Financial Performance - The company reported total operating expenses of $131.2 million for the year ended December 31, 2023, an increase of 4% from $125.6 million in 2022[483]. - The company incurred a net loss of $124.1 million for the year ended December 31, 2023, compared to a net loss of $123.7 million in 2022, reflecting a marginal increase of $419, or 0%[491]. - Net cash used in operating activities for the year ended December 31, 2023, was $102.1 million, compared to $104.4 million in 2022[501][502]. - Net cash provided by investing activities for the year ended December 31, 2023, was $48.7 million, down from $83.7 million in 2022[503][504]. - Net cash provided by financing activities for the year ended December 31, 2023, was $4.0 million, significantly lower than $77.8 million in 2022[505]. - The company expects to incur operating losses in the foreseeable future, with operating expenses anticipated to remain relatively flat over the next twelve months[497]. Research and Development - Research and development expenses were $98.0 million in 2023, up 4% from $94.5 million in 2022, primarily due to an increase of $8.9 million in personnel-related costs[485]. - The company initiated dosing in the MyPeak-1 Phase 1b clinical trial for TN-201 in October 2023, with initial data expected in the second half of 2024[473]. - The FDA cleared the IND application for TN-401 in October 2023, with patient dosing planned to begin in the second half of 2024[476]. - TN-301 showed positive results in a Phase 1 clinical trial, demonstrating good tolerability and pharmacokinetic properties supportive of once-daily dosing[479]. - The company plans to advance its lead gene therapy product candidates, TN-201 and TN-401, and expand clinical trials into late-stage development[498]. Funding and Capital - The company completed a follow-on offering on February 12, 2024, raising approximately $46.5 million from the sale of 8,888,890 shares at $4.50 per share[493]. - The company raised approximately $76.9 million from the purchase of an additional 2,816,409 shares of common stock after deducting underwriting discounts and commissions[495]. - As of December 31, 2023, the company has approximately $71.0 million available for issuance under its "at-the-market" equity offering[496]. Company Status and Classification - The company has not generated any revenue to date and has an accumulated deficit of $403.3 million as of December 31, 2023[492]. - The company is classified as an emerging growth company and a smaller reporting company, with annual revenue below $100 million and market value of stock held by non-affiliates less than $700 million[517][519]. Lease Obligations - The company has future minimum lease payments of approximately $5.1 million and $10.9 million remaining on its South San Francisco and Union City leases, respectively[506]. Off-Balance Sheet Arrangements - The company has not engaged in any off-balance sheet arrangements since inception[509]. Interest Income - Interest income increased significantly by 261% to $7.1 million in 2023, up from $2.0 million in 2022, primarily due to higher interest rates on investments[490].

[Overview and Key Milestones](index=1&type=section&id=Tenaya%20Therapeutics%20Reports%20Fourth%20Quarter%20and%20Full%20Year%202023%20Financial%20Results%20and%20Provides%20Business%20Update) Tenaya Therapeutics reported Q4/FY2023 results, emphasizing genetic medicine progress and extended cash runway [Corporate Update and 2024 Outlook](index=1&type=section&id=Corporate%20Update) Tenaya reported Q4/FY2023 results, highlighting genetic medicine progress, upcoming trial data, and extended cash runway - Initial data from the MyPeak™-1 Phase 1b trial of TN-201 for HCM is expected in the **second half of 2024**[1](index=1&type=chunk) - The first patient in the RIDGE™-1 Phase 1b trial of TN-401 for ARVC is expected to be dosed in the **second half of 2024**[1](index=1&type=chunk) - Net proceeds of **$47 million** from a recent financing extended the company's cash runway into the **second half of 2025**[1](index=1&type=chunk) - CEO Faraz Ali highlighted key 2023 achievements, including IND clearances for TN-201 and TN-401, dosing the first patient with TN-201, and in-house cGMP manufacturing of clinical trial materials[2](index=2&type=chunk) [Clinical Program Updates](index=1&type=section&id=Business%20and%20Program%20Updates) Tenaya provides updates on its gene therapy programs for HCM and ARVC, and its small molecule program for HFpEF [TN-201 for MYBPC3-Associated HCM](index=1&type=section&id=TN-201%20%E2%80%93%20Gene%20Therapy%20for%20MYBPC3-Associated%20Hypertrophic%20Cardiomyopathy%20%28HCM%29) MyPEAK-1 Phase 1b trial for TN-201 dosed its first patient in October 2023, with initial data expected in H2 2024 - The first patient in the MyPEAK-1 Phase 1b trial was dosed in **October 2023**[3](index=3&type=chunk) - Initial data on safety, tolerability, and clinical efficacy from the first cohort is anticipated in the **second half of 2024**[3](index=3&type=chunk) - Interim data from a related study indicated that low levels of preexisting neutralizing antibodies to AAV9 could make a majority of MYBPC3-associated HCM patients eligible for TN-201[4](index=4&type=chunk) [TN-401 for PKP2-Associated ARVC](index=2&type=section&id=TN-401%20%E2%80%93%20Gene%20Therapy%20for%20PKP2-Associated%20Arrhythmogenic%20Right%20Ventricular%20Cardiomyopathy%20%28ARVC%29) Tenaya plans to initiate TN-401 RIDGE-1 Phase 1b trial dosing in H2 2024, following FDA Fast Track Designation - Patient dosing in the RIDGE-1 Phase 1b clinical trial is on track to begin in the **second half of 2024**[9](index=9&type=chunk) - TN-401 received **Fast Track Designation** from the U.S. FDA in **November 2023**[9](index=9&type=chunk) [TN-301 Small Molecule for HFpEF](index=2&type=section&id=TN-301%20%E2%80%93%20Small%20Molecule%20HDAC6%20Inhibitor%20for%20Heart%20Failure%20with%20Preserved%20Ejection%20Fraction%20%28HFpEF%29) TN-301, an HDAC6 inhibitor, showed positive Phase 1 results with good tolerability, once-daily dosing potential, and additive preclinical benefits - Phase 1 results showed TN-301 was generally well-tolerated with a half-life supportive of **once-daily dosing**[9](index=9&type=chunk) - Robust pharmacodynamic effects, including **HDAC6 inhibition**, were observed and correlated with increasing doses[9](index=9&type=chunk) - New preclinical data showed **additive benefits** when combining TN-301 with empagliflozin in validated HFpEF mouse models[9](index=9&type=chunk) [Financials and Corporate Developments](index=2&type=section&id=Financials%20and%20Corporate%20Developments) This section details Tenaya's Q4/FY2023 financial performance, including expenses, net loss, and recent financing activities [Fourth Quarter and Full Year 2023 Financial Highlights](index=2&type=section&id=Fourth%20Quarter%20and%20Full%20Year%202023%20Financial%20Highlights) Tenaya reported a **$124.1 million** net loss for FY2023, with **$98.0 million** in R&D expenses and **$104.6 million** cash Full Year 2023 Financial Summary | Metric | Full Year 2023 | | :--- | :--- | | R&D Expenses | $98.0 million | | G&A Expenses | $33.2 million | | Net Loss | $124.1 million | | Net Loss Per Share | $1.68 | Q4 2023 Financial Summary | Metric | Q4 2023 | | :--- | :--- | | R&D Expenses | $22.9 million | | G&A Expenses | $8.6 million | | Net Loss | $29.9 million | | Net Loss Per Share | $0.40 | [Financing and Cash Runway](index=2&type=section&id=Follow-on%20Financing) Tenaya secured **$46.5 million** in February 2024 financing, extending its cash runway into H2 2025 - Completed a follow-on offering in February 2024 with net proceeds of **$46.5 million**[7](index=7&type=chunk) - As of **December 31, 2023**, cash, cash equivalents, and marketable securities were **$104.6 million**[8](index=8&type=chunk) - The company expects its current funds to be sufficient to support operations into the **second half of 2025**[8](index=8&type=chunk) [Financial Statements](index=5&type=section&id=Financial%20Statements) This section presents Tenaya's condensed statements of operations and balance sheet data [Condensed Statements of Operations](index=5&type=section&id=Condensed%20Statements%20of%20Operations) For FY2023, total operating expenses increased to **$131.2 million**, resulting in a net loss of **$124.1 million** or **($1.68)** per share Annual Statement of Operations (in thousands, except per share data) | Account | Year Ended Dec 31, 2023 | Year Ended Dec 31, 2022 | | :--- | :--- | :--- | | Research and development | $98,038 | $94,537 | | General and administrative | $33,155 | $31,084 | | **Total operating expenses** | **$131,193** | **$125,621** | | Interest income | $7,056 | $1,954 | | **Net loss** | **$(124,084)** | **$(123,665)** | | Net loss per share, basic and diluted | $(1.68) | $(2.76) | | Weighted-average shares used | 73,786,126 | 44,823,597 | [Condensed Balance Sheet Data](index=6&type=section&id=Condensed%20Balance%20Sheet%20Data) As of December 31, 2023, cash, cash equivalents, and marketable securities were **$104.6 million**, with total assets at **$170.5 million** Balance Sheet Highlights (in thousands) | Account | December 31, 2023 | December 31, 2022 | | :--- | :--- | :--- | | Cash, cash equivalents and marketable securities | $104,642 | $204,230 | | Total assets | $170,515 | $278,945 | | Total liabilities | $31,091 | $35,569 |

Financial Performance - Net loss for Q3 2023 was $29.1 million, compared to a net loss of $30.7 million in Q3 2022, reflecting a decrease of $1.6 million[95]. - The net loss for the nine months ended September 30, 2023, was $94.1 million, compared to a net loss of $90.1 million in 2022, reflecting a 4% increase in losses[100]. - Cash used in operating activities was $80.1 million for the nine months ended September 30, 2023, slightly improved from $81.7 million in 2022[109]. - The company had cash, cash equivalents, and investments in marketable securities totaling $128.1 million as of September 30, 2023, with an accumulated deficit of $373.3 million[101]. - The company expects ongoing increases in expenses and operating losses due to continued product development and regulatory approval efforts[104]. Research and Development - Research and development expenses for Q3 2023 were $23.1 million, a decrease of 3% from $23.8 million in Q3 2022[86]. - Research and development expenses increased to $75.2 million for the nine months ended September 30, 2023, up from $68.8 million in 2022, representing a 9% increase[97]. - The company expects research and development expenses to remain flat for the remainder of 2023[90]. - TN-201, a gene therapy for hypertrophic cardiomyopathy, began dosing patients in a Phase 1b trial in October 2023, with initial data expected in 2024[78]. - TN-401, a gene therapy for arrhythmogenic right ventricular cardiomyopathy, received FDA clearance for clinical testing in October 2023[80]. - TN-301, a small molecule for heart failure with preserved ejection fraction, showed positive Phase 1 trial results, indicating robust HDAC6 inhibition[82]. - The company has initiated two non-interventional studies to support the development of TN-201, focusing on MYBPC3-associated cardiomyopathy[79]. - The Genetic Medicines Manufacturing Center is strategically located near research labs to support clinical studies and AAV-based gene therapies[85]. Expenses - General and administrative expenses increased to $7.8 million in Q3 2023, up 4% from $7.5 million in Q3 2022, primarily due to higher stock-based compensation[92]. - General and administrative expenses rose to $24.6 million in 2023, compared to $22.3 million in 2022, marking a 10% increase primarily due to higher stock-based compensation[98]. Income and Financing - Interest income rose significantly by 198% to $1.8 million in Q3 2023, up from $596,000 in Q3 2022, driven by higher interest rates on investments[86]. - Interest income surged to $5.6 million in 2023, a 509% increase from $917,000 in 2022, driven by higher interest rates on investments[99]. - The company raised $3.7 million from financing activities in 2023, primarily from at-the-market sales[113]. - The company has not generated any revenue since inception and relies on equity securities for funding operations[101]. Regulatory and Reporting Status - The company qualifies as a smaller reporting company under Rule 12b-2 and is not required to provide certain disclosures[122]. - As a smaller reporting company, the company may present only the two most recent fiscal years of audited financial statements in its Annual Report on Form 10-K[121]. - The company has reduced disclosure obligations regarding executive compensation due to its status as a smaller reporting company[121].

[PART I—FINANCIAL INFORMATION](index=5&type=section&id=PART%20I%E2%80%94FINANCIAL%20INFORMATION) This section presents the unaudited financial statements, management's discussion and analysis, market risk disclosures, and controls and procedures for the company [Item 1. Financial Statements (Unaudited)](index=5&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) This section presents the unaudited condensed financial statements for Tenaya Therapeutics, Inc. as of June 30, 2023, including balance sheets, statements of operations, stockholders' equity, and cash flows, reporting a **$65.0 million** net loss and **$151.6 million** in cash and equivalents Condensed Balance Sheet Summary (in thousands) | Account | June 30, 2023 | December 31, 2022 | | :--- | :--- | :--- | | **Total Current Assets** | $138,906 | $193,754 | | Cash and cash equivalents | $75,565 | $95,272 | | **Total Assets** | $220,754 | $278,945 | | **Total Current Liabilities** | $20,917 | $24,248 | | **Total Liabilities** | $30,814 | $35,569 | | **Total Stockholders' Equity** | $189,940 | $243,376 | Condensed Statement of Operations Summary (in thousands) | Metric | Three Months Ended June 30, 2023 | Three Months Ended June 30, 2022 | Six Months Ended June 30, 2023 | Six Months Ended June 30, 2022 | | :--- | :--- | :--- | :--- | :--- | | Research and development | $26,477 | $20,876 | $52,082 | $45,031 | | General and administrative | $8,627 | $7,743 | $16,745 | $14,742 | | **Loss from operations** | $(35,104) | $(28,619) | $(68,827) | $(59,773) | | **Net loss** | $(33,269) | $(28,397) | $(65,006) | $(59,453) | Condensed Statement of Cash Flows Summary (Six Months Ended June 30, in thousands) | Cash Flow Activity | 2023 | 2022 | | :--- | :--- | :--- | | Net cash used in operating activities | $(56,510) | $(54,186) | | Net cash provided by investing activities | $33,146 | $46,644 | | Net cash provided by financing activities | $3,678 | $275 | | **Net change in cash, cash equivalents and restricted cash** | $(19,686) | $(7,267) | - As of June 30, 2023, the company had an accumulated deficit of **$344.2 million** and held **$151.6 million** in cash, cash equivalents, and marketable securities; management believes these funds are sufficient to support operations for at least the next twelve months[28](index=28&type=chunk)[29](index=29&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=18&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) This section analyzes the company's financial condition and operations, detailing its clinical-stage biotechnology business, lead product candidates, increased operating expenses, and liquidity, confirming sufficient funds for the next twelve months - Tenaya is a clinical-stage biotechnology company focused on developing curative therapies for heart disease, with a pipeline including gene therapies and small molecules[73](index=73&type=chunk) - Lead product candidates include: **TN-201** (gene therapy for HCM, Phase 1b trial expected Q3 2023, data 2024); **TN-301** (small molecule for HFpEF, Phase 1 topline data Q4 2023); **TN-401** (gene therapy for ARVC, IND submission expected H2 2023)[75](index=75&type=chunk)[76](index=76&type=chunk)[78](index=78&type=chunk)[79](index=79&type=chunk) - The company has established an in-house cGMP manufacturing facility, the Genetic Medicines Manufacturing Center, to support its portfolio of gene therapy and cellular regeneration candidates[82](index=82&type=chunk) - As of June 30, 2023, the company had **$151.6 million** in cash, cash equivalents, and marketable securities, believed sufficient to fund operations for at least the next twelve months[98](index=98&type=chunk)[101](index=101&type=chunk) [Results of Operations](index=19&type=section&id=Results%20of%20Operations) Operating expenses and net loss increased for both three and six-month periods ended June 30, 2023, primarily driven by higher research and development and general and administrative expenses Comparison of Three Months Ended June 30, 2023 and 2022 (in thousands) | Metric | 2023 | 2022 | $ Change | % Change | | :--- | :--- | :--- | :--- | :--- | | Research and development | $26,477 | $20,876 | $5,601 | 27% | | General and administrative | $8,627 | $7,743 | $884 | 11% | | **Total operating expenses** | $35,104 | $28,619 | $6,485 | 23% | | **Net loss** | $(33,269) | $(28,397) | $(4,872) | 17% | Comparison of Six Months Ended June 30, 2023 and 2022 (in thousands) | Metric | 2023 | 2022 | $ Change | % Change | | :--- | :--- | :--- | :--- | :--- | | Research and development | $52,082 | $45,031 | $7,051 | 16% | | General and administrative | $16,745 | $14,742 | $2,003 | 14% | | **Total operating expenses** | $68,827 | $59,773 | $9,054 | 15% | | **Net loss** | $(65,006) | $(59,453) | $(5,553) | 9% | - The increase in R&D expenses for the six months ended June 30, 2023, was primarily driven by a **$5.7 million** increase in employee-related costs (higher stock-based compensation and 2022 tax credits) and a **$2.0 million** increase in facility and laboratory costs[94](index=94&type=chunk)[97](index=97&type=chunk) [Liquidity and Capital Resources](index=22&type=section&id=Liquidity%20and%20Capital%20Resources) The company primarily funds operations through equity sales, holding **$151.6 million** in cash and equivalents as of June 30, 2023, with recent capital raises including a **$76.9 million** offering and **$3.9 million** from an ATM offering, sufficient for the next twelve months but requiring future funding - The company completed an underwritten public offering in November 2022, receiving total net proceeds of **$76.9 million**[99](index=99&type=chunk) - Through its "at-the-market" (ATM) equity offering, the company sold 535,767 shares during Q2 2023, resulting in proceeds of **$3.9 million**, net of commissions[100](index=100&type=chunk) - Net cash used in operating activities was **$56.5 million** for the first six months of 2023, compared to **$54.2 million** for the same period in 2022, primarily driven by the net loss[105](index=105&type=chunk)[106](index=106&type=chunk)[107](index=107&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=24&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a smaller reporting company, the company is exempt from providing quantitative and qualitative disclosures about market risk - As a smaller reporting company, Tenaya Therapeutics is not required to provide quantitative and qualitative disclosures about market risk[119](index=119&type=chunk) [Item 4. Controls and Procedures](index=24&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of June 30, 2023, with no material changes in internal control over financial reporting during the quarter - Management concluded that as of the end of the period, the company's disclosure controls and procedures are effective to provide reasonable assurance that required information is recorded, processed, and reported in a timely manner[120](index=120&type=chunk) - There were no changes in internal control over financial reporting during the quarter ended June 30, 2023, that have materially affected, or are reasonably likely to materially affect, internal controls[121](index=121&type=chunk) [PART II—OTHER INFORMATION](index=26&type=section&id=PART%20II%E2%80%94OTHER%20INFORMATION) This section covers legal proceedings, risk factors, unregistered sales of equity securities, and other miscellaneous information including exhibits [Item 1. Legal Proceedings](index=26&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently involved in any material legal proceedings expected to adversely affect its business - The company is not currently involved in any material legal proceedings[125](index=125&type=chunk) [Item 1A. Risk Factors](index=26&type=section&id=Item%201A.%20Risk%20Factors) This section outlines significant investment risks, including the company's early development stage, history of losses, need for capital, uncertain drug development, manufacturing challenges, competition, and intellectual property concerns - The company is in the early stages of development with a limited operating history, has only completed one clinical trial, and has no products approved for commercial sale[127](index=127&type=chunk)[128](index=128&type=chunk) - The company has a history of significant net losses (**$344.2 million** accumulated deficit as of June 30, 2023) and expects to continue incurring losses for the foreseeable future[127](index=127&type=chunk)[131](index=131&type=chunk) - Substantial additional capital is required to finance operations; failure to raise capital when needed could force the company to delay, reduce, or eliminate research and development programs[127](index=127&type=chunk)[137](index=137&type=chunk) - Drug development is a lengthy, expensive, and uncertain process; preclinical and clinical trials may not demonstrate the required safety and efficacy, and early positive results may not be predictive of future success[127](index=127&type=chunk)[164](index=164&type=chunk) - The company faces risks related to manufacturing its complex gene therapy products, both in-house and through third parties, and must comply with significant government regulations (cGMP)[127](index=127&type=chunk)[198](index=198&type=chunk)[203](index=203&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=73&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) No unregistered equity sales occurred during the period, and the **$188.5 million** net proceeds from the August 2021 IPO remain unchanged in their planned use - There were no sales of unregistered securities in the period[386](index=386&type=chunk) - The company's IPO on August 3, 2021, generated net proceeds of **$188.5 million**; there has been no material change in the planned use of these proceeds[387](index=387&type=chunk) [Item 3. Defaults Upon Senior Securities](index=73&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) This section is not applicable to the company [Item 4. Mine Safety Disclosures](index=73&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This section is not applicable to the company [Item 5. Other Information](index=73&type=section&id=Item%205.%20Other%20Information) No other information is reported in this section [Item 6. Exhibits](index=74&type=section&id=Item%206.%20Exhibits) This section lists exhibits filed with the Form 10-Q, including bylaws, compensation plans, officer certifications, and XBRL data files [Signatures](index=76&type=section&id=SIGNATURES) This section contains the required signatures for the filing

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2023 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ________ to _________ Commission File Number: 001-40656 TENAYA THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) Delaware 81-3789973 (St ...

13 MyPeak-1 Phase 1b Clinical Study TN-201 for MYBPC3 HCM 70%nonobstructive 30%obstructive Disease severity higher with pathogenic sarcomeric gene mutations such as MYBPC3, but no treatments address underlying genetic cause1 Characteristics Symptoms Disease burden • Thickening of left ventricle (hypertrophy) due to excessive contraction • May be characterized as "obstructive" or "nonobstructive" based on location of thickening • Shortness of breath, fainting, chest pain, fatigue, palpitations and arrhythmia ...

Part I [Business](index=6&type=section&id=Item%201.%20Business) Tenaya Therapeutics is a clinical-stage biotechnology company developing curative therapies for heart disease using gene therapy, cellular regeneration, and precision medicine platforms - Tenaya is a clinical-stage biotechnology company focused on developing curative therapies for heart disease, the leading cause of death globally[16](index=16&type=chunk) - The company's strategy is built upon three distinct product platforms: Gene Therapy, Cellular Regeneration, and Precision Medicine, supported by five core internal capabilities[20](index=20&type=chunk)[28](index=28&type=chunk)[31](index=31&type=chunk) Product Pipeline Overview | Program | Indication(s) | Stage | US Prevalence | Commercial Rights | | :--- | :--- | :--- | :--- | :--- | | **TN-201** | MYBPC3+ HCM | Phase 1 | > 115K | Tenaya | | **TN-301** | HFpEF | Phase 1 | > 3MM | Tenaya | | **TN-401** | PKP2+ ARVC | Preclinical | > 70K | Tenaya | | **DWORF** | DCM and/or HFrEF | Research | Prevalent | Tenaya | | **Reprogramming** | Post-MI Heart Failure | Research | Prevalent | Tenaya | [Our Programs](index=14&type=section&id=Our%20Programs) The company's pipeline includes lead candidates TN-201 (HCM), TN-301 (HFpEF), and TN-401 (ARVC), alongside early-stage gene therapy and cellular reprogramming programs - **TN-201 (MYBPC3-associated HCM):** Received IND clearance for a Phase 1b clinical trial, with patient dosing expected in Q3 2023 and data in 2024[66](index=66&type=chunk)[67](index=67&type=chunk) - **TN-301 (HDAC6 Inhibitor for HFpEF):** Currently in a Phase 1 clinical trial, with SAD stage complete and MAD stage initiated in February 2023, and data expected in 2H 2023[86](index=86&type=chunk) - **TN-401 (PKP2-associated ARVC):** IND-enabling activities are underway, with IND submission planned for 2H 2023[130](index=130&type=chunk) - **Early-Stage Programs:** Include a DWORF gene therapy for DCM and a cellular reprogramming therapy for post-MI heart failure, both at candidate selection stage[131](index=131&type=chunk)[148](index=148&type=chunk) [Our Product Platforms and Core Capabilities](index=40&type=section&id=Our%20Product%20Platforms%20and%20Core%20Capabilities) Tenaya's innovation is driven by integrated Gene Therapy, Cellular Regeneration, and Precision Medicine platforms, supported by five core in-house capabilities including disease models and cGMP manufacturing - **Gene Therapy Platform:** Utilizes AAVs to deliver healthy genes to heart cells, enhanced by internal capsid engineering for improved heart targeting[29](index=29&type=chunk)[168](index=168&type=chunk)[172](index=172&type=chunk) - **Cellular Regeneration Platform:** Focuses on in vivo reprogramming of cardiac fibroblasts into new cardiomyocytes to replace cells lost due to disease[32](index=32&type=chunk)[178](index=178&type=chunk) - **Precision Medicine Platform:** Employs human genetic data with iPSC-cardiomyocyte models and machine learning to identify novel heart disease targets[32](index=32&type=chunk)[185](index=185&type=chunk) - **Core Capabilities:** Five key internalized capabilities, including Disease Models and Manufacturing, aim to accelerate development and reduce third-party reliance[31](index=31&type=chunk)[191](index=191&type=chunk)[193](index=193&type=chunk) [Competition, IP, and Manufacturing](index=51&type=section&id=Competition,%20IP,%20and%20Manufacturing) Tenaya faces competition in heart disease therapies, protects its innovations with patents, and has in-house cGMP manufacturing for gene therapies while using CDMOs for small molecules - Key competitors include Bristol Myers Squibb for oHCM, Novartis and Eli Lilly for HFpEF, and preclinical gene therapy programs for ARVC[221](index=221&type=chunk)[222](index=222&type=chunk)[224](index=224&type=chunk) - The company's IP portfolio includes issued U.S. patents and pending applications for its programs, with expirations between 2037 and 2043[228](index=228&type=chunk)[229](index=229&type=chunk)[232](index=232&type=chunk) - Tenaya has internalized AAV manufacturing with non-GMP, technology development, and cGMP facilities, including a 1000L GMMC for clinical and commercial supply[217](index=217&type=chunk)[223](index=223&type=chunk) [Government Regulation](index=55&type=section&id=Government%20Regulation) The company's products are subject to extensive FDA and international regulation, involving complex approval processes for biologics and small molecules, with potential for expedited pathways and significant post-approval reimbursement challenges - In the U.S., biologic products require a BLA and small molecules an NDA from the FDA, involving extensive preclinical and clinical data for approval[247](index=247&type=chunk)[248](index=248&type=chunk) - The company may seek expedited development pathways like Fast Track and Breakthrough Therapy designations to accelerate review for serious conditions with unmet needs[272](index=272&type=chunk)[275](index=275&type=chunk) - Orphan Drug Designation grants seven years of market exclusivity for diseases affecting fewer than **200,000** people, a designation received by TN-201 and TN-401[267](index=267&type=chunk)[269](index=269&type=chunk)[455](index=455&type=chunk) - Commercial success depends on third-party payor reimbursement, with recent legislation like the IRA introducing Medicare price negotiation and inflation rebates that could impact revenue[316](index=316&type=chunk)[323](index=323&type=chunk) [Risk Factors](index=71&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant financial, development, regulatory, manufacturing, competition, and intellectual property risks due to its early stage, lack of revenue, and need for substantial capital - **Financial Risks:** The company has a history of significant net losses, **$123.7 million** in 2022, and requires substantial additional capital, risking program delays or elimination[341](index=341&type=chunk)[347](index=347&type=chunk) - **Development & Regulatory Risks:** Product candidates are early-stage with unproven mechanisms, facing complex and uncertain gene therapy regulations, and preclinical results may not predict clinical success[357](index=357&type=chunk)[363](index=363&type=chunk)[373](index=373&type=chunk) - **Manufacturing & Commercialization Risks:** Gene therapy manufacturing is complex with limited company experience, risking production problems and potential lack of market acceptance or adequate reimbursement post-approval[410](index=410&type=chunk)[412](index=412&type=chunk)[422](index=422&type=chunk) - **Intellectual Property Risks:** Success depends on obtaining and defending patents, with risks of infringement claims from third parties and inability to protect trade secrets[515](index=515&type=chunk)[526](index=526&type=chunk) [Properties](index=129&type=section&id=Item%202.%20Properties) Tenaya Therapeutics leases its corporate headquarters in South San Francisco and a manufacturing facility in Union City, CA, with leases expiring in 2025 and 2031 respectively - Corporate headquarters are leased in South San Francisco, CA, approximately **32,370 sq. ft.**, with the lease expiring on May 31, 2025[627](index=627&type=chunk) - A manufacturing and office facility is leased in Union City, CA, with its lease expiring in July 2031[628](index=628&type=chunk) [Legal Proceedings](index=129&type=section&id=Item%203.%20Legal%20Proceedings) The company is not currently involved in any material legal proceedings expected to adversely affect its business - As of the filing date, the company is not involved in any material legal proceedings[629](index=629&type=chunk) Part II [Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities](index=130&type=section&id=Item%205.%20Market%20for%20Registrant's%20Common%20Equity,%20Related%20Stockholder%20Matters%20and%20Issuer%20Purchases%20of%20Equity%20Securities) The company's common stock trades on Nasdaq under "TNYA" since its 2021 IPO, has never paid dividends, and generated **$188.5 million** in net IPO proceeds - The company's common stock trades on the Nasdaq Global Select Market under the symbol **"TNYA"**[633](index=633&type=chunk) - The company has never declared or paid cash dividends and does not anticipate doing so in the foreseeable future[635](index=635&type=chunk) - Net proceeds from the Initial Public Offering (IPO) on August 3, 2021, were **$188.5 million** after deducting offering expenses[638](index=638&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=131&type=section&id=Item%207.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Tenaya reported a **$123.7 million** net loss in 2022, a **70%** increase from 2021, driven by higher R&D and G&A expenses, with **$204.2 million** in cash expected to fund operations for at least 12 months [Results of Operations](index=132&type=section&id=Results%20of%20Operations) Total operating expenses increased **73%** to **$125.6 million** in 2022, driven by a **74%** rise in R&D and a **69%** rise in G&A, resulting in a **$123.7 million** net loss Results of Operations Summary (2022 vs. 2021) (in thousands) | (in thousands) | 2022 | 2021 | $ Change | % Change | | :--- | :--- | :--- | :--- | :--- | | Research and development | $94,537 | $54,393 | $40,144 | 74% | | General and administrative | $31,084 | $18,413 | $12,671 | 69% | | **Total operating expenses** | **$125,621** | **$72,806** | **$52,815** | **73%** | | Loss from operations | ($125,621) | ($72,806) | ($52,815) | 73% | | **Net loss** | **($123,665)** | **($72,721)** | **($50,944)** | **70%** | - Research and development expenses increased by **$40.1 million (74%)** in 2022, driven by higher outside services, personnel costs, and facility expenses[655](index=655&type=chunk)[659](index=659&type=chunk) - General and administrative expenses increased by **$12.7 million (69%)** in 2022, primarily due to higher employee-related expenses, professional services, and insurance costs[658](index=658&type=chunk) [Liquidity and Capital Resources](index=134&type=section&id=Liquidity%20and%20Capital%20Resources) As of December 31, 2022, the company held **$204.2 million** in cash, cash equivalents, and marketable securities, bolstered by a **$76.9 million** follow-on offering, expected to fund operations for at least 12 months - As of December 31, 2022, the company held **$204.2 million** in cash, cash equivalents, and marketable securities[663](index=663&type=chunk) - In November 2022, the company completed a follow-on public offering, raising total net proceeds of **$76.9 million**[664](index=664&type=chunk) - Management believes existing cash is sufficient to fund operations through at least the next twelve months from the report filing date[667](index=667&type=chunk) Cash Flow Summary (2022 vs. 2021) (in thousands) | (In thousands) | 2022 | 2021 | | :--- | :--- | :--- | | Net cash used in operating activities | $(104,424) | $(60,812) | | Net cash provided by (used in) investing activities | $83,652 | $(238,564) | | Net cash provided by financing activities | $77,767 | $208,970 | [Financial Statements and Supplementary Data](index=140&type=section&id=Item%208.%20Financial%20Statements%20and%20Supplementary%20Data) Audited financial statements for 2022 and 2021 are presented, showing total assets of **$278.9 million** and a net loss of **$123.7 million** in 2022, with notes detailing accounting policies and commitments Key Balance Sheet Data (as of Dec 31) (in thousands) | (In thousands) | 2022 | 2021 | | :--- | :--- | :--- | | Cash, cash equivalents & marketable securities | $204,230 | $251,300 | | Total current assets | $193,754 | $255,358 | | Total assets | $278,945 | $314,189 | | Total current liabilities | $24,248 | $21,774 | | Total liabilities | $35,569 | $35,663 | | Total stockholders' equity | $243,376 | $278,526 | Key Statement of Operations Data (Year Ended Dec 31) (in thousands) | (in thousands) | 2022 | 2021 | | :--- | :--- | :--- | | Research and development | $94,537 | $54,393 | | General and administrative | $31,084 | $18,413 | | **Loss from operations** | **($125,621)** | **($72,806)** | | **Net loss** | **($123,665)** | **($72,721)** | | Net loss per share | ($2.76) | ($4.10) | [Controls and Procedures](index=163&type=section&id=Item%209A.%20Controls%20and%20Procedures) Management concluded that the company's disclosure controls and internal control over financial reporting were effective as of December 31, 2022, with no attestation report required as an emerging growth company - Management concluded that the company's disclosure controls and procedures were effective as of December 31, 2022[818](index=818&type=chunk) - Management concluded that the company's internal control over financial reporting was effective as of December 31, 2022, based on the COSO framework[819](index=819&type=chunk) - No material changes in internal control over financial reporting occurred during the fourth quarter of 2022[821](index=821&type=chunk) Part III [Directors, Executive Officers, Corporate Governance, Executive Compensation, and Other Matters](index=165&type=section&id=Items%2010-14) Information for Items 10 through 14, covering directors, executive officers, corporate governance, and compensation, is incorporated by reference from the company's definitive Proxy Statement - Information for Items 10 through 14 is incorporated by reference from the company's definitive Proxy Statement for its 2022 Annual Meeting of Stockholders[826](index=826&type=chunk)[828](index=828&type=chunk)[831](index=831&type=chunk) Part IV [Exhibits, Financial Statement Schedules](index=166&type=section&id=Item%2015.%20Exhibits,%20Financial%20Statement%20Schedules) This section lists all documents filed as part of the Annual Report on Form 10-K, including financial statements and an index of exhibits - This section contains the list of financial statements and an index of all exhibits filed as part of the 10-K report[834](index=834&type=chunk)[836](index=836&type=chunk)

| --- | --- | --- | --- | --- | |-------------------------------------|-------|-------|-------|-------| | | | | | | | in the Fight Against Heart Disease | | | | | | | | | | | | Corporate Presentation | | | | | | September 2022 | | | | | | | | | | | | | | | | | Forward-looking Statement This presentation contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended, that are based on our manag ...

| --- | --- | --- | --- | --- | |-------------------------------------|-------|-------|-------|-------| | | | | | | | in the Fight Against Heart Disease | | | | | | | | | | | | Corporate Presentation | | | | | | September 2022 | | | | | | | | | | | | | | | | | Forward-looking Statement This presentation contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended, that are based on our manag ...

| --- | --- | --- | --- | --- | |-------|-------|-------|-------|-------| | | | | | | | | | | | | Forward-looking Statement This presentation contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended, that are based on our management's beliefs and assumptions and on information currently available to our management. Forward-looking statements are inherently subject to risks and uncertaint ...