Terns Pharmaceuticals Inc TERN-701: Interpreting Early Datasets in CML Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Etzer Darout - BMO Capital Markets - Analyst : Great. Thanks for taking the question, and thanks for this event today. First question for me is when you think about the efficacy measures in this update, is the best way to think about the update is really just maybe patient-by-patient history, prior therapy, BCR-ABL levels to get a sense on

Question: Etzer Darout - BMO Capital Markets - Analyst : Got it. Thank you. And the second question, think about sort of the second-line opportunity for 701, just in terms of, ultimately, the way you would enroll patients, are these patients that would be -- that's maybe refractory and tolerant to first and second generation and those intolerant to [Scemblix], I guess, similar to CARDINAL, in terms of the types of patient you would enroll in that second-line trial? And does the change, or maybe sort of the rate of penetration of Scemblix in front line sort of change sort of the way you think about that second-line design?

Question: Etzer Darout - BMO Capital Markets - Analyst : Great. Thank you.

Question: Ellie Merle - UBS - Analyst : Hey, guys. Thanks so much for taking my question and for providing all the color. Maybe just starting with Dr. Hochhaus, how would you think about potentially switching a patient who is in MMR on asciminib to 701 for say better convenience? Maybe specifically, I guess, how burdensome is the fasting requirement for your patients? And then I have some follow-up questions. Thanks. Andreas Hochhaus - Jena University Hospital - Professor, Internal Medicine and Head, Department of Hematology and Medical Oncology To be honest, I think that's a little too much expectation. I think it's in general an advantage for 701 to have this profile. But I would not expect to switch, just for this reason, a patient in MMR from one to the other allosteric inhibitor. I think that sets too much expectation here. And if you want to be realistic, but if there's any other intolerance, of course, I would switch.

Question: Ellie Merle - UBS - Analyst : Great. Thanks.

Question: Graig Suvannavejh - Mizuho Securities USA - Analyst : Hey, thanks. Thanks so much for the presentation today, and thanks for taking my questions. I had a question with regards to the 701 data that has been generated by your partner. And I was just wondering if you could remind us on what has been seen in the hands of Hansoh and whether you feel that there is translatability of that data over to what you might expect with your own study. And then secondly, I just want to make sure that I understand this correctly, but it seems as if there are going to be a fair amount of caveats with the interim CARDINAL readout. And so with that in mind, just to confirm, it is really more the six-month data that you would expect to be more confirmatory of the profile for the product, or perhaps is there a later time point that you think would be a good representation of the product? Thanks.

Question: Graig Suvannavejh - Mizuho Securities USA - Analyst : Thank you. Just one follow-up for the doctor. Doctor, just thank you for your participation today, but given the interim data that is expected in December and relative to what you know about asciminib, are you anticipating at that time point any meaningful differences? And if you don't see meaningful differences, is that, in any way, a sign of whether your enthusiasm for the 701 profile would be more or less, depending on what that data show? Thanks. Andreas Hochhaus - Jena University Hospital - Professor, Internal Medicine and Head, Department of Hematology and Medical Oncology We don't have a comparative study between asciminib and TERN-701. Therefore, from the scientific point of view, we cannot expect meaningful differences. We have meaningful differences in the preclinical profile, and that's important for the development of the drug. But of course, eventually, when you want to see specific differences for specific situations, you need a direct comparison scientifically. But of course, overall, with more data and with more patients, we may see differences in the tolerability, but also -- and that's what I expect specifically -- differences in the activity in the specific mutations.

Question: Corinne Jenkins - Goldman Sachs & Co. LLC - Analyst : Good morning, guys. Maybe a couple for me. First, from the company, I guess, what will you be looking for within this dataset as you think about determining the registrational path, whether you'll go into 1L or 2L? So what in the data could influence that decision, and then what else are you monitoring that will help you make that final decision around registrational development path? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies.

Question: Corinne Jenkins - Goldman Sachs & Co. LLC - Analyst : Okay. Thank you.

Question: Ritu Baral - TD Cowen (Research) - Analyst : Hi, guys. Thanks for taking the question. I wanted to ask some further questions about the dose. As mentioned, you are starting at the current trial at the 160, and you mentioned two doses over the course of the presentation. Have you dosed down to 80 milligrams as you previously had the option of doing, or have you elected to dose up? And how are you viewing stratification across the doses in CARDINAL for now, and what could we expect in the interim data? And then I have a follow-up. Thanks.

Question: Ritu Baral - TD Cowen (Research) - Analyst : Got it. And then my follow-up is just on how the data will be released. I guess, even though MMR would be far too preliminary to be useful or achieved, do you anticipate disclosing transcript decline rates on an individual patient, sort of like by spaghetti plot, and will you clarify, to help us discern, what sort of transcript decline is seen in these different groups? At the beginning of the description of CARDINAL, you mentioned patients could be enrolling -- moving to second line because of intolerability, inadequate response, or relapse. So how will we visualize that transcript decline?

Question: Ritu Baral - TD Cowen (Research) - Analyst : Got it. And last question, when could we see first meaningful data on the differential tolerability or safety profile of 701 versus the Novartis compound? Is that something that could emerge from the final CARDINAL data, or would that require the pivotal? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies.

Question: Ritu Baral - TD Cowen (Research) - Analyst : Dr. Hochhaus, how would you expect -- sorry, where would you expect to start seeing signals just given your real-world experience with asciminib? Andreas Hochhaus - Jena University Hospital - Professor, Internal Medicine and Head, Department of Hematology and Medical Oncology Where? At which time point or -- what do you mean?

Question: Ritu Baral - TD Cowen (Research) - Analyst : Thank you.

Question: Eric Joseph - J.P. Morgan Securities LLC - Analyst : All right, thanks. And thanks for taking the questions. Maybe a first one for Dr. Hochhaus. Maybe you can just kind of speak to the extent to which speed to response, or speed to MMR, is a priority with the currently available treatment options in CML. I guess, how long will you typically keep a patient on therapy before concluding, perhaps, suboptimal response and then moving them on to another line of therapy? And then perhaps for the company, can you speak to sort of how well characterized or understood the mutational profile is of patients either non-responding or progressing with asciminib, and whether those might be represented in the CARDINAL trial? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies.

Question: Josh Warman - Citizens JMP - Analyst : Hi. Thank you to the Terns team for putting on this great event. Thank you, Dr. Hochhaus, for the really informative session, and thank you for taking my question as well. So I guess this is for Dr. Hochhaus. From the asciminib trials, we did see discontinuations, and that most likely will be the case with any new inhibitors. So can you briefly touch on how physicians think about after treatment failure or discontinuation of allosteric TKIs, and therefore, how that may impact physicians' decisions to use the allosteric TKIs, such as 701, in earlier lines? Thank you. Andreas Hochhaus - Jena University Hospital - Professor, Internal Medicine and Head, Department of Hematology and Medical Oncology It depends, of course, on the specific situation, again. What was the intention of the trial? If it was a third-line situation, we know from the ASCEMBL trial that about 55% of patients have the 1% level and the others don't respond. And after two years of therapy, of course, I would like to see a less than 1% level, and therefore, it's not surprising that these colleagues will discontinue the drug. The competitor against this situation, and we must not forget this, is allogeneic stem cell transplantation. Allogeneic stem cell transplantation is the way to cure a CML patient. There's all the disadvantages, of course, but we should offer the option for a cure for a patient who did not achieve a molecular response to three or four lines of therapy with resistance. And therefore, in such a situation, I would be very cautious with any new drug. You could ask about ponatinib as well here in this situation, but I would be very cautious with any of the other drugs and should consider allotransplant in this late-line situation. Overall, we transplant 3% of all CML patients for the time being, but too late -- some of them too late. That means we should consider allotransplant in this setting as well.