Q4 2022 INmune Bio Inc Earnings Call
Speaker 1: Part that now C.
Speaker 1: of the many me a new more we'll have the
Speaker 2: Greetings and welcome to the Immune Bio fourth quarter and full year 2022 earnings call.
Speaker 3: This conference will be recorded.
Speaker 2: The brief question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. It is now my pleasure to introduce Mr. David Moss, CFO of InMean Bio. David, the floor is yours.
Speaker 4: Thank you, Paul, and good afternoon, everybody. We thank you for joining us for the call for Immune Bio's full year 2022 financial results.
Speaker 4: With me on the call is Dr. R.J. Teske, CEO of Immune Bio, and Dr. C.J. Barnum, VP of Neuroscience, who together will provide a business update on our dominant negative TNF platform.
Speaker 4: Dr. R.J. Teske, CEO of Immune Bio, and Dr. C.J. Barnum, VP of Neuroscience, who together will provide a business update on our dominant negative TNF platform, or X-Pro.
Speaker 4: Also on the call is Dr. Mark Lodell, Chief Scientific Officer of Immune Bio, who will provide an important update on Immune, our memory-like natural killer cell oncology platform.
Speaker 4: Before we begin, I remind everyone that except for statements of historical facts, the statements made by management and responses to questions on this conference call are forward-looking statements under the Safe Harbor provisions of the Private Security Use Litigation Reform Act of 1995.
Speaker 4: These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements.
Speaker 4: Please see the forward-looking statements disclaimer on the company's earnings press release, as well as risk factors in the company's SEC filings, including our most recent quarterly filing with the SEC.
Speaker 4: There's no assurance of any specific outcome. Undo reliance should not be placed on forward looking statements, which speak only as the date they are made and as of the facts and circumstances underlying these forward looking statements may change.
Speaker 4: Accept as required by law, immune biodisclaims, any obligations to update these forward-looking statements to reflect future information, events, or circumstances.
Speaker 4: Now I'd like to turn the call over to Dr. RJ Tessie, CEO of Immune Bio. RJ.
Speaker 5: Yeah, thank you, David. And I thank everyone for joining us today.
Speaker 5: As usual, I will arrange my remarks to highlight key takeaways from the first...
Speaker 5: fourth quarter, and provide updates on our platform programs.
Speaker 5: I will start by reviewing our developments in XPro. CJ Barnum, the VP of CNS Development will help me with those comments.
Speaker 5: I will then hand it over to Professor Mark Weddell, our CSO, who will focus on what's going on with the Inkbeam program before I pass it back to David.
Speaker 5: to go over the financial results and provide an update.
Speaker 5: for results and provide an update on upcoming and new milestones.
Speaker 5: This will be followed by a Q&A.
Speaker 5: I will begin with our Phase II program in Alzheimer's.
Speaker 5: Actually, AVI is what we call an Alzheimer's disease due to inflammation.
Speaker 5: We continue to enroll patients in the US and Canada. The FDA's full clinical hold has affected our timeline.
Speaker 5: This has encouraged us, the company, to develop alternative strategies to meet our primary goal of completing the Phase II Alzheimer's program in a timely fashion.
Speaker 5: We have implemented several important changes.
Speaker 5: And it's several important changes in the last.
Speaker 5: changes in the last few months.
Speaker 5: to help us reach that goal.
Speaker 5: We will modify the enrollment criteria in the larger, longer Phase II mild AD trial to include both mild AD and MCI patients.
Speaker 5: mild cognitive improvement patients. As you know, they're kind of a pro drum for Alzheimer's.
Speaker 5: So adding the MCI patients.
Speaker 5: Adding the MCI patients is a new change.
Speaker 5: This consolidates the MCI and the mild Alzheimer's disease trials into an early Alzheimer's disease phase two study. As you recall, we had separated them previously.
Speaker 5: into separate trials. The combined trials should approve our ability to demonstrate a clinical benefit in patients receiving X-Pro, should accelerate enrollment.
Speaker 5: and reduce costs.
Speaker 5: The consolidation should help us achieve our goal of reporting top-line data from the Blinded, Randomized, Tecebo-controlled, Phase II program in early Alzheimer's disease.
Speaker 5: our goal of reporting top-line data from the Blindest Randomized Receivable-Controlled Phase II program in early Alzheimer's disease in the second half.
Speaker 5: of 2024. Consolidating the trials allows an estimated 8 million U.S.
Speaker 5: dollar savings.
Speaker 5: from the budgeted costs of the MCI trial.
Speaker 5: We will use these savings to open additional clinical sites and other regulatory venues to help speed enrollment.
Speaker 5: The new early ADI trial design conforms to industry standards and then makes what we would plan to do in the phase 3.
Speaker 5: registration trials.
Speaker 5: During the FDA clinical hold, we have expanded our clinical development.
Speaker 5: horizons beyond the US.
Speaker 5: We are aggressively looking for ways to enroll patients globally while working our way through the FDA hold. By operating in foreign jurisdictions now during the phase two that we hadn't originally intended to, we should improve the efficiency as we enter the pivotal phase three study, that is the efficiency of the patient.
Speaker 5: of getting that phase three up and running.
Speaker 5: To be clear, the consolidation of the two trials does not increase regulatory or clinical risk.
Speaker 5: In fact, we believe it reduces clinical risk.
Speaker 5: while also conserving resources and positively benefiting enrollment.
Speaker 5: CJ Barnum, VP of CNS Development will comment on this further when he speaks.
Speaker 5: We describe the XPro asset as an iceberg with multiple CNNs.
Speaker 5: and applications and a hint of applications.
Speaker 5: outside the CNS therapeutic silo.
Speaker 5: Given the broad swath of diseases that can benefit from dominant negative TNF therapy.
Speaker 5: I often call it an expertly pharmaceutical company in a bottle.
Speaker 5: A review of the more than 75 publications on our website provides a window into the many clinical.
Speaker 5: opportunities. Each of these clinical applications outside of the CNS therapeutic silo are business development opportunities.
Speaker 5: How can Immune Bio take its scarce resources to be serious about business development?
Speaker 5: How can we leverage XPro into that business development program?
Speaker 5: In January , we unveiled how we plan to solve these two problems.
Speaker 5: We formed a wholly owned subsidiary, DNO2, Inc.
that will hold the intellectual property to facilitate partnering and business development in the Duchenne muscular dystrophy.
that will hold the intellectual property to facilitate partnering and business development in the Duchenne muscular dystrophy. I'll call that DMD as I go forward.
This structure allows us to pursue a partnership in DMD without compromising the company's E.C. and S. franchise.
Why is DMD the inaugural partnering effort? Well, TNF has long been, soluble TNF that is, has long been known to be part of the pathology of the same muscular dystrophy.
Attempts to use non-selective TNF inhibitors to treat DMD Never reached the clinic because...
Sorry.
because of cardiac toxicity.
We believe that the DMTNF solves this problem.
because of its selectivity by protecting transmembrane TNF function.
while neutralizing the devastating effects of soluble TNF on skeletal muscle.
The DMZ therapeutic landscape has been focused on controlling inflammation, primarily with corticosteroids, and by replacing dystrophin, primarily using gene therapy strategies.
In animal models of DMD,
DNTNF therapy decreases fibrosis and...
promotes muscle regeneration.
Muscle regeneration is the holy grail of DMD therapeutics.
The apparent ability of DMTNF to promote muscle regeneration is unique.
Hence, we are seeking a partner to drive this clinical program forward because we think it will benefit patients.
investors. In addition to the right business structure for partnering you need a drug to place into the partnership.
Partnering our crown jewel expo is not an option at this time. We have work to do to add value to that prized asset.
Over the past 18 months, we've been working to develop new compounds.
with the biologic capabilities of EXPROW.
but that are considered new chemical entities, that is new drugs.
considered new chemical entities, that is new drugs. We call these the PSARs.
Curipath, the company in Spain, has developed these polysarcopene polymers.
that are half-life extenders that replace the peg.
X-Pro. You remember X-Pro has a 10 kilo Dalton linear
peg that is a taff life extender.
The PSARs, we call them the sons of expro, are
function as selective inhibitors of soluble TNF, but they have novel IP.
and have slightly different biologic characteristics that can be leveraged into the new indications, in some ways tuned to fit the indication that they are earmarked for.
We have earmarked one of these novel PSAR compounds for DMD. Put simply, the PSAR program converts XTRO, the drug, into DNTNF, dominant negative TNF inhibitors, the drug platform, with applications across many areas of medicine.
You will learn more about this important program in the near future.
We do plan to launch the treatment-resistant depression program in the U.S. in 2023. It will happen after the FDA hold is resolved. We anticipate top-line data from the early AD phase 2 program in the second half of 2020.
the exact timing of that data release in the second half of the point.
2024 is it's a little early to predict exactly where that end because we are moving in a lot of different regulatory jurisdictions at the same time.
But now I will pass it over to CJ Barnum, the Vice President of CGA.
in this development who can speak more about the early ADI program.
out the early ADI program. CJ?
Are you on mute?
Thanks, RJ. As RJ mentioned, the ADO2 phase 2 trial in mild Alzheimer's patients with inflammation is open in Australia and Canada. As a reminder, ADO2 is a blinded, randomized, placebo-controlled study evaluating cognition in mild AD patients.
biomarkers of inflammation.
We have started the process to include MCI patients also with biomarkers of inflammation.
into that trial. This complex regulatory process is underway. Once complete, this trial will enroll early AD patients.
a group that includes both MCI and mild AD patients.
These patients will be treated with X-Pro for six months.
including MCI patients has two important benefits.
First, it improves our ability to observe a clinical response, as our expectation is that X-Pro will have a greater benefit in MCI patients than in even mild AD patients.
This is further driven by extending the treatment of MCI patients from three months as we were in ADO3 to six months of treatment.
With longer therapy, both the number of MCI patients responding and the magnitude of that response should be greater.
Second, our clinical sites have told us that including MCI patients increases the number of eligible patients for the trial and should positively impact enrollment. Importantly, consolidating trials allows us to save costs by treating fewer patients in a single trial.
The primary reason we had two separate studies for MCI and MILD-AD were based on the MRI biomarkers of primary interest, not clinical outcome.
As you may recall, the primary endpoint for both ADO2 and ADO3 is the EMAC, a cognitive composite that was empirically derived to measure clinical cognitive changes during early AD. As it relates to the differences in imaging biomarkers, we will address these differences.
by pre-specifying the expected change in MCI and mild AD patients.
Patients that complete the six-month Phase II early ADI study are eligible to enroll into a 12-month Open Label Extension Trial, or OLE. The OLE study is a 12-month study where safety and efficacy of X-Pro will continue to be evaluated. For more information, visit www.
Efficacy will be assessed every three months by MRI and clinical rating scales.
All patients that enroll in the OLE study receive XPro regardless of previous treatment assignment.
The OLE serves multiple purposes.
First, it provides long-term safety data. We believe regulatory authorities will expect 18 months of safety data for marketing authorization.
The OLE strategy will provide this critical safety data.
Second, the OLE provides long-term efficacy data. Third, the OLE is a recruitment tool.
Guaranteed access to 12 months of treatment following a six-month study provides significant advantages over other trials.
Patients and clinical teams like this trial design, and so far patient participation in the OLE is high. We expect to share some of this data in due time.
Now I'd like to pass the call back to RJ.
Thank you, CJ. I will now move to InCune, our memory-like natural tiller cell priming program. The high-risk MDS-AML InCune Phase 1 program continues to make progress in the UK with the second site now open at the Royal Hanson.
Shear Hospital and at Sheffield University Medical School.
A patient was consented this week and treatment is planned for March 7th, a week from today. Excuse me, March 9th, a week from today. In addition, we will also be expanding the...
MDSAML program into Europe for the third site.
Atakan University Hospital in Athens, Greece.
is expected to open later this month.
We've previously stated that InQM may be an ideal therapy to...
treat solid tumors because of its performance in the hostile environment of the TME.
Mark Liddell will discuss this more in a moment.
In October , we announced positive solid tumor preclinical data in prostate, renal cell, ovarian and nasopharyngeal.
cancer cell tumor lines.
consumer lines that are all resistant to NK killing.
that when the NK cells are treated with ink man.
they now can kill these NK-resistant tumors.
We implied we were pivoting to solid tumors because we thought the effects of these means were somewhat unique.
And today we are pleased to announce that the company will be filing for an IND to use the IND to treat patients with metastatic castrate resistance.
And today we are pleased to announce this company will be filing for an IND to use in commune to treat patients with metastatic castrate-resistant prostate cancer in the US.
Prostate cancer is the most common cause of cancer in men, if you exclude non-melanoma skin cancers. Prostate cancer is the most common cause of cancer in men, if you exclude non-melanoma
The trial is expected to take place in four or more medical centers in the US.
It will enroll approximately 30 patients in a flexible Bayesian
design that will allow us to determine safety.
proof of biology and confidently pick the dose of InKimmune to move into
a blinded, randomized, potentially pivotal trial.
As you have come to expect we are using a mix of standard and novel biomarkers to measure your tumor response.
Wouldn't finish.
we should have a
a good understanding of how the drug works in the disease and have a credible biomarker package to move into the blinded.
randomized trial.
If I can paraphrase the quote from Professor Matt Redding, the principal investigator from the Johnson Comprehensive Cancer Center at the UCLA School of Medicine.
There are no good options for metastatic catfish.
resistant prostate cancer, especially given the recent failures of checkpoint inhibitors." End quote.
We are excited about the potential of ink means in treating solid tumors and hope to make a difference in men with prostate cancer.
With that, I'll pass it to Professor Mark Weddell, CSO.
Mark. Thank you, RJ. And thank you once again to everyone that's joining us to hear what I think is some really exciting progress that we've been able to make.
So some of you will know that we recently shared with the investment community positive solid tumor efficacy data with immune in multiple cancer cell lines as RJ alluded to and As we highlighted in our recent press on the topic solid tumors of the majority of human cancers I'm sure you will know that but cell therapies currently focus on the 10% hemochromatic tumor or liquid cancers
The recent data that we've shown and shared with people provides insights into why the company believes that the immune harms natural killer cells to override the impressive risk of spine presentation.
high-proxier and regulatory cells in the term environment or the TME for short. The interaction of the TME with cancer cells and it can drive tumor progression and that's well known and it's thought to prevent many cell therapies from being effective and we've seen that increasing in the over the last few years. These complex interactions have to be considered when designing cell therapies to treat solid çek
And the TME is hostile to cell therapies because of these two things, the presence of the immunosuppressive immunoregulatory cells and the extreme hypoxia or lack of oxygen within the tumour. So a cell therapy to be effective must operate in that environment.
And what we've shown over the last 12 months and more recently
InqN converts resting normal NK cells in patients into what are now known in the field as memory-like NK cells and these can target solid tumors directly even in the presence of immunosuppressive regulatory cells as we've shown and particularly in hypoxic environments.
The company's preclinical data with human-in-case cells and cancer cells show that in primers-in-case cells from patients and indeed from healthy donors, to lies in-case resistant solid-chimous cell lines. We've worked with ovarian cancer and published those data, breast cancer, prostate cancer, more recently renal cell carcinoma, and now straight out of the box, nasopharyngeal cancer cells.
And when compared to resting NK cells, which are normal NK cells from healthy donors or patients before treatment with InKMune, the InKMune-primed NK cells demonstrate this enhanced ability to kill these.
resistant tumour cell lines and you'll see some of those images on the website if you if you have time. I was fortunate enough to present the on behalf of the company at the Innate Killer Summit in Europe in London on October the 19th and the data were very well received and have led to a lot of discussion.
And a video of that presentation is currently available on the company's website under the Therapists tab. It's also on the videos on the company's YouTube channel if you get a chance. So in the field of cell and gene therapies, it's becoming increasingly apparent that regulatory agencies such as the FDA require extensive understanding of the
of the mechanism of action of these novel therapies before they'll consider licensing as a commercial drug for attaining the BLA. And at ImmuneBio, we've been lucky. We've been focused on the MOA of InqMune since we really conceived this drug back in 2006 before the company was formed. Latest proteomic data, genomic and metabolomic data, so called omics, clearly explains how InqMune works.
and delineate the differences between immune stimulation and cytokine stimulation used by our competitors.
The recent video presentation explains some of these data and I'm very happy to take questions.
In parallel with increasing our knowledge about immune mechanisms of action, we've continued to treat patients and expand our clinical activity. Four patients have received the complete three-dose regimen with complete safety. In fact, the most recent patient was treated on an outpatient basis, which is our planned treatment scenario with a licensed medicine. And it's a world away from the days of hospitalization.
associated with current adoptive cell therapies. Three of the four patients treated so far have shown evidence of sustained NK cell activation in their blood, and we're analyzing the biomarker data from those patients to identify those which best predict outcome.
I'm pleased to say that the first MDS patient we treated in the clinical trial remains alive 20 months post treatment, so he's now had his 80th birthday, and he's enjoyed a much improved quality of life with fewer hospital visits.
The second patient, a young lady with acute mild leukaemia, which transformed from mild dysplastic syndrome, and with bone marrow failure after a third failed allogeneic stem cell transplant.
She'd been hospitalized six months and she received inc-mune within a month, had stabilized her blood counts adequately with an adequate neutral recovery to allow her to be discharged from hospital and go home. Clinically she'd had reduced bone pain and was scheduled for a fourth transplant.
but eight months post-Ink Moon treatment, she sadly relaxed repeatedly and rapidly died. But the third patient treated had chemotherapy refractory AML, and much as the first patient had failed twooma transplants. Post-Ink Moon has to be stabilized for four months.
before relapse again with a new clone of acute mild leukemia, and he has recently received a third unrelated donor transplant. So this emphasises how sick these patients are that we've been treating.
The most recent patient is a 17-year-old young lady with MDS who relapsed with acute myeloid leukemia, post-unrelated transplant in 2020, and again after a second cord blood transplant in 2022. After further chemotherapy, she achieved remission and was treated compassionately in July last year. But interestingly, the majority of her cells were immature NK cells.
which may reflect the fact that she's had a core blood transplant, and they showed little evidence of impromptu function after inguine stimulation. Her disease progressed and she received further chemotherapy to prepare her for a third unrelated donor transplant, and she remains the one patient we've treated who doesn't appear to have responded significantly to inguine.
So whilst very early in the development of the immune and being restricted to using the lowest dose at this time, there's one but one cells that's Alabama's issue.
So whilst very early in the development of the immune and being restricted to using the lowest dose at this the chief trial investigator
has treated all four patients said, and I all enjoyed an improvement in general fitness and resolution of fevers, stabilized or improved counts, and we were able to give breaks from low dose chemotherapy that they had been receiving. There was definite improvement in subjective parameters of wellbeing, mood, appetite, and clinical performance data.
The clinical experience of these four patients was presented at the American Institute of Hematology annual conference in December . Also in Q4 last year, we received approval to widen the trial inclusion criteria to allow patients like the three compassionate cases to be enrolled in the future.
And moreover, as RJ said, the second clinical Trita site opened in the UK. We have enrolled the first patient from that site and soon a third site will be opening in Europe , in Athens, in yet another regulatory environment.
So in preparation for the increased recruitment into the Loral trial in myelospastic syndrome and opening of new trials in metastatic castration resistant prostate cancer as you've heard, the company has invested in upscaling the manufacturing process and the validation of that new process to CGMP is now complete. This forms the basis of the IND application to the FDA.
and we're delighted that our tight budget control of the immune development so far has allowed us to invest now in the additional manufacturing capacity and clinical trial staff to support our expansion into solid tumors and to open our first immune trial in the US. This invest is the way for our ambitious plans for trials in other solid tumors.
going back to the original plan for ovarian trials, but also in renal and shortly, we hope, nasopharyngeal cancer, as we have relevant supporting data that are submitted to regulatory agencies.
So I think the combination of basic research into mechanisms of action, the manufacturing improvement in clinical trial operations in the UK, broader Europe and the US.
Plus, the continued preclinical research in new diseases such as renal and nasopharyngeal put the company in an excellent position to support the immune trials in solid tumors in the US and elsewhere. And I'll now pass the call back to Audrey. Thank you.
Thank you, Mark.
So we kicked off 2023 with our heads down focused on continuing to expand and advance.
existing and contemplated trials in the ways that we can manage our resources including our costs.
and contemplated trials in the ways that we can manage our resources, including our costs and our goals to get.
approved that make a difference at the bedside. David will touch on the financial issues later in his remarks. As we enter the second quarter, the conference and events calendar comes back to life.
We will be attending the annual ADPD conference, the largest ADPD
Medical event in Europe the last week of March. April , we are presenting two abstracts at the AACR on our...
the role of DNTNF targeting MUC4 expressing tumors as part of combination therapy.
of DNTNF targeting, look for expressing tumors as part of combination therapy.
MBO3 is the product that is part of the DNT oncology branch of the X-Pro platform that we have designated for oncology activities.
In July , AAIC, the Alzheimer's Association International
Conference in Amsterdam will be the center of the AD world. We will be there providing insights into that vaccine disease that do not include amyloid or tau.
As you might expect, we are frequently asked about the FDA hold. We continue to work closely as the FDA works to resolve issues that are unique to the FDA. We continue to enroll patients.
in Australia and Canada and are focused on how we can accelerate our core Phase II program in early AD in venues outside of the US that will be beyond Australia and Canada.
To be clear, the problems we are facing with the Phase II program will not compromise the potential of X-Pro.
long term in Alzheimer's disease. We expect the US will open in time to include phase 2 patients.
in the current trial.
And we fully expect the US will be a very big part of any successful global phase 3 registration program.
for X-Pro and early AD. We are planning for success.
We are planning for success in early AD.
beyond in diseases like TRD and the many other CNS diseases where X-ray will have value.
At this point, I will turn it over to David Moss, our CFO , to review financial items.
printed over to David Moss or CFO to review financial items. David?
Thank you, RJ. I'll provide a brief overview of our financial results and upcoming milestones before we head to our Q&A session.
Net loss attributable to common stockholders for the year end of December 31, 2022 was approximately $27.3 million, compared with approximately $30.3 million for 2021.
Research and development expense totaled approximately $17.1 million for the year end of December 31, 2022, compared with approximately $20.5 million for 2021. General and administrative expense was approximately $9.3 million for the year end of December 31, 2022, compared to $8.8 million for 2021.
As of December 31, 2022, the company had cash and cash equivalents of approximately $52.2 million. I'll remind everyone this does not include the recent $6.4 million we received in early Q1. Based on our current operating plan, we believe our cash is sufficient to fund our operations.
shares that went only to insiders.
As RJ previously mentioned, we are focused on achieving our research and trial program's objectives while remaining prudent on costs.
To that end, we estimate that the consolidation of the AD and MCI trials will reduce the forecasted budget outlay for the two combined trials by approximately $8 million.
Further, as we continue to dialogue with the FDA, our budgeted spend in the U.S. is not occurring as forecasted, thus resulting in less capital outlays.
As previously pointed out, our cash burn has been less than budgeted because both the delay in starting the trials in the US, in tandem with the broad-based strength of the US dollar reducing foreign costs, particularly in Australia. Further, we were pleased to report last month the receipt of the combined $6.4 million in total research related to rebates from Australia and the United States.
that will now include MCI patients, as well along with potentially other foreign jurisdictions to facilitate the enrollment of early AD patients into the ongoing Phase II trial. All of the aforementioned items better position us to manage our CAHPS runway more efficiently to reach our target and goals of recruitment.
stones. Top-line results for our phase 2 early AD trial in patients with inflammation and Alzheimer's disease.
is expected in the second half of 2024. We will initiate a Phase II trial of XPro 1595 in patients with treatment-resistant depression upon resolution of the FDA manufacturing review.
Additional, open-label Phase I trial data of InKMUN in high-risk MDS and AML in 2023, along with the initiation of more sites in the UK and Europe , as Mark mentioned earlier.
Initiation of a Phase 1-2 program in metastatic castration-resistant prostate cancer upon the acceptance of the IND by the FDA, which should occur in the first half of 2023.
Finally, we are pursuing business development opportunities and there could be no assurance the company can complete any such transaction as they are complex and difficult. We have two great platforms and as a small company we will try to expand the application of these platforms in areas that we do not have the resources or expertise to pursue ourselves in order to benefit shareholders.
Naturally, we will update investors should material business development events occur.
In summary, we were pleased with our progress during the quarter and full year of 2022 during a turbulent time in the market and unexpected regulatory hindrances.
As we continue to navigate our way through this challenging time, we are grateful to our shareholders' trust and support in our company as we continue to work hard to bring value from our platform technologies by carefully managing our shareholder resources.
At this point, I'd like to thank you for your time and attention. I'd like to turn it back to the operator, Paul, to poll for questions.
for your time and attention. I'd like to turn it back to the operator, Paul, to poll for questions. Paul?
We will now be conducting a question and answer session.
If you would like to ask a question, please press star 1 on your telephone keypad. The confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question from the queue.
For participants using speaker equipment, it may be necessary to pick up your handset before processing the therapy.
The ice cream can use its bigger equipment and may be necessary to pick up your handsets before pressing the star sheet. One moment please while we pull for questions.
Thank you. Our first question is from Jason McCarthy with Maxum Group. Please proceed with your question. Please proceed with your question.
Hey, guys. Thanks for taking the questions. First question on InqMune as it relates to your mention of several solid tumor types where it seems to be effective but you've chosen to go to metastatic castration-resistant prostate cancer. I'd like to know what prompted that decision. And as a second part to that question, I'd like to know what prompted that decision.
We've just seen, you know, Pluvicto is out there now and Merck just the other day pulled the plug on Keytruda and Xtandi combination.
Yeah, thanks Jason. So, you know, in our minds, the choice, and we didn't make this alone. We worked closely with the experts in ecology on this.
on this decision. The choice is pretty clear and it's really based on what you just said. There are no effective immunotherapy for patients with metastatic acid, resistant prostate cancer that have failed an energy therapy of some sort and the adzyme, the various inhibitors. So these patients kind of go into a...
into a status of dealer's choice at many institutions. And although chemotherapy is often used, the patients can often be elderly. It's not a great choice for them. Quite frankly, they don't work. So.
What excites the people we're talking about is the fact that you may have an immunotherapy which as you know every other tumor that has had an effect of the immunotherapy there's been a different problem. Cross-stake cancer doesn't have one, is incfuted it? Well, the preclinical data suggests it's it.
but we will have to do this randomized trial or this trial, this multi-step trial to actually determine if InCommune is an adequate therapy. The second reason we like prostate cancer.
As you know, we're kind of the king of the biomarkers and prostate cancers, particularly metastatic chemistry, resistant prostate cancer, has a lot of very informative biomarkers. There's the traditional biomarkers, you know, GSA in the blood, CT scan and bone scans, but...
There are some developing biomarkers that are much more interesting for under-turning understanding tumor-driven burden including circulating term with DNA and the PMSA PET scan, which helps you quantify residual disease. This gives you really quantitative evidence.
of disease status in which way it's been. So we like.
status in the way it's been. So we like
We think it's quite a large opportunity that's growing in size.
And quite frankly, the competitive landscape out there is not well defined because most almost every region of the country treats the disease to.
Can I just add, sorry I didn't interrupt it.
Absolutely, now I'm glad, go ahead Mark. Now I'm just going to say, one of the things that frustrates me as someone who trained as an immunopethologist is a lot of the attempts at immunotherapy are based upon a natural assumption that T cells are the king of cancer immunotherapy.
And yet, as my old boss said, over 40 years ago, you should go and look at the patient. If you look at the publications of the cells that are infiltrated, prostate cancer and the infiltrates that are associated with outcome, it's in case I'll infiltrate. It's not T-cell input.
And checkpoint inhibitors that have been used so far don't target NK cell function. So what we're effectively giving, if you like, and I wouldn't use this sort of lightly, but we're giving NK checkpoint inhibitor. InKune takes the resting NK cells that are in the tumour and hopefully will pump away the way that they do in the lab.
So, yeah, I think what we're looking at here is going for a tumor where there is good evidence from public literature that the number of NK cells that are there and the type of NK cell is potentially prognostically valuable. So that's another good reason for prostate cancer.
Got it. And this shifting gears to the all-time-reside, if you enroll all the patients in the AD trial before you get off clinical hold, does it hurt any standing with the company and the FDA?
Good question. The answer is absolutely not. I think I've been clear that we will death. We're going to have to do a Phase 3 trial. The Phase 3 trial will look
We assume is going to look very similar to what this Phase 2 trial looks like. So it will be a global trial that will include obviously North America, Europe , and parts of Asia. So the US will be a very big part of that. So there's absolutely zero risk that even if we, you know, enroll every patient. and ä VELAB1 doesn't want to be even attached to that. This is the same case for SI.
outside the US, that that will compromise our ability to move forward.
Okay, are you selecting countries or more international countries for this trial? So it does at the stage then for... Oh, absolutely. Absolutely. Absolutely. I mean, all of the countries we're selecting would be countries that you would have on your list for a global...
Just like at just three of your last question, if you combine or when as you are combining the MCI and mild AD trials into one quote unquote early AD trial, how does it not increase the trial size or what will the total trial size end up being now?
Yes, CJ, why don't you go ahead there?
DJ, why don't you go ahead there? Can you hear me?
Yes. So it's a good question. It really, I mean, it comes down to you when you're powering the study and what your assumptions are. So the assumptions that MCI patients will perform better than even mild AD patients.
So when we do that power calculation, we actually increase our likelihood of seeing a positive result on the EMAC. Now, we believe it's gonna increase the trial size a little bit, but we're talking 10, 20 patients, not talking 100 patients. So the total size would be, ish, range.
Okay, great. Thank you guys. Thank you. Just to reinforce with, just to reinforce with CJ said, remember the trial power comes from the difference between the treatment arm.
Okay, great. Thank you guys. Yeah, just to reinforce with just to reinforce with CJ said remember the trial Power comes from the difference between the treatment arm and the placebo on
And the kind of the unsound hero here is that by doubling the length of the MCI trial.
As CJ said in his comments, we anticipate more response in the MCI group.
So you will increase that delta between the MCI treatment group and the placebo group, and that's an only good thing to happen when you do that. Got it.
increase that delta between the MCI treatment group and the placebo group. Only good things happen when you do that. Got it. Thank you guys.
Thank you. Our next question is from Tom Schrader with BPIG. Please proceed with your question. Good afternoon, and thank you, Mark, for answering my big question about why castrate-resistant prostate cancer. That's a tough one.
Is that idea or the expro gets around it or would a partner need to do some work to show that this is no longer an issue? And then I have an AD question. Yeah, so I think that's an excellent question. Let me give you the D risk and then I will give you an educated guess on whether a partner is going to have these specific issues. So what happened when they use the original
a decrease in cardiac function over time, part of the muscular effects of the dystrophin abnormalities, but actually the TNF inhibitors made it worse. So that basically they just stopped. And what I found pretty interesting from the literature is they stopped.
And this literature is kind of old, let's call it early 2000s. They're not because they became contented with the results they were getting with cortical steroids. So the reason worked quite confident.
that this is not going to be an issue because of the selective nature of soluble TNF. We have one published.
paper that shows in a model of exercise-induced atrial hypertrophy in mice that actually the X-pro decreases, I have hypertrophy and decreases.
the fibrosis is part of the pathology of D&D. And we have unpublished data in another cardiac model that shows that X-Pro, you should see that data probably in the near, that X-Pro has benefit on cardiac disease.
So, in fact, we have pretty good evidence in animal studies that...
that X-Brow is actually beneficial to the heart. And we are soon completing a six-month DMD study in the mice where the primary endpoint is cardiac output. So at that point, I'm pretty confident we'll completely derest it. Now. So.
Does this mean that when someone takes this and drops it into kids, are they going to have to somehow be risk it beyond the standard clinical trial perspective? I don't think so, but you know, because...
because of the benefits of the drugs that are beyond just anti-inflammatory. But I would rather wait until we ask someone, hopefully a partner actually talks to the.
to the FDA. But the bottom line is our data and cardiac with X-Pro is quite positive. We will have, you know, really...
unequivocal data based on the animal models quite soon, but everything is pointing to that should not be a problem, and the fact that X-Pro actually improves cardiac function in most disease models. Got it, thank you. And maybe probably a CJ question. I understand you want to get X-Pro approved as a standalone therapy.
a reasonable way to think about getting a quick signal that I think a lot of people would be interested in.
I think we've said previously that's something we think we agree with you. And we think about all sorts of things, not just aria but across the board. And we think Xpro is going to be an excellent drug for combination therapy in general.
So I guess the answer to your question is yes, we thought about it quite a bit. We thought about a lot of things and hopefully in the near future, you know, as we get going in our programs here, we can start entertaining them a little more. Yeah, Tom Arche here. I mean, that is obviously...
a bi-amyloid drug to a rat or a mouse. Nothing happens. To our knowledge, the only area model is a spontaneous area model in some strain of monkey, which is not one of the standard strains. And these animals are extremely rare. So it's not like we could just buy a bunch of monkeys.
Give them an anti-ameloid drug and see who develops the area and then treat it because that would be the fastest way forward. We have some ideas. We're talking to people, but we believe we agree with you that the Achilles heel of the anti-ameloid strategies side. If I can be snarky, besides the fact that they only work.
somewhat versus well, they only work somewhat, is their safety signals associated with ARIA. And I think that moving forward, people will be a lot more comfortable using a drug with its efficacy profile if the safety profile can be solved. So it's on our radar screen and stay tuned.
Thank you. Thank you. Our next question is from Daniel Carlson with tailwinds research. Please proceed with your question. Thanks for taking my questions. Just a quick one on the timeline for the AD MCI trial.
The second half of 2024, do you need US approval at some point to reach that timeline or is that based on just what you have going on? Thanks. We are quite confident we are going to be off.
We'll solve the FDA problems this year, and so we'll include patients. But the more successful we are in getting site-cups and running outside of the US and how fast they enroll. Some of these areas we're looking at are historically quite rapid enrollers.
dictates whether it's going to be mid-year or later in the year. So, at the end of the day, it's going to be 2024, it's going to be the second half. Don't let us get a little farther on.
And there will be US patients in that in the face to trial. It's just, you know, I don't want to give you what the percentage will be.
Okay, fair enough, thanks. And then, DJ had mentioned that you're going to get some data from the open label extension. And he said in due time. So I was wondering if you could just sort of tell us what to expect from that. And I...
It was curious, in particular, if you're measuring cognition in the Open Label Extension, if we'll get a chance to see that at some point. Hey, Jay. Hey, Dan. So, yeah, so we will be measuring all the clinical rating scales that we have in the AD-02 study will be continued.
in the open label extension study. So we'll get those every three months, along with MRI data. The, like I said, our intention is to share that data, but I don't have a timeline as to when we'll see that, at this point. all right.
Okay. An interesting problem, Dan. An interesting problem, Dan, is, you know, since the phase two is blinded, we actually won't know if a patient has been a placebo patient or an active patient. Okay.
Okay. An interesting problem, Dan. An interesting problem, Dan, is, you know, since the phase two is blinded, we actually won't know if a patient has been a placebo patient or an activation. So suddenly they show up day one on the OLE.
Right. They could be a denovo patient or they could be someone who's already had six months of therapy. So it's not like we're going to know in the first month or two what's going on. We're going to need some time to figure this out. But remember the three values or the three important elements of the trial of the OLE that CJ mentioned. One, it gives us that.
long term safety data that we know the regulatory authority. Two, it gives us the long term efficacy data that we know the regulatory.
authorities are gonna want. And the third thing is it's trade bait, what I mean, trial bait rather. In other words, we're trying to encourage clinical teams to enroll their patients. We know it's competitive out there. One of the great advantages of the X-Pro trials being only six months is that, you know, even if you end up on the placebo trial,
your progression rate is not going to be so catastrophic that you potentially can't benefit from some other things.
You don't become unrollable, so to speak. And if you do participate in the trial, you're guaranteed to get what we think is going to be a beneficial drug after the period of that trial, whether you're on placebo or not. So we, the investigators have been very supportive.
of this strategy because at the end of the day, you know, when you walk into a memory clinic now, they've got three or four or five trials that they can choose between to enroll their patients. And, you know, they're always trying to look out for the best wishes of their patients. And we think this puts us high on the list.
One last question, I just looked briefly since your press release, but your PI and the IncMune prostate trial seems to be a pretty big deal. I'm just wondering what his motivation was to work with you guys on this. Well, I'll let you ask. I don't want to put words in his mouth.
other buddies in the cancer world, whether you're lung cancer or melanoma docs, have all these interesting immunotherapy tools to use. Checkpoint inhibitors.
ADCs, etc. and he doesn't have anything, right? He states that we've reached the limit.
I think this is in his quote in the press release. We've reached the limit with what we can do with the effective therapies we have, and those are inhibitors, anti-androgen strategies, and chemotherapy. He believes the only way he's going to progress. That he's added takingophone hand to get our new
is with a immunotherapy and Mark, you heard Mark's comments, Mark convinced him that what they really need is a therapy that targets NK cells and he's on board. So we're pretty excited. He's a very good guy.
But he's been there, done that, and he's been involved in every immunotherapy failure in prostate cancer going forward because that's what the field has been focused on. They're trying to replicate the success they've had.
in breast cancer and in lung cancer with immunotherapy and prostate cancer. And so far, it's been a disappointment. Thank you. And thanks for your answers, guys. And I'm looking forward to a big year from you.
you know, in breast cancer and in lung cancer with immunotherapy and prostate cancer and so far, it's been a disappointment. Thank you. I thank you for your answers, guys, and I'm looking forward to a big year for me.
Thank you. There are no further questions at this time. I'd like to turn the floor back over to Dr. RJ Tessie for closing comments.
I think you're on mute RJ.
I think you're on mute, RJ. OK, thank you.
Thank you everyone for participating in the call. We continue to make progress despite the regulatory challenges and the dislocations in the capital markets. We believe we have novel products that will be valuable to clinical teams and
I have a broad variety of clinical applications and you're beginning to see that. And we are afraid to innovate in our clinical regulatory and financial activities. You and Bio have this can-do attitude that we think will benefit patients and investors alike. And I personally will put Alzheimer's disease and prostate cancer on those. We're coming after you. 5
a lot of clinical applications and you're beginning to see that. And we are afraid to innovate in our clinical regulatory and financial activities. You and Bio have this can-do attitude that we think will benefit patients and investors alike. And I personally will put Alzheimer's disease and prostate cancer on those. We're coming after you. So with that. Then.
We will close and thank you very much. This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation. Now we're staying up. You