Annexin Pharmaceuticals focuses on the development of the biological drug candidate ANXV. The candidate is being evaluated in a Phase II clinical study in the US in the eye disease retinal vein occlusion (RVO), as well as in an imaging study in the same indication in the Netherlands. Since the beginning of the year, the company has also made investments in the cancer area. Read more here. In both RVO and cancer, the candidate has the potential to become First-in-Class, that is, a treatment with a completely new mechanism of action.
Positive initial data
In mid-April, Annexin reported encouraging initial data from the Dutch imaging study SIGHT, to which the company provides ANXV for evaluation in patients with RVO. The study tracks ANXV over time, which is labeled with a fluorescent marker, and can thus be detected by special eye cameras. The results show an accumulation of ANXV in the area of the retinal blood vessels, which is the area of damage in RVO. This provides an important indication that the drug candidate is reaching its target molecule. In addition, the observation showed an overexpression of phosphatidylserine (PS) on the surface of the patient's red blood cells, which provides further support for PS as an underlying disease mechanism in RVO. Read more about RVO here.
The data justify continuation of the study through dose escalations and may guide Annexin regarding future selection of patients in studies with RVO. Recently, Dutch regulatory authorities approved the inclusion of patients with diabetes-related retinal damage, so-called diabetic retinopathy. The study may therefore also provide support for ANXV's potential in this disease. In total, up to 16 patients will be included, and SIGHT is expected to be completed by the end of 2023.
CMO tells more
BioStock got in touch with Annexins CMO/CFO and co-founder Anna Frostegård who told more about the first results and a recent congress he attended.
Anna, you recently presented at the ARVO congress in New Orleans in the USA, tell us a little about this?
– The Association for Research in Vision and Ophthalmology (ARVO) has over 10 members in nearly 000 countries and holds annual gatherings for ophthalmologists, researchers and industry to share the latest research findings and to find innovative solutions in ophthalmology. This year, the congress was held in New Orleans, US and was the first meeting after the pandemic with several thousand participants from all over the world in attendance. It is an honor to be selected to speak about the ANXV program in retinal vein occlusion at such a premiere meeting. We presented the general overview of ANXV's development in RVO, data from our Phase I study, and touched on our ongoing Phase II study.
If we look at the first reported data from the SIGHT study – how important are these for Annexin and ANXV?
– The preliminary results from the SIGHT study through which we are collaborating with partners in the Netherlands are significant for Annexin and the development of our drug candidate ANXV for several reasons.
– First, the results are an important proof of the technical feasibility of this project. Our ANXV was linked to a novel fluorescent molecule, CW800, which was then injected intravenously into a patient with RVO and followed in the back of the eye in real time with a sophisticated eye camera. This has not been attempted before and it is therefore not surprising that we had to optimize our approach somewhat and use e.g. a more sensitive camera to detect the fluorescent signal.
– Second, it is important to see these data as potential evidence that ANXV, when injected intravenously into an RVO patient, actually behaves as a targeting protein, reaching the back of the eye and accumulating where we want it to be – namely at the blood vessels affected by RVO. This is encouraging and supports our ongoing phase II study in patients with RVO.
How do the initial results compare to your expectations?
– Although fluorescently labeled Annexin A5 has been investigated in eye diseases such as glaucoma before, using a so-called DARC technique, there has never been an attempt to study RVO patients. We had expectations that we would be able to visualize ANXV during occlusion and we are pleased that this was possible even with the lowest ANXV dose investigated so far.
– It is also encouraging that an overexpression of phosphatidylserine (PS) on the surface of the red blood cells in the patient in this study is consistent with data from previous independent studies, providing support for PS as an underlying disease mechanism in RVO.
How might the study guide Annexin for future clinical trials?
– The use of labeled ANXV in the SIGHT study is expected to provide us with knowledge and images of ANXV distribution in the back of the eye. Such knowledge may be important for the design of future studies and cannot be generated from our ongoing phase II study, where ANXV is administered without a fluorescent label.
Do you plan to provide more updates from SIGHT during the rest of the year?
– The SIGHT study is an investigator-sponsored study (ISS), which means that the investigators in the Netherlands take sponsorship responsibility for the study while Annexin supports the study by providing ANXV and sharing our knowledge with researchers. It is the sponsor who decides how and when study results are communicated. We look forward to the continuation of this study, as well as data from more RVO patients and at higher ANXV doses. But also that this study will include patients with diabetic retinopathy, which is an important chronic eye disease where ANXV may be of interest in the future. It is important for us to build knowledge and expand the data regarding ANXV in patients, which is crucial to strengthen ANXV's potential. The SIGHT study is expected to contribute to this.