Spero Therapeutics (Nasdaq: SPRO) inks SP001 deal and $105M royalty financing
Rhea-AI Filing Summary
Spero Therapeutics entered an exclusive license with Innovent Biologics for SP001, a third-generation Fc-silent anti-CD40L monoclonal antibody. Spero receives a worldwide license outside mainland China, Hong Kong, Macau and Taiwan and grants Innovent exclusive rights in that territory. Spero will pay Innovent a $35.0 million upfront fee, up to approximately $1.05 billion in development, regulatory and commercial milestones, and tiered royalties on net sales, and has agreed to file a U.S. IND for a Licensed Product within 12 months and use commercially reasonable efforts to develop and commercialize at least one indication in major markets.
On July 8, 2026, Spero also completed a non-recourse royalty financing tied to tebipenem HBr (Utebzi) economics under its GSK license. A special-purpose subsidiary issued senior secured notes with $105,000,000 aggregate principal, a 10% annual interest rate and nine-year maturity, subject to a $3,150,000 original issue discount, payable primarily from GSK milestone and royalty payments. A related agreement sold 65% of GSK milestone and royalty proceeds arising after repayment of the notes for $1,575,000, with Spero retaining 35%. The company estimates that net proceeds from this royalty financing, together with existing cash and cash equivalents, will fund operations into the second half of 2029.
SP001 (IBI355) has completed two Phase 1 studies in healthy volunteers and a Phase 1b multiple-ascending-dose trial in Sjögren’s disease, showing a generally benign safety profile and signals of disease-activity improvement. Spero currently expects to initiate a Phase 2 trial in IgG4-related disease in the second quarter of 2027, while Innovent plans a Phase 2 trial in Sjögren’s disease in China by early 2027, with potential expansion of SP001 into additional autoimmune and inflammatory indications.
Positive
- $105 million non-recourse, largely non-dilutive royalty financing backed by Utebzi milestones and royalties, combined with existing cash, is expected to extend Spero’s funding runway into the second half of 2029.
- In-licensing SP001 provides a Phase 2-ready anti-CD40L program with completed Phase 1 and Phase 1b trials and clear plans to start an IgG4-related disease Phase 2 study in Q2 2027.
Negative
- The Innovent license includes up to approximately $1.05 billion in contingent milestones plus ongoing royalties, and Spero sells 65% of post-repayment GSK milestone and royalty proceeds, reducing long-term economics from both SP001 and Utebzi.
Insights
Analyzing...
8-K Event Classification
Key Figures
Key Terms
Royalty Term financial
non-recourse financial
original issue discount financial
Fc-silent medical
Investigational New Drug (IND) regulatory
FAQ
What is the Innovent license agreement for SP001 announced by Spero Therapeutics (SPRO)?
How is Spero Therapeutics (SPRO) funding SP001 and its new immunology strategy?
How long does Spero Therapeutics (SPRO) expect its cash runway to last after these transactions?
What is SP001 and what are Spero Therapeutics’ (SPRO) development plans?
What obligations does Spero Therapeutics (SPRO) have under the Innovent SP001 agreement?
How are the SP001 and Utebzi transactions structured to limit recourse to Spero Therapeutics (SPRO)?
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of The Securities Exchange Act of 1934
Date of Report (Date of earliest event reported):
(Exact name of registrant as specified in its charter)
| (State or other jurisdiction of incorporation) |
(Commission File Number) |
(I.R.S. Employer Identification No.) |
| (Address of principal executive offices) | (Zip Code) |
Registrant’s telephone number, including area code
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered or to be registered pursuant to Section 12(b) of the Act:
| Title of each class |
Trading Symbol(s) |
Name of each exchange on which registered | ||
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).
Emerging growth company
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 1.01 | Entry into a Material Definitive Agreement. |
Innovent License Agreement
On July 8, 2026, Spero Therapeutics, Inc. (the “Company”) entered into a license agreement (the “Innovent Agreement”) with Innovent Biologics (Suzhou) Co., Ltd. and Fortvita Biologics (USA), Inc. (collectively, “Innovent”), pursuant to which Innovent granted the Company an exclusive (even as to Innovent and its affiliates, subject to Innovent’s right to directly or indirectly conduct certain research, non-clinical development and manufacturing activities), sublicensable right and license under certain patent rights and know-how (the “Licensed Intellectual Property”) to research, develop, manufacture, and commercialize Innovent’s proprietary monoclonal antibody targeting CD40 Ligand (“CD40L”), which is referred to as SP001, and certain backup monoclonal antibodies and derivative monoclonal antibodies, in each case targeting CD40L (the “Licensed Compounds”) and products containing the Licensed Compounds (“Licensed Products”) worldwide, excluding the Innovent Territory (as defined below) (the territory excluding the Innovent Territory, the “Licensed Territory”). Innovent also granted the Company a non-exclusive, sublicensable license under the Licensed Intellectual Property to research, non-clinically develop and manufacture the Licensed Compounds and Licensed Products in the mainland of the People’s Republic of China, Taiwan, Hong Kong and Macau (the “Innovent Territory”) in connection with the Company’s exploitation of the Licensed Compounds and Licensed Products in the Licensed Territory.
Under the Innovent Agreement, the Company granted Innovent an exclusive (even as to the Company and its affiliates, subject to the Company’s right to directly or indirectly conduct certain research, non-clinical development and manufacturing activities), sublicensable right and license under certain patent rights and know-how (the “Spero Intellectual Property”) to develop, manufacture, and commercialize the Licensed Compounds and Licensed Products in the Innovent Territory. The Company also granted Innovent a non-exclusive, sublicensable license under the Spero Intellectual Property to research, non-clinically develop and manufacture the Licensed Compounds and Licensed Products in the Innovent Territory.
Each party has agreed that, for five years from the date of the Innovent Agreement, it will not, directly or indirectly, alone or with or for any other person or entity, clinically develop or commercialize any monoclonal antibody, bispecific antibody, or multispecific antibody targeting CD40L in the Licensed Territory. If, within three years from the date of the Innovent Agreement, Innovent or any of its affiliates initiates development of a bispecific or multispecific antibody targeting CD40L, in specified circumstances the Company has an option to include that antibody as a Licensed Compound under the Innovent Agreement subject to certain financial terms. If the Company declines to exercise that option, then Innovent is free to clinically develop and commercialize that antibody in the Licensed Territory.
The Company has agreed to use commercially reasonable efforts to develop, obtain regulatory approval for, and commercialize a Licensed Product in at least one indication in the United States and any one of France, Germany, Italy, Spain, the United Kingdom or Japan. The Company has agreed to file an investigational new drug (“IND”) application for a Licensed Product in the United States within 12 months from the date of the Innovent Agreement, subject to extensions for specified justifiable delays.
Under the terms of the Innovent Agreement, the Company is obligated to pay to Innovent a $35.0 million upfront payment, as well as aggregate milestone payments of up to approximately $1.05 billion upon the achievement of certain development, regulatory and commercial milestones.
The Company is also obligated to pay Innovent tiered royalties ranging from a high single-digit percentage to a mid-teen-digit percentage on annual net sales of all Licensed Products. The Company is obligated to pay royalties on a Licensed Product-by-Licensed Product and country-by-country basis until the latest of: (i) the expiration of the last valid claim of the licensed patents covering the composition of matter of the Licensed Compound contained in such Licensed Product in such country; (ii) the expiration of the last applicable regulatory exclusivity right with respect to such Licensed Product in such country; and (iii) 11 years following the first commercial sale of such Licensed Product in such country (each, a “Royalty Term”). The royalty rate is subject to specified reductions on a Licensed Product-by-Licensed Product and country-by-country basis under specified circumstances.
The Innovent Agreement contemplates that the Company will enter into ancillary arrangements with Innovent, including a clinical supply agreement and a pharmacovigilance agreement. The Company has also granted Innovent a right of first negotiation to be a secondary manufacturer of the Licensed Compounds and Licensed Products for commercialization in the Licensed Territory.
Unless earlier terminated, the Innovent Agreement will expire on the expiration of the last to expire Royalty Term. Unless the Innovent Agreement is earlier terminated, on expiration of each applicable Royalty Term, the Company will have a fully paid-up, irrevocable and perpetual license under the Licensed Intellectual Property to develop, manufacture and commercialize each applicable Licensed Product in the applicable country, which license will become non-exclusive after a specified point in time. Either party may terminate the Innovent Agreement for the other party’s uncured material breach, following a customary notice and cure period, or insolvency. Innovent may terminate the Innovent Agreement if the Company challenges the scope, validity, or enforceability of the licensed patents. The Company may terminate the Innovent Agreement for any reason upon 90 days’ written notice to Innovent prior to the first commercial sale of a Licensed Product, or upon 150 days’ written notice to Innovent after the first commercial sale of a Licensed Product. Additionally, if the Company has the right to terminate the Innovent Agreement for certain uncured material breaches by Innovent, the Company may, in lieu of termination, elect to keep the Innovent Agreement in force and reduce the Company’s subsequent payment obligations. Upon a termination of the Innovent Agreement prior to expiration of an applicable Royalty Term, the Company’s licenses from Innovent will terminate and Innovent will have the right to obtain a license under the Spero Intellectual Property, with a right to sublicense, with respect to specified terminated products, which license will be either non-exclusive and fully paid-up or exclusive and subject to milestone and royalty obligations, at Innovent’s election.
The foregoing description of the Innovent Agreement does not purport to be complete and is qualified in its entirety by reference to the full text of the Innovent Agreement, a copy of which will be filed as an exhibit to the Company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2026.
SP001
SP001 (IBI355) is a third-generation, fully humanized, Fc-silent IgG1 monoclonal antibody targeting CD40L, an upstream immune activation signal involved in T-cell, B-cell, antigen-presenting cell, and platelet biology. SP001 is designed to address platelet activation concerns associated with earlier anti-CD40L antibodies, while preserving key monoclonal antibody properties, including FcRn interaction that supports IgG-like half-life.
Innovent has evaluated this antibody in two healthy volunteer Phase 1 trials: a single ascending dose (“SAD”) study and a multiple ascending dose (“MAD”) study. It has also evaluated SP001 in a Phase 1b MAD study in patients with primary Sjögren’s disease (“SjD”). Data from the Phase 1b SjD study were presented in a poster session at the EULAR 2026 Congress.
The Company currently expects to advance SP001 into a Phase 2 trial in patients with Immunoglobulin G4 related disease (“IgG4-RD”) in the second quarter of 2027. IgG4-related disease is a serious, chronic fibroinflammatory condition that can affect multiple organs, including the pancreas, salivary glands, lacrimal glands, kidneys, lungs, lymph nodes, and other tissues. The disease can cause immune-mediated inflammation, fibrosis, organ damage, relapse risk, and significant treatment burden.
The Company believes there is a broad range of other indications for SP001, including in SjD. Innovent plans to initiate a Phase 2 trial in China for SjD by early 2027, and the Company may opt to expand into this indication at a later date. The Company may also explore other therapeutic areas where the Company believes targeting CD40L presents a compelling biological rationale to impact disease progression.
Royalty Financing Agreements
On July 8, 2026 (the “Closing Date”), the Company, Spero Holdings SPV, LLC, a Delaware limited liability company and wholly owned subsidiary of the Company (“Holdings”), and Spero SPV, LLC, a Delaware limited liability company and wholly owned subsidiary of Holdings (“Issuer”), entered into the following agreements with affiliates of Healthcare Royalty Management, LLC: (i) a non-recourse Note Purchase and Guaranty Agreement (the
“NPA”), by and among Holdings, Issuer, the purchasers party thereto (the “NPA Purchasers”) and HCR Spero SPV, LLC, as the purchaser representative for such NPA Purchasers (the “NPA Purchaser Representative”), (ii) a Royalty and Milestone Payment Interest Purchase and Sale Agreement (the “RPA”), by and among Issuer, the purchasers party thereto (the “RPA Purchasers”), and HCR Spero SPV, LLC, as the purchaser representative for such RPA Purchasers (the “RPA Purchaser Representative”) and (iii) a Limited Recourse Guaranty (the “Limited Guaranty”), by the Company in favor of the NPA Purchaser Representative and RPA Purchaser Representative.
Immediately prior to the Company’s entry into the NPA and RPA, the Company: (i) transferred to Issuer that certain Exclusive License Agreement between the Company and GlaxoSmithKline Intellectual Property (No. 3) Limited (“GSK”), dated as of September 21, 2022 (as amended, the “GSK Agreement”), which provides GSK certain rights to develop and commercialize the tebipenem HBr program, and intellectual property, including license rights, related thereto and (ii) transferred to Holdings the Company’s equity interests in Issuer. Holdings and Issuer are both special purpose vehicles, whose purposes are limited to entering into and performing their obligations under the NPA, RPA and the transaction documents related thereto.
Under the terms of the NPA, Issuer sold to the NPA Purchasers, on the Closing Date, senior secured notes in an aggregate principal amount of $105,000,000 (the “Notes”), which Notes (i) were issued net of an original issue discount in the amount of $3,150,000, which, after giving effect to the RPA Purchase Price referenced below, reduces the aggregate $105,000,000 in gross proceeds of the NPA and RPA by 1.5%, (ii) accrue interest at 10% per annum, which interest, to the extent not paid in cash from available GSK Proceeds (as defined below) in accordance with the terms of the NPA, is capitalized and added to the principal amount of the Notes on a quarterly basis and (iii) mature nine years after the Closing Date. The Notes are secured by substantially all of Holdings’ and Issuer’s assets (collectively, the “Collateral”), which includes the equity interest of Issuer held by Holdings and rights to certain milestone and royalty payments (the “GSK Proceeds”) arising under the GSK Agreement, but excludes intellectual property as to which the grant of security interests is restricted. The Notes and other obligations under the NPA are generally payable solely from the GSK Proceeds, unless voluntarily prepaid at the option of Issuer prior to maturity with a premium or subject to certain mandatory prepayment triggers and foreclosure rights.
Under the terms of the RPA, Issuer sold to the RPA Purchasers, on the Closing Date, 65% of the GSK Proceeds arising after the payment in full of the Notes (the “Purchased Proceeds”) in exchange for a cash payment of $1,575,000 (the “RPA Purchase Price”). Issuer’s obligations under the RPA are secured by a customary back-up lien in the Purchased Proceeds and proceeds thereof. The Company retains an interest in 35% of the GSK Proceeds arising after payment in full of the Notes.
Issuer transferred substantially all proceeds received from the NPA Purchasers and RPA Purchasers in connection with these transactions to the Company as consideration for the asset transfers made by the Company to Holdings and Issuer.
Pursuant to the Limited Guaranty, the Company guarantees, subject to limitations set forth therein, the obligations of Issuer and Holdings under the NPA and RPA. In connection with the NPA and RPA, the Company will provide certain servicing, management and administrative functions on behalf of Holdings and Issuer.
Each of the NPA, RPA and Limited Guaranty contain certain customary terms and conditions, including representations and warranties, indemnities, affirmative and negative covenants, and events of default. Upon the occurrence and during the continuance of an event of default under the NPA, the NPA Purchaser Representative may declare the Notes and other obligations under the NPA to be immediately due and payable, and if such Notes and other obligations are not repaid, foreclose on the Collateral and use the proceeds thereof to repay the Notes, and, in limited circumstances, seek payment from the Company pursuant to the Limited Guaranty. The obligations of the Company in respect of the Limited Guaranty in circumstances where the Company is liable are, except in very limited circumstances, subject to a cap and limited to contract breaches, defaults and other liabilities customary for similarly structured royalty financing transactions.
The foregoing descriptions of the NPA, the RPA and the Limited Guaranty and related documents do not purport to be complete and are qualified in their entirety by reference to the full texts of the NPA, the RPA and the Limited Guaranty, copies of which will be filed as exhibits to the Company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2026.
| Item 2.03 | Creation of a Direct Financial Obligation or an Obligation under an Off-Balance Sheet Arrangement of a Registrant. |
The information set forth under “Royalty Financing Agreements” in Item 1.01 of this Current Report on Form 8-K is incorporated by reference into this Item 2.03.
| Item 7.01 | Regulation FD Disclosure. |
On July 14, 2026, the Company and Innovent issued a joint press release announcing the entry into the Innovent Agreement.
On July 14, 2026, the Company issued a press release announcing the closing of the NPA, the RPA and the transactions contemplated thereby.
The full text of each press release is attached as Exhibit 99.1 and Exhibit 99.2, respectively, to this Current Report on Form 8-K and incorporated herein by reference.
An updated Company presentation is attached as Exhibit 99.3 to this report and is incorporated herein by reference.
The information in Item 7.01 of this Current Report on Form 8-K and Exhibits 99.1, 99.2 and 99.3 attached hereto shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to liability under that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act or the Exchange Act, except as expressly set forth by specific reference in such a filing.
| Item 8.01 | Other Events. |
Cash Runway
Based upon the Company’s current plans and forecasted expenses, the Company estimates that the net proceeds from the royalty financing transaction, together with the Company’s existing cash and cash equivalents, will enable the Company to fund its operating expenses and capital expenditure requirements into the second half of 2029. The Company has based this estimate on assumptions that may prove to be wrong, and the Company could use its available capital resources sooner than it currently expects.
Cautionary Note Regarding Forward Looking Statements
This Current Report on Form 8-K contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, including, without limitation, statements regarding the Company’s potential payment of certain milestone payments as well as royalty payments on net sales in connection with the Innovent Agreement; statements regarding the Company’s future plans or expectations for SP001, including plans and timing with respect to future clinical trials as well as trial design; statements regarding the Company’s receipt of payments pursuant to the NPA and RPA; and statements regarding the Company’s cash runway. In some cases, forward-looking statements may be identified by terms such as “may,” “will,” “should,” “expect,” “plan,” “aim,” “anticipate,” “could,” “intent,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue,” the negative of these terms or other similar expressions; however, the absence of these words does not mean that statement is not forward looking. Any forward-looking statements in this Current Report are based on management’s current expectations and beliefs and are subject to a number of important risks, uncertainties and other factors that may cause actual results to differ materially from those indicated by such forward looking statements, including the anticipated benefits from the Innovent Agreement and the NPA and RPA; the risks associated with the Company’s ability to maintain the Innovent Agreement and the NPA and RPA; the Company’s expectations regarding the potential therapeutic benefits of SP001; the Company’s expectations for clinical and preclinical development, including additional IND filings, expansion into additional indications and geographies, enrollment in clinical trials, and availability of clinical trial data; the implementation of the Company’s business model and strategic plans for our business and current and future product candidates; the Company’s need for
additional funding; the Company’s ability to retain key personnel; whether the Company’s cash resources will be sufficient to fund its continuing operations for the periods anticipated; and other factors discussed in the “Risk Factors” set forth in filings that the Company periodically makes with the Securities Exchange Commission. The forward-looking statements included in this Current Report represent the Company’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, the Company explicitly disclaims any obligation to update any forward-looking statements.
| Item 9.01 | Financial Statements and Exhibits. |
| Exhibit No. |
Description | |
| 99.1 | Joint press release issued by Spero Therapeutics, Inc. and Innovent on July 14, 2026 | |
| 99.2 | Press release issued by Spero Therapeutics, Inc. on July 14, 2026 | |
| 99.3 | Spero Therapeutics, Inc. Corporate Presentation, dated July 2026 | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document and incorporated as Exhibit 101) | |
SIGNATURE
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.
| Date: July 14, 2026 | SPERO THERAPEUTICS, INC. | |||||
| By: | /s/ Esther Rajavelu | |||||
| Esther Rajavelu | ||||||
| Chief Executive Officer and Chief Financial Officer | ||||||
Exhibit 99.1
Spero Therapeutics and Innovent Biologics Announce Exclusive License for SP001 (IBI355), a
Phase 2-Ready Third-Generation Anti-CD40L Antibody
| • | Under the terms of the agreement, Spero will receive exclusive global rights, excluding Greater China, to develop, research, manufacture, and commercialize SP001 (IBI355) |
| • | Innovent will receive an upfront payment, and is eligible to receive development, regulatory and commercial milestone payments, totaling approximately US$1.1 billion, as well as tiered royalties on net sales |
| • | Spero plans to initiate a Phase 2 trial for SP001 in Q2 2027 in IgG4-related disease (IgG4-RD), a serious, chronic fibroinflammatory condition with significant treatment burden and limited therapeutic options |
| • | Innovent plans to initiate a Phase 2 trial in China by early 2027 for Sjögren’s disease (SjD), a chronic autoimmune disorder with limited therapeutic options |
CAMBRIDGE, Mass., SAN FRANCISCO and SUZHOU, China, July 14, 2026 – Spero Therapeutics, Inc. (Nasdaq: SPRO) and Innovent Biologics, Inc. (01801.HK) today announced an exclusive license agreement for SP001 (Innovent R&D code: IBI355), a third-generation Fc-silent anti-CD40L antibody. Spero will receive exclusive rights to develop, research, manufacture, and commercialize SP001 worldwide, excluding Greater China, where Innovent retains rights. Spero currently expects to advance SP001 into a Phase 2 study in IgG4-RD patients in Q2 2027; Innovent expects to initiate a Phase 2 trial in China for SjD by early 2027.
“Having successfully advanced and delivered a therapy for patients with serious infectious diseases, we are now applying the same disciplined development approach to immune-mediated diseases. This in-licensing transaction establishes the foundation of our new pipeline and positions Spero to pursue potentially transformative therapies for patients living with chronic, debilitating conditions,” said Esther Rajavelu, President and Chief Executive Officer of Spero Therapeutics. “We view CD40L as a clinically validated pathway with broad applicability across several immune-mediated diseases. In IgG4-RD, we believe this approach has the potential to meaningfully address the burden patients face from a chronic, relapsing condition with limited treatment options. Beyond IgG4-RD, we see opportunities to explore the role of CD40L inhibition across multiple autoimmune and inflammatory conditions. We are delighted to partner with Innovent Biologics, whose scientific leadership, development expertise, and commitment to innovation have been instrumental in advancing this program to its current stage.”
“CD40L is an important upstream mediator of immune activation and T-cell/B-cell collaboration, both of which are relevant to IgG4-RD progression,” said Dr. Arezou Khosroshahi, MD, Professor of Medicine, Emory University School of Medicine. “A non-B cell depleting approach that interrupts CD40L signaling could represent an important area for clinical evaluation in IgG4-RD, where patients need additional options that address chronic inflammation, relapse, and treatment burden.”
SP001 (IBI355) targets CD40L, an immune signal protein that sits upstream of multiple immune pathways and has the potential to redefine treatment paradigms across a range of immune-mediated diseases. Innovent has evaluated this antibody in two healthy volunteer Phase 1 trials: a single ascending dose (SAD) study and a multiple ascending dose (MAD) study. Innovent has also evaluated SP001 in a Phase 1b MAD study in patients with SjD. Data from the Phase 1b SjD study were presented in a poster session at the EULAR 2026 Congress.
“IgG4-related disease, Sjögren’s disease, and other autoimmune conditions impose significant burdens on patients worldwide, with many facing limited treatment options.” said Dr. Lei Qian, Chief R&D Officer (General Biomedicine) of Innovent Biologics. “We are pleased to partner with Spero Therapeutics on IBI355 to advance the development of this CD40L-targeted approach. By combining Innovent and Spero’s immunology expertise and development commitment, we aim to accelerate the delivery of differentiated therapies to patients living with these chronic conditions. Our shared goal is to bring meaningful new options to patients in need, wherever they are.”
Under the terms of the license agreement, Spero will receive exclusive rights to develop, research, manufacture, and commercialize SP001 worldwide, excluding Greater China (Mainland China, Hong Kong, Macau and Taiwan). Innovent will receive an upfront payment and is eligible to receive development, regulatory and commercial milestone payments, bringing total value of the deal to approximately US$1.1 billion. Innovent is also eligible to receive tiered royalties on net sales generated in Spero’s licensed territories.
About SP001 (IBI355)
SP001 (IBI355) is a third-generation, humanized, Fc-silent IgG1 monoclonal antibody targeting CD40L, an upstream immune activation signal involved in B-cell, antigen-presenting cell, and platelet biology. By blocking CD40L, SP001 has the potential to provide a targeted non-B-cell-depleting treatment across multiple immune-mediated diseases where immune-cell interactions drive chronic inflammation, relapse, and tissue damage. SP001 is designed to address platelet activation concerns associated with earlier anti-CD40L antibodies, while preserving key monoclonal antibody properties, including FcRn interaction that supports IgG-like half-life.
About IgG4-Related Disease
IgG4-related disease is a serious, chronic fibroinflammatory condition that can affect multiple organs, including the pancreas, salivary glands, lacrimal glands, kidneys, lungs, lymph nodes, and other tissues. The disease can cause immune-mediated inflammation, fibrosis, organ damage, relapse risk, and significant treatment burden. Current approaches can include steroids and B-cell-directed therapies, but additional options are needed to support durable disease control, reduce long-term treatment burden, and preserve immune function.
About Sjögren’s Disease (SjD)
Sjögren’s disease is a chronic, systemic autoimmune disorder that primarily affects the salivary and tear glands, but can also involve multiple organs in more severe cases. It is one of the most common autoantibody-driven diseases, yet no approved therapies address its underlying systemic nature, and it predominantly affects women. The disease is marked by autoantibody production, chronic inflammation, and lymphocytic infiltration, leading to symptoms such as dry eyes, dry mouth, joint pain, and fatigue. In some patients, organ involvement can include kidney or lung dysfunction, and there is an increased risk of non-Hodgkin’s B-cell lymphoma. More than half of patients develop moderate-to-severe disease, with a burden comparable to other serious autoimmune conditions.
About Innovent Biologics
Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 19 products in the market. It has 1 asset in NMPA NDA review, 5 assets in Phase 3 or pivotal clinical trials and 14 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Lilly, Takeda, Pfizer, Roche, Sanofi, Incyte, LG Chem and MD Anderson Cancer Center.
Guided by the motto, “Start with Integrity, Succeed through Action” Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.
Statement: Innovent does not recommend the use of any unapproved drug (s)/indication (s).
About Spero Therapeutics
Spero Therapeutics is a clinical-stage biopharmaceutical company focused on advancing next-generation medicines in immunology and inflammation for patients with serious diseases and major treatment gaps. The company’s lead program, SP001, is a third-generation, Fc-silent anti-CD40L monoclonal antibody being advanced first in IgG4-related disease, with a broad potential for additional immune-related conditions. For more information, visit www.sperotx.com
Forward-Looking Statements of Spero Therapeutics
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements include, but are not limited to, statements regarding Spero’s plans, strategy, and expectations for future development; the potential benefits of SP001; the potential of CD40L blockade in IgG4-related disease and other immune-related conditions; Spero’s plans to advance SP001 into clinical development; anticipated development timelines, regulatory activities, and future milestones; and the potential benefits of Spero’s agreement with Innovent. In some cases, forward-looking statements may be identified by terms such as “may,” “will,” “should,” “expect,” “plan,” “aim,” “anticipate,” “could,” “intent,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue,” the negative of these terms or other similar expressions. Forward-looking statements are based on Spero’s current expectations and assumptions and are subject to risks and uncertainties that could cause actual results to differ materially
from those expressed or implied by such statements. These risks and uncertainties include, among others, risks related to the completion and integration of the Innovent transaction; Spero’s ability to successfully develop SP001; the timing and outcome of clinical trials and regulatory interactions; the ability to obtain and maintain regulatory approvals; potential safety, efficacy, manufacturing, supply, intellectual property, financing, competitive, and market risks; and other risks described in Spero’s filings with the Securities and Exchange Commission. The forward-looking statements included in this press release represent Spero’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Spero undertakes no obligation to update any forward-looking statements, except as required by law.
Forward-looking statement of Innovent Biologics
This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words “anticipate”, “believe”, “estimate”, “expect”, “intend” and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent’s control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent’s competitive environment and political, economic, legal and social conditions. Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect.
Contact:
Spero Therapeutics:
Investor Inquiries:
Shai Biran, PhD
IR@Sperotherapeutics.com
Media Inquiries:
media@sperotherapeutics.com
Innovent Biologics:
Media Inquiries:
pr@innoventbio.com
+86 512-69566088
Investor Inquiries:
ir@innoventbio.com
+86 512-69566088
Exhibit 99.2
Spero Therapeutics Announces $105 Million Non-Recourse Non-Dilutive Financing Backed by
a Portion of Utebzi Milestones & Royalties
| • | Financing supports Phase 2 development of SP001, Spero’s first immunology drug candidate, in-licensed from Innovent Biologics |
| • | Transaction unlocks immediate value from future Utebzi (tebipenem pivoxil) milestones and royalties, and positions Spero to participate in potential long-term commercial upside |
| • | Spero updates its cash runway guidance into the second half of 2029 |
CAMBRIDGE, Mass., July 14, 2026 – Spero Therapeutics, Inc. (Nasdaq: SPRO), a clinical-stage biopharmaceutical company focused on advancing next-generation medicines in immunology and inflammation, today announced a $105 million non-recourse non-dilutive royalty financing transaction with affiliates of Healthcare Royalty, a business of KKR (HCRx). Under the agreement, HCRx will receive a portion of future milestone and royalty payments associated with sales of Utebzi™ (tebipenem pivoxil). The proceeds will primarily be used to support advancement of Spero’s lead immunology drug candidate, SP001, a Phase 2-ready, Fc-silent, third-generation anti-CD40L monoclonal antibody with potential for development across a range of immune-mediated diseases.
“Over the past year, in collaboration with GSK, we successfully advanced Utebzi through FDA approval, while executing on our strategy to strengthen Spero and position the Company for its next phase of growth. This transaction further strengthens our balance sheet and provides non-dilutive capital as we embark on an immunology-focused strategy,” said Esther Rajavelu, President and Chief Executive Officer of Spero Therapeutics. “By unlocking immediate value from a portion of future Utebzi milestone and royalty streams, we are well positioned to execute on the clinical development for SP001 and continue building a differentiated pipeline for patients with immune-mediated diseases.”
The financing was completed concurrently with the execution of an exclusive license agreement with Innovent Biologics for the SP001 asset and follows last month’s U.S. approval of Spero Therapeutics-developed Utebzi for complicated urinary tract infections. Spero Therapeutics has granted GSK an exclusive license to develop and commercialize Utebzi in all territories, except certain territories in Asia, where Meiji holds development and commercialization rights. Following the transaction, Spero updates its cash runway guidance into the second half of 2029.
“We are pleased to partner with Spero on this acquisition of certain Utebzi milestones and royalties. As the first approved oral carbapenem therapy, Utebzi represents a meaningful innovation and value proposition for patients, physicians and payers,” said Clarke Futch, Chairman and CEO of HealthCare Royalty.
Terms of the Agreement
Under the terms of the agreements, HCRx will provide Spero with a $105 million payment at closing, net of original issue discount and applicable fees, in exchange for rights to anticipated payments from sales of Utebzi owing from GSK. HCRx will receive quarterly principal and interest payments, derived solely from the GSK payments due to Spero, until the loan balance is repaid. Following repayment, Spero will retain 35% of subsequent GSK payments related to sales of Utebzi, preserving potential long-term upside from the asset.
J. Wood Capital Advisors acted as Spero’s exclusive financial adviser and WilmerHale acted as legal advisor to Spero on the financing transaction. Sidley Austin LLP acted as legal advisor to HCRx.
About SP001
SP001 is a third-generation, fully humanized, Fc-silent IgG1 monoclonal antibody targeting CD40L, an upstream immune activation signal involved in T-cell, B-cell, antigen-presenting cell, and platelet biology. By blocking CD40L, SP001 has the potential to provide a targeted non-B-cell-depleting treatment across multiple immune-mediated diseases where immune-cell interactions drive chronic inflammation, relapse, and tissue damage. SP001 is designed to address platelet activation concerns associated with earlier anti-CD40L antibodies, while preserving key monoclonal antibody properties, including FcRn interaction that supports IgG-like half-life.
About HealthCare Royalty
HealthCare Royalty (“HCRx”) is a leading royalty acquisition company founded in 2006 that is majority owned by KKR & Co. Inc. (NYSE: KKR). Over two decades, the HCRx team has developed a strong track record of investing in commercial-stage and near-commercial-stage biopharmaceutical assets, committing $7+ billion in over 110 biopharmaceutical products. With offices in New York, Stamford, San Francisco, Boston, London and Miami, HCRx continues to advance biopharmaceutical innovation by providing innovative capital solutions to counterparties. For more information, visit https://www.hcrx.com. HEALTHCARE ROYALTY®, HEALTHCARE ROYALTY PARTNERS® and HCRx® are registered trademarks of HealthCare Royalty Management, LLC.
About Spero Therapeutics
Spero Therapeutics is a clinical-stage biopharmaceutical company focused on advancing next-generation medicines in immunology and inflammation for patients with serious diseases and major treatment gaps. The company’s lead program, SP001, is a third-generation, Fc-silent anti-CD40L monoclonal antibody being advanced first in IgG4-related disease, with a broad potential for additional immune-related conditions. For more information, visit www.sperotx.com
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements include, but are not limited to, statements relating to the anticipated benefits of the non-dilutive royalty-backed transaction, including the anticipated use of proceeds; Spero’s expectations regarding its ability to advance SP001 into clinical development and the potential benefits thereof; anticipated cash runway, and future milestones; and the potential benefits of Spero’s agreement with Innovent. Forward-looking statements are based on
Spero’s current expectations and assumptions and are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. These risks and uncertainties include, among others, risks related to the completion and integration of the Innovent transaction; Spero’s ability to successfully develop SP001; the timing and outcome of clinical trials and regulatory interactions; the ability to obtain and maintain regulatory approvals; potential safety, efficacy, manufacturing, supply, intellectual property, financing, competitive, and market risks; and other risks described in Spero’s filings with the Securities and Exchange Commission. Spero undertakes no obligation to update any forward-looking statements, except as required by law.
Investor Relations Contact:
Shai Biran, PhD
Spero Therapeutics
IR@Sperotherapeutics.com
Media Inquiries:
media@sperotherapeutics.com
Corporate Presentation July 2026 Exhibit 99.3
This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding future expectations, plans and prospects for the Company; the ability to successfully achieve and execute on the Company’s goals, priorities and preclinical and clinical milestones; the Company’s expectations regarding the potential therapeutic benefits of SP001; the potential benefits from the Company’s current or future arrangements with third parties, including the anticipated benefits from the in-license of SP001; the Company’s expectations for clinical and pre-clinical development, trial design, additional Investigational New Drug (IND) filings, expansion into additional indications and geographies, the enrollment in clinical trials, and availability of clinical trial data; and other statements containing the words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would,” “working” 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 Company’s ability to advance SP001 on the timelines expected or at all; obtain and maintain necessary and desirable approvals from the U.S. Food and Drug Administration (FDA) and other regulatory authorities; implement the clinical plan for SP001, which is largely based on data generated by the licensor, Innovent Biologics, Inc., and may change based on data we observe which may be materially and adversely different compared to the results Innovent provided to the Company; compete successfully with other companies that are seeking to develop IgG4-related disease and Sjögren’s disease; raise the substantial additional capital needed, on the timeline necessary, to support development efforts and ongoing operations; manage expenses; maintain and defend our intellectual property rights for SP001 or any other product candidate; and the anticipated benefits of the non-recourse non-dilutive royalty-backed financing, including the anticipated use of proceeds. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company’s actual results to differ materially from those contained in the forward-looking statements, see the “Risk Factors” section, as well as discussions of potential risks, uncertainties and other important factors, in the Company’s most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this presentation represent the Company’s views as of the date hereof and should not be relied upon as representing the Company’s views as of any date subsequent to the date hereof. The Company anticipates that subsequent events and developments will cause the Company’s views to change. However, while the Company may elect to update these forward-looking statements at any point in the future, the Company specifically disclaims any obligation to do so. This presentation contains estimates and other statistical data made by independent parties and by us relating to market size and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such data and estimates. The Company has not independently verified the accuracy and completeness of the information obtained by third parties included in this presentation. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. SP001 is known as IBI 355 prior to the closing of the in-licensing agreement with Innovent. Cautionary Note Regarding Forward Looking Statements and Disclaimer
Developing Novel Medicines for Immune-Mediated Diseases Established operational and public company infrastructure SP001, a third-generation Fc-silent anti-CD40L mAb with potential for development across a range of immune-mediated diseases Cash runway into 2H 2029 Lead indication in IgG4-related disease (IgG4-RD)
Key Investment Highlights: SP001 Sjögren’s disease, additional rheumatological applications, and applications in non-rheumatological therapeutic areas Target with human proof-of-concept in several autoimmune diseases Differentiated mechanism compared to other B-cell targeting agents Preclinical data show high potency compared to key competitors Completed 2 healthy volunteer trials and Phase 1b in Sjögren’s disease Expansion opportunities Lead program in IgG4-RD Phase 2 ready antibody Potential best-in-class profile CD40L validated target
Indication Exploratory Phase 1 Phase 2 Phase 3 Catalyst / Expected timing IgG4-RD Phase 2 initiation Q2 2027 Sjögren’s disease (Innovent)* Phase 2 initiation by early 2027 * Development in greater China SP001 Development Plan for Rheumatological Disorders
Adapted from Laman JD, Molloy M, Noelle RJ. Switching off autoimmunity. Science. 2024 Aug 23;385(6711):827-829. CD28/CD80–CD86 T-cell co-stimulation not shown for clarity CD40-CD40L System: A Master Regulator of Immunity Antigen presentation: CD4 T cells present a CD40L “go” signal to antigen presenting cells (APC), promoting inflammation. SP001 thus blocks an upstream signal that sustains autoimmunity. B cells: SP001 blocks the upstream CD40L signal required for B cell survival, antibody production, cytokine secretion, and antigen presentation back to T cells SP001 blocks the immune-activating CD40/CD40L signals between CD4 & CD8 T cells and between CD8 T cells and APC
Sources: Wallace ZS et al. Ann Rheum Dis 2023; Stone JH et al. NEJM 2012; Lanzillotta M. et al. Rheumatology 2020.; De IgG4-RD DelveInsight Epidemiology, 2024. CD40L Mechanism Provides Multiple Development Opportunities Phase 2 ready in Sjögren's disease Additional rheumatological diseases Exploratory applications in non-rheumatological therapeutic areas Under-explored therapeutic areas may provide attractive entry points for longer-term expansion Rare chronic disease with fibroinflammatory burden leading to organ failure Substantial treatment burden with high relapse rates Approved therapy and agents in development target B-cells CD40L blockade affects both B and T cells; potential for use as chronic disease modifying therapy IgG4-Related Disease (IgG4-RD) Potential Expansion Opportunities
SP001 1,2. Lists may not be all inclusive. 2. Initiated by other industry sponsors developing CD40L targeting agents. Preliminary Indications Selected Offer Attractive Competitive Dynamics Spero’s Potential Development1 Ongoing Clinical Trials in Additional Indications2 IgG4-related disease – Sjögren’s disease Sjögren’s disease Type 1 diabetes Systemic Lupus Erythematosus Transplant rejection Thyroid eye disease Multiple sclerosis
SP001 Overview
SP001 is an IgG1 mAb designed to be Fc-silent (ΔP-LALA) No detectible Fc receptor and complement binding, eliminating platelet activation Normal FcRn interactions are preserved à IgG-like half-life Constant fragment (Fc) domain interacted w/ FcgRIIa on platelets, the putative MOA for the increased risk of thrombosis First-generation (ex. Ruplizumab) Second-generation (ex. Dazodalibep) Third-generation SP001 SP001 Is a Third-Generation, Fully Humanized, Fc-silent CD40L mAb Modified to Silence the Fc Region SP001 combines high affinity and selectivity with preserved mAb functionality and PK properties, while engineering out the Fc-region pathogenic sequence Alternative modalities utilized non-antibody formats to avoid Fc receptor binding. Most assets lack beneficial drug properties of mAbs (half-life, low ADA, CMC, etc.)* Active Fc Region Tn3 Tn3 HSA *Aglycosyl ruplizumab (Fc modified IgG1) considered 2nd Gen
SP001 demonstrated superior immune suppression in anti-KLH immunization model compared to leading Phase 3 mAb Anti-KLH (keyhole limpet hemocyanin) antibody evaluates immune function by measuring IgM (early response) and IgG (later response) antibodies following vaccination. Saghari M, Gal P, Ziagkos D, et al. A randomized controlled trial with a delayed-type hypersensitivity model using keyhole limpet haemocyanin to evaluate adaptive immune responses in man. Br J Clin Pharmacol. 2021;87:1953–1962. SP001 Presents Potent Immune Suppression In Vivo in-vivo immune response assay hlgG SP001-0.3mpk SP001-1mpk SP001-3mpk Frexalimab -3mpk Anti-KLH (ug/ml) (Human CD40L/CD40 mice) Anti-KLH response KLH
1. Phase 1b MAD in Sjögren’s disease patients completed in China. *Sponsor unblinded. N=10/cohort | Ratio 8:2 (active: placebo) within each cohort; two parallel placebo slots per cohort pooled as N=6. Poster presentation dated June 5, 2026, presented at the European Alliance of Associations for Rheumatology (the "2026 EULAR poster"), Method section; SP001 is known as IBI-355 prior to the closing of the in-licensing agreement with the licensor. Phase 1b1 Characterized Safety/Tolerability, PK, and Efficacy Signals R Treatment Period (Q4W × 4 doses | 12 weeks) Safety Follow-up (12 weeks) Cohort 1:SP001 7.5 mg/kg IV Cohort 2:SP001 15 mg/kg IV Cohort 3:SP001 30 mg/kg IV D1 Dose 1 Wk 4 Dose 2 Wk 8 Dose 3 Wk 12 Last dose Wk 16 Efficacy endpoints Wk 20 Wk 24 Safety assessment Primary Endpoint: Safety and tolerability of 4 infusions of SP001 Q4W (screening to Week 24) Secondary Endpoint: PK characteristics and immunogenicity (screening to Week 24) Other: Efficacy (ESSDAI, ESSPRI) Study Design: Double-blind*, placebo-controlled Multiple Ascending Dose (MAD) Study in Sjögren’s disease
Safety Parameter SP001 7.5 mg/kg (N=8) SP001 15 mg/kg (N=8) SP001 30 mg/kg (N=8) SP001 Total (N=24) Placebo (N=6) Any Adverse Event (%) 75.0 87.5 75.0 79.2 100.0 Upper Respiratory Tract Infection (%) 50.0 50.0 50.0 50.0 33.3 Hyperlipidemia (%) 37.5 12.5 0.0 16.7 16.7 Serious Adverse Events None reported Source: 2026 EULAR poster, results section, Safety sub-section, PK sub-section Safety Data Was Generally Benign
Source: 2026 EULAR poster, Efficacy section Demonstrated Improvements in Disease Activity and B-cell Biomarkers Rheumatoid factor, a classical autoantibody marker EULAR Sjögren's Syndrome Patient Reported Index EULAR Sjögren's Syndrome Disease Activity Index ESSDAI ESSPRI RF% 7.5 mg/kg N=7 15 mg/kg N=8 30 mg/kg N=8 Placebo N=5 SP001
*Study performed in China 1. 2026 EULAR poster, Efficacy section. SP001 PBO group had 3 patients w/ ESSDAI ≥5; LS mean change from week 0 to week 24 = -0.67 2. Xu et al. Rheumatology (Oxford). 2024;63:698–705 3. St. Clair et al. Nat Med. 2024;30:1583–1592 4. Bowman et al. Lancet. 2022;399:161–171. The clinical data comparing SP001 and other products and product candidates are based on cross-study comparisons and are not based on any head-to-head clinical trials. Differences exist between trial designs, patient characteristics and other factors, and caution should be exercised in drawing any conclusions from a comparison of the data across studies as cross-study comparisons are inherently limited and such data may not be directly comparable. Ph1b Trial of SP001 Demonstrates Favorable Efficacy over Competitor Candidates Placebo-Adjusted Efficacy in Moderate to Severe Patients (ESSDAI ≥5) SP0011 Telitacicept2 Dazodalibep3 Ianalumab4 Primary endpoints at: Week 16 Week 24 Week 24 Week 24
Data to Date Support Continued Development Low rate of anti-drug antibodies (ADA) SP001 well-tolerated across doses over the course of Phase 1b trial Preclinical toxicology and Phase 1 studies support continued development Chronic preclinical toxicology study currently underway to support longer duration dosing Safety Immunogenicity Linear PK across all doses Half-life of approximately 28 days 4-week (Q4W) dosing Pharmacokinetics Improvement in ESSDAI and ESSPRI scores vs placebo in all 3 doses Evidence of autoantibody reduction Efficacy
IgG4-Related Disease
Source: UpToDate; DelveInsight; Wallace ZS, et al. Ann Rheum Dis 2023;82:957–962 IgG4-Related Disease: Chronic, Immune-Mediated Fibroinflammatory Condition Back Abdominal Cavity Thyroid & Pituitary Gland Chest Cavity Pancreas Lungs Kidneys Liver and Biliary Tract Heart & Aorta Meninges Eye Sockets Salivary & Tear Glands IgG4-RD can manifest in nearly every organ system Approximately 20K-40K diagnosed US patients Historically underdiagnosed with recently increasing diagnosis rates 60% patients present with organ damage at diagnosis Age of onset 50-70 years Progression to fibrosis and organ failure with under-treatment
IgG4-RD Diagnosed Source: Syneos Health analysis. 1. Peyronel et al, Nature 2025. IgG4-related disease and other fibro-inflammatory conditions | Nature Reviews Rheumatology 2. Khosroshahi et al, A&R 20215 International Consensus Guidance Statement on the Management and Treatment of IgG4‐Related Disease - Khosroshahi - 2015 - Arthritis & Rheumatology - Wiley Online Library 3. Wallace et al, A&R 2019, bltfeda178976f1ad2a.pdf 4. Rare Disease Advisor: IgG4-RD updated Apr 2025 IgG4-Related Disease Treatment - Rare Disease Advisor. Abbreviations: DMARD- disease-modifying antirheumatic drugs. Note: Percentages represent share of patients receiving each therapy as 1L treated (n = 293). Current IgG4-RD Treatment Paradigm Results in Cycles of Relapse1-4 Biologics Other Non-steroidal, non-biologic DMARD Decision to Treat 57% Steroid Monotherapy 56% Biologics 29% DMARD +/- Steroid DMARD mono: 12% Combo: 3% Adequate Response? NO YES Adequate Response? FDA-approved for IgG4-RD IgG4-RD guidelines mention Neither of above 1 2 3 Relapse Remission YES NO Rituximab Uplizna Other ✓ ✓ Current therapies manage active flares, but do not provide durable long-term control
Asset Name Company Target Mechanism of Action Route of Administration Development Status SP001 CD40L T–B cell co-stimulation Intravenous Phase 2 planned Uplizna CD19 B-cell depletion Intravenous Launched Obexelimab CD19+FcgRIIb B-cell inhibition Subcutaneous Phase 3 Rilzabrutinib BTK B-cell inhibition Oral Phase 3 Sources: Citeline and BioMedTracker IgG4-RD Development Landscape Leaves Room for Differentiated Mechanism
1. Borges T, Silva S. IgG4-related disease: How to place it in the spectrum of immune-mediated and rheumatologic disorders? Mod Rheumatol. 2020 Jul;30(4):609-616.; 2. Kudo-Tanaka E, et al., A case of Mikulicz's disease with Th2-biased cytokine profile: possible feature discriminable from Sjögren's syndrome. Mod Rheumatol. 2009;19(6):691-5. ; 3. Akiyama M, et al.. Enhanced IgG4 production by follicular helper 2 T cells and the involvement of follicular helper 1 T cells in the pathogenesis of IgG4-related disease. Arthritis Res Ther. 2016 Jul 13;18:167. Biological Rationale for CD40L Inhibition in IgG4-RD CD40L sustains disease Promotes local T cell : B cell interactions required for B cell accumulation and IgG4 class-switching Activates macrophages (APC) and B cells that are both potential sources of pro-fibrotic factors (e.g. TNF, IL-6, PDGF, chemokines, etc.) Supporting evidence T cells in IgG4-RD express CD40L1 and CD40 and CD40L are both elevated in IgG4-associated disease2 CD40L is crucial for class switching of IgG4-RD patient cells in vitro3 SP001 designed to block CD40L driven antigen presentation and cytokines from APC 1 2 SP001 designed to block CD40L driven accumulation of IgG4 B cells / plasmablasts 1 2 IgG4+ plasma cells accumulate in tissues and are associated with a chronic inflammation, but multiple cells contribute to pathologic fibrotic remodeling
* Patient is flaring despite steroids Phase 2 Study Designed to Establish Proof of Concept Phase 2 Open Label Treatment (24 weeks) Optional Long-term Extension (to 52 weeks) SP001 Dose 1 N=15 SP001 Dose 2 N=15 R Population: IgG4-RD patients with >1 organ involved over time and active in at least one organ at enrollment Patients requiring steroids* protocol to incorporate a 4-week or 8-week steroid taper Primary Endpoint: Efficacy: Change from baseline in IgG4-RI at Week 24 Secondary Endpoint Number of patients with TEAEs following dosing with SP001
Expansion Opportunities
Neurological Problems concentration, memory loss (brain fog) Dry nose, recurrent sinusitis, nose bleeds Dry mouth, mouth sores dental decay, difficulty chewing, speech, taste Dry eyes, corneal ulceration and infections Difficulty swallowing, heartburn, reflux esophagitis Recurrent bronchitis pneumonia, interstitial lung disease Dry skin, vasculitis Raynaud’s Phenomenon Abnormal liver function tests, chronic active autoimmune hepatitis preliminary binary cirrhosis Peripheral Neuropathy (Numbness and tingling in extremities) Arthritis, muscle pain Stomach upset, gastroparesis, autoimmune pancreatitis Vaginal dryness, painful intercourse Sjögren’s Disease Is a Complex Disorder with Limited Treatments Available Chronic autoimmune disease targeting salivary and lacrimal glands Patients with severe disease (e.g., systemic involvement) progress to life-threatening complications including lymphoma, pulmonary diseases, neuropathy Initially treated with short term steroids Immunosuppressive therapies (methotrexate, azathioprine, MMF, leflunomide) are used second line based on physician preference Rituximab failed a pivotal trial but is still widely used third line
Epidemiology 1-4 *Potential to capture additional patients as market evolves with new and improved therapies. Sources: 1.Sjögren’s Foundation website – fast facts accessed 8 June 2026 (affecting as many as 4m Americans); 2. Willey C, Ali S, Alten R. Prevalence of Physician-Diagnosed versus Clinically Confirmed Primary Sjögren’s syndrome (SS) Among Adults in the United States [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9); 3. Datamonitor Healthcare forecast tool accessed February 2026; 4. Helmick et al. Arthritis Rheum. 2008;58:15–25. 5. Brito-Zerón et al. Nat Rev Dis Primers. 2016;2:16047. Sjögren’s Disease: US Epidemiology and Unmet Needs Unmet Needs 2nd most common rheumatic autoimmune disease Up to 4M in the US1 Estimated addressable segment for novel therapies / biologics 5 ~50K-80K addressable patients in US diagnosed US patients2,3,4 250K-400K Approved therapy for Sjögren’s Disease Disease-modifying therapies with high safety bar enabling chronic treatment Treatment for both systemic disease and patient reported symptoms Clear patient stratification
The Biological Rationale for CD40L in Sjögren’s Disease Is Well Established 1. Dimitriou et al. Clin Exp Immunol. 2002;127:386–392 2. Nakamura et al. Lab Invest. 1999;79:261–269 3. Goules et al. J Autoimmun. 2006;26:165–171 4. Belkhir et al. Scand J Immunol. 2014;79:37–42. 5. Wieczorek et al. Ann Rheum Dis. 2019;78:974–978 6. Voynova et al. ImmunoHorizons. 2018;2:54–66. 7. St. Clair et al. Nat Med. 2024;30:1583–1592. Pathology is orchestrated by CD40L-expressing T cells CD40L sustains disease by Stimulating immune activity from both antigen presenting cells and gland cells1 Promoting local production of destructive autoantibodies from B cells Supporting evidence indicates CD40L expression is elevated in Sjögren's2-4 Inhibition of CD40L blocks local, autoreactive lymphoid structures, and reduces pathology in animal models of Sjögren’s5-6 Importantly, CD40L inhibition has been clinically validated in published Ph2 studies7
Key Investment Highlights: SP001 Sjögren’s disease + applications in cardiology and endocrine disorders Target with human proof-of-concept in several autoimmune diseases Differentiated mechanism compared to other B-cell targeting agents Preclinical data show high potency compared to key competitors Completed 2 healthy volunteer trials and Phase 1b in Sjögren's disease Expansion opportunities Lead program in IgG4-RD Phase 2 ready antibody Potential best-in-class profile CD40L validated target
Thank You Spero Therapeutics www.sperotx.com