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224. Bull, Bear & Beyond – Oryzon Genomics: executive interview
1 Plays3 seconds ago
In this interview, we speak to Carlos Buesa, CEO of Oryzon Genomics, with a focus on the company’s top strategic priority, iadademstat, in first-line acute myeloid leukaemia (AML). We discuss the drug’s mechanism of action, Oryzon’s ongoing clinical programmes in AML – particularly in the first-line setting – and the interim data due to be presented at the EHA conference in June. We also explore the key unmet needs in first-line AML and how iadademstat is positioned to address them, as well as the broader opportunity for the drug, including its potential in sickle cell disease. Finally, we discuss the key expected milestones and next steps for iadademstat through 2026 and into 2027.
Oryzon Genomics is a Spanish biotech focused on epigenetics. Iadademstat is being explored for haematology-oncology, where the strategic priority is in first-line AML; there is potential for an accelerated approval pathway should clinical data continue to be supportive. It is also being evaluated in other indications, such as myelodysplastic syndrome, myeloproliferative neoplasms and sickle cell disease, as well as in small cell lung cancer. Central nervous system asset vafidemstat has completed a Phase IIb trial in borderline personality disorder and preparations are underway for Phase III. It is also currently involved in a Phase IIb trial for schizophrenia, and management is preparing for an additional Phase II trial in autism spectrum disorder.
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Transcript
Interview with Carlos Buesa
00:00:07
Speaker
Hello and welcome to this Edison TV interview where we're speaking with Carlos Buesa, CEO of Horizon in Genomics. Welcome, Carlos. Thank you. Good morning, Aaron. We're going to focus today on Yadademstat, the company's lead asset in hematological diseases.
Yadademstat Overview and Mechanism
00:00:22
Speaker
So Carlos, to jump right in, could we start with a summary of the mechanism of action of YADA?
00:00:27
Speaker
Certainly. Yadademstat, YADA as a nickname, it's easier, is a potent and selective LSD-1 inhibitor for oncology and hematology. Well, the function of LSD1 is a master, it's an epigenetic enzyme, which is basically a master gene in controlling gene expression. But it's also key to maintain the leukemic stem cells alive ah in an undifferentiated and proliferative state, the cancer cells.
00:00:55
Speaker
So when we inhibit LSD1, YADA basically promotes the differentiation of malignant myeloid cells to more differentiated status, which can enter into apoptosis. So it's a pro-apoptotic drug in that sense, but also it's acting as a synthetic lethality agent in leukemic stem cells.
00:01:17
Speaker
So we also know that they enhance synergistically sensitivity to our standard AML therapies and enhance enormously the immune response. So this is basically the mechanism of action of Yada and Stat.
Yadademstat's Unique Mechanism
00:01:30
Speaker
But i I would like to add that um beyond that, one thing which is particularly attractive is that Yada and Stat, because of this mechanism of action, is mutation agnostic and is not restricted to a single molecular subtype.
00:01:45
Speaker
um This clearly differentiates YADA from more mutation-specific approaches, like many inhibitors, for instance, or other ah like FLIF3 inhibitors, which are primarily targeting defined genetic AML subgroups.
00:02:02
Speaker
Excellent. So we've set the scene just
Clinical Programs in AML
00:02:04
Speaker
there. Could we move on now to an outline of the current clinical programs in AML, and particularly frontline AML, and encouraging interim data due to be presented at the EHA conference this June?
00:02:15
Speaker
Yeah, we have a dense pipeline in onchomatology, in second line, in MDS, in milop proliferative neoplasm. But certainly the key driver a program right now is in first line newly diagnosed AML patients in combination with Veneza.
00:02:34
Speaker
These programs that we call ALICE2 to differentiate from ALICE1 that we did in the past where we and ah treat the same population with only EISA is basically providing really highly encouraging data.
00:02:49
Speaker
We have reported at EHA in ah the cutoff data of the abstract presentation, 100% overall response rate and 93% composite complete remissions.
00:03:06
Speaker
So that also with a very high level of transitions to human stem cell transplantation. So we are presenting in a four weeks from now in Stockholm at EHA data, which will include more patients, a longer follow-up than in the AstraZeneca, obviously.
00:03:24
Speaker
So we are really excited. We expect that the data is going to be at least as compelling as the one that we have at BANCE, and hopefully more. And um this is something which is important because at EHA we are going to present data of approximately 75 80 percent of the whole plant LH2 recruitment, which is making this data, we think, a meaningful interim readout rather than an early signal from only a few patients.
00:03:55
Speaker
So um we see that this combination that we are proposing right now is very competitive versus other emerging triplets like many inhibitors or antibody-based approaches.
Yadademstat's Efficacy in AML
00:04:08
Speaker
Because and it basically has a broader applicability in terms of the, as I said, is is basically working in virtually any AML patient, stronger response rates so far, and a more favorable tolerability profile. So we are really excited excited about this ah and program, Alistud, that, as I said, is the key value driver for the program and right now. Fantastic. So take it a step back now.
00:04:35
Speaker
Could you summarize the key unmet needs in frontline AML and then how iDADAMSTAT is positioned to address these? Well, I mean, I think that we we need to remember, all of us, that one third of the patients that are currently treated with the currently current standard of care are not responding, are refractory to this. So one third of the patients cannot benefit already from from the current armamentarium.
00:05:03
Speaker
On top of that, um we are um proposing, well, we are so and we are basically showing here 100% of responses. So this third of patients, which are unfortunately not responding to the current standard of care, are responding to our word triplet.
00:05:23
Speaker
But on top of that, those ah cohorts of suit populations of AML patients, which are um really responding very poorly or at all to the current standard of care, like P53 mutant patients, like patients, like mielomonocytic leukemias.
Market Potential and Survey Results
00:05:43
Speaker
All these patients are responding and very well to the to our our drug, as we saw in ah an earlier trial, ALICE1, where we saw that we were able to double the median overall survival of TP53-mutated patients, and we were having 100% of responses in NRAS, KRAS patients. So um this creates a really strong clinical proposition.
00:06:15
Speaker
YADA could become a broadly applicable AML triplet with a particular value particular value in high-risk patients, like the the ones I mentioned, the high-risk P53 and also the intermediate risk in RAS, K-RAS patients.
00:06:31
Speaker
where regulatory and commercial opportunity are especially compelling. We have done a market survey, a market access survey with KOLs and payers in the US, and we have seen that they they anticipate a very good receptivity on this positioning.
00:06:51
Speaker
And because of the extremely um high and met medical need, particularly in P53, good flexibility for a high price and peak sales that will go north of $1 billion dollars only in the US.
Exploration of Other Diseases
00:07:06
Speaker
Excellent. So looking beyond AML now, could you outline for us the broader opportunity for the drug candidates, for example, in sickle cell disease? Sure, um but um before we go to that, which is also a very compelling and fascinating proposition, let me insist that thanks to the greater agreement that we have with the National Cancer Institute and with the agreement that we have with several um and prestigious universities in the U.S. We are also exploring Melody's platyce syndrome. We are also exploring meloproliferative neoplasms.
00:07:42
Speaker
We are also exploring a small cell lung cancer, but there are to currently two um two clinical trials going on, one which is being led by the Memorial Sloan-Kathrin Center, the second is being led by the Yale University. So, I mean, really, YADA is being explored in a very broad um landscape in oncologic indications.
00:08:07
Speaker
On top of that, we believe that there is um a very strong opportunity in sickle cell disease. Sickle cell disease is is well known. It's caused by a mutation on the hemoglobin gene.
00:08:19
Speaker
And um and um we know because there are beautiful examples of human genetics in in Saudi Arabia. we We know that there is a population which are carrier for this mutation, yet they don't develop the disease because there are other mutations which are suppressing and the phenotype of the primal.
00:08:37
Speaker
primary mutation on the beta-Amolevic gene. um And this is basically producing an overexpression of fetal hemoglobin. So we know we have data with our compounds that in rodents, in monkeys, we are able to overexpress the fetal hemoglobin. And we are also starting right now a clinical trial in sickle cell disease here in Europe.
00:09:01
Speaker
So we think that over the next quarter, we might have ah an idea on how this this program could be also being advanced.
Key Milestones for Iodadamstat
00:09:11
Speaker
for So to wrap up, what are the key expected milestones and next steps for Iodadam stats for throughout 2026 into Yeah, as I say, the key driver programs is Alice 2 in first line AML. So ah very easy for the investors, very easy for the for the community.
00:09:32
Speaker
They have to be to stay tuned on the data that we are going to present in four weeks, to stay tuned on the data that we are going to present at ASH, where we expect to present virtually the final results of this study.
00:09:46
Speaker
Following that, we are expecting to go to the FDA to propose a seamless Phase 2-3 program, our already named ALICE3, which we want to focus on these specific populations, P53, mutant patients, NN-RAS, K-RAS, mielomonocytic leukemias.
00:10:06
Speaker
um This is a design that has been followed by ah by others, by many inhibitor developers, for instance. So we are not inventing the wheel here. We expect that the regulators are going to ah to note on this proposition.
00:10:23
Speaker
And the company goal would be to initiate this study at least three in the first half of 2027. ah Given the unmet medical need, particularly in B53, we anticipate that we could complete the recruitment in only 24 months.
00:10:38
Speaker
And if the data of ALICE3 remain as strong as the data that we have been producing so far, we think that that could support a potentially accelerated approval strategy.
00:10:51
Speaker
So that would basically transform Horizon from a clinical late clinical development company to a company with a tangible path forward towards registration and commercialization. So I think that, yeah, the next months can be transformational for Horizon. And I think that these are the more basically valuable inflection points that we will expect.
Future Insights and Conclusion
00:11:18
Speaker
Looks like an exciting and few years ahead for Horizon.
00:11:22
Speaker
That brings us to a close for today. But if our audience would like to learn more, we direct them to the Edison website where our research is freely accessible. Carlos, thanks for the insightful discussion today. Thank you very much, Aaron. It has been a pleasure as always.
00:11:34
Speaker
Likewise.