Karyopharm Therapeutics Inc (KPTI) 2016 Q3 法說會逐字稿

Good afternoon. My name is Vicky and I will be your conference operator today. At this time I would like to welcome everyone to the Karyopharm Therapeutics' third quarter 2016 financial results conference call. There will be a question and answer session to follow. Please be advised that this call is being recorded at the Company's request.

I would now like to turn the call over to Mr. Justin Renz, Executive Vice President, Chief Financial Officer, and Treasurer of Karyopharm Therapeutics.

Thank you. Good evening and welcome to the third quarter 2016 earnings call. This is Justin Renz, and I'm joined today by Dr. Michael Kauffman, Chief Executive Officer; Dr. Sharon Shacham, our Founder, President and Chief Scientific Officer; and Chris Primiano, our Senior Vice President of Corporate Development, General Counsel, and Secretary.

On the call today, Michael will make some introductory comments, Sharon will provide a short update on the clinical development programs and plans, and I'll provide an overview of the third quarter financial results. Michael will then provide some summary remarks and we'll open the call up for your questions, for which Chris will also be available.

Earlier this afternoon, we issued a press release detailing Karyopharm's results for the third quarter 2016. This release is also available on our website at Karyopharm.com.

Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for purposes of the safe harbor provisions under Private Securities Litigation Reform Act of 1995. These include statements about our future expectations, clinical developments and regulatory timelines, the potential success of our product candidates, financial projections, and our plans and prospects.

Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factors section of our most recently filed report on Form 10-Q for the third quarter of 2016, which is on file with the SEC, and any other filings we may make with the SEC.

Any forward-looking statements represent our views as of today only and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today.

I will now turn the call over to Dr. Michael Kauffman, Chief Executive Officer of Karyopharm.

Thank you, Justin, and good evening, everyone. Thank you for joining us on our call today.

We continue to make good progress on our efforts to advance oral selinexor. During the third quarter, we communicated our planned development and regulatory path toward US Food and Drug Administration, or FDA, and European Medicines Agency, or EMA, filings for selinexor as a treatment for patients with multiple myeloma.

This plan is based on the positive responses from the FDA regarding the design of the Phase 3 BOSTON study and supported by data emerging from both the STORM and STOMP studies, where selinexor is demonstrating robust and durable responses in patients with heavily pretreated multiple myeloma.

Both of these studies were selected for oral presentations at the upcoming American Society of Hematology, or ASH, 2016 annual meeting, where we look forward to presenting even more mature and detailed datasets in early December. Sharon will provide more color on our ASH plans, in which a total of 21 abstracts, including nine oral presentations, have been selected.

In addition to key data presentations with updated data from STORM and STOMP, we would also like to highlight a few of the other presentations, including, one, results from a Phase 1 study sponsored by the Multiple Myeloma Research Consortium that is evaluating selinexor in combination with carfilzomib and dexamethasone in patients with relapsed refractory myeloma; two, results from a Phase 1 study evaluating selinexor in combination with pomalidomide and low dose dexamethasone in patients with relapsed refractory myeloma; three, updated data from the Phase 2 SAIL study evaluating selinexor in combination with Ara-C and idarubicin in patients with relapsed refractory acute myeloid leukemia; four, results from a clinical trial evaluating selinexor in combination with high dose cytarabine and mitoxantrone in patients with AML; and five, preliminary results from a Phase 1 study evaluating KPT-8602, our second-generation SINE compound, in patients with multiple myeloma.

One other ASH item I'd like to mention, we are hosting an analyst and investor dinner reception onsite in San Diego on Monday night, December 5th at 8:00 pm Pacific Time. We will be providing an overview of the updated results from the STORM and STOMP studies in multiple myeloma, and several well-regarded thought leaders in the treatment of myeloma will be participating in an interactive panel discussion and Q&A session.

The panel will highlight the growing population of myeloma patients and the current treatment landscape, including the increasing use of oral therapies along with the increasing population of myeloma patients whose disease has progressed despite all available therapies.

There will be a live webcast of the event which will begin at 8:15 Pacific Time. So, even if you aren't attending ASH in person, you can still tune in via the Web. We will certainly hope you can attend or join us in the webcast, as this should be a very informative session.

With that, I'd now like to turn the call over to Sharon to discuss the trials in more detail, as well as provide us an overview of key presentations that occurred during the quarter. Sharon?

Thank you, Michael. Starting with selinexor in multiple myeloma, as Michael mentioned we are scheduled to present updated clinical data from the ongoing Phase 2b STORM study at ASH in early December. Lead STORM investigator, Dr. Dan Vogl of the Perelman School of Medicine at the University of Pennsylvania, will give an oral presentation highlighting clinical data demonstrating that selinexor in combination with low dose dexamethasone achieved robust response rates in patients with quad-refractory and penta-refractory myeloma.

As a reminder, all patients in the study had multiple prior regimens, including glucocorticoids and prior alkylating agent therapies, and had myeloma that was refractory to their most recent therapy.

Patients with quad-refractory disease are defined as those with documented prior treatments including two proteasome inhibitors, bortezomib and carfilzomib, and two immunomodulatory agents, lenalidomide and pomalidomide, and documentation is available showing that their disease is refractory to at least one PI and at least one IMiD. Patients with penta-refractory myeloma have quad-refractory disease that is also refractory to an anti-CD38 monoclonal antibody, such as daratumumab or isatuximab.

The STORM study is a Phase 2 single arm study that was carried out at 19 sites and enrolled 70 patients over the course of 11 months, consistent with the high unmet medical need for this myeloma population. The primary endpoint was overall response rate, and all responses were adjudicated by an independent review committee.

As expected, patients in this initial cohort in STORM were very heavily pretreated, having received a median of seven prior treatment regimens. In addition, they had difficult to treat myeloma based on a short median time since diagnosis of only 4.7 years.

Among the 78 evaluable patients, the overall response rate was 21%, including both very good partial responses and partial responses. Most of the patients with quad-refractory disease received twice weekly selinexor for three or four full weeks. Among all the 48 patients in this quad-refractory group, the ORR was 21%.

Two-thirds of the patients with penta-refractory myeloma received twice weekly selinexor continuously. Among the 30 patients in penta-refractory group, the ORR was 20%. Clinical benefit rate, which in this study was ORR plus minor responses, was 32% across all patients, 29% for the quad-refractory patients, and 37% for the penta-refractory patients.

The median overall survival was 9.3 months for all patients, indicating that this population has very limited effective treatment options. Importantly, those without the partial response or better had a survival of 5.7 months, while the patients who responded had a median survival of more than 11 months. Moreover, as of the data cutoff date, median survival for the responders has not been reached.

These data suggest that patients responding to selinexor have a survival of approximately twice as long as non-responders. Median duration of response was approximately 5 months, and responses tended to occur in the first two cycles. Progression-free survival in this heavily pretreated population was 2.1 months, driven by early progressive disease.

Grade 3 or higher cytopenias were the most common side effect and were generally not associated with clinical sequelae. There were low rates of Grade 3 or higher non-hematological toxicity, with no new safety signal identified. In particular, there was only a single reported case of sepsis.

These results are particularly intriguing because oral selinexor is showing response rates comparable to those achieved in the quad-refractory setting with the intravenous anti-CD38 monoclonal antibody, Darzalex, or isatuximab. In addition, patients who responded to selinexor experienced longer survival, suggesting that there are limited available rescue therapies for patients who do not respond to selinexor.

To our knowledge, selinexor is the first agent to show durable activity in the very difficult to treat patients with penta-refractory myeloma. Therefore, based on these data, we have expanded the STORM study to include approximately 120 additional patients with penta-refractory myeloma, which we believe represents a significant unmet medical need.

We expect to report top line data from the expanded cohort in early 2018 and, assuming a positive outcome, we intend to use the data from the expanded STORM study to support an accelerated approval for selinexor in patients with myeloma.

In addition to STORM, we are also scheduled to present updated clinical data from the ongoing Phase 1b dose escalation portion of the STOMP study at ASH. STOMP principal investigator, Dr. Nizar Bahlis of the Southern Alberta Cancer Research Institute, will give an oral presentation discussing the high level of durable activity observed with selinexor in combination with bortezomib, including a patient whose disease is already refractory to proteasome inhibitors.

In addition, Dr. Christine Chen of Princess Margaret Hospital will present a poster of the impressive activity of selinexor in combination with pomalidomide, or Pomalys, with myeloma that is refractory to one or more proteasome inhibitors and/or lenalidomide.

Published preclinical results, as well as results we presented at this ASH, have shown the combination of proteasome inhibition with selinexor are highly synergistic. While various mechanisms are involved, super induction of high level of tumor suppressor proteins, marked inhibition of Nf-kappaB, and induction of both autophagy and apoptosis have been demonstrated. Based on these data, combination of selinexor with either Velcade or Kyprolis are anticipated to be highly active even against proteasome inhibitor resistant myeloma.

Patients enrolled in the Velcade combination arm of STOMP, designated SVd, received a median of four prior treatment regimens, most having previously received a proteasome inhibitor.

Of the 22 patients in this SVd cohort, 17 patients responded for an ORR of 77%. All 10 patients with disease that was not refractory to a proteasome inhibitor responded for an ORR of 100%. Patients tended to remain on study through multiple cycles, with most continuing on treatment as of the data cutoff. Updated durability and PFS data will be presented at ASH.

We are very encouraged by these response rates because the expected ORR for the combination of bortezomib and dexamethasone in patients with previously treated myeloma that is not refractory to a proteasome inhibitor is approximately 40% to 50%, and the ORR for those with refractory disease would be less than 10%. Based on these response rates, selinexor appears to have one of the most potent synergistic effects with bortezomib reported to date.

The most commonly reported adverse events are fatigue, anorexia, nausea, diarrhea, and thrombocytopenia. There was only reported case of Grade 1 peripheral neuropathy, and cumulative toxicities were uncommon.

Based on marked efficacy and tolerability, we have identified the combination dose to be used in future studies, 100 mg of selinexor once weekly, 1.3 mgs per meter squared of bortezomib sub-Q also once weekly for four out of five weeks, and 40 mgs of dexamethasone weekly. The ORR in the six patients who received this recommended Phase 2 dose of selinexor with bortezomib and dexamethasone was 100%.

Based on these results, we plan to initiate a pivotal randomized Phase 3 study, known as the BOSTON study, in early 2017. The BOSTON study will evaluate SVd compared to bortezomib and low dose dexamethasone in patients with myeloma who have had one to three prior lines of therapy.

These patients are most similar to the group of patients in STOMP, whose disease was not refractory to a proteasome inhibitor and where the current ORR is 100%. To our knowledge, this is the only Phase 3 study to date to utilize once weekly bortezomib dosing in the experimental arm along with the weekly oral selinexor and dexamethasone.

We expect that the study will enroll approximately 360 patients, and accrual will complete in mid 2018. We are currently finalizing the protocol, which includes feedback from the FDA, and we look forward to initiating the trial early next year.

In addition to STORM and STOMP, Dr. Andrzej Jakubowiak of the University of Chicago, will provide updates from the Phase 1 study sponsored by the Multiple Myeloma Research Consortium evaluating the combination of selinexor with proteasome inhibitor Kyprolis, also known as carfilzomib and dexamethasone, in patients with relapsed refractory myeloma.

The results of this proteasome inhibitor combination are similar to those observed with the SVd regimen with an overall response rate of 63%. And most of the patients in this study have carfilzomib refractory disease, consistent with the synergistic mechanism of action of selinexor and proteasome inhibition.

On the AML front, SAIL principal investigator, Dr. Walter Fiedler of the University Medical Center Hamburg, will give an oral presentation at ASH which highlights updated clinical data from the Phase 2 SAIL study, where enrollment is now complete. The data demonstrate that selinexor in combination with Ara-C and idarubicin achieved compelling response rates, leading to transplantation or donor lymphocyte infusions in patients with relapsed or refractory AML whose disease has already relapsed after, or was refractory to, initial intensive chemotherapy.

One additional AML presentation at ASH that I'd like to highlight is an oral overview of data from the clinical trial evaluating the combination of selinexor with high dose cytarabine and mitoxantrone in patients with AML. Here Amy Wang of the University of Chicago describes early stage clinical data demonstrating the feasibility and tolerability of selinexor in combination with chemotherapy in patients with AML, including in elderly patients, with very encouraging response rates.

Together, we believe the data from this study, along with the SAIL study discussed above, supports the thesis that the selinexor combination could be an effective AML treatment option and serve as a bridge to stem cell transplantation even in patients whose disease is refractory to standard chemotherapy regimens.

One final point regarding ASH. Dr. Frank Cornell of the Vanderbilt Ingram Cancer Center will be presenting a poster highlighting clinical data from a Phase 1/2 study evaluating second generation SINE compound KPT-8602 in heavily pretreated patients with relapsed or refractory myeloma. These data are important because they are the first clinical results for an oral KPT-8602, and show that it is well tolerated and is exhibiting encouraging early and durable signs of efficacy.

Finally, on the solid tumor front, in October at ESMO 2016 we were pleased to report updated clinical data from the Phase 2 SIGN study evaluating selinexor in patients with gynecological malignancies. In this study, single-agent selinexor demonstrated robust clinical benefit and a favorable tolerability in patients with heavily pretreated gynecologic cancers, including a 49% disease control rate in ovarian cancer and 45% in endometrial cancer.

Selinexor associated adverse events were found to be manageable with supportive care and dose modification, as demonstrated by the number of patients who have remained on study after achieving disease control, with some continuing treatment for longer than 12 months.

With that, I will turn the call over to Justin to discuss our financials.

Thank you, Sharon. Since we issued a press release earlier this afternoon outlining our third quarter 2016 financial results, I'll just review the highlights and then speak to our cash balance and our financial guidance.

For the quarter ended September 30th, 2016, Karyopharm reported a net loss of $25.4 million, or $0.69 per share, compared to a net loss of $30.4 million, or $0.85 per share, for the third quarter of 2015. Net loss includes stock-based

compensation expense of $5.6 million and $3.5 million for the quarter ended September 30, 2016 and 2015 respectively.

Research and development expense was $19.9 million for the quarter ended September 30th, 2016 compared to $25.9 million for the quarter ended September 30th, 2015. This decrease from prior year is due to reduced preclinical and manufacturing costs related to selinexor, as well as the timing of startup and patient enrollment costs related to our clinical trial pipeline.

General and administrative expense was $5.9 million for the quarter ended September 30th, 2016 compared to $4.8 million for the quarter ended September 30th, 2015, primarily due to non-cash stock compensation expense.

Cash, cash equivalents, and investments as of September 30th, 2016, including restricted cash, totaled $176.9 million compared to $166.2 million as of June 30th, 2016. This increased cash balance includes the net proceeds from the sales of common stock through the company's at the market financing facility through September 30th, 2016 of approximately $31.5 million dollars.

Excluding our ATM proceeds, Karyopharm's cash burn from operations was $20.4 million in the third quarter. Subsequent to the close of the quarter, in October we sold additional shares of common stock for net proceeds of approximately $15.4 million.

In total, Karyopharm sold approximately 5.2 million shares of common stock for net proceeds of approximately $46.9 million in September and October combined. As of October 31st, 2016, the company has approximately 41.3 million shares outstanding and approximately 47.2 million fully diluted shares outstanding, which is inclusive of all outstanding stock options and restricted stock units.

We expect to end 2016 with at least $170 million in cash, cash equivalents, and investments. Based on our current operating plans, we expect our existing cash and cash equivalents will fund our research and development programs and operations through the end of 2018, including through the data readout for the expanded STORM cohort, completion of enrollment for the BOSTON study, and advancement of the SOPRA, SADAL, and SEAL clinical studies to their

next data inflection points.

I will now turn the call back over to Michael for concluding remarks. Michael?

Thank you, Justin. I'd just like to take a moment to recap the upcoming milestones that we are expecting later this year and early next year.

First, we will focus on executing the STORM trial expansion, which will add 120 additional patients with penta-refractory myeloma. We expect to report top line data from this expanded cohort in early 2018. And assuming a positive outcome, we intend to use these data to request accelerated approval for selinexor in multiple myeloma.

Second, based on feedback from the FDA, the trial design for the planned BOSTON study evaluating selinexor in combination with bortezomib and dexamethasone in previously treated myeloma patients is being finalized, and we remain on track to commence this pivotal study in early 2017.

And third, at ASH 2016 we will present 21 clinical and preclinical abstracts, including updated clinical data from the ongoing Phase 2b STORM study and the Phase 1b STOMP studies in heavily pretreated patients with multiple myeloma.

In closing, I'd just like to highlight that we continue to have a strong balance sheet, which provides us with the flexibility to pursue our clinical and corporate objectives. Thank you for listening today, and we look forward to keeping you updated on our progress.

With that, I'd like to turn the call over now to the operator for questions. Operator?

(Operator instructions.) Brian Abrahams, Jefferies.

Hey, guys. Thanks for taking my questions, a couple of questions on STOMP. As you've seen the data evolve here, it looks like obviously the response rates are more than you would expect with bortezomib -- far more than you expect in this population for bortezomib alone. You have seen many patients respond, a few patients not respond. Just wondering, as you've looked at this data, are there any characteristics you're seeing that might predict selinexor potentiation of bortezomib activity, risk profile, time since last treatment, anything you can point to that would help predict response?

Yes, it's a great question. I'll start and I'll turn it over to Sharon in a minute.

I think the important point is that, in the patients whose disease was already refractory to a proteasome inhibitor, where you expect the response to Velcade-dex to be less than 10%, you're seeing about a 58% response here. And by the way, you're seeing a 63% response in a very similar group of patients in the Kyprolis data set, where almost all of those patients were already refractory to Kyprolis itself.

So, it looks pretty clear that more than half of the patients, even with proteasome inhibitor refractory myeloma, can respond to the selinexor combination. And we strongly believe this is true synergy rather than simply an effect of selinexor which, as you know, gives you about a 20% plus response rate in these heavily pretreated patients.

Thus far, unfortunately we don't have any particular markers for response. But I think it's important to remember that when response rates start to go north of 50% really, especially given that only one of the patients actually progressed in the STOMP dataset, that's a clinical benefit for many patients. And it's probably -- it would be a very high hurdle to come up with a marker that specifically targets the relatively few patients who don't derive a real clinical benefit here.

Sharon, do you want to add anything?

Yes, I just want to mention that we are looking, and we see that the activity is very similar. And I think that's true for both STORM and STOMP in the high risk patients as well as the others. So, p17 deletion, we see activity in those and as well as other high risk features. And our biomarker work is mostly focused in indentifying those who will receive a CR compared with a PR.

Got it. That's helpful. And then on the safety side, it looked like both the hematological and constitutional safety -- or side effects were perhaps a little bit lower in the combo STOMP study than in STORM. Is that representative of just a less refractory population, do you think, or are there mechanistic reasons why a combination, in addition to potentiating efficacy, might actually mitigate some of the side effects and toxicities of selinexor?

Yes, I'm going to turn that to Sharon directly.

So, the superior side effect profile we saw in this combination was true for both the combination of selinexor with bortezomib as well in the other study of selinexor with carfilzomib. And some of it, we believe, is mechanistically, and we described some of the preclinical effect in abstracts at ASH and in the papers.

And some, we believe -- oh, but also take in mind that most of the patients -- at least in the selinexor/bortezomib study, many of them received selinexor once weekly. And we definitely see -- and there's no need to give twice weekly, as we see based on the recommended Phase 2 dose. And the once weekly selinexor has a very good tolerability profile.

On the carfilzomib study, we do give selinexor twice weekly, and we still see a very good tolerability profile. And that might be due to the synergistic activity such as the inhibition of Nf-kappaB and others that is related for the specific combination.

Got it. And just one last question and I'll hop back in the queue. On 8602, obviously very early data in the ASH abstract. It does look like the grade 3 hem tox and constitutional symptoms may be a little bit -- were less than we might expect versus historical data for selinexor. Is it, I guess, too early to conclude that 8602 may have a better tolerability profile? You're seeing this tolerability difference carry through consistently as that trial continues. And do you have any data yet from the PD markers that you're maybe looking at suggesting relative XPO1 inhibition versus selinexor? Thanks.

Yes, thanks. I'll turn it to Sharon in a second.

But please do keep in mind that we've treated over 1,800 patients with selinexor alone or in combination, and we do have very early and potentially interesting data with 8602. And Sharon can describe the mechanism and what we think may be going on, but we're at way fewer numbers of patients. Sharon?

Yes. So, I just want to remind that this is an ongoing Phase 1 study, and dose escalation is not complete yet. And we are definitely still behind the dose that we give of selinexor. The highest dose we dose patients with selinexor is 120 mgs, and with 8602 we are not there yet.

Keeping this, we are very encouraged by the good tolerability profile of both constitutional side effects and cytopenias. And this is probably due to a reduced brain penetration of 8602.

Very helpful color. Thanks, guys.

Whitney Ijem, JP Morgan.

Hi there, just a question on STORM. So, the ASH abstract indicated that the IL-16, IL-8, and the IGF-1 pathways were enriched in responders. So, I'm just wondering if there's any plans to maybe enrich the additional 120 patients you're enrolling by those or stratify those patients, or kind of what the significance of that is.

Yes, I'm going to turn this over to Sharon.

So, some of the biomarker work will be described at the presentation of the STORM study. We are not using these new findings to define the inclusion/exclusion criteria, but we are definitely having exploratory endpoints to follow these biomarkers.

And --.

Got it. And then, again just -- oh, yes.

Sorry. We can just add to that. We will -- we are looking at also some clinical markers for -- looking for the patients who stay on study for a prolonged period of time and therefore are more likely to respond. And we'll hope to have some update at ASH on that.

Got it. And this may be another wait for ASH question, but just curious if you can say anything as to the breakout of AEs or efficacy of response rate in the eight doses per cycle patients versus the six doses per cycle patients.

Sharon?

So, I think the best to answer this is to say that in the expansion cohort of STORM, we are going to use eight doses for a cycle schedule. So, it's definitely a schedule with manageable tolerability. But we will outline the differences in the ASH presentation.

Great. Thanks for taking the questions.

Michael Schmidt, Leerink Partners.

Hey, good evening. Thanks for taking my questions. And I certainly appreciate all the updates on the upcoming ASH conference and the efforts in multiple myeloma. But I wanted to ask whether there are any updates on your trial in DLBCL or whether that's still on track for data early next year, and whether there is any other work going on in combinations in DLBCL. Thanks.

Yes, let me give you an update on the timing, and we'll talk about some of the other interesting studies we're doing in DLBCL.

Yes, we will have early data -- I'm sorry, we'll have data in early 2017 on DLBCL. This is to remind people the SADAL study, which is 100 milligrams twice weekly of selinexor versus 60 milligrams twice weekly of selinexor. It's a fully single agent study, and it's in patients with relapsed refractory DLBCL whose disease has been recurrent after chemotherapy and/or transplantation and who are not eligible for chemo or transplantation.

And this is a single agent study, as I mentioned, a study that FDA has discussed with us and could potentially serve for an accelerated approval. So, we'll have updated data on that in the early part of 2017.

And then as a follow on to that where we've had activity, Sharon can describe some of the ongoing combination studies we're doing.

So, there are three ongoing ISTs currently in non-Hodgkin's lymphoma and several still in the queue. The ongoing one includes the combination of selinexor plus RICE in second line. This is a study that is being led by Peter Martin at Cornell.

There is an ongoing study of selinexor plus ibrutinib from the Ohio State University that includes both patients with CLL and patients with non-Hodgkin's lymphoma. It's a phase 1/2 study. And there is a study looking at platinum-based regimens such as DHAP and GDP with selinexor. And this is done by the French lymphoma group with the two different cohorts.

And several other studies are still in design phase, including first and second line studies of combination selinexor and first and second line studies in DLBCL.

Thanks. And maybe a follow up, Michael. And I think in terms of sort of hurdle -- in terms of approval hurdle for the DLBCL SADAL study, I think you've in the past talked about a 20% to 30% response rate at a minimum. I was wondering if that is still sort of the minimum goal for the study and what -- based on your interaction with the FDA, what would be good data in terms of durability or PFS in those types of patients. Thanks.

Right, a couple of points. So, FDA never and they continue to never -- will never give, at least so far, any guidance on specific numbers. They always say it's a review issue, which translated means it's a risk-benefit issue. They acknowledge that in this particular population of DLBCL patients, there really isn't -- there is nothing approved, and there isn't really a standard of care for these patients as well, which is very important.

In particular, patients who have the GCB, or germinal center B subtype of diffuse large B cell, there are really not any known active or very active drugs around. As some of you are aware, in the ABC subtype, ibrutinib and lenalidomide, or Revlimid, do have activity with response rates in the 30% to 40% range, and some durability with several months. But in GCB, there isn't really much active so far.

We've shown activity in the past in our Phase 1 study of about 30% overall and pretty similar, if not slightly higher, in GCB compared with the ABC subtype. So, we're pretty comfortable that we have an active drug in DLBCL.

And in terms of numbers, we believe that, again, responses in the 20% or higher range, these are bona fide responses by CAT scan or PET scan as is standard now based on the Lugano criteria for response in DLBCL. We think that's an important range. And we also think that -- durability of four months or longer, given that this is a single agent which is oral, we think would put us in the game.

But again, I emphasize this is not an FDA number. These are just our KOLs and our own research.

Great. Thanks for the added color.

Chris Raymond, Raymond James.

Hey, good afternoon. This is Laura Chico in for Chris; just a quick follow up, I guess, on a separate area as well. Just curious, I apologize if I missed this, do you have any updates with regards to SOPRA and future timing there?

We don't really have an update right now. What we can say is that the trial is accruing very nicely, and we will update on the completion of the 170 patients enrolling. The interim analysis is purely an event-based analysis, and therefore we don't track that exactly and we won't know exactly when those events come in.

So, we can't give any more color. If it doesn't happen by the end of the year, we expect it'll happen in the early part of next year, but this is all based on the survival of the patients. And that's pretty much all we can say right now except that we are accruing nicely, and we'll have an updated accrual forecast in the near future.

Would the accrual forecast I guess kind of shed light on potentially when the OS -- the final OS analysis might come then as well?

It looks like the final OS will still be midyear, some time in the mid time next year, but we are on track for that. That was originally planned by the end of this year, and we are on track for that. That is the full accrual.

For the full accrual by year-end?

Yes.

Okay. Thank you.

Mike King, JMP Securities.

Hey, guys. Can you hear me?

Very well.

All right, great. Thanks for taking the question. A couple of questioners I think touched upon the topic that I wanted to get into, which was biomarkers. I think Sharon's formal comments about the different durability of response based on whether patients responded or not makes it incumbent to find a biomarker. I don't know if you agree or disagree with that statement, but it just seems like, given at least when -- in the setting that the drug will be approved in and the large number of prior therapies that patients will receive, it just seems like it would be -- facilitate your commercial uptake if you had something resembling a biomarker.

Hey, Michael. Thanks. No, it's a very fair point. And please don't mistake our lack of finding a biomarker with a lack of desire to do so. We've spent now over 15 years trying to find a biomarker for proteasome inhibitors, and to date I don't think we've found one. And I got involved early on with Velcade and tried to do that.

And I suspect, although we continue to try and we have lots more technologies now available, that the complexity of XPO1 regulation and the added complexity of these patients now that we're getting will make finding a biomarker difficult.

That said, what's sort of evolved, as you're well aware, are a couple of points. One is that selinexor, although we'd like to pick the responders, clearly it takes -- to get a response with selinexor occurs typically in the first one or two cycles, which puts patients at a very low risk of exposure if the drug is not going to be active.

You usually know it very quickly. And given our side effect profile, there are seldom major toxicities that a patient would experience, especially in that period, before we knew whether the drug was working.

I think more importantly, though, and the way all of these drugs get used, all of the big drugs that were approved single agent and then subsequently went on to combination approvals, is that when you have the single agents they typically have response rates in the 20% to 30% range. But you start to combine them, as we mentioned, and you get over 50% to 60%. And then the biomarker actually becomes much more difficult because the predictivity of the marker and the accuracy of it is tougher when you have such high response rates.

So, I think we agree with you. We are trying. We continue to. There are a number of collaborators working in this. But what we think is really the future for this drug is to combine with proteasome inhibitors, IMiDs. We'll be doing some work with Darzalex as well. And we have ongoing studies that are nearly complete with Doxil and so on that selinexor could really be an oral backbone therapy in combination with essentially anything in myeloma and will derive 50%, up to 100% response rates.

Yes, it's a fair point. Remind me, Michael, wasn't there -- when Velcade launched in the relapsed refractory setting, wasn't there sort of an algorithm that if patients didn't respond by -- I forget exactly what the number of cycles was, but if patients didn't respond by a certain number of cycles, docs would just continue therapy, or am I misremembering that?

I don't think we quite had that.

No? Okay.

We certainly had issues for neuropathy and -- unfortunately.

Yes.

And we gave twice weekly therapy for a limited period and then moved to once weekly. But back then, especially with limited -- very, very limited options, people tended to just switch them over to then thalidomide, or even early on Revlimid, after 2006, or do the combination studies, which is where everyone has moved to.

Okay. If I could just ask a quick question on STORM, I just wonder if you're -- if you could share your thoughts about the patient characteristics as you continue to enroll the additional 120 patients and whether those would be more like what you've been enrolling. Do you think they might be more beat up? Any thoughts in that regard?

Yes, let me turn that over to Sharon, who's very close to this.

So, in general the population is similar to the population of penta-refractory patients that we had, the 30 penta-refractory patients we had. We did some analysis I think Michael mentioned earlier about clinical parameters that collates with very short time on study, or essentially with the kinetics of the disease at study entry.

And this enabled us to a little bit tweak the inclusion/exclusion criteria, and hopefully will result in a longer time on study and a bit improved response rate. And we will present those findings at the ASH presentation.

At ASH, okay. And let me congratulate you for an astounding number of abstracts accepted for the ASH conference. I know you guys work really hard to get your data submitted, so hats off to you on that. Thanks for taking my questions.

Thank you, Michael.

(Operator instructions.) Ying Huang, Bank of America Merrill Lynch.

Hi. This is Jenny Leeds on for Ying. Thanks for taking my question. I just had a quick question about whether or not the response to selinexor changes depending on what was the last therapy that the patient was refractory to. As we see Darzalex kind of change in the treatment paradigm and move farther up, how could that change your responders?

And then also for the development strategy of KPT-8602, as many people have said, it looks like the safety profile might be a little bit better. How are you kind of thinking about that as you develop that drug alongside selinexor? And could we see even more patients and more efficacy data at ASH?

Yes, I'll turn both of those questions over to Sharon.

So, regarding the second question, as we mentioned we are on the ongoing Phase 1 study of 8602. And this study was focused on myeloma. In the future, as we are completing to characterize the side effects profile and the efficacy of 8602 in myeloma, we might look at other indications and then decide on the development path of 8602 and selinexor.

And can you remind me quickly about your first question?

Just about, as the treatment paradigm for multiple --.

Oh, yes.

Changes and Darzalex moves kind of up the paradigm.

Yes. So, very early in the preclinical work on selinexor or in the other XPO1 inhibitors, we learned that the inhibition of XPO1, the activity of these compounds is essentially agnostic to prior therapies.

And we have seen this in the Phase 1 and we are seeing it in the STORM study, that the activity of -- or the response to selinexor does not depend on the last line, which means that not necessarily patients that received daratumumab, for example, in the last line will respond to selinexor -- will or will not respond to selinexor, or any other therapy.

Great. Thank you.

Lars Brichta, Canaccord.

Hi, guys. It's actually Arlinda. Would you guys mind providing an update on the DLBCL trial, and if we're still expecting to see some kind of an update early next year? Thanks.

Yes. We're accruing to that trial. There will be an update early next year, and we're pleased with the results to date. That's all we're able to say at this point.

Okay, great. Thanks. And then maybe just a follow up on the myeloma -- sorry, we're just hopping between calls. I'm sorry if I missed this. But on the 8602 data, the next generation, I'm kind of curious. You guys have alluded to the fact that this is potentially more tolerable and therefore might be able to get a better therapeutic window. What kind of data should we expect at ASH for that? Thanks.

Yes. To some extent Sharon answered, but I'll ask her to just answer one more time.

So, Arlinda, this is -- we are in the midst of the Phase 1 study. We'll have more patients than what we had in the abstract. Keep in mind this is a three plus three design, so the number of patients grows gradually in a study like that.

And I think, as you will -- as will be presented in the poster, we are encouraged by the tolerability profile of this drug. We are looking forward to continue to escalate it, to identify -- completely identify the toxicities and the MTD. And then we will evaluate the development of 8602 compared to that of selinexor, which we have studied in many, many indications in many patients and know exactly where to go and how to treat the side effect profile.

Okay, great. Thank you.

And I'm showing no further questions at this time. I would now like to turn the call back over to Dr. Kauffman for closing remarks.

Thank you again for your interest in Karyopharm and for participating in our call today. We look forward to seeing many of you at upcoming medical and investor conferences, and hope you can join us for our webcast multiple myeloma panel discussion at ASH next month. Have a great day, everybody.

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program and you may all disconnect. Everyone have a great day.