The third quarter of 2024 was yet another positive and eventful quarter for AlzeCure Pharma. During the quarter, we published and presented new preclinical results with TrkA-NAM ACD137, with positive effects in several different pain models, at the world-leading pain conference IASP. In addition, we had new data on our clinical candidate NeuroRestore ACD856 accepted for presentation at the CTAD Alzheimer’s conference. We also published a new scientific article on NeuroRestore, with a focus on Alzheimer’s treatment. Furthermore, we raised additional capital through a directed share issue, associated with the issuance carried out in May.
During the quarter we shared further preclinical data on ACD856, our clinical drug candidate in the NeuroRestore platform, highlighting its anti-inflammatory and immunomodulating effects. The results indicate that with ACD856, we can also target inflammatory processes that are part of the disease progression in Alzheimer’s and other neurodegenerative diseases. The study was presented at CTAD (Clinical Trials in Alzheimer’s Disease), the world-leading Alzheimer’s conference, held from October 29 to November 1. The study results have also prompted us to expand our collaboration with researchers at Karolinska Institutet. Previous preclinical studies indicate that ACD856 can enhance learning and memory abilities, while the latest results suggest that the drug candidate also has disease-modifying and neuroprotective effects, which are of significant value in treating Alzheimer’s and other neurodegenerative diseases.
During the third quarter we also published a new scientific NeuroRestore article1), focusing on the history, biology and concept underlying the development of a new class of drug substances, Trk-PAM. This unique pharmacological mechanism underlying the NeuroRestore platform allows for multiple indications, such as Alzheimer’s and Parkinson’s disease, as well as depression. ACD856 is a first-in-class drug candidate for Alzheimer’s disease and we are now preparing phase II studies, while also engaging in discussions with external parties regarding potential partnerships or out-licensing.
Alzstatin, our disease-modifying and preventive treatment in tablet form for Alzheimer’s disease, continues to be developed according to plan. The drug candidates in the platform are currently in the preclinical development phase, with preparations underway to enter the clinical development phase. For the further studies we have now chosen to proceed with ACD680 ahead of ACD679, based on an overall assessment of the generated data. Moreover, ACD680 can provide a longer patent term, which is of course also valuable.
The compounds in Alzstatin are gamma-secretase modulators (GSMs), which reduce production of the harmful amyloid-beta-42 protein that generates plaques in the brain. The process is considered a primary cause of Alzheimer’s disease. This new class of Alzheimer’s drugs has received growing attention during the year as the target mechanism has been validated by the Swiss pharmaceutical company Roche, which is also developing GSMs. The company presented positive clinical Phase I data for its GSM, RG6289, and is now preparing a Phase II clinical trial, which has resulted in growing interest in our Alzstatin project from both other pharmaceutical companies and investors.
Alzstatin and NeuroRestore differ from the new antibody drugs in several important respects. Alzstatin is being developed to prevent Alzheimer’s and both drugs are small molecules. The latter means that they can be administered as tablets and they are not expected to cause the side effects associated with existing antibody therapies, such as microbleedings and cerebral edema. NeuroRestore also differs from antibody therapies by potentially enhancing learning and memory functions in patients.
Medical need remains high in the field of Alzheimer’s. Studies show that only five to eight percent1) of Alzheimer’s patients attending memory clinics are suitable candidates for being prescribed the antibody drugs. Taken together, this shows that both NeuroRestore and Alzstatin could be attractive adjuncts or alternatives to antibody therapy, thus fulfilling a high unmet medical need for patients, families and healthcare professionals.
Regarding the Painless platform, which includes the ACD440 and TrkA-NAM projects, we continue to make good progress. With our TRPV1 antagonist ACD440, which we are primarily developing for topical treatment of peripheral neuropathic pain (nerve injury pain), we have previously obtained positive clinical phase II results in patients with chronic neuropathic pain. We have also conducted a Phase Ib clinical trial in nociceptive pain (tissue pain), which, as in the Phase II study in patients, we were also able to reduce by about 50%. The results from our clinical studies have shown that ACD440, a gel that is applied to the skin, demonstrates good suitability for further clinical development.
Neuropathic pain is an area with great unmet medical need, especially with respect to finding alternatives to opioids, and we believe that ACD440 could significantly improve quality of life for patients suffering from this type of pain. Only one of five patients is satisfied with their current treatment. We are now preparing for continued Phase II clinical trials.
Our second pain project, TrkA-NAM, focuses on arthritis of the knee. Over 300 million people suffer from the disease and the patient population is growing due to an aging population and obesity-related problems. The project continues to make good progress, and we have conducted additional preclinical studies with favorable results during the year. Earlier this year, we selected a candidate drug for the project, ACD137, which we then advanced to safety studies. The compound has powerful analgesic effects in several different preclinical models, indicating a wide range of uses for the compound.
ACD137 has previously been shown to have anti-inflammatory effects, which may further strengthen its pain-relieving properties, as well as potentially opening up for other possible indications. In early August we presented new ACD137 data at the IASP World Congress on Pain, which was held in Amsterdam this year. The results we presented show good efficacy in both neuropathic and nociceptive pain, which in turn demonstrates the broad potential of the project.2) Interest in TrkA-NAM has risen as Asahi Kasei initiated a Phase IIb study with its candidate drug AK-1830 last winter. TrkA-NAM is being developed to reduce peripheral NGF signaling and thus pain; because of the selective targeting mechanism of the molecules, TrkA-NAM is expected to maintain the good analgesic effects but without the side effects that NGF antibodies have previously demonstrated. This is validated by new pre-clinical data with ACD137 in a model of osteoarthritis that we reported on in October 2024. The results show significant pain relief in both movement induced and evoked pain as well as a significant anti- inflammatory effect. The analgesic effect of ACD137 is as potent as the effect of the anti-NGF antibody Tazenumab, which has in several clinical trials demonstrated significant and robust pain relief. Treatment with ACD137 resulted in significantly less chondral lesions and prevented deterioration of the articular cartilage and significantly improved a number of cartilage and knee joint structural parameters suggesting a protective effect on knee-joint function in a model of osteoarthritis.
We continue to focus on marketing communications and actively participate in various meetings and congresses to present our research to investors and potential partners. In September, we participated in events such as Nordic Life Science Days, the largest business development and partnership conference in the pharmaceutical industry in the Nordic countries, which was held in Malmö this year. We continue to encounter growing interest from pharmaceutical companies and other stakeholders that may be interested in investing in or in-licensing our development projects, or alternatively in entering into a partnership.
During the quarter, we also raised additional capital associated with the issuance carried out in May. This was based on an agreement that we entered into in the second quarter, but which was only finalized in the third quarter and brought in SEK 3.7 million.
In the third quarter, we continued to make progress in the Alzheimer’s and pain projects with exciting new results that strengthen our position for the future. In collaboration with renowned institutions both in Sweden and internationally, we have generated promising new results in our projects this year, further enhancing our business development opportunities going forward. Backed by these encouraging studies, I look forward to continuing to develop AlzeCure together with our partners and my colleagues.
Stockholm, November 2024
Martin Jönsson