Alaunos Therapeutics Inc (TCRT) 2019 Q4 法說會逐字稿

Ladies and gentlemen, thank you for standing by.

And welcome to the Ziopharm Oncology Fourth Quarter and Year-End 2019 Conference Call.

(Operator Instructions) Please be advised today's conference is being recorded.

(Operator Instructions)

I would now like to hand the conference over to your speaker today, Mr. Chris Taylor, Vice President of Investor Relations.

Thank you.

Please go ahead.

Thank you, operator, afternoon, and welcome to the Ziopharm Oncology conference call and webcast to review results for the fourth quarter of 2019.

This afternoon, we filed our 10-K and issued our 2019 year-end results release, both of which are available in the Investors section of our website, ziopharm.com.

For informational purposes, we have also included in our webcast, a set of PowerPoint slides to accompany today's commentary these slides can also be found on our website in the Investors section.

During this call, the company will make a number of forward-looking statements, including statements regarding the potential therapeutic candidates in our development pipeline, regulatory status, financial information and business trends.

Forward-looking statements are subject to numerous risks and uncertainties as described in our 10-K and within other filings that we may make with the SEC from time to time.

Participating on our call today for Ziopharm will be Dr. Laurence Cooper, Chief Executive Officer; Sath Shukla, CFO; and Dr. David Mauney, President.

Following commentary from our management team, we will open the call for Q&A.

In the interest of time, we kindly request that you ask one question and a follow-up as needed, and then please feel free to return to the queue.

Thank you.

And to get started, I'll turn the call over to Dr. Cooper.

Good afternoon, Lawrence.

Thank you, Chris, and good afternoon, everyone.

We are pleased to have the opportunity to speak with you today, and we welcome those of you who are new to Ziopharm.

By way of introduction, we took dramatic steps forward in 2019 to build upon our plan to offer treatment of patients with solid tumors.

We believe Ziopharm stands alone in the vision to be able to treat all solid tumors.

We have advanced multiple innovative technologies that have been widely published based upon convincing preclinical and clinical data.

We have Phase I and II INDs across each of our clinical programs, and have alignment to execute on them with world-class partners.

Finally, we are addressing the largest possible oncology markets by going after solid tumors.

With approximately $177 million in our treasury, Ziopharm is now in its strongest fundamental position to date under my tenure.

Our balance sheet gives us the ability to accelerate towards the size and scale needed to successfully execute on our vision.

It has been just 16 months since we forged our corporate independence and could truly focus on solid tumors.

We have accomplished a great deal during this time period, and I will highlight a few.

In addition to having multiple trials under INDs for all of our programs, we have secured contracts in cooperation with MD Anderson, extending into TCR-T.

We have licensed critical intellectual property, and we have expanded our business developments in Wall Street outreach.

We also spent much of 2019 working with well-known third parties to gain a deeper understanding of the long-term valuation proposition for each of our core assets.

We are using that information to develop our blueprint for 2020 and beyond.

Based on feedback, anticipated need and competitive analysis, we are accelerating our ability to manufacture T cell products.

Our path to commercial viability starts and finishes with the requirement to control manufacturing.

This is true whether it be for our upcoming clinical trials or our longer-term plans to offer commercial therapy.

Since 2019, we've been investing in talent and infrastructure to produce T cell products for ourselves and are accelerating these efforts in Houston, Texas.

We have leased facilities from MD Anderson Cancer Center, and we'll open additional laboratory space within the next 2 months.

We have already begun to execute on expanding our manufacturing plans for TCR-T, which will include scaling up for GMP manufacturing, and we will share more details about this work this year.

At JPMorgan in January, we had multiple A-tier meetings with the buy side, sell-side and large pharma.

It is readily apparent that going after solid tumors is the dominant T cell oncology theme for 2020, and we have 5 areas of competitive advantage that collectively, we believe are unique to us.

First, we're infusing T cells to attack and kill cancer cells.

As a reminder, the administration of T cells has a proven ability to eliminate kilograms of tumor.

Second, we are using TCRs to target neoantigens, which are present in multiple types of solid tumors and are their Achilles' heel; third, we are genetically modifying T cells from their peripheral blood, which have the staying power to recycle killing function to eliminate tumor; fourth, we harness cytokines to engage and control the immune response; and fifth, we use nonviral manufacturing based on DNA plasmids from the Sleeping Beauty system to achieve the scale needed to address multitude of patients with different types of solid tumors.

We are in the right place with the right assets and executing on our plan with a strong financial base.

Especially, as we gain clinical data, we have tremendous upside potential as a public company right now and throughout the year.

Laying out the agenda for this call.

I will update the time lines for each of our core programs.

Our CFO, Sath Shukla will then discuss the recent financing as well as our Q4 2019 financial returns, and then our President, David Mauney will conclude the prepared remarks before turning the call over to the operator for questions.

With that, let me start with an update on our TCR-T program.

The Phase II IND with Dr. Steve Rosenberg at the NCI is the first of several game-changing trials to come for Ziopharm.

We recognize the delays relative to past guidance in dosing the first patients on this trial.

And therefore, I wanted to provide more granular information on the study status, and why we remain, and the NCI remains, excited by this study.

Thus, I'll provide an update on where we stand based on our most recent feedback to relieve concern about this trial starting.

In recent months, we have learned a great deal about the NCI process.

After an NCI IND is cleared, there are several steps that puts -- that the NCI puts in place for any trial before the first patient is enrolled.

This includes transfer of production for research group to the manufacturing team.

As we near patient enrollment, Dr. Rosenberg and his group have been working diligently with Dr. Drew Deniger and our team and have identified improvements to the manufacturing process used to produce Sleeping Beauty-modified TCR-T.

These new learnings benefit not only the study at the NCI, but also the production of T cells, which will be undertaken in our clinical program at MD Anderson.

I have reviewed these data, and they significantly build upon the use of the Sleeping Beauty system.

This is exactly what we want our partner to do as they are a proven engine of ingenuity.

Their efforts have also helped derisk the TCR-T trial as Ziopharm moves to control our own program at MD Anderson.

I'm happy to report that the NCI is moving towards the final engineering runs, which when completed, will ready then to enroll the first patient.

In the interim, patients who come to the NCI continue to be evaluated and considered for this study.

The most appropriate candidates are going through the TCR procurement process with their tumors resected, neoantigens identified as TCR is made.

Based on the very recent input from the NCI, we estimate that Dr. Rosenberg will treat the first patient in the first half of this year.

We are confident with the updates to the NCI process and plans for enrollment, and we're eager to share news of the first patient enrolled.

As mentioned in January's webcast update, we are also implementing plans to bring the TCR-T program under our control.

One of last year's important milestones was our announcement on October 28 of an expanded research and development agreement with MD Anderson to encompass our TCR-T program, and which provides a new home for our growing team and interest in Houston.

The relationship with MD Anderson is a significant competitive differentiator as it enables us to execute on 2 Ziopharm-led approaches infusing TCR-T for solid tumors.

One uses TCRs existing in a library of target neoantigens occurring in hotspots.

The other is based on the work at the NCI under IND to target personalized neoantigens.

Both approaches use the same methodology to produce TCR-T using the Sleeping Beauty system developed at the NCI.

These 2 paths provide us and patients the best chance to treat many types of solid tumors.

At MD Anderson, we can enroll patients with a variety of solid tumors, and we anticipate significant patient flow to our TCR-T program.

Indeed, our set of licensed TCRs in the NCI is already enough to begin enrollment to the hotspot trial.

The access to patients and tissues will accelerate the expansion of the library of TCRs targeting neoantigens in hotspots.

We continue to work on our regulatory road map and are currently engaged with the FDA on our 2 approaches targeting neoantigens in solid tumors.

We believe that already having an opened Phase II IND with the NCI provides us with a head start and a template for these discussions.

We will provide updates regarding the protocols and timing as those discussions progress.

The TCR-T program is a tremendous opportunity for patients in the company.

With everything we have seen to date, we believe we have a strong chance of success and tremendous value creation.

Next, I will touch on our IL-12 program.

In 2019, we made considerable clinical progress in our controlled IL-12 program and received positive FDA feedback granting us Fast Track Designation.

And in Europe, where we received an orphan drug designation.

We have completed enrollment to our 2 recurrent glioblastoma or GBM Phase I studies with 36 patients in the monotherapy expansion study and 21 patients in the dose escalation combination study with OPDIVO, which included an additional 12 patients treated at the highest dosing level.

Beginning in the third quarter of 2019, we commenced a Phase II study for recurrent GBM in combination with Regeneron's Libtayo, and that study should complete enrollment in the first half of 2020.

Since our last quarterly call, 5 additional clinical sites have come online with now 7 of 10 sites enrolling patients.

In total, more than 95 patients with recurrent GBM have been treated at the desired 20-milligram dosing of veledimex with over 80 patients enrolled since 2018 alone.

More than 3/4 of those patients received low dose steroids, which we believe helps IL-12 achieve an immune-mediated antitumor effect.

The encouraging results we have seen to date and the expected data from these additional patients will help inform our decision on later-stage clinical studies in recurrent GBM and potentially expand the program outside of recurrent GBM.

We believe that if IL-12 can meaningfully improve patient outcomes in this cancer, then it can be effective in many other indications, either alone or in combination with immune checkpoint inhibitors.

Considerable data were published and presented from these studies during 2019, including at ASCO in June and at the Society of Neuro-Oncology or SNO in November.

Results from the Phase I monotherapy main trial were also published in the journal Science Translational Medicine last August.

Links to these presentations can be found on our website.

Our team's presentation at SNO a few months ago, provided evidence for the first time of regression of glioblastoma based on imaging.

We also presented confirmatory data demonstrating 16-month median overall survival in patients with recurrent unifocal disease receiving low dose steroids.

We are pleased to note that the Ziopharm team received the top 5 award at SNO based on these data, and we are encouraged by the increasing enthusiasm among the investment community and potential partners in this program.

This interest is also consistent with our meetings at JPMorgan.

We continue to monitor the patients enrolled in these studies and anticipate providing additional updates with the potential for submission of multiple abstracts at major medical meetings in the first half of this year.

I will conclude with an update on our CAR-T program.

In another important 2019 milestone, we announced in October that the FDA had cleared an investigator-initiated IND for a Phase I clinical trial to be conducted at MD Anderson.

As we have previously stated, this study will evaluate infusion of donor-derived CAR-T created through rapid personalized manufacturing, or RPM, in patients with CD19 expressing leukemias and lymphomas, who have relapsed after allogeneic bone marrow transplantation.

Under the RPM process, we can dose patients as soon as the day after gene transfer, including verification that the CAR-T meets release criteria.

During our last quarterly call, we said our team is working hard with MD Anderson to get the trial started by the end of 2019.

As a reminder, MD Anderson is manufacturing the product for this study.

And as we rounded out the year, some delays were experienced as the technology transition to their GMP facility.

But I'm pleased to tell you things have gone well since.

Final qualification batches are underway with the required regulatory step, referred to as the site initiation visit, or SIV, planned in the coming weeks.

Indeed, the first patient is being identified by our principal investigator for this trial and initiation of this study is an important near-term milestone for our company.

And we look forward to sharing news with you in the first half of this year.

There are 2 additional recent items to mention regarding our use of the Sleeping Beauty system to reprogram T cells.

Last month, we published in the Journal Blood, encouraging long-term outcome data after infusion of Sleeping Beauty modified CAR-T based on a prior generation of this technology.

This describes outcomes of patients with relapsed or refractory B-cell lymphoid malignancies, all of whom had received CD19-specific CAR-T infused after autologous bone marrow transplantation.

4 patients demonstrated sustained persistence of CAR-T many years after infusion.

5-year progression-free survival and overall survival was 71% and 86%, respectively.

Last December, our team presented at the 2019 ASH annual meeting, new preclinical data validating rapid personalized manufacturing with TCR.

These results show that T cells genetically modified using DNA plasmids from the Sleeping Beauty system to express TCR with membrane-bound IL-15 exhibited antitumor effects.

These data build on our approach to reduce the cost and complexity of T cell therapies.

Finally, an update on our joint venture, Eden BioCell.

Things continue to progress well with our colleagues in Greater China.

The tech transfer for the RPM technology is largely complete, the GMP manufacturing facility is staffed and equipped and the scientists are currently conducting test runs of the RPM process.

They have also commenced discussions with the Taiwanese FDA as we expect the first trials to start at a large hospital in Taipei.

Our partners at Eden BioCell advise us, the IND for the autologous RPM CD19 CAR-T trial will be filed this year.

It is worth noting that the travel restrictions with new coronavirus in China have to date not prevented Eden's ability to work in Taiwan.

And while the situation will continue to be monitored, we are not experiencing significant delays.

In summary, over the past 16 months, we have assembled the technology, people and funds and made significant progress in all our programs.

This bodes well for the future as throughout the year, we expect to have data on TCR-T, deeper clinical insight into controlled IL-12 and RPM for CAR-T.

These programs provide significant value-creating opportunities.

And this breadth of upside potential appears unique to Ziopharm.

And now I will hand the call to our CFO, Sath Shukla.

Thanks, Laurence, and good afternoon, everyone.

Let me begin by saying a few words about our recent financing efforts.

To achieve our vision to develop treatments for all patients with solid tumors, it is essential that we keep the company well capitalized in comparison to competitors in the cell and gene therapy space.

As we disclosed at the end of the third quarter of 2019, our cash balances at that time provided a runway into the first half of 2021, which meant that to avoid a going concern audit opinion, we would need to raise capital in the first several months of 2020.

We carefully evaluated this timing and considered it to be risky.

We do have market catalysts expected this year, but we came to the conclusion that hoping and waiting for the exact right time while exposing the company to capital markets and political risks, was imprudent.

Furthermore, given that many other biotechs were secure capital in late 2019 and early 2020, potential deal fatigue and limited available funding could post substantial additional risks if we waited too long to secure financing.

We, therefore, began executing on fortifying our balance sheet starting in December, first, engaging in some ATM financing for approximately $16 million.

However, following a successful GBM event, where we shared the company's prospects with multiple top-tier biotech investors, management turned off the ATM and engaged in a traditional financing.

This financing was achieved quickly, derisked our balance sheet and will now enable us to accelerate and achieve many important goals for the next 2 pivotal years for the company.

The proceeds in addition to current market prices and conditions also precludes the necessity of using the ATM anytime in the near future.

The new capital serves many critical purposes and to drill down a bit more concretely related to the use of these proceeds we can, first, accelerate the build-out of our new Houston facility on the campus of MD Anderson, which will serve as the foundation for the commercial path for our TCR program.

Second, exploratory expansion of our TCR library to support our TCR hotspot trial.

Next, advance the recruitment of specialists personnel for our TCR program, and also to support potential broadening clinical initiatives for our controlled IL-12 program as we advance towards later-stage studies and potentially other indications.

And we can now take control of manufacturing with both personnel and infrastructure, which has clearly been a limiting factor for us compared to our peers, many of whom, control manufacturing.

We see almost daily news of substantial gene and cell therapy manufacturing investment, and we think this new area alone will provide great value for Ziopharm in the medium and long term.

Turning to the specific financial results for Ziopharm's fourth quarter of 2019.

As noted in our news release, research and development expenses were $10.2 million for Q4 of 2019, compared to $8.2 million for Q4 of 2018.

This increase reflects expansion of the company's clinical programs, including the initiation of the Phase II combination trial of controlled IL-12 with Libtayo as

well as work for both TCR and CAR-T programs.

G&A expenses were $5.8 million for the fourth quarter of 2019 compared to $4.6 million for the fourth quarter of 2018.

This increase reflects our increased headcount, recruitment of key personnel and expanded capabilities.

On a cumulative basis for the fourth quarter of 2019, we reported a net loss applicable to common shareholders of $15.7 million or $0.09 per basic and diluted share.

Comparably, in the fourth quarter of 2018, Ziopharm recorded net income applicable to the common shareholders of $194.5 million or $1.29 per share, basic and diluted.

The increased income attributable to common shareholders in 2018 resulted primarily from the forfeiture and return of all the company's Series 1 preferred stock, helped by its former partner, and the relinquishment of Ziopharm's obligations under a pharma agreement, accounting for approximately $207 million.

For the full year 2019, R&D expenses came in at approximately $38.3 million compared to $34.1 million in 2018, while G&A came in at $19.5 million slightly below the $19.9 million in 2018.

The ramp in R&D spend, while maintaining discipline on the G&A spend, reflects the company's continued commitment to optimal capital allocation to focus on progressing the science.

We are dedicated to growing our business and putting Ziopharm in the best possible position to capitalize on our compelling technologies.

In addition to the $80 million in cash at year-end, we also had a prepayment balance of approximately $20.3 million for work to be conducted by the company at MD Anderson under the new agreement.

Incorporating our recent financing activity, our cash position now enables us to provide funding for all our programs and infrastructure build into mid-2022.

And now I will turn the call over to David for final comments.

Thanks, Sath.

Before I provide some comments on our business, I'll share a brief word on new coronavirus or COVID-19.

Our thoughts go out to all of those affected by this difficult illness.

We are currently assessing the impact, a broader spread of the illness may have on our business and have begun identifying mitigation plans as needed.

As Laurence noted, our colleagues at Eden and TriArm have confirmed that they continue making progress, and they do not currently expect significant business disruption in our CD19 program in Greater China.

Further, enrollment in our IL-12 clinical trials, all of which are in the U.S., are either complete or nearing completion, and we have drug available to complete our ongoing studies.

Our planned TCR-T clinical trials appear unaffected by the outbreak.

We expect to discuss the possible impact of the new coronavirus with our other partners, including the NCI and MD Anderson as the situation in the U.S. evolves.

And of course, we will be evaluating the impact this may have on our employees' day-to-day activities.

Fortunately, we already have the IT systems in place that allow most of our employees to work remotely if needed.

We have obviously achieved many things in the last 16 months and look forward to a prosperous future.

I would like to strongly reinforce our vision, which is to provide next-generation therapeutic options to treat any patient with a solid tumor.

And if we achieve that goal, significant rewards can be seen.

We have worked hard and fast to create unique attributes to Ziopharm, which Laurence has covered today and the market opportunity for us is tremendous as Ziopharm has commercial rights to multiple billion dollar markets.

We are, of course, engaged in multiple continued dialogues with potential partners.

And as Laurence mentioned, we have increasing data on the timing and value propositions for each of our assets.

With the recent financings, we can move beyond our out-licensing discussions to now also have additional efforts where we are considering in-licensing technology and IP to build upon our foundational assets.

We have expanded our business development capacity internally, and we have engaged third parties to review and advise on valuation and longer-term plans for each of these assets.

We expect to have human data in hand across our 3 programs over the course of this year.

This will put us in an enviable position, providing us significant flexibility for both in-licensing additional technologies and pursuing collaborative transactions for our existing therapies.

A few comments on the organization we are building.

We hired over 30 people last year and expect even more this year, including in the C-suite.

And with the resumes already in hand, we expect to continue the trend of landing top-tier people with excellent capabilities.

We are building up and expanding on our investor relations efforts and have activated plans to have scheduled monthly outreach calls, and we will increase our face-to-face meetings with our major shareholders, especially going forward.

We have engaged a West Coast firm and are in the process for a full corporate rebranding.

Especially as we get all of our trials rolling, we are a completely different company than we were in October of 2018, and that should include a new look and feel, a new name and a new stock ticker.

We expect this rebranding effort to rollout in the second half of this year and look forward to updating the market on more specific timing and process as we get closer.

It hasn't always been easy, but Laurence's vision many years ago was to provide a rational, scalable, cost-effective immunotherapy that could have an impact on not just some markets of cancer patients, but all of them.

If there is one thing I can say with certainty, Laurence's training gives him an uncanny knack for seeing the movie play out before the script is even written.

And we have the fortitude, commitment and now the backing to see his predictions come true for all of us.

Thank you for your continued support.

And with that, I turn the call over to the operator for questions.

(Operator Instructions) Our first question comes from I-Eh Jen with Laidlaw & Company.

Congrats on the progress.

That's quite remarkable altogether.

Maybe 2 quick questions here.

The first one is for the MD Anderson in terms of TCR-T development.

Are you guys going to wait for the NCI to complete their protocol and start to enroll patients before the work over in MD Anderson, so you have a more homogenized the protocol -- clinical study protocols?

Or you will have additional sort of modification or adjustment on that?

Yes, thanks.

Yes, I'll take that question first.

So the clinical trials at MD Anderson, you can anticipate those to start alongside the NCI.

The NCI to us is a program that has great value, not only today, but going forward.

You can, I think, expect continued iteration by Dr. Rosenberg and his group.

And those learnings under our CRADA will feed back into MD Anderson and thus, our clinical trials.

So to put it all together, we enjoyed the relationship with Steve and his group as essentially the foundry.

But we're a commercial leading company.

We want to develop drugs for solid tumors.

And so we'll execute on that vision at MD Anderson, and you'll have -- we'll have more to say about that going forward.

And maybe just to follow-up a little bit on that, on from a revenue -- cost perspective.

Should we anticipate that once you start the MD Anderson work on TCR-T, the R&D expenditure could increase more substantially, I guess?

Than otherwise we'll model?

Yes.

So we'll review the model one more time then we'll try and get back to you on that I-Eh.

But yes, there will be a ramp in the R&D expenditure, obviously, for sure, because we are an R&D company.

And if you look at how much we actually put in OpEx this year and our run rate on cash.

When we disclose that right now, we are anticipating our cash taking us into the middle of 2022.

You can sort of back into some of the ramp expected, obviously, this year, also next year and then going into 2022.

So certainly, the expectation is that we will execute more, and therefore, we will spend more.

Our next question comes from Thomas Flaten with Lake Street Capital.

To follow-up on the earlier question with respect to the MD Anderson TCR study running alongside NCI.

Given that you're still in discussions with FDA around protocols and things like that, could you provide some more granularity on those specific discussions, IND submissions, clearances, et cetera?

Just so we understand how those things will run alongside one of those.

Yes.

Thanks, Thomas.

So the -- I think the way I think about it is the playbook in terms of the IND has been established by Steve Rosenberg.

We take that playbook now and adapt it to our own commercial-facing needs at MD Anderson.

Those discussions are underway with the regulators.

They will come to rest, and then we will update you and the market on our plans in fuller detail.

And then, I guess, kind of tied into that, and then I'll jump back in the queue.

With respect to having data for -- across all 3 programs in 2020, could you comment a little bit upon what types of data we might have expect to see?

I'm having trouble seeing the time lines come together with kind of the broad first half, second half guidance?

Sure.

We've got a slide actually that we -- that's on the deck.

So the way we're positioning the company is really just to bookend this in the first half of 2020 at the moment.

So as you look at those programs, we'll have the dosing at the NCI trial, that's a Phase II.

We'll have enrollment to our Phase I trial for the rapid personalized manufacturer of CAR-T.

We'll have announcement around the completion of enrollment and the initial data readout for our controlled IL-12 in combination with Libtayo.

We'll have Phase I data readout with controlled IL-12 in combination with OPDIVO.

And we'll have Phase I data readout from controlled IL-12 as a monotherapy in that expanded cohort.

So those 5 activities will be in the first half of this year.

And then as we get into essentially the next quarter or so, we'll then move that time line so that you can look deeper into the company for the second half of this year.

But that's a pretty significant package for just this first half.

Just a follow-up, sorry.

So if you're going to see dosing in the first half at NCI, do you have a sense from Rosenberg with respect to number of patients, cadence of enrollment, so that you can actually get data out in 2020?

Yes.

We -- so that time line and with respect to the public is governed by Dr. Rosenberg.

That's really a lot of the impetus for us to be moving the technology under our own INDs down to Houston with MD Anderson.

But having said that, Steve's been an excellent steward of our technology.

And quite frankly, the field, and regularly put out important updates.

And I expect him to do the same with rapidity around our program.

Our next question comes from RK of H.C. Wainright.

Just on the NCI program, as you're learning more about the process itself.

So after NCI runs these successful manufacturing runs for the clinical material to get started, is there anything else that they need to do before they get the study going?

Yes, that's an excellent point.

So as -- the manufacturing, obviously, is an important part that's governed under the IND.

You've heard my comments around how then learning was added on top of the IND.

And then once Steve is ready to go, the patients then essentially, that are in the queue, can then be treated.

So there's going to be, I think, an important part of the story where not only at the manufacturing solution, I think, when he's checked that box, but the patients then essentially have that clinical need that they need to essentially receive that TCR therapies.

And Steve governs that transition essentially as patients come off the queue into essentially the clinical trial.

Okay.

And then on the controlled IL-12 program, outside of GBM, what other tumors would you be -- would you think are a likely target and if cost is no issue, which ones would you be going after?

Yes.

That's a great question.

So for us, we are -- our clinical data really teaches us that IL-12 can turn cold tumors hot.

And we think that's important, especially for tumors that have failed immune checkpoint inhibitors.

So we are looking closely at those types of tumors.

In other words, immunological deserts, ones in which then can benefit from an influx of T cells.

And as I said, of those tumors out there, RK, and often, those tumors match up, actually, quite frankly, to the ones that don't benefit from immune checkpoint inhibitors.

Okay.

And then the last question is regarding the data expected during the first half, is that pretty much -- wait til the end of the enter the first half into ASCO?

Or it could be any other...

Could be any time.

It could be anytime.

We see a continued divulgence of data throughout this first half.

Our next question comes from Jim Birchenough with Wells Fargo.

It's Nick on for Jim this afternoon.

Just congratulations on, it seems like this is going to be the year for the company.

So I'm sure you're very excited about all of the programs.

Just in terms of the hotspot trial -- sorry, the neoantigen trials, it seems like that the differential difference here between the NCI approach and your approach will be in terms of the algorithms and technologies used to identify the hotspots.

Outside of that, the 2 trial will be very similar.

Is that the case?

Yes, I think that's a good starting point, Nick.

Both the NCI and Ziopharm will be pursuing the personalized TCR-T therapy.

That's a very broad solution really for like -- for most patients, actually, quite frankly, with solid tumors.

In addition, though, Ziopharm with its partner at MD Anderson, will be developing the hotspot trial.

And as you know, that's a way to treat a subset of patients, but to do so much faster because you're screening the patients for the mutated antigen.

Right.

Right.

And on that trial, Laurence, will you be in a position to essentially -- I think you made the comment that you already have enough TCRs in your library to execute a trial.

Will it be an all-comer trial?

Or will you initially say, well, let's look at a certain subset of KRAS, for example?

Yes, yes.

No, that's exactly the right question.

Nick, we'll -- we're in dialogue about that.

There's basically those kinds of trial designs, and we want feedback from the FDA on that type of trial design, and then we'll get back to you.

Okay.

And then last one and I'll hop back in the queue.

Can you -- refer to IL-12.

And so now you have cash through the middle of '22, you're going to have critical data by midyear for this program.

What are you assuming in terms of additional trials beginning through the middle of '22?

Because I think at one point in the past, I seem to recall that your preferred way forward with IL-12 was with a partnership?

Yes.

No, I think as the data come in, especially through the expansion study and the Phase I trial study with OPDIVO, we've seen really reassuring data, Nick.

I mean, we've got pretty significant long-term survival, 16-or-so months now.

We've got clear evidence of anti-tumor effect based on MRI scan.

We have serially biopsied these patients and shown an influx of T cells.

So these data are -- means that the company has done a lot of work since essentially those comments were put out there.

At the time, that was correct that there was a look for a potential partner.

But now, I think there are many options to Ziopharm, and we're going to really essentially look at these data coming in through the year and see what makes the best sense for the company.

Sorry, Laurence, so just to clarify, do you have money then assigned for additional -- starting additional trials in '21, '22?

Sure.

I'll turn it over to Sath here.

Sure, Nick.

So I think what I can say is that our cash runway conservatively does not assume any partnership input at this point.

So whatever we want to do with that program and progress it in our GBM and potentially other indications, we have assumed that the funding for that today comes from the company for our planning purposes, and we lay out the cash runway.

Obviously, when data roll out and we decide whether -- and which partnerships to explore, that number could change.

But conservatively, we have not built in any partnership funding in any of our analysis.

Our final question is a follow-up from I-Eh Jen.

Are you guys going to announce when you start the phase on the TCR-T study at MD Anderson in the press release or some other sort of methods.

Yes.

Thanks, I-Eh.

So just to clarify, we will announce when the TCR-T starts or rolls at the NCI.

We will also guide the market on our plans for our own commercial activities at MD Anderson.

Okay.

And maybe just one more question for you, which is that in terms of the combo study, OPDIVO data you intend to report this half of this year.

Do -- should we anticipate anything related to the time or the duration of the study, the endpoints, such as sort of progression-free survival or others or simply, which was mainly focused on the response rate and other relevant data set?

Yes.

I -- what I try and do -- what the company tries to do is show survival because that is the benchmark.

That's by which the EMA as well as the FDA will allow potential product to move forward.

But in addition, because we work with academic centers, we're often able to add additional color to those data, for instance, the immune response data, whether that be through biopsy or through imaging.

So that type of package will be put together, I anticipate, for the first half of this year.

And as a guide, you can look back at the SNO poster that we put out last November as essentially -- as a template for the way the company is keeping the Street apprized of our activities.

Congrats on the progress so far.

Okay.

Thank you very much for questions, and I think that now concludes the call.

And everybody, have a good day.

Ladies and gentlemen, thank you for your participation on today's conference.

This does conclude your program, and you may now disconnect.