$Larimar Therapeutics (LRMR.US)$ Friedreich's ataxia The com...

The company's raison d'être is nomlabofusp, a recombinant fusion protein by subcutaneous injection aimed at delivering the mitochondrial protein furataxine [FXN] to patients suffering from FA.

FA is a fearsome single autosomal recessive progressive disease, and 95% of cases are the result of homozygous guanine adenine [GAA] triplet repeat expansion in the 1st intron of the FXN gene on chromosome 9 encoding FXN.

Symptoms typically appear around puberty. There are walking difficulties, sensory impairment in hands and feet, scoliosis, hearing and vision loss, diabetes, etc.

In early adulthood, most patients live in a wheelchair, and it is common for people in their late 30s to die due to hypertrophic cardiomyopathy (60%). According to Biogen (BIIB), around 8,300 people are suffering in the US and around 7,600 people in Europe.

The number of repeats ranges from up to 30 GAA triplets in healthy people to ~300 to 1,000 or more in FA patients, reducing the ability to produce FXN protein, and as a result, levels are approximately one-quarter of normal values.

Interestingly, heterozygous carriers usually have FXN levels that are half normal and function asymptomatically. In other words, less than twice as much FXN protein may be all necessary to provide therapeutic effects.

Larimar is tenaciously trying to continue developing Nomura Bofusp. The ordeal began in May 2021.

After obtaining reliable top-line results in phase 1 clinical trials, deaths were reported in primates other than humans at the highest dose level of a 26-week preclinical trial designed to support long-term administration to humans, so this program was put on clinical hold by the FDA.

In human trials, nomlabofusp was 100 mg once a day, with no serious adverse events [AES] when administered for up to 13 days, there were no dose-dependent AEs, and tolerability was good.

After submitting a complete response and a plan for a low-dose phase 2 trial, the FDA transferred complete clinical hold to partial clinical hold and limited the dosage to 25 mg. Larimar then completed a 4-week phase 2 trial (n=13) in 2023/5, and submitted a complete response to partial suspension one month later. In 2023/7, the FDA gave the go-ahead for the 50 mg administration cohort (n=15) of the same trial.

In 2024/2, the company announced top-line data for this trial, and it was revealed that FXN concentration increased in a dose-dependent manner when administered every other day until the 28th day after 14 days of daily administration. In phase 1 and phase 2 trials, nomrabovspp was injected into 46 patients, and 44 completed their respective trials. Of the 2 cases that dropped out, 1 case (50 mg) was due to mild to moderate nausea and vomiting, and the other case (25 mg) was due to an allergic reaction, but it disappeared after treatment.

Larimer will then begin administration to patients in 2024/3 as part of an open-label extended (OLE) phase 2 trial, and 25 mg of nomura bovspp will be administered once a day to participants in the phase 1 or phase 2 trial for at least 1 year. Interim data will be announced in 4Q24.

On 2024/5/20, the FDA lifted some clinical holds on Nomlabofusp, and the company finally received the news it had been waiting for. Larimar has discussed with the FDA and intends to begin a placebo-controlled registration test for children aged 2 to 17 using the FXN value as a surrogate endpoint, supports early approval of the 50 mg dose, and wants to apply in the second half of the year 25. It is unclear when the test will begin, but it is necessary to do it as soon as possible in order to make BLA application targets realistic. Nomlabofusp has received rare disease drug, rare pediatric disease, and fast track designation from the FDA, and has received rare disease drug and PRIME designation in the EU.

While the market yawned at the announcement that the hold was lifted, LRMR's stock price rose 9% to 7.89 dollars due to subsequent transactions, but then retreated to 7.10 dollars in 6 business days. What actually worked (34% increase in the past 4 sessions) was after announcing in the 2024/5/30 press release that Nomlabofasp had been selected as part of an FDA testing program designed to accelerate the development of rare disease therapeutics with unmet medical needs. Programs such as Operation Warp Speed for rare disease drugs are called START. It is unclear what impact it will have on the company's registration tests and schedule.