LeonaBio (NASDAQ: LONA) boosts cash to fund Phase 3 breast cancer drug
Rhea-AI Filing Summary
LeonaBio, Inc. reported full-year 2025 results and highlighted a major strategic shift toward oncology and neurodegeneration. For the year ended December 31, 2025, cash, cash equivalents and investments rose to $88.3 million from $51.3 million, helped by a $90 million private placement of common stock and warrants that could bring in up to an additional $146 million if fully exercised.
Research and development expenses increased to $85.6 million, mainly from $68.1 million of acquired in‑process R&D tied to the lasofoxifene license, while general and administrative expenses fell to $16.7 million. Net loss widened modestly to $105.6 million, or $24.70 per share, compared with $96.9 million, or $25.19 per share, in 2024.
The company acquired an exclusive global license (excluding Asia and certain Middle East countries) to late‑stage breast cancer drug candidate lasofoxifene and is running the Phase 3 ELAINE‑3 trial, expecting enrollment completion in 4Q 2026 and topline data in 2H 2027. Its ALS candidate ATH‑1105 showed favorable Phase 1 safety and CNS penetration, with a Phase 2 proof‑of‑concept study in ALS planned to start in the second half of 2026.
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Insights
LeonaBio adds a late‑stage oncology asset, strengthens cash, but remains loss‑making.
LeonaBio has reshaped its story around lasofoxifene in ER+/HER2‑, ESR1‑mutated metastatic breast cancer and ATH‑1105 in ALS. The December 2025 license for lasofoxifene brings a Phase 3, potentially registrational asset into the portfolio, supported by prior Phase 2 data showing a 13‑month median PFS in combination with abemaciclib.
Financially, cash, cash equivalents and investments increased to $88.3 million as of December 31, 2025, boosted by a $90 million private placement plus warrants that could add up to $146 million. This is offset by a larger net loss of $105.6 million and new balance sheet items such as a $37.5 million Sermonix pre‑funded warrant liability and $15.1 million milestone liability.
From an execution standpoint, the key value drivers are the Phase 3 ELAINE‑3 trial and the planned Phase 2 ALS study. ELAINE‑3 is over 50% enrolled with topline results targeted for 2H 2027, while ATH‑1105 is scheduled to enter Phase 2 in 2H 2026. Subsequent disclosures around enrollment progress, warrant exercises and clinical readouts will determine how effectively the bolstered capital base is converted into clinical and, ultimately, commercial value.
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, DC 20549
FORM
CURRENT REPORT
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
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If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act). ☐
Item 2.02 Results of Operations and Financial Condition.
On March 26, 2025, LeonaBio, Inc. (the “Company”) issued a press release reporting its financial results for the year ended December 31, 2025. A copy of the press release is furnished herewith as Exhibit 99.1.
Item 7.01 Regulation FD Disclosure.
On March 26, 2026, LeonaBio, Inc. posted on the investor relations page of its website at investors.leonabio.com an investor presentation furnished as Exhibit 99.2 to this Current Report on Form 8-K (the “Investor Deck”) and incorporated herein by reference. This presentation is expected to be used by the Company in connection with certain future presentations to investors and others. The information contained in the Investor Deck is summary information and contains forward-looking statements that are subject to risks and uncertainties, including those set forth in the Company’s filings with the Securities and Exchange Commission (the “SEC”). The information in the Investor Deck is as of March 26, 2026, except for information that is specifically identified as being as of an earlier date. The Company undertakes no obligation to publicly update or revise the information contained in the Investor Deck or this Item 7.01, except as required by law, although it may do so from time to time. Any such updating may be made through the filing of other reports or documents with the SEC, press releases, disclosure on the Company’s website or other means of public disclosure.
The Company announces material information to the public through a variety of means, including filings with the Securities and Exchange Commission, press releases, public conference calls, the Company’s website (www.leonabio.com), its investor relations website (investors.leonabio.com), and its news site (investors.leonabio.com/news-and-events/press-releases). The Company uses these channels, as well as social media, including its X account (@leonabioinc), LinkedIn account (www.linkedin.com/company/leonabio), Instagram account (@leona.bio) and Facebook page (www.facebook.com/leonabioinc/), to communicate with investors and the public about the Company, its product candidates, and other matters. Therefore, the Company encourages investors, the media, and others interested in the Company to review the information it makes public in these locations, as such information could be deemed to be material information.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
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Description |
99.1 |
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LeonaBio, Inc. press release dated March 26, 2026 |
99.2 |
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LeonaBio, Inc. investor presentation |
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Cover Page Interactive Data File (formatted as Inline XBRL) |
The information furnished in this Current Report under Items 2.02 and 7.01 and the exhibits attached hereto are being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in such a filing.
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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LeonaBio, Inc. |
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Date: |
March 26, 2026 |
By: |
/s/ Mark Litton |
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Mark Litton |
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President and Chief Executive Officer |
LeonaBio Reports Full Year 2025 Financial Results and Provides Business Update
Acquired License to Phase 3 Lasofoxifene Development Program of Novel Selective Estrogen Receptor Modulator (SERM), a Potential Multi-Billion Dollar Opportunity as Treatment Option for Breast Cancer Patients with ESR1-Mutations
Received Gross Proceeds of $90 Million in Private Placement Financing of Common Stock and Warrants with Cash-Exercisable Warrants Potentially Providing up to an Additional $146 Million to Support Development of Lasofoxifene Through Key Clinical and Regulatory Milestones
Expect to Complete Enrollment of Phase 3 Clinical Trial of Lasofoxifene in ER-positive (ER+), HER2-negative, ESR1-mutated Metastatic Breast Cancer in 4Q 2026 with Topline Data Anticipated in 2H 2027
On-track to Initiate Phase 2 Proof-of-Concept Study of ATH-1105 in ALS patients in 2H 2026
BOTHELL, Wash., March 26, 2025 – LeonaBio, Inc. (NASDAQ: LONA), a clinical-stage biopharmaceutical company dedicated to the development of novel therapeutics for diseases with high unmet medical needs, today reported financial results for the year ended December 31, 2025, and provided recent pipeline and business updates.
“2025 was a truly transformational year for LeonaBio. With our license for lasofoxifene, we added a late-stage drug candidate that has the potential to become the endocrine therapy of choice in the multi-billion-dollar second line metastatic breast cancer setting” stated Mark Litton, Ph.D., President and Chief Executive Officer of LeonaBio. “Coupled with our successful $90 million fundraise with the potential for $146 million in additional capital available through warrant exercises, we enter 2026 with the financial resources needed to advance both our oncology and neurodegeneration programs with confidence.”
“Our transition from Athira Pharma to LeonaBio reflects far more than a name change; it represents our evolution into a more focused, diversified, and opportunity-driven biopharmaceutical company. We now have two clinical-stage programs and an experienced team aligned around focused execution. As we look ahead to meaningful clinical milestones in 2026 — including the anticipated completion of enrollment of the Phase 3 ELAINE-3 clinical trial and initiation of patient dosing in our ATH-1105 ALS program — we are energized by what lies ahead. We are building a company that we believe has the potential to change the treatment landscape for patients who urgently need better options, and I couldn’t be more optimistic about the momentum we carry into 2026 and beyond,” concluded Dr. Litton.
Clinical Development & Pipeline Programs
Lasofoxifene – A novel, nonsteroidal selective estrogen receptor modulator (SERM) with a unique binding profile, designed to confer potent activity against both wild-type and mutant estrogen receptors, including the clinically significant ESR1 mutations commonly associated with resistance to endocrine therapy in metastatic breast cancer.
In December 2025, LeonaBio acquired an exclusive global license (excluding Asia and certain countries in the Middle East) from Sermonix Pharmaceuticals, Inc. for rights to develop and commercialize lasofoxifene.
ATH-1105 – A novel, orally available, brain-penetrant, next-generation small molecule drug candidate designed to positively modulate the neurotrophic HGF system for potential treatment of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and Parkinson’s disease. ATH-1105 is currently being developed for the potential treatment of ALS.
Corporate Updates
Financial Results
About LeonaBio
LeonaBio, headquartered in the Seattle, Washington area, is a clinical-stage biopharmaceutical company dedicated to the development of novel therapeutics for diseases with high unmet medical needs, including treatment-resistant metastatic breast cancer and amyotrophic lateral sclerosis (ALS), with the goal of improving patients’ lives. Our lead drug candidates, lasofoxifene and ATH-1105, are novel, small molecule therapies with the potential to address devastating diseases where current treatment options are limited or ineffective. With a strong commitment to scientific excellence and patient-centered innovation, we are dedicated to developing meaningful new therapies for those who need them most.
For more information, visit www.leonabio.com.
Forward-Looking Statements
This communication contains “forward-looking statements” within the meaning of Section 27A of the Securities Act, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. These forward-looking statements are not based on historical fact and include statements regarding: the beneficial characteristics, safety and efficacy of LeonaBio’s drug candidates; the potential of any subsequent clinical trials to show the beneficial characteristics, safety and efficacy of ATH-1105; the potential of LeonaBio to complete the Phase 3 ELAINE-3 clinical trial for lasofoxifene and to meet the trial endpoints, and any subsequent clinical trials to show the clinical benefits of lasofoxifene; LeonaBio’s drug candidates as potential treatments for metastatic breast cancer, amyotrophic lateral sclerosis and other diseases; LeonaBio’s future development plans and the timing thereof; the potential learnings from preclinical studies and other nonclinical data and their ability to inform and improve future clinical development plans; LeonaBio’s ability to obtain regulatory approval for any of its product candidates and to successfully commercialize any approved products; the rate and degree of market acceptance of LeonaBio’s drug candidates, if approved for commercial use; the size and growth potential of the markets for LeonaBio’s drug candidates, if approved for commercial use, and LeonaBio’s ability to serve those markets; anticipated development milestone timelines, such as the initiation of clinical trials and the timing of data releases, and LeonaBio’s ability to meet such timelines; the potential for lasofoxifene to be a new standard of care in its target genetically defined patient group; LeonaBio’s ability to obtain and maintain regulatory approval of its drug candidates in the United States and other jurisdictions and the timing thereof, and any related restrictions, limitations or warnings in the label of any approved drug candidate; and the sufficiency of LeonaBio’s capital resources to advance both its oncology and neurodegeneration programs. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as “may,” “will,” “should,” “on track,” “would,” “expect,” “plan,” “believe,” “intend,” “pursue,” “continue,” “suggest,” “potential,” “target” and similar expressions. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with the possible failure to realize certain anticipated benefits of the license relating to lasofoxifene and the recent private placement financing, including with respect to future financial and operating results; the data from preclinical and clinical trials may not support the safety, efficacy and tolerability of LeonaBio’s drug candidates; development of drug candidates may cease or be delayed; regulatory authorities could object to protocols, amendments and other submissions; future potential regulatory milestones for drug candidates, including those related to current and planned clinical studies, may be insufficient to support regulatory
submissions or approval; whether LeonaBio’s trials are sufficiently powered to meet the planned endpoints; LeonaBio may not be able to recruit sufficient patients for its clinical trials; the outcome of legal proceedings that may in the future be instituted against LeonaBio, its directors and officers; possible negative interactions of LeonaBio’s drug candidates with other treatments; FDA regulatory delays and uncertainty and new policies, including executive orders, changes in the leadership of federal agencies such as the FDA and SEC, staff layoffs, budget cuts to agency programs and research and changes in drug pricing controls; LeonaBio’s assumptions regarding its financial condition and the sufficiency of its cash, cash equivalents and investments to fund its planned operations may be incorrect; adverse conditions in the general domestic and global economic markets, including as a result of tariffs; the impact of competition; the impact of drug candidate development and clinical activities on operating expenses; the impact of new or changing laws and regulations; as well as the other risks detailed in LeonaBio’s filings with the SEC from time to time. These forward-looking statements speak only as of the date hereof and LeonaBio undertakes no obligation to update forward-looking statements. LeonaBio may not actually achieve the plans, intentions or expectations disclosed in its forward-looking statements, and you should not place undue reliance on the forward-looking statements.
Investor & Media Contact:
Julie Rathbun
LeonaBio
Julie.rathbun@leonabio.com
206-769-9219
LeonaBio, Inc.
Condensed Consolidated Balance Sheets
(Amounts in thousands)
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December 31, |
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December 31, |
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2025 |
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2024 |
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(unaudited) |
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Assets |
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Cash and cash equivalents |
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$ |
69,276 |
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$ |
48,438 |
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Short-term investments |
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19,055 |
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2,837 |
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Other short-term assets |
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1,127 |
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3,566 |
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Other long-term assets |
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2,693 |
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3,938 |
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Total assets |
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$ |
92,151 |
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$ |
58,779 |
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Liabilities and stockholders' equity |
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|
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|
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Current liabilities |
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$ |
10,015 |
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$ |
13,135 |
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Sermonix pre-funded warrant |
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37,488 |
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— |
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Milestone liability |
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15,116 |
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— |
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Long-term liabilities |
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1,742 |
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803 |
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Total liabilities |
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64,361 |
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13,938 |
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Stockholders' equity |
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27,790 |
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44,841 |
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Total liabilities and stockholders' equity |
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$ |
92,151 |
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$ |
58,779 |
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LeonaBio, Inc.
Condensed Consolidated Statements of Operations and Comprehensive Loss
(Amounts in thousands, except share and per share amounts)
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Year Ended |
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2025 |
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2024 |
Operating expenses: |
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Research and development |
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$ 17,500 |
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$ 70,682 |
Acquired in-process research and development |
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68,088 |
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— |
General and administrative |
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16,678 |
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26,093 |
Legal expense |
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— |
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4,127 |
Total operating expenses |
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102,266 |
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100,902 |
Loss from operations |
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(102,266) |
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(100,902) |
Other income, net |
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1,236 |
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3,962 |
Sermonix pre-funded warrant change in fair value |
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(4,579) |
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— |
Net loss |
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$ (105,609) |
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$ (96,940) |
Unrealized (loss) gain on available-for-sale securities |
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(5) |
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350 |
Comprehensive loss attributable to common stockholders |
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$ (105,614) |
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$ (96,590) |
Net loss per share attributable to common stockholders, |
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$ (24.70) |
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$ (25.19) |
Weighted-average shares used in computing net loss per share attributable to common stockholders, basic |
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4,275,762 |
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3,848,044 |
Corporate Presentation March 2026 © LeonaBio, Inc.
This presentation and any accompanying oral commentary contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are based on our management’s beliefs and assumptions and on information currently available to our management. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. In some cases, you can identify forward-looking statements by terminology such as “may,” “will,” “should,” “could,” “expect,” “plan,” anticipate,” “believe,” “estimate,” “predict,” “intend,” “potential,” “would,” “continue,” “on track,” “ongoing” or the negative of these terms or other comparable terminology. Forward-looking statements include all statements other than statements of historical fact contained in this presentation, including information concerning our future financial performance and financial condition, business plans and objectives, our ability to obtain funding for our operations, including funding necessary to develop and commercialize our drug candidates and funding necessary for the payment of future milestone and other payments that may be earned by our collaboration partners, timing and success of our planned or future development activities, our ability to obtain regulatory approval, the potential therapeutic benefits and economic value of (1) ATH-1105 as a potential treatment for Alzheimer’s disease, Parkinson’s disease, Parkinson’s disease dementia, amyotrophic lateral sclerosis, neuropathic pain and other neurodegenerative diseases and disorders, and (2) lasofoxifene as a potential treatment for breast cancer, the anticipated reporting of data, the potential learnings from preclinical studies and other nonclinical data and clinical studies and their ability to inform and improve future clinical development plans and to demonstrate the safety and efficacy of our drug candidates, our ability to initiate and successfully advance clinical trials for the development of our product candidates, the rate and degree of market acceptance of our drug candidates, anticipated milestone timelines, such as the timing of data releases, and our ability to meet such timelines, our plans related to commercializing our drug candidates, if approved, the success of competing therapies that are or may become available, potential growth opportunities, our plans for any potential financing, strategic transaction, or partnership, including for ATH-1105 and lasofoxifene, competitive position, and industry environment and potential market opportunities. We do not undertake any duty to update these forward-looking statements. Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors, including, but not limited to, risks associated with the possible failure to realize certain anticipated benefits of the license relating to lasofoxifene and the recent private placement financing, including with respect to future financial and operating results; the data from preclinical and clinical trials may not support the safety, efficacy and tolerability of our drug candidates; development of drug candidates may cease or be delayed; regulatory authorities could object to protocols, amendments and other submissions; future potential regulatory milestones for drug candidates, including those related to current and planned clinical studies, may be insufficient to support regulatory submissions or approval; whether our trials are sufficiently powered to meet the planned endpoints; we may not be able to recruit sufficient patients for our clinical trials; the outcome of legal proceedings that may in the future be instituted against us, our directors and officers; possible negative interactions of our drug candidates with other treatments; U.S. Food and Drug Administration (“FDA”) regulatory delays and uncertainty and new policies, including executive orders, changes in the leadership of federal agencies such as the FDA and U.S. Securities and Exchange Commission (“SEC”), staff layoffs, budget cuts to agency programs and research, and changes in drug pricing controls; our assumptions regarding our financial condition and the sufficiency of our cash, cash equivalents and investments to fund our planned operations may be incorrect; adverse conditions in the general domestic and global economic markets, including as a result of tariffs; the impact of competition; the impact of drug candidate development and clinical activities on operating expenses; the impact of new or changing laws and regulations; as well as the other risks detailed in our filings with the SEC from time to time. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. These factors, together with those that are described in greater detail in our filings with the SEC may cause our actual results, performance or achievements to differ materially and adversely from those anticipated or implied by our forward-looking statements. In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this presentation, and although we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted a thorough inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain, and readers are cautioned not to unduly rely upon these statements. Furthermore, if our forward-looking statements prove to be inaccurate, the inaccuracy may be material. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame, or at all. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. By attending or receiving this presentation you acknowledge that you will be solely responsible for your own assessment of the market and our market position and that you will conduct your own analysis and be solely responsible for forming your own view of the potential future performance of our business. This presentation contains estimates, projections and other information concerning market, industry and other data. We obtained this data from our own internal estimates and research and from academic and industry research, publications, surveys, and studies conducted by third parties, including governmental agencies. These data involve a number of assumptions and limitations, are subject to risks and uncertainties, and are subject to change based on various factors, including those discussed in our filings with the SEC. These and other factors could cause results to differ materially from those expressed in the estimates made by the independent parties and by us. While we believe such information is generally reliable, we have not independently verified any third-party information. This presentation concerns drug candidates that are under clinical investigation and which have not yet been approved for marketing by the FDA. The drug candidates are currently limited by federal law to investigational use, and no representation is made as to their safety or effectiveness for the purposes for which they are being investigated. We announce material information to the public through a variety of means, including filings with the SEC, press releases, public conference calls, our website (www.leonabio.com/), our investor relations website (investors.leonabio.com), and our news site (investors.leonabio.com/news-and-events/press-releases). We use these channels, as well as social media, including our X account (@leonabioinc) and Facebook page (https://www.facebook.com/leonabioinc/), to communicate with investors and the public about LeonaBio, our products, and other matters. Therefore, we encourage investors, the media, and others interested in LeonaBio to review the information we make public in these locations, as such information could be deemed to be material information. Disclaimer © LeonaBio, Inc.
Management team with significant drug development and approval experience LEADERSHIP Mark Litton, PhD President and CEO Mark Worthington, JD General Counsel Kevin Church, PhD CSO Javier San Martin, MD CMO Robert Renninger CFO Mark Kubik CBO Collectively involved in multiple developed products and exits Select prior companies Approved therapies David Portman, MD CEO, Sermonix (consultant) © LeonaBio, Inc.
Expected key inflection points within ~2 years Lasofoxifene Phase 3 registrational study ongoing with >50% enrolled ATH-1105 Phase 2 POC study in ALS planned to start in 2H2026 Topline results expected in 2H2027 Topline results expected 2027 © LeonaBio, Inc.
LATE-STAGE PROGRAM DIVERSIFIES PIPELINE Exciting opportunity in metastatic breast cancer Large Market Opportunity Differentiated Mechanism of Action Positive Phase 2 data Strategic Fit ER+/HER2- disease remains most common breast cancer subtype1 Represents approximately 70% of all breast cancers1 Global metastatic ER+/HER2- market expected to grow from ~$10.9B in 2025 to ~$15.9B by 20292 Designed to overcome resistance that limits current endocrine agents3,4,5 Tissue-selective pharmacology6 Strong combinability profile7 Demonstrated compelling signals of clinical activity7,8 Achieved 13 months of progression free survival (PFS)7 Favorable safety profile and well tolerated with potential QoL benefits6,7,8 Right company and team to bring this program forward Builds on LeonaBio’s late-stage development infrastructure Leverages deep regulatory and development expertise of LeonaBio leadership Sources: 1. NCI. Retrieved from https://seer.cancer.gov/statfacts/html/breast-subtypes.html; 2. Research and Markets. Retrieved from: https://www.researchandmarkets.com/reports/6076080/metastatic-hrher2-breast-cancer-global-market; 3. Venetis et al. Cancer Treat Rev 2023; 4. Laine et al. Breast Cancer Res 2021; 5. Adreano et al, Mol Cancer Ther 2020; 6. Goldfarb et al, Clinical Breast Cancer 2024; 7. Damodaran et. al, Annals of Oncology 2023; 8. Goetz et. al, Annals of Oncology 2023 © LeonaBio, Inc.
Small molecule selective estrogen receptor modulator (SERM) Lasofoxifene for the potential treatment of metastatic breast cancer © LeonaBio, Inc.
DESIGNED TO OVERCOME RESISTANCE, IMPROVE QOL, AND REDEFINE THE STANDARD OF CARE AS THE ENDOCRINE PARTNER OF CHOICE Key Differentiators: Potential best-in-class combination efficacy (13 months PFS)1 Recent outcomes (EMBER-3, EvERA) validate the combination approach to 2L+ mBC2,3 Active against WT and mutant ESR1 where SoC can fail Reduced new onset breast cancer by 83% in a large prevention trial4 As the only SERM in the 2L+ mESR1 space, advantages in tolerability, QoL, and additional clinical benefits (bone, urogenital health)5,6 Lasofoxifene: Differentiated SERM for mESR1+ metastatic breast cancer Sources: 1. Damodaran et. al, Annals of Oncology, 2023; 2. Jhaveri et al NEMJ 2024; 3. Mayer et al, ESMO 2025; 4. LaCroix et al, J Natl Cancer Inst, 2010; 5. Goldfarb et al, Clinical Breast Cancer 2024; 6. Cummings et al. NEJM 2010; Lasofoxifene + Abema combo led to a potential best-in-class median PFS in a heavily pre-treated mESR1 population in Phase 2 ELAINE-2 trial2 Potential best-in-class median PFS of 13 months in 2L/3L post-CDK4/6i setting FDA-aligned registrational Phase 3 trial is ongoing © LeonaBio, Inc.
Treatment-resistant ER+ breast cancer is a critical unmet need 1. Initial Tumor ER+ tumors depend on estrogen signaling via estrogen receptor (ESR1) to grow and survive 2. Therapy response (1L) 1L endocrine therapies (AIs, SERMs, SERDs) are highly effective at shrinking and stabilizing tumor cells 3. Tumor cell dormancy In response to effective therapies, a portion of tumor cells enter a “quiet” state where they rewire survival pathways via ESR1 activating mutations 4. Tumor resistance ESR1 mutated tumor cells are resistant to endocrine therapies; lasofoxifene overcomes this resistance Aromatase inhibitors (AIs) inhibit estrogen production SERMs inactivate ESR1 ESR1 activating mutations cause resistance to current therapies; lasofoxifene addresses this critical unmet need ~70% of breast cancers are driven by estrogen receptor signaling (ER+)2 30% progress to mBC3 ~480k patients Global ER+ breast cancer ~1.6M patients1,2* 40% acquire ESR1 mutations4 ~192k patients *1.6M estimated using global breast cancer incidence (2.3M; Bray et al) and ER+ prevalence (~70%; NCI) Sources: 1. Bray et al. American Cancer Society 2022; 2. NCI. Retrieved from https://seer.cancer.gov/statfacts/html/breast-subtypes.html; 3. OncLive. Retrieved from https://www.onclive.com/view/targeted-agents-expand-the-hr-her2-metastatic-breast-cancer-treatment-arena; 4. Venetis et al. Cancer Treat Rev 2023. © LeonaBio, Inc.
Active ESR1 signaling drives tumor growth and metastasis in ER+ breast cancer1 Current endocrine therapies (SERDs, SERMs) aim to inhibit ESR1 signaling2 ESR1 mutations cause resistance to endocrine therapies3 Structural features of lasofoxifene inhibit mutant ESR1, overcoming resistance4,5 Lasofoxifene is a SERM that blocks ESR1 breast cancer signaling even in the presence of mutations Sources: 1. Miziak et al. Cancers (Basel) 2023; 2. Cao et al. Front Pharmacol 2024; 3. Venetis et al. Cancer Treat Rev 2023; 4. Laine et al. Breast Cancer Res 2021; 5. Adreano et al, Mol Cancer Ther 2020. © LeonaBio, Inc.
OUTPERFORMS SOC SERDS AND SERMS ACROSS ESR1 MUTATIONS, SUSTAINING INHIBITORY POTENCY, AND DRIVING SUPERIOR ANTI-TUMOR ACTIVITY Lasofoxifene retains potency against ESR1 mutations, overcoming a key driver of endocrine resistance Affinity assay: Tested in luciferase reporter lines transfected with WT or mutant versions of ESR1. ESR1 was stimulated with a constant concentration of 17β-estradiol and inhibition of activation was assessed by reduction in luciferase reporter signal. Cell proliferation assay: ESR1-mutant cells treated with antiestrogen in the presence of 100 pmol/L E2. Proliferation assessed by CyQUANTreagent is normalized to E2-treated vehicle. Adapted from Adreano et al, Mol Cancer Ther 2020 Competitors (e.g., fulvestrant) lose potency against mutant ESR1 resistance Superior anti-tumor activity in ESR-1 mutant breast cancer models Inhibition of proliferation of CAMA-1 ESR1Y537S Drug IC50 (nM) Lasofoxifene 1.9 Vepdegestrant 22 Elacestrant 90 4OH-Tamoxifen 14 Fulvestrant 15 Imlunestrant 13 OP-1250 14 Adapted from Parisian et. al, Mol Cancer Ther, 2023 Lasofoxifene maintains similar potency against WT and mutant ESR1 sustained inhibition © LeonaBio, Inc.
Lasofoxifene reduces tumor growth in in vivo animal models and maintains potency in lines with mutated estrogen receptors1,2 Long half-life (6 days), excellent bioavailability, and volume of distribution optimizes receptor antagonism and tumor engagement2,3 No receptor degradation necessary and lack of DDIs potentially allow for favorable dosing, tolerability, and combinability characteristics Unique lasofoxifene MOA and pre-clinical data establish PoC in ESR1 mutations Figure: Multiple bars under the same group denote different dose combinations 1. Adreano et al, Mol Cancer Ther 2020; 2. Laine et al Breast Cancer Res 2021; 3. Gennari, Expert Opin Pharmacother 2009 Adapted from Laine et. al, Breast Cancer Ther, 2021 In the hardest to treat Y573S ESR1-mut MCF7 xenograft mouse model, lasofoxifene demonstrates superior anti-tumor activity compared with fulvestrant Tumor weight (mg) vehicle laso fulv palb fulv/palb laso/palb Figure: Effect of combination therapies on primary tumor growth in the Y537S ERα mutant model © LeonaBio, Inc.
ESTABLISHING LASOFOXIFENE AS THE NEXT-GENERATION ENDOCRINE BACKBONE FOR ER+ METASTATIC BREAST CANCER ELAINE Program: Stepwise validation toward a new standard of care Randomized Ph2 trial to demonstrate lasofoxifene’s targeted mechanism and establish its activity vs SoC fulvestrant in mutant ESR1+ metastatic breast cancer ELAINE-1 Proof of Concept (Complete) Ph2 single-arm study trial to evaluate efficacy of lasofoxifene + abemaciclib (CDK4/6 inhibition) in mutant ESR1+ metastatic breast cancer ELAINE-2 Combination Study (Complete) Global Ph3 pivotal trial to confirm lasofoxifene’s superiority in combination vs SoC fulvestrant and establish laso as new 2L/3L standard of care ELAINE-3 Registrational Trial (Ongoing) Building on an extensive safety database, a systematic step-wise clinical development plan was designed to establish confidence in lasofoxifene through proof-of-concept (ELAINE-1) and a combination study (ELAINE-2), leading to a registrational Phase 3 trial to confirm superiority and establish lasofoxifene as a new standard of care for ER+ metastatic breast cancer © LeonaBio, Inc.
LASOFOXIFENE CLINICAL ACTIVITY VS. FULVESTRANT (SOC) IN ESR1-MUTANT BREAST CANCER IN A POC PHASE 2 STUDY ELAINE-1: Increased PFS and anti-tumor activity with lasofoxifene compared to SoC fulvestrant in mESR1 population HR, Hazard ratio Source: Goetz et. al, Annals of Oncology 2023. Clear efficacy advantage: Lasofoxifene delivered longer progression-free survival and higher tumor response rates vs SoC fulvestrant. Validated targeted approach: ctDNA confirm lasofoxifene’s direct activity against ESR1 mutations. Strong differentiation: Well-tolerated with added quality-of-life benefits, including improvement in urogenital symptoms. ELAINE-1 Proof of Concept Laso (n=52) Fulv (n=51) Median PFS, weeks (95% CI) 24.2 (11.3-32.1) 16.2 (11.7-24.1) Log-rank p-value 0.138 HR (95% CI) 0.699 (0.434 – 1.125) Figure: Kaplan-Meier estimates of progression-free survival Table: Tumor response rates for lasofoxifene vs fulvestrant Laso Fulv CBR 37% 22% ORR 13% 3% Figure: Proportions of patients with ESR1 mutant allele fraction decreased with lasofoxifene treatment © LeonaBio, Inc.
LASOFOXIFENE COMBINATION WITH CDK4/6I ABEMACICLIB IN ESR1-MUTANT BREAST CANCER, 100% PRIOR CDK4/6I (PHASE 2) ELAINE-2: Demonstrated potential best-in-class 13 months PFS with lasofoxifene combination with abemaciclib in a heavily pre-treated mESR1 population No head-to-head trials have been conducted comparing lasofoxifene combination regimens to SoC combination regimens. Therefore, such data may not be directly comparable due to differences in trial protocols, dosing regimens, and patient populations. Accordingly, these cross-trial comparisons should not be relied on. Source: Damodaran et. al, Annals of Oncology 2023. Potential best-in-class durability: Laso+Abema delivered 13-month (56 weeks) median PFS – among the longest seen in 2L/3L post-CDK4/6i. Strong efficacy: High tumor response (56% ORR, 66% CBR) with durable disease control Robust biology: Deep ctDNA and ESR1 clearance correlated with PFS, with benefits extending even to patients with co-mutations. ELAINE-2 Combination Study Median PFS of 13 months; among the longest seen in 2L/3L post-CDK4/6i setting Figure: Kaplan-Meier estimates of progression-free survival © LeonaBio, Inc.
EMERGING DATA SUPPORT COMBINATION ENDOCRINE APPROACHES IN CDK4/6 INHIBITOR–PRETREATED ER+ BREAST CANCER In the 2L+ space, endocrine monotherapy approaches appear to reach a ceiling of ~6 months PFS Durable disease control is increasingly pursued through biomarker-driven combination strategies, rather than next-generation endocrine monotherapy alone With combination therapy, safety and tolerability become even more important With combination therapy, particularly laso + abema, median PFS can extend beyond 12 months, surpassing the one-year benchmark in 2L+ post-CDK4/6 ESR1-mutant disease No stacking of toxicity, laso + abema was well-tolerated with favorable safety profile Treatment landscape is shifting toward combination regimen Abema, abemaciclib; Elac, elsacestrant; Evero, everolimus; Fulv, fulvestrant; Gired, girdestrant; Imlun, imlunestrant; Laso, lasofoxifene; SoC, standard-of-care; Vepdeg, vepdegestrant Comparisons are based on independently published study results. No head-to-head trials have been conducted comparing lasofoxifene combination regimens to SoC combination regimens. Therefore, such data may not be directly comparable due to differences in trial protocols, dosing regimens, and patient populations. Accordingly, these cross-trial comparisons should not be relied on. Sources: EMERALD – Bardia et al, SABCS 2021; VERITAC – Campone et al, NEMJ 2025; postMONARCH – Kalinsky et al, JCO 2024; acelERA – Martin et al, ESMO 2022; evERA – Mayer et al, ESMO 2025; EMBER-3 – Jhaveri et al NEMJ 2024; ELAINE-1, Goetz et al, Annals of Oncology 2023; ELAINE-2 – Damodaran et. al, Annals of Oncology 2023 © LeonaBio, Inc.
FDA-ALIGNED PH3 REGISTRATIONAL TRIAL TO ESTABLISH IMPROVED EFFICACY OF LASOFOXIFENE + ABEMACICLIB COMPARED TO CURRENT SOC COMBINATION ELAINE-3: Registrational trial of lasofoxifene in mESR1 population Adapted from Goetz et. al, Future Oncology, 2025. Stratification Factors: Visceral vs. non-visceral disease Prior chemotherapy in metastatic setting Prior use of palbociclib or ribociclib Key Inclusion Criteria Pre- or post- menopausal women or men Positive ESR1 mutation Locally advanced or metastatic ER+/HER2- breast cancer Measurable or non-measurable lesions Evidence of progression on AI with either palbociclib or ribociclib 500 mg monthly fulvestrant (IM) + 150 mg BID abemaciclib N ≈ 300 5 mg QD lasofoxifene + 150 mg BID abemaciclib N ≈ 300 Primary Endpoint Progression-free survival Key Secondary Endpoints Objective response rate, overall survival Other Secondary Endpoints Clinical benefit rate, duration of response, time to response, time to cytotoxic chemotherapy, quality of life, and safety Screening (30 days) Treatment Period (up to 48 mo) Study Milestones FPI: 1Q2024 (recruiting) LPI: Expected 2H2026 Topline: Expected 2H2027 Study Outcomes ELAINE-3 aims to demonstrate the potential of lasofoxifene as a new standard-of-care for ESR1-driven post-CDK4/6i metastatic breast cancer Randomization (1:1) © LeonaBio, Inc.
OVER 50% ENROLLED – EXPECTED TO READOUT IN 2H2027 Global study with >200 sites Europe, North America, and APAC (including China) Study is being executed by Medpace, a full-service global CRO with extensive experience running large, successful breast cancer trials Primary endpoint is determined by an independent review of centralized scans using industry standard RECIST criteria Primary readout conducted when 285 patients have been determined as meeting the RECIST criteria for progression ELAINE-3 is on track to complete enrollment in 2H2026 © LeonaBio, Inc.
Lasofoxifene was generally well-tolerated and had a differentiated impact on women’s quality of life over standard of care in early trials VAS, vaginal assessment scale; VuAS, vulvar assessment scale Sources: 1. Goldfarb et al. ISSWSH Annual Meeting 2023 (Poster); 2. Sermonix Conf Presentation (Slide #82). Figure: Self-assessed urogenital symptoms (composite VAS/VuAS) for lasofoxifene vs fulvestrant. Improvement Lasofoxifene is a SERM that primarily reduces estrogen signaling in breast tissue sparing healthy signaling in other tissues such as bone and urogenital Participants in the ELAINE-1 trial participated in self-assessed urogenital symptom surveys1 Lasofoxifene treatment tended to reduce incidence of VAS/VuAS symptoms Fulvestrant, the SoC comparator tended to increase symptoms MD, the iSPY-2 EOP study’s principal investigator “Lasofoxifene is reported to promote vaginal and sexual health benefits […] this could have broad implications for both the survival and quality of life for women in the metastatic and early-stage adjuvant settings.” 2 © LeonaBio, Inc.
Lasofoxifene exhibits added clinical benefits over other endocrine therapies important to breast cancer patients and clinicians No head-to-head trials have been conducted comparing combination lasofoxifene therapy to other endocrine therapies Sources: 1. McClung et al. American Society of Bone and Mineral Res Annual Meeting 2015 (Poster); 2. Cummings et al. NEJM 2010; 3. Lewiecki et al., Ther Clin Risk Manag. 2009; 4. Ensrud et al Circulation AHA Journal, 2010; 5. Kagan et al., Menopause 2024 The effects of lasofoxifene have been extensively investigated in several clinical studies Increased bone density and reduced vertebral and non-vertebral fractures1,2 Reduced LDL and coronary heart disease events 2,3,4 Improved symptoms of vaginal atrophy in two Phase 3 studies5 Figure: Cumulative incidence of nonvertebral fractures showing placebo, lasofoxifene 0.25 mg (low dose), lasofoxifene 5 mg (high dose) © LeonaBio, Inc.
BUILT ON ESTABLISHED BIOLOGY, PRIOR CLINICAL SIGNAL, AND ESTABLISHED STANDARD-OF-CARE BENCHMARKS ELAINE-3 is a registrational Phase 3 program Comparisons are based on independently published study results. No head-to-head trials have been conducted comparing lasofoxifene combination regimens to SoC combination regimens. Therefore, such data may not be directly comparable due to differences in trial protocols, dosing regimens, and patient populations. Accordingly, these cross-trial comparisons should not be relied on. Sources – Laso+abema: Damodaran et. al, Annals of Oncology 2023; Palazestrant + Ribo: Olema oncology, ESMO 2025; Vepdegestrant + Palbociclib: Arvinas and Pfizer, ESMO 2024; Elacestrant + abema: Rugo et al, SABCS 2025; Imlunestrant + abema: Jhaveri et al NEMJ 2024; Fulvestrant + abema: Kalinsky et al, JCO 2024; Fulvestrant + Palbociclib (2): Mayer et al, JCO 2024; Fulvestrant + Ribociclib: Kalinsky et al, JCO 2023; Elacestrant monotherapy: Bidard et al, JCO 2022; Vepdegestrant monotherapy: Campone et al NEJM 2025; Imlunestrant monotherapy: Jhaveri et al NEMJ 2024 Clear, validated comparator: Fulv + abema is a well-established 2L SoC in mESR1 mBC, enabling a clear and interpretable superiority test Promising prior efficacy signal: ~13 mo PFS exceeds historical benchmarks Mechanistically differentiated backbone: SERM profile enables mESR1 suppression with favorable tolerability and potential for added clinical benefit Aligned with emerging treatment paradigm: Oral SERD/SERM + CDK4/6i combinations increasingly defining the post-CDK4/6 treatment landscape © LeonaBio, Inc.
Competitive advantages of Laso combo in 2L/3L ESR1-mutant BC ER, estrogen receptor; SERD, selective estrogen receptor degrader; SERM, selective estrogen receptor modulator; ESR1 (gene), estrogen receptor 1; ORR, objective response rate; QoL, Quality of life; PFS, progression-free survival. Comparisons are based on independently published study results. No head-to-head trials have been conducted comparing combination lasofoxifene therapy to other combinations presented in this slide. Therefore, such data may not be directly comparable due to differences in trial protocols, dosing regimens, and patient populations. Accordingly, these cross-trial comparisons should not be relied on. Sources: 1. Jhaveri et al, NEJM 2025; 2. Jhaveri et al SABCS presentation 2025; 3. Goldfarb et al. ISSWSH Annual Meeting 2023 (Poster); 4. Damodaran et. al, Annals of Oncology 2023. Imlunestrant + Abema1,2 Lasofoxifene + Abema3,4 Administration Oral, 400 mg daily tablet, must be taken fasting Oral, 5 mg daily tablet, no food effect MOA SERD (ER degradation) SERM (ER modulation; tissue selectivity) Efficacy EMBER-3, mESR1 population, 60-75% prior CDK4/6i: PFS 11.1 mo (n=67) ORR 39% (n= 54) ELAINE-3, mESR1 population, 100% prior CDK4/6i: PFS ~13 mo (n=29) ORR 56% (n=29) Safety & Tolerability Dose reductions: 42% Grade 3 diarrhea: 9% Anemia: 46% Dose reductions: 21% Grade 3 diarrhea: 0% Anemia: 28% QoL & Clinical Benefits None Improved urogenital symptoms (ELAINE-1) Potential bone density and lipids health benefits (PEARL, CORAL, OPAL studies) Ongoing Phase 3 registrational trial (ELAINE-3) will directly evaluate lasofoxifene + abema vs fulvestrant + abema (SoC) and potentially establish lasofoxifene as endocrine backbone 2L/3L SOC Lasofoxifene profile: Differentiated MOA Competitive efficacy profile Strong safety and tolerability profile Exhibits QoL & clinical benefits over SERDs Large pivotal Phase 3 (n ≈ 600) underway in all post-CDK4/6i ESR1 mutations to support potential registration FDA-recommended combination comparator as opposed to monotherapy in EMBER-3 © LeonaBio, Inc.
LASOFOXIFENE + ABEMACICLIB vs. SERD + CDK4/6I REGIMENS Endocrine backbone choice drives long-term risk and differentiation Comparisons are based on independently published study results. No head-to-head trials have been conducted comparing combination lasofoxifene therapy to other combinations presented in this slide. Therefore, such data may not be directly comparable due to differences in trial protocols, dosing regimens, and patient populations. Accordingly, these cross-trial comparisons should not be relied on. Safety and tolerability While cross trial comparisons should be interpreted with caution, lasofoxifene exhibits a favorable safety and tolerability profile, specifically with regards to dose reduction and serious AEs, and additional QoL benefits No stacking with abemaciclib for diarrhea Combination treatment strategy drives long-term risk Regimens rely on chronic CDK4/6 inhibition, which defines the dominant toxicity burden Endocrine backbone choice therefore determines safety risk, tolerability, combinability and long-term adherence Chronic exposure considerations Oral SERDs are entering longer-duration use across lines and combinations While short-term safety is reassuring, SERD chronic toxicity profiles are still maturing, and longer-term use may impact ER in healthy tissues (e.g. bone, vagina) SERMs bring decades of human exposure and predictable long-term safety characteristics Lasofoxifene has the potential to deliver durable efficacy, minimize long-term safety risks, and provide QoL and clinical benefits that may position it as the next backbone endocrine therapy © LeonaBio, Inc.
Lasofoxifene’s targeted activity in mutant ESR1 presents a billion-dollar precision oncology opportunity in 2L/3L ER+ mBC Sources: 1. Fortune Business Insights. Retrieved from https://www.fortunebusinessinsights.com/industry-reports/breast-cancer-therapeutics-market-100163; 2. LifeSci 1Q2023 Quantitative Survey, Sermonix; 3. Calculated from Komen MBC prevalence (~170k) × NCI ER+/HER2− share (~70%), Komen: Retrieved from https://www.komen.org/breast-cancer/facts-statistics/breast-cancer-statistics, NCI: Retrieved from https://seer.cancer.gov/statfacts/html/breast-subtypes.html; 4. Calculated based on 80% transition to 2L+ (Almekinders et al. Breast Cancer Res Treat 2025); 5. Calculated based on 40% ESR1 mutation incidence (Venetis et al. Cancer Treat Rev 2023). Global breast cancer market: $55B (2027)1 Expected payer acceptance: Fulvestrant, elacestrant precedents Favorable outlook: Physician enthusiasm and QoL advantages may help increase adherence and compliance Number of ER+/HER2- mBC 119k3 Number of ER+/HER2- mBC cases in 2L+ therapy 95k4 Number of patients who will develop ESR1 mutation 38k5 Lasofoxifene peak market sale potential >$1B Assuming ~10% market penetration US Market 2 © LeonaBio, Inc.
Orserdu sales illustrate the commercial opportunity for lasofoxifene’s precision oncology opportunity in 2L/3L ER+ mBC Sources: 1. IQVIA, RBC Capital Markets; 2. Bidard et al, J Clin Oncol 2022 Orserdu (elacestrant) achieved rapid commercial uptake, validating ESR1 mutation as a commercially viable biomarker Commercial success was achieved despite modest clinical efficacy with PFS of ~4 months and low ORR in post-CDK4/6 setting2 Adoption occurred despite notable tolerability challenges, including GI adverse events and lipid abnormalities, underscoring strong physician willingness to use targeted endocrine agents in ESR1-mutant disease Lasofoxifene has the potential to meaningfully expand this validated market, with: Superior efficacy signals including prolonged PFS Improved tolerability, QoL profile, and exhibits added clinical benefits Combination-ready positioning aligned with evolving treatment paradigm Orserdu sales1 © LeonaBio, Inc.
DRIVEN BY COMBINABILITY, TOLERABILITY, AND DIFFERENTIATED CLINICAL BENEFIT Lasofoxifene has the potential to be a backbone endocrine candidate with expansion potential beyond ESR1 mutant disease Treatment landscape schematic is illustrative and not intended to be comprehensive ESR1 and PIK3CA wild-type ESR1 mut PIK3CA mut AI or fulvestrant + CDK4/6 inhibitor or other targeted therapies 1L 2L-3L Lasofoxifene + abemaciclib Lasofoxifene combo regimens Lasofoxifene combo regimens Today Future Future If lasofoxifene demonstrates superiority vs fulvestrant, we believe it has the potential to: Replace fulvestrant as the preferred endocrine partner in CDK4/6-based regimens Expand beyond ESR1-mutant disease into broader post-CDK4/6 populations with other targeted therapies Opportunity to move into earlier lines including the adjuvant setting, and serve as a more tolerable and combinable endocrine backbone © LeonaBio, Inc.
A DIFFERENTIATED THERAPY DESIGNED TO OVERCOME RESISTANCE, IMPROVE QOL, AND ESTABLISH A NEW STANDARD OF CARE IN ER+ ESR1-MUTANT BREAST CANCER Lasofoxifene: Ongoing registrational Phase 3 trial with anticipated readout in 2027 Expansion potential as endocrine partner of choice Oral administration Large unmet need Favorable safety profile and generally well-tolerated Superior PFS from Ph2 Exhibits improved QoL and clinical benefits © LeonaBio, Inc.
Small molecule positive modulator of HGF ATH-1105 for the potential treatment of ALS © LeonaBio, Inc.
Slowing neurodegeneration in ALS is a critical unmet need Sources: 1. Packard Center. Retrieved from https://packardcenter.org/answer-als-partners-to-launch-the-end-als-challenge-digital-competition; 2. CDC. Retrieved from https://www.cdc.gov/als/php/abstracts-publications-reports/prevalence-2022-2030.html; 3. ALS United. Retrieved from https://alsunitedchicago.org/als-life-expectancy-by-age/; 4. ALS Association. Retrieved from https://www.als.org/understanding-als; 5. ALS Association. Retrieved from https://www.als.org/advocacy/federal-public-policy-priorities; 6. ALS Association. Retrieved from https://www.als.org/navigating-als/living-with-als/therapies-care. ALS is a devasting neurodegenerative disease in which people progressively lose muscle control 225,000 people globally affected by ALS1 with ~33,000 of those cases in the US2 Average life expectancy is 2-5 years post-diagnosis3 Every 90 minutes someone is diagnosed with ALS4 Estimated annual out-of-pocket cost for care is $250,0005 Burden of ALS There is no cure for ALS and few effective treatment options Approved therapies only modestly slow progression and improve survival No current ALS drugs significantly protect motor neurons from the complex pathology and progressive degeneration Treatment Limitations6 There is an urgent need for therapies that meaningfully slow neurodegeneration, preserve motor function, improve quality of life, and prolong survival Significant Unmet Need © LeonaBio, Inc.
ATH-1105: A CNS-penetrant positive modulator of HGF as a potential treatment for ALS HGF, hepatocyte growth factor Sources: 1. Ishigaki et al., J Neuropathol Exp Neurol 2007; 2. Lee et al., Acta Neuropathol Commun 2019; 3. Vallarola et al., Int J Mol Sci 2020; 4. Berthiaume et al., Front. Neurosci 2024. ATH-1105 enhances activity of HGF, a critical neurotrophic factor in the nervous system Activation of HGF signaling through MET (HGF receptor) on the surface of neurons and glia initiates processes that counteract neurodegeneration Strong rationale from literature to support HGF modulation in ALS Improves motor function, preserves motor neurons, and delays disease progression1,2,3 ATH-1105 has demonstrated robust effects in preclinical models of ALS4 © LeonaBio, Inc.
CELLS DERIVED FROM FOUR PEOPLE WITH SPORADIC ALS ATH-1105 enhanced MET activation and survival in ALS-patient derived motor neurons MET activation: Data presented as mean ± SEM. Statistical significance was determined via paired t-test comparing MET activation (pMET/Total MET) in motor neurons treated with vehicle or ATH-1105 10 nM for 24 hours ; n = 2-3 technical replicates from each donor. Neuronal survival: Representative image highlighting effect of ATH-1105 on ALS patient-derived motor neurons (ALS 1) in culture. Neuronal survival (number of Tuji1+ neurons) was measured as surviving neurons on Day 6 divided by number of neurons on Day 1 (control expressed as 100%). Scale bar = 100 µm. Data expressed as fold-change between vehicle and ATH-1105 and presented as mean ± SEM. Statistical significance was determined via paired t-test comparing vehicle (containing HGF 0.05 ng/ml) with ATH-1105 10 nM; n = 3-6 technical replicates from each donor . Select doses shown. Source: Reda et al. ALS Drug Development Summit 2025 (Poster). *Results from ALS 4 cell line were uninterpretable as vehicle-treated group did not exhibit a significant reduction in survival. ALS patient-derived motor neurons treated with ATH-1105 exhibited an increase in MET activation (pMET) resulting in improved neuronal survival confirming neuroprotective activity in ALS relevant tissue © LeonaBio, Inc.
PRP-TDP43A315T TRANSGENIC MOUSE MODEL OF ALS ATH-1105 preserved motor function and prolonged survival in preclinical model of ALS Motor Function: Data presented as mean ± SEM. Statistics applied: 2-way ANOVA with the Dunnett’s test versus ALS + vehicle. ****p < 0.0001. n=10 mice per group Survival: Data presented as Kaplan-Meier survival curves. Statistics applied: Log-rank (Mantel-Cox) test, n=20 mice per group at start. Treatment initiated at 28 days old. Source: Berthiaume et al., Front. Neurosci 2024. 85 days 75% survival 35% survival 129 days Treatment initiated 28 days Survival Motor Function © LeonaBio, Inc.
PRP-TDP43A315T TRANSGENIC MOUSE MODEL OF ALS ATH-1105 preserved motor function and prolonged survival in preclinical model of ALS Two months of treatment, Prp-TDP43A315T transgenic mice, “ALS” or “ALS mice.” WT = wild type (healthy control). Sciatic nerve sections stained with toluene blue to highlight axon structure. Scale bar = 10 µm. Data presented as mean ± SEM. Statistics applied: One-way ANOVA with Dunnett’s multiple comparisons test ; ****p<0.0001 vs ALS + vehicle. n=10 mice/group Source: Berthiaume et al., Front. Neurosci 2024. In ALS mice (center), axons in the sciatic nerve are smaller, fewer, and more poorly myelinated Neurodegeneration ATH-1105 (right) normalizes axon morphology Sciatic nerve histopathology In ALS mice, ATH-1105 reduces NfL, a robust marker of neurodegeneration NfL in plasma WT + Vehicle ALS + Vehicle ALS + ATH-1105 20 mg/kg NfL release from degenerating neurons is a translatable biomarker of ALS © LeonaBio, Inc.
PRP-TDP43A315T TRANSGENIC MOUSE MODEL OF ALS Disease progression was attenuated in ALS mice following early or delayed treatment initiation with ATH-1105 Data presented as mean ± SEM. Statistics applied: 2-way ANOVA with the Dunnett’s test versus ALS + vehicle. **p < 0.01; ***p < 0.001; ****p < 0.0001. n=10 mice per group Source: Berthiaume et al., Front. Neurosci 2024. Delayed treatment start Delayed treatment start Motor function Nerve function Neurodegeneration Delayed treatment start Delayed intervention with ATH-1105 resulted in a slowing of further disease progression from time of treatment onset A reduction in plasma NfL levels observed once delayed ATH-1105 treatment begins © LeonaBio, Inc.
COMPLETED PHASE 1 SINGLE AND MULTIPLE DOSE STUDIES IN HEALTHY VOLUNTEERS Phase 1 results support continued development of ATH-1105 for the treatment of ALS Source: Ooi et al. NEALS Annual Meeting 2025 (Poster). All doses studied were generally well tolerated with no dose-limiting adverse events All adverse events were mild There were no serious adverse events No trends suggestive of a safety signal Favorable PK profile Dose linearity Rapid absorption; consistent elimination No accumulation after repeat doses for 10 days Good CNS penetration reaching target exposures that were effective in preclinical studies Encouraging exploratory findings in a potential target engagement biomarker from plasma samples Time post-dose (hours) ATH-1105 Mean Plasma Concentration (ng/mL) ATH-1105 Plasma Concentration-Time Profiles Following Single Oral Doses LLOQ (0.500 ng/mL) © LeonaBio, Inc.
EXPLORATORY ANALYSIS OF NEURONAL-DERIVED EXOSOMES (NDE) IN THE PLASMA FROM PHASE 1 STUDIES Biomarker results indicated a biological effect of ATH-1105 in humans and suggest potential to improve protein pathology in ALS In vitro data: **p<0.01 vs. glutamate alone. One-way ANOVA with Fisher’s multiple comparison post-test; n = 3-4 biological replicates. NDE: Data expressed as percent change from baseline (Day 1 Pre-dose). Mean ± SEM. Mixed effects model analysis with Dunnett’s multiple comparison test vs placebo at 8h-post dose; n = 5-6 subjects per treatment group Mechanism NDEs in human plasma ATH-1105 treatment led to increased expression of phospho-GSK3β (inactive form), a potential biomarker of target engagement that may be relevant for TDP-43 pathology In vitro (spinal motor neurons) HGF/METAKT is known to phosphorylate GSK3β at Ser9 inhibiting its activity and ability to promote protein pathology (pTDP-43) ATH-1105 treatment inhibited GSK3β activity in vitro (increased phosphorylation at Ser 9) shown above, and reduced phospho-TDP-43 in the Prp-TDP43 mouse model of ALS Preclinical data supports mechanism Exploratory biomarker analysis suggests translation of effects on GSK3β © LeonaBio, Inc.
ATH-1105 is ready for a Phase 2 study in people living with ALS Planning underway for a Phase 2 proof-of concept study to explore functional measures, biomarkers, and safety in people living with ALS Design considerations: ≥ 6 months treatment duration Biomarkers, including plasma NfL and NDEs Functional measures ALSFRS-R Vital capacity Grip strength Aim is to explore safety and preliminary efficacy to inform a potentially pivotal clinical trial © LeonaBio, Inc.
A NOVEL THERAPY DESIGNED TO ADDRESS THE COMPLEX PATHOLOGY AND MITIGATE NEURODEGENERATION IN ALS ATH-1105 is a Phase 2 ready asset for the treatment of ALS *in preclinical models Expansion potential Oral administration Neuroprotective* Favorable safety profile and generally well-tolerated Reduces plasma NfL* Biomarker signals in Phase 1 © LeonaBio, Inc.
Transforming our future Compelling clinical development programs in areas of profound need Multibillion-dollar market opportunities Key clinical readouts within 2 years Advancing 2 programs that have the potential to deliver life-changing therapies in breast cancer and ALS © LeonaBio, Inc.
PIPE financing up to $236 million Financing up to $236M supports lasofoxifene development program through topline data with sufficient capital runway into 2028 $90M upfront priced at a greater than 50% premium to our December 17, 2025 closing price of $6.35/share If exercised, warrants provide up to additional $146M for further support © LeonaBio, Inc.
Expected key inflection points within ~2 years Lasofoxifene Phase 3 registrational study ongoing with >50% enrolled ATH-1105 Phase 2 POC study in ALS planned to start in 2H2026 Topline results expected in 2H2027 Topline results expected 2027 © LeonaBio, Inc.
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What are the key upcoming clinical milestones for LeonaBio’s pipeline?
How did LeonaBio’s R&D and G&A expenses change in 2025?
What stage is LeonaBio’s ALS candidate ATH-1105 and what did Phase 1 show?
Filing Exhibits & Attachments
3 documentsPress Releases
