Atossa at H.C. Wainwright: Zinhoxifen’s Dual Pathway Strategy

On Monday, September 8, 2025, Atossa Therapeutics (NASDAQ:ATOS) presented at the H.C. Wainwright 27th Annual Global Investment Conference, focusing on its lead asset, Zinhoxifen. The discussion highlighted the drug’s potential in breast cancer prevention and treatment, emphasizing its unique mechanism and promising clinical data. While the company is optimistic about Zinhoxifen’s market potential, challenges remain in advancing clinical trials and regulatory approvals.

Key Takeaways

• Zinhoxifen is positioned as a potential replacement for tamoxifen, with improved tolerability.
• Atossa plans to file an IND for a dose-ranging study under the FDA’s Project Optimus by fall.
• The company is pursuing dual pathways: low-dose for prevention and high-dose for metastatic treatment.
• Pricing strategies suggest a significant market opportunity, with prevention drugs priced lower than metastatic treatments.
• Upcoming milestones include FDA feedback on the low-dose program and progress in the iSpy 2 trial.

Financial Results

• The conference call did not focus on Atossa Therapeutics’ financial performance.
• Potential pricing for Zinhoxifen was outlined: $100,000 to $240,000 annually for metastatic use and $6,000 to $20,000 annually for prevention.

Operational Updates

• Atossa has requested a Type C meeting with the FDA for the low-dose Zinhoxifen program, expecting feedback by year-end.
• The company is preparing to file an IND for the Project Optimus trial, targeting the fourth quarter.
• The iSpy 2 trial, combining Zinhoxifen with abemaciclib, is progressing well in recruitment.
• Contract research organization PSI has been engaged to support ongoing studies.

Future Outlook

• The focus remains on advancing both low-dose and high-dose programs for Zinhoxifen.
• Atossa anticipates FDA feedback on the low-dose program by December, potentially paving the way for a new drug application.
• Preparations are underway for the high-dose Project Optimus dose-ranging study.
• The improved tolerance of Zinhoxifen, especially regarding hot flashes, is expected to capture a significant market share from tamoxifen.

Q&A Highlights

• The potential combination of Zinhoxifen with CDK4/6 inhibitors, like abemaciclib, is being explored.
• A Phase 2 trial is anticipated to determine the optimal dose for monotherapy and combination therapy.
• The FDA’s Project Optimus concept is guiding the trial to identify the best dose for efficacy and safety.
• Atossa is investigating Zinhoxifen’s role in identifying patients with circulating tumor cells in the metastatic setting.

For more detailed insights, please refer to the full conference call transcript below.

Full transcript - H.C. Wainwright 27th Annual Global Investment Conference:

Emily Bodnar, Equity Research Analyst, H.C. Wainwright: Good afternoon, everyone. Thanks for joining the H.C. Wainwright 27th Annual Global Investment Conference. My name is Emily Bodnar, and I’m an equity research analyst at H.C. Wainwright. I’m pleased to introduce Dr. Steven Quay, who’s the Chief Executive Officer of Atossa Therapeutics. We’ll be doing a fireside chat this afternoon. Maybe to start, can you give us some background on your lead asset, Zinhoxifen? Specifically, what is it and how does it differ from the prodrug tamoxifen, which obviously is approved for different variations of breast cancer treatment? How could it potentially be superior, either on efficacy and/or safety?

Steven Quay, Chief Executive Officer, Atossa Therapeutics: Good starting question, Emily. (Z)-endoxifen is the second step from tamoxifen, which is a well-known drug. When you take tamoxifen, you make 21 other things. One of the challenges for a tamoxifen-taking patient is some of those other chemicals have certain side effects or other kinds of things. By giving pure (Z)-endoxifen, you get all of the efficacy and fewer of the side effects associated with it. It also allows you to give (Z)-endoxifen at doses that you can’t achieve with tamoxifen. (Z)-endoxifen has three unique properties. It not only blocks estrogen in its interaction with the receptor, but it actually stimulates degradation of the receptor. The only current drug that does that is an injectable selective estrogen receptor degrader that’s given once a month. All the others simply block the estrogen interaction. Being able to degrade the receptor is a very stronger way to inhibit the pathway.

Finally, at higher doses, it works with a completely different pathway called PKC beta, which, unlike the estrogen low-dose pathways, is apoptotic, which means that the cells are killed by the process. It’s kind of a Janus molecule with two functions, both at the receptor and at PKC beta.

Emily Bodnar, Equity Research Analyst, H.C. Wainwright: Right. You mentioned it has both SERM and SERD qualities. How does it kind of function as both, and how does that fit into the current treatment landscape for HR positive, HER2-negative breast cancer?

Steven Quay, Chief Executive Officer, Atossa Therapeutics: I mean, for molecular biologists and scientists in the laboratory, this distinction is important. For clinicians, it’s simply how well does it work, and does it give you a complete response? By degrading the receptor, you have a greater ability to stop estrogen-driven growth than by simply blocking it with the endoxifen. Because every day when you take a drug, you have a trough 24 hours after the last dose where the receptor can be activated again by estrogen. When it’s degraded, it simply doesn’t work. Typically, finasteride is considered the best drug among the molecules because of the degradation activity. Being able to give endoxifen alone will allow us to compete with that particular activity.

Emily Bodnar, Equity Research Analyst, H.C. Wainwright: One of the main concerns with tamoxifen is the high rate of vasomotor adverse events, like hot flushes. Do you believe Zinhoxifen could potentially have a differentiated safety profile? What’s the experience been like in clinical trials to date?

Steven Quay, Chief Executive Officer, Atossa Therapeutics: our clinical trials, which involve both Atossa Therapeutics, National Cancer Institute, and Mayo Clinic, about 700 women, there has been, in general, a reduced incidence of these hot flashes, which are irritating for clinicians trying to save people’s lives. They don’t seem important, but for patients, there are high compliance issues. Many times, patients will stop taking the therapy because of these. We’ve seen fewer of them in our trials. More importantly, there was a prospective study where they asked if the hypothesis was higher (Z)-endoxifen levels after tamoxifen related to these hot flashes and vasomotor symptoms. It must have been a very interesting day when the statistician came back and said, "Look, we proved that there’s a statistical difference between hot flashes and (Z)-endoxifen, but it’s inverse.

The higher the (Z)-endoxifen levels, the lower the hot flashes and adverse events, to the point where severe events didn’t occur at all in patients in the highest group with (Z)-endoxifen." There’s some cool endocrine physiology going on there, but I think we should stick with the topic.

Emily Bodnar, Equity Research Analyst, H.C. Wainwright: You actually had an announcement this morning talking about progressing low-dose Zinhoxifen to reduce risk of breast cancer. You also obviously have your program for metastatic breast cancer. Can you walk us through how you’re currently thinking about use of Zinhoxifen and the various doses to kind of treat the whole landscape in breast cancer?

Steven Quay, Chief Executive Officer, Atossa Therapeutics: Yeah, great question. Again, it could be complicated, but we’ll try to simplify it here. If you think about two aspects of breast cancer, one is what we’ll call prevention, but the official word is reducing the incidence in the future because you really can’t prevent something in an FDA sense. There’s prevention, which can happen at very low doses, typically doses that mimic the amount of (Z)-endoxifen you get with tamoxifen. Then there’s metastatic conditions where the disease has progressed. There’s been some additional mutations. It’s now escaping endocrine therapy, and there you need a much higher dose. I think the way you should think of the anchors is that maybe 1 to 4 milligrams in the prevention space and then 20 to 80 milligrams in the metastatic space.

One of the things that happens in the prevention space is in three classes of clinical situations, there’s 1.7 million women taking tamoxifen. The five years after they had definitive surgery for positive breast cancer, the time after DCIS surgery when they’ve had the surgical removal and you’re trying to reduce the incidence of cancer in the future, and then in women who either have high density or for other reasons are at higher risk of breast cancer, those women, again, a population of them will take tamoxifen for prevention in the future. We think that (Z)-endoxifen, being sort of cleaner in terms of the hot flashes, is very attractive in that prevention space. Of course, when you need the full, you know, horsepower of high dose with PKC beta inhibition, you can have it at that higher dose.

Emily Bodnar, Equity Research Analyst, H.C. Wainwright: Maybe narrowing down to metastatic breast cancer, what kind of gives you confidence that Zinhoxifen could work in the metastatic cancer setting? What clinical data have you generated compared to tamoxifen?

Steven Quay, Chief Executive Officer, Atossa Therapeutics: Yeah. We have our own clinical data. First, I’d like to speak about data from the National Cancer Institute and the Mayo Clinic, where approximately 80 patients who were advancing on all current endocrine therapy, so that’s fulvestrant, AIs, or tamoxifen, were put on (Z)-endoxifen at higher doses, again, you know, in the 20, 40, and even higher levels. They showed a clinical response in about 25% and partial response in about 50%. That data is what gave us confidence to go into an iSpy 2 trial where we’re looking at (Z)-endoxifen plus the CDK4/6 inhibitor abemaciclib from Eli Lilly. That trial is being done in the iSpy network. It’s recruiting very well. Finally, our plan is that with our finding with the dose finding Project Optimus Phase 2, that will give us the dose in monotherapy.

We want to very quickly couple that with a CDK4/6 inhibitor in that more challenging space of metastatic disease where they’re beginning to escape endocrine therapy.

Emily Bodnar, Equity Research Analyst, H.C. Wainwright: Maybe going a bit more off of that, do you think Zinhoxifen in the metastatic setting makes most sense in combination with another agent? Are you expecting that your initial data from the iSpy 2 trial will kind of provide you with more confidence in that combination approach?

Steven Quay, Chief Executive Officer, Atossa Therapeutics: Yeah, I mean, I think it will. Look, as I said, there is evidence that you can get partial clinical response with monotherapy in the setting of endocrine escape metastatic disease. We’re wanting to get as much bang for the buck in these patients as we can, so a combination therapy is probably where it’s going to be best. We started this trial with Lilly’s abemaciclib some time ago. It’s recruiting very well, which, having been in seven drugs and done a lot of clinical trials, the recruitment phase is an important test of whether the clinicians and the patients like the combination. It’s going well.

Emily Bodnar, Equity Research Analyst, H.C. Wainwright: Maybe you could talk a bit more about the trial design for the trial that you plan to start later this year, and what feedback you received from the FDA regarding the trial design.

Steven Quay, Chief Executive Officer, Atossa Therapeutics: Yeah, so this is a trial under a concept the FDA put forward last August called Project Optimus. What it is literally is a new step in addition to all the steps that oncology companies have to take their drugs through. It’s a reasonable step because in the past, we would do a phase III study primarily on tolerance, and then we’d very quickly transition to a phase III study. We all know that there have been drugs that have been at an inadequate dose by the time they got to the market, or maybe there were side effects that were due to an excessive dose when the dose could have been lowered.

Project Optimus was put in place to really force everyone to say, you know, what’s the Goldilocks of your drug, which is too low and you don’t get the efficacy you want, too high you’re getting side effects and good efficacy. Is there a sweet spot in the middle? That sort of defines it. They’re typically three-dose studies. They typically use progression-free survival as a typical endpoint. They’re typically, obviously, multicenter and probably multinational. They’re international because you can do some of these studies a little bit quicker in other countries that may not have some of the other options for patients.

Emily Bodnar, Equity Research Analyst, H.C. Wainwright: I guess based on clinical trials you’ve had so far, is there a dose that you think is likely to be the go-forward dose? Are you able to transition this dose escalation into a potentially pivotal trial?

Steven Quay, Chief Executive Officer, Atossa Therapeutics: We’ve done trials at the Mayo Clinic in Evangeline at 20, 40, and 80. We’ve done trials in the iSpy 2 trial at 10, 20, and 40. If I had to make a bet today, I feel like 40 is a good dose. We know through tissue sampling that we are really hammering PKC beta at that dose because we get about 8 to 10 times as much drug in the cancer tissue as is in the bloodstream. If you know in the lab what PKC beta needs to be inhibited, you look at your plasma levels, you multiply by 8 to 10, you’re getting full saturation of that pathway. If I had to bet now, I’m going to say we’re going to end up at 40 milligrams, but I have been fooled before by that.

Emily Bodnar, Equity Research Analyst, H.C. Wainwright: Maybe you can talk a bit about benchmarks with some of the current combination approaches that are coming out in the metastatic setting, for example, the MBR3 trial and other kind of second-line plus combination approaches.

Steven Quay, Chief Executive Officer, Atossa Therapeutics: Yeah, there is sort of a new concept which isn’t fully baked into the FDA process yet, but which involves identifying women who are not clinically advancing in the metastatic setting but have circulating tumor cells that give an indication of a partial extension. This is sometimes called line 1.5. We believe that we’ll have strong activity in that setting. We did some in vitro work, which shows that the characteristic three mutations that happen in the estrogen receptor with endocrine therapy, all that particular receptor can be inhibited almost fully with (Z)-endoxifen at its current doses. We’re quite excited about being able to step in as those mutations begin to occur, measured typically by circulating tumor cells.

Emily Bodnar, Equity Research Analyst, H.C. Wainwright: What remaining steps do you have to get toward IND filing this year? What kind of timelines have you provided for the trial?

Steven Quay, Chief Executive Officer, Atossa Therapeutics: Yeah, I mean, the timeline is an IND as quickly as possible, which translates into sometime early this fall. We put our contract research organization in place, PSI, very familiar with this space, just finishing trials with other drugs in the breast cancer space. We’re working on protocols and what dosing would be optimal in those protocols, some of the details. All of that will be put into the IND in the package to begin trials, filing an IND hopefully, you know, early part of the fourth quarter, mid-fourth quarter.

Emily Bodnar, Equity Research Analyst, H.C. Wainwright: For your neoadjuvant trial, the iSpy 2 trial, which we talked briefly about already, you’ve guided to data next year. What should we be looking out for in that trial? What kind of endpoints and patient numbers are you looking at there?

Steven Quay, Chief Executive Officer, Atossa Therapeutics: Yeah, you do typically 60 to 80 patients in a setting like this. In the neoadjuvant setting with high-risk breast cancer or maybe locally advanced breast cancer, you’re looking at Ki-67 at 28 days to show biological activity in the tumors. You’re looking at MRIs at two to three to four months where you’re seeing actually tumor shrinkage. At the time of definitive surgery, you look at the pathology for either a complete or partial pathologic response. We’ve already seen encouraging data in prior trials where (Z)-endoxifen alone in sort of lower proliferation cancers can shrink tumors very substantially at two to three months. That can sometimes change the clinical course, whether between a mastectomy and a lumpectomy or whether an axial node dissection is necessary in that setting.

Emily Bodnar, Equity Research Analyst, H.C. Wainwright: Right. When do you plan to schedule your Type C meeting with the FDA regarding the use of low-dose Zinhoxifen for breast cancer risk reduction, and what could a trial in that setting look like?

Steven Quay, Chief Executive Officer, Atossa Therapeutics: The press release this morning indicated that last week we submitted our request. These things have statutory timelines associated with them. We expect to hear by the end of the year what the trial will be and what the path will be. It’s pretty hard to give guidance at this point. We have some very specific beliefs about what we think would be a new drug application pathway. We’re asking them in the context of this, and we’ll certainly report as soon as we know what the status will be.

Emily Bodnar, Equity Research Analyst, H.C. Wainwright: Great. Maybe you could touch a bit about the CRISPR trial that you had, which kind of looked at reduction and what the efficacy looked like there.

Steven Quay, Chief Executive Officer, Atossa Therapeutics: Yeah, yeah. About six or seven years ago, the concept that high mammographic breast density was associated with both difficulty in finding cancers in mammograms and increased risk became apparent. This last September, finally, the FDA has formalized that with a requirement that all women who do a mammogram get a letter afterwards. The 39 million mammograms a year, they get a letter which will most of the time say, you know, the good news is you don’t have breast cancer. The other news is that you do have high density and maybe you need to do another imaging test and maybe you’re at an increased risk of cancer.

We took that biological marker of increased risk in a trial in the Karolinska Institute in Stockholm, Sweden, where we had three groups of placebo, 1 milligram and 2 milligrams of (Z)-endoxifen for six months in a double-blind format with mammograms at day zero, three months, and six months. The results were very encouraging. The results at six months showed about a 17-18% reduction in the 1 milligram, about a 23-25% reduction in the 2 milligram. Those reductions have been shown in a very large trial called the IBUS trial with tamoxifen to lead to about a 60% reduction in five-year risk of breast cancer. Biologically, the biomarker in the mammogram is exactly where we think we should be. Again, with a profile where the 1 milligram dose was not different from placebo, the sugar pill.

When you think about prevention or reducing risk, these are women who do not have breast cancer. Having a drug that has, you know, even hot flashes and night sweats, which for an oncologist is kind of, you know, keeping you alive, aren’t they? In that case, it’s not a strong position for you. If you have reduced side effects in that area, I think (Z)-endoxifen has a lot of promise.

Emily Bodnar, Equity Research Analyst, H.C. Wainwright: Great. How are you thinking about the potential market opportunity there, given currently there’s really nothing on the market and what willingness from patients could look like to take a drug?

Steven Quay, Chief Executive Officer, Atossa Therapeutics: Yeah, so, there’s nothing, but there’s something, if I could. We did some work in the press release and talked about it. 1.7 million women are taking tamoxifen in the three settings of the five years after in adjuvant after breast cancer, the three to five years after DCIS surgery, and the lowest is, you know, 120,000 or so in true prevention in high-risk women. That’s a really big number, 1.7 million. We think that a drug that has much better tolerance in terms of hot flashes will have a real strong market there.

Emily Bodnar, Equity Research Analyst, H.C. Wainwright: Great. How do you think about potential pricing of Zinhoxifen across these different doses, like the lowest dose trials and also high dose?

Steven Quay, Chief Executive Officer, Atossa Therapeutics: Yeah, yeah. We’re all familiar with a new drug in sort of metastatic setting or in a mutation setting where the price will be anywhere from $100,000 per year per patient to, I guess, LSSR came out at $240,000 per year per patient. That is the typical entry point for a metastatic drug. It certainly is not something that would be tolerated in the prevention space. Prevention space can, you know, are typically pricing in the $6,000 a year to $20,000 a year. There was just a paper in the New England Journal on Bayer has a drug for inhibiting the hot flashes from tamoxifen because they know that that’s a legitimate indication. People are saying that that’s going to be $8,000 to $10,000. If you can prevent the breast cancer with a drug that doesn’t have the hot flashes, you don’t need to take their drug.

Emily Bodnar, Equity Research Analyst, H.C. Wainwright: Great. I guess to close out, can you walk us through upcoming milestones and catalysts that we should be looking out for for the next 12 months?

Steven Quay, Chief Executive Officer, Atossa Therapeutics: Yeah, so obviously, there’s a catalyst around the information that we have with the low-dose program in prevention. That’ll come in the December timeframe. That will lay out a series of events that would lead up to a new drug application at some time in the future on that program. We’re working very hard on the high-dose program to prepare the protocol for Project Optimus dose ranging study, getting that into the NDA. We’ll share the details so all of you have clear visibility on that at the time. Filing it into an NDA and then beginning that trial will be a major set of milestones. There’ll be other activities as we look at the full nuts and bolts of what (Z)-endoxifen can do both in prevention and in metastatic. There may be some surprises.

Emily Bodnar, Equity Research Analyst, H.C. Wainwright: Perfect. Thank you very much, Steven. Thanks, everyone, for listening. We’ll conclude the call here.

Steven Quay, Chief Executive Officer, Atossa Therapeutics: Thank you, Emily.

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