Full Press Release Details
Market Opportunities JANUARY 2025
2 DISCLAIMER 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 ongoing Phase 1b and Phase 2 clinical trial for TX45, in Group 2 Pulmonary Hypertension; the
expected timing of program updates and data disclosures; the timing of filing INDs and other regulatory documents; the timing and likelihood of seeking regulatory approval for our product candidates including TX45; the competitive landscape for our
product candidates; and our ability to identify and develop additional product candidates. 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 12, 2024, 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
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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.
3 Tectonic Tx: GPCR-Targeted Therapies for High-Value Opportunities TECX
focused on discovery & development of GPCR-target biologics with significant unmet need Clinical-Stage Biotech Founded in 2019 by Tim Springer and Andrew Kruse, TECX went public via reverse merger (AVROBIO) in June 2024 with a concurrent
private placement of approximately $131 million Tenured Team Executive team with numerous accomplishments, resulting in 20 "first" approvals TX45 Lead Long-acting relaxin in Phase 2, with de-risking Phase 1b topline results expected in
Q1'25 Pipeline Asset Initial indication targeting Group 2 Pulmonary Hypertension (PH) associated with Heart Failure with Preserved Ejection Fraction (HFpEF), or PH-HFpEF Positive Phase 1a clinical trial results support
best-in-class potential, including favorable safety profile Potential to target other indications, including other PH groups, heart failure and renal disease Relaxin Potentially Relaxin physiologic and hemodynamic effects demonstrated in
prior clinical studies Ideal for PH-HFpEF Prior clinical development of relaxin by Novartis adds to clinical rationale for TX45 targeting PH-HFpEF * PH-HFpEF Significant >1M+ patients in the U.S. with no approved therapy ; high 5-year
mortality Market Potential Eli Lilly and Astra Zeneca also pursuing relaxin programs targeting heart failure indications and renal disease TX2100 Second Targeting rare bleeding disorder called Hereditary Hemorrhagic Telangiectasia (HHT)
Pipeline Asset Significant market potential, no approved therapies for HHT, estimated ~75K patients in the U.S. alone (15-20% severe) Phase 1 clinical trial initiation expected in Q4'25 / Q1'26 Near-term Catalyst TX45
Phase 1b, hemodynamic topline results in PH-HFpEF subjects (Part A) expected in Q1'25 Topline results from Part B of Phase 1b, hemodynamic trial evaluating PH-HFrEF subjects expected in 2H'25 Well-Capitalized ~$159 million in
cash as of 9/30/24, expected to provide a cash runway into mid-2027 JANU AR Y 2025 * Estimates based on company sponsored market analysis conducted by Health Advances
4 This Accomplished Team Has Delivered for Patients and Investors Alise
Daniel Peter Anthony Marcella Marc Reicin, M.D. McNamara, Ph.D. Muslin, M.D. Ruddy, M.D. Schwabish, Ph.D. Lochner CEO, Director CSO CDO CMO CBO CFO FOUNDED MULTIPLE GPCR EXPERT, SUCCESSFUL COMPANIES FORBES "30 under 30" Timothy Andrew
LeukoSite Springer, Ph.D. Kruse, Ph.D. Co-Founder Co-Founder Multiple Awards and Fellowships 2022 Lasker Award (Biomedical Research, NIH, Amgen, Sloan Research) JANU AR Y 2025
5 Biologics Offer Advantages Over Small Molecules in Targeting GPCRs,
Hold Potential to Transform Therapeutic Landscape Of the approved drugs that target GPCRs only three are antibodies When difficult to target with small >18%* >470 ~12% molecule, biologic captures complexity remain approved drugs unexploited
approved of ligand/receptor engagement (~33% of all) drugs target 100 GPCRs Biologic minimizes off-target binding Non-Sensory to improve safety/tolerability Orphan >$180B GPCRs 800+ In annual sales (~20%) GPCRs Engineer biologic to target or
exclude tissue or compartment Predominantly small molecules Sensory GPCRs Bispecific approach enables dual (~50%) target engagement when multi- Address broad modal action is required range of therapeutic areas (*) Hauser, A.S. et al., Cell. 2018 Jan
11; 172(1-2): 41-54.e19. * 18% = 100% - 12% (approved drug targets) - 50% (sensory) - 20% (non-sensory, orphan) JANU AR Y 2025
6 Our Unique Pipeline Opportunities are Enabled by Biologic Targeting of
GPCRs Group 2 Pulmonary Hypertension Long-Acting Relaxin Potential Best-in-Class Profile (PH) due to HFpEF in Phase 2 1 to Target RXFP1 Positive Phase 1a clinical data Hereditary Hemorrhagic 2 GPCR Antagonist Potential First-in-Class Telangiectasia
(HHT) (anti-angiogenic) Target pathway linked to disease pathway Fibrosis 2 GPCR Modulator Bispecific Approach Supporting clinical data for one (anti-fibrotic) component of bispecific Scale of proof-of-concept studies: ~50-200 subjects per
indication; 3-6 months treatment endpoints 1. Fc-Fusion protein - lead molecule in-licensed from Harvard U., optimized using GEODe platform JANU AR Y 2025 2. GPCR targeted therapeutics discovered internally using GEODe platform
7 Unique Pipeline of GPCR-Targeted Biologics Underpinned By TX45
Targeting PH-HFpEF with P1b Results Expected Q1'25 PROGRAM / INDICATION DISCOVERY IND ENABLING PHASE 1 PHASE 2 ANTICIPATED MILESTONES Phase 1b hemodynamic PH-HFpEF GROUP 2 PH-HFpEF results expected in Q1'25, with PH- TX45
Potential Best-in-Class HFrEF results expected in 2H'25 1 RXFP1 Agonist Phase 2 results expected in 2026 Phase 1 trial initiation expected in HEREDITARY HEMORRHAGIC Q4'25 / Q1'26 TELANGIECTASIA (HHT) TX2100
Potential First-in-Class & Indication Phase 2 trial planned late Q4'26 / 2 GPCR Antagonist (anti-angiogenic) early Q1'27 FIBROSIS Bispecific Approach 2 GPCR Modulator (anti-fibrotic) Bispecific / anti-fibrotic and
other GPCR modulators ongoing GPCR MODULATORS 1. Fusion protein - lead molecule in-licensed from Harvard U., optimized using GEODe platform 2. GPCR-targeted biologics discovered internally using GEODe platform JANU AR Y 2025
8 TX45: Long-acting relaxin to address large, unmet need in Group 2 PH
RXFP1 agonist with differentiated profile
9 TX45 TX45: Potential Best-in-class Treatment for Group 2 PH-HFpEF
Protein engineering has extended pharmacologic half-life to support monthly dosing Relaxin with optimized PK Rigorous Phase 1 PK/PD model enabled robust Phase 2 dose selection * Group 2 PH-HFpEF has no approved therapy High
unmet need ** >1M+ patients in US and high 5-year mortality Pulmonary and systemic vasodilator; improves cardiac relaxation during diastole Mechanism appears ideal to Reversal of fibrosis in pulmonary vasculature and heart
address disease pathology Anti-inflammatory Serelaxin demonstrated clinical and hemodynamic benefits in acute heart failure Supporting clinical and pre-clinical data Clear benefit observed with TX45 in rodent PH and
congestive heart failure models Enrichment strategy for CpcPH patients where there is the greatest unmet need Streamlined and differentiated No outcome study needed clinical strategy Enables potential early launch relative to
broad heart failure indication Potential to expand market Other PH Groups, heart failure, renal disease * Heart Failure with preserved Ejection Fraction, ** US prevalence numbers for Class 2 and 3, estimates based on company sponsored market
analysis conducted by Health Advances
10 TX45 Significant Pharma Interest in Relaxin Tectonic has potential
best-in-class molecule Half Life Patient Phase 2 Company Format Formulation Dosing* in NHV Population Endpoints Group 2 PH / Change in pulmonary Fc-Fusion Sub Q 14-20 days Q4 Weeks HFpEF (enriched vascular resistance (TX45) for CpcPH) (PVR) Change
in pulmonary Fc-Fusion Group 2 PH / Sub Q 7-9 days** Q2 Weeks* vascular resistance (AZD3427) HFpEF and HFrEF (PVR) Change in Small Molecule PO 3-6 hours QD* CHF echocardiography (AZD5462) parameters h-Albumin-mAb- Sub Q Change in left atrial Fusion
8-10 days Q Weekly* HFpEF Injection site reservoir strain (LARS) reactions (LY3540378) * Expected dosing frequency, AZN and LLY based on dosing frequency in Phase 2 studies listed in clinical trials database ** Half life of 13-14 days reported in
patients with CHF based on sparse PK profiling JANU AR Y 2025
11 TX45 Hemodynamic and Anti-fibrotic Properties of Relaxin
Demonstrated by its Role in Pregnancy Pharmacology Facilitates Gestation AGONIST PULMONARY AND Natural Ligand of SYSTEMIC VASODILATOR RXFP1 Receptor Increases cardiac output to accommodate the Relaxin-2 increased demand from No RXFP1 developing
fetus internalization from relaxin agonism no desensitization with ANTIFIBROTIC chronic therapy Prepares musculoskeletal Relaxin upregulated in tissues for pregnancy pregnancy and childbirth RXFP1 active state JANU AR Y 2025
12 TX45 The First Recombinant Relaxin (Serelaxin) Demonstrated Safety
and Benefit in Acute Heart Failure (AHF) in Trials of >11,000 Patients Background Program sponsored by Novartis META ANALYSIS: Serelaxin was Efficacious in AHF Serelaxin half life <9 hours, a major hurdle for development for
chronic disease Study Relative Risk N N 2-day continuous IV dosing in patients with acute heart failure (WHF Day 5) [95% CI] (Drug) (PBO) 0.77 [0.67 - 0.89] Results and Insights Meta Analysis 6,090* 5,239 p = 0.0002
Serelaxin demonstrated safety in greater than 6,000 patients Pre-RELAX AHF 0.56 [0.22 - 1.45] 42 61 Meta-analysis showed significant benefit Development halted after pivotal study, AHF-2, failed to RELAX-AHF 0.54 [0.37 -
0.78] 581 580 achieve co-primary endpoints Trial design and operational challenges may have contributed * RELAX-AHF-2 0.90 [0.76 - 1.07] 3,274 3,271 to failure More recently, Biomarker sub-study (N=1020) accepted Nov. 12, 2024
RELAX-AHF-EU 0.71 [0.52 - 0.98] 1,756 894 showed 45% improvement in 5-day worsening heart failure (p= 0.025) and biomarker changes, including reduction in NT-proBNP and 1 RELAX-AHF-ASIA 0.42 [0.21 - 0.84] 437 433 Troponin replicated
prior studies RXFP1 agonism is beneficial in cardiovascular disease A long-acting relaxin in the ideal indication could benefit patients 1. A.A. Voors et al., European Journal of Heart Failure 2024 JANU AR Y 2025 * Teerlink J.R. et
al. Eur. J. Heart Fail. 2019; 22: 315-329; patients from RELAX-AHF-JP (N=30 total) not listed in table
13 TX45 TX45 is Engineered to Solve a Critical PK Problem Observed With
Other Relaxin Molecules TX45 Exhibits Superior Profile vs. Parent Compound 2,3 and Comparator Molecules Preclinical Rat Pharmacokinetic Data Relaxin has very short in vivo half-life Fc-fusion needed to improve PK Half-life extended relaxins have
steep decline pI <9, TX-45 in exposure after dosing (>90%) because of 1 glycocalyx binding due to high pI pI >9, Comparator pI >9, TX early Engineering TX45 to reduce net positive charge (and lower pI) prevents rapid clearance 1.
Isoelectric Point 2. High pI Fc-relaxin fusion protein described in literature 3. Source: Tectonic internal data JANU AR Y 2025 Concentration
14 TX45 TX45 Initial Indication: Group 2 Pulmonary Hypertension (PH)
Pulmonary hypertension consists of 5 distinct diseases, or groups Idiopathic, hereditary or drug-induced Group 1 Connective tissue disease-associated PAH Group 2 PH is chronic, progressive Congenital heart disease-associated
and the largest category of * Pulmonary Hypertension Due to left heart failure (HFpEF, HFrEF ) or valvular heart disease Group 2 ** CAD, HTN, T2DM , high cholesterol are risk factors PH Elevated blood pressure in the
Two Subtypes: CpcPH & IpcPH pulmonary arteries Due to lung disease or hypoxia Chronically elevated pulmonary May be due to COPD, interstitial lung disease (i.e., IPF) or Group 3 arterial pressures taxes the right side
obstructive sleep apnea of the heart Pulmonary artery narrowing and Group 4 Chronic thrombo-embolic pulmonary hypertension - i.e., as a muscularization consequence of blood clots CTEPH Over time, the disease can lead to
right heart failure and death Group 5 Miscellaneous group including sickle cell, polycythemia vera, No approved therapies and sarcoidosis Misc. * Heart Failure with reduced Ejection Fraction JANU AR Y 2025 ** CAD: Coronary Artery
Disease, HTN: Hypertension, T2DM: Type 2 Diabetes Mellitus
15 TX45 Initial Focus on Group 2 PH due to Heart Failure With Preserved
EF (HFpEF), Enriched for CpcPH Patients Clinical program designed to enable evaluation of efficacy in overall population and CpcPH IpcPH (Isolated, post capillary PH) Heart Increased Left Ventricle Filling Pressures HFpEF Normal HFpEF 1
Increased Pulmonary Venous Pressures (~4M) Passive Pressure Backflow Pulmonary Hypertension Group 2 PH 1 (~1.4M) IpcPH CpcPH (Combined, pre- and post capillary PH) 2 CpcPH (~1M) (~400K) Chronic PH and/or Other Drivers Pulmonary
Vasculature Permanent Vascular Changes, e.g. Pulmonary Artery Remodeling Increased Vascular Resistance Normal PAH-like Right Heart Failure 1. US prevalence numbers for Class 2 and 3, estimates based on company sponsored market
analysis conducted by Health Advances JANU AR Y 2025 2. Assumes diagnosis based on pulmonary vascular resistance (PVR) of > or equal to 3 wood units
16 TX45 Group 2 PH vs. PAH (Group 1) Significant opportunity for a
first-in-indication therapy Highly motivated physicians and patients No Therapeutic Options 4 US Prevalence >> PAH 5-Year Survival PAH For Group 2 PH 1 ~1,400,000 Group 2 PH PAH ~ 50% 50% No approved Multiple drugs/ IpcPH therapies
mechanisms (~1M) approved 23% Limited pipeline ET1R antagonists PDE5 inhibitors PAH Drugs have GC stimulators CpcPH not demonstrated Prostaglandins (~400K) 2 convincing ACTRII-Trap >25,000 efficacy in Group 2 PH with cpcPH IpcPH PAH Group
2 PH PAH the exception of PDE5i in CpcPH Multi-$ Billion Market >$4 Billion Market in Group 2 PH 3 Opportunity US Today 1. US prevalence numbers for Class 2 and 3, estimates based on company sponsored market analysis conducted by Health Advances
2. www.pahinitiative.com 3. GlobalData 4. Caravita S. et al. https://doi.org/10.1371/journal.pone.0199164; Gall H. et al The Journal of Heart and Lung Transplantation, Vol 36, No 9, September 2017; estimates from synthesis of different studies JANU
17 TX45 Relaxin Agonism of RXFP1 Elicits Changes in Multiple Organs and
Organ Systems Important in PH-HFpEF Vasodilation RV / LV* Pulmonary & Systemic Afterload NO Endothelin-1 Relaxin LV Relaxation Improved LV agonist Diastolic Function SERCA2 function Fibrosis RV /
LV and Pulmonary Artery Anti-Inflammatory MMPs TGF Reverse Remodeling RXFP1 + Na Excretion Renal Blood Flow RV / LV Preload * RV: right ventricle; LV: left ventricle JANU AR Y 2025
18 TX45 Relaxation and Anti-Fibrotic Effects of Relaxin Have Potential
for Disease Modification in PH-HFpEF Heart and vascular dysfunction contribute to disease pathology Renal dysfunction also present in many of these patients CHARACTERISTICS OF PH-HFpEF ANTICIPATED RELAXIN EFFECTS Pulmonary
Vasodilation Pulmonary artery narrowing, thickening, stiffening, fibrotic remodeling Anti-inflammatory, anti-fibrotic Peripheral vasodilation, improved Thickening and stiffening of Left Ventricle cardiac relaxation, left ventricular remodeling
Compromised kidney function Improvement in kidney function, natriuresis Combined decrease in pulmonary pressure and increased cardiac function are expected to be needed for efficacy in PH-HFpEF JANU AR Y 2025
19 TX45 In Acute Heart Failure (AHF), Serelaxin Improves LV Function
(Lowering 1 PCWP), and Lowers Pulmonary Pressures and Resistance (mPAP, PVR) Furosemide given 4h prior to serelaxin infusion, and 8h after initiation of serelaxin PCWP mPAP PVR Lung capillary pressure - Pulmonary (lung) Blood flow resistance
in measure of left atrial pressure artery pressure pulmonary arteries Hours post dose Hours post dose Hours post dose In a similar study in patients with chronic heart failure, 2 a reduction in PCWP and an increase in cardiac output was demonstrated