Aceclidine

New Drug Application (NDA) for LNZ100 for treatment of presbyopia accepted for review by the U.S. Food and Drug Administration (FDA); PDUFA target action date of August 8, 2025 CORXEL and LENZ Therapeutics announced positive topline data from Phase 3 study in China for the treatment of presbyopia Cash, cash equivalents and marketable securities of $217.2 million as of September 30, 2024; cash runway anticipated to extend to post-launch positive operating cash flow Company to host a conference call today at 8:00 a.m. ET SAN DIEGO, Nov. 06, 2024 (GLOBE NEWSWIRE) -- LENZ Therapeutics, Inc. (Nasdaq: LENZ or “LENZ” or the “Company”), a pre-commercial stage biopharmaceutical company focused on the development and commercialization of the first and only aceclidine-based eye drop to improve near vision in people with presbyopia, today reported financial results and operational highlights for the third quarter ended September 30, 2024 and recent period. “The third quarter and recent period has continued to be a time of tremendous execution and focus on our primary objective, which is to advance LNZ100 towards approval in the United States and a commercial launch as early as the fourth quarter of 2025,” said Eef Schimmelpennink, President and Chief Executive Officer of LENZ Therapeutics. “In addition, we believe the recently announced data from the Phase 3 clinical study in China is extremely important, further enhancing the potential for LNZ100 to become a global therapy for the treatment of presbyopia. With an estimated 128 million people in the United States and 400 million people in China with presbyopia, we look forward to the prospect of unlocking significant access to LNZ100 worldwide and further generating shareholder value through that effort.” Third Quarter 2024 and Recent Highlights Announced New Drug Application (NDA) acceptance by the U.S. Food and Drug Administration (FDA) for LNZ100 as a treatment for presbyopia. In October 2024, the Company announced that the FDA accepted the NDA for LNZ100 for the treatment of presbyopia, a condition that impacts an estimated 1.8 billion people globally and 128 million people in the United States. The Company previously announced the submission of its NDA in August 2024. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of August 8, 2025 for LNZ100. The FDA noted that it is not planning to hold an advisory committee meeting to discuss this application. The NDA submission for the treatment of presbyopia is supported by positive data from the pivotal Phase 3 CLARITY study. Aceclidine is a new chemical entity in the United States and is not approved for the treatment of presbyopia in any country. CORXEL and LENZ Therapeutics announced positive topline data from Phase 3 study in China for the treatment of presbyopia. In October 2024, CORXEL and the Company announced topline data from the Phase 3 safety and efficacy study in China. In the Phase 3 study, LNZ100 (1.75% Aceclidine) achieved the primary endpoint and key secondary endpoints, with statistically significant three-lines or greater improvement in Best Corrected Distance Visual Acuity (BCDVA) at near, without losing one-line or more in distance visual acuity. The primary endpoint was met with 74% of patients dosed with LNZ100 achieving three-lines or greater improvement at 3 hours. The difference in efficacy was statistically significant in the LNZ100 treatment group compared to the vehicle-controlled group (p<0.0001). US Commercial launch preparations underway and on track for mid-2025 approval. Building upon the acceptance of the Company’s NDA application by the FDA with an August 8, 2025 target action date, LENZ continues to progress its launch readiness for an anticipated approval of LNZ100 for the treatment of presbyopia in the United States. The Company has hired and established its full commercial leadership team across sales, marketing and commercial operations. In addition, the Company has also hired both Regional Sales Directors adding key sales force leadership, with significant eye care and pharmaceutical sales experience. Market research of surveyed Eye Care Professionals (“ECPs”) confirmed enthusiasm for LNZ100 clinical data and likelihood to prescribe. The Company commissioned a survey of 426 Optometrists and Ophthalmologists, to further define the presbyopia market and evaluate the interest for LNZ100. Key results of the surveyed ECPs included: ECPs see an average of approximately 300-400 patients per month, of which 61% are presbyopic87% of ECPs’ eye exams include a retinal eye exam, confirming that the retinal exam is already a common practice in these evaluations78% of ECPs agree with the statement that LNZ100 was a “well tolerated and safe” option for the treatment of presbyopia, if approved78% of ECPs agree with the statement that LNZ100 was “attractive as a presbyopia treatment”, if approved83% of ECPs would be likely to sample, based on its clinical data profile82% of ECPs would be likely to prescribe, based on its clinical data profile Completed $30 million private placement financing: In July 2024, LENZ executed a stock purchase agreement with Ridgeback Capital Investments L.P. (“Ridgeback Capital”) for a $30 million private investment in public equity (“PIPE”) common stock financing. Financial Results for Third Quarter 2024 Cash Position: Cash, cash equivalents and marketable securities were $217.2 million as of September 30, 2024, which is anticipated to fund operations to post-launch positive operating cash flow. Research and Development (R&D) Expenses: R&D expenses decreased to $6.5 million for the three months ended September 30, 2024, compared to $17.0 million during the same period in 2023. R&D expenses decreased to $23.9 million for the nine months ended September 30, 2024, compared to $40.0 million during the same period in 2023. The declines in our R&D expenses were primarily due to the conclusion of our positive Phase 3 CLARITY study in March 2024. Selling, General and Administrative (SG&A) Expenses: SG&A expenses were $6.5 million for the three months ended September 30, 2024, compared to $2.9 million during the same period in 2023. SG&A expenses increased to $19.5 million for the nine months ended September 30, 2024, compared to $7.5 million during the same period in 2023. The increases in our SG&A expenses were primarily driven by increases in personnel-related expenses due to a growth in headcount, pre-commercial planning activities, and other legal and professional services associated with being a publicly traded company. Net Loss: Net loss for the three months ended September 30, 2024, was $10.2 million, or $0.38 per share (basic and diluted), compared to a net loss of $18.9 million, or $9.62 per share (basic and diluted) during the same period in 2023. Net loss for the nine months ended September 2024, was $37.1 million, or $1.93 per share (basic and diluted), compared to a net loss of $46.3 million, or $23.66 per share (basic and diluted) during the same period in 2023. Net loss per share (basic and diluted) considers only the weighted-average common shares outstanding for the respective periods. Conference Call InformationThe Company will host a conference call and webcast today, Wednesday, November 6, 2024, at 8:00 a.m. ET. To participate in the conference call via telephone, dial (800) 715-9871 (Domestic) or (646) 307-1963 (International) and enter code 7959303. The live webcast from today’s conference call can be accessed here and on the LENZ Therapeutics website at www.LENZ-Tx.com in the Investors & Media section. A replay of the webcast will be available on the Company’s website for 30 days following the event. About LENZ TherapeuticsLENZ Therapeutics is a pre-commercial biopharmaceutical company focused on the development and commercialization of the first and only aceclidine-based eye drop to improve near vision in patients with presbyopia. LENZ’s product candidate, LNZ100 is a preservative-free, single-use, once-daily eye drop containing aceclidine. LNZ100 was evaluated in the registration-enabling Phase 3 CLARITY study as a potential therapy for the treatment of presbyopia, a condition impacting an estimated 1.8 billion people globally and 128 million people in the United States. The U.S. Food and Drug Administration (FDA) has assigned a Prescription Drug User Fee Act (PDUFA) target action date of August 8, 2025 for LNZ100. LENZ is committed to commercializing an ideal pharmaceutical presbyopia solution that enhances vision for “all eyes, all day”. LENZ is headquartered in San Diego, California. For more information, visit: LENZ-Tx.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of federal securities laws. You can identify forward-looking statements by words such as “may,” “will,” “could,” “can,” “would,” “should,” “expect,” “intend,” “plan,” “anticipate,” “believe,” “estimate,” “predict,” “project,” “potential,” “poised,” “continue,” “ongoing” or the negative of these terms or other comparable terminology, but not all forward-looking statements will contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding the review and potential approval of our NDA by FDA for the potential regulatory approval; approval and commercialization of LNZ100 as a global therapy; our plans relating to commercialization, including engagement with key opinion leaders and eye care professionals and the development of commercial capabilities; the size of the market opportunity for LNZ100; the beneficial characteristics of LNZ100 and its expected impact on presbyopes; and expectations regarding shareholder value creation. These statements are based on numerous assumptions concerning the development of LENZ’s product candidates and target markets and involve substantial risks, uncertainties and other factors that may cause actual results, levels of activity, performance or achievement to be materially different from the information expressed or implied by these forward-looking statements, including those risk factors described in the section titled “Risk Factors” in our Quarterly Report on Form 10-Q to be filed for the quarter ended September 30, 2024 and our subsequent filings with the SEC. We cannot assure you that the forward-looking statements in this press release or the assumptions upon which they are based will prove to be accurate. The forward-looking statements in this press release are as of the date of this press release. Except as otherwise required by applicable law, LENZ disclaims any duty to update any forward-looking statements. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this press release. Contact: Dan Chevallard LENZ TherapeuticsIR@LENZ-Tx.com LENZ Therapeutics, Inc.Selected Balance Sheet Highlights(in thousands) September 30, 2024 December 31, 2023 (unaudited) Cash and cash equivalents$41,046 $35,140 Marketable securities$176,061 $30,654 Total assets$224,007 $70,376 Total liabilities$8,727 $19,698 Total stockholders’ equity (deficit)$215,280 $(92,712) LENZ Therapeutics, Inc.Condensed Consolidated Statement of Operations and Comprehensive Loss(in thousands, except share and per share data)(unaudited) Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Operating expenses: Research and development$6,451 $17,004 $23,933 $39,968 Selling, general and administrative 6,494 2,861 19,452 7,472 Total operating expenses 12,945 19,865 43,385 47,440 Loss from operations (12,945) (19,865) (43,385) (47,440)Other income (expense): Other income (expense) (6) (101) 281 (174)Interest income 2,736 1,086 5,987 1,338 Total other income (expense), net 2,730 985 6,268 1,164 Net loss$(10,215) $(18,880) $(37,117) $(46,276)Other comprehensive loss: Unrealized loss on marketable securities 585 9 517 (5)Comprehensive loss$(9,630) $(18,871) $(36,600) $(46,281)Net loss per share, basic and diluted$(0.38) $(9.62) $(1.93) $(23.66)Weighted-average common shares outstanding, basic and diluted 27,172,330 1,961,822 19,195,399 1,956,282

Primary endpoint was met with 74% of participants dosed with LNZ100 achieving three-lines or greater improvement at 3 hours post treatment，and maintaining their optimal distance visual acuity (i.e., not losing 5 or more letters). The difference in efficacy was statistically significant in the LNZ100 treatment group compared to the vehicle group (p<0.0001) Rapid onset and long duration shown with 69% of participants achieving three-lines or greater improvement at 30 minutes and 30% at 10 hours 91% of participants indicated they noticed an improvement in their near vision LNZ100 could potentially be the best-in-class non-invasive treatment for presbyopia SHANGHAI, China and SAN DIEGO, Oct. 27, 2024 (GLOBE NEWSWIRE) -- Corxel Pharmaceuticals (CORXEL) and LENZ Therapeutics (Nasdaq: LENZ) today announced positive topline data from the Phase 3 JX07001 clinical trial of LNZ100 in patients with presbyopia in China. CORXEL is a leading biotech company committed to bringing innovative science and medicines to underserved patients with serious and life-threatening diseases. LENZ Therapeutics is a pre-commercial biopharmaceutical company focused on developing the first and only aceclidine-based eye drop to improve near vision in people with presbyopia. In this China Phase 3 safety and efficacy trial, LNZ100 (1.75% aceclidine HCl) achieved the primary endpoint and key secondary endpoints, with statistically significant three-lines or greater improvement in Best Corrected Distance Visual Acuity (BCDVA) at near, and maintaining their optimal distance visual acuity (i.e., not losing 5 or more letters). More results showed (all p<0.0001): Rapid onset: 84% and 69% achieved two-lines and three-lines or greater improvement at 30 minutes respectively.3 hours post treatment: 88% and 74% achieved two-lines and three-lines or greater improvement at 3 hours respectively，and maintained their optimal distance visual acuity (i.e., not losing 5 or more letters).Long duration: 61% and 30% achieved two-lines and three-lines or greater improvement at 10 hours respectively. LNZ100 was well-tolerated with no serious treatment-related adverse events observed in the trial. The study was a Phase 3, multicenter, randomized, double-blind, vehicle-controlled study, including a 4-week efficacy study followed by a 5-month extension safety study, designed to evaluate the efficacy and safety of LNZ100 (an aceclidine-based ophthalmic solution) in participants with presbyopia. The objectives were to assess the potential of LNZ100 to improve near vision among Chinese presbyopia patients and to evaluate the efficacy and safety profiles.  The trial has enrolled 300 participants, with a broad enrollment criteria of between 45 and 75 years of age with a refractive range of -4.0D SE to +1.0D SE, including those who had undergone laser-assisted cornea refractive surgery/monofocal IOL implantation. Professor Jia Qu, Principal Investigator and Co-Principal Investigator，Vice Chairman of Ophthalmology Branch, Chinese Medical Association, Director of optometry department, Wenzhou Medical University said: “we are very pleased with the results of the LNZ100 trial, particularly the significant efficacy and favorable safety profile of LNZ100 in patients with presbyopia, demonstrating an important advance in the field of presbyopia treatment in China. Currently, patients mainly rely on wearing eyeglasses as treatment for presbyopia. There is a large unmet need for non-invasive and reversible treatments. We expect that LNZ100 will fill this vacuum and become an innovative force in the treatment of presbyopia in China, providing more patients with the hope of clear vision." Professor Fan Lyu, Principal Investigator and Co-Principal Investigator，Head of optometry working-group under Ophthalmology Branch, Chinese Medical Association, Director of National Clinical Medical Research Centre for Eye Diseases said: "The main active ingredient of LNZ100, aceclidine, causes temporary pupil constriction, resulting in an optical effect that significantly extends the depth of focus and improves the quality of vision. The statistically significant data and clinically meaningful outcomes observed in the trials provide strong support for the efficacy and safety of LNZ100. We anticipate that LNZ100 will be a practical treatment option for a wide spectrum of patients and will have a favorable impact on paradigm shift of helping improve near-vision in the Chinese presbyopia population. “We are especially grateful to all the hard-working and dedicated researchers, partner organizations and all the volunteers who participated in the study,” Sandy Mou, Board Executive Director and Chief Executive Officer of CORXEL, said. “The common goal is to benefit hundreds of millions of people around the world, to set an international leading research benchmark, and to introduce novel treatment concepts and potentially optimal products to China first, providing a safe and convenient treatment option for the vast number of presbyopia patients. Looking ahead, we will actively communicate and cooperate with drug regulatory authorities to expedite the submission and approval of LNZ100. We believe that LNZ100 will not only significantly improve patients' vision and quality of life, but will also have a profound impact on the field of presbyopia treatment and research in China.” “We would like to first congratulate the team at CORXEL for their effort in their Phase 3 clinical study in China. We are pleased with the impressive and consistent performance demonstrated by LNZ100 in our collective studies, further validating the vision of targeting an ‘all eyes, all day’ solution,” said Eef Schimmelpennink, President and Chief Executive Officer of LENZ Therapeutics. “With this data, we believe LNZ100 has further enhanced its potential as a global therapy and is further on its path towards providing access to the estimated 400 million people with presbyopia in China. This data signifies a tremendous joint effort between the CORXEL and LENZ teams and comes in rapid succession to the recent FDA acceptance of our New Drug Application for LNZ100 in the United States.” About PresbyopiaPresbyopia is a physiological phenomenon associated with aging that results in a progressively worsening ability to see nearby objects clearly. It is caused by the gradual hardening of the lens. This results in a decline of the eye's adjustment function, and the inability to focus the image of nearby objects on the retina, leading to a decline in near vision. Studies have shown that the onset of presbyopia typically occurs around the age of 38, reaching a prevalence rate of nearly 100 percent at the age of 52 in China. It is estimated that more than 400 million people in China suffer from presbyopia.  Currently, the treatment options for presbyopia are very limited. Wearing glasses requires frequent removal and insertion, causing many inconveniences in work and life. Surgery, as an irreversible invasive operation, has a very limited acceptance. There are no approved drugs for the treatment of presbyopia in China and the medical need for non-invasive, safe, efficient and reversible treatments for presbyopia remains unsolved.  About LNZ100LNZ100 (aceclidine) eye drops are being developed by LENZ Therapeutics and CORXEL acquired the Greater China rights for the development and commercialization in April 2022. LNZ100 is formulated with aceclidine, a miotic, and designed to achieve optimal pupil diameter without impacting distance vision, a key limitation of other miotics. Miotics are compounds that cause pupil constriction, or miosis, creating a pinhole effect that enables better focus of incoming light from near objects onto the retina. Research has shown that a pupil diameter below two millimeters (2 mm) is optimal for presbyopia treatment and results in clinically meaningful improvement in near vision. Unlike other miotics such as pilocarpine and carbachol, aceclidine’s mechanism of action is pupil-selective, meaning it can activate the iris sphincter muscle and cause miosis of the pupil to a diameter below 2 mm without overstimulating the ciliary muscles that can cause a myopic shift and impair distance vision. As a result, aceclidine does not require any remaining accommodation to improve near vision, broadening its benefits to older presbyopes whose lens has lost this capacity. Therefore, we expect that users may be able to benefit from treatment even as they age from mid-40s to well into their mid-70s and across a broad range of refractive errors, as demonstrated in clinical testing to date. About CORXELCORXEL, formerly named Ji Xing Pharmaceuticals, is a leading biotech company headquartered in US and China committed to bringing innovative science and medicines to underserved patients with serious and life-threatening cardiometabolic diseases. Backed by RTW Investments, CORXEL was founded in 2019 to develop and commercialize novel, innovative therapeutics to treat unmet medical needs in diseases. With a strong and further developing asset pipeline, industry leading talent, and patient-centric focus, CORXEL is dedicated to deliver a meaningful and lasting impact on patients. The full portfolio of CORXEL consists of 2 assets with global rights and 4 assets with Greater China rights in late-stage clinical development. The portfolio with global rights are JX09 for hypertension and JX10 for acute ischemic stroke (AIS), while the portfolio with Greater China rights include aficamten, etripamil, varenicline solution nasal spray/US brand name TYRVAYA®, and LNZ100. For further information about CORXEL, please visit www.corxelbio.com.   About LENZ TherapeuticsLENZ Therapeutics is a pre-commercial biopharmaceutical company focused on the development and commercialization of the first and only aceclidine-based eye drop to improve near vision in patients with presbyopia. LENZ’s product candidate, LNZ100 is a preservative-free, single-use, once-daily eye drop containing aceclidine. LNZ100 was evaluated in the registration-enabling Phase 3 CLARITY study as a potential therapy for the treatment of presbyopia, a condition impacting an estimated 1.8 billion people globally and 128 million people in the United States. The U.S. Food and Drug Administration (FDA) has assigned a Prescription Drug User Fee Act (PDUFA) target action date of August 8, 2025 for LNZ100. LENZ is committed to commercializing an ideal pharmaceutical presbyopia solution that enhances vision for “all eyes, all day”. LENZ is headquartered in San Diego, California. For more information, visit: LENZ-Tx.com. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of United States federal securities laws. You can identify forward-looking statements by words such as “may,” “will,” “could,” “can,” “would,” “should,” “expect,” “intend,” “plan,” “anticipate,” “believe,” “estimate,” “predict,” “project,” “potential,” “poised,” “continue,” “ongoing” or the negative of these terms or other comparable terminology, but not all forward-looking statements will contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding the potential of LNZ100 to have best-in-class performance and LNZ100 as a global therapy; the size of the addressable population for LNZ100; expectations regarding the commercial opportunity and beneficial characteristics of LNZ100; and plans and expectations regarding commercialization of LNZ100, if approved. These statements are based on numerous assumptions concerning the development of LENZ’s products and target markets and involve substantial risks, uncertainties and other factors that may cause actual results, levels of activity, performance or achievement to be materially different from the information expressed or implied by these forward-looking statements, including those risk factors described in the section titled “Risk Factors” in LENZ’s Quarterly Report on Form 10-Q filed for the quarter ended June 30, 2024 and in LENZ’s subsequent filings with the SEC. LENZ cannot assure you that the forward-looking statements in this press release or the assumptions upon which they are based will prove to be accurate. The forward-looking statements in this press release are as of the date of this press release. Except as otherwise required by applicable law, LENZ disclaims any duty to update any forward-looking statements. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this press release. LENZ Therapeutics Contact: Dan Chevallard IR@LENZ-Tx.com