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.

Drp1-dependent peptide reverse mitochondrial fragmentation, a homeostatic response in Friedreich ataxia

Johnson J, Mercado-Ayón E, Clark E, Lynch D, Lin H.; Pharmacol Res Perspect. 2021 May;9(3):e00755. doi: 10.1002/prp2.755. PMID: 33951329.

This paper demonstrates that frataxin deficiency causes excessive mitochondrial fragmentation that is dependent upon Drp1 activity in Friedreich ataxia cellular models. Drp1 inhibition by the small peptide TAT-P110 reverses mitochondrial fragmentation but also decreases ATP levels in frataxin-knockdown fibroblasts and FRDA patient fibroblasts, suggesting that fragmentation may provide a homeostatic pathway for maintaining cellular ATP levels. The cardiolipin-stabilizing compound SS-31 similarly reverses fragmentation through a Drp1-dependent mechanism, but it does not affect ATP levels. The combination of TAT-P110 and SS-31 does not affect FRDA patient fibroblasts differently from SS-31 alone, suggesting that the two drugs act through the same pathway but differ in their ability to alter mitochondrial homeostasis. In approaching potential therapeutic strategies for FRDA, an important criterion for compounds that improve bioenergetics should be to do so without impairing the homeostatic response of mitochondrial fragmentation.

Scoliosis in Friedreich's ataxia: longitudinal characterization in a large heterogeneous cohort

Rummey C, Flynn JM, Corben LA, Delatycki MB, Wilmot G, Subramony SH, Bushara K, Duquette A, Gomez CM, Hoyle JC, Roxburgh R, Seeberger L, Yoon G, Mathews KD, Zesiewicz T, Perlman S, Lynch DR.; Ann Clin Transl Neurol. 2021 May 5. doi: 10.1002/acn3.51352. Epub ahead of print.

Well over 90% of early or typical FRDA patients (as determined by age of onset) developed intermediate to severe scoliosis, while patients with a later onset (>14 years) had no or much lower prevalence of scoliosis. Diagnosis of scoliosis occurs during the onset of ataxia and in rare cases even prior to that. Major progression follows throughout the growth phase and puberty, leading to the need for surgical intervention in more than 50% of individuals in the most severe subgroup. The youngest patients appear to delay surgery until the end of the growth period, leading to further progression before surgical intervention. Age of onset of FRDA before or after reaching 15 years sharply separated severe and relatively mild incidence and progression of scoliosis.

A multi-stakeholder multicriteria decision analysis for the reimbursement of orphan drugs (FinMHU-MCDA study)

Fernando de Andrés-Nogales, Encarnación Cruz, Miguel Ángel Calleja, Olga Delgado, Maria Queralt Gorgas, Jaime Espín, Jorge Mestre-Ferrándiz, Alba Ancochea, Rosabel Arce, Raquel Domínguez-Hernández, Miguel Ángel Casado on behalf of the FinMHU-MCDA Group; Orphanet J Rare Dis 16, 186 

(2021). doi:10.1186/s13023-021-01809-1 

To ensure adequate OMP access and reimbursement, it is necessary that decisions be arrived at through a process in which the preferences over the financing criteria are transparent and explicit, in which all types of agents involved in the field of rare diseases are incorporated, and in which practical tools that favor this process, such as MCDA, are applied. From a multi-stakeholder perspective, the financing of an orphan drug will be conditioned by its effect on the health-related quality of life, the degree of its therapeutic benefit, and the availability of other treatment options. The severity of the rare disease for which the OMP is indicated is also relevant, as is the extent to which the treatment can avoid the costs associated with this pathology.

Revisión Bibliográfica: Ataxia de Friedreich y sus manifestaciones cardiovasculares

Santiago Andrés Vintimilla Pesántez; Ocronos. Vol. IV. Nº 4–Abril 2021. Pág. Inicial: Vol. IV; nº4: 150. ORCID: https://orcid.org/ 0000-0003-1450-6128 

El objetivo de esta revisión bibliográfica es informar a la comunidad científica de la presencia de manifestaciones sistémicas, sobre todo cardiovasculares, en la Ataxia de Friedreich; ya que, esta enfermedad no solamente se caracteriza por la presencia de alteraciones neurológicas, sino de afecciones a diferentes aparatos y sistemas del cuerpo humano, como el corazón, debido a la alteración celular que la Ataxia de Friedreich provoca.

LEXEO Therapeutics Announces Upcoming Data Presentations at the American Society of Gene and Cell Therapy (ASGCT) 2021 Virtual Annual Meeting

NEW YORK, April 28, 2021 (GLOBE NEWSWIRE) -- LEXEO Therapeutics, a clinical-stage gene therapy company, today announced upcoming presentations regarding its investigational gene therapy programs at the American Society of Gene and Cell Therapy (ASGCT) 24th Annual Meeting, taking place virtually from May 11-14, 2021. he AAVrh.10 vector is currently being evaluated by LEXEO in pre-clinical studies for the treatment of cardiomyopathy associated with Friedreich’s ataxia (FA). Cardiomyopathy is the most common cause of mortality in patients with FA; it is the cause of death in nearly 70% of the patient population. 

LEXEO plans to initiate a Phase 1 clinical trial of LX2006 in patients with cardiomyopathy associated with FA and expects initial data from the Phase 1 trial of LX1001 in APOE4 associated Alzheimer’s disease in 2021.