aTYR PHARMA INC Q4 FY2021 earnings call

• 2021年是里程碑年，efzofitimod的Phase 1b/2a研究显示临床概念验证，tRNA synthetase生物学平台得到验证。
• 获得efzofitimod治疗肉瘤样瘤的FDA孤儿药指定，与FUJIFILM Diosynth Biotechnologies达成efzofitimod生产协议。
• 2810的临床前数据在癌症方面有进展，计划2022年下半年启动1期临床。
• 2021年底现金约1.08亿美元，财务状况良好以推进临床项目。

无明确产品细分的财务贡献披露，主要聚焦于临床项目进展和研发投入

• 计划2022年第三季度启动efzofitimod的注册研究。
• 预计2022年下半年启动2810在癌症患者中的1期临床。
• 期望从Kyorin获得双位数的里程碑付款。

前瞻性陈述涉及风险，包括实际结果与预期不同的风险，如临床开发失败、监管审批不通过等风险因素

Q: On 2810, as you’re moving that into the clinic, are there any indications or sort of broad classes of oncologic indications that stand out as potentially the most amenable to treatment, whether solid or liquid tumors or are there any biomarkers that could potentially be indicative of a higher likelihood of response based on your preclinical data? And then second question is on efzofitimod, and just wondering what the final steps are towards a – the Phase 3 design finalized and implemented as we get a little bit closer to Q3?

A: Great. Thanks, Kennen, for the question. So your first question about 2810, we’re very much anchored to solid tumors. And there was quite a bit of literature early on, which is why we targeted neuropilin here that neuropilin-2 was basically associated with some really poor prognosis in some pretty aggressive forms of cancer, triple-negative breast cancer, lung cancer, also renal cell, neuroendocrine phenotypes. So we really focused on solid tumors first and foremost, and we are now looking at those particular tumors where we’ve seen 2810 most effective in our preclinical animal models. So what I’ve said here is we’re focusing on those neuropilin-enriched tumors. It appears as though when resistance starts to develop for many of these cancers to current agents, we may be able to look at how neuropilin is further expressed, perhaps as a resistance mechanism. And this is the sort of work that we’re currently going to be highlighting at AACR coming up here next month. So I would say stay tuned here as we get closer to an indication. But just based on historically what you’ve seen here, we see some really nice effects of 2810 in solid tumors, expect this next indication to be a solid tumor that is enriched with a neuropilin signature. We continue to look at other biomarkers right now to hone in on which tumor types are most responsive. And we’re doing so in a very sort of systematic data-driven manner so that once we launch the Phase 1 trial, we expect 2810 to demonstrate hopefully good objective response in whatever subclass of solid tumors we go after. So stay tuned there. I think that’s work that’s nearly – we progressed quite a bit here in the last couple of years, and nearly complete. To your second question around efzofitimod, really, at this point, Kennen, we’ve taken the feedback from the FDA, there was a significant amount of feedback. One of the most productive meetings I’ve ever had in my career as a drug developer, very collegiate, very collaborative. And I think we are going to now be able to – we have a clear understanding on how to prioritize the endpoints, the design of this trial, the statistical modeling and the assumptions. And this will now be submitted as part of an IND package. Once we actually receive approval, that’s the time for us to sort of then really get into all of the details. I want to allow the FDA the ability to approve what they told us to go after. No reason, I think sometimes biotech companies can jump the gun here, and we don’t want to annoy our partners at the FDA. We feel pretty good about following the path that they have sort of mapped out for us around with their guidance. And I expect a successful IND here in the short future.

Q: Ted Tenthoff: Yes, really helpful. I appreciate that color. And maybe just a quick follow-up. So how big of a safety database is the FDA looking for or how many patients do you think you might need to enroll per arm with the control?

A: Yes. So that’s another great question. I mean my general view is the safety database, the FDA, for most indications, they like around 200 patients that have had long-term exposure. It’s what I’ve always been trained in drug development team for that number within rare disease, it can be sometimes hard to get to that number. Remember, we thus far have experience human data, north of 30, 40 patients, if you even go back to our healthy volunteer trial. So in this next trial, for example, if we were to have these two doses going forward you might actually have, say, closer to 150 patients exposed in a trial that might be out to a year. You add that to the 30 or 40 patients that we previously have exposed to efzofitimod, we’re getting closer to that safety database. This is another reason why it’s good to also look at another dose in the next study. It adds to the body of evidence that your drug is safe and well tolerated. And then you can basically say, well, what does the efficacy look like between 3 and 5? Because both of them performed outstandingly in our last trial.

Q: Zegbeh Jallah: Yes. Thanks for taking my question. Just had couple of ones here for you. I think the first is just about whether or not for efzofitimod, you will need to go lower than 3 milligrams just because you mentioned leading to determine whether 3-milligram was the minimum efficacious dose. So could you maybe have to exploit 2 milligram, for example?

A: No, I think at this point, having tested 3 and 5, both observed as safe and both showing really nice activity in our previous trial, we’re going to go with what works. And I think that’s primarily what the discussion was with the FDA. I think those are the two doses to anchor on as we think about the next trial.

Q: Yale Jen: Good afternoon. Thanks for taking the questions and my congrats to you guys as well. Just got two here. The first one is for Sanjay that you did mention about the functional end point during your prepared remarks. Are you suggesting or potentially that will be the primary endpoint to be considered for the Phase 3 study or are we reading into too much of that and still to be determined?

A: No. We know the following feedback from the FDA, what I can tell you is steroid reduction was a big discussion that we had. And I think you read some of the comments from Dr. Baughman that there was a real appreciation that this, in many ways, may be the most meaningful endpoint for patients and providers. We also know FVC has been used for the IPF drugs to get approved. But there’s an understanding that IPF may not – FVC may not be best moved in a really nice direction, steroid reduction, FEC improvement, symptom improvement. So, I think we had a sort of a bevy of opportunity here for the FDA to guide us. We have taken that guidance. We have now written a protocol and as I have said stay tuned here. But what I can maybe highlight here is how impressed everyone has been around the ability to reduce and potentially even get off steroids. That could really change treatment paradigm for really millions of patients worldwide who suffer from fibrotic lung disease. We are really the first as I have said therapy that show jumps physiologic and QoL effects, while also reducing steroids. And I think that is something that has the experts worldwide wildly excited about this as a therapy in the future.

Q: Hartaj Singh: Great. Thank you. Thanks for the questions. Sanjay, Jill everyone, really, really nice update. I just got a few questions, just go through them quickly. Sanjay, I know you got to win when I ask the 18th question on the primary end point. It’s not a primary endpoint question, but – let me put it another way on the pivotal study. If you were, could it be possible, for example, to have an endpoint analysis to a primary where you have steroid reduction, let’s say, over 24 weeks and then FVC for the full readout. So, meaning that you could show a steroid reduction over 24 weeks for over the placebo arm or the control arm get approval an interim on that and then read out the full study for a full approval. Is something like that even possible in pulmonary sarcoidosis. And then I just got a couple of questions follow-up.

A: Well, I like your question, Hartaj. It’s a very – you should come into our clinical development strategy meetings. I like that. Our statisticians would love some of these ideas. One thing about doing interim readouts you give up some of your alpha when you do things like that. I am not sure necessarily if I would agree with that element of it. However, if you think about our trial, having three people getting off steroids, DSMB could certainly look at the risk benefit. And certainly, in our next trial, we have a number of patients getting off steroids that might be a better way for us to perhaps look at things in the interim. But again, I don’t want to get into that yet until we actually put out the design. But I like the way you are thinking about things here with regards to an objective and a subjective endpoint. So, steroid reduction, FVC, those two endpoints are going to play key roles here in the hierarchy as we start to actually design our next trial, because I think those two start to represent a pathway in my mind for a drug label that’s really meaningful here. Patients really want to reduce their steroids. Providers want to get people off steroids. FVC is another way for them to also look at that objectively to look at lung function. We are fortunate in our trial that we saw the kinds of reductions, 58%, 49% with our two top doses and FVC improvement more than 2.5%, we had 2.8% and 3.3%. That kind of improvement has not been observed in this area of lung disease really ever, maybe for 15 years here. And as I mentioned, none of this has ever been observed in a trial where we also are reducing steroids. So, I think we have something really profound here with efzofitimod, bare with me with the primary endpoint. As I said, once we launch that protocol, you will start to get a view on that hierarchy.