Q4 2019 Earnings Call
Good afternoon, and welcome to the M E <unk> pharma 2019 fiscal year end conference call.
Please be advised that this conference call is being recorded at the company's request.
Later, we will conduct a question and answer session and during the question and answer session. If you have a question. Please press Star then one on your Touchtone phone.
At this time I would like to turn the call over to Mr., David wealthy Emmy Ice Vice President Investor Relations and corporate Communications. Please proceed.
Thank you good afternoon, everyone and thank you for joining us after the market close today, we filed our Form 10-K for the fiscal year ended June 32019, with the Securities and Exchange Commission and issued our final results and corporate highlights press release, both of which are available in the Investor section of our website at Www <unk> pharma Dot com.
On our call today, we will provide a summary of financials from the fiscal year ended June 32019, and then review progress in our programs in business over the last year. We will then open the call up to your questions before we get started I want to call. Your attention to the fact that this conference call may contain forward looking statements within the meaning of the safe Harbor provisions of the private Securities Litigation Reform Act of 1995, you should be aware that our actual results could differ materially from those contained in any forward looking statements, which are based on management's current expectations and are subject to a number of risks and uncertainties as discussed in our SEC filings, including our most recent annual report on Form 10-K filed earlier today.
A replay of this call will be available on our website at approximately <unk> approximately an hour after its conclusion.
I'd now like to introduce you to our speakers for today with me are Dan Gold, our President and Chief Executive Officer, Brian draws, but our Chief Financial Officer, and David are so our chief operating officer. Additionally, Richard Collier Senior Vice President of clinical development and Karen Potts, Our senior Vice President of regulatory Affairs are also with us today.
Brian will start with a summary of our financial results after which Dan and David will provide remarks after that we'll open the line for your questions I'll now turn the call over to Brian .
Thank you David.
I'll provide a brief overview of our financial results for more detailed information regarding our results.
Invite you to review our Form 10-K that was filed earlier today.
I'm pleased to report that we finished the year with $79.8 million in cash cash equivalents short term investments and common stock proceeds receivable with no outstanding debt.
Additionally.
For the year ended June Thirtyth, we cash used in operations was $39.4 million compared to 21 million.
The last year research and development expenses were $32.3 million for the year ended compared to $17 million last year.
The increase was primarily related to increased activities and all clinical programs, including development costs associated with me for one and Bruce a clip.
General and administrative expenses were 14.6 million for the year compared to $9.8 million last year. The increase primarily relates to professional services expenses share based compensation and general corporate expenses.
We recognized revenues of $4.9 million for the year ended June 30, compared to $1.6 million for the year ended June 30 last year revenues resulted from the recognition of fees allocated to research and the development activities related to the health.
Karen license agreements.
Revenue increased due to higher levels of research and development activities. During this year.
Net loss was 16.8 million or 24 cents per share for the fiscal year ended compared to a net loss of $40.1 million or 97 cents per share for 2018. The company had 73.5 million shares of common stock.
Outstanding at June 32019, compared with 70.4 million shares at June 32018, the adjusted net loss for the fiscal year ended June 32019, excluding non cash expenses related to changes in the fair value of warrants issued in connection with the May 2000 financing a non-GAAP measure was 44.5 million.
In summary, we started fiscal year 2020 in a strong position to continue advancing our programs with that I will turn the call over to Dan.
Thanks, Brian and thanks, everyone for joining us this afternoon.
Over the last year, we've executed on a straightforward purposeful strategy to advance our pipeline of four clinical stage oncology candidates, while building a strong strong foundation to deliver value to our stakeholders and importantly to continue our ultimate mission of delivering patient benefit beyond what is currently achieved through existing therapies.
As I go through my prepared remarks, I'll update you on each of our programs, including the upcoming milestones and plans for the next few quarters.
Let's start with Emmy for a one which we believe based on the clinical evidence. So far is emerging as the potential best in class Pithree.
Delta inhibitor for the treatment of B cell malignancies.
Please recall that we have two ongoing studies a phase two clinical trial evaluating patients with relapsed or refractory follicular lymphoma intended to support a strategy for an accelerated approval of a marketing application with the FDA.
As well as a phase one B study that currently is evaluating Emmy for a one primarily in combination with agents such as Rituxan or Zana Bruton to an investigational BTK inhibitor being developed by Beijing.
Hi, guys three Delta inhibitors are clinically validated for the treatment of B cell malignancies. This is not surprising given that given that Pithree Delta is found at the crossroads of several b cell signaling pathways and as such Pciethree Delta is a target for treating b cell disease in general.
Hold significant potential that matches and I believe may actually exceed the potential of other drug classes targeting these other b cell pathways, even the BTK inhibitors.
However, historically.
Three Delta inhibitor class has been challenged by dose limiting toxicities restricting their clinical utility.
This presents an opportunity for the development of a next generation candidate with pharmaceutical properties that can better maximize the biologic potential of Pithree Delta inhibition, while limiting toxicities that hinder their clinical utility.
With me for a one we believe we have the opportunity to open a new chapter in the utility of Pithreek Delta inhibitors, particularly in combination with other therapies to treat b cell malignancies.
This is in large part because of the unique molecular structure of Emmy for a one that results in pharmacodynamic characteristics, which are distinct from FDA approved delta inhibitors and others in development.
And before a one is characterized by prolonged target binding preferential cellular accumulation significant distribution throughout the body tissues into 28 hour half life suitable for once daily oral administration.
We believe these attributes are important to the potential differentiation and clinical utility within the class of three K. inhibitors.
Specifically, we believe Emmy for one's properties allow exploration of flexible dosing regimens.
Such as in an intermittent dosing schedule, which has the potential to maintain clinical benefit while minimizing immune related toxicities common to the other pithree Delta agents.
Either as a monotherapy or in combination with other therapies or investigational agents.
On the intermittent schedule Emmy for one is administered once daily for two cycles or eight weeks followed by administration once daily for the first seven days of a 28 day cycle, followed by 21 days of placebo versus the continuous schedule where for a one is administered daily.
Based on the maturation of our data to date.
Which now includes over 100 patients treated with Emmy for a one either on the continuous or intermittent schedules. We believe there is strong evidence for this view of Emmy for one as a potentially differentiated next generation Pithree K Delta inhibitor.
Recently, we presented data at the ASCO 2019, and I CML 2019 meetings, demonstrating that follicular and CLL patients on the intermittent schedule achieved an overall response rates similar to that in patients on the continuous schedule, but with nearly a two thirds reduction in the adverse events of special interests, such as diarrhea and collide us.
Two levels of 10% or less.
This highlights the importance of the intermittent dosing schedule as a key part of this development program and we believe a key factor in the emerging clinical profile as observed in the ASCO in CML data.
In this data, we see strong clinical support for the intermittent schedule consistent with the scientific basis for Pithree K Delta as an important b cell target.
And the rationale for the intermittent dosing schedule that being intermittent schedule provides sufficient.
Delta inhibition in B cell tumors, while potentially allowing the recovery of T regulatory cells, the likely catalyst for the adverse events of special interest in the periphery.
Based on these data around the beginning of calendar 2019, we initiated a phase two clinical trial evaluating Emmy for one as monotherapy.
For the treatment of adults with relapsed or refractory for liquid lymphoma. After failure of at least two prior systemic therapies, including chemotherapy and an anti cdtwenty antibody.
We intend to submit the results to support an accelerated approval of a marketing application with the FDA.
We anticipate complaint completing enrollment in this trial sometime around this time next year.
The phase two is evaluating both the continuous and intermittent dosing regimens approximately 166 patients will be randomized in the trial and the primary efficacy endpoint will be the rate of the objective response to therapy. The phase two study represents an opportunity for an expedited regulatory path to marketing approval for third line Follicular lymphoma.
Through the FDA has accelerated approval mechanism.
While third line Follicular lymphoma represents an important opportunity.
To meet an unmet medical need and as an attractive and is attractive commercially we are targeting a broader opportunity.
As such in the Phase one B study, we are continuing to further explore the intermittent schedule as part of a combination approach for the treatment of other b cell malignancy indications, David Urso, our Chief operating officer, who leads our business development efforts will speak to some of our work around these combination treatments with Emmy for one since they are related to the expanded opportunity and our strategic partnering activities over the last year and our plans moving forward.
And with that I'll turn it over to David.
Thanks, Dan as Dan mentioned, the phase one b is ongoing and of particular interest to our programs clinical and commercial value or potential combinations of Emmy for along with other therapies.
To that end of phase one b has already evaluated Emmy for one in combination with Rituximab disarm was primarily to evaluate safety since general since in general the patients in the study were tux amount of experienced.
As presented in June of this year at CMO, we observed no change in the safety profile of the combination compared to monotherapy with Emmy for one and again, a very high response rate.
In the second arm of the one B study, we are evaluating the safety and efficacy of Emmy for one in combination with anti burden is an investigational BTK inhibitor being developed by our partner be gene.
This is being done under collaboration finalized with Beijing in October of 2018. This arm of the study is evaluating the combination in patients with mantle cell lymphoma diffuse large b cell lymphoma, and second line fully Carol lymphoma.
The cost of the combination trial is being equally share with Beijing.
With each company supplying its own compound, we retain all commercial rates to Emmy for one and Beijing retains all commercial rights to anniversary.
The collaboration with Beijing is an example of our efforts to be mindful of deploying resources efficiently and to make decisions to develop and commercialize our drug candidate strategically either independently or via partnerships to most effectively leverage the potential of our candidates and resources in this past year. We also license Japanese rights to Emmy for one to Kyowa Kirin company in a transaction completed last October . This is another example from the recently completed fiscal year of the strategic trends of a strategic transaction that effectively leverages, a partner's resources, while advancing the development of one of our candidates as we continued to develop Emmy for one as a next generation Pithree K Delta inhibitor. We believe that there is significant potential to treat a range of b cell malignancies in combination with other therapies, including not only rituximab and BTK inhibitors legs and Ibrutinib, but also bcl two in.
Inhibitors, such as Veneta, clecs and potentially agents with other mechanisms of action as well where practical we're exploring additional clinical collaborations to advance evaluation of combinations of Emmy for one and other agents in various b cell malignancies.
We anticipate having an update on the zana burden of combination potentially around mid 2020 .
And we will also look forward to other opportunities to update on the phase one b data as it matures, including publication of the data in a peer reviewed journal.
In short taking a combination approach to development across multiple b cell indications may open opportunities in earlier lines of treatment for flicker lymphoma, as well as opportunities to treat select significant addressable markets with unmet medical needs in multiple treatment paradigms, including CLL SLM, though.
Mantle cell lymphoma marginal zone lymphoma.
And DLP Seattle.
Overall, we estimate the addressable markets in these b cell malignancies represents roughly 50000 patients in the United States.
We also see this program as an opportunity for me to transition to a commercial organization either independently or via a relationship with a strategic partner, while the nature of the indications allows them to pursue commercialization independently. We believe there may be value and strategic benefits to partner and to that end. We have regular discussions with potential strategic partners, we are pursuing opportunities and avenues of development and commercialization both independently and with partners that we believe will best build the clinical utility of Emmy for one for patients and realize value for EMEA.
Stakeholders.
I will now turn the call back to Dan Troop to review our other three clinical programs Dan Thanks, David.
I'd now like to update you on our remaining programs starting with our CDK inhibitor Virtusa club. Another exciting program that we believe has tremendous potential to improve on existing treatments for b cell malignancies, and day ml, particularly in combination setting with fanatic KLAX, an FDA approved bcl two inhibitor.
Roosa club is an orally available CDK inhibitor differentiated by potent inhibition of CDK nine in addition to CDK six four in one.
As you May know cdknine in regulates the myeloid leukemia cell differentiation protein or mcl one.
A member of the family of anti apoptotic proteins, which when elevated may prevent cells from undergoing cell death.
Inhibition of CDK nine blocks the production of Mcl, one which is an established resistance mechanism to bcl two inhibitor Vannatter clecs.
CDK nine also regulates Mick a transcription factor regulating cell proliferation and growth, which contributes to many human cancers and is frequently associated with poor prognosis and unfavorable patient survival.
Last year at Ash in 2018, we presented preclinical data demonstrating that Bruce eclipse Synergizes with fanatic KLAX to induce a pop doses in both phonetic CLEC sensitive and resistant AML cells and cell lines. The preclinical data further demonstrate that Arista clip transfer transiently down regulates mcl, one and that Mcl, one down regulation is likely responsible for much of the synergies seen with for roosa clip and fanatic lax.
These data add too earlier studies, demonstrating for roosa clip dose Dependently suppresses mcl, one and that's a combination of Teresa club.
The dose ranging phase one clinical trial for roosa clip in which we started treating patients. This past year. The trial was initially intended to evaluate Bruce a clear primarily for safety as a monotherapy in patients with relapsed or refractory b cell malignancies or AML after failure of prior standard therapies.
In parallel we have submitted an amended protocol to the FDA to evaluate for Roosa club in combination with fanatic KLAX to confirm the synergies and the opportunity for combination treatments across multiple indications. We look forward to updating you on this program likely around a medical meeting in the first half of the calendar year.
2020.
Next up this M 44, our novel and tumor selective mitochondrial inhibitor target targeting the Occidental phosphorylation complex in the mitochondria.
As reported at Ash ASCO 2019.
Mm 344 recently completed a multi centered investigator initiated randomized open label clinical trial evaluating the combination of M 44, and the VEGF inhibitor Beth.
To kick them out or a vast and much easier to say.
42 patients.
With early Hertwo negative breast cancer patients were randomized one to one to receive either Emmy 30, 44 in combination with avastin or sailing in combination with Avastin.
This study was designed based on the observation that while anti angio genex like a vast and or the small molecule kinase inhibitors are able to reduce the rate of glycol assists in tumors as a mechanism to block cell growth tumor metabolism will shift to mitochondria metabolism to continue energy production in support continue tumor proliferation in such cases of tumor plasticity in the presence of of treatment of NTM Geo Genex. It was hypothesized that simultaneously targeting the alternative medical source with metabolic source with M. For 344 May open an important therapeutic opportunity. The primary objective of the trial was to show proof of M 44, biologic activity as measured bake by K. I 67 reductions a measure of cell proliferation that is highly correlated with tumor response data from this study demonstrate significant.
Biologic activity in the Emmy 344 treated group as measured by the mean relative K. I 67 reduction compared to patients from the Avastin monotherapy group treatment was generally well tolerated. There were just two grade three adverse events of high blood pressure one in each arm.
The next step for M 44, as to evaluate it in combination with an anti angiogenic and look at more meaningful clinical endpoints. This is a very exciting tumors metabolism approach and program and we are evaluating the best path forward, including the potential for collaborations.
Now moving to our final and fourth clinical candidate percentage stat, the oral h. DAC inhibitor being evaluated in a pivotal phase three global registration clinical trial for the treatment of adults with newly diagnosed AML, who are unfit to receive intensive chemotherapy.
Percentage that is also being evaluated in a phase two trial in patients with high or very high risk Mds.
Recall, we received breakthrough designation from the FDA in 2016, 4% a stat in the treatment of AML and in January 2018, the M&A granted orphan drug designation also for the treatment of AML.
Percentage that is fully partnered under an exclusive worldwide license development manufacturing commercialization agreement with health and healthcare Helston is primarily responsible for funding global development and commercialization costs, 4% of staff. We are responsible for conducting the phase two Mds trial, the cost of which is being shared equally with Hilton.
Upon successful completion of the phase two study all future development in commercialization costs will be the responsibility of health.
The phase two study completed enrollment earlier this year and patients are now being followed for survival.
The data from this study are encouraging and in discussions with our partner health and we are targeting to report 12 months survival data, possibly at a medical meeting in the first half of calendar 2020. After we have 12 month follow up on every patient.
In summary, we are very encouraged with the progress we've made over this last year, we have a diverse clinical stage pipeline. We have two candidates in global studies to support marketing authorization pipeline that we expect to continue to generate exciting data over the coming quarters and a healthy balance sheet.
We are in a strong position to continue building value for our shareholders.
As we work diligently to advance our clinical candidates towards approval for patients.
With that update I think we're now ready for questions. Operator could you open the line to questions. Please yes. Thank you we will now begin the question and answer session.
If you have a question. Please press Star then one on your Touchtone phone.
If you wish to be removed from the Q press, the pound sign or the hash key.
If you are using your speaker phone that you may need to pick up on your handsets first before pressing the numbers.
Once again to ask a question. Please press star one on your Touchtone phone at this time.
The first question in the queue comes from Tom Shrader with the BTI Ji. Please proceed.
Good afternoon, everybody. Thanks for holding the call I, just had a little bit of a.
Philosophical question about this is anup.
Combinations just your thought process. There are this drug is.
Neither is a simple drug to dose.
Do you think you're back to square one with dosing. Your drug are you only interested if you can sort of use what you've learned in in the.
Intermediate dosing just just your thoughts about where that stands and dosing and similarly your thoughts on the diseases. You gave a list of diseases, which CLL isn't on which I find interesting and I just love to get your thoughts.
Yes, Thanks, Tom Good question.
About the dosing so we feel from the safety profile of the drugs that.
We're starting at the recommended phase two dose of both agents.
We had a lot of discussions with Beijing about this and we both felt there was no reason to go down we have the option of course to go down and there are always dose modification.
Pre defined in the protocol.
The first part of the study actually is and it is fully enrolled now is is specifically addressing your question about the safety. We're looking at to make sure there are no.
No issues with that.
And we should know that answer relatively soon.
And assuming that.
That is the case, we will then proceed.
To doing the dose expansion cohorts.
That David mentioned in his remarks.
You are correct, we specifically at this time are not.
Looking at CLL.
That doesn't mean that that isn't a target for us in the future.
I think.
This question May come up.
In with others CLL as an interesting disease that.
We've given a lot of thought too as you know Tom the our response rate of with for a one is extraordinarily high we have a 100% response rate so far.
CLL is not one of those diseases, where there is a lot of white space. Currently it is very well served by the BTK inhibitors.
A brute nib.
As as a as a model.
And.
As such we felt that it would probably be difficult to discern in a timely fashion.
An effect of the combination because you really then looking at prolong progression free survival endpoints.
Or MRT negativity and therefore, we decided to look at the other indications where BTK.
Has some indication of activity, although not as strong as it does in CLL.
That said of course, if it turns out that there is good indication in some of the other indications that.
The combination is potent we obviously could revisit CLL, but I think you know with the with the data that have been presented most recently at ash and ASKO with various be teekays.
It would be a very long protracted development plan to look at especially in a frontline or second line setting with.
With the combination.
All right and just just to make sure I got you. This first cohort with the Beijing drug that's that we really should be looking for efficacy there.
That's that's designed to be an active combination.
Yes, totally yes, absolutely it's just.
For the first I think does half dozen patients where it was really a.
A quick look at safety to make sure there's no acute safety issues in the first month and then.
We will do it expands coats and it is a efficacy.
As well yes.
Alright, great. Thank you just to finish up on CLL is BTK. This is David as BTK gets used more and more.
Upfront, we do think that in the future.
There is a place to play with BTK progression, whether as a single agent or potentially in combination with banana clocks.
Okay great.
The next question in the queue comes from Peter Lawson with Suntrust. Your line is open. Please proceed.
Hi, everyone. Congrats on the progress this quarter. This is and then long on for Peter Lawson.
Just really quick I might have missed this can we expect an update from floral one around December or as time this year and if so how many more patients do you think we may get.
Yes, Hi, Niamh I think.
Well there because we have been putting all of our efforts in the registration study or the accelerated approval intended study.
We the any patient who would have typically been rolled in the phase one b in per froehlich EULAR for relapse refractory. If like you were encouraging are going onto the registration say, so we really don't have a lot more.
We tend not to one just continue to dribble out information so I think for this upcoming ash.
There won't be any.
Significant updates in the patients that we reported on I mean.
We kind of had a complete comprehensive response rate update at ASKO in an ice CML.
The only thing that would be.
New would be continued look at the duration of those responses.
And I think we're going to probably.
The thinking is right now we might incorporate that into a manuscript rather than continuing to just dribble out new information.
In small and the amount of new information.
Great. Thank you Thats Super helpful.
And then I guess around a registrational trial the phase two let's enrollment effectively compete around sometime next year are you waiting for all the patients have thought six months follow up before presenting the data so it's probably.
Early 2020, and then the filing Hum.
Sorry early.
Yes, 2020 and then.
Hi, early 2021, and then filing afterwards.
Compound question, there, yes, so working backwards.
Yes, the intention is to file sometime late 2021.
In terms of the data presentation.
Recall this is being run as a blinded study the patients don't they know that they are receiving.
Continual dosing for the first two cycles and then.
Their rent there theyve been already randomized and they're receiving blinded drug from then on.
Either on the Internet and the continuous schedule. So the only data that we would know for sure would be after two months of the response rates at two months.
And then whatever blended response rates only from the investigators. This is this will be done by independent radiology as well so.
The.
Whether we will.
Talk about the two month.
Dose response rates or not.
We haven't decided that yet.
But you are correct that once the last patient is in.
And has a two month evaluation that would be a six month clock from there before we would report topline data.
Okay, I guess last question will follow.
Your talks and then looking into possible combinations can we expect initiation of a new combo arm. It sometime this year or anytime soon.
Yeah. So.
I think as David was alluding to we know we are currently we're exploring we've explored restocks and as we've mentioned that was primarily a safety question.
And the responses are very good because we're dealing with a drug that has very high responses anyway. There is then in Britain is really the one were focusing on right now.
And as David alluded to.
We have received interest from investigators.
To consider looking at combinations with fanatic lax.
And we're looking at that very carefully.
If we decide to go down that road.
It probably wouldn't be a 2019 and probably be more in the early 2020 timeframe. Just because you know once we've made the decision to write the protocol and get it to the FDA and all that good stuff takes some time, so I think I wouldn't look for new combination.
Studies, starting this year, but quite possibly the beginning of next year.
Great. Thank you so much for taking my questions I'll get back in the queue. Thank you.
The next question the Q comes from Stephen Willey with Stifel. Your line is open Sir.
Yeah. Good afternoon, thanks for taking the questions.
Dan I was just wondering if you could maybe speak a little bit.
Enrollment.
Registrational right now.
Kind of what the 12 month guidance currently contemplates perspective.
Additional sites.
Okay.
Yes, I guess, whether or not there is any kind of.
Legal room built into that guidance to accommodate some of the other competitive.
Therapies.
Yeah.
Good question Steve.
So.
First off I'll, just say it.
Just flat out we will not be giving regular enrollment updates, it's a slippery slope and we just decided we're not going to go down there.
We have spent a lot of time since we decided since we had our discussion with the agency and got the blessing and.
To initiate this study weve done a lot of work with the CR ROE and the sites in evaluating there.
Their patient turnovers, the their expected enrollment and based on everything they say just like you know my my golf scores scratch right. They always over estimate the number of patients. So we discounted that and we came up with that calculation that we needed to open about 100 sites internationally and that is what our goal is we're well on our way to doing that.
And based on that calculation, we feel that currently from where we sit and what we've said that sometime.
Mid year to around now we should be able to enroll the 166 patients that Weve said.
We would.
In terms of wiggle room, Theres no wiggle room until there is wiggle room, well if it looks like we're following fall far short we will update you as.
As appropriate, but from where were sitting now with the pace of opening sites and the pace of enrollment I think we're still.
Comfortable with making that guidance and as I said, if that should change, we'll let you know.
Okay. That's that's actually helpful commentary.
Just one.
Respects the discussions regarding worldwide.
Partnering it sounds like you guys are.
Kind of still evaluating strategy go forward there.
Presumably any strategy.
Quickly incorporate some level.
The next us partner.
Have you guys given any additional thoughts.
Registrational strategy looks like at this point or one.
Just any commentary around what trial design might look like in terms of supporting.
Thats helpful.
Yes as far as the this is David as far as the partnering strategy goes we are thinking about regional strategies as well as a global partner.
And the go it alone scenario, obviously, we don't have the capability to commercialize the drug ex us.
I think our preferred partnering strategy if.
Would be to have one global partner, if we go down that route and do I think we've talked about this before ASCO co promotional arrangement, where you have profit and loss sharing in the United States and then.
Basically just milestones and royalties outside of the United States and with the partner do the heavy lifting on the whatever incremental development there might be ex us and certainly the commercialization.
And in terms of.
The E U strategy.
I think what we're currently obviously since we're going down accelerated path, we have to be already planning or considering planning our confirmatory strategy.
And.
We kicked around a lot of things, we've bounced them off of a lot of our advisors.
We are having an important discussion with our steering committee.
Staring to me.
Shortly and I think at that point, we will have as much clarity as.
As we can in how we're going to proceed into phase three I mean, I think their choices are obviously limited based on whats approved in whats used in second line public EULAR.
You know obviously it will incorporate some sort of a CD 20 treatment. That's why we did the rituxan arm just to be sure.
And then the question is is it a doublet triplett or is it other potential combinations and I think we will have a lot more to be we'll be able to say a lot more to that Steve.
In the coming months, but right now I think it's fairly obvious what the possibilities are and we're exploring all of them both from a medical feasibility as well as truly just operational feasibility in terms of.
Which combinations would be more or less received by the investigators.
Okay. That's helpful and then just for clarification.
On the recycling.
Update I think you mentioned that there is a chance we could so some data first half of 2000.
At a medical meeting is is that the dose ranging model therapy.
Results that we could see.
Yes.
Yeah, I think that.
Obviously since that trial has been up and running.
That would be the most data we have.
In terms of.
The monotherapy.
And hopefully we'll start to get some early.
Looks at the combination certainly in terms of safety.
And PK and that kind of stuff.
But in terms of efficacy I think it would be a stretch to imagine we'd have something within the next six to nine months.
Okay, and then are there monotherapy expansion cohorts that are specified in the phase one or or is it just still.
Paul dose range.
Yes ill, let Richard.
Yes ill, let Richard answer that yes, Steve it's following the dose escalation the protocol contemplates expansion cohort in B cell malignancies.
And we have specific b cell malignancies that our disk drive as well as an ATM now where we could also look at monotherapy and or the combination with venetoclax.
Steve I think that from we are.
We would love to be surprised that we get a very good monotherapy response, and obviously, if we do we would go running with that very quickly.
The when we acquired this agent and when we develop we looked at the development plans for it we really felt like just like the CDK four sixes in breast cancer. The monotherapy effects are not nearly as high.
As the combinations and I think thats really sort of what our focus is but we would love to be wrong.
Okay and should we assume that you guys would have announced that theres been a dose declared for dose expansion.
This is within the trial or.
Yeah.
Yes, I mean in the future you mean.
Yes, correct, yes, yes, absolutely, yes, yes, once where we're still doing the dose escalation for safety and.
And looking for when the hints of efficacy if there are any.
Great. Thanks for taking the questions guys.
Sure.
Thank you. The next question comes from Yale Jen with Laidlaw <unk> Company. Your line is open. Please proceed.
Good afternoon, and thanks for taking the questions.
Just first want to be clear that the full one combination what.
Okay.
Is that in the intermittent dosing, even those ranges or continuous dosing.
Yes, hi.
All of our combination work is done in the intermittent schedule.
Okay great.
That's very helpful.
One other question just about the from that person a stat.
In.
And now.
Is that anticipate the patient recruitment will be completed by end of this year.
I'm going to let Richard handle that.
How sand Hill is running this study is.
It does not make any public statements on when it is.
But the intent is to complete enrollment.
In the next 12 months I would say Thats based on my best to.
A judgment based on what I'm seeing the study, but again there is no public information made from house and on that completion of enrollment.
Okay, that's fine and.
Would you guys.
In this or any kind of financial guidance terms all.
The next fiscal years sort of offline, maybe a little bit on the bottom line type of suggestions.
Right. So yes, you know we typically don't.
Make forward looking statements you beyond a year and we clearly have more than enough cash a year's worth cash.
You can see pretty consistently over the past several quarters going back a year or more that our burn is fairly consistent somewhere between nine to 11.
Million per quarter.
And it's just hard because it all depends on the the clinical activities. We have ongoing we've we've had a lot of clinical activity is slowing down and now with the the registration study, we have more and new clinical activity. So it's a little hard to judge from quarter to quarter, but I think you know historically, we've been in that.
10 million per quarter, and that's about as best as we are that we are willing to speculate on.
Okay. That's helpful. And then maybe final one is for 344 I know you mentioned.
You want to.
You will provide more colors in terms of the future.
Development, but could you just give a general framework us how you think about so next sets off demand might be.
Yeah, Yeah, you know, we we really love this drug.
The data that.
We presented at Astro there were presented at ASCO was very encouraging him as the culmination of several years of a lot of hard work and trying to understand how this drug could be best used and it does appear that the hypothesis driven study.
Was fulfilled that if you block one source of energy the tumors in vivo will use the other source.
Interchangeably and that the only true way of getting a tumor metabolism is to blur both avenues.
We over the years given a lot of thought on how to best develop this drug and I think with the anti angiodynamics.
We're really looking at spaces, where.
These drugs have been shown to have activity that obviously is less than optimal and there's still a lot of space.
We are preclinical work that was done in Spain was actually done both with the mostly with the small molecule. So the tyrosine kinase receptor inhibitors and I think the.
So we're looking at the whole gamut of of what's possible. There are clearly advantages with an antibody like a vast and compared to the small molecules and the context in which they are used with or without chemotherapy. So there is a lot of moving parts that were trying to get our arms around and as we've said, we would ideally like to do it with a potential collaboration with.
With another entity that has one of these agents whether its small molecule or antibody. So we can really best to explore the full potential of the combination. So right now where we're really focusing our energy and resources on for a one and Bruce a clip for the most part.
But thats not to say that we're not we're ignoring threeforty four we're just trying to.
To really understand where the opportunities are and what our partners potential collaborators would have interest as well.
Okay, great. Thanks law, that's a lot of details and appreciate the online.
Well Ryan in causeway.
Sure, Yes, nice to talk to you.
The next question comes from Jim Birchenough with Wells Fargo. Your line is open. Please proceed.
Thank you hany nickel or James can you.
Can you hold cash for the first question on cash loan rating.
He had aspirations for loan Paul <expletive> .
To extend the passionately runway beyond.
To read which is maybe 2021.
I mean, I don't think thats the rationale for doing the deal the rationale for doing the deal is to.
Optimize the development and leverage resources of a bigger partners. So that we can go broader within b cell malignancies, and potentially have more muscle behind launch that would be the rationale for the partnership I mean, obviously, there would be an upfront payment that would have non dilutive capital in it if we did it.
So, yes and yes.
Okay.
And then I mean, Nick let me I don't mean to be facetious I think the no.
We we always look at what's what's really best in the long run for the company and for the shareholders and.
If bringing in non dilutive cash in a powerhouse.
Partner would be much better in the long term, we would definitely do that.
And if we don't think there's a good deal then we would we would.
Look at other sources of capital but.
We always take this very seriously we are not trying I'm not trying to make a joke and neither is David we.
We always look at it very care both aspects very carefully.
Okay, and then sorry.
I think you talked about openings.
20 patients were talking for lone combinations.
Is that still part of the plan or is that sort of shifted now more towards.
Well I think we've pretty much done that Nick Weve.
I am not.
Yeah, we've kind of completed our evaluation.
As we've said before and I think you know to echo what our investigators said to us is.
Guys, you're you're working with a drug that is showing you 80% response rate what do you expect to see from an efficacy what we really wanted to see was the safety aspect and we've kind of done that I'm not sure. If its 15 or 20 patients that we've treated collectively it's in that ballpark weve not seen any safety issues. We see very high response rates and now. The question is I think it really the purpose of getting to an earlier question I think from Steve was how do you incorporate your thinking into register confirmatory studies, and obviously CD 20 will be an important part of that so I think in terms of continuing down the road with CD 20.
But right now we've accomplished what we wanted to we know it's safe, we know that the drugs work well together and.
We will just incorporate that knowledge into future planning.
With various combinations, whether its doublets and triplets down the road.
Okay. Thanks.
And then just aging agreement couple more advanced entities.
And would there be an opportunity for example that you cited in China.
Clearly drive expansion, particularly in indications such as being one of them, obviously challenging so long as the original goal.
The agreement is two part of the attractiveness of doing it was to be able to leverage the ongoing one b study that we're conducting so we just opened up another arm with a quick amendment.
To the study and we're in the same sites.
Then if where we see a signal in one of those initial cohorts I think thing.
You would move forward into an accelerated approval study and more than likely that would be a global study, but we have to get back together with Beijing and both strategize on how to execute that trial with that.
Thats beyond the initial scope of our agreement.
Okay.
And then just last one for me in terms of doing so.
Is that expected to be a 30 day turnaround time.
Yes.
Yes.
The clock is ticking yes.
Okay excellent okay.
Sure.
Thank you.
The next question comes from Adam efforts with less capital. Your line is open. Please proceed.
Great Hi, everyone, just going back to the indication choice for the.
And improved NIM arm of the phase one b I think it seems clear why you're not including CLL, but maybe anything else you can say on why you chose mantle cell lymphoma deal PCL and then second line Follicular. It was a based on unmet need fees.
Okay.
Did we lose Adam or operator, we still aren't.
Adam.
Are you there sir.
Can you hear me all right now yes.
Yes, I think Thats, Alright, hi, everyone, Yes, yes, I think I understood the question Adam.
The rationale was really to look at.
Settings, where there is clear activity with the BTK and with a with a.
Delta, but that you could hopefully improve on and with the combination. So for mantle cell. For example responses are quite good with the teekays, but they're not as deep as they could be and probably not as durable as as you would like Dl Bcl clearly they are not nearly as good as one would expect and I think the decision in Follicular and second line was to see if you could come up with a chemo alternative combination that was safe and rather durable so.
We did put thought into each and every one of those indications.
And it really was a question of.
Looking at potential synergies, where the agents had activity with it could be better or perhaps providing clinical alternatives for physicians, where there is existing.
Therapies, but that you maybe you could replace the use of chemotherapy as an example.
Great and then I guess, considering that Santa Britain and for one or both targeting proteins in the B cell receptor pathway are we expecting.
In terms of response rates deepening deepening of responses more durable responses both of those what is the sort of baseline expectation there.
Yes, I think that.
You hit it on the head the hope is that we'll we'll get deeper and more durable responses I mean I think.
As we understand those pathways they do overlap at they are distinct.
So.
Three signals through a Katie I think BTK, probably signals more through Nf Kappa B and so there are reasons to think that there should be additivity or or even synergies certainly the preclinical work in the knockout mice suggests that the double knockouts are much more depleted than either the single knockouts.
So I think there is reason to believe that the combination should be better than either the agents that by themselves.
And so we're clearly are looking for deeper more durable responses I mean after all I think it's important that we hear the message loud and strong from a lot of investigators that.
They're looking for the ability to get their patients into a deep remission and stopped treating them patients don't want to be treated forever.
And that's really our goal to because that's what we hear back from the community and that's what our goal is to get these patients into a very deep durable remission and give them a break but let them go about their lives.
Fruitfully and.
So that is really where a lot of the motivation of trying these various combinations.
Great. Thank you.
Thank you Sir I will now turn the call back over to Mr., Dan Gold for any closing remarks.
Thank you.
Again, I just want to thank you all for joining US today, we're beginning our new fiscal year and a very strong position with a continuing record of success.
In our execution on the development programs and our business strategy, we look forward to reporting on our progress across our entire portfolio in the coming quarters and I wish you all the best in the waning days of the summer.
Thanks again for joining.
Ladies and gentlemen. This concludes today's teleconference. Thank you for participating you may now disconnect.
Yes.
[noise].