#BIOSPAIN2023 Interview | "The Administration of LAM561 Shows Promising Results in the Treatment of Aggressive Brain Tumors like Glioblastomas"

Glioblastoma stands as the most common and malignant tumor among glial neoplasms. It is a rapidly growing tumor that can manifest at any age but primarily affects adults between 45 and 70 years old. It typically occurs in the cerebral hemispheres, with its localization in the brainstem or spinal cord being less common. Like other brain tumors (except in very rare cases), it does not spread beyond the structures of the central nervous system.

The survival rate for glioblastomas has hardly increased over the past 50 years, underscoring the urgent need to research and develop new therapeutic strategies. Among the latest developments in the fight against the most common and aggressive brain tumor, there is a notable phase III clinical trial for newly diagnosed glioblastoma being conducted by Laminar Pharmaceuticals, a Spanish biotechnology company in the clinical phase focused on developing new therapies for various high-need medical conditions.

The focal point of this research is the compound LAM561 for glioblastoma treatment, currently in phase 3, and it has surpassed recruiting 78 patients for its clinical trial. This accounts for more than 50% of the total required for the final analysis, which is set at 140.

LAM561 is administered orally and, while initially intended for glioblastoma treatment, has shown promising preliminary results that suggest its potential expansion to other oncological indications in the future. Regarding its composition, it is a synthetic derivative of oleic acid that, among other things, does not produce the adverse effects traditionally associated with chemotherapy. The clinical study of LAM561 for glioblastoma treatment is being conducted in various hospitals across Spain, Italy, the United Kingdom, and France.

To learn more about the status of this trial, we spoke with Cati Ana Rosselló, Head of CMC at Laminar Pharma, a Bronze Sponsor of BIOSPAIN 2023, a flagship event in the biotechnology sector.

AseBio. What are the current therapeutic options available for glioblastoma, and what survival rates do they offer?

Cati Ana Rosselló. Unfortunately, for patients, the options have remained largely the same for the past 18 years: radiotherapy and chemotherapy with Temozolomide. This is the standard treatment for newly diagnosed glioblastoma patients.

Despite minor improvements in radiotherapy over this time, the median survival rate remains at 14 months post-diagnosis, just over a year. Moreover, the quality of life is low due to the numerous and bothersome side effects of Temozolomide, which can only be administered for 6 months due to its associated toxicity.

In the United States, some other compounds have been approved for use in glioblastoma, such as Avastin, but unfortunately, it has been observed to only extend the time until disease progression without improving overall patient survival. Currently, in Europe, Optune, a patch-like device that emits electrical fields to the brain, is starting to be used. It appears to offer an additional average survival of 5 months, but it needs to be worn for 18 hours a day, which has implications for quality of life.

AseBio. What is LAM561?

Cati Ana Rosselló. LAM561 is a synthetic derivative of oleic acid. This is the differentiating component of our company: we use lipids as both drugs and therapeutic targets, which is uncommon and seems to yield promising results. LAM561 can be administered orally and has the potential to cross the blood-brain barrier to reach brain cells. This drug alters the composition of the cancer cell's plasma membrane, reducing the activity of membrane-associated signaling proteins known to drive tumor growth, such as Ras, PI3K/AKT, DHFR. The administration of LAM561 shows promising results in the treatment of aggressive brain tumors like glioblastomas.

AseBio. What results have you been obtaining?

Cati Ana Rosselló. We can discuss the results obtained in the two successfully completed clinical trials, the phase 1/2a and the 1b. As for the phase 3 results, even though we hope they will be positive, we cannot provide any details because the study is double-blind, and the first comparative analysis between the placebo and LAM561 will not take place until early 2024.

In terms of safety, LAM561 has proven to be safe so far, with no serious side effects reported at doses as high as 12 grams per day, which is the dose patients in the phase 3 study for newly diagnosed patients are currently taking. We can directly extract the summary of results from the article recently published in the British Journal of Cancer. However, it's important to note that this clinical trial was conducted as a rescue trial in patients with progressing tumors and poor clinical conditions, so we expect better results in newly diagnosed patients.

Overall, the treatment was well-tolerated, with reversible grade 1-2 nausea, vomiting, and diarrhea being the most common treatment-related adverse events (AEs). Four patients experienced dose-limiting gastrointestinal toxicities (DLT) of nausea, vomiting, and diarrhea (three patients at 16g/day and one patient at 12g/day), establishing a maximum tolerated dose of 12g/day. Potential activity was observed in patients with recurrent high-grade gliomas (HGG). Of the 21 HGG-treated patients, 8 (38.1%) had clinical benefit, either partial response or stable disease by RANO criteria, with clinical benefit lasting for at least 6 months in five patients, and one patient showing an exceptional response lasting more than 2 and a half years.

AseBio. The trial's goal is to enroll a total of 140 patients. Where are you currently in terms of recruitment?

Cati Ana Rosselló. Currently, in the study, we have recruited 78 patients, which is over 50% of the target. We are very pleased because recruitment has accelerated considerably in recent months.

AseBio. Do you plan to open the trial to other hospitals in participating countries to expedite patient participation?

Cati Ana Rosselló. In the very near future, another center will be opened in Italy, and we have recently opened two more in the United Kingdom. However, it's essential to consider that having more centers open implies higher costs, so this is something that always needs to be studied in-depth. Nevertheless, we believe that the current recruitment rate is very positive.

AseBio. LAM561 has already received orphan drug designation for glioma treatment from the EMA and the FDA, as well as "Fast-Track" designation from the FDA in August 2022 for glioblastoma treatment. What are the implications of these designations?

Cati Ana Rosselló. Let's start with the orphan drug designation we received first. This designation is granted to drugs with therapeutic potential intended for diseases that affect a very small percentage of the population and have unmet clinical needs. The implications of this designation include cost savings, reduced regulatory and clinical requirements, and the possibility of market exclusivity for 7-10 years after approval, regardless of the patent's lifespan.

As for the Fast-Track designation, its approval means becoming part of a process designed to facilitate the development and expedite the review of drugs intended to treat very serious diseases and demonstrate their potential to address unmet medical needs for such diseases. Very few drugs receive this designation, so it is a source of pride for us. What's most important is what it signifies: the U.S. FDA and Laminar will work closely together to, in case of positive clinical results, expedite the product's arrival to patients as much as possible. In other words, it reduces the final approval time for the compound.

These designations are obtained by indication, in our case, glioblastoma (malignant brain tumors). To obtain them, there must be indications that the applicant compound meets the following conditions:

It can provide therapy with significant clinical benefit if there is none previously available.
It can demonstrate superior efficacy and lower toxicity than therapies already available for treating the disease.
These are two designations that indicate the potential of the compound, which can only be confirmed after the comparative analysis of the phase 3 clinical trial, which will take place in early 2024.

AseBio. LAM561 has shown, in preliminary results, the potential for expanded use in other oncological indications. What might those be?

Cati Ana Rosselló. Again, citing the recently published article summarizing the results of our phase 1/2a clinical trial, LAM561 has shown potential clinical benefit in patients with solid tumors, specifically: mesothelioma, lung metastasis from a bile duct adenocarcinoma, pancreatic adenocarcinoma, metastatic lung adenocarcinoma, and colorectal adenocarcinoma.

AseBio. What does Laminar Pharma expect from BIOSPAIN 2023?

Cati Ana Rosselló. For biotechnology and innovative companies like Laminar, it is crucial to showcase their work and connect with other companies from which they can obtain or sell products or services or simply form synergies. Therefore, BIOSPAIN is key to the development of the entire industry and promotes the necessary shift toward a new business model: leveraging the economic potential of high-quality science conducted in Spain.

We hope to promote and be part of that necessary change.