All right, everyone. I am now joined by Marc Le Bozec, CEO of OSE Immunotherapeutics. OSE is a French clinical-stage company in immuno-oncology and immuno-inflammation. Its lead asset is the IL-7R targeting antibody, lusvertikimab. It also has a cancer vaccine in non-small cell lung cancer called Tedopi. Marc, thanks for being here. Introduce the company and tell us how should a U.S. investor think about OSE.
Thank you for the opportunity. Hello, everyone. OSE is an old French company. It is more than 15 years. It is the outcome of a merger between two small companies that went public on Paris stock market in 2015. It has a very special profile because this is a very mature company at clinical level. We had one product that has delivered positive readout in phase II in ulcerative colitis last year. We have a product which is in a registrational phase III, which is about to be, let us say, going to the finish line within few weeks now, in non-small cell lung cancer. We are very immature at financial level, because the company has made only two financing rounds since inception, one at the IPO, in 2015, and one in 2021. The outcome of that is that we have almost only retail shareholders, only French retail shareholders.
We are here with Thomas Gidoin, my CFO and Deputy CEO, to attract U.S. investors to make it a company visible in the financial community and go to the next level.
Well, let us talk about lusvertikimab. In ulcerative colitis, your placebo-adjusted remission benefit was about 12 points, but in biomarker positive patients, it was 46, and in biomarker negative patients, nothing at all. Tell us about that biomarker.
Yeah, this biomarker is a great promise. It is based on a series of parameters, clinical, histological, transcriptomic. It has the potential to become an entry point for further clinical development. We must confirm that in further clinical trials, which will be the case in the next clinical trial we are about to incept in a smaller indication called chronic pouchitis. We will use this biomarker as a secondary endpoint, but yes, it potentially represents 30%-40% of the global UC population.
That subgroup was 22 patients on drug and eight on placebo. The biomarker came out of that. What does a partner need to see before that number is worth anything?
We believe at this stage that we probably need 100 more patients. With the next clinical trial, we will have about 50 more patients. In the next phase II-B/III trial for ulcerative colitis, we will use it primarily as a secondary endpoint to confirm, hopefully, that this is a consistent biomarker for the future.
Okay. Very good. You hinted at the next step for lusvertikimab, not UC, but chronic pouchitis. About 45,000 patients with no FDA-approved biologic. Why go there first?
This is a subset of ulcerative colitis. First, we know that our compound works in IBD, in particular in ulcerative colitis. There is a strong rationale at scientific level with a high expression of IL-7 receptor, and pretty much the same inflammatory pattern as in ulcerative colitis. On top of that, there is no FDA-approved drug for the moment. There is one drug which has been approved in Europe, which is vedolizumab by Takeda, called Entyvio commercially. There is a great opportunity there. On top of that, we have, thanks to our presence in IBD for a while now, we have a strong network of KOLs that helped us building up the designing the new clinical trial on 47 patients. Even more than that, we already have identified some patients for this further clinical trial.
It was the idea also to harness the GMP material that we still have with lusvertikimab IV. We will go further with lusvertikimab in ulcerative colitis, but subcutaneously. We are preparing a subcutaneous formulation that will be clinically validated in June 2027. We still have some material, GMP material, of IV formulation of lusvertikimab, and that was a great opportunity to use this material.
Was there anything else about that asset that you think investors might be overlooking or missing?
Yeah. We are also investigating other indications. Of course, many investors and big pharmas are asking us for additional data in dermatology, as an example. We are gathering data at the preclinical level on this. On top of that, what we are working on is on combination with other existing mechanism of action, typically anti-IL-23, JAK inhibitors. We have found some intellectual property on this because we have demonstrated that we have some synergistic effects in combination with our compound.
Okay. Let's switch gears and talk about your other asset, Tedopi. It has already won one phase III in second-line lung cancer, with median survival 11.1 months against 7.5 in patients who had progressed after a checkpoint inhibitor. Tell us what your plan is for running another trial.
First it was in third line, the first phase III. This is not fashionable for the moment here in the U.S., those cancer vaccine, I regret that. Some are fashionable or is not. We have treated more than 800 patients so far in series of clinical trials. We made a beautiful announcement on Monday that an additional trial, phase II on 106 patients, read out positively with a doubling of survival in non-small cell lung cancer, second line as a combination with nivo and/or chemo, versus chemotherapy as a standalone. We need to have this additional data in our phase III, which is a registrational phase III, both in the U.S. and in Europe on 363 patients, where we have recruited ca. 260 patients so far. We are going close to the finish line. We will have a readout early 2028.
We had to postpone the futility analysis because this is an event-driven trial. Unfortunately, each event is a death, as you can imagine, in non-small cell lung cancer with metastasis. We have way less death than anticipated. That is the rationale for us to postpone early 2027, the next futility analysis.
Tedopi is a subcutaneous injection, and the comparator is intravenous chemotherapy. How much of a difference does that make to a second-line lung patient?
At this stage, it doesn't make any difference because this is a fantastic hope for patients to extend their survival with a better quality of life. Knowing if it will be IV or subcutaneous is not of the essence at this stage. Still, the way we give it to patient is subcutaneously, but we monitor them for a few hours, four hours to be more precise, to prevent CRS, those terrible events that we can monitor, and we can address rapidly if they are in a hospital environment. That's what we do for the moment. In the future, we anticipate that with the numbers that we have now gathered on more than 800 patients, there will be less monitoring on patients. But for the moment, we try to be very cautious and close to them.
Okay. The sub-q isn't the difference-maker for now, but fair enough. But three academic groups are running phase IIs of Tedopi in three different tumors, two already positive, and you didn't have to pay for any of that. What does that model give you?
We pay something because we provide with the Tedopi, we provide the drug itself, so it comes at a cost for us. But of course, it's a very good way to make it more popular in the clinical community. They're very enthusiastic, very supportive. We made a webinar last June with Stephen Liu of Georgetown University, with Benjamin Besse and Alexandra Leary of Institut Gustave Roussy. They're super positive with this compound. There will be a presentation at ESMO on Sunday by Federico Cappuzzo of Istituto Nazionale Tumori Regina Elena, who run Combi-TED, this trial on non-small cell lung cancer. The model is that they want to improve the way patients are treated. That's what happened with TEDOVA that has been presented orally at ASCO this year. For Combi-TED, that will be presented orally at ESMO on Sunday.
Then, of course, if we want to move forward, we have the capacity to repurchase, let's say, or purchase the data still down the road. The compound is our compound, and that's our property. If we want to commercialize it, that will be our take.
You've noted that adding pembrolizumab increased adverse events, including immune-related events. What did the combination cost you on tolerability?
The combination is showing more severe effects than Tedopi as a standalone, but it's manageable at this stage. Once again, when you look at the profile of those patients in ovarian cancer, in non-small cell lung cancer, once again, it's a hope for them to extend their life in better conditions that with chemotherapy as a standalone. As you know, it's terrible for them. We observe more side effects, whether with PD-L1 or with chemotherapy as a combination with Tedopi, more than with Tedopi by itself. But we also provide them with some fantastic hope to have a few months with their family, with their friends. That's what we can say today.
Okay. Let's shift gears a little more and just talk about the balance sheet. You ended June with EUR 11.1 million, and runway was stated through December. Your last equity raise was in March 2021, five years funded on partnership money. Where do you stand with financing right now, and what's your strategy?
The company historically has been financed mostly through partnerships. That was the beauty of these founders, who have gathered south of $200 million in partnership with J&J, Boehringer Ingelheim, AbbVie, and so on. They made only two financing rounds, which is very peculiar in that context. Yes, we disclosed that we have a cash runway, which is within the next few months, weeks. Obviously, we're contemplating attracting some investors, in particular in the U.S., and hence our presence today.
Understood. We are coming up close to the end of our time. Marc, for the investors who are hearing about OSE for the first time today, what should they take away from this conference?
As a veteran of the European biotech industry, it is very rare to see such a mature company, clinically speaking, with phase II data, phase III data, with a market cap of EUR 50 million, five zero, with no institutional shareholders. That is the beauty of what the founders succeeded in building up over the years. But now if we want to move forward, we need to have institutional investors on board becoming institutional shareholders to lead the company to the next stage, which could be eventually a dual listing here on the Nasdaq.
Okay. Marc, thank you so much for joining us.