TECX 8-K
Tectonic Therapeutic, Inc. (TECX)
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
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| Item 5.02 | Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensatory Arrangements of Certain Officers. |
On February 23, 2026, the Board of Directors (the “Board”) of Tectonic Therapeutic, Inc. (the “Company”), upon recommendation of the Nominating and Corporate Governance Committee of the Board (the “Nominating and Corporate Governance Committee”), approved an increase in the size of the Board from six directors to seven directors effective as of the Effective Date (as defined below) and appointed François Nader as a member of the Board and as a member of the Nominating and Corporate Governance Committee, effective as of the Effective Date, to serve until his successor is duly appointed and qualified, or until his earlier death, resignation or removal. Dr. Nader will serve as a Class III director whose term will expire at the Company’s 2027 annual stockholder meeting. The Board has determined that Dr. Nader qualifies as an “independent director” as determined in accordance with Rule 5605(a)(2) of the Nasdaq Rules and listing standards.
Also on February 23, 2026, Terrance McGuire notified the Board of his intent to (i) resign as Chair of the Board, effective as of April 1, 2026 (the “Effective Date”) and (ii) resign from the Board, including its committees, effective as of the Company’s 2026 annual stockholder meeting (the “2026 Annual Meeting”). Mr. McGuire will continue to serve as a member of the Board and as a member of the Nominating and Corporate Governance Committee and the Audit Committee of the Board until the Company’s 2026 Annual Meeting. Upon recommendation of the Nominating and Corporate Governance Committee, the Board appointed Dr. Nader to serve as Chair of the Board, effective as of the Effective Date.
There is no arrangement or understanding between Dr. Nader and any other person pursuant to which he was selected as a director, and there is no family relationship between Dr. Nader and any of the Company’s other directors or executive officers. Additionally, there are no transactions involving the Company and Dr. Nader that the Company would be required to report pursuant to Item 404(a) of Regulation S-K.
As a non-employee director of the Company, Dr. Nader is eligible to participate in the Company’s non-employee director compensation policy, as amended (the “Compensation Policy”), pursuant to which he will receive, as of the Effective Date, (a) an annual cash retainer of $40,000 per year for service on the Board, (b) an additional $30,000 per year for his service as Chair of the Board and (c) a one-time initial equity award of options to purchase 20,400 shares of the Company’s common stock (the “Initial Award”). The Initial Award will be made pursuant to the Company’s 2024 Equity Incentive Plan (the “2024 Plan”). One-third of the Initial Award will vest on the first anniversary of the date of grant, with the remainder vesting in equal monthly installments thereafter until the third anniversary of the date of grant, subject in each instance to his continued Board service.
In addition, on the business day following each annual stockholder meeting of the Company (with the exception of the Company’s 2026 Annual Meeting), and assuming Dr. Nader continues to serve as a non-employee member of the Board following such stockholder meeting, Dr. Nader will automatically be granted an option to purchase shares of the Company’s common stock in accordance with the Compensation Policy then in effect, vesting in full on the earlier of the first anniversary of the grant date or the date of the Company’s next following annual stockholder meeting, subject to his continued Board service.
Notwithstanding any vesting schedule, if Dr. Nader remains in continuous Board service until immediately prior to a “change in control” as defined under the 2024 Plan, all of Dr. Nader’s then-outstanding equity awards granted in connection with the Compensation Policy shall vest and become exercisable in full immediately prior to the closing of such change in control.
In connection with Dr. Nader’s election to the Board, the Company and Dr. Nader entered into the Company’s standard form of indemnification agreement, a copy of which was filed as Exhibit 10.2 to the Company’s Current Report on Form 8-K (File No. 001-38537), filed with the SEC on June 20, 2024.
| Item 7.01 | Regulation FD Disclosure. |
On February 23, 2026, the Company issued a press release announcing the appointment of Dr. Nader to the Board and to his role as Chair of the Board. A copy of the Company’s press release is attached as Exhibit 99.1 to this Current Report on Form 8-K.
On February 24, 2026, the Company posted a presentation titled “TX2100: A Differentiated Anti-Angiogenic Therapy for HHT and Other Bleeding Disorders” on its website, a copy of which is attached as Exhibit 99.2 to this Current Report on Form 8-K.
The information under Item 7.01 in this Current Report on Form 8-K, including Exhibits 99.1 and 99.2 attached hereto, is 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 otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing of the Company under the Securities Act of 1933, as amended, or the Exchange Act, whether made before or after the date hereof, regardless of any general incorporation language in such filing, except as shall be expressly set forth by specific reference in such filing.
| Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits.
| 99.1 | Press Release of Tectonic Therapeutic, Inc. dated February 23, 2026 | |
| 99.2 | Corporate Presentation dated February 24, 2026 | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |
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.
| Tectonic Therapeutic, Inc. | ||||||
| Date: February 24, 2026 | By: | /s/ Daniel Lochner | ||||
| Daniel Lochner | ||||||
| Chief Financial Officer | ||||||
Exhibit 99.1
Tectonic Therapeutic Appoints François Nader, M.D., as Chair and Independent
Director of the Board
WATERTOWN, Mass., February 23, 2026 (GLOBE NEWSWIRE) — Tectonic Therapeutic, Inc. (NASDAQ: TECX) (“Tectonic”), a clinical-stage biotechnology company focused on the discovery and development of therapeutic proteins and antibodies that modulate the activity of G-protein coupled receptors (GPCRs), today announced it has appointed François Nader, M.D., MBA, as an independent director to its Board of Directors, effective April 1, 2026, at which time he will also assume the role of Chair of the Board.
Dr. Nader brings more than 30 years of leadership experience across the biotechnology and pharmaceutical industry and currently serves as an Independent Director of Moderna, Inc. (NASDAQ: MRNA), a global biotechnology company. Upon Dr. Nader assuming the role as independent director to the Board of Directors, Terry McGuire will resign from his role as Chair of the Board, a role which Dr. Nader will immediately assume. In order to provide for a smooth leadership transition, Mr. McGuire will remain a member of the Board of Directors until Tectonic’s 2026 Annual Meeting of Stockholders, which is anticipated to be in June 2026.
“We are delighted to welcome François Nader to Tectonic’s Board of Directors. François brings exceptional and broad leadership experience, deep expertise in corporate governance and strategic transactions, and a strong track record of building and scaling innovative biotechnology companies. His perspective will be invaluable as we continue advancing our GPCR-targeted pipeline and positioning Tectonic for long-term growth and shareholder value creation,” said Alise Reicin, M.D., President and Chief Executive Officer of Tectonic Therapeutic. “We would also like to express our sincere appreciation to Terry McGuire for his strong leadership and continued support since Tectonic’s inception, and for his instrumental contributions in helping us build our company.”
“I am excited to join Tectonic at this important stage of its development,” said Dr. Nader. “The company’s approach to targeting GPCR biology has the potential to unlock meaningful therapeutic advances. I look forward to working with the Board and management team to help guide Tectonic’s strategy and support its continued growth.”
“I strongly support the appointment of François Nader to Tectonic’s Board as the company continues to evolve to its next stage of growth,” said Mr. McGuire. “It has been an honor for me to serve as the Chair of Tectonic’s Board, and I’m proud to have been part of the Company’s progress in advancing innovative GPCR-targeted therapies for patients with serious diseases.”
Dr. Nader was appointed as an Independent Director of Moderna in 2019, where he chairs both the Talent & Compensation Committee and the Nominating & Governance Committee. He has served as Chairman, Executive Chairman, and/or Independent Director of numerous biotechnology companies which culminated in significant strategic transactions, including Acceleron Pharma (acquired by Merck), Alexion Pharmaceuticals (acquired by AstraZeneca), Prevail Therapeutics (acquired by Eli Lilly), Clementia Pharmaceuticals (acquired by Ipsen), Advanced Accelerator Applications (acquired by Novartis), Baxalta (acquired by Shire), NPS Pharmaceuticals (acquired by Shire), and Noven Pharmaceuticals (acquired by Hisamitsu). He also previously served as President and Chief Executive Officer of NPS Pharmaceuticals, where he led the company’s transformation into a global rare disease leader. Earlier in his career, he held senior leadership roles spanning medical, regulatory, and commercial functions at Aventis and its predecessor companies. Dr. Nader earned his French Doctorate in Medicine from St. Joseph University in Lebanon and a Physician Executive MBA from the University of Tennessee.
About Tectonic
Tectonic Therapeutic is a clinical-stage biotechnology company focused on the discovery and development of therapeutic proteins and antibodies that modulate the activity of GPCRs. Leveraging its proprietary technology platform called GEODe™ (GPCRs Engineered for Optimal Discovery), Tectonic is focused on developing biologic medicines that overcome the existing challenges of GPCR-targeted drug discovery and harness the human body to modify the course of disease. Tectonic focuses on areas of significant unmet medical need, often where therapeutic options are poor or nonexistent, as these are areas where new medicines have the potential to improve patient quality of life. Tectonic is headquartered in Watertown, Massachusetts. For more information, please visit www.tectonictx.com and follow us on LinkedIn.
Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. All statements in this press release other than statements of historical facts are “forward-looking statements.” These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding: the anticipated timing of Tectonic’s 2026 Annual Meeting of Stockholders and the expected changes in board leadership roles. These forward-looking statements are based on Tectonic’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties that may cause Tectonic’s actual results to differ from those expressed or implied in the forward-looking statements in this press release. These risks and uncertainties include those that are identified under the heading “Risk Factors” in Tectonic’s quarterly report on Form 10-Q filed with the SEC for the quarter ended September 30, 2025, and in other filings that Tectonic makes and will make with the SEC in the future. Tectonic expressly disclaims any obligation to update any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise, except as otherwise required by law.
Contacts:
Investors:
Dan Ferry
LifeSci Advisors
(617) 430-7576
Media:
Kathryn Morris
The Yates Network
(914) 204-6412
TX2100: A Differentiated Anti-Angiogenic Therapy for HHT and Other Bleeding Disorders FEBRUARY 24, 2026 Exhibit 99.2
Statements contained in this presentation regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as "anticipates," "believes," "expects," "intends," “plans,” “potential,” "projects,” “would” and "future" or similar expressions are intended to identify forward-looking statements. Each of these forward-looking statements involves substantial risks and uncertainties that could cause actual results to differ significantly from those expressed or implied by such forward-looking statements. Forward-looking statements contained in this presentation include, but are not limited to, statements regarding: the design, objectives, initiation, timing, progress and results of current and future preclinical studies and clinical trials of our product candidates, including the expected timing of program updates and data disclosures for TX2100; the timing and likelihood of seeking regulatory approval for TX2100; and the competitive landscape for and market potential of TX2100. These forward-looking statements reflect our current beliefs and expectations. Many factors may cause differences between current expectations and actual results, including the early stage of our development efforts; success in preclinical testing and earlier clinical trials does not ensure that later clinical trials will generate the same results or otherwise provide adequate data to demonstrate the efficacy and safety of a product candidates; clinical site activation rates or clinical trial enrollment rates that are lower than expected; changes in expected or existing competition; changes in the regulatory environment; the uncertainties and timing of the regulatory approval process; the impact of macroeconomic conditions, including the conflict in Ukraine and the conflict in the Middle East, heightened inflation and uncertain credit and financial markets, on our business, clinical trials and financial position; and unexpected litigation or other disputes. These and other risks are described more fully in our filings with the Securities and Exchange Commission (“SEC”), including the risks detailed in our Quarterly Report on Form 10-Q filed with the SEC on November 6, 2025, and other documents we subsequently filed with or furnished to the SEC. All forward-looking statements contained in this presentation speak only as of the date on which they were made. Except as required by law, we assume no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth 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 estimates. Neither we nor any other person makes any representation as to the accuracy or completeness of such data or undertakes any obligation to update such data after the date of 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. DISCLAIMER
FEBRUARY 2026 Agenda Welcome and Introduction Alise Reicin, MD Chief Executive Officer, Director HHT: The Disease and Unmet Need Hanny Al-Samkari, MD Mass. General Hospital, Harvard Medical School TX2100: Discovery and Rationale Peter McNamara, PhD Chief Scientific Officer TX2100: Clinical Update Marcie Ruddy, MD Chief Medical Officer Questions and Answers
PROGRAM / INDICATION DISCOVERY IND-ENABLING PHASE 1 PHASE 2 GROUP 2 PH-HFpEF TX45 (RXFP1 Agonist) GROUP 3 PH-ILD TX45 (RXFP1 Agonist) HEREDITARY HEMORRHAGIC TELANGIECTASIA (HHT) * TX2100 (APJ Antagonist) FIBROSIS Bispecific GPCR Modulator (anti-fibrotic) GPCR MODULATORS Advancing a High-Value Pipeline of GPCR-Targeted Therapies TX45 TX2100 TX45 Clinical-stage biotech Biologics to target GPCRs Significant therapeutic opportunities Diseases with high unmet need and limited options Robust, multi-product pipeline Two clinical programs, three indications, and an emerging preclinical pipeline TX45 being explored in Phase 2 for both Group 2 PH HFpEF and PH-ILD TX2100 for Hereditary Hemorrhagic Telangiectasia and other bleeding disorders Company with clinical momentum Well-capitalized to advance high-value pipeline * Subject to positive Phase 1 data
TX2100 for Hereditary Hemorrhagic Telangiectasia (HHT) APJ: The GPCR Target for the Hormone Apelin Orphan Indication Preclinical to Clinical Translation TX2100 Phase 1 Study Initiated Blockbuster Potential HHT is a genetic disorder of dysregulated angiogenesis leading to recurrent bleeding, anemia, arteriovenous malformations (AVMs) and reduced life expectancy with no approved therapies Estimated ~75K HHT patients in the US; anti-angiogenic drugs (e.g., bevacizumab, pomalidomide) reduce bleeding but chronic use limited by toxicity Highly selective/specific anti-angiogenic target. APJ expressed mainly in endothelial cells, Apelin/APJ pathway is usually quiescent and upregulated during pathologic angiogenesis for greater selectivity vs. other anti-angiogenic agents Potential to expand into a broader group of bleeding disorders caused by dysregulated angiogenesis A potential first-in-class APJ antagonist with subcutaneous administration designed to treat HHT with anticipated benefit of anti-angiogenic therapy with improved safety Anti-angiogenic agents demonstrate activity both in HHT preclinical models and in patients Efficacy of TX2100 shown in two HHT preclinical models, increasing probability of success Phase 1a healthy volunteer clinical trial ongoing TX2100 FEBRUARY 2026
Today’s Call Features Dr. Hanny Al-Samkari, Joined by Company Management Alise Reicin, M.D. CEO, Director Peter McNamara, Ph.D. CSO Marcella Ruddy, M.D. CMO Hanny Al-Samkari, MD Dr. Al-Samkari is the Peggy S. Blitz Endowed Chair in Hematology/Oncology at the Massachusetts General Hospital and an Associate Professor of Medicine at Harvard Medical School. He is a classical hematologist and NIH-funded clinical investigator and serves as the Co-Director of the MGH HHT Center of Excellence. He is the current Chair of the Cure HHT Global Research and Medical Advisory Board. His clinical and research interests are in hemostasis, thrombosis and hemolysis, with focuses in HHT and other bleeding disorders. He is an internationally recognized expert in the clinical development of novel therapeutics for these disorders and serves as the principal investigator for many clinical trials. Dr. Al-Samkari cares for several hundred patients with HHT and has clinics dedicated to the care of patients with HHT. FEBRUARY 2026
Unmet Need in Hereditary Hemorrhagic Telangiectasia Hanny Al-Samkari, M.D. The Peggy S. Blitz Endowed Chair in Hematology/Oncology Classical Hematologist and Clinical Investigator Co-Director, HHT Center of Excellence Massachusetts General Hospital Associate Professor of Medicine Harvard Medical School
Typical Patient Case 41-year-old man with severe nosebleeds and chronic intestinal bleeding working in the biomedical field Diagnosed with HHT in his 20s, but not cared for at HHT center; sent for regular nasal and intestinal cautery procedures that each worked for a couple of months but provoked worse nosebleeding as time went on Ultimately went on disability and career halted because of: Constant blood gushing from his face limiting him at work Chronic severe anemia despite regular intravenous iron and blood transfusions Constant ER visits for severe nosebleeds and hospitalizations from severe intestinal bleeding Diagnosis of major depressive disorder from nosebleeding; started on antidepressant which worsened his bleeding (prescribing doctor did not recognize this as a side-effect of the antidepressant) Then saw me at the MGH HHT CoE; “I am barely 40 but I feel like my life is nearly over. I just want to go back to work, and maybe one day be able to have a girlfriend.”
Another Typical Patient Case 37-year-old man, father of three children, diagnosed with HHT one month prior to his visit Came from Maine to HHT Center of Excellence at MGH in Boston Gushing nosebleeds and chronic intestinal bleeding causing severe anemia, resulting in severe fatigue, reducing work hours, threatened employment (works in a construction job), ability to care for family One son died of a brain hemorrhage at birth; another son had a brain hemorrhage shortly after birth but lived with severe disability Daughter has recurrent nosebleeds causing anxiety, distress, social isolation at school
The Spectrum of Inherited Bleeding Disorders 3,800
Al-Samkari H., Blood 2021; Al-Samkari H, Blood 2024 HHT is a Multisystem Hereditary Bleeding Disorder with Numerous Morbid and Potentially Fatal Manifestations Progressive, multisystem bleeding disorder due to abnormal vessel formation Mucocutaneous telangiectasias à severe recurrent epistaxis and chronic gastrointestinal hemorrhage Iron deficiency anemia, often iron infusion and RBC transfusion-dependent Visceral and CNS arteriovenous malformations (AVMs) in lung, liver, brain, others Hemorrhagic and embolic stroke Liver disease and cirrhosis Pulmonary hypertension, pulmonary hemorrhage High output heart failure Patients rank bleeding as most important clinical manifestation (by a wide margin) AVMs and anemia tie for second No approved therapies worldwide to date
HHT is the Second-Most-Common Inherited Bleeding Disorder Autosomal dominant inheritance, 1 in 3800 people Occurs in all sexes equally Most clinically significant and morbid inherited bleeding disorder of women Patients with HHT have reduced overall survival compared with healthy controls ~80,000 people with HHT in US HHT Affects 1.6 Million Worldwide Al-Samkari H., Blood 2021; Zhang et al., Blood Advances 2024
HHT is Caused by Mutations in Genes in the BMP9/ALK1 Pathway Genetic Drivers of HHT HHT arises from loss-of-function mutations in key vascular-signaling genes: BMP9 (GDF2), Endoglin (ENG), ALK1 (ACVRL1), and SMAD4 (MADH4) These mutations disrupt BMP9/ALK1 signaling, a pathway required for vascular quiescence and controlling angiogenesis Consequences of BMP9/ALK1 pathway loss Loss of this pathway shifts endothelial cells into a persistent pro-angiogenic state, driving abnormal vessel growth and AVM formation
Mouse Models of HHT Replicate Disease, Are Predictive of Clinical Efficacy Multiple mouse models of HHT Anti-BMP9/10 immunoblocked neonatal model Endoglin (ENG) inducible knockout (iKO) mouse SMAD4 (MADH4) iKO mouse ALK1 (ACVRL1) iKO mouse (most severe model with profound GI bleeding) Response to drug in mouse model predicts clinical efficacy Mouse models of HHT have a phenotype similar to human disease, with GI bleeding and AVMs in numerous locations Drug efficacy in mouse models predicts human response (bevacizumab1, pazopanib2, and thalidomide3 have efficacy in mouse models and in humans with HHT) 1Walker EJ et al. Stroke. 2012; 2Kim YH et al. J Thromb Haemost. 2017; 3Lebrin F et al. Nat Med 2010.
Prevalence is Increasing Because More People Are Getting Diagnosed Ferry AM, et al. Am J Rhinol Allergy. 2020. Increase in Prevalence, 2013-2017
Mucocutaneous Telangiectasias: Gastrointestinal Tract
Mucocutaneous Telangiectasias: Nasal Cavity
Arteriovenous Malformations (AVMs) Liver Lung Brain
What is the MOST FEARED Complication of Any Bleeding Disorder?
Incidence of Moderate-to-Severe HHT-Associated Mucosal Bleeding in Centers of Excellence Mod- Severe 76% Mild 24% Moderate-to-Severe HHT Mucosal Bleeding: (1) ESS>4.00, (2) Systemic medical or surgical intervention for epistaxis and/or GI bleeding, (3) intravenous iron and/or red cell transfusion to manage anemia Al-Samkari et al., Blood 2025
HHT is an Expensive Disease Al-Samkari et al., American Journal of Hematology 2025
HHT is an Expensive Disease ~$500M per year in one sample ~$2B per year estimated total U.S. cost 12% of all diagnosed patients are hospitalized at least once per year Al-Samkari et al., American Journal of Hematology 2025 $21M spent on one patient treated outside of an HHT Center on huge amounts of a (wrong) expensive medication to treat bleeding in 1 year
Many New and Striking Findings from First CHORUS Report (Comprehensive HHT Outcomes Registry of the United States) 3 in 4 people with HHT develop moderate-to-severe mucosal bleeding, including epistaxis, gastrointestinal, and/or heavy menstrual bleeding 1 in 3 people with HHT develop chronic GI bleeding 1 in 3 menstrual-age women with HHT develop heavy menstrual bleeding 7 in 10 people with HHT develop iron deficiency and/or anemia 1 in 4 people with HHT develop severe enough anemia to merit RBC transfusion 1 in 50 people with HHT develop pulmonary hemorrhage 1 in 30 people with HHT develop intracranial hemorrhage 1 in 10 people with HHT develop arterial thromboembolism 1 in 10 people with HHT develop serious cardiopulmonary complications (PH and/or HF) 1 in 5 people with HHT develop serious CNS complications (bAVM, stroke, ICH, epilepsy)
Current Treatment Paradigm in HHT is Deeply Inadequate Al-Samkari H. How I Treat Bleeding in Hereditary Hemorrhagic Telangiectasia. Blood 2024
Limited Tolerability of Currently Used Anti-Angiogenic Drugs Al-Samkari H. How I Treat Bleeding in Hereditary Hemorrhagic Telangiectasia. Blood 2024 Bevacizumab: Limited by hypertension, proteinuria, thromboembolism risk, waning efficacy Pomalidomide: Limited by neutropenia, rash, neurologic side effects, constipation, thromboembolism risk, waning efficacy No marketed drugs, including bevacizumab and pomalidomide, are currently approved by the FDA for the treatment of HHT
TX2100 A Differentiated Anti-Angiogenic Therapy for HHT Peter McNamara, Ph.D. Chief Scientific Officer
Apelin (Peptide Ligand) Human APJ (APLNR) TX2100: A Potential First-in-Class APJ Antagonist for HHT and Angiogenesis-Driven Bleeding FEBRUARY 2026 Validated approach Anti-angiogenesis reduces bleeding in HHT and related bleeding disorders, but no approved therapies Toxicity of oncology anti-angiogenic agents are challenging for chronic use De-risked translation and path to value Demonstrated preclinical activity in two validated HHT models with normalization of vasculature in model of severe disease Clean NHP GLP tox and durable non-clinical PK Phase 1a ongoing, Phase 1b and Phase 2 proof-of-concept planned Differentiated target APJ is endothelial-enriched and apelin/APJ pathway is activated during abnormal angiogenesis TX2100 is designed to deliver anti-angiogenic efficacy with improved safety
APJ is an endothelial-enriched GPCR Apelin/APJ pathway is upregulated in pathological sprouting angiogenesis Low baseline apelin/APJ activity during normal vascular homeostasis FEBRUARY 2026 APJ is a Highly Selective, Highly Specific Anti-Angiogenic Target APJ antagonism AVM Blocked apelin/APJ signaling Upregulated apelin/APJ signaling
Three Decades of Progress Lead to Convergence on APJ Antagonism to Treat HHT FEBRUARY 2026 2011 First anti-angiogenic clinical signal (bevacizumab) 2017-2018 Real-world data: anti-VEGF improves bleeding/ anemia 2019-2021+ Multiple anti-angiogenic modalities show efficacy 2025 HHT broadly accepted as dysregulated angiogenesis 1994 - 1996 ENG / ACVRL1 establish angiogenic etiology of HHT 1993 - 1998 Apelin/APJ axis identified 2004 Apelin/APJ defined as pro-angiogenic signaling axis 2023 Apelin is part of a conserved angiogenic signature in HHT models Angiogenesis emerges as a key driver of HHT APJ/apelin biology converges with HHT angiogenesis 2004–2021: Pharma focus on APJ agonism (CV/HF) Limited translation beyond Phase 1 Tectonic recognized that HHT biology reframes APJ as a target for inhibition — leading to TX2100 TX2100
Anti-Angiogenesis (VEGF blockade) is Clinically Effective in HHT but On-Target Toxicities Limit Long-Term Use FEBRUARY 2026 Mechanistic proof-of-concept for anti-angiogenesis comes from use of oncology drugs where anti-VEGF therapies show reduced bleeding, increased hemoglobin and less need for transfusions Problem: Those drugs were not designed for long-term use in a non-malignant vascular disease Solution: Develop an APJ antagonist for treatment of HHT and other angiogenesis-driven disorders that captures the benefit of anti-angiogenic therapy with improved safety Anti-VEGF improves hemoglobin in severe HHT anemia Haematologica. 2021 Aug 1; 106(8): 2161–2169
VEGFR antagonism: Proven efficacy but poor long-term safety APJ antagonism: Potential for durable efficacy without VEGFR toxicity Selectivity VEGFR and AKT signaling broadly required across adult tissues and vascular beds APJ is endothelial cell enriched and pathway is most active in pathological sprouting angiogenesis Normal biological function Central to vascular homeostasis, renal microvascular integrity and repair biology Low baseline activity in quiescent adult vasculature Signaling pathways activated APJ Antagonist: A More Selective & Tolerable Anti-Angiogenic Agent AKT ERK NO NFkB ERK AKT Apelin/APJ VEGF/VEGFR2 FEBRUARY 2026
Cell-Type APJ Expression is Endothelial-Enriched While VEGFR2 Shows Broader Multi-Tissue Expression Endothelial Cells Cell-Type Barrier Epithelial Cells Glial Cells Tissues Endothelial Cells Tissues Glial Cells Transcript Level APJ is enriched in endothelial cells for more selective targeting VEGFR2 appears in more tissues leading to broader on-target biology 300 250 200 150 100 50 0 nCPM 300 250 200 150 100 50 0 nCPM FEBRUARY 2026
Apelin is Upregulated in Endothelial Cells in Mouse Models of HHT 1Zhou et al ATVB 2023 ****=p<0.0001 one-way Students t-test Apelin highly upregulated in endothelial cells in ALK1 KO mice1 Apelin expression upregulated in HHT BMP9/10ib model EC transcriptomics: iALK1-KO vs f/f controls Potential for local apelin/APJ pathway activation in disease PBS Anti-BMP9/10 Shared angiogenic gene signature across HHT models PBS Anti-BMP9/10 FEBRUARY 2026
TX2100 is a Highly Potent and Selective Human APJ Antagonist Receptor Pathway IC₅₀ (nM) Human-APJ cAMP 3.1 β-arrestin 5.6 Most closely related GPCR β-arrestin >1,000 Mouse-APJ cAMP >1,000 Human APJ IC₅₀ ≈ 3 nM VHH-Fc fusion Highly specific, limits off-target toxicities Long half-life, less frequent dosing TX2100 Low-nanomolar potency at human APJ with >1,000-fold selectivity vs. related GPCRs cAMP measured in vitro in HEK293 cells TX2100 blocks cAMP signaling with nanomolar potency FEBRUARY 2026
AKT inhibition ERK inhibition TX2100 Inhibits AKT and ERK Signaling Through APJ Antagonism, Blocking Pathways Important in Angiogenesis AKT and ERK signaling measured in vitro in HEK293 cells FEBRUARY 2026 APJ is primarily expressed in endothelial cells leading to AKT and ERK inhibition selectively in those cells In contrast, VEGF/TKIs/AKT inhibitors are broadly expressed leading to systemic pathway inhibition which can result in safety and tolerability issues
APJ Antagonism1 Shows Robust and Durable Preclinical Activity in Two Complementary HHT Models * AVMs = Arteriovenous Malformations 1TX1351 (surrogate anti-mAPJ VHH-Fc; potency matched to TX2100 against APJ) enables translatable in vivo testing Preclinical result of APJ antagonism Neonatal anti-BMP9/10 Translational model of HHT generated by injection of anti-BMP9/10 antibodies into neonatal mice Reduced AVMs Increased hemoglobin Improved bleeding Severe adult inducible ALK1-KO Most severe, clinically relevant model where disease is generated in a mature vascular system by tamoxifen-induced knockout of ALK1 in adult mice Durably increased hemoglobin (compared to anti-VEGF that waned over time) Improved bleeding Improved vascular architecture (reduced hypervascularization, abnormal dilation and AV shunts) FEBRUARY 2026
TX13511 Delivers Robust Disease-Modifying Phenotype in the Anti-BMP9/10 Model 1TX1351 = TX2100 surrogate, anti-mouse VHH-Fc; Isotype Ctrl Ab = non-targeting VHH-Fc control *=p<0.05, **=p<0.01, ***=p<0.001, ****=p<0.0001 One-way ANOVA followed by Tukey’s multiple comparison test Decreases AVM formation Isotype Ctrl Ab TX1351 Anti-APJ Anti-BMP9/10 treated mice No Disease Ctrl Mice Reduces bleeding (retinal) Isotype Ctrl Ab TX1351 Anti-APJ Anti-BMP9/10 treated mice No Disease Ctrl Mice Increases hemoglobin Isotype Ctrl Ab TX1351 Anti-APJ Anti-BMP9/10 treated mice No Disease Ctrl Mice FEBRUARY 2026
Anti-VEGFA, AKT Inhibition Provide Less Robust Disease Modification in the Anti-BMP9/10 Model Data represent mean ± SEM; each dot = pups/group. *=p<0.05, **=p<0.01, ***=p<0.001, ****=p<0.0001 One-way ANOVA followed by Tukey’s multiple comparison test AKT inhibitor AVM formation Hemoglobin No Disease IgG ctrl VEGFA antagonist ibBMP9/10 Anti-VEGFA Both mechanisms decrease AVM formation Neither improved hemoglobin levels FEBRUARY 2026 No Disease IgG ctrl AKT inhibitor ibBMP9/10
TX13511 Reduces Anemia & Bleeding in the iALK1-KO Model GI Bleeding VEGFA blockade fails to reduce GI bleeding despite modest Hb benefit Hemoglobin Levels APJ antagonism maintains durable benefits while VEGFA antagonism effects diminish over time 1TX1351 = TX2100 surrogate, anti-mouse VHH-Fc; GI bleeding score measured on day 12 *=p<0.05, **=p<0.01, ***=p<0.001, ****=p<0.0001 One-way ANOVA followed by Tukey’s multiple comparison test WT Littermate Ctrl Isotype Ctrl Ab TX1351 APJ antagonist G6.31 VEGFA antagonist APJ antagonism reduces GI bleeding FEBRUARY 2026 Day 7 Day 12 Day 12 Anemia threshold (~10 g/dL)
TX13511 Significantly Reduces GI Hypervascularization, Hemorrhage, and Vein Dilation in iALK1-KO Mice TX1351 restores vascular architecture toward normal in a severe HHT model APJ antagonism provides more complete vascular rescue than VEGFA antagonism Latex dye restricted to arterial circulation Venous dye filling reflects AVMs Isotype Ctrl Ab TX1351 APJ antagonist G6.31 VEGFA antagonist FEBRUARY 2026 1TX1351 = TX2100 surrogate, anti-mouse VHH-Fc; Isotype Ctrl Ab = non-targeting VHH-Fc control *=p<0.05, **=p<0.01, ***=p<0.001, ****=p<0.0001 One-way ANOVA followed by Tukey’s multiple comparison test
FEBRUARY 2026 Preclinical Program Did Not Show TX2100 or Target-Related Safety Signals Apelin/APJ pathway has been studied mostly in the context of agonist pharmacology Clinical agonist programs did not show meaningful benefit Discontinued for lack of efficacy Were generally safe and well tolerated, without major on-target liabilities Previously reported physiological effects of apelin1 and APJ antagonism were not reproduced in multiple in-house preclinical studies Blood pressure Renal function Platelets and bleeding time Glucose homeostasis Inflammation Completed 13-week GLP toxicology study in non-human primates, showed no safety findings No CV, renal, muscle, or hematology findings No changes in glucose No BP or fluid balance issues NOAEL = 100 mg/kg/week (highest dose tested) 1Szokodi I Circ Res 2002, Coqueral D Am J Physiol 2021, Dray C Cell Metab 2008, Hus-Citharel A Endo 2014, Tatemoto K Reg Peptide 2001
Robust preclinical activity across multiple, translatable models of HHT Clean safety profile in IND-enabling GLP toxicology studies, with no molecule specific or target-related safety signals Patient-friendly SC formulation identified Drug product readiness with favorable properties to support early clinical development FEBRUARY 2026 TX2100 Preclinical Package Supports Phase 1a Clinical Development
TX2100 Clinical Update Marcella Ruddy, M.D. Chief Medical Officer
Overview of TX2100 Clinical Development Plans 2027 Ongoing Phase 1a first-in-human clinical trial in healthy volunteers Assess safety, tolerability and PK of single doses of TX2100 Phase 1a first subject randomized in Feb 2026, expect topline results in Q4’26 Phase 1b clinical trial in patients with severe HHT Open label, multiple dose TX2100 study to assess safety and tolerability in patients Explore efficacy endpoints of epistaxis, anemia, and hematologic support Phase 2 proof-of-concept clinical trial in moderate to severe HHT patients Randomized double blind placebo-controlled dose ranging study Assess safety and efficacy of TX2100 Improvement in epistaxis, anemia, hematologic support, and other HHT endpoints FEBRUARY 2026
Potential Opportunity to Expand TX2100 Patient Population FEBRUARY 2026 Anti-angiogenic mechanism of TX2100 offers opportunity to expand into other bleeding disorders caused by dysregulated angiogenesis Anti-angiogenic agents such as bevacizumab and thalidomide have demonstrated efficacy in treatment of other bleeding disorders caused by dysregulated angiogenesis Preclinical data demonstrating activity of the APJ antagonist TX1351 in a non-HHT model of dysregulated angiogenesis-driven bleeding will be presented at a future scientific congress
TX2100: A Potential First-in-Class APJ Antagonist to Treat HHT FEBRUARY 2026 Validated approach Anti-angiogenesis improves bleeding/anemia in HHT Oncology agents can’t be used chronically De-risked translation + path to value Preclinical activity in two validated HHT models + vascular normalization imaging Clean NHP GLP tox + durable PK → Phase 1a ongoing with first subject randomized in Feb 2026; Phase 1b and Phase 2 PoC planned Differentiated target / design APJ is endothelial-enriched + pathology-biased Built to capture anti-angiogenic benefit with improved safety TX2100 VHH Human APJ (APLNR)
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