VB-517

Phase 3 trial of izokibep in hidradenitis suppurativa met primary endpoint of HiSCR75 at 12 weeks Company to prioritize development of lonigutamab; dose confirmation ongoing in Phase 2 trial with plans to initiate Phase 3 program in Q1 2025 Cash, cash equivalents, and short-term marketable securities at June 30, 2024 of $635.2 million; projected to extend cash runway to mid-2027 Company to hold webcast and conference call at 5:00pm ET today LOS ANGELES, Aug. 13, 2024 (GLOBE NEWSWIRE) -- ACELYRIN, INC. (Nasdaq: SLRN), a late-stage clinical biopharma company focused on accelerating the development and delivery of transformative medicines in immunology, today announced that the Phase 3 trial of izokibep in Hidradenitis Suppurativa (HS) achieved its primary endpoint of HiSCR75 at 12 weeks, as well as a refocused pipeline strategy that prioritizes lonigutamab in thyroid eye disease (TED) and is projected to extend cash runway. “While today’s positive HS data and previously announced psoriatic arthritis (PsA) data support a path to approval for izokibep, we have determined that a program of this breadth and size is best brought to market by a larger organization with the resources and existing footprint in these indications,” said Mina Kim, Chief Executive Officer of ACELYRIN. “We remain excited by the opportunity for lonigutamab to address unmet needs of patients with TED. Consistent with our commitment to disciplined capital allocation, we have decided to focus our efforts toward rapidly advancing lonigutamab through late-stage development with our existing cash resources. Combined with a reduction in force, this strategic shift allows us to extend our cash runway to mid-2027 and fully fund both Phase 3 trials for lonigutamab.” Izokibep In the global Phase 3 trial in HS, izokibep demonstrated statistically significant responses across multiple efficacy endpoints at 12 weeks, including 33% of patients receiving izokibep 160mg weekly (QW) achieving HiSCR75, compared to 21% receiving placebo (p-value=0.0294). In higher order endpoints, 25% of patients achieved HiSCR90, compared to 9% on placebo (p-value=0.0009), and 22% of patients achieved HiSCR100, compared to 8% on placebo (p-value=0.001). While the primary endpoint was measured at 12 weeks, ACELYRIN has continued dosing patients in a placebo-controlled manner through week 16. The Company has data from two-thirds of patients at week 16 and the preliminary data demonstrate continued deepening of HiSCR responses over time. No new safety signals for izokibep were observed. The most common adverse events were mild-to-moderate injection site reactions, headache, nasopharyngitis, fatigue and diarrhea. Notably, there were no cases of candida infection, liver toxicity or suicidal ideation/behavior in the izokibep treatment arm. ACELYRIN will complete the on-going PsA and HS trials, but will suspend new investment in these indications. The ongoing Phase 2b/3 trial of izokibep in uveitis will continue through its primary endpoint, with top line data expected in the fourth quarter of 2024. Lonigutamab ACELYRIN has completed the Phase 1 proof-of-concept portion of the ongoing lonigutamab trial and the dose-ranging Phase 2 portion in TED patients is continuing. This Phase 2 trial is testing different doses and dose regimens with a goal of establishing a minimum effective dose and enabling selection of the optimal dose and dose regimen for the Phase 3 program. Dose administration every three or four weeks is now being tested. With this dose ranging experience in hand, ACELYRIN plans to forgo the originally planned Phase 2b/3 trial design and move directly into a Phase 3 program, potentially with concurrent trials, which is anticipated to be initiated in the first quarter of 2025. The Company will hold an EOP2 meeting with the FDA later this year and thereafter host an investor presentation to provide additional Phase 2 data and details for the planned Phase 3 program. “ACELYRIN has taken a patient-centered approach to developing lonigutamab, being the first company to conduct dose exploration work with a subcutaneous anti-IGF-1R treatment in patients with Thyroid Eye Disease,” said Shoaib Ugradar, MD, Department of Orbital and Oculoplastic Surgery, private practice, Beverly Hills, California. “I am encouraged by this approach and look forward to participating in the pivotal trials.” SLRN-517 ACELYRIN has completed a single ascending dose study of SLRN-517, the Company’s early anti-C-KIT program, in healthy volunteers and has stopped further development of this program. Corporate Reorganization Aligned with the Company’s prioritization of lonigutamab and associated strategic shifts for izokibep and SLRN-517, ACELYRIN is completing an approximately 33% reduction in its workforce. “I want to thank our colleagues who will be departing from ACELYRIN as part of the restructuring and acknowledge their many contributions to the development of izokibep, and to the evolution of our company. We wish them the very best in the future,” added Ms. Kim. The Company expects these combined efforts will extend cash runway to mid-2027, guidance which includes both the financial impact of the corporate reorganization and clinical program reprioritization. Specifically, the Company’s existing cash resources are expected to fund the ongoing Phase 2 trial and two planned registrational Phase 3 trials for lonigutamab in TED, the on-going izokibep Phase 3 trial in uveitis, and the completion of the ongoing izokibep HS and PsA trials. Q2 2024 Financial Highlights Cash Position: Cash, cash equivalents and short-term marketable securities totaled $635.2 million at June 30, 2024. The Company expects these to fund operations to mid-2027. R&D Expenses: Research and development expenses were $76.4 million for the second quarter as compared to $30.0 million for the same period in 2023. The increases were primarily a result of additional clinical development activity across the pipeline and a $14.3 million expense related to the termination of a supply agreement. G&A Expenses: General and administrative expenses were $16.6 million for the second quarter as compared to $12.7 million for the same period in 2023. The expenses include stock-based compensation expense of $5.3 million, which decreased from $7.2 million for the same quarter in 2023. Net Loss: Net loss for the quarter ended June 30, 2024 was $85.7 million, compared to $26.0 million for the same period in 2023. Webcast and Conference Call Information ACELYRIN will host a conference call and webcast today, August 13, 2024, at 5:00pm ET to discuss these announcements. A live webcast of the conference call can be accessed in the “Events & Presentations” section of ACELYRIN’s website at www.acelyrin.com. A recording of the webcast will be available and archived on the Company’s website for approximately 30 days. Upcoming Investor Presentations ACELYRIN management will participate in webcasted presentations and 1x1 meetings at several upcoming investor conferences including the 2024 Wells Fargo Healthcare Conference, the 22nd Annual Morgan Stanley Global Healthcare Conference and the H.C. Wainwright 26th Annual Global Investment Conference. About LonigutamabLonigutamab is a humanized IgG1 monoclonal antibody targeting the IGF-1 receptor and is delivered subcutaneously. Relative to standard of care, lonigutamab binds to a distinct epitope, which results in internalization of the receptor within minutes, and in preclinical binding and functional laboratory assays, it has been shown to be 75-fold more potent. The characteristics of lonigutamab that enable subcutaneous delivery also enable the potential for longer-term, convenient dosing, which can potentially improve depth and durability of clinical response. About IzokibepIzokibep is a small protein therapeutic designed to inhibit IL-17A with high potency through tight binding affinity, the potential for robust tissue penetration due to its small molecular size, about one-tenth the size of a monoclonal antibody, and an albumin binding domain that extends half-life. Clinical trial data supports the hypothesis that these unique characteristics of izokibep may provide clinically meaningful and differentiated benefits for patients, including resolution of key manifestations of disease. The late-stage izokibep PsA and HS data have demonstrated levels of clinical response comparable with next generation approaches to IL-17 inhibition. These data also demonstrate that targeting IL-17A alone with greater potency can achieve the same or better clinical responses than agents targeting IL-17 subunits more broadly than IL-17A, without their associated safety liabilities. Izokibep is currently being evaluated in multiple late-stage trials in moderate-to-severe hidradenitis suppurativa (HS), moderate-to-severe psoriatic arthritis (PsA), and noninfectious uveitis. About ACELYRIN, INC.ACELYRIN, INC. (Nasdaq: SLRN) is focused on providing patients life-changing new treatment options by identifying, acquiring, and accelerating the development and commercialization of transformative medicines. ACELYRIN’s lead program, lonigutamab, is a subcutaneously delivered monoclonal antibody targeting IGF-1R being investigated for the treatment of thyroid eye disease. For more information about ACELYRIN, visit us at www.acelyrin.com or follow us on LinkedIn and X. Forward Looking StatementsThis press release contains forward-looking statements including, but not limited to, statements related to the overall advancement of ACELYRIN’s programs and ability to accelerate the development and delivery of transformative medicines; the therapeutic potential of ACELYRIN’s product candidates; ACELYRIN’s ability to address unmet needs of patients with thyroid eye disease (TED) anticipated development activities including the planned initiation of Phase 3 trials in TED and the ability for such trials to serve as registrational studies, anticipated cash runway guidance to mid-FY2027, and the ability for such funds to support development of lonigutamab through both Phase 3 trials, plans to continue the ongoing izokibep Phase 2b/3 trial in psoriatic arthritis and the ongoing izokibep Phase 3 trial in hidradenitis suppurativa; the anticipated timing and availability of clinical data from the ongoing izokibep Phase 2b/3 trial in uveitis; and other statements that are not historical fact. These forward-looking statements are based on ACELYRIN’s current plans, objectives and projections, and are inherently subject to risks and uncertainties that may cause ACELYRIN’s actual results to materially differ from those anticipated in such forward-looking statements. Such risks and uncertainties include, without limitation, those associated with the successful completion of development and regulatory activities with respect to ACELYRIN’s product candidates, the risk that future results could differ materially and adversely from early clinical data, the risk that preliminary week 16 data of the Phase 3 trial in HS is not indicative of any future, final week 16 data in such trial, and other risks and uncertainties affecting ACELYRIN including those described from time to time under the caption “Risk Factors” and elsewhere in ACELYRIN’s current and future reports filed with the Securities and Exchange Commission. Forward-looking statements contained in this press release are made as of this date, and ACELYRIN undertakes no duty to update such information except as required under applicable law. ACELYRIN, Inc.Condensed Consolidated Statement of Operations and Comprehensive Loss(in thousands, except share and per share data) (unaudited) Six months ended June 30, Six months ended June 30, 2024 2023 2024 2023 Operating expenses Research and development$76,382 $30,030 $134,414 $197,950 General and administrative$16,643 $12,666 $41,385 $24,579 Total operating expenses 93,025 42,696 175,799 222,529 Loss from operations (93,025) (42,696) (175,799) (222,529) Change in fair value of derivative liability - 10,144 - 10,291 Interest income 8,447 6,685 17,597 9,984 Other income (expense), net (1,094) (172) 37,557 (235)Net loss (85,672) (26,039) (120,645) (202,489)Other comprehensive gain/(loss) Unrealized gain (loss) on short-term marketable securities, net (62) 44 (329) 130 Total other comprehensive gain (loss) (62) 44 (329) 130 Net loss and other comprehensive loss$(85,734) $(25,995) $(120,974) $(202,359)Net loss per share attributable to common stockholders, basic and diluted$(0.86) $(0.40) $(1.22) $(4.71)Weighted-average common shares outstanding, basic and diluted 99,161,710 65,210,117 98,537,685 42,974,640 ACELYRIN, INC.Selected Consolidated Balance Sheet Data(unaudited)(in thousands) June 30, December 31, 2024 2023 Cash and cash equivalents$128,211 $218,097 Short-term marketable securities 507,029 503,229 Total assets 651,739 742,690 Total liabilities 83,521 86,353 Accumulated deficit (609,364) (488,719) ACELYRIN Contact:Tyler MarciniakVice President of Investor Relations and Corporate Affairsinvestors@acelyrin.commedia@acelyrin.com

Completed enrollment in izokibep Phase 3 trial in hidradenitis suppurativa and enrollment completion in Phase 2b/3 trial in uveitis expected this month; top line data for both trials now expected by end of third and fourth quarter of 2024, respectively Reported positive proof-of-concept for lonigutamab in thyroid eye disease patients and positive top-line Phase 2b/3 data for izokibep in psoriatic arthritis Cash, cash equivalents, and short-term marketable securities at March 31, 2024 of $678.5 million Company also announced changes to leadership team LOS ANGELES, May 09, 2024 (GLOBE NEWSWIRE) -- ACELYRIN, INC. (Nasdaq: SLRN), a late-stage clinical biopharma company focused on accelerating the development and delivery of transformative medicines in immunology, today provided an update on various corporate milestones. “Our top priority is executing on our strategy to accelerate the development and delivery of transformative medicines for patients, and we are confident that we can accomplish this mission while being disciplined in our decision-making and responsible in our capital allocation,” said Mina Kim, CEO of ACELYRIN. “We recently reported positive proof-of-concept data for lonigutamab as a subcutaneously delivered treatment for thyroid eye disease, and we are executing on a plan that allows us to take lonigutamab through late-stage development milestones in a capital efficient way.​ Additionally, the top-line results from our recent PsA trial for izokibep were positive, and we look forward to the upcoming results of the hidradenitis suppurativa program, which will help inform our strategy. Given the capital intensity required to fully develop izokibep in multiple indications, we will consider all available options in our efforts to ensure its future success and to enable a successful development and commercialization path.” Pipeline Update and Upcoming Milestones Izokibep in Hidradenitis Suppurativa (HS): The ongoing Phase 3 trial, expected to be the first of two registrational trials, enrolled more rapidly than forecasted and enrollment is now completed with 258 patients. Top line data are now expected in the third quarter of 2024.Lonigutamab in Thyroid Eye Disease (TED): Data from the ongoing Phase 1/2 proof-of-concept (POC) trial are continuing to be evaluated to determine the optimal dose and dose regimen for a Phase 2b/3 trial. This Phase 2b/3 trial, designed to be the first of two registrational trials in TED, is planned to be initiated in the second half of 2024.Izokibep in Uveitis (UV): ACELYRIN expects to complete enrollment in the ongoing Phase 2b/3 trial this month and top line data are anticipated by year-end 2024.SLRN-517: Early evaluation of SLRN-517 is ongoing. Financial Position ACELYRIN expects to report cash, cash equivalents, and short-term marketable securities of $678.5 million at March 31, 2024. The company previously stated that its cash position is expected to fund operations into 2026. ACELYRIN is reiterating this guidance and is actively considering alternatives to further extend its cash runway. Recent Pipeline Updates LonigutamabLonigutamab is a subcutaneously (SC) delivered humanized IgG1 monoclonal antibody targeting the insulin-like growth factor-1 receptor (IGF-1R), a validated mechanism of action for the treatment for thyroid eye disease (TED). ACELYRIN recently reported positive proof of concept for lonigutamab, the first reported subcutaneous anti-IGF-1R to demonstrate clinical responses in thyroid eye disease. In the recently reported data from the Phase 1/2 trial, lonigutamab demonstrated rapid improvements in proptosis and clinical activity score (CAS) at the first measurement – within three weeks after the first subcutaneous dose.These results, along with clinically meaningful improvements in diplopia and mean changes in proptosis from baseline, were at least comparable to intravenous approaches.Lonigutamab was well-tolerated across clinical experience to date and there were no reports of hyperglycemia or hearing impairment and no serious adverse events. There were three cases of mild tinnitus reported, which all resolved without intervention and were not associated with changes in audiology function. IzokibepIzokibep is a small protein therapeutic designed to inhibit IL-17A with high potency and small molecular size, approximately 1/10th the size of a monoclonal antibody. Izokibep is currently being evaluated in multiple late-stage trials in moderate-to-severe hidradenitis suppurativa, psoriatic arthritis, and noninfectious uveitis. Psoriatic Arthritis ACELYRIN recently reported positive top line data from the Phase 2b/3 clinical trial evaluating izokibep in PsA. The global trial met the primary endpoint of ACR50 at 16 weeks with high statistical significance and showed significant, multi-domain responses for the high hurdles of ACR70, PASI100, as well as composite endpoints ACR50/PASI100 and Minimal Disease Activity.The improvements in magnitude of responses relative to the earlier Phase 2 study were notable given the higher burden of disease of the patients in the Phase 2b/3 trial. Further, the results demonstrated higher clinical responses than those reported by the approved IL-17A agents, and responses comparable to those reported by the IL-17A&F agents without evidence of the associated safety liabilities.The Phase 2b/3 clinical trial is expected to be registration-enabling and the dose selection of 160mg every two weeks (Q2W) has been determined to be the optimal clinically effective dose. Hidradenitis Suppurativa While ACELYRIN previously reported that the primary endpoint of HiSCR75 at week 16 did not meet statistical significance in the primary analysis in a global Phase 2b clinical trial in HS, ACELYRIN recently reported longer-term data for izokibep in the Phase 2b clinical trial with the longer-term results demonstrating rapid, dose-ordered improvement across multiple disease manifestations through week 32, with HiSCR100 consistently achieved in approximately 1/3 of patients on the 160 mg every week (QW) dose including in those patients who switched from placebo to izokibep at week 16.The longer-term results showed consistent improvement in resolution of abscesses, nodules, and draining tunnels with marked reduction in skin pain and clinically meaningful improvements in overall quality of life.Additionally, HiSCR100 was achieved earlier in the longer-term results than reported by other IL-17A agents and the IL-17A&F agents without evidence to date for increased risk of infection, especially fungal, or suicidal ideation and behavior, in a patient population predisposed to infection and clinical depression. Leadership Team ChangesIn a separately issued press release, ACELYRIN announced that Mina Kim has been appointed Chief Executive Officer and that ACELYRIN Founder Shao-Lee, M.D., Ph.D. has stepped down as Chief Executive Officer. In addition, Shephard (Shep) Mpofu, M.D., MRCP, FRCP, who most recently served as ACELYRIN’s Senior Vice President of Development and Translational Sciences, has been promoted to the role of Chief Medical Officer. Gil Labrucherie, who serves as ACELYRIN’s Chief Financial Officer, has also been named Chief Business Officer in addition to Chief Financial Officer. Sanam Pangali, who most recently served as ACELYRIN’s Senior Vice President, Corporate Legal, has been promoted to the role of Chief Legal Officer and Head of People. The press release is available on the Investor Relations section of the company’s website. Upcoming Investor PresentationsACELYRIN management will attend the Jefferies Global Healthcare Conference and Ms. Kim will participate in a moderated fireside chat on June 5, 2024 at 1:25 p.m. ET. A webcast of the fireside chat will be available in the “Events & Presentations” section of ACELYRIN’s website. A recording of the webcast will be archived on the company’s website for approximately 30 days. ACELYRIN will forego hosting the previously scheduled Q1 2024 earnings call and the company will file the related 10-Q report no later than May 14, 2024.About ACELYRINACELYRIN, INC. (Nasdaq: SLRN) is a Los Angeles area-based late-stage clinical biopharma company – with additional operations in the San Francisco Bay area – focused on providing patients life-changing new treatment options by identifying, acquiring, and accelerating the development and commercialization of transformative medicines. ACELYRIN has two programs in late-stage clinical development. Lonigutamab is a subcutaneously delivered monoclonal antibody targeting IGF-1R advancing into Phase 2b/3 development for the treatment of thyroid eye disease. Izokibep is a next generation inhibitor of IL-17A in Phase 2b/3 development for the treatment of psoriatic arthritis, hidradenitis suppurativa and uveitis. For more information about ACELYRIN, visit us at www.acelyrin.com or follow us on LinkedIn and X. Forward Looking Statements This press release contains forward-looking statements including, but not limited to, statements related to ACELYRIN’s expectations regarding its cash runway and sufficiency of its cash resources; ACELYRIN’s plan to take lonigutamab through late-stage development milestones; the potential future success of ACELYRIN’s izokibep program; anticipated development activities including the planned initiation and timing of clinical trials, and/or the availability of clinical data; the therapeutic potential of ACELYRIN’s product candidates; and other statements that are not historical fact. These forward-looking statements are based on ACELYRIN’s current plans, objectives and projections, and are inherently subject to risks and uncertainties that may cause ACELYRIN’s actual results to materially differ from those anticipated in such forward-looking statements. Such risks and uncertainties include, without limitation, those associated with the successful completion of development and regulatory activities with respect to ACELYRIN’s product candidates; the timing and results of ACELYRIN’s clinical trials, including the risk that future clinical trial results could differ materially and adversely from prior clinical trial results or data; maintaining and defending intellectual property protection; delays or failures to secure adequate supply of its product candidates; ACELYRIN’s failure to realize the expected benefits of its acquisition of additional programs; legal proceedings and other risks and uncertainties affecting ACELYRIN including those described from time to time under the caption “Risk Factors” and elsewhere in ACELYRIN’s current and future reports filed with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2023. Forward-looking statements contained in this press release are made as of this date, and ACELYRIN undertakes no duty to update such information except as required under applicable law. ACELYRIN Contacts:Tyler MarciniakVice President of Investor Relations, Communications and Advocacyinvestors@acelyrin.commedia@acelyrin.com