Generation of a Friedreich’s Ataxia patient-derived iPSC line USFi001-A

Mariana Burgos Angulo, Jiajia Yang, Mariana A. Argenziano, Alexander C. Bertalovitz, Maliheh Najari Beidokhti, Thomas V. McDonald; Stem Cell Research, Volume 54, 2021, 102399, doi:10.1016/j.scr.2021.102399. 

We generated an induced pluripotent stem cell (iPSC) line from an FA patient with a homozygous GAA expansion in intron 1 of the FXN gene. The IPSCs display pluripotent cell morphology, expression of pluripotency markers, normal karyotype, and the capability to differentiate into all three germ layers.

Larimar Therapeutics Announces $95 Million Private Placement Financing

BALA CYNWYD, Pa., May 21, 2021 (GLOBE NEWSWIRE) -- Larimar Therapeutics (“Larimar”) (Nasdaq: LRMR), a clinical-stage biotechnology company focused on developing treatments for Friedreich’s ataxia (FA) and other complex rare diseases, today announced that it has executed a securities purchase agreement to raise gross proceeds of approximately $95 million in a private placement financing of common stock.

Larimar intends to use the net proceeds from the private placement to support the clinical development of CTI-1601, for additional research and development and for working capital and general corporate purposes.

Larimar Therapeutics Receives European Medicines Agency Priority Medicines (PRIME) Designation for CTI-1601 in Friedreich’s Ataxia

BALA CYNWYD, Pa., May 20, 2021 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (“Larimar”) (Nasdaq: LRMR), a clinical-stage biotechnology company focused on developing treatments for Friedreich’s ataxia (FA) and other complex rare diseases, today announced that the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) designation to CTI-1601 for the treatment of FA. CTI-1601 is a recombinant fusion protein intended to deliver human frataxin into the mitochondria of patients with FA who are unable to produce enough of this essential protein.

We look forward to CTI-1601’s continued clinical development and to the planned initiations of our Jive open label extension and pediatric multiple-ascending dose trials, which are expected in the second half of the year. 

In addition to PRIME designation, CTI-1601 has also been granted Rare Pediatric Disease designation, Fast Track designation and Orphan Drug designation by the U.S. Food and Drug Administration and Orphan Drug Designation by the European Commission.

Reata Announces that The FDA Has Asked The Company to Request a Pre-NDA Meeting for Omaveloxolone for the Treatment of Friedreich’s Ataxia

PLANO, Texas, May 19, 2021 (GLOBE NEWSWIRE) -- Reata Pharmaceuticals, Inc. (Nasdaq: RETA) (“Reata,” the “Company,” or “we”), a clinical-stage biopharmaceutical company, today announced that it received a communication from the Division of Neurology Products 1 (“Division”) of the U.S. Food and Drug Administration (“FDA”) stating that, after a preliminary review of briefing materials for an upcoming Type C meeting, a pre-NDA meeting is the most appropriate format for a discussion of the development program for omaveloxolone in Friedreich’s ataxia (“FA”). The Division suggested that the Company withdraw the current meeting request for a Type C meeting and instead request a pre-NDA meeting, which the Division will grant upon receipt. The Division asked the Company to focus the new briefing package on questions, issues, and needs applicable to a pre-NDA meeting. As requested by the FDA, the Company plans to withdraw the current request for a Type C meeting and submit a request for a pre-NDA meeting as soon as practicable. 

“We welcome the opportunity to have a pre-NDA meeting regarding our omaveloxolone development program for the treatment of patients with FA,” said Warren Huff, Reata’s President and Chief Executive Officer. “We look forward to working with the FDA on our goal of securing the regulatory review and approval necessary to make omaveloxolone available to patients with FA.”

Reverse phase protein array reveals correlation of retinoic acid metabolism with cardiomyopathy in Friedreich’s ataxia

Jill S. Napierala, Kimal Rajapakshe, Amanda Clark, Yu-Yun Chen, Shixia Huang, Clementina Mesaros, Peining Xu, Ian A. Blair, Lauren A. Hauser, Jennifer Farmer, David R. Lynch, Dean P. Edwards, Cristian Coarfa, Marek Napierala; Molecular & Cellular Proteomics, DOI:10.1016/j.mcpro.2021.100094 

 Among sixty-two fibroblast samples (44 FRDA and 18 controls) analyzed, 30 proteins/phosphoproteins were significantly changed in FRDA fibroblasts compared to control cells (p<0.05), mostly representing signaling molecules and metabolic enzymes. As expected, frataxin (FXN) was significantly downregulated in FRDA samples, thus serving as an internal control for assay integrity. Extensive bioinformatic analyses were conducted to correlate differentially expressed proteins with critical disease parameters (e.g. selected symptoms, age of onset, GAA sizes, FXN levels, FARS scores). Members of the integrin family of proteins specifically associated with hearing loss in FRDA. Also, RPPA data, combined with results of transcriptome profiling, uncovered defects in the retinoic acid (RA) metabolism pathway in FRDA samples. Moreover, expression of ALDH1A3 differed significantly between cardiomyopathy positive and negative FRDA cohorts, demonstrating that metabolites such as retinol, retinal or RA could become potential predictive biomarkers of cardiac presentation in FRDA.

Exicure, Inc. Reports First Quarter 2021 Financial Results and Corporate Progress

CHICAGO & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Exicure, Inc.® (NASDAQ: XCUR), a pioneer in gene regulatory and immunotherapeutic drugs utilizing spherical nucleic acid (SNA™) technology, today reported financial results for the quarter ended March 31, 2021 and provided an update on corporate progress.

Neurology – XCUR-FXN: The Company hosted a virtual R&D Day in January 2021 to discuss progress within its neurology pipeline, which included an overview of the Company’s XCUR-FXN path to clinical validation for the treatment of Friedreich’s Ataxia (FA). During the first quarter of 2021, the Company continued to advance preclinical and IND-enabling studies of XCUR-FXN in FA and disclosed encouraging preclinical mouse data, demonstrating significant upregulation of XCUR-FXN components in the brain and spinal cord. The Company believes these data support the potential for XCUR-FXN as a disease-modifying treatment for the disease. The Company is on track with prior guidance to submit an IND for XCUR-FXN in FA by year-end 2021 and expects to initiate a first-in-patient Phase 1b clinical trial of XCUR-FXN in FA in the first half of 2022.

Toxicity concerns send Larimar down

Evaluate Vantage. May 12, 2021. 

Slightly further behind is Larimar, which yesterday reported phase 1 results with its candidate CTI-1601. Although biomarker data looked promising, the group’s stock sank 36% yesterday on toxicity concerns in non-human primate studies. The company will need to iron out these issues if its asset is to progress. 

Source

We also have conducted several non-clinical toxicology studies, including 28 and 90-day studies in rats and non-human primates, and have an on-going 180- day non-human primate study. In the 90-day non-human primate study a mortality was observed, which was determined to be due to a bacterial meningitis infection and was unrelated to study drug. In addition, mortalities have been observed in the ongoing 180 day-non-human primate study at the highest dose levels. We have informed FDA of these findings and we are continuing to dose non-human primates in the study and are continuing to collect and evaluate data. While additional non-clinical information may be required before we initiate further clinical studies, based on all the information we have from the non-clinical program to date together with extensive input from toxicologists and other relevant experts, we currently expect to remain ontrack with our previously disclosed timeline of initiating both our open-label extension (the JIVE trial) and a pediatric MAD trial in Friedreich’s ataxia patients during the second half of 2021.

Larimar Therapeutics Reports Positive Topline Phase 1 Clinical Trial Data Showing Dose-Dependent Increases in Frataxin Levels in Patients with Friedreich’s Ataxia

BALA CYNWYD, Pa., May 11, 2021 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (“Larimar”) (Nasdaq: LRMR), a clinical-stage biotechnology company focused on developing treatments for Friedreich’s ataxia (FA) and other complex rare diseases, today announced topline data from its Phase 1 multiple ascending dose (MAD) clinical trial (n=27) evaluating CTI-1601 as a treatment for FA.

FXN Change from Baseline in Buccal Cells Units: pg FXN / μg total protein Data presented as: n median (25th percentile, 75th percentile)
Dose Group	Day 4/7*						Day 13
Placebo (n=7)	-0.03		(-0.18, 0.97			)	0.35		(-0.02, 0.46	)
Cohort 1 Active (25 mg, n=6)	0.39		(0.01, 0.72			)	0.92		(0.48, 0.94	)
Cohort 2 Active (50 mg, n=6)	1.28		(1.09, 1.69			)	0.39		(0.35, 1.08	)
Cohort 3 Active (100 mg, n=7)	3.06		(1.70, 4.16			)	2.64		(1.93, 3.99	)
FXN Change from Baseline in Skin Biopsies# Units: pg FXN / μg total protein Data presented as: median (25th percentile, 75th percentile)
Dose Group	Day 4/7*						Day 13
Placebo (n=7)	N/A						0.92		(0.10, 1.17	)
Cohort 1 Active (25 mg, n=6)	N/A						0.87		(-0.07, 1.69	)
Cohort 2 Active (50 mg, n=6)	N/A						2.82		(1.93, 4.01	)
Cohort 3 Active (100 mg, n=7)	N/A						10.6		(7.20, 18.1	)
FXN Change from Baseline in Platelets Units: pg FXN / μg total protein Data presented as: median (25th percentile, 75th percentile)
Dose Group	Day 4/7*				Day 13
Placebo (n=7)	-0.38	(-1.23, 0.60		)	-0.65			(-1.71, 1.03		)
Cohort 1 Active (25 mg, n=6)	-0.15	(-2.18, 0.60		)	-0.53			(-1.01, 0.80		)
Cohort 2 Active (50 mg, n=6)	0.30	(-0.18, 0.75		)	-0.87			(-1.14, -0.70		)
Cohort 3 Active (100 mg, n=7)	2.54	(2.27, 2.70		)	3.55			(2.71, 4.93		)

Larimar Therapeutics Reports First Quarter 2021 Operating and Financial Results

BALA CYNWYD, Pa., May 10, 2021 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (“Larimar”) (Nasdaq: LRMR), a clinical-stage biotechnology company focused on developing treatments for complex rare diseases, today reported its first quarter 2021 operating and financial results. “Our Phase 1 program in Friedreich's ataxia (FA) made strong progress over the past few months and we will be announcing topline data from the program tomorrow,” said Carole Ben-Maimon, MD, President and Chief Executive Officer of Larimar. “In addition to safety and tolerability findings, the upcoming announcement will include pharmacodynamic data assessing frataxin levels in buccal cells, skin, and platelets. These data provide important insights that we expect will inform CTI-1601’s further development, as FA is caused by patients’ inability to produce sufficient amounts of frataxin and CTI-1601 is the only drug candidate that we are aware of in clinical development that is designed to address the root cause of the disease by delivering this crucial protein to patients.” 

Upcoming and Anticipated 2021 Milestones 

Announce topline data from placebo-controlled, Phase 1 program in FA patients on May 11, 2021 

Initiate Jive open-label extension clinical trial: expected in 2H 2021 

Initiate Multiple Ascending Dose (MAD) trial in patients under 18 years of age: expected in 2H 2021

Reata Pharmaceuticals, Inc. Announces First Quarter 2021 Financial Results and Provides an Update on Clinical Development Programs

May 06, 2021, Source: Reata Pharmaceuticals, Inc. 

Data from the registrational Part 2 portion of the MOXIe Phase 2 trial of omaveloxolone in patients with FA (“MOXIe Part 2") and the open-label extension study (the “MOXIe Extension”) were analyzed in additional exploratory analyses (the “Delayed-Start Analyses”), whereby parallel trajectories between the patients randomized to placebo (placebo-to-omaveloxolone group) and those randomized to omaveloxolone (omaveloxolone-to-omaveloxolone group) in the double-blind period from MOXIe Part 2 through 48 weeks in the MOXIe Extension could provide evidence of disease-modifying activity. A total of 73 out of 75 (97%) patients without pes cavus who completed MOXIe Part 2 enrolled in the MOXIe Extension. 

The FDA has granted us a Type C meeting, which is scheduled to occur in the second quarter of 2021, to discuss the Delayed-Start Analyses and the FA development program. We plan to initiate a second pivotal study in the fourth quarter of 2021, incorporating input from both the FDA and the European Medicines Agency into the protocol before we initiate enrollment.