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Edited Transcript of SBPH earnings conference call or presentation 11-Nov-19 9:30pm GMT

Q3 2019 Spring Bank Pharmaceuticals Inc Earnings Call

HOPKINTON Nov 28, 2019 (Thomson StreetEvents) -- Edited Transcript of Spring Bank Pharmaceuticals Inc earnings conference call or presentation Monday, November 11, 2019 at 9:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Martin J. Driscoll

Spring Bank Pharmaceuticals, Inc. - President, CEO & Director

* Nezam H. Afdhal

Spring Bank Pharmaceuticals, Inc. - Chief Medical Officer

* Radhakrishna P. Iyer

Spring Bank Pharmaceuticals, Inc. - Co-Founder & Chief Scientific Officer

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Conference Call Participants

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* Edward Andrew Tenthoff

Piper Jaffray Companies, Research Division - MD & Senior Research Analyst

* Maurice Thomas Raycroft

Jefferies LLC, Research Division - Equity Analyst

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Presentation

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Operator [1]

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Good afternoon, ladies and gentlemen. And welcome to the Spring Bank Pharmaceuticals Corporate Update Conference Call. (Operator Instructions) As a reminder, this conference call is being recorded.

Please note that today's call will contain statements about Spring Bank's future expectations and plans that constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. The words believe, anticipate, plan, potential and expect and other words denoting future events identify statements as forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those disclosed in the Risk Factors section of Spring Bank's Form 10-K and other SEC filings.

In addition, any forward-looking statements represent Spring Bank's views only as of today, November 11, 2019, and should not be relied upon as representing its views as of any subsequent date.

I would now like to introduce your host for this conference call, Martin Driscoll, Chief Executive Officer at Spring Bank Pharmaceuticals. Please go ahead.

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Martin J. Driscoll, Spring Bank Pharmaceuticals, Inc. - President, CEO & Director [2]

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Thank you, and good afternoon, everyone. Welcome, as the operator said, to our Spring Bank Pharmaceuticals corporate update call. Joining me here on this call from the Spring Bank team are Dr. Kris Iyer, our co-Founder and Chief Scientific Officer; and Dr. Ned Afdhal, the Chair of our Scientific Advisory Board.

During this call, we will provide you with a summary of the progress we're making with our key development programs at Spring Bank. Also, Dr. Afdhal will share his views on the current landscape in the chronic hepatitis B development space and how our HBV development programs at Spring Bank have been positioned relative to this landscape. We think this is a good occasion to have this discussion about the HBV development field, since the annual scientific conference for the American Association for the study of liver diseases is just wrapping up here in Boston. The last few weeks have been quite active for the HBV development space, including the news from another company of the discontinuation of a core inhibitor program; the announcement of an acquisition of an siRNA development program from another company; and the presentation of several new data sets for HPD development compounds at the AASLD conference that's wrapping up tonight or tomorrow.

I will summarize the progress we achieved during the third quarter of this year before I turn the call over to Ned, who will go through this landscape. Following Dr. Afdhal's remarks, Dr. Iyer will provide you with an update on an exciting and innovative new HBV development program at our company, the chimeric antisense oligonucleotide program that we also call the CASO program. In the third quarter this year, we made significant progress with all of our development programs and announced several new collaborations to advance our efforts at Spring Bank. Most recently, we released top line results from the first co-administration cohort of a Phase II trial being conducted by Gilead Sciences that's evaluating -- that evaluated 12 weeks of a low dose 50 milligrams of inarigivir, co-administered with Gilead's Vemlidy, in treatment-naive chronic HBV patients. Dr. Afdhal will provide additional detail related to this trial. But I can tell you, as we disclosed earlier, that 23% of the patients dosed with the combination therapy of Vemlidy plus the low dose of 50 milligrams of inarigivir were surface antigen responders, which compares quite favorably with the results from our completed Phase IIa ACHIEVE trial, involving the monotherapy use of inarigivir 50 milligrams, where only 7% of those patients were surface antigen responders. This higher number of surface antigen responders with the co-administration with the NUC signals to us that the addition of the immunomodulator inarigivir to a NUC could elevate functional cure rates in treatment-naive HBV patients. Of course, we continue to be pleased that inarigivir continues to be safe and generally well tolerated at the doses we have studied thus far.

We are highly encouraged by the efficacy, the safety and the tolerability observed thus far for inarigivir over a limited 12-week duration of treatment period. However, we know that 12 weeks of treatment will not be sufficient to achieve elevated rates of functional cure in HBV. In our efforts to demonstrate functional cure with inarigivir monotherapy and co-administered with the NUC, we embarked on a comprehensive Phase IIb clinical trial program earlier this year. We call this the CATALYST trials program and it involves treatments for up to 48 weeks. Combined with the Gilead inarigivir plus Vemlidy 12-week trial, and our own unique liver biopsy study that is ongoing,

inarigivir is now being studied in 4 ongoing Phase II trials. The goal of these studies is to develop in 2020 the company's Phase III clinical trial strategy, affirm that, and be prepared to launch into Phase III before the end of next year. Another area of excitement for us is the development of our innovative chimeric antisense oligonucleotide compounds for the treatment of HBV. As I said earlier, we refer to this as the CASO program. This program incorporates the immunomodulatory capability of inarigivir with the classical gene knockdown attributes of an antisense oligonucleotide. Dr. Iyer is going to provide additional details on this program for you in just a few minutes. With the anticipated advancement of the CASO program to clinical trials late next year, Spring Bank will have chalked out a comprehensive strategy evolving monotherapy, 2-drug and even 3-drug combinations, with the objective to have a portfolio that could yield functional cure for the majority of the global heterogenous chronic HBV patient population. In addition to our efforts in HBV, we have now added another clinical development program at Spring Bank with our intravenously administered STING agonist for immuno-oncology. We have launched our Phase Ia/Ib trial for the IV SB 11285 at multiple sites across the U.S. We see many potential advantages to the use of our intravenously administered STING agonist to many of the other STING agonists out there that are being administered intratumorally. We plan to be in a position to disclose data from that trial next year.

Of course, to support 5 clinical trials at our company, including 4 global studies involving inarigivir in HBV and the oncology study for our IV STING agonist, plus accelerating our CASO program in HBV, substantial capital is required. At Spring Bank, we are aggressive in seeking out non-dilutive funding opportunities to supplement these capital needs. We have been successful in these efforts, evidenced by the substantial non-dilutive support that we have received from our collaborations with Gilead and also with the National Institutes of Health. The NIH right now is supporting our CASO program. In addition, we were recently fortunate to execute a favorable financing event in September with Pontifax, a health care dedicated investment firm with over $775 million in assets under management. We were able to significantly extend our cash runway into 2022 with the $20 million in gross proceeds raised from the strategic debt financing transaction. The extension of our cash runway resulting from the NIH support of our antisense clinical program together with the capital infusion from the strategic debt financing, allows us to focus on the execution of our development programs without having to consider equity raises at our currently depressed share price, that simply is not valued, in our view, relative to the progress we have achieved. We are now in a position to have multiple data readouts every quarter in 2020, beginning with the end of the first quarter. We believe these data readouts have the potential to be catalysts for our company.

With that, I'd now like to turn the call over to Ned, who will take you through the HBV development landscape. Ned?

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Nezam H. Afdhal, Spring Bank Pharmaceuticals, Inc. - Chief Medical Officer [3]

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Thank you, Marty. First, I'd just like to discuss the current status of HBV research and give you a brief update from ASLD 2019 here in Boston. We can consider that HBV drugs in development are really defined in 3 major clinical areas. These include the direct-acting antiviral agents such as the capsid inhibitors; the gene knockdown strategy evolving both antisense and siRNA therapies; and lastly, the immune modulators involving compounds that act through the RIG-I pathway and TLR-8. It's likely that all of these agents will be developed as part of combination strategies, since there has been no evidence developed to date that indicate any of these new treatment modalities will be sufficient as a monotherapy to achieve HBV functional cure. It's also unclear whether 2 or perhaps even more agents will be necessary to result in either durable hepatitis B surface antigen loss or HBV DNA suppression. One of the issues is that we have seen data that has varying durations of treatment, some now as long as 48 weeks, and despite viral suppression by biomarker measurement we have yet to see any significant reported sustained HBsAg loss with any of these mechanisms. However, what is clearly emerging is that the HBV patient population is quite heterogeneous. The HBV patient populations being studied include treatment-naive, nucleotide treatment-suppressed patients as well as HB antigen-positive and HB antigen-negative patients, which makes treatment comparisons extremely difficult. Perhaps the key question is whether simply long-term suppression is adequate, or suppression plus dosed immune activation is necessary for sustained loss of surface antigens and HBV DNA. We are now seeing trials that are being designed looking at significantly longer treatment duration, perhaps even greater than 48 weeks, the demonstration of HBV cure off treatment. With these caveats, there are some really exciting and encouraging data coming from the ASLD meeting this year. And I believe this data mainly demonstrates proof of principle of activity of drug rather than necessarily functional HBV cure.

I'm going to mention a few of the notable studies in each category, but obviously can't review them all. I think we're all excited by the Phase II study of ABI-H0731, a capsid inhibitor, which was given in combination with entecavir for up to 48 weeks and showed significant reduction in all viral biomarkers. Over time, there was continued suppression of HBV DNA and HBV RNA with a more gradual reduction in hepatitis B e-antigen, surface antigen and correlated antigen, and this is felt to be predictive of cccDNA pool reduction, a true goal of HBV cure. However, it's important to note that, again, patient heterogeneity is important, that these results were reported in the subset of HB antigen-positive patients who were naive to therapy. The study plans to continue for the undefined duration, but probably 72 weeks at least. And I look forward to seeing more data from this exciting combination.

A further development was we see the first triple combination study. And this was interesting because the combined 3 different classes of agents; it combined an siRNA JNJ-398.9, given once per month, a daily capsid inhibitor, JNJ-6379 and a daily NUC for 12 weeks. And there was a further follow-up of 64 days of the NUC alone. We did see significant reductions in biomarkers, but it's unclear based on this study whether the addition of a capsid to the siRNA plus NUC combination was additive or synergistic, and it's hard to determine this from such a small heterogeneous cohort study, which included both treatment-naive, treatment-suppressed and e antigen positive and negative patients.

In the immunomodulatory space, the first data on the TLR-8 agonist GS-9688 in NUC-suppressed patients was reported for 24-week treatment duration. One patient met the primary endpoint of a 1 log reduction in surface antigen, 1 patient lost HbsAg for a total response rate of 5%. Again, this is a NUC-suppressed patient and we await data for treatment-naive patients. The safety profile of GS-9688 was favorable, with GI side effects as the potential dose-limiting tolerability and there was clear and effective evidence by biomarkers of activation of the target IL-12 pathway. So this is an effective TLR-8, but it's again unclear duration and patient population.

Finally, it's worth mentioning, though, there were 2 studies with antisense compounds, which showed early and effective suppression of HBsAg. A small 4-week, 12-patient treatment-naive study with [ISIS] 505538 was associated with sustained reduction of HBsag below the lower limit of quantitation in 2 patients. And interestingly, both of these patients post the antisense compound had significant ALT flares when the surface antigen was reduced, which may reflect an attempt for immune clearance, but however, this was not sustained. I think this data has some very good implications for the development of Spring Bank's chimeric antisense oligonucleotide with inarigivir, as you will hear in a minute from Dr. Iyer.

Now I'd like to turn to Spring Bank's other development program in HBV. As Marty indicated, Spring Bank has announced preliminary top line data from our collaborative study with Gilead on the combination of the low dose 50 milligrams of inarigivir with Vemlidy 25 milligrams. Just to remind you, this is a large trial with 30 patients in multiple cohorts of treatment-naive patients receiving Vemlidy at the 25-milligram dose along with inarigivir at 50, 200 and 400 milligrams, but for a short duration of 12 weeks and then continuing Vemlidy alone for 36 weeks. The primary endpoint for the trial is surface antigen reduction with measurement of multiple secondary biomarkers. The data that we were allowed to share and that we have seen is essentially the low dose 50-milligram cohort in which there were reductions in all viral biomarkers, including DNA, RNA core-related antigen at 12 weeks, with 1 patient having a loss of P antigen. For the primary endpoint, 7 to 30 patients or 23% were surface antigen responders and received significant reductions in surface antigen. And as Marty said, this is very favorable to our ACHIEVE trial results where only 1 of 14 patients had a similar response in surface antigen. These results at such a low dose of inarigivir in combination with the NUC at this very early treatment point of 12 weeks are encouraging as we await the higher [doses] and full study readout for next year.

The top line results do indicate the potential for both synergy or an additive effect of inarigivir with a NUC. The tolerability profile remains excellent, with no significant safety and tolerability issues reported with either the combination treatment or in all the doses with inarigivir alone currently within this program, and inarigivir has been given to over 200 patients. In the ACHIEVE trial completed earlier this year, inarigivir demonstrated proof of principle of antiviral activity as a 12-week monotherapy regimen. We disclosed and showed dose-dependent antiviral activity, and this was in the e antigen-positive and e antigen-negative patients. We demonstrated activation of the immune system and reduction of all viral biomarkers including DNA, RNA, e antigen, core-related antigen and surface antigen that again suggests depletion of cccDNA, the viral reservoir of HBV in the hepatocyte.

Much was discussed at this weekend's AASLD meeting about the growing recognition of serum HBV pregenomic RNA as an important surrogate marker for reduction in the cccDNA pool without a clear understanding of how this will correlate with HBV cure. Clearly, we do wish to deplete cccDNA, but we have to remain cognizant that the only information that we have shown so far is biomarker data.

In view of the biomarker data not being conclusive, Spring Bank initiated a unique clinical study in the first half of this year, looking at a combination of both intrahepatic immunology and virology impaired liver biopsies in NUC-suppressed patients after 6 weeks of inarigivir monotherapy. To my knowledge, Spring Bank is the only company in the HBV development space to embark on a trial that seeks to examine the effect on cccDNA directly within the liver, utilizing a new treatment modality. This trial is recruiting well, and we expect to disclose data from this unique biopsy study in the first half of 2020.

We know that 12 weeks is an insufficient dosing period for inarigivir with either a monotherapy or in combination with a NUC to see sustained DNA, RNA and surface antigen loss. We have had no safety signals, and continue to push the dose of inarigivir and the Phase IIb program is now focused on longer durations of treatment with the 400-milligram dose of inarigivir. While awaiting the short-term 12-week 200 and 400-milligram dose data on the coadministration of inarigivir with Vemlidy from the Gilead trial, we have launched 2 key Phase IIb studies, called CATALYST 1 and 2. These are global trials, they are currently recruiting for longer-term monotherapy and combination therapy, with multiple endpoints including the potential for long-term treatment and cessation of therapy, to see if a functional cure is possible. The key questions are focused on duration of treatment and the sustainability of response after treatment cessation. The CATALYST 2 trial with HB antigen-negative NUC-suppressed patients is almost fully recruited for both of its cohorts. The cohort called Suppress & Shock, which looks at high dose inarigivir 400 milligrams added to a NUC with a long duration of treatment up to 1 year, which has a focus not just on biomarkers, but also on surface antigen loss and post-treatment HBV DNA suppression. This study is fully enrolled.

In addition, CATALYST 2 has a unique cohort called Stop & Shock, with 20 patients being evaluated post stopping the NUC treatment and subsequently given subsequent immune stimulation with inarigivir to evaluate viral clearance. The Stop & Shock cohort of the CATALYST 2 study could present Spring Bank with an opportunity to observe a monotherapy functional cure approach within a recover in NUC-suppressed e antigen-negative patients. We might be in the position to have data from the Stop & Shock population as early as the middle of next year during a planned 24-week interim analysis.

The CATALYST 1 study is looking at treatment-naive patients, and is currently enrolling patients with the 400-milligram dose of inarigivir co-administered with Vemlidy for a 48-week treatment period, with the objective of showing sustained HBsAg loss in at least 10% of patients, which has -- which is what has been reported in this population with interferon plus a NUC. The approach involves coadmission of inarigivir and a NUC to present a very simple, safe, effective modality of treatment for treatment-naive chronic HBV patients.

The signals that we have seen to date really have given us confidence that there is a potential for this simple treatment to be effective in patients who are HBV-naive to therapy. Doses of inarigivir from 25 to 200 milligrams at 12 weeks demonstrate a numerically superior effect on surface antigen reduction time period when compared to the results for published data for interferon interview, giving us hope that we may see with further continued therapy even higher rates of decline and potentially loss of surface antigen. Spring Bank will be in a position throughout 2020, probably beginning in the second quarter, to share data for inarigivir 400 milligrams alone and in combination with a NUC for longer durations of treatment. In both very suppressed e-negative patients and treatment-naive e-positive and e-negative patient population.

I think the last thing I would say is that one of the most exciting developments in the HBV space is the move towards 3 drug regimens to enable potentially shortening of treatment duration. In the ACHIEVE trial, we demonstrated that HBsAg baseline levels were highly predictive of the response to inarigivir. And we have been working on strategies to reduce HBsAg to complement the inarigivir response.

I'm going to turn the call over to Spring Bank's CSO, Dr. Kris Iyer, who will tell you about a novel chimeric antisense oligonucleotide, or CASO, which is designed with the specific role in mind for the shortening of the treatment duration and higher knockdown of surface antigen in combination with immunomodulation. Kris, let me turn it over to you.

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Radhakrishna P. Iyer, Spring Bank Pharmaceuticals, Inc. - Co-Founder & Chief Scientific Officer [4]

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Thank you, Ned. As we've disclosed on several occasions earlier this year, our team has been working to develop a series of novel chimeric antisense oligonucleotide or CASOs. We have been utilizing our proprietary internal expertise to apply chimeric chemistry technology to develop these antisense compounds. These compounds are designed to combine the gene silencing and immunomodulation properties to inhibit the production of all viral transcripts, and additionally activate innate and adaptive immunity for viral clearance in chronic hepatitis B. We are developing our CASOs for potential use in the combinatorial treatment of chronic hepatitis B. These compounds will most likely be used for high viral burden chronic hepatitis B patients as part of a triple therapy regimen which would include the antisense plus inarigivir plus a NUC. Our lead development compound from our CASO program is named SB 527. The truly novel feature of SB 527 as compared to the multiple siRNA and antisense compounds in development for a hepatitis B at other companies is that we have linked our dine fluid inarigivir to the oligonucleotide antisense sequence. This enables us to design a compound that delivers the oligonucleotide to the hepatocyte, along with the immunomodulator, with the goal of achieving sustained suppression of the viral [gene] transfers along with the induction of intrahepatic immune response. Earlier this year, we initiated a study of SB 527 in the AAV HBV mouse model, and in collaboration with the NIH, a study the HBV transgenic mouse model with intend to demonstrate in vivo proof of principle. These studies have been completed, and the data indicates that we have an agent that provides highly potent knockdown of HBV DNA, HBV RNA, HBe antigen and HBs antigen at doses that have been well tolerated by the animals. The level of knockdown on the viral gene target with 527 is comparable to that reported in nonclinical studies of antisense compounds currently in development. We will be presenting early data from this program at the annual [Hevdar] Scientific Conference next month. It is our intention to present the remainder of our in vivo proof of principle data at a scientific conference in the first half of 2020. With evidence of strong potency with 527 in animal studies, we have begun to accelerate our manufacturing efforts for this compound. We anticipate that our CMC efforts will continue to progress with the initiation of our IND or CTA enabling studies by the middle of next year.

It is our current plan to accelerate our SB 527 program in an effort to potentially enter our first clinical trial with a CASO in HBV patients in the latter part of next year. Given the recent sizable interest in siRNA and antisense therapies for chronic hepatitis B, we are accelerating our CASO program to broaden our HBV portfolio with the goal to have a truly unique compound that combines the benefits of antisense therapy with an immunomodulator.

Marty, I'll now pass the discussion back to you.

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Martin J. Driscoll, Spring Bank Pharmaceuticals, Inc. - President, CEO & Director [5]

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Thank you, Kris. We are excited at Spring Bank about our comprehensive HBV development program with, as you heard, the multiple efforts that we're employing designed to achieve functional cure in the heterogeneous chronic HBV patient population. We're also excited about our IV-administered STING agonist program in immuno-oncology, which, as we've mentioned, has just entered clinical development. Both of these clinical programs and the ongoing discovery programs, led by Dr. Iyer, which is derived from our proprietary and innovative nucleic acid platform, have significantly strengthened our company's pipeline last year to 1.5 years to create significant future value, we believe, for our shareholders. I want to thank everyone for listening to our program update and I'll now turn it over to the operator who's going to initiate a Q&A session.

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Questions and Answers

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Operator [1]

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(Operator Instructions) Our first question is from Ted Tenthoff, Piper Jaffray.

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Edward Andrew Tenthoff, Piper Jaffray Companies, Research Division - MD & Senior Research Analyst [2]

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Great. Thank you very much, and thanks, everybody, for the updates. Very thorough, a lot of progress we're making. So I wanted to ask, with respect to the CATALYST data coming next year, assuming that we find the right dose that [then] gets antigen knockdown, what would be the potential registrational path there? And kind of a second related question, would you ultimately seek partners overseas for the HBV programs in general?

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Martin J. Driscoll, Spring Bank Pharmaceuticals, Inc. - President, CEO & Director [3]

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So let me take that, Ted. Thank you for the question. So first to the registrational pathway. Obviously, the data is going to drive our decisions. So first, CATALYST 2 is focused on the virally-suppressed population, and CATALYST 1, as we said, is the treatment-naive. In the CATALYST 2, if we're fortunate to see this impressive effect in the Stop & Shock population, that would then allow us to drive the monotherapy into Phase III in the virally-suppressed NUC-experienced population. If with the Gilead 12-week data we see an even more impressive surface antigen responder population from the 12-week data at the higher doses -- plus in CATALYST 1, as you know, Ted, we're doing inarigivir 400 milligrams plus Vemlidy -- if we see that at the 6 months that we're on the path, then we would likely then take our fixed-dose combination into Phase III. We have the fixed-dose combination of inarigivir plus tenofovir. So the simple fact is we have multiple options. The data will guide us, but we could be taking the fixed-dose combination in for treatment-naive and the monotherapy into Phase III in the NUC-experienced population. Go ahead, please.

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Unidentified Analyst, [4]

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And then, I really love the fact that you're using your NUC expertise to get Kris and his team working on some ASOs. I wanted to ask you about the importance of transcript selection here in terms of getting appropriate knockdown. I believe we learned last year or 2 years ago, from some of the RNA experience, about where you really need to pick the sequence in order to get maximal knockdown. So maybe you could tell us a little bit about your sequence selection and whether there'll be more than one ASO in the compound?

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Radhakrishna P. Iyer, Spring Bank Pharmaceuticals, Inc. - Co-Founder & Chief Scientific Officer [5]

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Okay. That's a great question. Now in terms of ASO selection, obviously, one of the most important criteria that we have taken into account is that the sequence must to be homologous to all the different genotypes of HBV. That is the first criteria. The second criteria is that the sequence that we have selected will be targeted against all the viral [gene] trackers. For example, the HBs antigen, e antigen, the pregenomic RNA as well as the X gene. So taking into account we did an extensive BLAST search analysis and picked the ASO of the target region for making our ASO. And then, of course, as you know, in our design of the article, we have integrated the concept of gene silencing with immunomodulation. And I believe this is a very unique approach to ASO design.

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Martin J. Driscoll, Spring Bank Pharmaceuticals, Inc. - President, CEO & Director [6]

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Ted, if I may. You asked in your first question, a second part about potential partnerships. I just returned last week from 8 days in China. As you know, it's -- in terms of patient prevalence, the world's largest chronic HBV population. There's substantial interest in HBV treatment modalities. You probably know that the Chinese regulatory authorities are making the path for development of Western based medicines easier. When we disclosed the first cohort from the co-administration study, the Gilead study, we had inbound interest. I met with more than 20 companies while I was in China, so we're certainly having discussions about how we might co-develop in collaborations there. In Europe, we've had inbound interest in there as well. So we'll look at -- we're looking, as we progress our data, at all global collaborations and, if necessary, also region specific, whether it be Europe or China.

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Operator [7]

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Our next question is from Maury Raycroft, Jefferies.

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Maurice Thomas Raycroft, Jefferies LLC, Research Division - Equity Analyst [8]

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Congrats on the progress. To start, I was wondering, maybe for Ned, if you can talk about HBV virus genotype and how that's factored into competitor data, like the Assembly data shown today, and how you're thinking about it in your studies, too.

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Nezam H. Afdhal, Spring Bank Pharmaceuticals, Inc. - Chief Medical Officer [9]

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So genotype is important in antiviral responses. So there's a couple of factors associated with genotypes. As you know, the ACHIEVE data showed excellent response rates in genotype A&D, although the numbers were small, 4 out of 5 patients -- 80% -- had significant response to monotherapy treatment, and genotype A&D are the predominant genotype in Europe and the United States, in the non-Asian population. The Asian population is predominantly B and C, of which B responds better. It's interesting that in the poster presentation from the Assembly capsid, that the best responder to their capsid was also a genotype A patient. So we know that genotype A patients respond better, particularly naive patients, because they just have a better reaction to all types of antiviral. So genotype is important, but one has to realize that the global issue includes all the genotypes, but particularly B and C for the Asian population. So we do not limit genotype in any way in our studies. We try to keep our study that we designed to be appropriate for all HBV patients.

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Maurice Thomas Raycroft, Jefferies LLC, Research Division - Equity Analyst [10]

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Got it. Okay. And then for the core biopsy study, just wondering if you can comment on whether you were able to quantify cccDNA at baseline in some of the patients in your study or if other programs have been able to reliably quantify cccDNA at baseline?

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Nezam H. Afdhal, Spring Bank Pharmaceuticals, Inc. - Chief Medical Officer [11]

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We always forget what we've done in the past. And if you look at the data from the early entecavir trials for the approval of entecavir, there are many liver biopsy studies that included up to 150 patients that were biopsies at baseline and then after 12 months of entecavir. And they will show that entecavir has a significant effect on reducing cccDNA, more of an effect than a less powerful NUC such as lamivudine. And so we know that therapies that reduce the viral burden result in less infection of hepatocytes, and therefore less cccDNA. These biomarkers that you measure are all important to show the proof of principle that you're moving in the right direction. But as clinicians, what we want to do is we want to see the full spectrum of treatment duration, followed by that off-treatment period to see that these biomarkers are going to reflect what actually happens in terms of outcome. I am very excited by the AASLD data that is now talking about treatment cessation, because that's where we actually have to get to. We have to get to the point where we stop treatment and see what happens. So it's being discussed by the [capsid] company, Assembly, and Spring Bank's plan is also involves the cessation of therapy and looking at response and whether that response is sustained. So I'm excited that studies are beginning to now think that way, and it's going to be important. With respect to our data that is being generated from the clinical trial by professors [Sangli Lim] and Bertoletti in Singapore, this data is not yet available to us either a baseline or at 6 weeks post-treatment when the second biopsy is done. Our goal is to get the totality of the data, including all the immune and viral biomarkers and when that totality is in, I will review with the principal investigators, and hopefully, we can come up with a good dissemination of that data at a scientific meeting in the first half of next year.

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Maurice Thomas Raycroft, Jefferies LLC, Research Division - Equity Analyst [12]

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Got it. And how many patients are in that study again, the biopsy one?

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Nezam H. Afdhal, Spring Bank Pharmaceuticals, Inc. - Chief Medical Officer [13]

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It starts off with 8 patients, and then there's a second set of 8 patients. The first 8 are NUC-suppressed and the second 8 might well be NUC-naive. But again, the data drives the concepts that are developed for how to perform these (inaudible).

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Martin J. Driscoll, Spring Bank Pharmaceuticals, Inc. - President, CEO & Director [14]

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Maury, this is Marty. In the liver biopsy study, as Ned said that there was the first 8 NUC-suppressed, we will likely -- we're on a pathway to complete treatment in the 8 patients here in the next several weeks. And then -- and then Ned, along with the principal investigators, we'll make the decision on going into the treatment-native. But once he has the totality of the data on the NUC-suppressed population, we'll then seek to present that at a conference as quickly as we can.

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Operator [15]

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Our next question is from Mayank Mamtani, B. Riley FBR.

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Unidentified Analyst, [16]

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This is [Wayne] on for Mayank. And so my first question is related to the STING platform, could you please remind us the dosage level for the SB 11285 Phase Ia/b trial? And what do you consider as a success readout in the 2020?

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Martin J. Driscoll, Spring Bank Pharmaceuticals, Inc. - President, CEO & Director [17]

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So first, we have not disclosed the dose levels for strategic reasons. You can go to our website and see in our corporate presentation the trial design for the Phase Ia/Ib. If you don't mind, we've tried to stay strategic with the doses we're starting at. But it's a classic monotherapy dose escalation, and then as we get through our first 2 dosing cohorts, if successful with no DLTs, we then, in parallel, do our combination with the checkpoint inhibitor. And then for the second part of that question, can you remind -- can you restate the second part of that question, Mayank?

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Unidentified Analyst, [18]

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What do you think will be a success readout for this trial? So as I think you guys will disclosed the readout data in 2020, right?

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Martin J. Driscoll, Spring Bank Pharmaceuticals, Inc. - President, CEO & Director [19]

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Yes. So let me give you a time, and then I'll turn it over to Ned. So timing-wise, we've started the study. We're in the first dosing cohort now. As you probably know, typically with innate immune stimulators, the agency asks you -- asks us to typically wait 28 days between dosing cohorts. So if we continue to enroll as quickly as we are, I think -- we hope to be in a position to be disclosing data from the Phase Ia/Ib by the middle of the year, third quarter of next year. Now I'll let Ned go to your question, Mayank, about what we hope to see from this Phase Ia/Ib.

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Nezam H. Afdhal, Spring Bank Pharmaceuticals, Inc. - Chief Medical Officer [20]

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Obviously, using an IV STING, the first thing that we want to see is safety. We want to see a good safety profile. We want to see the ability to give an adequate dose. And we want to see target engagement, both peripherally and within the tumor microenvironment. These are all built into the study design. The other factors is that, obviously, we would like to escalate the dose and then get into the combination strategy, that's outlined on our website, with a checkpoint inhibitor, and look to see if we can get a partial response, or in the best case scenario, a complete response. But clearly, the first step of this is to demonstrate that the real first IV STING can be administered safely and that there is significant [data], both peripheral and preferably tumor-related target engagement.

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Martin J. Driscoll, Spring Bank Pharmaceuticals, Inc. - President, CEO & Director [21]

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Mayank, this is Marty. Mayank, this is Marty again. Again, in our corporate presentation on our website, you'll see the protocol design schematically. We can certainly send it to you, if you'd like. You'll see some of our current thinking of the expansion cohorts, if we're fortunate to get through the combination therapy. You'll see kind of our current thinking. Obviously, our data will drive us. But one point I'll mention is, in September, a team from Yale University revealed data at the ASTRO meeting showing impressive use of the IV STING agonist SB 11285 in a radio-sensitized animal -- in glioblastoma, as Kris reminds me. This gives us the thought that we'll probably have a cohort in our expansion group that is a cohort of patients that have been radio-sensitized and then get the IV STING agonist, probably in head and neck.

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Unidentified Analyst, [22]

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Okay. And also, I have a second question is about the CATALYST 1 and 2 trial. Are these going to be a single dose for the 400 milligrams and also, should we expect any readout at EASL for next year?

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Nezam H. Afdhal, Spring Bank Pharmaceuticals, Inc. - Chief Medical Officer [23]

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So the dosing is 400 milligrams daily and 400 milligrams 3 times a week as a monotherapy for 12 weeks in CATALYST 1 with then the third arm that's a combination right after that of 400 milligrams daily plus Vemlidy. So the monotherapy arms, after 12 weeks we add Vemlidy on top and then continue all of them for a duration of 48 weeks. And then we stop. The reason that we have the first 12 weeks of monotherapy, both daily and 3 times a week, is that we want to generate information on whether it's worthwhile turning on the immune system first and then giving the [polymerase] inhibitor, but the dose is at the 400-milligram dose. CATALYST 1 we -- Spring Bank can look at the data at the 12-week time point for the monotherapy arms, and there is the potential that that could be in the first half of next year. But I wouldn't want to commit to when we will have that data in our hands. Recruitment's going well, but we don't have it -- unlike CATALYST 2, we can't say that it's really fully recruited.

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Martin J. Driscoll, Spring Bank Pharmaceuticals, Inc. - President, CEO & Director [24]

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Mayank, to be specific, CATALYST 2, the study 400-milligram dose in the virally-suppressed population, we were able to enroll that study 2 to 3 months ahead of our schedule. So we should be in a position to be rolling out data from that in the first half of the year. CATALYST 1 is enrolling fine, it's just -- it doesn't appear it's going to be 2 to 3 months early like the other. So EASL might be tough, we'll see. We will have -- we believe -- we've submitted or will submit a great deal for EASL about the HBV program. Will it be any of the CATALYST data? We'll have to see.

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Operator [25]

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We have reached the end of the question-and-answer session. I will now turn the call back over to Martin Driscoll for closing remarks.

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Martin J. Driscoll, Spring Bank Pharmaceuticals, Inc. - President, CEO & Director [26]

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Thank you, everyone, for listening to our update tonight, and I appreciate the questions, and we look forward to keeping you updated on our continued progress. Thank you very much.

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Operator [27]

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This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.