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Xencor, Inc. (XNCR)

Q4 2016 Earnings Call· Tue, Feb 28, 2017

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Transcript

Operator

Operator

Good day, ladies and gentlemen, and welcome to the Xencor Incorporated Q4 2016 Earnings Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will follow at that time. [Operator Instructions] I would now like to introduce your host for today’s conference Hannah Deresiewicz with Stern Investor Relations. You may begin.

Hannah Deresiewicz

Analyst

Thank you. Good afternoon. This is Hannah Deresiewicz with Stern Investor Relations, and welcome to Xencor's fourth quarter and full year 2016 financial results conference call. This afternoon, we issued a press release, which outlines the topics that we plan to discuss today. The release is available at www.xencor.com. Today on our call, Bassil Dahiyat, Ph.D., President and Chief Executive Officer will discuss the company's business highlights, Paul Foster, M.D. Chief Medical Officer will provide an update on the Company’s clinical programs and pipeline progress and John Kuch, Vice President of Finance, will review the financial results from the fourth quarter and full year 2016 and then we will open the call up for your questions. Before we begin, I would like to remind you that during the course of this conference call, Xencor management may make forward-looking statements, including statements regarding the company's future financial and operating results, future market conditions, the plans and objectives of management for future operations and the company’s future product offerings. These forward-looking statements are not historical facts, but rather are based on Xencor's current expectations and beliefs and are based on information currently available to us. The outcome of the events described in these forward-looking statements is subject to known and unknown risks, uncertainties and other factors that could cause actual results to differ materially from the results anticipated by these forward-looking statements, including but not limited to, those factors contained in the Risk Factors section of its most recently filed Annual Report on Form 10-K and Quarterly Report on Form 10-Q. With that, let me pass the call over to Bassil.

Bassil Dahiyat

Analyst

Thanks, Hannah, and good afternoon everyone. 2016 was a busy year for us, we made a lot of progress across our entire business advancing on internal XmAb programs by starting five new clinical trials. I am also pleased to announce today that, that was followed by the sixth new clinical trial since the beginning of 2017, this month with the Phase 1 startup XmAb13676 that makes that the 11th XmAb antibody in clinical testing currently. We are continuing to grow our pipeline with multiple new bispecific oncology antibody as well behind this one. We also entered into a strategic collaboration with Novartis for a biospecific programs with platform last year. Our highlights of 2016 were in March we initiated two Phase 2 clinical trials of XmAb5871, one in IgG4-Related Disease or IgG4-RD and one in systemic lupus erythematosus or SLE. Both diseases have a high unmet need and know of few proved therapies and critically they share a strong rationale for B-Cell inhibition. We were encouraged by the preliminary data from our IgG4-RD trial presented at ACR in November which showed that 82% of patients achieved an initial response to therapy within two weeks of their first dose. With these responses typically deepening overtime. We also initiated a Phase 1 trial testing with subcutaneous delivery of XmAb5871 in 2016. Now in September of last year we initiated clinical trials for two more programs, the first was a Phase 1b trial which evaluates a subcutaneous formulation of XmAb7195, a potential treatment for allergic disease and a second is a Phase 1 trial that evaluates our lead bispecific oncology candidate XmAb14045 in patients with acute myeloid leukaemia or AML as well as other CD123-expressing hematologic malignancies We also expanded our preclinical pipeline last year with the addition of two new bispecific oncology…

Paul Foster

Analyst

Thank you, Bassil. I’ll start today by XmAb5871 our first in class monoclonal antibody in Phase 2 development for IgG4-RD and SLE. XmAb5871 targets CD19 with its variable demand and uses a proprietary XmAb immune inhibitor Fc domain to target Fc gamma receptor R2B, a receptor that inhibits B-cell function. Now at the ACR Annual Meeting in November, Dr. Johnstone the principal investigator presented preliminary data from our ongoing Phase 2 study in IgG4-RD we are very encouraged by these early results which show that 9 of 11 treated patients, or 82% achieved an initial response to therapy of at least a three point reduction in the IgG4-RD responder index within the first two weeks of the first dose. Five patients attaining disease remission or responder index is zero during this study and achievement that was well tolerated with no serious adverse events reported as of a data cut-off of October 31, 2016. As a reminder, this is a single-arm pilot study designed to evaluate the effective every other weak IV administration of XmAb5871 on disease activity in patients with active IgG4-RD. The last of 15 planned patients was enrolled this January. The patients will receive up to 24-weeks of treatment in the primary endpoint is to evaluate the portion of patients with an improvement in the IgG4-RD activity as defined by a decrease in the responder index. We are on track to report topline data from this trial this year and as Bassil noted, plan to engage with the FDA to discuss future development plans including clinical trial design and potential registration requirements in the months ahead. We also continue to progress our Phase 2 randomized double blind placebo control study in SLE and hope to report initial data in 2018. This study is designed to evaluate the ability…

Bassil Dahiyat

Analyst

Thanks Paul. I will just have a quick comment on our ongoing partnerships. We are proud that eight pharmaceutical companies and the NIH continue to advance novel drug candidates to use our Fc technology for bispecific structure, for higher cytoxicity, long half life and improved stability. Now seven of these programs are undergoing clinical testing, including a Phase 1 clinical trial initiated by the NIH in January 2016 and a Phase 2-3 trial initiated by Morphosys, which began dosing in September 2016. Also in December of 2016, Alexion initiated a phase 3 clinical trial for an undisclosed program under our license agreement for our Xtend technology, and then will receive a milestone payment of $5 million. Now with that, John will review our fourth quarter and full year year-end financial results.

John Kuch

Analyst

Thank you, Bassil. In this afternoon’s press release, we reported and cash and cash equivalents and marketable securities $403.5 million as of December 31, 2016, compared to $193.3 million on December 31, 2015. This increase reflects the net proceeds of $119.3 million received from the completion of our follow-on offering in the fourth quarter, in addition to the upfront payment of $150 million received in connection with our Novartis collaboration and other milestone revenue received from partners during 2016. Revenues for the fourth quarter of 2016 were $6.4 million, compared to $21.8 million in the same period of 2015. Revenues for the full year 2016 were $87.5 million compared to $27.8 million in 2015. Revenues are earned from technology licensing fees and milestone payments from Xencor's partners for the license of its drug candidates and use of its proprietary XmAb antibody engineering technologies. Revenue for the fourth quarter of 2016 related primarily to a milestone received from Alexion, while revenue for the same period in 2015 included milestone and option payments from Alexion and revenue earned from our Amgen collaboration. Total revenues earned in 2016 were higher than 2015 due to the revenue earned from our Novartis Collaboration. Research and development expenditures for the fourth quarter of 2016 were $13.4 million, compared to $10.9 million for the same period in 2015. Total R&D expenses for the full year 2016 were $59.1 million compared to $34.1 million in 2015. R&D spending in the fourth quarter and for the full year ended December 31, 2016 was greater than expenditures incurred over comparable periods in 2015 due to increased spending on our clinical programs including our Xmab5871 and XmAb7195 programs and also development of our pipeline of bispecific clinical candidates. General and administrative expenses in the fourth quarter of 2016 were $3.1 million,…

Operator

Operator

[Operator Instructions] And our first question comes from Michael Schmidt with Leerink Partners. Your line is now open.

Michael Schmidt

Analyst

Hi guys, and thanks for taking my questions. I had one regarding the 14045 study, the AML trial for the lead bispecific antibody, I was just wondering if you could provide some more information regarding the dose escalation schedule for this study, and I am just asking because it seems some of the other competitor bispecific antibody programs have taken quite some time to generate the clinical data, a couple of years in some cases, I'm just wondering how fast can you dose escalate in these studies and how confident are you that you are not moving too fast actually? Thanks.

Bassil Dahiyat

Analyst

I will let Paul take it on the details, but remember the design of the molecule XmAb14045 was based on the premise that by having a potency that is significantly lower than earlier bispecific technologies like the BiTE technology that Amgen acquired with Micromet in the order of 100 times more or less potent. You still have a molecule that is fantastically potent say in the range of a 1000 times more potent than are rituxans, but not 100,000 times more potent, but we compensate for this by having a dramatically longer – we hope in humans dramatically longer half life. We certainly showed this in pre-clinical models because of our Fc technology. And so that is the premise is that we will have something that is inherently less potent and hopefully more tolerable, and so we went with a standard approach for dose escalation and dosing in the format – maybe Paul can touch on the schedule and the way we dose it.

Paul Foster

Analyst

Well, we haven't disclosed the actual dose levels or the increments in change, but based on our preclinical program, we have selected what we thought was a safe starting dose and we are increasing those doses between cohorts in a manner that we think is prudent and safe.

Bassil Dahiyat

Analyst

Yes. And it's a standard 3.3 oncology Phase 1 dose escalation design and that's it, and we're moving forward, we're enrolling, we will be getting updates as we get more information.

Michael Schmidt

Analyst

Yes. And maybe can you elaborate a little bit more on your affinity titration I guess of your products and whether you think and you might be able to decouple some of the toxicities that are I guess are on target for the cancer therapy from the activity that is desirable?

Bassil Dahiyat

Analyst

Yes. And I think the key there is the format that we use which is based on having your tumor antigen binding domain and your T-cell binding domain, you see three binding demand, that format has both of those domains attached to an Fc just like they would be attached in a regular antibody. One domain on one, half of the Fc, the other domain on the other half of the Fc. And so, that arrangement inherently gives you this dramatically lower potency than first generation by specific antibodies. What those two binding remains literally stitched right to each other with say a peptide link or a disulphide bond. And so that much more flexible arrangement with these things are mobile relative to each other, seems to inherently give you at least a couple order remanded or at least a 100 fold lower potency. That's built in the design. Now, for certain programs, we've tested various affinities of both antigen binding and T-cell binding domain. So, to tune those affinities down, and we did that by examining the performance of these molecules in non-human primates to look at destruction of the target cell and the cytokine release that you get. For FORTUNE and 45, we went with a mid-single digit in animal or CD3 binding demand as we showed in a post release in our couple -- last couple of years ago and a similar affinity for the CD123 domain. I think this give us a pretty good set of properties in the primates for being able to give a simple infusion that gave long lasting depletion of the target cells and manageable tolerability. For us, it's now 13676 program, the CD20 CD3 program, the lower CD20 affinity because that gave us the best mix of properties. So, it's an empirical exercise, we're trying to decouple this sort of steady state T-cell killing activity from that initial pulse that happens usually within hours of in the dose, that initial pulse of cytokine release from the T-cells that can cause a lot of immune toxicities, cytokine release syndrome. So, usually about kinetics and intensity of that initial pulse that you tune down, would have a much longer half-life so that your activities can still go on and on. So, it's that balancing act between potency and half-life.

Michael Schmidt

Analyst

Okay, thanks. Very interesting. And then a question on 5871, actually regarding the subcue formulation and obviously desires to take that into pivotal studies as opposed with the IV. And maybe can you share if the Phase 1 PKPD study, whether that is enough, you only has to show bioequivalence to the IV to take that forward that's additional work that might be necessary before starting a pivotal study with a subcue formulation?

Bassil Dahiyat

Analyst

I think given that we've -- we have this pilot state to have been able to study IgG4-Related Disease. Really, it's really a judgment call of hours based on how reliable we think the performance of the formulation is in the context of that bioequivalent study to go forward. We think that given that we have not yet started any large randomized studies, that we have a lot of flexibility on determining what we want to do there. It's not like we're switching in the middle of a large pivotal study and maybe having additional requirements. Because we're prior to that beginning of any kind of large study. Kind of up to us, and we just have to look at our data and have confidence in it. And we'll be guiding on that in the first half on how we're going to go forward on the results of that bioequivalent study, the PKPD study.

Michael Schmidt

Analyst

All right, yes. Great, thanks a lot and congrats on the progress.

Bassil Dahiyat

Analyst

Thank you, very much.

Operator

Operator

Thank you. And our next question comes from Arlinda Lee with Canaccord Genuity. Your line is now open.

Arlinda Lee

Analyst · Canaccord Genuity. Your line is now open.

Hi, guys. Back to the subcue results. That was supposed to be in the first half, did you say?

Bassil Dahiyat

Analyst · Canaccord Genuity. Your line is now open.

Yes.

Arlinda Lee

Analyst · Canaccord Genuity. Your line is now open.

And probably 7195 as well?

Bassil Dahiyat

Analyst · Canaccord Genuity. Your line is now open.

5871 is the first half, 7195 will be sometime during this year.

Arlinda Lee

Analyst · Canaccord Genuity. Your line is now open.

And then can you remind us of the thrombocytopenia that you saw with 7195 and what you think was the cause of that and whether this subcue might be able to help address that? Thanks.

Bassil Dahiyat

Analyst · Canaccord Genuity. Your line is now open.

Well I guess in terms of what we saw in the single dose study maybe Paul can touch on the results we presented in ATS last year.

Paul Foster

Analyst · Canaccord Genuity. Your line is now open.

Yes, so we saw a dose dependent affect on platelet count, that was transient after single-dose it raises [Indiscernible] by 24 hours and by 48 hours after the dose recovery was already occurring. And it doses at 2mg per kg above it got below 150,000 which would be the definition of thrombocytopenia. We don’t have a known mechanism for that as of yet, and when we talk about the results of the subcutaneous study, we can guide them whether we see that formulation as well.

Arlinda Lee

Analyst · Canaccord Genuity. Your line is now open.

So you will be looking for that in the subcue trial as well?

Bassil Dahiyat

Analyst · Canaccord Genuity. Your line is now open.

That’s a little say standard safety measure to be looking at pilot accounts.

Arlinda Lee

Analyst · Canaccord Genuity. Your line is now open.

Okay, fantastic. Thank you very much.

Operator

Operator

Thank you. [Operator Instructions] And at this time I am showing no further questions. I would now like to turn the call back over to Bassil Dahiyat for closing remarks.

Bassil Dahiyat

Analyst

Thank you very much. 2017 will be an exciting and busy year for Xencor as we continue to expand our -- expand and advance our XmAb pipeline. Now based on our current operating plans, we have a strong financial position that was bolstered by partnership and our recent financing, and which will support operations through key data readout and milestones from multiple internal and partnered programs. Finally, I like to thank the entire Xencor team for incredibly productive year in 2016 and I really look forward to updating everybody on our progress as we move forward. Thanks again for your time. Bye, bye.

Operator

Operator

Ladies and gentlemen, thank you for your participation in today’s conference. This concludes the program. You may now disconnect. Everyone have a great day