C1 Esterase Inhibitor (Human) (ViroPharma)

The FDA has signed off on three drugs in the last two months to treat the rare genetic condition hereditary angioedema. The newest to come online is Ionis Pharmaceuticals' Dawnzera. Since 2008, the FDA has approved 11 treatments for a rare genetic condition called hereditary angioedema (HAE), three of which have occurred in the last two months.The latest drug to join this cohort of medicines arrived Thursday with the FDA approval of Ionis Pharmaceuticals’ Dawnzera (donidalorsen). Despite entering a competitive, crowded market, it shouldn’t be difficult for Dawnzera to differentiate itself. As the first RNA-targeted treatment for HAE, it is a first-in-class therapy and further distinguishes itself with its dosing schedule and ability to be injected at home.The U.S. regulator has signed off on Dawnzera for prophylactic use by those age 12 years and older to reduce the likelihood of the sudden, unpredictable episodes of severe swelling in the limbs, face, abdomen and larynx that characterize HAE. The disorder, which affects 7,000 people in the U.S., can be fatal when it strikes the airways and inhibits breathing.Dawnzera was designed to target plasma prekallikrein, a protein that activates inflammatory mediators associated with acute attacks of HAE.Paving the way for approval was a phase 3 trial in which Dawnzera reduced the HAE attack rate by 81% compared to placebo over 24 weeks. The attack rate reduction increased to 87% when measured beyond the second dose of Dawnzera.Dawnzera is the third in a run of recent approvals that give patients new options to combat the disease. The products will take on Takeda’s blockbuster standard of care, an injected treatment called Takhzyro, and BioCryst Pharmaceuticals’ fast-rising oral challenger Orladeyo.“Orladeyo has less benefit than Takhzyro, with respect to reducing attack rates, and it has tolerability issues, particularly (gastrointestinal) because it is oral,” Ionis CEO Brett Monia, Ph.D., said in an interview with Fierce. “With those two drugs alone, we’re seeing that patients are switching from one drug to another trying to get a better treatment. My point is—they’re unsatisfied.”Last month, the FDA endorsed Ekterly, the first approved product from small Massachusetts biotech KalVista Pharmaceuticals, which has become the first oral on-demand medicine to address the symptoms of HAE, while others are delivered by intravenous or subcutaneous administration.Adding to the competition in the HAE prophylactic space is CSL, which scored a June FDA nod for Andembry, a self-administered prefilled pen. The treatment is dosed monthly and inhibits factor XIIa, a plasma protein that plays a key role in triggering the swelling episodes.“It’s a quite different mechanism of action, with respect to the targets its going after—we’re targeting RNA, they’re targeting a protein with an antibody,” Monia said of Andembry. “It looks like a good drug. We think donidalorsen has an overall profile that will be more attractive to many patients.” CSL will be a formidable rival as it has vast experience in the HAE space. Its drugs Berinert and Haegarda, which were approved in 2009 and 2017, respectively, were the premier HAE treatments before Takhzyro became a blockbuster in 2022.Ionis believes Dawnzera’s advantage is in its dosing regimen, which calls for patients to begin with one injection every four weeks, with an option to switch to dosing every eight weeks. In an extension study of Ionis’ phase 3 trial, eight-week dosing performed at the same level as four-week dosing, limiting swelling episodes by 94% versus placebo.Meanwhile, Takhzyro starts patients on a two-week dosing schedule, with the option to switch to every four weeks. Andembry follows a monthly dosing regimen.Ionis will charge $57,462 per dose, which works out to a $747,000 price tag for annual injections, assuming a patient stays on the four-week schedule. While the annual pricing exceeds that charged by Takeda and CSL for their prophylactic treatments, it will be significantly less for patients who shift to the eight-week dosing plan.“We’re right in line with where the market is today,” Kyle Jenne, Ionis’ chief global product strategy officer, said during a post-approval webcast Thursday. “We expect the majority of (physicians) to start patients at every four weeks and then if they’re performing well and are well controlled, they could potentially have the option of moving them to every eight weeks. We’ll have to see what that split looks like over time.” Ionis also pointed to a switch cohort in its phase 3 study that evaluated the performance of Dawnzera in patients previously treated with Takhzyro, Orladeyo or Takeda's C1 inhibitor Cinryze. In switching to Dawnzera, patients reduced their mean HAE attack rate by 62% from prior prophylactic treatment over 16 weeks, with no mean increase in breakthrough attacks observed during the switch.Additionally, a total of 84% of patients surveyed preferred Dawnzera over their prior prophylactic treatment, citing better disease control, less time to administer and less injection site pain or reactions.The switch data are not included on Dawnzera’s label but will “remain important for Ionis’s messaging on market positioning and reimbursement,” according to William Blair analyst Myles Minter, Ph.D.“Overall, we see Dawnzera’s profile as superior to current prophylactic options, with less frequent dosing and at-home auto-injector dosing being further differentiators. We also view Dawnzera’s profile as comparable to CSL Behring’s Andembry,” Minter added in an Aug. 21 note.

First patient dosed in open label extension (OLE) study with 25 mg daily dosing of nomlabofusp; interim data on track for Q4 2024 Positive top-line Phase 2 dose exploration study data demonstrated nomlabofusp was generally well-tolerated with dose-dependent increases in tissue frataxin levels, reinforcing therapeutic potentialBiologics License Application (“BLA”) submission targeted for 2H 2025; discussions initiated with Food and Drug Administration (“FDA”) on potential to pursue accelerated approval pathwaySuccessful $161.8 million financing strengthens cash, cash equivalents, and marketable securities to $239 million as of March 31, 2024, extending projected cash runway into 2026 BALA CYNWYD, Pa., May 09, 2024 (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 2024 operating and financial results. “We have started 2024 off strong, achieving critical milestones that support late-stage advancement of our nomlabofusp clinical program. Positive Phase 2 dose exploration study data demonstrated that nomlabofusp appears to be generally well-tolerated, and observed dose dependent increases in tissue frataxin levels that have the potential to address the underlying frataxin deficiency that is the root cause of Friedreich’s ataxia (FA). In March, we dosed the first patient in our OLE study and continue to enroll patients and activate additional sites. We are on track to report interim data in the fourth quarter of the year which will inform on the long-term safety and tissue frataxin levels of nomlabofusp,” said Carole Ben-Maimon, MD, President, and Chief Executive Officer of Larimar. “Together, these datasets will help support our BLA submission which we are targeting for the second half of 2025. We are continuing our regulatory discussions with the FDA on the potential use of frataxin as a novel surrogate endpoint to support accelerated approval and are planning for a global double-blind placebo-controlled confirmatory study which we expect to initiate prior to BLA submission. With our recent capital infusion and runway extended through key registrational catalysts, we are well positioned to further advance the first potential therapy to increase frataxin levels in patients with FA.” Recent Highlights In February 2024, Larimar announced positive top-line data and successful completion of its four-week, placebo-controlled Phase 2 dose exploration study of nomlabofusp (CTI-1601) in patients with FA. Nomlabofusp was generally well-tolerated throughout the four-week treatment periods, had a predictable pharmacokinetic profile, and led to dose-dependent increases in frataxin in skin and buccal cells after daily dosing for 14 days followed by every other day dosing until day 28 in the 25 mg and 50 mg cohorts. Increases in frataxin levels in skin cells were seen in all treated patients, and in buccal cells for the majority of patients. At Day 14, all patients (with quantifiable levels at baseline and Day 14) treated with 50 mg of nomlabofusp achieved frataxin levels in skin cells greater than 33% of the average level observed in healthy volunteers, with 3 patients achieving levels greater than 50% of the average healthy volunteer level.In February 2024, Larimar announced the Company had initiated discussions with the FDA on use of tissue frataxin levels as a potential novel surrogate endpoint. Larimar received FDA acknowledgement that frataxin deficiency appears to be critical to the pathogenic mechanism of FA, and that there continues to be an unmet need for treatments that address the underlying disease pathophysiology. The Company intends to pursue an accelerated approval using FXN levels, supportive pharmacodynamics and clinical information, and safety data from the OLE study, along with additional nonclinical pharmacology information needed to support the novel surrogate endpoint approach, with a BLA submission targeted for the second half of 2025.In February 2024, Larimar raised net proceeds of approximately $161.8 million through a public offering of common stock.In March 2024, the first patient was dosed in the OLE study evaluating daily subcutaneous injections of 25 mg of nomlabofusp self-administered or administered by a caregiver. Participants who completed treatment in the Phase 2 dose exploration study, or who previously completed a prior clinical trial of nomlabofusp, are potentially eligible to screen for the OLE study. The OLE study will evaluate the safety and tolerability, pharmacokinetics, and frataxin levels in peripheral tissues as well as other exploratory pharmacodynamic markers (lipid profiles and gene expression data) following long-term subcutaneous administration of nomlabofusp. Dose escalation in the OLE study is contingent on the FDA’s review of data from the 50 mg cohort of the Phase 2 study and available data from the OLE study, due to the continued partial clinical hold. Interim data is expected in the fourth quarter of 2024. In addition, clinical assessments collected during the study will be compared to data from a matched control arm derived from participants in the Friedreich’s Ataxia Clinical Outcomes Measures Study (FACOMS) database.In March 2024, Larimar began to build its commercial team with the appointment of Frank Nazzario, RPh, as Vice President of Commercial. Mr. Nazzario brings nearly 30 years of leadership experience in drug launches for rare diseases. Most recently, he served as Senior Vice President of Sales at BioCryst Pharmaceuticals. Previously, he held commercial leadership roles at Spark Therapeutics where he led the commercialization of Luxturna®, the first FDA-approved gene therapy for an inherited retinal disorder, and at ViroPharma, Inc., where he led the launch of Cinryze®, the first approved biologic for Hereditary Angioedema. First Quarter 2024 Financial Results As of March 31, 2024, the Company had cash, cash equivalents and marketable securities totaling $239 million. In February 2024, we raised approximately $161.8 million in net proceeds through a public offering of common stock. The Company reported a net loss for the first quarter of 2024 of $14.7 million, or $0.27 per share, compared to a net loss of $6.5 million, or $0.15 per share, for the first quarter of 2023. Research and development expenses for the first quarter of 2024 were $12.9 million, compared to $4.6 million for the first quarter of 2023. The increase in research and development expenses was primarily driven by an increase of $5.7 million in nomlabofusp manufacturing costs, an increase of $1.0 million in clinical costs primarily associated with the initiation of the OLE study, an increase of $1.0 million in personnel expense driven by increasing headcount, an increase of $0.3 million in consulting fees and an increase of $0.2 million in stock compensation expense. General and administrative expenses were $3.8 million in the first quarter of 2024, compared to $3.1 million in the first quarter of 2023. The increase in general and administrative expenses was primarily driven by an increase of $0.2 million in personnel expense, an increase of $0.2 million in legal fees, and an increase of $0.1 million in stock compensation expense. About Larimar TherapeuticsLarimar Therapeutics, Inc. (Nasdaq: LRMR), is a clinical-stage biotechnology company focused on developing treatments for complex rare diseases. Larimar’s lead compound, nomlabofusp, is being developed as a potential treatment for Friedreich's ataxia. Larimar also plans to use its intracellular delivery platform to design other fusion proteins to target additional rare diseases characterized by deficiencies in intracellular bioactive compounds. For more information, please visit: https://larimartx.com. Forward-Looking StatementsThis press release contains forward-looking statements that are based on Larimar’s management’s beliefs and assumptions and on information currently available to management. All statements contained in this release other than statements of historical fact are forward-looking statements, including but not limited to statements regarding Larimar’s ability to develop and commercialize nomlabofusp (also known as CTI-1601) and other planned product candidates, Larimar’s planned research and development efforts, including the timing of its nomlabofusp clinical trials, interactions with the FDA and overall development plan and other matters regarding Larimar’s business strategies, ability to raise capital, use of capital, results of operations and financial position, and plans and objectives for future operations. In some cases, you can identify forward-looking statements by the words “may,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “anticipate,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “ongoing” or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. These statements involve risks, uncertainties and other factors that may cause actual results, performance, or achievements to be materially different from the information expressed or implied by these forward-looking statements. These risks, uncertainties and other factors include, among others, the success, cost and timing of Larimar’s product development activities, nonclinical studies and clinical trials, including nomlabofusp clinical milestones and continued interactions with the FDA; that preliminary clinical trial results may differ from final clinical trial results, that earlier non-clinical and clinical data and testing of nomlabofusp may not be predictive of the results or success of later clinical trials, and assessments; that the FDA may not ultimately agree with Larimar’s nomlabofusp development strategy; the potential impact of public health crises on Larimar’s future clinical trials, manufacturing, regulatory, nonclinical study timelines and operations, and general economic conditions; Larimar’s ability and the ability of third-party manufacturers Larimar engages, to optimize and scale nomlabofusp’s manufacturing process; Larimar’s ability to obtain regulatory approvals for nomlabofusp and future product candidates; Larimar’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators, and to successfully commercialize any approved product candidates; Larimar’s ability to raise the necessary capital to conduct its product development activities; and other risks described in the filings made by Larimar with the Securities and Exchange Commission (SEC), including but not limited to Larimar’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the SEC and available at www.sec.gov. These forward-looking statements are based on a combination of facts and factors currently known by Larimar and its projections of the future, about which it cannot be certain. As a result, the forward-looking statements may not prove to be accurate. The forward-looking statements in this press release represent Larimar’s management’s views only as of the date hereof. Larimar undertakes no obligation to update any forward-looking statements for any reason, except as required by law. Investor Contact:Joyce AllaireLifeSci Advisorsjallaire@lifesciadvisors.com(212) 915-2569 Company Contact:Michael CelanoChief Financial Officermcelano@larimartx.com(484) 414-2715 Larimar Therapeutics, Inc.Condensed Consolidated Balance Sheet(unaudited) March 31, December 31, 2024 2023 Assets Current assets: Cash and cash equivalents $110,125 $26,749 Short-term marketable securities 117,171 60,041 Prepaid expenses and other current assets 3,657 3,385 Total current assets 230,953 90,175 Long-term marketable securities 11,711 — Property and equipment, net 604 684 Operating lease right-of-use assets 2,920 3,078 Restricted cash 1,339 1,339 Other assets 678 659 Total assets $248,205 $95,935 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable $1,918 $1,283 Accrued expenses 10,098 7,386 Operating lease liabilities, current 825 837 Total current liabilities 12,841 9,506 Operating lease liabilities 4,520 4,709 Total liabilities 17,361 14,215 Commitments and contingencies (See Note 8) Stockholders’ equity: Preferred stock; $0.001 par value per share; 5,000,000 shares authorized as of March 31, 2024 and December 31, 2023; no shares issued and outstanding as of March 31, 2024 and December 31, 2023 — — Common stock, $0.001 par value per share; 115,000,000 shares authorized as of March 31, 2024 and December 31, 2023; 63,800,017 and 43,909,069 shares issued and outstanding as of March 31, 2024 and December 31, 2023, respectively 64 43 Additional paid-in capital 434,013 270,150 Accumulated deficit (203,208) (188,554)Accumulated other comprehensive gain (loss) (25) 81 Total stockholders’ equity 230,844 81,720 Total liabilities and stockholders’ equity $248,205 $95,935 Larimar Therapeutics, Inc.Condensed Consolidated Statements of Operations(In thousands, except share and per share data)(unaudited) Three Months Ended March 31, 2024 2023 Operating expenses: Research and development $12,939 $4,562 General and administrative 3,795 3,075 Total operating expenses 16,734 7,637 Loss from operations (16,734) (7,637)Other income, net 2,080 1,111 Net loss (14,654) (6,526)Net loss per share, basic and diluted $(0.27) $(0.15)Weighted average common shares outstanding, basic and diluted 53,553,707 43,897,603 Comprehensive loss: Net loss $(14,654) $(6,526)Other comprehensive gain (loss): Unrealized gain (loss) on marketable securities (106) 31 Total other comprehensive gain (loss) (106) 31 Total comprehensive loss $(14,760) $(6,495)