Q4 2019 Earnings Call
Ladies and gentlemen, todays conference is scheduled to begin shortly we should continue to stand by thank you for your pension.
[music].
Ladies and gentlemen, thank you for standing by welcome to the Infinity Pharmaceuticals, corporate update and full year 2019 financial results Conference call.
My name is Daniel and I'll be your operator for today's call.
This time, all participants are not listen only mode.
There will be a question and answer session to follow up.
Please be advised that this call is being recorded and Infinitys request.
Now I would like to introduce your host for todays call Jane Kaufman Senior executive coordinator and Infinity Pharmaceuticals. Please go ahead.
Thank you Daniel and good afternoon, everyone. Welcome to today's call. We're pleased to discuss our recent significant business progress we view our full year 2019 financial results and provide our key milestones for Twentytwenty with me here today, our Adelene Perkins Chief Executive Officer, Larry Block.
President Dr., Jeff could you talk our Chief Scientific Officer, we will open up the call for Q1 eight following our remarks.
A press release issued this afternoon details our results and are available at our website at MP Dot com.
Please note that during this call we may make forward looking statements about our future expectations on plans, including clinical development objectives. The therapeutic potential of our product candidates are strategic plans and strategies and financial projection.
Our actual results may differ materially from what we project today due to a number of important factors, including the considerations described in the risk factor section of our annual report on form 10-K for the full year up 2019 and in other filings, we make with the FCC.
These forward looking statements represent our views only as of today and we caution you that we may not update them in the future whether as a result of new information future events or otherwise.
Now I would like to turn the call overcrowding.
Thank you, Jim Jane and thanks, everyone for joining us.
This is an exciting time for infinity pharmaceutical today, we look forward to providing an overview of our recent corporate highlights upcoming I pets, I was wondering clinical milestones and financial guidance for Twentytwenty.
Most important thing for you to know is that we have five significant I pets I put on clinical study readout that are expected this year through mid 2021.
His data read out all within our current cash runway, creating significant near term value creation potential for our shareholders.
Our ability to generate data with IP I phone line in over 500 patients across five study all of which are now enrolling was enabled by our now earlier. It earlier this year have a non dilutive $20 million financing with biotech value fund or be via a top tier investor and also our largest shareholder.
This financing is that like the central royalty payments due on future sales had to dig in hedge hub in pathway inhibitor discovered by Infinity and licensed to California in 2013.
With this Lady latest financing, we had access over $90 million completely non dilutive capital and contributions in calling over the past 18 months alone, reflecting our commitment to access the capital necessary to fund the advancement of Ipi 549 for patients with the dilution sensitivity necessary.
You create value for shareholders.
Our upcoming clinical data read outs are significant given that I picked by phone line is a first in class oral immuno oncology product candidate targeting immune suppressive macrophages in my like derived suppressor cells or M.D.S. eat through selective P.S., we kind of gamma inhibition and is the only.
Yes, we kinda scams specific inhibitor in clinical development.
And to macrophages and M.D.S. ease their circulating the equivalent which we will refer to interchangeably in today's call generate a pro tumor immunosuppressive tumor micro environment.
Attributing to tumor regrow and inhibiting anti tumor T cell activity.
Research and Infinity and elsewhere showed that the presence of these immune suppressive Mds season into macrophages, maybe a key reason that only a small percentage of patients benefit from checkpoint inhibitors and that most patients who responds initially to checkpoint inhibitors ultimately rollout.
I P. Aside for nine is designed to provide a solution to the problem tumor immune suppression by reprogramming Mds sees an mtwom that pages from a pro tumor I mean presses function tunein stimulant Tory anti tumor function characteristic of M macrophages.
[noise] Maria one or phase one study has generated clinical and translational evidence of this deep reached immune suppression in increased immune activation with I'd guess buys for nine both as a monotherapy and combination with checkpoint inhibitor therapy.
These initial data have laid the foundation for and informed our ongoing development.
Yes, I phone line has also demonstrated an excellent safety and Tolerability profile again, as both a monotherapy and combination with a checkpoint inhibitor, enabling a robust clinical development plan with a number of innovative combination therapies in several tumor type intended to improve upon Bergen standards of care.
As well as approved front in second line regimen.
These compelling mechanistic safety in activity day, the data has enabled us to attract top tier partners for the development of IP aside for nine resulting in collaboration with Bristol Myers Squibb Roche Genentech in Arkansas Life Sciences.
These partnerships are truly collaborative enabling us to benefit from the expertise in inside a world renowned leaders in oncology and our invaluable for the successful development of I've kept by phone on.
Oh collaboration with BMS leverage is important data from their checkmate 275 study, which resulted in the approval of Opdivo as a monotherapy in bladder cancer patients following progression on a frontline platinum based chemotherapy.
Translational analyses from the Checkmate 275 study led by Dr. Pam Sharma at MD Anderson demonstrate that we stopped evil monotherapy, there's a stunning correlation between patients with the highest baseline level of Mds seized and poor outcome, including a significant six.
Gold production in overall survival compared to patients with low baseline levels of M.D.C.
These findings support the premise that Mds sees our immune suppressive.
Tribute to tumor re growth following chemotherapy and limits the effectiveness of checkpoint inhibitors Duff minimizing the patient population that may benefit from these immuno oncology therapies.
The Checkmate 275, finding came at a very interesting in important time as in parallel infinity generated data in our Marriott phase one study showing a raft set and dramatic reduction in Mds. These following credence IP aside for nine.
These complementary finding in identifying both a problem and its potential solution served as the inspiration for Myrio to 75 and accelerated our path forward in combination with Opdivo in patients with Urothelial cancer.
[noise] marry up to 75 is the Companys ongoing global randomized controlled phase two study in immune therapy naive second line urothelial or bladder cancer patients in collaboration with Bristol Myers Squibb.
Working closely with BMS arc trial was designed with tremendous fidelity.
Design of Checkmate 275, with the primary difference being the addition of Ipi 5.92 up do you go with the goal of improving patient outcomes.
In marry up to 75 patients first stratified based on starting India Sea level, and then a randomized two to one to either the Ipi 549, plus up the though for Opdivo plus the siebel arm, regardless of PD L. One status.
The primary endpoint of this study is overall response rate was equally important secondary end point of patient benefit in median progression free for all the median progression free survival overall survival and duration of response, which are particularly important given the correlation of high end do you feel.
Leveled with poor time to event, most notably significantly shorter overall survival shown in BNS is checkmate 275 study.
We plan to enrol hundred 60 patients at approximately 50 sites in both the U.S. in Europe, and anticipate completion of enrollment by the end of this year followed by data in mid Twentys. When he won approximately six months after the completion of enrollment.
We're also excited about our novel combination studies with I.P.S. lifeline insight on cancer patients in a phase two study called Marriott three.
Marriotts three is a 90 patients study being conducted in collaboration with Roche Genentech.
The cohort of 30 patients with renal cell cancer, or RCC, and 60 patients with triple negative breast cancer for T.N.B.C., all of whom we expect to roll. This year with initial data also expected later this year.
These studies are evaluating I guess I'm wondering in novel Triple combination and our first applications of Ipi 549 in frontline setting.
Importantly, these RCC in T.N.B.C. cohorts.
Designs with great fidelity to the inclusion exclusion in other key 12 characteristics utilized by Roche Genentech and their evaluation of double combination therapy in each indication such that we will have a benchmark against which to evaluate the benefit of adding IP I 5.92 previously.
The weighted Roche Genentech regimen.
In front line RCC Roche tested to centric lots of Aspen in a study called in motion 151.
In front line TNBC Roche received accelerated approval for the combination of Abraxane into centric in this study called impassioned 130.
In both our RCC in CNBC cohort half the patients enrolled will have high levels of PDL, one expression and the other half will have low levels of PDL, one expression with a checkpoint inhibitors have shown little activity.
The primary endpoint for all Myrio three cohorts is complete response rate to improve upon the benchmarks of complete response rate of 10% or less seen with the Roche Genentech double.
We're also collaborating with arc five sciences with a checkpoint inhibitor free novel Triple combination regimen of Ipi 5.9, with 89 to wait ARCUS is dual adenosine receptor antagonist and a chemotherapy doxil in second line or greater advanced T.N.B.C.
Jason.
This studies being conducted by ARCUS completed the dose escalation phase of the study in 2019 and are now enrolling up to 40 TNBC patients in an expansion cohort.
This phase one one be study is adding I guess I phone line two parallel study underway ARCUS evaluating the doublet a baby nine to wait with Doxil in the same patient population of second line or greater TNBC patients.
The primary objective is safety and Tolerability of IP I thought for nine and 89 to wait in combination with Doxil.
Secondary objectives include overall response rate disease control rate progression free survival and pharmacokinetics and pharmacodynamics will also be monitored.
Jeff will describe the scientific rationale for all of these studies in more detail.
Finally, we completed enrollment in or Marissa, one study evaluating ipi 549, as a monotherapy and in combination with Opdivo in patients with advanced solid tumors at the end of 2019.
Data from this clinical study have played a critically important role in substantiating, our mechanistic in preclinical findings on the role yes, we kinda gamma inhibition with I.P.S. I phone line in reducing the number of M.D.S. sees thereby reducing immune suppression with a corresponding activation of an immune response.
We will provide an update on this data which provided the foundation for phase two studies now underway later this year.
Next a few word on or partnerships.
We're delighted to have strong clinical collaborations with Bristol Myers Squibb Roche Genentech in our bio sciences all of them are global leaders in developing innovative cancer treatment.
So we have chosen to retain worldwide development and commercial rights to Ipi 5.9 in advance of phase two data collaborations are critically important to us it's partners bring tremendous insight on unmet patient needs from their previous studies on a specific areas for improvement with future treatment regimen.
Our partners also provide meaningful financial support for our trials through contributions of combination therapies free of charge.
In turn our partners look to leverage Infinity scientific insights on the role of Ipi 549 in reprogramming, that's pages and modulating Mds east overcome resistance to checkpoint inhibitors as.
As well Infinity medical inside based on a political experienced in treating patients with Ipi 5.9, who are no longer responsive to checkpoint inhibitor therapy.
Our phenomenal clinical team led by our be VP of clinical development Dr. housing and our VP of clinical operations, Jennifer Robert are supported by the 70, plus clinical investigator on our trials and expanded network of clinical advisors and collaborators some of whom have recently joined our exceptional clinical.
Buys report.
We're pleased to announce today the additions of Dr., Pam Sharable co leader of the MD Anderson cancer centers immunotherapy platform and the principal investigator on the BMS Checkmate 275 study that first demonstrated the association of high Mpsvs to lower lower overall survival in patients with Urothelial cancer.
And we provided the inspiration for our married to 75 study for with her unique insights will be invaluable.
We're also pleased the Doctor told me Cherry the director of the length Center Virgin until urinary oncology at Dana Farber Cancer Institute has also joined or clinical Advisory Board Dr. trade areas are recognized thought leader in the G. you field who's done extensive work and the development of better treatments for patients with RCC and we'll bring his.
Unique insights to the interpretation of our data for Marius free in RCC and the development of next step.
[noise] Dr., Michael popped out, but also drilling or clinical advisory board. He co leads the melanoma disease Min management team at Memorial Sloan Kettering Cancer Center and was the principal investigator <unk> clinical trial, which led to FDA approval of the Nibali MEP, let's get the Lumileds combination to treat melanoma and we'll bring.
Tremendous insight to the identification of potential future path for IP I Fourninety melanoma.
And finally, our clinical advisory boards chaired by Dr. Samaras, Cresta Infinity Board member and Chief Medical Officer about when therapeutic.
Dr. Aggressive played key roles the approval of several important drugs, including to Sobon I defer wallet audio and can cycle, which is approved for breast cancer wallet Genentech.
Dr. Aggressive also played a key role in design me Infinity trials now underway in is actively engaged with the company in advancing these trials.
With our great clinical team investigators and advisors 2020 is a very important here for the clinical development of Ipi four nine for the company.
We're totally focused on completing enrollment in married to 75 and married three this year and on generating data from all five of our study cohorts, which will be in a total of over 500 patients between now and mid 2021.
Before turning the call over to John Dr., Jeff, who taught our chief Scientific officer I'd like to highlight the announcement, we made today that with the inbound advancement of I can't talk for nine into Phase two development, Jeff has officially pass the baton undeveloped in the broadcast platform onto our clinical team.
With this baton passing Jeff will be leading infinity at the end of March to focus his considerable research talent on leading drug discovery and another life Science company and we will assume the role of chair of Infinity Scientific Advisory Board.
In this new capacity working with internal and external scientists, Jeff will continue to play a critically important role in interpreting new scientific insights on P.S., we kinda scana specific inhibition and in helping to God potential future development path broadcast thoughts on line.
Just played an instrumental role in the discovery of Ipi 549, and in its transition into a robust clinical development program and we are for ever grateful for the enormous contributions he's made bringing ipi 549 to this point and for his ongoing commitment to the program into Infinity.
It is with profound appreciation then I now turn the call over to Jeff to review the strength of the scientific rationale underlying each of our clinical studies now underway.
Thank you how do we.
Well certainly list the daily interactions with you and all my colleagues at Infinity and despite my upcoming transitions I remain incredibly excited enthusiastic about the path, but I'd characterize where no one is on.
The strong scientific rationale that underlies the design of our studies, which I'll now review.
As you just mentioned our Merial one data is provided important proof of mechanism supporting the potential of Ipi five for nine to decrease immune suppression and increasing inactivation after treatment.
With demonstrated clinical activity in patients.
Equally excited to see activity with the combination of I'd just like when I do not do you go in patients that would not.
<unk> expected to respond to help people monotherapy.
These data bleed in important foundation for ongoing clinical programs in the future don't directions, which I'd like to highlight.
I will summarize the scientific premise behind her to 75 or global randomized controlled phase two clinical trial, but vivo plus but for now I mean urothelial cancer patients.
I'd like to take a step back and touch on the breadth of the impact good immune suppressive Mds using them to macrophages have across a number of different tumor types.
Broadly speaking and be a season mtwo macrophages are rapidly being appreciated as a key mechanism by which tumors creed protective microenvironment and defend against immune attack.
[noise] distinct from targeted therapies directed to genetic mutations that drive to grow can survival specific tumors that harbor those indications the macrophages in Mds sees that infiltrate nearly all tumors are fundamental biological mechanism of immune suppression that is relevant across most if not all tumor types weve. It.
Dense was critical preclinical.
Mechanistic studies that support the key role of pure fujiyama signaling in the immune suppressive function of these macrophages and MBS use but also clinical and translational data to show that selective inhibition of Cadthree to gamma biotech funding for nine can overcome their suppresses effects and lead to immune activation tumors.
[noise] mechanism of action of I'd, just like for non can therefore, potentially synergize with many other therapies, but either target other aspects immune suppression tumors like checkpoint inhibitors are adenosine pathway for with chemotherapy like doxil with abraxane or targeted therapies like have asked and all of which we are currently pursuing clinical studies.
There are additional preclinical and scientific rationale for combining with I.P. outside for nine with other therapies and we look forward to pursuing these in the future.
With respect to our existing studies the do it BMS generated in tricky to 75.
Reinforcing the association of high levels of MTO sees the poor outcomes in bladder cancer provided the foundation of our married to sort of on trial.
Has been seen in many other settings in tumor types through extensive publications on the correlation of high MBS use with poor prognosis melanoma, Mick long and other cancer types.
Such Primero to 75 study serves as an important test of the potential value on reducing MBS cheese, which could be much more broadly relevant across many tumor types and settings.
This approach maybe representative of the next wave of cancer therapies, which are not tied to tumor histologies, rather two fundamental biologic posses along the lines with the recent approval for checkpoint inhibitors based on high levels of microsatellite instability, regardless of tumor type.
Against this backdrop I'd like to describe how the fundamental roll them, you'll see is drive the underlying biologic rationale of each for trials beyond Marriotts you soon.
Let's start with barrier three our phase two study being conducted in collaboration with Roche Genentech study has different cohort two different cohorts broke my renal cell carcinoma was IPO class were nine in combination with two centric and of Aston and frontline triple negative breast cancer with Ipi four nine in combination with to centric and Abraxane.
[noise] and renal cell carcinoma is a strong scientific and biologic rationale for combining of asked him to centric and I'd characterize for nine.
No tires eugenics combined with checkpoint inhibitors are provided recent meaningful advances in the treatment of real real cell carcinoma.
Hi, Andrew Genic served that Jeff inhibitors, regardless of whether they're antibodies are tyrosine kinase inhibitors lead to damage in blood vessels and reduced blood flow to the tumors by design.
In addition, the tumors utilize checkpoints to suppress the immune response, such that adding a checkpoint inhibitor like to centric augment your anti tumor T cell response to provide additional patient benefit.
But importantly, an additional affected this treatment regimen, particularly the vascular disrupting agents is the creation of tissue hypoxia or lack of oxygen leading to the recruitment of macrophages.
These macrophages contribute to both vascular and tumor regrow as well as suppression of anti tumor responses of the T cells.
Given the role of Ipi, four nine and reducing Mds season, reprogramming immune suppressive Mtwo macrophages.
The addition of Ipi 5.92, you can enter into agenda can a checkpoint inhibitor liked to centric shuts down multiple mechanisms that lead to tumor resistance to these agents.
Study with Roche Genentech in Triple negative breast cancer also has a similar hypothesis based on a trial Roche Genentech dude, combining abraxene into centric in front line TNBC patients.
Abraxane leads to tumor cell death into centric all beds anti tumor T cell response, reducing immune suppression.
Based on the impassioned 130 trial most received the first ever approval of a checkpoint inhibitor in triple negative breast cancer with accelerated approval, but only in patients with high levels of PDL one expression.
Well this approval was very encouraging it's clear there's room for improvement.
Which is where the addition of I'd just like when on comes in.
We hope to show benefit for both the PDL, one positive and negative sub groups with the addition of Ipi five for nine to Abraxane into centric given the fact that chemotherapy like abraxane can recruit additional macrophages in Mds east tumors that will contribute to tumor re growth and further immune suppression.
We're very enthusiastic about these phase two studies with actually I 5.9, moving to a frontline combination therapy with real potential to improve upon regimens in real cell carcinoma in triple negative breast cancer.
Now, let's turn to the ARCUS Biocides collaboration.
As opposed to marry a three new Yorkers Trauson phase one de study that's the second line and leader therapy Triple negative breast cancer.
Triple combination includes IP outside for non with 89 to read a dual adenosine receptor antagonist and doxil acute chemotherapeutics.
As a strong scientific rationale, but should so familiar at this point.
Using doxil chemotherapy to induce tumor cell death.
Tumor cell death, resulting in cumulating of immune suppressive the Denison.
The target of ARCUS is dual adenosine receptor antagonist 89 trade.
But just as in the other mechanisms. We reviewed this tumor cell death also leads to recruit been approved tumor macrophages, which suppressed T cell responses. So adding I'd just like we're now entered this combination provides a complementary mechanism for help stimulate an immune response.
Importantly, the combination with arc is is a checkpoint inhibitor free regimen, given the importance of the suppressing the effects of macrophages in MBS using most tumor settings and lines of therapy. This will enable us to evaluate the potential of Ipi 5.9, as a treatment backbone across several lines.
There would be indistinct combinations.
This will be particularly interesting to evaluate and triple negative breast cancer, given that we have TNBC trials now underway with Ipi 549 in the fault line with married or three and the second line with ARCUS and then the third plus log with BMS.
There are two key aspects to the design of all of our trials now underway.
Adding IPO five fernanda regimens that provide a clear benchmark upon which we can compare its activity and we're exploring IPO side for nine settings, where the immune suppressive pro tumor macrophages in Mds season, or an important mechanism of resistance to these regimens.
Finally, I want to recognize the outstanding work of our clinical collaboration partners Dms those genentech in arc is as we continue to make great strides in advancing not satisfied for nine combination clinical programs.
I also wanted to take this opportunity to thank all of my colleagues and infinity for their years of support camaraderie and professionalism I look forward to remaining involved in the I'd like for nine program as chair of Infinity Scientific Advisory Board.
I'll now turn the call over to our President third walk.
Thank you Jeff.
Although certainly Miss working with you on a daily basis as part of this executive team.
But I am truly gratified that we will continue to collaborate together well development I played for noise in her new role was chair of our scientific Advisory Board.
Triggered strategic outlook, we have maintained worldwide rights I paid five for nine with a total net sales royalty burden of only up to 4%.
On January 2020, we completed $20 million Nondilutive asset backed financing with biotech value Fund partners.
We sold recourse central royalty payments due on future sales appended to give.
Hedgehog pathway inhibitor discovery by Infinity can likely to pull apart from 2013.
If it is also eligible to receive from BVF, an additional 5 million dollar payment upon positive data from cold farms. These three trial in patients with Korlym syndrome, which completed enrollment in November 2019.
Even with a central milestone payment, we have a cash runway to fund over ongoing a good pipe were nine clinical studies two key data readouts expected by mid 2021.
At December 31st 2019, we had total cash cash equivalents in of you'll still securities or 42.4 million compared 50.6 million at December 31st 2018.
And then subsequent to our biotech value fund financing a January 2020.
We had cash balance of approximately $62 million.
Revenue for the full year 2018 was $3 million compared to 22.1 billion the full year 2018.
R&D expense for the full year 2019 was 27.1 billion compared to 19.8 billion. The full year 20 team that has increased R&D expense was primarily due to increasing clinical into Goldman activities for okay. Bye for now.
Turning to general <unk> expense for the full year 2018.
This was 14.3 million compared to 14.2 million the full year 2080.
Net loss for the full year 2019 was 47.1 billion or basic and diluted loss per common share of 83 cents compared to net loss of 1.3 million, where basic and diluted loss per common share of 20 cents the full year 2018.
This increase that loss was mostly driven by two factors between $2 million milestone payment received from Verastem and 28 team for their approval could peak trough.
And some 43 million dollar royalty expense to Takeda and 29 team for their share let's go peaker royalty monetization with healthcare royalty partners in the first quarter of 2000 and like T.
Now looking forward, our previously announced plans for got is as of January through 2020 remains unchanged. We expect tweets when that loss to range between 40 $50 million and 2020 with the cash investment bells in the range of $15 million to $25 million.
We anticipate that our existing cash cash equivalents interview still securities will be adequate to satisfy the company's capital needs into the second half between 21.
Our 2020 financial guidance is based upon the Companys current operating plans that does not include additional financing Orbitz development activities.
For the central $5 million milestone payment upon by took value fund for positive phase three how does it get data you had any milestones milestones from or the sale the company's equity interest in California.
At this time would go up the call for questions operator.
Ladies and gentlemen to ask a question you will need a press star one on your telephone to withdraw your question press the pound.
Please standby, while we compile the Q and a roster.
Our first question comes from Andrew Dsilva B. Riley FBR. Your line is now open.
Hey, good afternoon, Thanks for taking my questions and congrats on all the progress over the last 12 months.
Just a few quick questions for me.
Yeah, one modeling one out of the gate as far as the Bbs financing goes.
Is that going to be accounted for in the same way as HCR verastem royalty stream or.
Will that be recognized as an asset sale I didnt see a cap amount or.
Reversion carve out so it just looks more like an asset sale to me.
Yes, it's a great question so because of the subsequent event, we're actually working through the accounting with.
And why and so we'll have that reflected in the first quarter two in a in may but.
But it is although they may look analogous there's definitely some.
Of the sort of financial components of it that still need to be analyzed to make a final determination.
Okay, Okay, great and and then as it relates just.
Finally, the competitive landscape actually more specifically to get your gamma.
Has there been any updates on Astrazenecas candidate and have any other development programs emerged as well.
So the thanks Andrew.
There I'm not aware and we're not aware of any updates on they these program. They didn't do an update at HCR last year and they had data.
In preclinical models that looks somewhat similar to our program. The only discernible difference was for the preclinical studies. They were dosing twice a day in and we're a once a day oral drugs. We there's no evidence of any pithree kinase gamma specific inhibitor in clinical development. So we.
We believe that we remain the only.
Yes, we kinda scan the specific inhibitor in clinical development.
Okay, that's good to hear.
Good segue to my last question.
I guess really two parts to it.
There has clearly been just an increase in programs.
Targeting macrophages lately I'm just curious.
If your enrollment rate to date is keeping up with what you were expecting when you originally gave guidance in January or if you know some trials are trending behind or ahead.
What you would have initially thought and then [noise].
When you step back and look at the broader backdrop I'd love to get your thoughts on how you see five for nine or Infinity, just feeding into the broader landscape with everything that's evolving lately.
Sure.
So uh huh.
It's two months ended the year. So it's it's early but we remain really pleased with the status of the trial enrollment in the site initiation.
We just came back from the G. you ESCO meeting in San Francisco in mid February and it was just a lot of enthusiasm for our investigators from our investigators. So you know I would highlight with our Mariano to 75 study with the 500 sites. The majority of those are outside the U.S. and so there's.
Oh really compelling rationale for patients to enrolling that study because they will either be receiving the standard of care up de novo plus placebo or the standard of care plus Ipi 549, and in some of the sites that were studying the opdivo is is not available to those patients as well as the second line therapy.
So we've seen great enthusiasm for investigators and and our enrollment is off to a good start.
I'll remind you in our Marriott three study, we're going to the front line, where we're adding again when you look at Marriotts free in triple negative breast cancer, the abraxane plus to centric isn't approved regimen and world thrilled with that but it has from shortcomings and that it is not approved in patients with low levels of PDL, one expression and.
Fleet response rate is low so we find is we talk with our investigators their keenly aware of the need for better therapies and the fact that I've got five for nine so well tolerated you know enables us to go into those triple therapy. So so far so good.
And you know with a broader.
<unk> landscape.
In addition to the fact that we're the only pithree kinase gamma specific inhibitor in development.
We're not aware as well as Jeff mentioned Theres, a lot of excitement about Mds season. The macrophage compartment. There are no other drugs that were aware of that reduce the M.D. These are particularly reprogram the mtwo macrophages and one for which there is any phase two data to.
Evaluate so there's a lot of excitement it's still relatively early days and so we'll be monitoring and looking carefully at those so.
From both our mechanism and preclinical date and where we are clinics. We believe five for nine still has the potential be quite differentiated from other approaches.
Okay. Thank you have that was really good color. Thank you very much and congrats on all the progress and best of luck in 2020.
Thanks, Andrew.
Thank you. Our next question comes from Kevin Degeeter with top <unk>. Your line is no.
Okay, great. Thanks for taking my questions guys out is we think about the I guess two primary clinical data Readouts in 2020, Mario one and Mario's free is it reasonable too.
So let me get the Mario one data that final octane currently Ernie Air and then then Mario three yeah breakaway later in the air.
I would expect both of them to be later in the year cabin, because we completed enrollment in our Marissa one study at the end of 2019. So we have patients who were still waiting to get data from their first scan. So what we will be collecting both the clinical and translational data on those patients during year we.
Also.
I have to date present to just at major medical meeting and so you know will will most likely just given that we don't even have for scans on some of those patients be looking towards the second half the year and you know with abstract submission deadline that you know, there's there's a long long lead time so.
That's the story with Mary one with Marriott three feel the same thing where you know in the early days of enrolling patients. So by the time, we have you know a couple of scams and and date on those patients will have a more robust and set of safety data by the end of the year, but the activity data will still be early and it will be like.
During the year.
All right I mean, maybe a financial question for malaria and follow up.
With regard to the cash burn guidance from yeah reasonably wide Delta there can you sort of walk us through what some of the puts and takes yeah, finding and that $10 million potential swing on for on might include.
Yes, so is that instead of we're it's still early days on in terms of our enrollment and most of our expenses are driven by our clinical.
<unk> expenses are our Gina expenses are relatively you know a costs in your from your as you can tell from or or 10, 10-K, a and so we basically want to give a $10 million range, because you can't get much more precision to that.
And a 12 month period of time, yeah, it will be driven by the the cadence of our clinical trials.
And kind of following up on that I mean with regard to some of the Tobin 19 related.
Travel restrictions and other variables here, how do you think about the visibility you have on patient enrollment I guess, specifically with regard to Mario to 75, given you know configuration, where most of those those sites [noise].
Yes, Kevin it's it's a great point you know we're monitoring it carefully eat I think we in the rest of the world are trying to figure out exactly where this is going to go. So I can't say, we have any better crystal ball than anyone else. You know, we don't have any issues and others. Then discussion about you know drug supply coming from China.
We were not we don't have any concern it really will depend for us because we do have several sites in Europe, what happens with garbage throughout Europe, and what it does to travel. So it's really too early to tell and we're watching this thing news you are to try to keep you know a good sense for where that's likely to though.
Alright listen thanks for taking my questions and congrats on the progress.
Thanks, Kevin.
Thank you Sir our next question comes from Onempower Rama with JP Morgan Your line is now.
Hi, guys. Thanks, so much for taking my question I've, a broader strategic question, so over last year or so I've been some transition from the medical scientific management team to sort of more advisory roles, but we've kind of multiple important data sets coming here in 2020, and 2021 are you thinking about the scope.
And sort of the brought our management team overall, thanks, so much.
Sure. Thanks <unk>.
So as I mentioned, you know we've got a terrific team, we're very focused on the clinic right now and on the clinical data. So we've got you know senior leaders of both clinical development and clinical operations and you know as well as in the translational analysis arena. So we've we've got a team that.
Like firing on all cylinders to execute their there supported by our great investigators and then they the.
Does the clinical advisory board that we put in place which was very much by design. These are people who have really unique insights on our trial. So you know Dr. Sharma ran the chair Checkmate 275 study, we couldn't have a better advisor as our data comes in to really roll up per sleeves and help us.
Interpret that and determine next steps.
Same thing with Tony Cherry. He is really a thought leader in renal cell Dr. progressed does done a lot of working in breast cancer.
In Marissa one we're studying melanoma patients and docking like pasta, we've got truly world class thought leaders. So what we feel like we've got what we need to deliver on the data that you know we're really excited in minutes 15 months, we're going out a lot of data.
Hi, Thanks for taking my question.
Sure.
Thank you. Our next question comes from Sumit Roy Jones trading you want to snow.
[noise] Hello, everyone and thanks for taking my question Congrats on staying on track on multiple fronts [noise].
[noise] to get a little granularity on the detail what kind of BW gonna see at the end up.
For the fourth quarter on [noise].
Both tomorrow, you will see and Mario once starting tomorrow, you'll see maybe to tee NBC core.
Oh.
We expect out of the 60 patients should we take at least 30 patient data.
And.
What are you going to see how are we going to see.
No no response rate, possibly be if it's a C marsouin and.
Cycle beyond cycle to like Psyches, dutifully holiday MDC levels have panning out just to get some kind of sense. So how.
How much granular detail.
Yes.
So clearly you know the data that will read out sooner. It kind of goes you know as you know in sequential the first thing we'll see a safety. The next thing that we'll see his response rates our primary endpoint in CR rate. So those will be the first thing it'll be unlikely that we'll see time to event right out of PFS or older overall survival just.
Given that we're enrolling those patients now so we wouldn't expect to have the time to event and point exactly how many patients will have it on depends on the kit the cadence of enrollment as we said we you know what two months ended the year, where we've got a lot of excitement and got.
Lots and lots of sites initiation is underway and sites that are up already so we'll as as we get closer to abstract deadlines. When we know how many patients we both have enrolled and how many patients will be reporting on will be able to update that but we do expect have data later this year that will be most likely.
You know at safety and activity measured by response rate.
Thanks, maybe this is the question for Jeff and I'm Kinda blanking on this thing.
When do you have you looked into like a preclinical model, where MDC knockouts like it's 189 mouse models do you see if you do as they know guff Dnbi. Since you know got do you see.
Them surviving more or less the females, even come comping in mice or better.
Give any sense, how this might find.
So.
Shoom that is your question more around safety no envious.
Efficacy in fact like how much of really MDC is contributing in a dnbi sitting we have a fairly good understanding and oh bladder cancer from the Checkmate 275.
Right.
I'm trying to think of the no other than.
Our own data showing you know I kept buck four nights effect on those cells.
And and those who don't decreased tumor growth and.
Indexed or decreased.
Ah, yes delay in tumor growth in those models I I'm trying to sit here and think of but I can't really come up with the off the top of my head on a model that specifically.
Targeted the Mds season, we may genetic way that that could answer your question. Unfortunately.
Got you can circle back on that and it's a good question yeah.
Lastly, just part I mean, you have you guys are kind of pushing forward.
Combining with the standard of care and.
Do you have any thoughts on once you are correct, you're trying to target them DSE, but then there are other factors that are playing a pivotal role in the tumor micro environment like this.
Mtwo macrophages fund agents to converted back in one or maybe.
T regs agents to block do you make accumulation.
Have you done any kind of those combination at least in the preclinical sitting to see.
They are a better combinations and just combining the tough standard of care.
Combo.
Soon so just just to be clear the you know our I clarified for nine does both a target would be a season and blocks there there of migration as well as converting a these immune suppressive cells to more pro inflammatory cell types, who get but for now.
We will do both of those sort of both of those functions.
We've looked at a variety of different models that targeted a number of different pathways, specifically, but T. Regs I. I think there there are fewer models that that are are you don't specifically targeting T regs, but we do.
Pretty extensively in publish most of the data targeting other mechanisms immune suppression ARCUS is published or presented the meetings on a combination of an benson antagonist and 5.9 and and those are data that are largely have been published Oh.
We've done.
[noise].
Okay. Thank you so much for taking my question.
Yes are we should the best Tony if we try and diverse I'm, hoping to see you soon.
Thank you.
Thank you. Our next question comes from Jim Birchenough with Wells Fargo. Your line is no.
Oh good afternoon, it's a nickel Tim this afternoon.
First off thank you to Jeff so putting out what he is often I know in question.
From a [laughter] [laughter].
[laughter] pleasure.
[laughter] images.
And maybe just Saudi Weve with Mary one soon become votes have now been fully enrolled could I just confirm that where we should expect the day to Ron.
And 10 patients each me just feeling merger Yukos coal.
C.
Non small cell lung screws and.
And you see high 29, triple negative breast and then schools in melanoma.
Yeah. So Nick I think are guidance that we've provided for the last years really remains intact that we will be presenting the data that support trials that we're going forward with <unk>, while the data you know it while the data is is yet still evolve.
Then we will of course present on all of the patients at some point when we completed all the translational analyses, but our current focus will be on those.
Cohorts for which we want to pursue a path forward, while we don't have any other.
There are no other pithree kinase gamma specific inhibitors in development today, we know that there are some that will be coming behind and so we'd like to keep any insights that we have.
Confidential as long as we can until we see a path forward and that will be clear that were announcing a new trial and going forward with them.
Okay. So just to be clear that focuses on really T. The t. NBC.
Sure.
Yes, I think you can look at all about hypotheses that we have in our studies today that we're going forward with you know that the <unk>. The fact that and we've already presented some of this that we see reductions in Mds fees that are the cornerstone for a the marriotts.
To 75 study and then anything else that either supports our existing studies or to the extent that were launching the new study.
Okay, Okay, and that's to be announced a new studies obviously.
Correct.
And then I noticed on the did a new clinical Advisory Council. If there is no t. NBC exports.
Why why is that.
Well, yes, Sam has it was what played a key role at Genentech on the CAD six <unk> approval and so while it was in her two positive breast cancer. He's done a considerable work in a in the 10 and in the breast cancer space.
Okay, but but it doesn't suggest that we will limit it to that we may well you know this is the first establishment of a clinical advisory Board and you know well work with them and if we decide that we want to add an expert in T.N.B.C., we may still do that as well.
Okay.
And then the fund want to me is it just goes back to Marianne. Three then are there any somebody looks at this stage for futility.
No not really the you know it's given that we're gonna be completing enrollment this year by the time. We have date you know, it's it's always the timing will probably have completed enrollment by the time, we have enough data to look at futility and we're not going to stop it for that so we're really powering through so we will.
Don't be an interim.
Okay fair enough. Thank you very much.
Thanks, Mike.
Thank you at this time I'm showing no further questions I'd like to turn the call back over to idling for closing remarks.
Thank you Daniel as you've heard today all of us of an affinity are very excited about our progress on the near term I cant five point on milestone that we stated on this call and in closing I'd like to briefly reader reiterate several key point that I pass 5.9 is up potentially transformative first in class agent with promising activity.
Okay that enables innovative combination treatment. It is today, the only pithree kinase gamma inhibitor in.
Ah clinical development and we have.
Strong support for targeting Mds sees that underscore, particularly are a randomized phase two trial and married to 75.
So we're excited about the potential of my P.I. I pets I've put on to make current immuno oncology drugs better.
And with five ongoing studies look forward to providing.
Updates with a near term out.
Data read outs building on a strong financial position so thanks.
Particularly to our clinical investigators patients partners and the team that Infinity, who have contributed to the development and progress apply for nine and to all of our investors. Thank you for joining us and we look forward to keeping you apprised of our continued progress.
Ladies and gentlemen, this concludes todays conference call. Thank you for participating you may now disconnect.
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