Tie-2

Findings offer potential mechanistic and clinical insights in the development of cellular therapy Lomecel-B™ for mild Alzheimer’s disease (AD) Lomecel-B™ capacity to inhibit MMP14 correlates with improved clinical and biomarker outcomes in mild AD Immunomodulatory and pro-vascular effects of Lomecel-B™ in mild AD potentially driven by ability to exert MMP14 inhibition which may protect TIE2 receptor integrity in human AD patients Oct. 29, 2024 -- Longeveron Inc. (NASDAQ: LGVN), a clinical stage regenerative medicine biotechnology company developing cellular therapies for life-threatening and chronic aging-related conditions, today announced that its submission entitled “Lomecel-B inhibition of MMP14 activity predicts Lomecel-B bioactivity in the treatment of mild Alzheimer’s disease” was presented as a late breaking poster presentation at the 17th edition of the Clinical Trials on Alzheimer’s Disease Conference (CTAD24) taking place October 29 -November 1, 2024 in Madrid, Spain. “As a medicinal signaling cell therapy that has multiple potential mechanisms of action to address inflammatory responses in the brain, Lomecel-B™ offers the potential to address the underlying pathology of Alzheimer’s disease,” said Joshua Hare, M.D., Co-founder, Chief Science Officer, and Chairman at Longeveron. “This data adds to the positive clinical information from the Phase 2a CLEAR MIND clinical trial that showed Lomecel-B™ improved cognitive function, quality of life, and brain volume in the treatment of mild Alzheimer’s disease. We are very encouraged by the safety profile and efficacy evidence that support the differentiated therapeutic potential of Lomecel-B™ in Alzheimer’s disease.” From the Poster: Matrix metalloprotease (MMP) activity is reportedly upregulated in AD. The researchers hypothesized that excess MMP14 activity may contribute to AD pathogenesis, at least in part, by cleaving TIE2 (Tyrosine kinase with Immunoglobulin and Epidermal growth factor homology domains), a cell-surface tyrosine kinase receptor for the angiopoietins, which activates downstream signaling pathways that regulate endothelial cell health and inflammatory responses. They tested the hypothesis that Lomecel-B™ capacity to inhibit MMP14 correlates with improved clinical and biomarker outcomes in mild AD. The researchers measured MMP14 inhibitory (MMP14i) activity, levels of TIMP2 (tissue inhibitor of metalloprotease 2), and VEGF-A (vascular endothelial growth factor-A) in the lots of Lomecel-B used in the CLEAR MIND trial. Supernatant from Lomecel-B CLEAR MIND lots contained MMP14i activity, high levels of TIMP2 and VEGF-A protein. Patients receiving Lomecel-B lots with higher levels of MMP14i activity demonstrated enhanced responses vs. placebo on the composite Alzheimer’s disease score (CADS, the study secondary endpoint) than those who received low potency lots. Similar associations were evident with responses in the MoCA, ADCS-ADL, and left hippocampal volume. High MMP14i lots were also more effective in suppressing elevations in soluble (degraded) TIE2 in study patients, suggesting a potential role for MMP14i in AD treatment. Poster Conclusion: Together these findings suggest that ability to exert MMP14 inhibition may protect TIE2 receptor integrity and underlie, at least in part, the immunomodulatory and pro-vascular effects of Lomecel-B in mild AD. The findings offer potential mechanistic and clinical insights in the development of cellular-based therapy for AD. Late Breaking Poster PresentationDate: Tuesday, October 29, 2024, 3:00 p.m. CEST to Wednesday, October 30, 5:00 p.m. CESTTheme:11. New Therapies and Clinical TrialsTitle:LP029 “Lomecel-B inhibition of MMP14 activity predicts Lomecel-B bioactivity in the treatment of mild Alzheimer’s” The abstract of the poster will also be included in the special CTAD edition of the Journal of Prevention of Alzheimer’s Disease (JPAD), the official journal of the CTAD conference. Lomecel-B™ is a living cell product made from specialized cells isolated from the bone marrow of young healthy adult donors. These specialized cells, known as medicinal signaling cells (MSCs), are essential to our endogenous biological repair mechanism. MSCs have been shown to perform a number of complex functions in the body, including the formation of new tissue. They also have been shown to respond to sites of injury or disease and secrete bioactive factors that are immunomodulatory and regenerative. We believe that Lomecel-B™ may have multiple potential mechanisms of action that may lead to anti-inflammatory, pro-vascular regenerative responses, and therefore may have broad application for a range of rare and aging related diseases. Longeveron is a clinical stage biotechnology company developing regenerative medicines to address unmet medical needs. The Company’s lead investigational product is Lomecel-B™, an allogeneic medicinal signaling cell (MSC) therapy product isolated from the bone marrow of young, healthy adult donors. Lomecel-B™ has multiple potential mechanisms of action encompassing pro-vascular, pro-regenerative, anti-inflammatory, and tissue repair and healing effects with broad potential applications across a spectrum of disease areas. Longeveron is currently pursuing three pipeline indications: hypoplastic left heart syndrome (HLHS), Alzheimer’s disease (AD), and Aging-related Frailty. Lomecel-B™ development programs have received five distinct and important U.S. FDA designations: for the HLHS program - Orphan Drug designation, Fast Track designation, and Rare Pediatric Disease designation; and, for the AD program - Regenerative Medicine Advanced Therapy (RMAT) designation and Fast Track designation. For more information, visit www.longeveron.com or follow Longeveron on LinkedIn, X, and Instagram. The content above comes from the network. if any infringement, please contact us to modify.

WATERTOWN, Mass., Oct. 29, 2024 (GLOBE NEWSWIRE) -- EyePoint Pharmaceuticals, Inc. (NASDAQ: EYPT), a company committed to developing and commercializing innovative therapeutics to improve the lives of patients with serious retinal diseases, today announced the pricing of an underwritten public offering of 12,727,273 shares of its common stock at a public offering price of $11.00 per share. The aggregate gross proceeds from this offering are expected to be approximately $140.0 million, before deducting underwriting discounts and commissions and other offering expenses payable by EyePoint. All of the shares of common stock are being sold by EyePoint. The closing of the offering is expected to occur on or about October 31, 2024, subject to the satisfaction of customary closing conditions. In addition, EyePoint has granted the underwriters an option for a period of 30 days to purchase up to an additional 1,909,090 shares of EyePoint’s common stock at the public offering price, less underwriting discounts and commissions. J.P. Morgan, Citigroup and Guggenheim Securities are acting as joint book running managers for the offering. Baird, Mizuho and Jones are acting as co-managers for the offering. EyePoint intends to use the net proceeds that it will receive from the offering to advance clinical development of DURAVYU™ for wet age related macular degeneration (wet AMD) and diabetic macular edema (DME), as well as support its earlier stage pipeline development initiatives, and for general corporate purposes. The securities described above are being offered by the Company pursuant to a shelf registration statement on Form S-3 (No. 333-281391) previously filed with the Securities and Exchange Commission (SEC) on August 8, 2024 and declared effective by the SEC on August 16, 2024. The securities are being offered by means of a prospectus supplement and accompanying prospectus relating to the offering that form a part of the registration statement. A preliminary prospectus supplement relating to the offering was filed with the SEC on October 28, 2024 and is available on the SEC’s website at www.sec.gov. The final prospectus supplement relating to and describing the terms of the offering will be filed with the SEC and also will be available on the SEC’s website at www.sec.gov. Before investing in the offering, you should read each of the prospectus supplement and the accompanying prospectus relating to the offering in their entirety as well as the other documents that EyePoint has filed with the SEC that are incorporated by reference in the prospectus supplement and the accompanying prospectus relating to the offering, which provide more information about EyePoint and the offering. Copies of the final prospectus supplement, when available, and accompanying prospectus relating to the offering may be obtained from J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by email at prospectus-eq_fi@jpmchase.com and postsalemanualrequests@broadridge.com; Citigroup, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (800) 831-9146; or Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, NY 10017, by telephone at (212) 518-9544, or by email at GSEquityProspectusDelivery@guggenheimpartners.com. This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. About EyePoint Pharmaceuticals EyePoint Pharmaceuticals (Nasdaq: EYPT) is a clinical-stage biopharmaceutical company committed to developing and commercializing innovative therapeutics to help improve the lives of patients with serious retinal diseases. The Company's pipeline leverages its proprietary bioerodible Durasert E™ technology for sustained intraocular drug delivery. The Company’s lead product candidate, DURAVYU™ (f/k/a EYP-1901), is an investigational sustained delivery treatment for VEGF-mediated retinal diseases combining vorolanib, a selective and patent-protected tyrosine kinase inhibitor with bioerodible Durasert E™. DURAVYU is presently in Phase 3 global, pivotal clinical trials as a sustained delivery treatment for wet AMD, the leading cause of vision loss among people 50 years of age and older in the United States, and in a Phase 2 clinical trial in DME. EyePoint expects full topline data from the Phase 2 clinical trial in DME in Q1 2025 and topline data from both Phase 3 pivotal trials in wet AMD in 2026. Pipeline programs include EYP-2301, a TIE-2 agonist, razuprotafib, formulated in Durasert E™ to potentially improve outcomes in serious retinal diseases. The proven Durasert® drug delivery technology has been safely administered to thousands of patient eyes across four U.S. FDA approved products. EyePoint Pharmaceuticals is headquartered in Watertown, Massachusetts. Vorolanib is licensed to EyePoint exclusively by Equinox Sciences, a Betta Pharmaceuticals affiliate, for the localized treatment of all ophthalmic diseases outside of China, Macao, Hong Kong and Taiwan. DURAVYU™ has been conditionally accepted by the FDA as the proprietary name for EYP-1901. DURAVYU is an investigational product; it has not been approved by the FDA. FDA approval and the timeline for potential approval is uncertain. SAFE HARBOR STATEMENTS UNDER THE PRIVATE SECURITIES LITIGATION ACT OF 1995: To the extent any statements made in this press release deal with information that is not historical, these are forward-looking statements under the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements regarding the timing of the closing of the offering, as well as the anticipated use of proceeds for the offering, EyePoint’s clinical development plans and the expected timing thereof; and other statements identified by words such as “will,” “potential,” “could,” “can,” “believe,” “intends,” “continue,” “plans,” “expects,” “anticipates,” “estimates,” “may,” other words of similar meaning or the use of future dates. Forward-looking statements by their nature address matters that are, to different degrees, uncertain. Uncertainties and risks may cause EyePoint’s actual results to be materially different than those expressed in or implied by EyePoint’s forward-looking statements. For EyePoint, this includes satisfaction of the customary closing conditions of the offering; delays in obtaining required stock exchange or other regulatory approvals; stock price volatility and uncertainties relating to the financial markets, the medical community and the global economy; the timing, progress and results of the company’s clinical development activities; uncertainties and delays relating to the design, enrollment, completion, and results of clinical trials; unanticipated costs and expenses; the company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated; the risk that results of clinical trials may not be predictive of future results, and interim and preliminary data are subject to further analysis and may change as more data becomes available; unexpected safety or efficacy data observed during clinical trials; uncertainties related to the regulatory authorization or approval process, and available development and regulatory pathways for approval of the company’s product candidates; changes in the regulatory environment; changes in expected or existing competition; the success of current and future license agreements; our dependence on contract research organizations, and other outside vendors and service providers; product liability; the impact of general business and economic conditions; protection of our intellectual property and avoiding intellectual property infringement; retention of key personnel; delays, interruptions or failures in the manufacture and supply of our product candidates; the availability of and the need for additional financing; the company’s ability to obtain additional funding to support its clinical development programs; uncertainties regarding the timing and results of the August 2022 subpoena from the U.S. Attorney’s Office for the District of Massachusetts; uncertainties regarding the FDA warning letter pertaining to the company’s Watertown, MA manufacturing facility; and other factors described in our filings with the Securities and Exchange Commission. More detailed information on these and additional factors that could affect EyePoint’s actual results are described in EyePoint’s filings with the SEC, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2023, as revised or supplemented by its Quarterly Reports on Form 10-Q and other documents filed with the SEC. All forward-looking statements in this news release speak only as of the date of this news release. EyePoint undertakes no obligation to update or revise any forward-looking statement, whether as a result of new information, future events or otherwise. Investors:Christina TartagliaPrecision AQ (formerly Stern IR)Direct: 212-698-8700christina.tartaglia@sternir.com Media ContactAmy PhillipsGreen Room CommunicationsDirect: 412-327-9499aphillips@greenroompr.com

– DURAVYU 2.7mg demonstrated an early and sustained improvement in BCVA with a gain of +8.9 letters compared to baseline - – DURAVYU 2.7mg demonstrated an early and sustained anatomical improvement mirroring BCVA results with a 68 micron reduction in CST - – Favorable safety profile continues with no DURAVYU-related ocular or systemic SAEs to date – – Full topline data anticipated in Q1 2025 – Oct. 28, 2024 -- EyePoint Pharmaceuticals, Inc. (NASDAQ: EYPT), a company committed to developing and commercializing innovative therapeutics to improve the lives of patients with serious retinal diseases, today announced positive interim 16-week data for the ongoing Phase 2 VERONA clinical trial evaluating DURAVYU, an investigational sustained delivery therapy delivering patent-protected vorolanib, a selective tyrosine kinase inhibitor formulated in proprietary bioerodible Durasert E™, for patients with diabetic macular edema (DME). DURAVYU 2.7mg demonstrated an early, sustained, and clinically meaningful improvement in best-corrected visual acuity (BCVA) and anatomical control versus the aflibercept control arm. A favorable safety and tolerability profile continued for both DURAVYU arms. The 2.7mg dose is also being evaluated in the Phase 3 pivotal trials for wet AMD. The Company expects to report the full topline results in the first quarter of 2025, once all patients complete the trial. “We are encouraged and excited by these highly positive interim results demonstrating clinically meaningful functional and concomitant structural improvement with a continued favorable safety profile of DURAVYU,” said Jay S. Duker, M.D., President and Chief Executive Officer of EyePoint. “DME is a prevalent disease with a significant need for more durable treatments. The interim data from the VERONA trial demonstrates that after a single DURAVYU 2.7mg treatment there was a meaningful, early and maintained improvement in BCVA paired with strong anatomical improvement in retinal thickness, demonstrating the potential for DURAVYU in DME as a sustained delivery therapy. One of the most notable aspects of these data is that both DURAVYU doses showed an immediate benefit over aflibercept control in both BCVA and CST. We believe these compelling interim results support DURAVYU’s potential to advance to non-inferiority pivotal trials in DME. With pivotal wet AMD clinical trials underway and promising DME interim data, DURAVYU has the potential to be the first sustained release therapy to market in two significant indications.” All patients (n=27) have completed the week 16 visit. DURAVYU 2.7mg demonstrated an early and sustained improvement in both BCVA and CST (central subfield thickness) as measured by optical coherence tomography (OCT). BCVA improved +8.9 letters versus +3.2 letters for aflibercept control compared to baseline. CST improved 68.1 microns versus 30.5 microns for aflibercept control compared to baseline. Visual and anatomical gains were observed at Week 4 demonstrating the immediate bioavailability of DURAVYU. Positive trend in BCVA and anatomy continued for patients that have reached the Week 24 visit. Continued positive safety and tolerability profile with no DURAVYU-related ocular or systemic serious adverse events. Additionally, there were no cases of: Endophthalmitis Retinal vasculitis (occlusive or non-occlusive) Insert migration to the anterior chamber Intraocular inflammation (IOI) 82% of eyes in the DURAVYU 2.7mg arm were supplement-free versus 50% in the aflibercept control arm at 16 weeks. “DME is a sight-threatening complication of diabetes that can lead to severe visual loss and eventual blindness,” said Charles Wykoff, M.D., Ph.D., Director of Research, Retina Consultants of Texas and Co-Chair of EyePoint’s Scientific Advisory Board. “There remains a significant need for differentiated and longer-acting treatments, as the current standard of care involves frequent intravitreal injections that can be a burden and have been associated with under-treatment. The interim data from the Phase 2 VERONA trial suggests promising activity in patients with active DME versus aflibercept alone and a favorable safety profile. These results support the potential for DURAVYU to bring substantial value to patients through stable, durable disease control.” “Reducing the treatment burden in patients with DME is a critical unmet need,” said Adam Gerstenblith, M.D., a principal investigator in the VERONA clinical trial and vitreoretinal surgeon at Mid Atlantic Retina Specialists. “As a clinician dedicated to advancing retinal care, I am encouraged by the interim clinical data demonstrating the potential for DURAVYU 2.7mg to extend treatment intervals while improving vision without sacrificing anatomy. The VERONA trial is an important step in the pursuit of treatment options for patients that are safe and durable, and I am pleased to be participating in research that has the potential to shift the treatment paradigm in DME and ultimately improve patient outcomes.” VERONA is a randomized, controlled, single-masked, open label Phase 2 trial of DURAVYU in DME patients previously treated with a standard-of-care anti-VEGF therapy. The trial enrolled 27 patients assigned to one of two intravitreal doses of DURAVYU (1.3mg or 2.7mg) or aflibercept control. The primary efficacy endpoint of the VERONA trial is time to first supplemental aflibercept injection up to 24 weeks based on established supplement criteria. Key secondary endpoints include safety, mean change in best corrected visual acuity (BCVA), mean change in central subfield thickness (CST) as measured by optical coherence tomography (OCT) and change in diabetic retinopathy severity scale (DRSS) over time. More information about the trial is available at clinicaltrials.gov (identifier: NCT06099184). Diabetic macular edema (DME) is the leading cause of vision loss in people with type 1 and type 2 diabetes. DME results when damaged blood vessels leak fluid into the macula, the central portion of the retina responsible for the sharp vision needed for routine tasks such as driving or reading. This resulting retinal swelling can cause blurred vision and may lead to severe vision loss or even blindness. DME is a common form of sight-threatening retinopathy in people with diabetes, with approximately 28 million people afflicted worldwide. As the prevalence of diabetes continues to grow, an increased number of people will be affected by diabetic eye diseases such as DME. The current standard of care for patients experiencing DME include intravitreal injections of short-acting anti-VEGF biologics, corticosteroids, or laser photocoagulation which can become a burden on patients, caregivers, and physicians due to the longevity of the disease. DURAVYUTM, f/k/a EYP-1901, is being developed as a potential paradigm-altering treatment for patients suffering from VEGF-mediated retinal diseases. DURAVYU delivers vorolanib, a potent, selective and patent-protected tyrosine kinase inhibitor (TKI) as a solid bioerodible insert using EyePoint’s proprietary sustained-release Durasert E™ technology. Vorolanib brings a new mechanistic approach to the treatment of VEGF-mediated retinal diseases as a pan-VEGF receptor inhibitor, inhibiting all VEGF receptors. Further, in an in-vivo model of retinal detachment, vorolanib demonstrated neuroprotection and may have antifibrotic benefits as it also blocks PDGF. DURAVYU is shipped and stored at ambient temperature and is administered with a standard intravitreal injection in the physician's office. DURAVYU is immediately bioavailable with zero-order kinetics release for up to nine months. Positive data from both the Phase 1 DAVIO and Phase 2 DAVIO 2 clinical trials of DURAVYU in wet AMD demonstrated clinically meaningful efficacy data with stable visual acuity and CST and a favorable safety profile. Further, data from DAVIO 2 demonstrated an impressive treatment burden reduction of approximately 88% at eight months, six months after treatment with DURAVYU, with over 80% of patients supplement-free or receiving only one supplemental anti-VEGF injection through up to eight months, six months after treatment with DURAVYU. The data from the DAVIO 2 clinical trial supported the advancement of the wet AMD program and the initiation of the Phase 3 LUGANO trial, with the LUCIA pivotal trial to follow by year end 2024. DURAVYU is also currently being studied in the Phase 2 VERONA trial for diabetic macular edema (DME). Full topline data is expected in the first quarter of 2025. EyePoint (Nasdaq: EYPT) is a clinical-stage biopharmaceutical company committed to developing and commercializing innovative therapeutics to help improve the lives of patients with serious retinal diseases. The Company's pipeline leverages its proprietary bioerodible Durasert E™ technology for sustained intraocular drug delivery. The Company’s lead product candidate, DURAVYU™ (f/k/a EYP-1901), is an investigational sustained delivery treatment for VEGF-mediated retinal diseases combining vorolanib, a selective and patent-protected tyrosine kinase inhibitor with bioerodible Durasert E™. DURAVYU is presently in Phase 3 global, pivotal clinical trials as a sustained delivery treatment for wet age-related macular degeneration (wet AMD), the leading cause of vision loss among people 50 years of age and older in the United States, and in a Phase 2 clinical trial in diabetic macular edema (DME). EyePoint expects full topline data from the Phase 2 clinical trial in DME in Q1 2025 and topline data from both Phase 3 pivotal trials in wet AMD in 2026. Pipeline programs include EYP-2301, a TIE-2 agonist, razuprotafib, formulated in Durasert E™ to potentially improve outcomes in serious retinal diseases. The proven Durasert® drug delivery technology has been safely administered to thousands of patient eyes across four U.S. FDA approved products. EyePoint Pharmaceuticals is headquartered in Watertown, Massachusetts. Vorolanib is licensed to EyePoint exclusively by Equinox Sciences, a Betta Pharmaceuticals affiliate, for the localized treatment of all ophthalmic diseases outside of China, Macao, Hong Kong and Taiwan. DURAVYU™ has been conditionally accepted by the FDA as the proprietary name for EYP-1901. DURAVYU is an investigational product; it has not been approved by the FDA. FDA approval and the timeline for potential approval is uncertain. The content above comes from the network. if any infringement, please contact us to modify.