR T cell product.

As Avi mentioned this wide flexibility for patient scheduling and treatment and reduced 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 <unk> that highlighted the ability of membrane bound IL 15, TCR T cells to specifically target and kill tumors. While also establishing long lived tumor specific TCR T 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, and 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 brings significant experience to the creator and TCR discovery and clinical trials with T cell therapy.

We believe that this personalized approach may be 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.

As a reminder, if you'd like to ask a question at this time. Please press star one one on your telephone.

Our first question comes from the line of <unk> Agarwal with Cantor Fitzgerald. Your line is now open.

Hi, Good morning, everyone. Thanks for taking my questions. Congratulations on all the progress on the commissioning of the <unk>.

My first question is.

Patients were dosed in June based on my estimates with almost sticking.

Last month for the next set of patients to be dosed, maybe talk about why that why things go along the key bottlenecks that you are working through.

And if you could also comment on what dose will go toward patient would be given and I had a couple of follow ups.

Hi, <unk>, thanks for the questions.

So as you see in the early Sycon 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 this icon.

<unk> talk at the end of September was a really great accelerant to this trial and for enrollment.

In fact, just recently this.

Once it was presented at <unk> was shared with all of the doctors on the stem cell transplant team over at MD Anderson.

The interest is really strong and the pipeline is building and by adding these two new tcr's in the IND filing.

That will even further expand the patient funnel and allowing even more patients to be tracked and to benefit from this therapy.

The cryo preservation 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 is a reason that we've been investing in increasing our manufacturing capacity as we expect.

Enrolment to build and to treat many more patients in 2023.

Okay. Thank you Kevin.

Couple of follow ups. So maybe a question for drew for patient Ron I think the target was not lost and there are some persistent diesels at six months. So any color on the level of memory stem cells and or if you could provide more details from your transformation of work on possible reasons for progression at six months and how could we improve.

With higher doses.

Yes. Thanks <unk>. Good morning, Thanks for the questions were very excited to see.

Persistence in this patient up to six months in the circulation.

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 loans. So we note. The TCR T cells are getting into this harsh tumor microenvironment. So that's very encouraging.

We're also encouraged that the Cara sheetrock D and the HLA <unk> or both.

<unk>.

And the tumor so those are 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 were very encouraged by.

The results of the clinical results of the patient adds.

And really looking forward to treating other patients.

Got it and lastly, Kevin.

This is a key question point investments if you can talk about the cash run rate I might have missed this kind of possible financing avenues, you think might make sense for the company given the next clinical catalyst sometime in 2023. Thank.

Thank you.

Certainly per car 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 are supportive and loyal shareholder base and have also been.

Experiencing a lot of interest from new perspective, investors, who see the potential and power of our TCR T cell therapy.

A reminder, we do have the ATM in place. So that's yet another option. In addition to we work very hard earlier this year to have the shelf in.

In place as well so we have many different options and have teed ourselves up to be able to fund raise.

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.

Thank you.

Thank you.

Our next question comes from the line of James Sheehan with Wells Fargo. Your line is now open.

Hey, good morning, guys. Thanks for taking my question 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 <unk> still present tumor which is great. So will.

Would you be looking at any exhaustion signals.

Maybe that's why the response is going to persist.

And then related when you guys move to the Cryopreserved product can you say what sort of changes as you saw from disease process relative to the current warm cells.

Okay. Thanks, James drew here and good morning.

The first one and then kick over to Avi for.

Manufacturing questions. So in regards to patient one.

Very encouraged with the target's still theyre very encouraged that the T cells are infiltrating the tumor.

Booking ads exhaustion markers there because we actually have some of the cells that are alive from that tumor.

Their ability.

So to be responsive to not only that mutation.

But.

Vitro tumor system. So we're looking at all that we are quite encouraged and wanting to use the clinical data that we get to drive.

Kind of hypotheses around.

What's going on in the clinical setting so.

Kick over to Avi for the Cryo preserve question.

Thanks Sue.

I wanted to start by saying that our manufacturing platform is very robust and reproducible.

<unk> been able to produce high purity of high reliability and high DTI positivity self product.

When it comes to.

Moving from first to Cryopreserved product Theres, not theres not any change in our overall manufacturing process et cetera, we have just added a formulation.

Please that went in the population and we have done a process qualification done and based on that we can say that our overall manufacturing process is very similar to what we have.

Got it.

Yeah.

Thanks, guys I appreciate it.

Thanks James.

Our next question comes from the line of Chris Howerton with Jefferies. Your line is now open.

You may be on mute.

Hey, guys. The next caller please.

Our next question comes from the line of Yale Jen with Laidlaw. Your line is now open.

Hello.

Good morning Al.

Hey, sorry.

My name is.

Thanks for taking my questions My first question.

The next page.

That will be the second dose level.

There's a lot of patients.

So it goes to <unk> 4 billion.

How should we think.

The next one would that be in the same ballpark.

Sure.

Oh.

Then I have a follow up.

Alright, Thanks, Yale, Yes, indeed, the patient number three will be at the second dose level, that's where we intend to treat the patient as you are aware there is a range for the dose levels and so the dose level. Two is anywhere from approximately 10 billion TCR T cells.

Two.

<unk>.

70, TCR T 70 billion TCR T cells, and so no we're not communicating on the exact number in that range, we would anticipate and that's really the guidance of the treating physician where the dose level is.

Okay, Great. That's very helpful. One more question here.

In terms of the two added new TCR T.

I didn't get it quite clearly could you just repeat what specifically those are.

The complication of that those two.

Yes, Thanks sale district here, we're very excited.

Cited to add these new TCR library as part of India Amendment that we're filing yet.

We haven't gotten clearance from the FDA for that those ccr's just yet so we haven't announced the specific identities of them will once they've cleared we anticipate it will be clear because we've already expanded the library from six to 10 late last year. So that's our expectation, but we don't want to be presumptuous with the FDA.

So taken 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 that we can bring.

<unk> TCR T cell therapy to.

As we move forward.

Okay, Great. That's very helpful and maybe the last just housekeeping question here in terms of this quarter you have.

So two night.

Million revenues from the ladder.

<unk> pharma.

Do we anticipate this to be a one time event or occur periodically going forward. Thanks.

Mike you want to take them.

Sure. Thanks, Yeah.

Alright.

Google.

The achievement of our commercial setup there.

And in Japan.

This non dilutive funding for the <unk>.

Company.

We would anticipate the upfront payment that we received from Malaysia, and the third quarter of 2022 will be the most meaningful payment that will receive over the next few years.

Okay, Great that's very helpful and congrats on all the progress.

Thank you.

Our next question comes from the line of Thomas Flaten with Lake Street Capital markets. Your line is now open.

Great. Thanks for taking the questions drew just back to this TCR is I'm, assuming it's safe to assume that they are within the three genes that you guys are already focused on rent.

Yes that is correct Thomas will be within Kers GBP three <unk>.

<unk> Egfr and <unk>.

Again to reiterate that we are looking to add more mutations within the existing genes and to add more HLA is within the existing mutation. So it's consistent with that thesis it'll be along those same lines.

Got it and then going back to the first question about enrollment pacing. If you look at the at the time that has elapsed since patient number two enrolled has it been availability of patients was there was there manufacturing that kind of stood in the wave.

Another patient enrolling sooner I'm, just trying to get some more.

Insight into that timeframe that that has elapsed.

I can assure you that manufacturing has never been a rate limiting step whatsoever, we have a very strong manufacturing platform and.

Simply.

Building up the throughput capacity for anticipation of the enrollment to come.

We.

All along 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 proper talk at Si com. The confirmed partial response at the lowest dose level is really building momentum there had been a few patients that unfortunately. These are these are patients that have <unk>.

Just very tragic diseases with heavy disease burden and as a result, there were patients that did match the HLA and TCR mutation the tcr's.

But unfortunately had other exclusion criterias because of their worsening.

Their health declining at a fast pace so its 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 <unk>.

And so what we're excited about with the two new Tcr's coming in.

With the move from fresh to cryo preserve product, we believe that we'll be able to produce cells even earlier.

Ah patients 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.

Geographies people responding to the.

Our presentation of that.

Case studies mentioned Providence and NCI.

So again a reminder, three different TCR, it's on our clinical trial.

Now they are clinically validated by having confirmed partial responses.

So there 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.

Alright, 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 no DLP zarai counts.

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.

Excellent I appreciate you guys, taking my questions. Thank you.

Thank you.

As a reminder, if you'd like to ask a question at this time. Please press star one one on your Touchtone telephone.

Yes.

Our next question comes from the line of Chris Howerton with Jefferies. Chris Your line is now open.

Hi, This is Chris Howerton, sorry about the audio issue earlier.

Thank you for taking our questions and congratulations on a great quarter.

Two questions first is there any differences in the purity and viability of the TCR T cells using the cryo preserved process and second and what tumor types are you expecting to dos and your next patient and what the next data cut will be thank you.

Thank you.

Quick question.

Let me start by saying you got to know class II patients when they looked at.

Without these two the principle.

Holly liability.

<unk> and Dci positively.

We compare <unk> versus kind of preserve products based on our early PQ qualification runs.

Do not be any differences in terms of appetite at this point, we still maintain the same amount of liabilities.

And ECR the productivity.

Great.

We have not disclosed what the.

Education.

Patients ahead.

Yeah.

<unk> International value increased 23 at a major medical conference and at that time share much more translational background of patients that we have and share additional information about the indications, though again, we reiterate that we have six different solid tumor indications that we're trading with our phase one two basket trial.

Got it thank you for taking our questions.

Thank you.

I'm showing no further questions in queue at this time.

This concludes today's conference call.

Thank you for participating you may now.