Taysha Gene Therapies, Inc. (NASDAQ:TSHA) Q3 2021 Earnings Conference Call November 10, 2021 8:00 AM ET Company Participants Kimberly Lee - SVP, Corporate Communications & IR RA Session II - President, CEO & Founder Suyash Prasad - CMO & Head, R&D Kamran Alam - CFO Conference Call Participants Joon Lee - Truist Securities Gil Blum - Needham and Company Laura Chico - Wedbush Securities Elizabeth Webster - Goldman Sachs Mike Ulz - Morgan Stanley Kevin DeGeeter - Oppenheimer Yun Zhong - BTIG Kristen Kluska - C ...

Bringing New Cures to Life CLN1 Disease Investor Day August 30, 2021 | 9:00 — 11:30 AM CT : 0 . 1 : 1 0 . ： ： ： | ： ● ○ Ⅰ ： ● … : | 0 · ： 0 · | ： ♥ 0 | Legal disclosure FORWARD LOOKING STATEMENTS This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements regarding our strategy, future operations, future financial position, future revenues, projected cos ...

Taysha Gene Therapies, Inc. (NASDAQ:TSHA) Q2 2021 Earnings Conference Call August 16, 2021 8:00 AM ET Company Participants Kimberly Lee - Senior Vice President, Corporate Communications and Investor Relations RA Session II - President, Chief Executive Officer and Founder Suyash Prasad - Chief Medical Officer and Head, R&D Kamran Alam - Chief Financial Officer Conference Call Participants Elizabeth Webster - Goldman Sachs Joon Lee - Truist Securities Laura Chico - Wedbush Securities Gil Blum - Needham & Comp ...

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 June 30, 2021 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: 001-39536 Taysha Gene Therapies, Inc. (Exact Name of Registrant as Specified in its Charter) Delaware 84-31995 ...

PART I. FINANCIAL INFORMATION [Item 1. Condensed Consolidated Financial Statements (Unaudited)](index=3&type=section&id=Item%201.%20Condensed%20Consolidated%20Financial%20Statements%20(Unaudited)) Taysha's unaudited Q1 2021 consolidated financial statements report a **$32.0 million** net loss, primarily from increased R&D and G&A [Condensed Consolidated Balance Sheets](index=3&type=section&id=Balance%20Sheets) Balance sheets show total assets decreased to **$242.8 million** by March 31, 2021, with liabilities rising and equity falling Metric | Metric | March 31, 2021 (in thousands) | December 31, 2020 (in thousands) | | :--------------------------------- | :----------------------------- | :----------------------------- | | Cash and cash equivalents | $228,684 | $251,253 | | Total current assets | $239,629 | $257,879 | | Total assets | $242,829 | $258,881 | | Total current liabilities | $18,958 | $7,129 | | Total liabilities | $19,957 | $7,579 | | Total stockholders' equity | $222,872 | $251,302 | - Cash and cash equivalents decreased by **$22.6 million** from December 31, 2020, to March 31, 2021[11](index=11&type=chunk) - Total current liabilities increased by **$11.8 million**, primarily due to increases in accounts payable and accrued expenses[11](index=11&type=chunk) [Condensed Consolidated Statements of Operations](index=4&type=section&id=Statements%20of%20Operations) Net loss significantly increased in Q1 2021, primarily due to higher R&D and G&A expenses Metric | Metric | Three Months Ended March 31, 2021 (in thousands) | Three Months Ended March 31, 2020 (in thousands) | Change (YoY) | | :--------------------------------- | :--------------------------------------------- | :--------------------------------------------- | :----------- | | Research and development | $23,854 | $5,514 | +$18,340 | | General and administrative | $8,236 | $70 | +$8,166 | | Total operating expenses | $32,090 | $5,584 | +$26,506 | | Net loss | $(32,024) | $(5,431) | -$(26,593) | | Net loss per common share (basic & diluted) | $(0.87) | $(0.50) | -$(0.37) | | Weighted average common shares outstanding | 36,992,377 | 10,894,999 | +26,097,378 | - Research and development expenses increased by **$18.3 million** (**332%**) year-over-year[14](index=14&type=chunk) - General and administrative expenses increased by **$8.2 million** (**11666%**) year-over-year[14](index=14&type=chunk) [Condensed Consolidated Statements of Convertible Preferred Stock and Stockholders' Equity (Deficit)](index=5&type=section&id=Statements%20of%20Convertible%20Preferred%20Stock%20and%20Stockholders'%20Equity%20(Deficit)) Accumulated deficit increased to **$93.2 million** by March 31, 2021, primarily due to net loss, while paid-in capital rose Metric | Metric | December 31, 2020 (in thousands) | March 31, 2021 (in thousands) | | :--------------------------------- | :----------------------------- | :----------------------------- | | Additional Paid-in Capital | $312,428 | $316,022 | | Accumulated Deficit | $(61,126) | $(93,150) | | Total Stockholders' Equity | $251,302 | $222,872 | - Stock-based compensation for the three months ended March 31, 2021, was **$3.6 million**[17](index=17&type=chunk) - Net loss for the period was **$32.0 million**, directly increasing the accumulated deficit[17](index=17&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=7&type=section&id=Statements%20of%20Cash%20Flows) Cash and cash equivalents decreased by **$22.6 million** in Q1 2021, mainly from operating activities and license fees Cash Flow Activity | Cash Flow Activity | Three Months Ended March 31, 2021 (in thousands) | Three Months Ended March 31, 2020 (in thousands) | | :--------------------------------- | :--------------------------------------------- | :--------------------------------------------- | | Net cash used in operating activities | $(22,035) | $(1,699) | | Net cash used in investing activities | $(534) | $0 | | Net cash provided by financing activities | $0 | $18,027 | | Net (decrease) increase in cash and cash equivalents | $(22,569) | $16,328 | | Cash at the end of the period | $228,684 | $16,328 | - Operating activities used **$22.0 million** in cash in Q1 2021, a significant increase from **$1.7 million** in Q1 2020[23](index=23&type=chunk) - Investing activities used **$0.5 million** in Q1 2021 for property, plant, and equipment purchases, with no activity in Q1 2020[23](index=23&type=chunk) [Notes to Financial Statements](index=8&type=section&id=Notes%20to%20Financial%20Statements) The notes provide comprehensive details on the company's financial structure, operational agreements, and accounting practices [Note 1—Organization and Description of Business Operations](index=8&type=section&id=Note%201%E2%80%94Organization%20and%20Description%20of%20Business%20Operations) Taysha, a gene therapy company, completed its IPO in September 2020, reporting a **$93.2 million** accumulated deficit and **$228.7 million** cash - Taysha Gene Therapies, Inc. was formed in September **2019** and converted to a Delaware corporation in February **2020**[25](index=25&type=chunk) - The company focuses on developing AAV-based gene therapies for monogenic diseases of the central nervous system[26](index=26&type=chunk) - Completed an IPO on September **28**, **2020**, issuing **9,050,000** shares of common stock for net proceeds of **$165.9 million**[28](index=28&type=chunk) - Accumulated deficit as of March **31**, **2021**, was **$93.2 million**[32](index=32&type=chunk) - Cash of **$228.7 million** as of March **31**, **2021**, is expected to fund operations for at least **twelve months**[34](index=34&type=chunk) [Note 2—Summary of Significant Accounting Policies](index=9&type=section&id=Note%202%E2%80%94Summary%20of%20Significant%20Accounting%20Policies) Financial statements adhere to GAAP, with key estimates for common stock, accruals, and tranche liability; no material policy changes - Financial statements are prepared in conformity with GAAP for interim information[36](index=36&type=chunk) - Significant estimates relate to fair value of common stock, preclinical manufacturing accruals, and preferred stock tranche liability[38](index=38&type=chunk) - No changes in significant accounting policies from the **2020** Annual Report[39](index=39&type=chunk) - Evaluating the impact of ASU No. **2016-02**, Leases (Topic **842**), effective for annual periods beginning after December **15**, **2021**[40](index=40&type=chunk)[41](index=41&type=chunk) [Note 3—Balance Sheet Components](index=10&type=section&id=Note%203%E2%80%94Balance%20Sheet%20Components) Balance sheet components are detailed, showing increases in prepaid R&D, accrued license fees, and construction in progress Prepaid Expenses and Other Current Assets | Prepaid Expenses and Other Current Assets (in thousands) | March 31, 2021 | December 31, 2020 | | :------------------------------------------------------- | :------------- | :---------------- | | Prepaid research and development | $6,281 | $2,462 | | Total prepaid expenses and other current assets | $10,817 | $6,626 | Property, Plant and Equipment, net | Property, Plant and Equipment, net (in thousands) | March 31, 2021 | December 31, 2020 | | :------------------------------------------------ | :------------- | :---------------- | | Construction in progress | $1,889 | $201 | | Property, plant and equipment, net | $2,497 | $287 | Accrued Expenses and Other Current Liabilities | Accrued Expenses and Other Current Liabilities (in thousands) | March 31, 2021 | December 31, 2020 | | :------------------------------------------------------------ | :------------- | :---------------- | | Accrued research and development | $5,672 | $2,106 | | Accrued license fees | $5,500 | $0 | | Accrued construction in progress | $1,029 | $173 | | Total accrued expenses and other current liabilities | $14,875 | $5,135 | [Note 4—Research, Collaboration and License Agreements](index=10&type=section&id=Note%204%E2%80%94Research,%20Collaboration%20and%20License%20Agreements) This note details key research and license agreements, including the **$5.5 million** acquisition of TSHA-120 rights for GAN - UT Southwestern Agreement (November **2019**): Exclusive worldwide, royalty-free license for AAV-based gene therapies for CNS monogenic diseases. Issued **2,179,000** common shares to UT Southwestern as partial consideration[44](index=44&type=chunk)[46](index=46&type=chunk)[49](index=49&type=chunk) - Queen's Agreement (February **2020**): Exclusive, perpetual, royalty-bearing license for certain patent rights and know-how. Paid **$3.0 million** upfront cash payment in April **2020**. Obligated to pay up to **$10.0 million** in regulatory milestones and up to **$10.0 million** in commercial milestones, plus low single-digit royalties[51](index=51&type=chunk)[52](index=52&type=chunk) - Abeona CLN1 Agreements (August **2020**): Worldwide exclusive rights for ABO-202 (TSHA-118) for CLN1 disease. Initial cash payments of **$3.0 million** license fee and **$4.0 million** for clinical materials. Obligated to pay up to **$26.0 million** in regulatory milestones and **$30.0 million** in sales milestones, plus high single-digit royalties[53](index=53&type=chunk) - Abeona Rett Agreement (October **2020**): Exclusive worldwide license for Rett syndrome gene therapy (TSHA-102). Paid **$3.0 million** upfront license fee. Obligated to pay up to **$26.5 million** in regulatory milestones and **$30.0 million** in sales milestones, plus high single-digit royalties[55](index=55&type=chunk)[57](index=57&type=chunk) - Acquisition of Worldwide Rights for TSHA-120 for GAN (March **2021**): Acquired exclusive worldwide rights from Hannah's Hope Fund (HHF). Upfront payment of **$5.5 million** recorded as R&D expense, not yet paid as of March **31**, **2021**. Eligible for up to **$19.3 million** in clinical, regulatory, and commercial milestones, plus low single-digit royalties[60](index=60&type=chunk)[62](index=62&type=chunk)[63](index=63&type=chunk) [Note 5—Stockholders' Equity (Deficit), Convertible Preferred Stock and Tranche Liability](index=13&type=section&id=Note%205%E2%80%94Stockholders'%20Equity%20(Deficit),%20Convertible%20Preferred%20Stock%20and%20Tranche%20Liability) Capital structure changes are detailed, including the **$181.0 million** IPO, preferred stock conversion, and a **$0.2 million** tranche liability gain - Authorized common stock increased to **200,000,000** shares and preferred stock to **10,000,000** shares as of September **28**, **2020**[64](index=64&type=chunk) - IPO in September **2020** resulted in gross proceeds of **$181.0 million** from the sale of **9,050,000** common shares[65](index=65&type=chunk) - Series A and B convertible preferred stock (totaling **15,647,048** shares) converted into **17,047,378** common shares upon IPO closing[70](index=70&type=chunk) - A preferred stock tranche liability of **$1.1 million** was recorded at the Series A issuance date, and a **$0.2 million** gain was recognized from its remeasurement at March **31**, **2020**[72](index=72&type=chunk) [Note 6—Stock-Based Compensation](index=14&type=section&id=Note%206%E2%80%94Stock-Based%20Compensation) Stock-based compensation plans are detailed, with **1,621,900** options granted in Q1 2021 and **$3.6 million** total expense - The New Plan became effective upon IPO, with **3,390,168** new shares and **209,841** remaining shares from the Existing Plan available for issuance[74](index=74&type=chunk) - On January **1**, **2021**, the board increased shares reserved under the New Plan by **1,434,934**[74](index=74&type=chunk) - **1,621,900** stock options were granted in Q1 **2021** with a weighted-average grant date fair value of **$18.75** per share[77](index=77&type=chunk) - Total unrecognized compensation for unvested stock options was **$37.0 million**, for RSUs **$15.4 million**, and for RSAs **$3.0 million** as of March **31**, **2021**[77](index=77&type=chunk)[78](index=78&type=chunk)[79](index=79&type=chunk) Stock-Based Compensation Expense | Stock-Based Compensation Expense (in thousands) | Three Months Ended March 31, 2021 | | :---------------------------------------------- | :-------------------------------- | | Research and development expense | $1,579 | | General and administrative expense | $2,015 | | Total | $3,594 | [Note 7—Net Loss Per Common Share](index=16&type=section&id=Note%207%E2%80%94Net%20Loss%20Per%20Common%20Share) Basic and diluted net loss per common share were both **$(0.87)** in Q1 2021, with anti-dilutive equivalents excluded Metric | Metric | Three Months Ended March 31, 2021 | Three Months Ended March 31, 2020 | | :---------------------------------------------------------------- | :-------------------------------- | :-------------------------------- | | Net loss | $(32,024) | $(5,431) | | Weighted-average shares of common stock outstanding | 36,992,377 | 10,894,999 | | Net loss per common share, basic and diluted | $(0.87) | $(0.50) | Anti-Dilutive Common Stock Equivalents | Anti-Dilutive Common Stock Equivalents | March 31, 2021 | March 31, 2020 | | :------------------------------------- | :------------- | :------------- | | Unvested RSUs | 2,850,053 | — | | Unvested RSAs | 769,058 | — | | Stock options | 2,286,142 | — | | Series A convertible preferred stock | — | 6,000,000 | | Total | 5,905,253 | 6,000,000 | [Note 8—Related Party Transactions](index=17&type=section&id=Note%208%E2%80%94Related%20Party%20Transactions) Related party transactions are disclosed, including CEO RA Session II's repaid notes and PBM Capital Group's administrative services - RA Session II, President and CEO, personally guaranteed a research grant agreement with Queen's and provided **$1.67 million** in secured promissory notes, which were repaid by July **2020**[83](index=83&type=chunk) - PBM Capital Group, LLC, an affiliate of a major stockholder, provides accounting and administrative services for **$2,500** per month[84](index=84&type=chunk) [Note 9—Income Taxes](index=17&type=section&id=Note%209%E2%80%94Income%20Taxes) No income tax provision was recorded due to operating losses and a full valuation allowance, with no material changes to tax positions - No provision for income taxes due to operating losses and a full valuation allowance against net deferred tax assets[85](index=85&type=chunk) - No material changes to uncertain tax positions as of March **31**, **2021**[86](index=86&type=chunk) [Note 10—Commitments and Contingencies](index=18&type=section&id=Note%2010%E2%80%94Commitments%20and%20Contingencies) No material legal proceedings; significant lease commitments for Durham manufacturing and Dallas office facilities are detailed - Not a party to any material legal proceedings[87](index=87&type=chunk) - Durham Lease: Commenced April **1**, **2021**, for a **187,500** sq ft manufacturing facility with a **15.5-year** term. Incurred **$0.8 million** in initial direct costs[89](index=89&type=chunk)[91](index=91&type=chunk) - Dallas Lease: Expected to commence May **15**, **2021**, for **15,000** sq ft office space with a **10-year** term. Total future minimum lease payments are approximately **$4.9 million**. Recognized **$0.6 million** lease construction incentive[92](index=92&type=chunk)[93](index=93&type=chunk)[96](index=96&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=20&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses Taysha's financial condition, AAV-based gene therapy pipeline, increased R&D, and future funding needs beyond **2023** [Overview](index=20&type=section&id=Overview) Taysha, a gene therapy company with **26** candidates, incurred a **$32.0 million** net loss in Q1 2021, with expenses expected to rise for development - Taysha is a patient-centric gene therapy company focused on AAV-based gene therapies for monogenic diseases of the central nervous system[101](index=101&type=chunk) - Advancing a product portfolio of **26** gene therapy product candidates[101](index=101&type=chunk) - Incurred net losses of **$32.0 million** for Q1 **2021** and **$5.4 million** for Q1 **2020**, with an accumulated deficit of **$93.2 million** as of March **31**, **2021**[104](index=104&type=chunk) - Expects significant expense increases due to advancing preclinical/clinical development, manufacturing, regulatory approvals, and operating as a public company[105](index=105&type=chunk) [Our Pipeline](index=22&type=section&id=Our%20Pipeline) Taysha is developing a broad pipeline of **26** gene therapy candidates for neurodegenerative, neurodevelopmental, and genetic epilepsy disorders - The company is advancing a portfolio of **26** gene therapy product candidates for monogenic CNS diseases[106](index=106&type=chunk) - Pipeline targets neurodegenerative diseases, neurodevelopmental disorders, and genetic epilepsies[106](index=106&type=chunk) [Recent Developments](index=22&type=section&id=Recent%20Developments) In March 2021, Taysha acquired exclusive worldwide rights to TSHA-120 for GAN, involving a **$5.5 million** upfront payment and potential milestones - Acquired exclusive worldwide rights to TSHA-120 for GAN in March **2021**[107](index=107&type=chunk) - Upfront payment of **$5.5 million** to Hannah's Hope Fund (HHF)[107](index=107&type=chunk) - HHF is eligible for up to **$19.3 million** in milestones and low, single-digit royalties on net sales[107](index=107&type=chunk) [TSHA-120 for Giant Axonal Neuropathy](index=22&type=section&id=TSHA-120%20for%20Giant%20Axonal%20Neuropathy) TSHA-120, an AAV9 gene therapy for GAN, shows statistically significant slowing of disease progression in Phase 1/2 trials - TSHA-120 is an AAV9 gene therapy for Giant Axonal Neuropathy (GAN), a rare autosomal recessive CNS disease with an estimated prevalence of **2,400** patients in the US and EU[108](index=108&type=chunk)[109](index=109&type=chunk) - Received orphan drug and rare pediatric disease designations from the FDA[112](index=112&type=chunk) - Preclinical studies demonstrated improved motor function, nerve pathology, and long-term safety in animal models[115](index=115&type=chunk) - Phase **1/2** clinical trial: **14** patients dosed; **1.8x10^14** total vg dose showed an **8-point** improvement in MFM32 vs. historical control, and **1.2x10^14** total vg dose showed a **6-point** improvement, both statistically significant[121](index=121&type=chunk)[122](index=122&type=chunk) - Patients dosed with **1.8x10^14** total vg and **1.2x10^14** total vg have shown sustained dose-dependent improvements in MFM32 scores for more than **three years**[123](index=123&type=chunk) - Bayesian analysis confirmed a nearly **100%** probability of clinically meaningful slowing of disease progression for the **1.8x10^14** total vg dose and approximately **85%** for the **1.2x10^14** total vg dose[126](index=126&type=chunk)[129](index=129&type=chunk)[130](index=130&type=chunk) [Preclinical Program Updates](index=29&type=section&id=Preclinical%20Program%20Updates) Taysha provides updates on several preclinical programs, including AAV9 redosing, and gene therapies for Rett syndrome, Leigh syndrome, and other CNS disorders [Vagus Nerve Redosing](index=29&type=section&id=Vagus%20Nerve%20Redosing) Preclinical research supports AAV9 redosing via direct vagus nerve injection, showing robust expression and immune privilege in rats - Direct injection into the vagus nerve allows for AAV9 redosing after intrathecal administration in preclinical models[132](index=132&type=chunk) - Robust GFP expression was observed in the injected vagus nerve and associated nodose ganglia in rats[133](index=133&type=chunk) - The vagus nerve space appears immune privileged enough to permit redosing, even with pre-existing neutralizing antibodies[137](index=137&type=chunk) [TSHA-102 for Rett Syndrome](index=32&type=section&id=TSHA-102%20for%20Rett%20Syndrome) TSHA-102 for Rett syndrome uses miRARE, extending knockout survival by **56%** and regulating gene expression in preclinical studies - TSHA-102 uses miRARE (miRNA-Responsive Auto-Regulatory Element) to prevent MECP2 gene overexpression-related toxicity[138](index=138&type=chunk) - Preclinical studies showed TSHA-102 extended knockout survival by **56%** via intrathecal delivery[140](index=140&type=chunk) - miRARE attenuated miniMECP2-mediated aggravation in wild type aggregate phenotype severity scores[141](index=141&type=chunk) - TSHA-102 demonstrated regulated expression in brain regions, achieving MECP2 expression levels similar to normal physiological parameters[142](index=142&type=chunk)[143](index=143&type=chunk) - Plans to submit an IND/CTA for TSHA-102 in the second half of **2021** and initiate a clinical trial by year-end[144](index=144&type=chunk) [TSHA-104 for SURF1-Associated Leigh Syndrome](index=33&type=section&id=TSHA-104%20for%20SURF1-Associated%20Leigh%20Syndrome) TSHA-104 for SURF1-associated Leigh syndrome, an orphan drug, showed restored mitochondrial function and SURF1 expression in preclinical models - TSHA-104 is a gene replacement therapy for SURF1-associated Leigh syndrome, caused by mutations in the SURF1 gene[145](index=145&type=chunk)[146](index=146&type=chunk) - Received orphan drug and rare pediatric disease designations from the FDA[147](index=147&type=chunk) - Preclinical studies in SURF1 knockout mice showed TSHA-104 was well-tolerated, induced SURF1 expression in the brain, partially rescued COX activity, and restored blood lactate levels on exhaustive exercise[148](index=148&type=chunk)[150](index=150&type=chunk) - Plans to submit an IND/CTA for TSHA-104 in the second half of **2021** and initiate a Phase **1/2** clinical trial by year-end[147](index=147&type=chunk) [TSHA-113 for Tauopathies](index=35&type=section&id=TSHA-113%20for%20Tauopathies) TSHA-113 for tauopathies aims for lifelong tau protein reduction, showing significant mRNA and protein level reductions in preclinical models - TSHA-113 aims to deliver life-long reduction of tau protein levels in neurons using AAV-mediated gene silencing[153](index=153&type=chunk) - Preclinical studies in transgenic mouse models showed TSHA-113 significantly reduced tau mRNA and protein levels[154](index=154&type=chunk) - Mice dosed with TSHA-113 demonstrated widespread function and GFP expression in neurons and glia[156](index=156&type=chunk) [TSHA-105 for SLC13A5 Deficiency](index=37&type=section&id=TSHA-105%20for%20SLC13A5%20Deficiency) TSHA-105 for SLC13A5 deficiency, an orphan drug, normalized EEG activity and reduced seizures in preclinical knockout mouse models - TSHA-105 is a gene replacement therapy for SLC13A5 deficiency, a rare epileptic encephalopathy[158](index=158&type=chunk)[160](index=160&type=chunk) - Received orphan drug and rare pediatric disease designations from the FDA[161](index=161&type=chunk) - Preclinical studies in SLC13A5 knockout mice showed TSHA-105 significantly decreased plasma citrate levels, normalized EEG activity, and reduced seizure susceptibility[163](index=163&type=chunk)[165](index=165&type=chunk)[167](index=167&type=chunk) [TSHA-103 for SLC6A1 Haploinsufficiency Disorder](index=40&type=section&id=TSHA-103%20for%20SLC6A1%20Haploinsufficiency%20Disorder) TSHA-103 for SLC6A1 haploinsufficiency disorder, an orphan drug, improved nesting and EEG activity in preclinical mouse models - TSHA-103 is a gene replacement therapy for SLC6A1 haploinsufficiency disorder, a monogenic cause of epilepsy and intellectual disability[168](index=168&type=chunk)[173](index=173&type=chunk) - Received orphan drug and rare pediatric disease designations from the FDA[174](index=174&type=chunk) - Preclinical studies in SLC6A1 knockout and heterozygous mouse models showed TSHA-103 improved nesting, EEG activity, and reduced spike train activity[175](index=175&type=chunk)[176](index=176&type=chunk) [License Agreements](index=42&type=section&id=License%20Agreements) Key license agreements with UT Southwestern, Queen's, and Abeona grant Taysha exclusive worldwide rights to gene therapy programs - UT Southwestern Agreement: Exclusive, worldwide, royalty-free license for certain patent rights and know-how; issued **2,179,000** common shares as consideration[178](index=178&type=chunk)[179](index=179&type=chunk)[180](index=180&type=chunk) - Queen's University Agreement: Exclusive, perpetual, worldwide, royalty-bearing license; paid **$3.0 million** upfront fee and obligated for up to **$20.0 million** in milestones plus low single-digit royalties[181](index=181&type=chunk)[182](index=182&type=chunk) - Abeona CLN1 Agreement: Exclusive, worldwide, royalty-bearing license for CLN1 Disease; paid **$3.0 million** upfront license fee and **$4.0 million** for inventory/reimbursement; obligated for up to **$56.0 million** in milestones plus high single-digit royalties[184](index=184&type=chunk)[185](index=185&type=chunk)[186](index=186&type=chunk) - Abeona Rett Agreement: Exclusive, worldwide, royalty-bearing license for Rett syndrome; paid **$3.0 million** upfront license fee; obligated for up to **$56.5 million** in milestones plus high single-digit royalties[188](index=188&type=chunk)[190](index=190&type=chunk) [Impact of COVID-19 on Our Business](index=43&type=section&id=Impact%20of%20COVID-19%20on%20Our%20Business) COVID-19 did not significantly impact Q1 2021 financial results, but future effects on business and operations remain uncertain - Financial results for Q1 **2021** were not significantly impacted by COVID-19[192](index=192&type=chunk) - Remote working and travel restrictions had limited impact on internal operations[192](index=192&type=chunk) - Future impacts of COVID-19 remain highly uncertain and could adversely affect business and operations[192](index=192&type=chunk) [Components of Results of Operations](index=43&type=section&id=Components%20of%20Results%20of%20Operations) No revenue has been generated; operating expenses, particularly R&D and G&A, are expected to increase significantly as the pipeline advances - No revenue generated from product sales to date, and none expected in the foreseeable future[193](index=193&type=chunk) - Research and development expenses are recognized as incurred and include preclinical development, manufacturing, and clinical trial preparation[194](index=194&type=chunk) - Expects substantial increases in R&D expenses for the foreseeable future due to pipeline advancement[195](index=195&type=chunk) - General and administrative expenses are expected to increase due to headcount growth, expanded infrastructure, and public company operating costs (estimated **$6.0-$7.0 million** annually)[199](index=199&type=chunk) [Results of Operations for the Three Months Ended March 31, 2021 and for the Three Months Ended March 31, 2020](index=45&type=section&id=Results%20of%20Operations%20for%20the%20Three%20Months%20Ended%20March%2031,%202021%20and%20for%20the%20Three%20Months%20Ended%20March%2031,%202020) Net loss increased to **$32.0 million** in Q1 2021, driven by higher R&D and G&A expenses, and reduced other income Metric | Metric | Three Months Ended March 31, 2021 (in thousands) | Three Months Ended March 31, 2020 (in thousands) | Change (YoY) | | :--------------------------------- | :--------------------------------------------- | :--------------------------------------------- | :----------- | | Research and development | $23,854 | $5,514 | +$18,340 | | General and administrative | $8,236 | $70 | +$8,166 | | Total operating expenses | $32,090 | $5,584 | +$26,506 | | Net loss | $(32,024) | $(5,431) | -$(26,593) | - R&D increase of **$18.4 million** was due to **$3.1 million** in manufacturing/raw materials, **$3.1 million** in licensing fees (TSHA-120), **$5.2 million** in employee compensation (including **$1.6 million** stock-based), and **$2.4 million** in sponsored research[201](index=201&type=chunk) - G&A increase of **$8.1 million** was due to **$4.2 million** in compensation (including **$2.0 million** stock-based), **$1.5 million** in consulting/professional fees, and **$0.9 million** in legal expenses[202](index=202&type=chunk) - Other income decreased due to a **$0.2 million** non-cash gain from preferred stock tranche liability remeasurement in Q1 **2020** not recurring in Q1 **2021**[203](index=203&type=chunk)[204](index=204&type=chunk) [Liquidity and Capital Resources](index=46&type=section&id=Liquidity%20and%20Capital%20Resources) Taysha had **$228.7 million** cash as of March 31, 2021, expected to fund operations into **2023**, but substantial additional funding is anticipated - Cash and cash equivalents were **$228.7 million** as of March **31**, **2021**[205](index=205&type=chunk) - Funded operations through **$307.0 million** in gross proceeds from IPO (**$181.0 million**) and private placements of convertible preferred stock (**$30.0 million** Series A, **$96.0 million** Series B)[205](index=205&type=chunk) - Existing cash and cash equivalents are believed to fund operating expenses and capital requirements into **2023**[207](index=207&type=chunk) - Substantial additional funding will be required for continued operations, clinical studies, and potential commercialization[206](index=206&type=chunk)[208](index=208&type=chunk) Cash Flow Activity | Cash Flow Activity | Three Months Ended March 31, 2021 (in thousands) | Three Months Ended March 31, 2020 (in thousands) | | :--------------------------------- | :--------------------------------------------- | :--------------------------------------------- | | Net cash used in operating activities | $(22,035) | $(1,699) | | Net cash used in investing activities | $(534) | $0 | | Net cash provided by financing activities | $0 | $18,027 | [Off-Balance Sheet Arrangements](index=48&type=section&id=Off-Balance%20Sheet%20Arrangements) No off-balance sheet arrangements were present during the reported periods - No off-balance sheet arrangements were present during the reported periods[217](index=217&type=chunk) [Critical Accounting Policies and Significant Judgments and Estimates](index=48&type=section&id=Critical%20Accounting%20Policies%20and%20Significant%20Judgments%20and%20Estimates) No material changes to critical accounting policies were reported from the 2020 Annual Report - No material changes to critical accounting policies from the **2020** Annual Report[218](index=218&type=chunk) [Recent Accounting Pronouncements](index=48&type=section&id=Recent%20Accounting%20Pronouncements) Refer to Note 2 for details on recent accounting pronouncements - Refer to Note **2** for details on recent accounting pronouncements[219](index=219&type=chunk) [Emerging Growth Company and Smaller Reporting Company Status](index=48&type=section&id=Emerging%20Growth%20Company%20and%20Smaller%20Reporting%20Company%20Status) Taysha qualifies as an 'emerging growth company' and 'smaller reporting company,' benefiting from reduced disclosure and compliance - Qualifies as an 'emerging growth company' and has elected the extended transition period for new accounting standards[220](index=220&type=chunk)[221](index=221&type=chunk) - Benefits from reduced disclosure requirements, including an exception from auditor attestation for Section **404** of Sarbanes-Oxley Act and reduced executive compensation disclosures[222](index=222&type=chunk) - Also qualifies as a 'smaller reporting company' due to market value and annual revenue thresholds, allowing for further reduced disclosure obligations[223](index=223&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=49&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a smaller reporting company, Taysha is exempt from providing quantitative and qualitative market risk disclosures - The company is exempt from providing quantitative and qualitative disclosures about market risk due to its status as a smaller reporting company[224](index=224&type=chunk) [Item 4. Controls and Procedures](index=49&type=section&id=Item%204.%20Controls%20and%20Procedures) Management evaluated disclosure controls and procedures as effective, with no material changes to internal controls over financial reporting - Disclosure controls and procedures were evaluated and deemed effective as of March **31**, **2021**[225](index=225&type=chunk) - No material changes in internal control over financial reporting were identified during the period[226](index=226&type=chunk) - Management recognizes that internal controls provide reasonable, not absolute, assurance[227](index=227&type=chunk) PART II. OTHER INFORMATION [Item 1. Legal Proceedings](index=51&type=section&id=Item%201.%20Legal%20Proceedings) The company is not a party to any material legal proceedings or aware of any adverse pending claims - The company is not subject to any material legal proceedings[230](index=230&type=chunk) [Item 1A. Risk Factors](index=51&type=section&id=Item%201A.%20Risk%20Factors) No material changes to risk factors were reported from the **2020** Annual Report on Form **10-K** - No material changes to risk factors described in the Annual Report on Form **10-K** for December **31**, **2020**[231](index=231&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=51&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) No recent unregistered equity sales; the **$165.9 million** IPO net proceeds' planned use remains materially unchanged - No recent unregistered sales of equity securities[232](index=232&type=chunk) - IPO closed on September **28**, **2020**, with aggregate net proceeds of **$165.9 million**[233](index=233&type=chunk)[234](index=234&type=chunk) - No material change in the planned use of IPO proceeds[234](index=234&type=chunk) [Item 3. Defaults Upon Senior Securities](index=51&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) Not applicable - Not applicable[236](index=236&type=chunk) [Item 4. Mine Safety Disclosures](index=51&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) Not applicable - Not applicable[237](index=237&type=chunk) [Item 5. Other Information](index=51&type=section&id=Item%205.%20Other%20Information) Not applicable - Not applicable[238](index=238&type=chunk) [Item 6. Exhibits](index=52&type=section&id=Item%206.%20Exhibits) This section lists exhibits, including corporate documents, officer certifications, and XBRL taxonomy documents - Includes Amended and Restated Certificate of Incorporation and Bylaws[240](index=240&type=chunk) - Contains certifications of Principal Executive Officer and Principal Financial Officer[240](index=240&type=chunk) - XBRL Instance Document and Taxonomy Extension documents are filed[240](index=240&type=chunk)[241](index=241&type=chunk)[242](index=242&type=chunk) SIGNATURES The report is duly signed by President and CEO RA Session II and CFO Kamran Alam as of May 11, 2021 - Report signed by RA Session II, President and Chief Executive Officer, and Kamran Alam, Chief Financial Officer[246](index=246&type=chunk) - Signatures dated May **11**, **2021**[246](index=246&type=chunk)

Taysha Gene Therapies, Inc. (NASDAQ:TSHA) Q1 2021 Earnings Conference Call May 11, 2021 8:00 AM ET Company Participants Kimberly Lee – Senior Vice President of Corporate Communications and Investor Relations RA Session II – President, Founder, and Chief Executive Officer Suyash Prasad – Chief Medical Officer and Head-R&D Kamran Alam – Chief Financial Officer Fred Porter – Chief Technical Officer Conference Call Participants Salveen Richter – Goldman Sachs Raju Prasad – William Blair Eun Yang – Jefferies Ope ...

GAN Program Acquisition Highlights - The GAN program transforms Taysha into a pivotal-stage gene therapy company[13, 103] - TSHA-120 has shown clear arrest of disease progression and long-term durability in patients treated for 3+ years[13, 68, 103] - TSHA-120 is well-tolerated with efficacy established at multiple doses in an ongoing clinical trial[13, 61, 103] - The estimated prevalence of GAN is 2,400 patients in the US & EU, representing a potentially greater than $2 billion near-term commercial opportunity[13, 21, 25, 31, 103] TSHA-120 Clinical Data - Clinical data demonstrated arrest of disease progression[16] - Bayesian analysis confirmed documented natural history data of an 8-point decline in the MFM32 total % score per year[70] - TSHA-120 dose of 1.8x10^14 total vg resulted in an arrest of disease progression that was statistically significant[70, 71] - 1.8x10^14 total vg dose confirmed nearly 100% probability of clinically meaningful slowing of disease compared to natural history decline of GAN patients[83, 84] - 1.2x10^14 total vg dose confirmed approximately 85% probability of clinically meaningful slowing of disease and 100% probability of any slowing of disease[83, 84] Vagus Nerve Redosing Platform - There is an opportunity to achieve human POC for vagus nerve redosing platform with previously treated low dose patients[13, 89, 103]

Gene Therapy Pipeline - The company has a pipeline of 25 gene therapy product candidates targeting neurological indications, with the potential to address over 500,000 patients in the U.S. and EU[20] - The product portfolio currently consists of 25 gene therapy product candidates targeting various CNS indications, with exclusive options to acquire four additional development programs from UT Southwestern at no cost[41] - The company is advancing four new undisclosed programs focused on neurodevelopmental disorders and genetic epilepsies into preclinical development in 2021[20] - The company plans to advance four undisclosed programs into preclinical development in 2021[41] Clinical Trials - TSHA-101 is in development for GM2 gangliosidosis, with a Phase 1/2 clinical trial initiated in Canada, and preliminary safety data expected in the second half of 2021[25] - TSHA-118, targeting CLN1 disease, plans to initiate a Phase 1/2 clinical trial in the second half of 2021 under an open IND[26] - TSHA-102, for Rett syndrome, is set to submit an IND/CTA in the second half of 2021 and initiate a clinical trial by the end of 2021[27] - The company anticipates submitting INDs for multiple product candidates in the second half of 2021, including TSHA-102 and TSHA-104[20] - The company plans to submit an IND/CTA for TSHA-104 in the second half of 2021 and initiate a Phase 1/2 clinical trial by the end of 2021[29] - A Phase 1/2 clinical trial of TSHA-101 was initiated by Queen's University, with preliminary safety and biomarker data expected in the second half of 2021[41] - The global Phase 1/2 trial for TSHA-118 is expected to enroll up to 18 patients, focusing on safety, tolerability, and developmental milestones[93] - The Phase 1/2 clinical trial for TSHA-101 is expected to report preliminary safety and biomarker data in the second half of 2021 and preliminary clinical data by the end of 2021[82] Manufacturing and Facilities - The company is establishing a commercial-scale, GMP-compliant manufacturing facility in Durham, North Carolina, to meet clinical demand[19] - The manufacturing process utilizes scalable suspension HEK293 cell culture, which is expected to support the full pipeline of product candidates[19] - The company intends to utilize scalable manufacturing technologies, including a 187,000-square-foot commercial-scale cGMP manufacturing facility in Durham, North Carolina, expected to meet clinical and commercial demand[41] - An approximately 187,000-square-foot commercial-scale cGMP manufacturing facility is being configured in Durham, North Carolina, to support commercial scale manufacturing of pipeline programs[198] Partnerships and Collaborations - The partnership with UT Southwestern allows for exclusive, royalty-free access to develop and commercialize gene therapies, enhancing the speed and scale of development[21] - The company has established a strategic partnership with UT Southwestern, providing access to a GMP viral vector manufacturing facility capable of supporting multiple preclinical and early clinical development efforts[34][36] - The company has entered into a Sponsored Research Agreement with UT Southwestern to fund the discovery and development of novel gene therapy candidates[39] - The company has entered into a research, collaboration, and license agreement with UT Southwestern, which includes 15 product candidates and options for additional indications[199] - Under the UT Southwestern Agreement, the company issued 2,179,000 shares of common stock to UT Southwestern, with no future milestone or royalty obligations other than patent maintenance costs[201] - The Queen's University Agreement includes a one-time upfront fee of $3.0 million and potential milestone payments totaling up to $20.0 million, along with royalties on net sales of licensed products[205] Preclinical Studies and Efficacy - In preclinical studies, TSHA-101 demonstrated a significant improvement in survival rates, with high, medium, and low doses increasing survival by 3.4-fold, 2.3-fold, and 1.5-fold, respectively, compared to vehicle control[74] - Preclinical studies showed a dose-dependent decrease in GM2 ganglioside accumulation, indicating restoration of Hex A enzyme activity[78] - TSHA-118 has shown significant improvements in survival rates in preclinical studies, with treated CLN1 knockout mice surviving an average of 18.7 months compared to approximately 8 months for untreated mice[90] - TSHA-118 treatment resulted in supraphysiological levels of active PPT1 enzyme in serum, indicating effective restoration of enzyme activity[92] - Preclinical studies for TSHA-104 demonstrated restoration of mitochondrial function and reduction of elevated blood lactate levels in SURF1 knockout mice[102] - Preclinical studies for TSHA-111 showed effective knockdown of GYS1 expression and reduced insoluble glycogen in brain tissue[111] - TSHA-119 demonstrated a dose-dependent reduction of GM2 gangliosides in preclinical studies, indicating potential efficacy for the GM2 AB variant[120] - In preclinical studies, TSHA-102 extended survival in MECP2 knockout mice by 56%[144] - TSHA-102 demonstrated a favorable tolerability profile with no deaths associated with treatment in wild type mice[141] Regulatory Designations - The company has received orphan drug designation and rare pediatric disease designation from the FDA for TSHA-101[71] - The company has received orphan drug designation and rare pediatric disease designation from the FDA for both TSHA-103 and TSHA-105[169][172] Targeted Therapies and Conditions - TSHA-101 is designed to express the HEXA and HEXB genes in a 1:1 ratio to ensure therapeutic efficacy, addressing the critical threshold for normal hydrolysis of GM2 ganglioside[65] - TSHA-106 is being developed for Angelman syndrome, which affects approximately 55,000 patients in the United States and European Union[147] - TSHA-114 is being developed for Fragile X syndrome, with an estimated prevalence of 100,000 patients in the United States and European Union[151] - TSHA-116 is being developed for Prader-Willi syndrome, with an estimated prevalence of 40,000 patients in the United States and European Union[156] - TSHA-117 is being developed for FOXG1 syndrome, which has an estimated prevalence of 20,000 patients in the United States and European Union[157] - The company is also developing TSHA-103 for SLC6A1 haploinsufficiency disorder and TSHA-105 for SLC13A5 deficiency[162] - Approximately 81% of patients with SLC6A1 haploinsufficiency disorder have epilepsy, with 91% exhibiting developmental delays and over 80% characterized as having mild or moderate intellectual disability[165] - The estimated prevalence of SLC6A1 haploinsufficiency disorder is 17,000 patients in the United States and European Union, with an incidence of approximately 1 in 36,000 live births[167] - TSHA-103 is a gene replacement therapy for SLC6A1 haploinsufficiency disorder, currently in preclinical studies[168] - TSHA-105 is being developed for SLC13A5 deficiency, with an estimated prevalence of 1,900 patients in the United States and European Union[170] - TSHA-110 is planned for development targeting KCNQ2 Developmental and Epileptic Encephalopathy, with an estimated prevalence of 37,000 patients in the United States and European Union[176] Innovative Technologies - The company is utilizing a novel AAV dosing platform that allows for redosing by administering therapies directly to the vagus nerve, showing promising results in preclinical studies[55] - The company is developing a novel AAV capsid platform using machine learning and directed evolution to improve targeted delivery of gene therapies[58] - AAV9 delivery to the vagus nerve has shown efficient targeting of vagal neurons in preclinical studies, facilitating potential redosing of gene therapies[179] - The company is developing a novel miRNA target panel, miRARE, to regulate transgene expression levels in the brain for disorders requiring dose-sensitive gene replacement[183] - The company has access to a state-of-the-art AAV production facility through collaboration with UT Southwestern, equipped for both research-grade and GMP-grade AAV vector production[195][196]

Product Development - Taysha Gene Therapies has a product portfolio of 18 gene therapy candidates and exclusive options for four additional programs [106]. - Taysha plans to initiate a Phase 1/2 clinical trial of TSHA-101 for GM2 gangliosidosis by the end of 2020 and submit INDs for four programs by the end of 2021 [106]. - The company has entered into a license agreement with Queen's University, involving a $3.0 million upfront fee and potential milestone payments totaling up to $20.0 million [113]. - Under the Abeona CLN1 Agreement, Taysha will pay a one-time fee of $3.0 million and up to $56.0 million in regulatory and sales-related milestones per licensed product [116]. Financial Performance - Net losses were $1.1 million from inception through December 31, 2019, and $41.7 million for the nine months ended September 30, 2020, with an accumulated deficit of $42.8 million as of that date [108]. - Taysha has not recognized any revenue from product sales to date and does not expect to generate revenue in the foreseeable future [119]. - The net loss for the nine months ended September 30, 2020, was $41.7 million, compared to a net loss of $31,000 for the same period in 2019 [129]. - Total operating expenses for the nine months ended September 30, 2020, were $24.6 million, compared to $31,000 for the same period in 2019 [129]. - The company anticipates an increase in general and administrative expenses by $6.0 million to $7.0 million annually due to expanded infrastructure and compliance costs [125]. - The company expects to need substantial additional funding for ongoing operations and research and development activities [136]. Research and Development - Research and development expenses are expected to increase significantly as the company advances its product candidates and manufacturing processes [121]. - Research and development expenses for the three months ended September 30, 2020, were $11.1 million, compared to no expenses for the same period in 2019 [127]. Cash Flow and Financing - Cash and cash equivalents as of September 30, 2020, were $278.6 million, funded through equity financings totaling $307.0 million [135]. - Financing activities generated $292.5 million in cash during the nine months ended September 30, 2020, primarily from $167.1 million in net proceeds from the initial public offering [145]. - Net cash used in operating activities for the nine months ended September 30, 2020, was $10.9 million, primarily due to research and development spending [143]. - Investing activities used $3.0 million of cash for the upfront fee paid pursuant to the Queen's University Agreement during the nine months ended September 30, 2020 [144]. - The company believes existing cash will fund operations into 2023, but estimates may prove imprecise [137]. Operational Challenges - The company has incurred significant operating losses and anticipates continued losses as it scales its operations [108]. - The company has not experienced material impacts from COVID-19 on its financial results for 2020, but future developments remain uncertain [118]. - General and administrative expenses for the three months ended September 30, 2020, were $4.0 million, a significant increase from less than $0.1 million for the same period in 2019 [128]. Accounting and Compliance - The company qualifies as an "emerging growth company," allowing it to delay the adoption of certain accounting standards until they apply to private companies [153]. - The company is classified as a "smaller reporting company," with a market value of shares held by non-affiliates below $700 million and annual revenue under $100 million [155]. - The company has not included milestone or royalty payments in its financial statements due to their uncertain timing and amounts [147]. - There are no off-balance sheet arrangements currently in place [148]. - The company evaluates its estimates and judgments on an ongoing basis, which may affect the reported amounts of assets and liabilities [149]. Market Risks - The primary market risk exposure is interest rate sensitivity, influenced by changes in U.S. interest rates [156]. - The company has not engaged in hedging foreign currency transactions, with most assets and liabilities denominated in U.S. dollars [157]. - Inflation has not materially affected the company's business or financial condition for the nine months ended September 30, 2020 [158].