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Transforming the Discovery of Novel GPCR- Targeted Therapies J A N U A R Y 2 0 2 4 DISCLAIMER This communication contains "forward-looking statements" within the meaning of the "safe harbor" provisions of the Private Sec

Key Takeaway: This article discusses the proposed merger between AVROBIO and Tectonic, highlighting the uncertainties surrounding the merger's completion, including necessary shareholder approvals and regulatory permissions. It outlines the potential risks associated with managing expenses and the anticipated operational strategies of the combined company. Additionally, the article addresses the uncertainties linked to the clinical development of product candidates and the broader financial outlook for the combined entity. Investors are urged to rely on future filings for comprehensive details related to the merger.

Market Sentiment Analysis

CONCERNS & RISKS

  • The proposed merger's completion is uncertain and subject to various approvals.
  • There are risks related to AVROBIO's ability to manage operating expenses during the merger process.
  • Potential adverse reactions or changes to business relationships may impact the merger's success.
  • The clinical development and regulatory approval process for product candidates may face delays.

Full Press Release Details

Therapies J A N U A R Y 2 0 2 4
DISCLAIMER This communication contains "forward-looking
statements" within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including but not limited to, express or implied statements regarding the structure, timing and completion of
the proposed Merger; the combined company's listing on Nasdaq after closing of the proposed Merger; expectations regarding the ownership structure of the combined company; the anticipated timing of closing; each company's and the
combined company's expected cash position at the closing of the proposed Merger and cash runway of the combined company; the future operations of the combined company; the nature, strategy and focus of the combined company; the development and
commercial potential and potential benefits of TX45; anticipated preclinical and clinical drug development activities and related timelines, including the expected timing for data and other clinical results; the competitive landscape of the combined
company; and other statements that are not historical fact. All statements other than statements of historical fact contained in this communication are forward-looking statements. These forward-looking statements are made as of the date they were
first issued, and were based on the then-current expectations, estimates, forecasts, and projections, as well as the beliefs and assumptions of management. Forward-looking statements are subject to a number of risks and uncertainties, many of which
involve factors or circumstances that are beyond AVROBIO's, Tectonic's or the combined company's control. Actual results could differ materially from those stated or implied in forward-looking statements due to a number of factors,
including but not limited to (i) the risk that the conditions to the closing of the proposed Merger are not satisfied, including the failure to timely obtain shareholder approval for the transaction, if at all; (ii) uncertainties as to the timing of
the consummation of the proposed Merger and the ability of each of AVROBIO and Tectonic to consummate the proposed Merger; (iii) risks related to AVROBIO's ability to manage its operating expenses and its expenses associated with the proposed merger
pending closing; (iv) risks related to the failure or delay in obtaining required approvals from any governmental or quasi-governmental entity necessary to consummate the proposed Merger; (v) the risk that as a result of adjustments to the exchange
ratio, AVROBIO shareholders and Tectonic stockholders could own more or less of the combined company than is currently anticipated; (vi) risks related to the market price of AVROBIO's common stock relative to the value suggested by the
exchange ratio; (vii) unexpected costs, charges or expenses resulting from the transaction; (viii) potential adverse reactions or changes to business relationships resulting from the announcement or completion of the proposed Merger; (ix) the
uncertainties associated with Tectonic's platform technologies, as well as risks associated with the clinical development and regulatory approval of product candidates, including potential delays in the commencement, enrollment and completion
of clinical trials; (x) risks related to the inability of the combined company to obtain sufficient additional capital to continue to advance these product candidates and its preclinical programs; (xi) uncertainties in obtaining successful clinical
results for product candidates and unexpected costs that may result therefrom; (xii) risks related to the failure to realize any value from product candidates and preclinical programs being developed and anticipated to be developed in light of
inherent risks and difficulties involved in successfully bringing product candidates to market; (xiii) risks associated with the possible failure to realize certain anticipated benefits of the proposed Merger, including with respect to future
financial and operating results; (xiv) risks associated with AVROBIO's financial close process; (xv) the risk that the private financing is not consummated, among others. Actual results and the timing of events could differ materially from
those anticipated in such forward-looking statements as a result of these risks and uncertainties. These and other risks and uncertainties are more fully described in filings that AVROBIO makes and will make with the SEC in connection with the
proposed Merger, including the Proxy Statement described below under "Additional Information and Where to Find It." You should not place undue reliance on these forward-looking statements, which are made only as of the date hereof or as
of the dates indicated in the forward-looking statements. AVROBIO, Tectonic and the combined company expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to
reflect any change in its expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based. Tectonic obtained the industry, market and competitive position data used throughout this
presentation from its own internal estimates and research, as well as from industry and general publications, and research, surveys and studies conducted by third parties. Internal estimates are derived from publicly available information released
by industry analysts and third-party sources, Tectonic's internal research and its industry experience, and are based on assumptions made by Tectonic based on such data and its knowledge of the industry and market, which it believes to be
reasonable. In addition, while Tectonic believes the industry, market and competitive position data included in this presentation is reliable and based on reasonable assumptions, Tectonic has not independently verified any third-party information,
and all such data involve risks and uncertainties and are subject to change based on various factors. This presentation contains trademarks, services marks, trade names and copyrights of Tectonic and other companies, which are the property of their
respective owners. The use or display of third parties' trademarks, service marks, trade name or products in this presentation is not intended to, and does not imply, a relationship with Tectonic, or an endorsement of sponsorship by Tectonic.
Solely for convenience, the trademarks, service marks and trade names referred to in this presentation may appear with the , TM or SM symbols, but such references are not intended to indicate, in any way, that the company will not assert, to
the fullest extent under applicable law, their rights or the right of the applicable licensor to these trademarks, service marks and trade name.
DISCLAIMER (continued) Participants in the Solicitation This
communication relates to the proposed merger transaction involving AVROBIO and Tectonic and may be deemed to be solicitation material in respect of the proposed merger transaction. In connection with the proposed merger transaction, AVROBIO will
file relevant materials with the U.S. Securities and Exchange Commission (the "SEC"), including a registration statement on Form S-4 (the "Form S-4") that contains a proxy statement (the "Proxy Statement") and
prospectus. This communication is not a substitute for the Form S-4, the Proxy Statement or for any other document that AVROBIO may file with the SEC and or send to AVROBIO's shareholders in connection with the proposed merger transaction.
BEFORE MAKING ANY VOTING DECISION, INVESTORS AND SECURITY HOLDERS OF AVROBIO ARE URGED TO READ THE FORM S-4, THE PROXY STATEMENT AND OTHER DOCUMENTS FILED WITH THE SEC CAREFULLY AND IN THEIR ENTIRETY WHEN THEY BECOME AVAILABLE BECAUSE THEY WILL
CONTAIN IMPORTANT INFORMATION ABOUT AVROBIO, THE PROPOSED MERGER TRANSACTION AND RELATED MATTERS. Additional Information and Where to Find It Investors and security holders may obtain free copies of the Form S-4, the Proxy Statement and other
documents filed by AVROBIO with the SEC through the website maintained by the SEC at http://www.sec.gov. Copies of the documents filed by AVROBIO with the SEC are also available free of charge on AVROBIO's website at www.avrobio.com. AVROBO,
Tectonic, and their respective directors and certain of their executive officers may be considered participants in the solicitation of proxies from AVROBIO's shareholders with respect to the proposed merger transaction under the rules of the SEC.
Information about the directors and executive officers of AVROBIO is set forth in its Annual Report on Form 10-K for the year ended December 31, 2022, which was filed with the SEC on March 23, 2023, and in subsequent documents filed with the SEC.
Additional information regarding the persons who may be deemed participants in the proxy solicitations and a description of their direct and indirect interests, by security holdings or otherwise, are also included in the Form S-4, the Proxy
Statement and other relevant materials to be filed with the SEC when they become available. You may obtain free copies of this document as described above. No Offer or Solicitation This communication does not constitute an offer to sell or the
solicitation of an offer to buy any securities nor a solicitation of any vote or approval with respect to the proposed transaction or otherwise. No offering of securities shall be made except by means of a prospectus meeting the requirements of
Section 10 of the U S. Securities Act of 1933, as amended, and otherwise in accordance with applicable law.
Transforming the Discovery of Novel GPCR-Targeted Therapies J A N U A R
5 Merger of Tectonic Therapeutic and AVROBIO Tectonic
Therapeutic, a privately-held biotechnology company focused on discovering and developing GPCR-targeted therapies, intends to merge with AVROBIO, Inc. (Nasdaq: AVRO) OVERVIEW Supported by the Board of Directors of both companies and subject
to stockholder approval and other customary closing conditions Planned $130.7 million private financing from new and existing leading life sciences investors, together with existing cash from both companies at closing, expected to be
TRANSACTION approximately $165 million and provide cash runway into mid-2027 SUMMARY Expected pro forma ownership is approximately 40% pre-merger Tectonic shareholders, 22% pre-merger AVROBIO shareholders, and 38% purchasers in the private
financing Merger and financing expected to close in Q2 2024 Existing Tectonic management to lead the combined company MANAGEMENT Board of Directors of combined company will include one director from the AVROBIO BOD
6 Tectonic Therapeutic - Transforming the Discovery of Novel
GPCR-Targeted Therapies, Innovating in Their Development Validated platform to discover and optimize biologics that target GPCRs Prioritizing high value GPCR targets, where small molecules are not the right modality First two
assets address indications with no approved therapy 1 2 1. RXFP1 agonist - potential therapy for Group 2 PH in HFpEF >600,000 Patients in US alone (>20 times PAH) Initial Phase 1A PK/PD data demonstrated activity and favorable
PK with potential for monthly dosing; full data set from this study expected by mid 2024 Phase 1B hemodynamic proof of concept expected in 2025, randomized Phase 2 data expected in 2026 2. GPCR antagonist antibody addressing hereditary
hemorrhagic telangiectasia (HHT) Team with extensive track record of drug discovery and development success, resulting in 20 first approvals across multiple therapeutic areas Well capitalized by a syndicate of leading institutional
funds Transaction expected to provide runway into mid-2027 1. Pulmonary Hypertension 2. Heart Failure with Preserved Ejection Fraction
7 Our Team Has Delivered for Patients and Investors Alise Christian
Peter Anthony Marcella Marc Reicin, M.D. Cortis, Ph.D. McNamara, Ph.D. Muslin, M.D. Ruddy, M.D. Schwabish, Ph.D. CEO, Director COO CSO CDO CMO CBO 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)
8 Biologics Offer Advantages Over Small Molecules in Targeting GPCRs in
Multiple Settings ~12% >18%* Approved remain When difficult to drug with small molecules drugs target unexploited Biologic captures complexity of ligand / receptor engagement 100 GPCRs If target site similar to domains of different proteins
Biologic minimizes off target binding to improve safety / tolerability Non- 800+ Sensory Orphan GPCRs If use case requires tissue /compartment targeting GPCRs (~20%) Sensory Engineer biologic to target or exclude compartment as needed GPCRs (~50%)
When multi-modal action needed Bispecific approach enables dual target engagement >470 Approved drugs (~33% of all) >$180B in annual sales Predominantly small molecules Address broad range of therapeutic
areas Only 3 are antibodies (*) 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)
9 Our Unique Pipeline Opportunities are Enabled by Biologic Targeting
of GPCRs GROUP 2 PULMONARY HEREDITARY HEMORRHAGIC FIBROSIS HYPERTENSION (Group 2 PH) TELANGIECTASIA (HHT) First in Class & Indication Bi-specific Approach 2 2 Potential Best-in-Class GPCR Antagonist GPCR Antagonist 1 (anti-angiogenic)
(anti-fibrotic) RXFP1 Agonist Supporting clinical data Target pathway linked to disease Supporting clinical data for one genetics component of bispecific Scale of POC studies: ~50-200 patients per indication 3-6 months treatment 1. Fusion protein
- lead molecule in-licensed from Harvard U., optimized using GEODe platform 2. GPCR targeted mAbs discovered internally using GEODe platform
10 Post Close Cash to Support Pipeline Progression Into Mid-2027 and
Several Key Inflection Points Tectonic Pipeline and Expected Readouts RXFP1 Complete PK/PD Data: mid 2024 Phase 1a Ph 1b hemodynamic proof of concept data: 2025 Agonist Randomized Ph 2 data: 2026 (TX45 - Fc-relaxin)
GPCR Start of Ph 1: Q4 2025 / Q1 2026 Development Antagonist Candidate Selection Start of randomized studies: ~Q4 2026 (HHT Program) GPCR Discovery Develop internally or partner Antagonist (Fibrosis Program) GPCR
Discovery Develop internally or partner Modulators (Undisclosed) 1 Includes in vivo HHT validation
11 GEODe GEODe Designed to Solve Key Challenges in GPCR Targeted
Biologics Discovery GEODe Platform Features Challenges Designed for Success RETAIN 1. endogenous GPCR structure to enable Receptor Engineering, and Purification Technology screening against relevant form of receptor delivers abundant receptor
reagent in native conformation PURIFY target in sufficient quantities to power screening campaign 2. In-vitro Yeast Display Libraries INDUCE provide high-diversity, without immune editing immune response to human GPCR in animals if immunization
strategy is pursued 3. STABILIZE Protein Engineering receptor in active conformation to enable Optimize protein pharmacology Engineer antigen formats to enable screening for agonists or agonist discovery antagonists as needed
TX45: Fc-RELAXIN FUSION PROTEIN RXFP1 agonist with differentiated
13 TX45 Hemodynamic and Anti-fibrotic Properties of Relaxin
Demonstrated by its Role in Pregnancy Pharmacology Facilitates Gestation AGONIST PULMONARY AND SYSTEMIC VASODILATOR Increases cardiac output to Natural Ligand of RXPF1 accommodate the Receptor increased demand from developing fetus No RXFP1
internalization from relaxin agonism ANTIFIBROTIC no desensitization with chronic therapy Prepares musculoskeletal tissues for pregnancy and childbirth Relaxin upregulated in Local resolution cryo-EM map of full-length RXFP1-Gs complex
BioRxiv: https://doi.org/10.1101/2022.01.22.477343 pregnancy Pharmacologic properties of relaxin hold promise as a potential treatment for cardio- pulmonary and renal disease, but its short half-life has impeded its development
14 TX45 Evidence of Serelaxin's Safety and Benefit in Acute
Heart Failure (AHF) A meta-analysis of 6 studies and >11,000 patients demonstrated that a 2-day infusion of serelaxin was safe and resulted in a 23% decrease in 5-day worsening heart failure One of two pivotal studies include in
meta-analysis, RELAX-AHF-2, failed to achieve the co- primary endpoints, and we believe that two factors contributed to this outcome - It was ambitious to expect that a two-day infusion of serelaxin, with its short half-life and mechanism of
action, would demonstrate clinical benefit at day 5 and, more puzzlingly at 6 months - Operational challenges with patient enrollment may also have had an impact Limitations of serelaxin's PK inhibited further development, but its
clinical performance supports advancement of TX45 whose PK profile permits chronic dosing for chronic diseases such as pulmonary hypertension and heart failure * 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
15 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 MOLECULE Preclinical Rat Pharmacokinetic Data Relaxin has very short in vivo half-life Fc-fusion needed to improve PK Relaxin Fc-fusions have steep
decline in pI <9, TX-45 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 Concentration
16 TX45 TX45 Reflects Significant Protein Engineering to Optimize Its
Pharmacology 1 TX45 results in ~10x greater in vivo potency over comparator molecule than predicted based on PK 2 and in vitro activity - potentially from reduced trapping of drug in glycocalyx, resulting in increased free drug available to
activate RXFP1 in tissues Superior efficacy (Renal Blood Flow) in TX45 vs. Relative in Relative in Expected in Observed in 3 High PI Comparator Molecule at Same Dose vivo exposure vitro potency vivo activity at vivo activity at at same dose on
receptor same dose same dose 1X 10X 10X 1X 10X 10X 1X 10X TX45 0.3mpk TX45 0.03 mpk Comparator 0.3 mpk Vehicle Comp TX45 Comp TX45 Comp TX45 Comp TX45 2. ~0.03 mpk of TX45 has 1. High pI Fc-relaxin fusion protein described in literature 3. Source:
Tectonic internal data similar efficacy as 0.3 mpk of Comparator
17 TX45 TX45 - Optimized RXFP1Agonist for Group 2 PH in HFpEF
Potential Best-in-Class Relaxin Protein engineering has extended pharmacologic half-life to support monthly dosing Agonist with Optimized PK No approved therapy High Unmet Need in Group 2 >600,000
patients in US 1 PH with HFpEF High 5-year high mortality Pulmonary + systemic vasodilation, cardiac relaxation Mechanism may be Ideal to Reversal of fibrosis in pulmonary vasculature and heart Address Group 2 PH
Anti-inflammatory Supporting Clinical and Pre- Hemodynamic benefit in studies of serelaxin in AHF Clear benefit observed with TX45 in rodent PH and CHF models clinical Data No outcome study needed
Streamlined Development Enrichment strategy for CpcPH where there is greatest unmet need Strategy Enables potential early launch relative to congestive heart failure Other PH Groups, Heart failure, renal disease

Frequently Asked Questions

What is the proposed merger between AVROBIO and Tectonic about?

The merger involves AVROBIO and Tectonic, focusing on combining resources for future operations and drug development.

What are forward-looking statements in the merger context?

These statements include projections about ownership, financial positions, and operational strategies post-merger.

Are there risks associated with the proposed merger?

Yes, risks include delays in approvals, financial uncertainties, and operational challenges.

Where can shareholders find more information about the merger?

Shareholders can access details through the SEC's website and AVROBIO's official site.

What materials will AVROBIO file regarding the merger?

AVROBIO will file a registration statement and a proxy statement with the SEC.

Last updated: Jan 30, 2024